HW path notes Flashcards
POLYCYTHAEMIA VERA is
A myeloproliferative neoplasm that results in an excess of red blood cells
Typically presents in older patients, with slight male predilection
Varied presentation, most serious being venous and arterial thrombosis and transformation into acute myeloid leukaemia
Features:
Hypertension
Unbearable pruritis
Venous thrombosis
Arterial thrombosis
Conjunctival injection
Facial plethora
Gout
JAK2 mutation, found in >95% of people
MULTIPLE MYELOMA is
monoclonal gammopathy, the most common primary malignant bone neoplasm
Arises from red marrow due to the monoclonal proliferation of plasma cells
Four main patterns are recognised:
- Disseminated - multiple well defined, punched out lytic lesions
- Disseminated - diffuse skeletal osteopenia
- Solitary plasmacytoma - single large lesion
- Osteosclerosing myeloma
A common malignancy in patients >40yo
Clinical presentation
Bone pain - intermittent and then constant
Anaemia - normochromic, normocytic
Renal failure
Proteinuria
Hypercalcaemia
Complications :
Pathological fracture
Amyloidosis
Recurrent infection
Plasmacytomas typically progress to multiple myeloma
MULTIPLE MYELOMA path
Monoclonal proliferation of malignant plasma cells which produce immunoglobulins (commonly IgG) and infiltrate haemopoietic locations (red marrow)
Renal involvement is common and renal failure is multifactorial :
- Obstructive casts in the renal tubules
- Direct nephrotoxicity of Bence Jones proteins on the epithelial cells of the renal tubules
- Hypercalcaemia and dehydration
- Amyloidosis
- Increased risk of renal infection
PLASMACYTOMA is
Discrete, solitary tumours of neoplastic monoclonal plasma cells in either bone or soft tissue (extramedullary)
No/minimal systemic bone marrow involvement
Two groups:
Solitary bone - 70%
Extramedullary plasmacytoma - 30%
Usually in adults age 40-80yo
Can arise in any part of the body
LYMPHOMA is
A malignancy arising from lymphocytes or lymphoblasts
Can present as nodal or extranodal disease
Nodal: Hodgkin and low-grade NHL
High grade NHL: SVC, cauda equina
Often present with B symptoms: fever, night sweats and weight loss
Unknown aetiology, but potential lymphomatogenic risk factors:
- Viral infection - EBV, HIV, HCV
- Bacterial infection - Helicobacter pylori
- Chronic immunosuppression - post transplant
- Prior chemotherapy and drug therapy e.g. digoxin
Classification
Hodgkin lymphoma 40%
Non-Hodgkin lymphoma 60%
- Mature B-cell lymphoma - 85%, the remainder are T-cell
- Mature T-cell and NK-cell lymphoma
- Post-transplant lymphoproliferative disorders
HODGKIN LYMPHOMA is/path
Spreads contiguously along lymphatic pathways
Curable in ~90% of cases
Bimodal distribution, young 15-34, and older >55
Typically presents with painless lymphadenopathy
Pathology:
- Characterised by the presence of Reed-Sternberg cells (a type of B cell)
- These occupy a very small proportion of the overall cell population of the affected lymph node
Contiguous spread is another feature
EBV infection is present in 40-80%
5 subtypes, divided into two groups - classical and non-classical
Classical
- Positive for CD15/CD30 and negative for CD20/45/EMA
- Nodular sclerosing - 70%
- Mixed cellularity - 25%
- Lymphocyte rich - 5%
- Lymphocyte depleted - <5%
Worst prognosis
Non-classical
- Positive for CD 19, 20, 22, 79a/EMA and negative for CD15/CD30
- Nodular lymphocyte predominant - best proggy
HODGKIN LYMPHOMA location
Typically entirely confined to the lymph nodes, and starts in the upper body
Extranodal manifestations are uncommon, but can be found in any organ system
Spine
- Erosion of the anterior/anterolacteral aspect of the vertebral body - from enlarged lymph nodes
- Nodular sclerosing - diffusely increased density with or without anterior erosion, vertebral body heigh is unaffected
- Single, dense vertebra is suggestive in adults
Long bones - frequently lytic
NON-HODGKIN LYMPHOMA is
Catch all phase for any non-hodgkin lymphoma
- burkitt
- marginal zone
- follicular
- waldenstrom macroglobulinaemia
BURKITT LYMPHOMA is
An aggressive B-cell lymphoma predominantly affecting children
The most common NHL in children, ~40%
Median age is 8yo
Risk factors:
HIV/AIDs
Post transplant immunosuppression
Presentation:
- Extranodal involvement is common ~30%, most often as an abdominal or pelvic mass
- Most patients present with widespread disease
BURKITT LYMPHOMA pathology
Three forms are described:
- Endemic - linked to EBV and malaria
- Sporadic - aetiology unknown
- Immunodeficiency associated - occur in patients with HIV, post transplant or congenital immunosuppression
An aggressive tumour with a doubling time of 24hrs
Can present in a wide variety of locations:
- Head and neck
- Pleural space ~70%
- GIT, esp ileocaecal
- Mesentery, peritoneum, retroperitoneum
- Kidneys
- Gonads ~75%
Nodal involvement is more common in adults than children
MARGINAL ZONE LYMPHOMA is
A group of NHL
Three types, depending on the site of origin
Mucosa-associated lymphoid tissue (MALT), splenic and extranodal marginal lymphoma
The marginal zone in the germinal follicles undergoes hyperplasia in response to infection or antigen
The most common type of NHL, often in the stomach (associated with H-pylori infection) and thyroid
Genetic abnormalities: t(11, 18) and trisomy 3 are reported
FOLLICULAR LYMPHOMA is
subtype of NHL
Accounts for ~45% of all NHL
Markers:
CD10 positive
CD5 negative
CD20 positive
Translocation t(14;18) is found in majority of patients with follicular lymphoma
Can transform into a more aggressive type
WALDENSTROM MACROGLOBULINAEMIA
A lymphoplasmacytic lymphoma
rare
SICKLE CELL DISEASE is
A hereditary autosomal recessive condition resulting in the formation of abnormal haemoglobin, which manifests as multisystem ischemia and infarction, as well as haemolytic anaemia
No gender predilection
The highest incidence is in individuals of african descent > eastern mediterranean
Close relationship with malaria
Early manifestation in early childhood, commonly with a painful vaso-occlusive crisis - sudden onset bone or visceral pain due to microvascular occlusion and ischaemia, often in the setting of sepsis or dehydration
Presentation:
Bone pain - infarction, osteomyelitis
Pulmonary - acute chest syndrome, recurrent pneumonia, chronic lung disease
Abdominal - vaso-occlusive crises, sequestration syndrome (rapid pooling of blood in the spleen, leading to intravascular volume depletion)
Haemolytic anaemia and extra-medullary haematopoiesis
Impaired immunity from autosplenectomy
Multiple renal manifestations resulting in renal failure
Cerebral - stroke, cognitive impairment
Ocular and orbital complications - central retinal artery occlusion
SPLENIC SIDEROTIC NODULES
Splenic siderotic nodules - Gamna-gandy bodies of the spleen, most commonly encountered in portal hypertension. The pathological process is the result of microhaemorrhage resulting in haemosiderin and calcium deposition followed by fibroblastic reaction
SPLENOMEGALY
Massive splenomegaly: longer than 18cm, or extending into the pelvis or across the midline
Pathology:
Haematological disease
Haemodynamic
Infectious
Storage Diseases/metabolic/infiltrative disorders
Neoplastic - non haemorrhagic
Traumatic
Connective tissue disordERS
Massive: Chronic myeloid leukaemia, myelofibrosis, gaucher disease, lymphoma, Kala-azar, malaria, beta-thalassemia major, AIDs with mycobacterium, Sarcoidosis
Moderate :Rickets, hepatities, hepatic cirrhosis, lymphoma/leukaemia, EBV, pernicious anaemia, amyloidosis, abscess
LEUKAEMIA is
A haematological neoplasm characterised by the overproduction of immature (blasts) or abnormally differentiated cells of the haematopoietic system in bone marrow that often, but not always, extends into peripheral blood
Divided according to the percentage of blasts in the bone marrow or peripheral blood
Acute - when there is proliferation of mostly immature/poorly differentiated cells (blasts) in the bone marrow
- >20%
- Clonal cells build-up crowds out of the marrow in detriment of healthy blood lineage cells
- Disease becomes symptomatic early
Chronic - proliferation of mostly mature but abnormal leukocytes with or without cytopenia
LEUKAEMIA classification
Acute lymphoblastic leukaemia
- Commonly affecting children - ~80%
- Usually severely symptomatic
Chronic lymphocytic leukaemia
- Commonly affecting elderly patients >75yo
Acute myeloid leukaemia
- Commonly seen in adults, but also the second most common form in children
- Male predominance
Chronic myeloid leukaemia
- Male adults
- Philadelphia chromosome is present in 90%
CML is
Overproduction of granulocytes with fairly normal differentiation
Typically age 50-60
Risk factors - high-dose radiation exposure
Bloods: leucocytosis with a predominance of the neutrophil lineage
Genetics:
Chromosomal abnormality of the haematopoietic stem cell: where translocation between chromosomes 9 and 22 creates the fusion gene BCR-ABL1
The shortened chromosome 22 contains the fusion gene Philadelphia chromosome
Imaging:
Splenomegaly and diffuse marrow infiltration
VITAMIN K DEFICIENCY
A clotting dyscrasia, vital as a cofactor for the enzymatic activation of several key components of the clotting pathway, including the prothrombogenic proteins, prothrombin, factors VII, IV and X, and the anticoagulant molecules: proteins C, S and Z
Presents with bleeding tendency:
Spontaneous haematomas
Mucosal bleeding
Haematochezia and melena
Haematuria
Menorrhagia
Anaemia
Aetiology:
Fat malabsorption
Chronic broad spectrum antibiotics
Dietary fat insufficiency
EPSTEIN-BARR VIRUS
Exposure is widespread, 90% of adults are seropositive
When acquired in childhood it remains subclinical. If acquired as a young adults, 25% are symptomatic
In 5%, CMV is the causative pathogen
Clinical presentation
Fever/tonsillitis
Lymphadenopathy and splenomegaly - occasionally hepatosplenomegaly
Fatigue
Rash
Complications:
Splenic rupture - may be spontaneous
Splenic infarction
Pathology:
A herpesvirus - herpesvirus 4
Thought to be person-to-person spread, through salivary secretions
Infects B-cells in the lymphoid tissue
Becomes a chronic infection with periodic shedding of virus
May have elevated transaminases
Imaging
Splenomegaly
Lymphadenopathy
Tonsillar enlargement
Possible hepatomegaly
Complications
Myocarditis rarely seen
CNS infection, rarely seen
INVASIVE LOBULAR CARCINOMA general
The most common type of invasive breast cancer after invasive breast carcinoma of no special type
They represent 5-10% of all breast cancer
Association:
- Greater likelihood of contralateral breast cancer in invasive lobular carcinoma, with a 5yr rate of bilateral cancer of 8%
- 4% synchronous and 4% metachronous
INVASIVE LOBULAR CARCINOMA pathology/markers
Pathology:
Characterised by malignant monomorphic cells that form loosely dispersed linear columns that invade the normal tissues and encircle ducts.
Invasive carcinoma of no specific type more commonly presents as a mass with vigorous desmoplastic response
The cells often preserve the architecture of the ducts, which limits the sensitivity of detection using mammography
Markers:
- Loss of E-cadherin is a specific biomarker for invasive lobular carcinoma as opposed to invasive breast carcinoma of no special type
- Although 15% of ILC are positive for E-cadherin
- The majority of invasive lobular carcinomas have the following receptor profile:
- Oestrogen receptor +
- Progesterone receptor +
- HER2 amplification -
Variants:
Tubulolobular
Solid
Alveolar
Pleomorphic
Mixed
INVASIVE LOBULAR CARCINOMA imaging
Imaging
Often multicentric and bilateral 10-15%
Imaging of the contralateral breast is crucial
Can be subtle changes e.g. progressive shrinkage/enlargement or reduced compressibility of the involved breast
Mammography:
Sensitivity 57-81%
Spiculated mass lesion - most common
Asymmetrical densities 3-25%
Opacities or architectural distortion 10-25%
Microcalcifications <10%
16% are occult or benign
Ultrasound
Heterogenous, hypoechoic mass with angular or ill-defined margins and posterior acoustic shadowing
Characteristic: heterogenous infiltrating area of low echogenicity with disproportionate posterior shadowing
MRI is recommended due to propensity for multicentricity
ATYPICAL LOBULAR HYPERPLASIA
A premalignant lesion of the breast which falls at the milder end of the spectrum of lobular neoplasia
Considered borderline breast disease
Pathology:
Proliferation of monomorphic cells which are morphologically identical to lobular carcinoma in situ (LCIS)
The distinction is that ALH occurs in a non-distended lobule or small lobular duct, whereas LCIS is characterised by distension
Treatment is controversial. Some centres surgically excise, others do not.
The risk of subsequent breast cancer is 4-6x higher after diagnosis (11x after LCIS)
LOBULAR CARCINOMA IN SITU
Represents the next step up from atypical lobular hyperplasia along the malignant spectrum of lobular breast carcinoma
Predominately occurs in pre-menopausal women, average age ~45yo. 10-15yrs younger than the mean age when invasive breast carcinoma occurs
Pathology;
Like most other lobular breast pathology, LCIS originates in the terminal ductal lobular unit
Unlike ALH, the malignant cells fill and distend the lobular acini in LCIS
Unlike invasive, they leave the basement membrane intact
Do not express E-cadherin
Usually incidentally identified
The exception may be pleomorphic LCIS which is a more aggressive subtype
A high risk marker for future development of invasive 15-30% chance of developing an infiltrating ductal or lobular carcinoma in the breast in which LCIS is discovered or in the contralateral breast
Usually diagnosed with a core needle biopsy > excisional biopsy should be performed
MEDULLARY CARCINOMA OF THE BREAST
An uncommon subtype of breast cancer
Accounts for ~5% of all breast cancers
Tend to occur in younger women, more than other breast cancer types
Mean age of presentation varies 46-54yo, but in 10% under 35yo
Pathology:
- Typically arises from supporting stromal cells of the breast
- A well-circumscribed carcinoma composed of poorly differentiated cells with scant stroma and prominent lymphoid infiltration
- Large pleomorphic nuclei, prominent nucleoli and high mitotic activity may be seen
- The histological appearance can mimic poorly differentiated intraductal carcinoma no
- Areas of necrosis may be present
- More common in the BRCA 1 gene mutation setting
Two types:
Typical
Atypica
Better prognosis than for intraductal carcinoma. 89-95% 5yr survival
MEDULLARY CARCINOMA OF THE BREAST imaging
Mammography:
Typically seen as a circular/oval type mass lesion with ill-defined or circumscribed margins at mammography
There can be varying degrees of lobulation
Calcification isn’t usually a feature
Ultrasound:
Either homogenously hyperechoic, or hypoechoic with mild heterogeneity
Enhanced through transmission may be present
The level of hypoechogenicity can sometimes be marked
MRI :
May show diffuse enhancement post contrast
PAGET DISEASE OF THE BREAST/NIPPLE is
A form of breast malignancy characterised by infiltration of the nipple epidermis by malignant cells
Most cases have an underlying focus or foci of in situ or invasive carcinomas, some are confined to the skin of the nipple-areola without underlying neoplastic foci
Can represent 1-5% of breast malignancies
The average age at diagnosis is ~6th decade 53-59yo
Eczematous appearing changes of the nipple include reddening, scaling, hyperkeratosis and crusting of the nipple surface
Can be classified into 4 clinical stages:
0: lesion is confined to the epidermis, without underlying ductal carcinoma in situ of the breast
1: associated with DCIS just beneath the nipple
2: associated with extensive DCIS
3: associated with invasive ductal carcinoma
Treatment: traditionally a mastectomy with nodal dissection
PAGET DISEASE OF THE BREAST/NIPPLE path
In most cases there are malignant ductal cells that extend to the nipple surface through the terminal lactiferous ducts
Malignant epithelial cells infiltrate and proliferate in the epidermis, causing an eczema-like rash of the nipple and areolar skin
There are several histological variants:
Adenocarcinoma-like cell
Spindle cell
Anaplastic cell
Acantholytic cell
Pigmented cell
PAGET DISEASE OF THE BREAST/NIPPLE imaging
Undetectable in ~50% of cases on mammo
Apparent features:
Skin thickening, nipple retraction, subareolar or more diffuse malignant microcalcifications, and discrete subareolar masses
MRI:
Abnormal nipple enhancement and linear clumped enhancement indicative of DCIS in association with Paget disease
GYNAECOMASTIA is/path./causes
Benign excess of male breast tissue, usually reversible
Not a risk factor for male breast cancer
Greater prevalence in two groups:
Adolescent boys 50-60%
Older men 70%
Symptomatic cases are much lower
Pathology:
- Enlargement of the male breast due to benign ductal and stromal proliferation
- A hallmark is its central symmetrical location under the nipple
- Tends to be unilateral and/or asymmetrical
- Key is the imbalance between oestrogen action relative to androgen action at the breast tissue level
Aetiology:
Hormonal
Neonate – maternal oestrogen
Puberty – high oestradiol levels
Elderly – decline in testosterone levels
Hypogonadism/androgen deficiency states:
- Klinefelter syndrome
- Anorchism
- Testicular failure e.g. testicular cancer
Drugs
Systemic disorders
- Advanced alcoholic cirrhosis
- Chrnic pulmonary disease e.g. emphysema, - TB
- Haemodialysis in chronic renal failure
- Hyperthyroidism
- Malnutrition
Tumours – particularly oestrogenic tumours
- Adrenal carcinoma
- Hepatoma
- Lungcancer
- Pituitary adenoma
- Testicular cancer – including sex-cord stromal, and germ cell tumours
Idiopathic
LYMPHOCYTIC MASTITIS is
A rare benign inflammatory disease of the breast that can mimic breast cancer
Diabetic mastopathy is a closely related entity, sometimes used synonymously
May present as a palpable mass, may be painful, and may be bilateral
Associated with autoimmune disease e.g. Hashimoto thyroiditis, SLE and sjogrens syndrome
Dense fibrous tissue with hard lesions that can be large – up to 6cm.
PLASMA CELL MASTITIS is and imaging
A benign breast condition that represents calcification of inspissated secretions in or immediately adjacent to ectatic benign ducts
Typically seen in non-pregnant and non-lactating females
Thought to represent aseptic inflammation with infiltration of plasma cells and lymphocytes in the breast tissue from the extravasation of intraductal sections into periductal connective tissue
Imaging:
Thick, linear, rod-like or cigar-shaped calcifications
Can be up to 10mm long
Tend to be bilateral, often symmetrical and orientated to point towards the nipple. Branching may be seen
Larger in length and calibre than DCIS, with a smoother outline
Benign entitiy. No increased risk of malignancy
FAT NECROSIS IS
Within the breast, a pathological process that occurs when there is saponification of local fat
Benign inflammatory process, increasingly more common with the greater use of breast-conserving surgery and mammoplasty procedures
Most at risk are middle aged women with pendulous breasts
Onset can be delayed 10+ years after surgery
FAT NECROSIS PATH
Disruption of fat cells, with the formation of vaculoes containing the remnants of necrotic fat cells
The vaculoes are surrounded by lipid-laden macrophages, multinucleated giant cells and acute inflammatory cells
Fibrosis develops during the reparative phase, peripherally enclosing an area of necrotic fat and cellular debris
Eventually fibrosis may replace the area of degenerative fat with a scar, or loculated and degenerated fat may persist for years within a fibrotic scar
Aetiology:
Direct trauma
Nodular panniculitis
Plasma cell mastitis
FAT NECROSIS IMAGING
Variable appearance
Initially can be an ill-defined and irregular, spiculated mass-like area
Calcification may be present
- Usually peripheral with a stippled curvilinear appearance, creating the appearance of lucent ‘bubbles’ in the breast parenchyma
Low density centre
Tumour formation is not part of fat necrosis, although it may be clinically palpable
With time, becomes more well defined and well-circumscribed, giving rise to an oil cyst
- Oil cyst – fine curvilinear calcification of the walls
- The centre becomes increasingly homogenous with fat density
- Calcifies in 5%
Ultrasound:
- Acute – increased echogenicity due to oedema of the fatty tissue
- Subacute – ill defined complex cystic lesion surrounding oedematous fat
- Late – calcified walls, posterior shadowing
Aspiration: milky, emulsified fat appearance
- Can have fat globules drifting
RADIAL SCAR is
A rosette-like proliferative breast lesion
Not related to surgical scarring
An idiopathic process with sclerosing ductal hyperplasia
A mimicker of scirrhous breast carcinoma
Diagnosis cannot be made on imaging alone
Rare in women <40yo and >60yo
Clinically – not palpable, no skin thickening or retraction
Considered a high risk breast lesion, and histological differentiation is requried
Associations
30% of cases, associated with DCIS and tubular carcinoma of the breast
- Occurrence is higher when associated atypia on histology
Other associations:
Atypical ductal hyperplasia
Atypical lobular hyperplasia
FNA and core biopsies can underestimate the underlying associated malignancy = vacuum assisted biopsy is recommended
RADIAL SCAR path
Benign hyperplastic proliferative disease of the breast
Mechanisms include localised inflammatory reaction and chronic ischaemia with subsequent slow infarction
Histopathologically:
Hyperplastic tissue cells and a central fibrous core, with a radial extension of tubular structures mimicking infiltrating carcinoma
The tubular formation has two rows of cells, epithelial and myoepithelial
The malignant potential is 2x greater than in the normal population without radial scar
RADIAL SCAR imaging
Spiculated appearance, similar to carcinoma, but the centre tends to be translucent, low-density rather than a mass
Breast tissue behind the lesion is usually as dense centrally as peripherally
No mass
Spicules running from the centre are in general longer and gracile than those of a carcinoma
Long, thin with radiating radiolucent linear structures, which against a radiolucent fat background gives a black star appearance
Microcalcifications are possible but rare
Other features of a carcinoma are rare e.g. skin thickening and retraction
No visible scirrhous reaction in the radial scar
Ultrasound:
- Often ill-defined and disturbs the architecture of surrounding breast parenchyma
- Usually round, oval or lobulated
- Variable internal echoes can be found
DCIS IS
Breast carcinoma limited to the ducts with no extension beyond the basement membrane – so the disease has not infiltrated the parenchyma of the breast and lymphatics, and therefore cannot metastasize
Associations:
Up to 11% of predetermined ductal carcinoma in situ on imaging may have an invasive component at the time of biopsy
20-25% may have an invasive component following surgical excision
Risk factors:
Increasing age
Family history of breast cancer
Nulliparity
Age 30+ at the birth of first child
Most are asymptomatic
DCIS path
Pathology:
Precursor of invasive breast carcinoma
Represents a spectrum of disease
Ductal carcinoma in situ isn’t a single entity, but a spectrum of disease
Markers:
E-cadherin may help to differentiate from lobular
Subtypes:
Largely two, based on central necrosis, grade and cell type:
- Comedo – large cell: more aggressive form “comedocarcinoma”
- Non-comedo – small cell: less aggressive, can be further divided into
- Cribiform
- Micropapillary
- Papillary
- Solid
DCIS imaging
Varied manifestation, with casting-type calcifications being more common 50-75% of cases
Other manifestations include a soft tissue opacity either with or without associated calcifications
Linear calcs are more likely to be comedo-type, while granular calcs are more often non-comedo
Occasionally can present as a simple mass or asymmetry without calcification ~8%
Calc underestimates the distribution, since not all the DCIS calcifies
US
Microlobulated mild hypoechoic mass with ductal extension and normal acousitc transmission
MRI
Non-mass enhancement, most commonly with a segmental or linear distribution and clumped or heterogenous internal enhancement pattern
JUVENILE PAPILLOMATOSIS is, path, imaging
A relatively common benign localised proliferative lesion in the breast
Mainly seen in young women ~19-23yo, unusual over 30
Present with a firm, well-defined, mobile mass often in the periphery of the breast
Usually with no nipple discharge
Pathology:
- A papillary proliferation of the ductal epithelium which partly fills up smaller ducts and distends them
- Well-circumscribed mass containing multiple small cysts (<2cm) within a dense fibrous stroma
- Can vary in size 1-8cm
US:
- Ill defined, inhomogenous hypoechoic mass with multiple small (up to 4mm) predominantely peripheral cysts
Mammo: typically negative, occasionally may show pleomorphic or amorphous `microcalcifications, asymmetric density or a prominent intraductal pattern
Galactography: multiple irregular filling defects within the breasts
Benign, but considered to be a marker for familial breast cancer
TUBULAR CARCINOMA is
A subtype of invasive ductal carcinoma
Account for ~1% of breast cancer
Peak age at presentation may be comparatively younger than other types of breast cancer
Majority are non-palpable and invariably found incidentally at screening rather than manifesting with clinical findings
TUBULAR CARCINOMA path
Pathology:
May contain other histologic elements, but an excess of 75% tubular elements is usually required for the diagnosis of tubular carcinoma
A distinguishing feature is a single layer of cells lining tubules with loss of lobular architecture and surrounding infiltration
The glands in tubular carcinomas lack myoepithelial cells
Lesions may be multifocal or multicentric in ~15%
Variants :
Tubulolobular carcinoma - an invasive lobular carcinoma with features of tubular carcinoma, but behaves as other ILCs with regard to prognosis
Associations:
Ductal carcinoma in situ (DCIS) - can be an association in more than 50-65% of tubular carcinomas
TUBULAR CARCINOMA imaging
Typically small (<1cm), spiculated and can occur without calcifications
The appearance mimics typical IDC not otherwise specified, manifesting as one or more small spiculated masses
The spicules are often longer than the central mass
Amorphous microcalcifications may be present in 10-15%
US:
Also mimic IDC not otherwise specified, manifesting as a hypoechoic solid mass with ill-defined margins and posterior acoustic shadowing
The lesions are often rounded, tall as broad
Differentials:
Radial scar/complex sclerosing lesion
The tubular carcinoma is dense centrally, where the radial scar is not
Diabetic mastopathy also known as
Sclerosing lymphocytic lobulitis
SCLEROSING ADENOSIS is
A benign proliferative condition of the terminal duct lobular units characterised by an increased number of acini and their glands
Manifests as multiple small, firm, tender nodules, fibrous tissue and variable microcysts within the breast
Can be considered a borderline breast disease
Clinical presentation:
- Recurring pain that tends to be linked to the menstrual cycle
- Usually detected during screening, with biopsy confirmation
- Can appear as a focal or diffuse lesion
- Not palpable in 80% of cases, although in some it may cause skin retraction
Not premalignant, but an independent risk factor for the development of subsequent breast cancer
1.5-2x higher risk of developing breast cancer
SCLEROSING ADENOSIS path
A type of adenosis in which enlarged acini become slightly distorted by surrounded stromal fibrosis
The normal lobular architecture of the breast is maintained but becomes exaggerated and distorted
Assoc:
Can be seen as a component of other proliferative lesions
- Intraductal and/or sclerosing papilloma
- Complex sclerosing lesion
- Fibroadenoma
- Breast cancer, both invasive and in situ
SCLEROSING ADENOSIS imaging
Mammography - has a wide range of mammographic presentations, and can be difficult to distinguish from an infiltrating carcinoma
Mass - with irregular to well defined contours
Architectural distortion
Microcalcifications
- Present in 40-55% of cases
- May be amorphous, pleomorphic or punctate
- More commonly clustered, but may be diffusely scattered
DIABETIC MASTOPATHY is and path
The presence of a benign tumour like breast mass in women with long-standing type 1 or 2 insulin-dependent diabetes mellitus
Pathology:
- A form of lymphocytic mastitis and stromal fibrosis
- There is dense fibrosis and predominantly B-cell lymphocytic infiltrate surrounding the ducts, lobules and vessels
- The exact pathogenesis is poorly understood and likely multifactorial
US
Irregular hypoechoic masses with marked posterior acoustic shadowing
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA is
A benign, relatively uncommon form of stromal (mesenchymal) overgrowth within breast tissue that derives from a possible hormonal aetiology
Typically affects women of reproductive age, rarely affects males
Clinical presentation: the tumoural form of PASH commonly manifests as a single, circumscribed, palpable mass in a premenopausal female
Can be large (5-6cm) in diameter
Often grow over time and may recur after excisional biopsy in 10% of cases
Neither associated with malignancy or considered to be premalignant
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA path
Represents a clinicopathologic spectrum ranging from focal, incidental microscopic findings to clinically and mammographically evident breast masses
The development is presumed to be related to the interaction of progesterone receptions
Lesions can be microscopic or nodular (tumourous)
On gross pathology, typically a well-circumscribed, firm, rubbery mass with solid, homogenous, grey-white cut surface
Microscopic - characterised by the presence of open slit-like spaces in dense collagenous stroma which is lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei
Can also contain complex anastomosing spaces that may be confused with angiosarcoma on histo
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA imaging
Features are not specific enough for a prospective diagnosis
Mammography:
- A circumscribed or partly circumscribed mass
- Often present as an asymmetry/focal asymmetry
- Typically lack calcification
US
- Most often an oval or round circumscribed mass
- Often hypoechoic and may be slightly heterogenous - imaging appearance may be similar to that of a fibroadenoma
MUCINOUS BREAST CARCINOMA is
Tends to occur in older women, where prevalence of as much as 7% is found among women 75+ yo, whereas the prevalence is only 1% in women younger than 35
If palpable, tend to be soft masses
Purely mucinous subtype carries a good prognosis compared to other adenocarcinomas
5yr survival 95% stage 2, 75% stage 3 and 35% stage 4
Lower tendency to metastasise
MUCINOUS BREAST CARCINOMA path
The dominant feature is the presence of mucin within and surrounding cancer cells
- The mucin: cell ratio can vary from lesion to lesion
A core biopsy specimen usually gives a gelatinous appearance
Microscopically, it is formed by large mucin lakes surrounded by mucous-producing cancer cells
Histologically divided into:
- Hypocellular A - pure mucinous breast cancer
- Hypercellular B - variable area of DIC-NOS component
- Can be infiltrative and carries a worse prognosis
MUCINOUS BREAST CARCINOMA imaging
The majority of well-marginated breast masses are benign, but 10-20% of breast malignancies could be well-circumscribed, such as mucinous but also papillary, medullary, metaplastic carcinomas and a malignant phyllodes tumour
The presence of mucin results in a low-density and relatively well-defined lobular mass
Sometimes they have partly faded or obscure margins
Up to 20% can be occult on mammo
Calcifications an be rare in pure mucinous types
US
- Often display mixed echogenicity with mixed solid and cystic components
- Posterior acoustic enhancement is common
- At times, the lesion can be isoechoic to breast tissue on US
- Mixed cystic and solid components, distal enhancement and microlobulated margins are commonly found
- Homogeneity on sonography is associated with the pure type of MCB, where the margins are usually well defined, and the tumour is iso-echogenic relative to the fat surrounding the breast tissue on US
MRI
One of the few high T2 signal lesions
MALE BREAST CANCER is
Exceptionally rare, and only accounts of <0.25% of male malignancies
The diagnosis is sometimes delayed
The average age is 60-70yo, later than female breast cancer
Most commonly men present with a painless subareolar mass
Location
- Favours the subareolar area or upper outer quadrant
- Favours a slightly eccentric location relative to the nipple
MALE BREAST CANCER path, risk factors, imaging
Majority are invasive ductal carcinoma (85-90%) or ductal carcinoma in situ
Risk factors:
Exposure to ionising radiation
Cryptorchidism
Testicular injury/infectious orchitis
Increased levels of oestradiol
Klinefelter syndrome
Hepatic cirrhosis
BRCA2 gene mutation
Family history
Prostate cancer
Chest trauma
Imaging:
Subareolar mass, often round/oval/lobulated,
Calcifications tend to be fewer in number and coarser than in female breast cancer
ANGIOSARCOMA is
A rare vascular breast malignancy
Tend to occur in younger women, in their 3rd-4th decades
Secondary angiosarcoma, related to prior therapy of breast cancer occurs in older women (peak 6th decade)
The classical presentation is painless localised blue or purple colour change of the breast skin, with singular or multifocal lesions which may resemble other benign vascular lesions such as angioma or telangiectasis
Patients may present with swelling, a sensation of fullness, or rapid breast growth
Extremely aggressive with a poor prognosis
ANGIOSARCOMA path and imaging
Pathology:
Primary
Secondary
- Radiation induced
- Lymphoedema-associated cutaneous angiosarcoma
Location
- Primary: within the breast parenchyma, with secondary involvement of the skin
- Secondary: mainly involves the skin, with or without involvement of the underlying breast parenchyma
Associations:
- Prior radiation induced breast angiosarcoma tends to occur after a significant latent period post-radiation ~5yrs
- Stewart-Treves syndrome
Imaging
Can be occult
MRI
BREAST LYMPHOMA is
Involvement of the breast with lymphoma, may be primary or secondary
Both primary and secondary are rare
Secondary is the most common type
Typically 60-70yo
Presents as a palpable mass or diffuse thickening of the breast
Axillary lymph nodes are enlarged in a substantial minority
BREAST LYMPHOMA path
Primary
- Typically a B-cell type non-Hodgkin lymphoma, usually diffuse large B cell lymphoma
It must:
- Disease should be in the breast or in close proximity to breast tissue
- No previous history of extramammary lymphoma
- No evidence of widespread disease, except ipsilateral axillary LN may be involved
Secondary
- More frequently NHL than HL
PAPILLARY CARCINOMA breast IS AND IMAGING
Papillary carcinoma of the breast is a rare ductal breast malignancy
Typically present in postmenopausal patients, 63-67yo
May manifest clinically as a palpable mass or nipple discharge
Approximately 50% arise in the retro-areolar/subareolar region of the breast
Better prognosis than commoner types of malignancy
Imaging
- The most common mammographic pattern is a round, oval or lobulated mass
- The margins are usually circumscribed, but may be obscured or indistinct
- Accompanying microcalcifications or a dilated ductal pattern may be present
US
- Hypoechoic and solid mass, often with posterior acoustic enhancement
- Complex cystic and solid masses may be evident
- Relatively vascular, often colour flow components
Galactography - may be helpful for patients with nipple discharge
May demonstrate ductal obstruction, filling defects or focal/diffuse ductal wall irregularity
MRI
Usually round or oval mass with well-defined margins
PAPILLARY CARCINOMA breast PATH
May be solitary or multiple
Several subtypes:
- Papillary ductal carcinoma in situ - features of intraductal carcinoma
- Intracystic papillary carcinoma - if a cystic component is present
- Solid papillary carcinoma - if no cystic component is detected
Typically well-circumscribed, often contain haemorrhagic and cystic areas
Characterised by a frond-like growth pattern on a fibrovascular core lacking a myoepithelial layer
Four potential cellular patterns:
- Cribriform
- Compact columnar epithelial
- Stratified spindle cell
- Transitional form - similar to urothelial tumours
PAPILLOMA is
The most common mass within the milk ducts of the breast
Benign, but may contain atypia or carcinoma
Epidemiology:
Exclusively women
Classically 40-50yo
Often asymptomatic or with nipple discharge
Discharge is more common in central vs peripheral papillomas
Bloody discharge may have a higher association with atypical or malignant lesions
PAPILLOMA path
Proliferative tumours originating from the walls of the milk ducts, typically growing within the ducts and tending to cause local ductal obstruction
Composed of monotonous epithelial/myoepithelial cells encompassing a papillary fibrovascular core
Characteristically grow to form smooth well-circumscribed nodules
Typically small <10mm
Most commonly ~3.5cm from the nipple, but can be anywhere from anterior to posterior depth
The central question is whether there is any evidence of cellular atypia
- Any > surgical excision
Can occur adjacent to other significant lesions e.g. atypical ductal hyperplasia or DCIS
May be solitary or multiple
Multiple = more than 5, papillomatosis
Increased malignancy
Subtypes
Sclerosing papilloma of the breast
Location:
Central - within a major subareolar duct, often solitary
Peripheral - with the terminal duct lobular unit, may be multiple
PAPILLOMA imaging
Mammogram
Frequently normal
Solitary or multiple dilated ducts, and a circumscribed benign-appearing mass, or a cluster of calcifications
Galactography
Filling defects, may outline the number, location, extent and distance from the nipple
US
A well defined solid nodule or intraductal mass which may either fill a duct or be partially outlined by fluid - either within a duct or by forming a cyst
Colour doppler will demonstrate a vascular stalk
MRI
T2 bright
Round ~75%, irregular ~25%
Spiculated margin suggests malignancy
90% are solid
HEREDITARY BREAST AND OVARIAN CANCER SYNDROME
Caused by a mutation to either BRCA1 or BRCA2 genes
These are tumour suppressor genes that encode proteins involved in DNA repair
- Located on chromosome 17 and 13 respectively
The risk of specific cancer types varies depending on the mutation
BRCA1
Breast cancer
Male breast cancer
Ovarian
Prostate
Pancreatic
Colorectal - 5x increase if <50yo
Primary fallopian tube cancer
BRCA2
Breast cancer
Male breast cancer
Ovarian cancer
Prostate cancer
Pancreatic cancer
Colorectal cancer
PHYLLOIDES is and imaging
A rare fibroepithelial tumour of the breast, which has some resemblance to a fibroadenoma
Typically a large, fast growing mass that forms from the periductal stroma of the breast
Predominantly a tumour of adults women, age 40-60yo
- About 15yrs older than the typical age of a patient with a fibroadenom
A locally invasive tumour . Treatment is usually with surgical excision
Imaging
Can be quite large at presentation
Typically a non-specific large rounded oval or lobulated, generally well circumscribed
Calcification may be seen in a very small proportion
US
- Non-specific
- Inhomogenous solid appearing mass
- Contain single or multiple, round or cleft-like cystic spaces and demonstrate posterior acoustic enhancement which is strongly suggestive of a phyllodes
- Vascularisation is usually present in the solid component
Indistinguishable from fibroadenomas on mammo and US
PHYLLOIDES path
Leaf-like pattern of growth
May be benign, borderline or malignant depending on the histologic features including stromal cellularity, infiltration at the tumour edge and mitotic activity
Can resemble a giant fibroadenoma with both epithelial and stromal components
INFLAMMATORY BREAST CANCER is
A relatively uncommon but aggressive form of invasive breast carcinoma with a characteristic clinical presentation and unique radiographic appearances.
Inflammatory carcinomas account for 1-4% of all breast cancers, typically occurring in women between the 4th to 5th decades.
Mimics mastitis: enlarged breast, indurated, erythematous, warm and may be tender and painful
The skin is thickened and oedematous, classically with a “peau d’orange” appearance.
Systemic symptoms of infection are absent
While any subtype of primary breast carcinoma may be present, invasive ductal carcinoma tends to be the most prevalent histological type.
Dermal lymphatic invasion is pathognomonic of inflammatory breast cancer, but doesn’t necessarily need to be demonstrated to make the diagnosis
The presence of tumorous cells in dilated lymphatics may be present in ~80% of cases
Inflammatory breast cancer is a T4 tumour according to the standard TNM staging classification of breast cancer.
If no results with biopsy, a skin biopsy may be indicated
Tends to metastasise early
Chemotherapy before surgery or radiation therapy is the current standard treatment
INFLAMMATORY BREAST CANCER imaging
Mammographic findings include tumour mass and malignant microcalcifications.
More specifically, inflammatory changes such as extensive skin and trabecular thickening/coarsening, and/or diffusely increased breast density are important clues that should lead the radiologist to suggest the diagnosis.
US
Hypoechoic shadowing mass which can be obscured on mammo by diffusely increased breast density
Skin thickening, pectoral muscle invasion and axillary involvement
ddx
- Infective mastitis: painful breast with prominent erythematous changes and fevers
- Locally advanced invasive breast carcinoma
- Lymphomatous involvement of the breast
- Other causes of breast oedema
- Venous or lymphatic obstruction
TAKAYASU ARTERITIS general
“idiopathic medial aortopathy” or “pulseless disease”
A granulomatous large vessel vasculitis that predominantly affects the aorta and its major branches
May also affect the pulmonary arteries
Strong female predominant 9:1 and tends to affect the younger patient
Typical onset 15-30yo
TAKAYASU ARTERITIS path
Segmental and patchy granulomatous inflammation of the aorta which results in stenosis, thrombosis and aneurysm formation
Half present with an initial systemic illness, the other 50% with late-phase complications
Two phases of the disease:
Pre-pulseless phase – characterised by non-specific symptoms
Pulseless phase – presents with limb ischaemia or renovascular hypertension
Chronically, there is inflammatory and obliterative changes in the aorta and its branches
Cardiac complications can occur in up to 60% of cases
Pulmonary artery involvement can occur in some situations
TAKAYASU ARTERITIS classification
Type 1 – solely the aortic arch branches
Type 2
A – ascending portion and/or at the aortic arch +/- branches of the aortic arch
B – descending thoracic aorta +/- ascending or aortic arch + branches
Type 3 – thoracic and abdominal aorta distal to the arch and its major branches
Type 4 – sole involvement of the abdominal aorta and/or renal arteries
Type 5 – generalised involvement of all aortic segments
POLYARTERITIS NODOSA general
A systemic inflammatory necrotising vasculitis that involves the small to medium-sized arteries
More common in males, typically presents ~5th- 7th decade
Associations: Hepatitis B and C
Presents with systemic or focal symptoms
Renal arteries are the most commonly involved, with pulmonary circulation typically spared
Renal 80-90% - prominent site and major cause of death
Cardiac ~70%
GIT 50-70%
Hepatic 50-60%
POLYARTERITIS NODOSA path
Transmural and necrotising inflammation of medium-sized arteries – mostly involving part of the circumference which causes weakening of the wall leading to microaneurysm formation and subsequent focal rupture
Predilection for branch points
Fibrinoid necrosis of vessels promotes thrombosis of vessels followed by infarction of the tissue supplied
Fibrous thickening and mononuclear infiltration occur at a later stage
Different stages of inflammation can occur in the same vessel at different points.
PANCA – may correlate with disease activity
GIANT CELL ARTERITIS general
A common granulomatous vasculitis, affecting medium to large-sized arteries.
Also known as temporal arteritis due to its propensity to involve the extracranial ECA branches –esp superficial temporal artery
The most common primary systemic vasculitis, typically in older individuals >50, with a peak ~70-80
Female predilection
Associations: polymyalgia rheumatica – seen in ~50%
Markers:
Serum erythrocyte sedimentation rate – markedly raised
Serum C-reactive protein (CRP) - often markedly raised
Complications:
Thoracic aortic aneurysm – commonly ascending aorta
Aortic dissection – more commonly the ascending aorta
Vision loss
Location:
Any medium – large sized vessel, affecting the aorta ~20% of cases and its major branches, particularly the extracranial branches of the carotid artery
Treatment: corticosteroid therapy and aspirin
Differentials:
Takayasu arteritis – young patients, and more proximal vessels
Atherosclerotic disease
GIANT CELL ARTERITIS path
Similar to others
Granulomatous inflammation of arteries with infiltration predominantly by histiocytes, lymphocytes and multinucleated giant cells
Characteristic multinucleated giant cells are only found in ~50% of cases
Areas of normal superficial temporal artery interspersed within inflamed sections – skip lesions in 8-28%
4 main histological patterns:
Adventitial pattern – inflammatory cells restricted to the adventitia
Adventitial invasive pattern – local invasion of the media with preservation of the intima
Concentric bilayer pattern – inflammatory infiltration of adventitia and intima with preservation of the media
Panarteritic pattern – inflammatory infiltrates in the three arterial layers
FIBROMUSCULAR DYSPLASIA general
A heterogenous group of vascular lesions is characterised by an idiopathic, non-inflammatory, non-atherosclerotic angiopathy of small and medium-sized arteries
Prevalence is unknown, typically young women 3:1
Diagnosed age 30-50yo
Presentation:
Hypertension, renal impairment – renal artery stenosis
CNS symptoms
Angina/MI/sudden death due to coronary artery
Symptoms of mesenteric ischaemia
Exact cause is unknown
Any layer of vessel wall can be affected – intima, media or adventitia
There is an absence of inflammatory cells
5 categories, according to vessel wall layer involvement:
Intima 5% Intimal fibroplasia
Media 90-95%
Medial dysplasia ~70%, most common
Perimedial (subadventitial) fibroplasia 15-20%
Medial hyperplasia 8-10%
Adventitia – rare, Adventitial fibroplasia 1%
The outcome is arterial stenoses
Typically a string of beads appearance
Weakens the vessel and predisposes to dissection
Location:
Renal arteries
Cervicoencephalic arteries
Iliac arteries
Coeliac trunk and mesenteric arteries
Subclavian and axillary arteries
GRANULOMATOSIS WITH POLYANGIITIS general
a multisystem necrotising non-caseating granulomatous c-ANCA positive vasculitis affecting small – medium sized arteries, capillaries and veins
Predilection for the respiratory system and kidneys
Slight male predilection, and onset approximately 50yo
Diagnostic criteria: at least two of the following
- Positive biopsy for granulomatous vasculitis
- Urinary sediment with red blood cells
- Abnormal chest radiograph
- Oral or nasal inflammation
An immune-mediated vascular injury
In 90% of cases, cANCA is positive and levels correlate with disease activity.
The classic triad of organ involvement:
- Lung – 95%
- upper respiratory tract/sinuses - 75- -90%
Kidneys – 80%
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME general
Small to medium vessel necrotising pulmonary vasculitis
Also classified under the spectrum of eosinophilic lung disease
Incidence typically ~3rd - 4th
Almost all patients have asthma and eosinophilia.
Markers: p-ANCA ~75%
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME dx criteria
Requires a positive biopsy for vasculitis, and at least 4/6 criteria:
Asthma
Blood eosinophilia
Mono/polyneuropathy
Transient pulmonary infiltrates
Paranasal sinus abnormalities - pain or radiographic abnormality
Presence of extravascular eosinophils on a biopsy specimen
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME pathology
Can be histologically identical to classic polyarteritis nodosa or microscopic polyangiitis
Around 25% will have renal disease
Biopsy of parenchymal opacities may show a mixture of necrotising granulomas, eosinophilic pneumonia and granulomatous vasculitis
BEHCETS general
A multisystemic and chronic inflammatory vasculitis of unknown aetiology
Mean age 20-30yo
Most prevalent in the Mediterranean region, middle east and east Asia
The highest incidence is in turkey
Men 2-5x: 1 female
The underlying process is vasculitis and perivascular inflammatory infiltrates affecting vessels of differing sizes in various organs
BEHCETS assoc and clinical
Associations:
- HLA-B51
- Factor V Leiden mutation
- Superficial thrombophlebitis
The classic clinical triad:
- Oral ulceration
- Genital ulceration
- Ocular manifestation
BEHCETS distribution
Cardiovascular manifestations 5-30% of cases
- Thickening of the aorta and SVC
- Inflammation of the veins leads to thrombosis, while arterial involvement includes arterial narrowing and aneurysmal dilatation
Thoracic manifestations 1-8%
- Pulmonary artery aneurysm: fusiform to saccular
- Subpleural infiltrates
GI manifestations 10-50%
CNS 10-50%
MSK > 50% develop articular disorders or arthralgia
VARICOSE VEINS general
Dilated tortuous superficially located venous channels that accompany the superficial veins of the upper or lower limbs
More common in women than men, and usually lower limb
Risk factors:
- Pregnancy
- Older age
- Female
- Prolonged standing
VARICOSE VEINS pathology
Incompetent saphenofemoral junction resulting from saphenofemoral valve insufficiency
Results in regurgitation of blood during expiration and consequently raises the venous pressure in the great saphenous and other superficial veins
Incompetent perforators are another causative factor when destruction of the valves inside the perforators allow the blood to move from the deep to superficial system and consequently increases the superficial venous pressure
MARFAN SYNDROME general
A multisystem connective tissue disease caused by a defect in the protein fibrillin 1 - encoded by the FBN1 gene
No recognised gender or racial predilection
Clinically:
General
Tall stature, long arm span, joint laxity
Spine
High arched palate, scaphocephaly, kyphoscoliosis
Hands
Arachnodactyly
Pelvis
Pes planus, hallux valgus, club foot
Chest wall deformity
Pectus excavatum, pectus carinatum
Ocular
Ectopia lentis, myopia
Cardiovascular
Aortic regurgitation or mitral regurgitation, dolichoectasia
MARFAN SYNDROME pathology
A multisystem connective tissue disease caused by a defect in the protein fibrillin 1 - encoded by the FBN1 gene
Majority are autosomal dominant, with high genetic penetrance and variable expression
Microscopic: the arterial walls may show cystic medial necrosis
FIBRINOID NECROSIS
Also known as lipohyalinosis
A disease affecting the small cerebral arteries associated with lacunar infarction and deep white matter changes related to small vessel chronic ischaemia
Histopathological landmarks:
Irregular fibrosis and hyaline of small cerebral arteries associated with leakage of plasma proteins
Often caused by chronic hypertension
Fibrinoid necrosis and/or endothelial dysfunction causing local inflammation leading to vascular narrowing
AORTIC DISSECTION pathology
When blood enters the medial layer of the aortic wall through a tear or penetrating ulcer in the intima and tracks longitudinally along the media
Majority occur in elderly hypertensive patients
Pathology:
The normal lumen lined by intima (true lumen) and blood channel in the media (false lumen)
Causes:
Hypertension - medial degeneration
Inherited connective tissue disorders - medial degeneration
Atheroscerlosis - penetrating ulcer
Vasculitis - inflammation
Pregnancy - unknown
HYPERALDOSTERONISM is and path
Primary hyperaldosteronism: excess aldosterone production
Occurs secondary to:
- Adrenal cortical adenoma ~35%
- Bilateral adrenal hyperplasia ~60%, or
- Adrenal carcinoma - rare
Conn syndrome: when primary hyperaldosteronism is due to an aldosterone-producing adenoma
Presentation:
- Diastolic hypertension
- Metabolic alkalosis
- Hypokalaemia
- Others: muscular weakness, paraesthesias, headache, polyuria and polydipsia
Pathology:
Differentiated from secondary hyperaldosteronism by measuring serum renin
- Primary - low renin levels
- Secondary - high renin levels
PHEOCHROMOCYTOMA assoc
Associations: majority are sporadic. 5-10% have an underlying condition
Multiple endocrine neoplasia type II - both MEN IIa and IIb
- Account for 3%, almost never extra-adrenal, always bilateral
Von Hippel-Lindau disease
Neurofibromatosis type I
Sturge-weber syndrome
Carney triad
Tuberous sclerosis
PHEOCHROMOCYTOMA path
A type of paraganglioma
Catecholamine-secreting tumours derived from chromaffin cells
Typically demonstrate a nesting (Zellballen) pattern on microscopy
Composed of well-defined clusters of tumours cells containing eosinophilic cytoplasm separated by a fibrovascular stroma
Various scores are used (PASS/GAPP) to predict differentiation and likelihood of metastases
Location: most frequently arise from the chromaffin cells of the adrenal medulla
- 10% are not located in the adrenal glands
- Extra-adrenal tumours are more likely to be malignant and metastasise
- Can be found along the sympathetic chain, as well as in the urinary bladder and Organ of Zuckerkandl
A rare but classical cause of uncontrolled secondary hypertension
Investigate with collection of urinary catecholamines
CUSHING SYNDROME is
Due to the effects of excessive glucocorticoids, which may be exogenous or endogenous
Cushing disease: glucocorticoid excess solely due to an adrenocorticotropic hormone-secreting pituitary adenoma
Cushing syndrome: encompasses all aetiologies of glucocorticoid excess
Presentation:
Round ‘moon-shaped’ face
Progressive centripetal obesity and weight gain
Prominent supraclavicular and dorsocervical fat pads “buffalo hump”
Purple skin striae
Easy skin bruising
Acanthosis nigricans
Proximal myopathy
Depression and other mood disorders
Osteoporosis
Hypertension
Hyperglycaemia and development of overt diabetes mellitus
Immunosuppression and recurrent infections
Signs of androgen excess: hirsutism/acne/changes in libido etc in females, but no so in men since the adrenal glands aren’t a major source of androgens
Investigation requires measurement of both cortisol and ACTH over a 24hr period - cortisol release is intermittent
Complications: bilateral adrenalectomy in a patient with Cushing disease can lead to development of Nelson syndrome
CUSHING SYNDROME path
Due to the effects of excessive glucocorticoids, which may be exogenous or endogenous
Source
- Adrenal adenoma 20%
- ACTH-secreting tumour 80%
- Pituitary adenoma 85%
- Ectopic production 15%
- Lung cancer - small cell lung cancer, broncial carcinoid
- Small cell cancers of the thymus
- Pancreatic neuroendocrine tumour
- Phaeochromocytoma
- Benign ovarian tumours
- Primary pigmented nodular adrenal dysplasia (PPNAD) - rare
- Adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH) - rare
- Corticotropin-releasing hormore-secreting tumour - very rare
- Hypothalamic tumours
- Ectopic production
ADRENAL INSUFFICIENCY is and path
Inadequate secretion of corticosteroids (glucocorticoids and mineralocorticoids)
Two types:
- Primary adrenal insufficiency - Addisons disease. From partial or complete destruction of the adrenal cortex
- Secondary adrenal insufficiency - due to lack of stimulation of the gland
Presentation:
- Acute - fever, backpain, hypotension, weakness
- Chronic - progressive lethargy, weakness, cutaneous pigmentation, weightloss
Biochemistry:
Low sodium, potassium, azotemia, hypercalcaemia, hypoglycaemia
Pathology:
Primary
Idiopathic autoimmune disorders - 80%
- Most common in developed countries
Granulomatous disease: TB and sarcoid
RENAL PAPILLARY NECROSIS is path and causes
Ischaemic necrosis of the renal papillae
Necrosis occurs in the medullary pyramids
Can present acutely or chronically
Calyceal or ureteral obstruction by sloughed papillae manifests with flank pain, haematuria and varying degrees of renal impairment
Anuria or oliguria may be present in the fulminant stage if renal failure develops
Pathology:
Characterised by necrosis and sloughing of papillary tissues which may result in a substantial loss of renal function
Causes:
NSAID
NSAID
Sickle cell disease
Acetaminophen (paracetamol) and phenacetin
Infection e.g. pyelonephritis, tuberculosis
Diabetes mellitus or dehydration
RENAL CORTICAL NECROSIS is and path
Occurs as a result of severe systemic illness in a variety of settings, and can result in permanent renal impairment
Pathology:
Aetiology:
Severe haemodynamic shock
Microangiopathic haemolysis
- Haemolytic uraemic syndrome
Renal transplantation
ARPKD is
Enlarged echogenic kidneys with multiple small cysts
One of the commonest inheritable infantile cystic renal diseases
No gender or racial predilection
Age of presentation is variable and divided into perinatal, neonatal, infantile and juvenile forms
Inverse relationship with the liver:
The worse the kidneys, the better the liver
The younger the presentation, the more the renal disease predominates
ARPKD path
Results from a mutation in the PKHD1 (polycystic kidney and hepatic disease) gene located on chromosome 6p
Results in bilateral symmetric microcystic disease occurring in the distal convoluted tubules and collecting ducts
The number of ducts involved determines the age of presentation
Perinatal type - most common
Oligohydramnios and pulmonary hypoplasia
75% die within 24hrs of delivery
Minimal hepatic fibrosis
Neonatal type - minimal hepatic fibrosis
Infantile type - moderate periportal fibrosis
Juvenile type - gross hepatic fibrosis
Portal hypertension with splenomegaly and portosystemic varices
Associations:
Caroli disease
Multiple biliary hamartomas
Congenital hepatic fibrosis
ADPKD is
The most common hereditary cause of ESRF
A number of conditions are recognised as being associated with ADPKD:
Cerebral berry aneurysms
- 6-16% - 16% if a family history of aneurysms, 6% if no family history
Intracranial dolichoectasia 2-3%
Hypertension - up to 80%
Colonic diverticulosis
Small bowel diverticula
Bicuspid aortic valve
Mitral valve prolapse
Aortic dissection
Multiple biliary hamartomas
Cysts in other organs
- Liver - most common, 75% by age 60
- Ovaries
- Spleen
- Seminal vesicles - 60% by age 40
- Prostate
- Pancreas - more common in VHL
Complications
Renal:
ESRF
Recurrent UTIs
Cyst haemorrhage
Cyst rupture
No increased risk of RCC, unless related to dialysis
Distant complications:
SAH
Aortic dissection
ADPKD path
Macroscopically demonstrated cysts of variable size in both the cortex and medulla
Autosomal dominant pattern of inheritance
Three genes with slightly different phenotypes:
PKD1
Chromosome 16p
85% of cases
Encodes polycystin-1
Presentation is earlier and more likely to progress to end stage renal failure
PKD2
Chromosome 4q
15% of cases
Encodes polycystin-2
Less severe
GANAB - rare
Chromosome 11q13
Liver cysts are common +/- hepatic dysfunction
Mild renal disease, ESRF unusual
The main abnormality is in the cilia-centromere complex of tubular epithelial cells
The defect results in cystic dilatation of the renal tubules (of all parts of the nephron) in a minority of nephrons
The cysts are variable in size, and result in compression of the remainder of the kidney, resulting in increased renin and erythropoietin secretion and gradual renal dysfunction
ALLAGILIE SYNDROME is
Arteriohepatic dysplasia
A congenital genetic multisystem disorder
Infants typically present with symptoms relating to the liver - one of the most common causes of hereditary cholestasis
Genetics:
Inherited in an autosomal dominant fashion, with a mutation of the JAG1 (90%) and NOTCH2 genes (1-2%), located on the short arm of chromosome 20
There is a diverse spectrum of disease:
Hepatic
Paucity +/- stenosis of the intrahepatic ducts that can lead to cirrhosis and hepatic failure
Renal
Variable, including cystic kidney disease, small kidneys, echogenic kidneys and nephrocalcinosis
Ocular
Posterior embyotoxon
Otic
Hypoplasia of the posterior semicircular canal
Skeletal
Butterfly type vertebrae (~50%)
Facial
Triangular facial
Cardiovascular
Coarctation of the aorta
Peripheral pulmonary artery stenosis
MCDK is and assoc
A type of non-heritable paediatric cystic renal disease
Results in multiple cysts being formed in utero in the affected kidney
Typically unilateral, with a predisposition for the left kidney.
Bilateral has a higher incidence in females
Can be a common cause of agenesis, following complete involution during childhood
Associations:
Vesicoureteric reflux - most common, seen in up to 20%
Pelviureteric junction obstruction
Ureteral ectopia
Vesicoureteric junction obstruction
Ureterocele
MCDK path
No functioning renal tissue, but replacement with multiple cysts
Two types have been described:
Pelvi-infundibular
Most common
Multiple small non-communicating renal cysts - representing the dilated calyces
Atresia of the ureter and renal pelvis
May sometimes regress spontaneously
Hydronephrotic-obstruction
Dominant cyst present in the renal pelvis
MEDULLARY SPONGE KIDNEY is
A sporadic condition where the medullary and papillary portions of the collecting ducts are dysplastic and dilated
Most patients are asymptomatic during life, incidentally diagnosed
Alternatively, patients may present with a complications, including:
- Urinary tract infection
- Haematuria
- Urolithiasis/ureteric calculi
Represents a developmental defect affecting the formation of collecting tubules and resulting in cystic dilatation of medullary and papillary portions of the collecting ducts
Associations:
- Ehlers-Danlos syndrome
- Congenital hemihypertrophy/ Beckwith-Wiedemann syndrome
- Caroli disease
Medullary nephrocalcinosis occurs in the majority of cases
- May be unilateral or bilateral and affect a single or multiple pyramids
TUBEROUS SCLEROSIS IS/PATH
Phakomatosis characterized by the development of multiple benign tumours of the embryonic ectoderm
Most are sporadic
The pathognomonic triad – only seen in 30%
Seizures: absent in ¼ of individuals
Intellectual disability: up to half have normal intelligence
Adenoma sebaceum: only present in ~¾ of patients
Pathology:
Spontaneous mutations account for 50-66%, the rest are inherited as an autosomal dominant condition
Two tumour suppressor genes are involved:
TSC1 – encoding hamartin, on chromosome 9q32-34
TSC2 – encoding tuberin, on chromosome 16p13.3
TUBEROUS SCLEROSIS manifestations
Neurology:
Cortical/subcortical tubers: 50% in the frontal lobe
- High T2, low T1 – 10% enhance, frequently calcify
Subependymal hamartomas – 88% associated with calcification
- Variable signal, high T1, iso-high T2
- Variable enhancement
- Only serial growth is reliable to differentiate from SEGA
Subependymal giant cell astrocytomas
- Peak occurrence 8-18yo
White matter abnormalities
-Radial bands – specific for TS
- Variable appearance – nodular, ill-defined, cystic and band-like lesions seen
Retinal phakomas
Rarer findings:
Cerebellar atrophy
Infarcts
Arachnoid cysts
Chordoma
Abdominal
Renal angiomyolipomas
- TS accounts for 20%
- Seen in 55-75% of patients with TS
- Tend to be multiple, large and bilateral
- Fat may not be visible in up to 4.5%
Renal cysts: TSC2 gene is located adjacent to the PCKD1 gene
- 18-53% of patients with TS
Renal cell carcinoma and oncocytomas
- RCC tends to occur earlier
Retroperitoneal lymphangiomyomatosis
- Histologically identical to pulmonary LAM
- Retroperitoneal cystic lesions
- Chylous ascites, enlarged lymph nodes, dilatation of the thoracic duct
GI polyps
Pancreatic neuroendocrine tumours
Hepatic angiomyolipomas
Thoracic
Lymphangioleiomyomatosis (LAM)
- Rare
- 25-40% of female pts with TS
- Indistinguishable from sporadic LAM
- Pneumothorax and chylous pleural effusions are common
- ~80% 10yr survival
Multifocal micronodular pneumocyte hyperplasia (MMPH)
- Rare
- Multicentric, well-demarcated nodular proliferation of type II pneumocytes
- Benign, non-progressive
- Differentials: miliary opacities
Cardiac rhabdomyomas
- Benign striated muscle tumour characterised by the presence of spider cells
- Seen in 50-65% of pts with TS
- 40-80% of patients with cardiac rhabdomyomas have TS
- Multiple or single
- Typically involve the ventricular septum
- Occur before the age of 1yo (75%)
- Spontaneous regression in 70% of children by age 4
Thoracic duct and aortic/pulmonary artery aneurysm
Myocardial fatty foci
MSK
Sclerotic bone lesions 46-66%
Hyperostosis of the inner table of the calvaria
Periosteal new bone
Scoliosis
Bone cyst
Skin
Cutaneous lesions in ~95% of cases
Facial angiofibromas
Hypopigmented macules – ash leaf spots
Fibrous plaques on forehead
Confetti lesions
VON HIPPEL LINDAU is
Numerous benign and malignant tumours in different organs, due to mutations in the VHL tumour suppressor gene on chromosome 3
Most are diagnosed with their first tumour in early adulthood
Classi
Can be according to the clinical phenotypes
Type 1 – low risk pheo, but higher risk CNS haemangioblastoma, RCC, pancreatic cyst and pNET
Type 2A – high risk pheo, low risk RCC
Type 2B – high risk pheo and RCC
Type 2C – high risk pheo only
VON HIPPEL LINDAU manifestations
Abdominal:
Renal cell carcinomas
- Usually clear cell and bilateral
- 70% lifetime risk
- Present earlier in pts with VHL
Renal cysts
- Often bilateral and multiple
- Can be simple, complex or cystic RCC
Renal angiomyolipomas
Adrenal:
Phaeochromocytomas 25-30%
Extra-adrenal phaeochromocytoma/paraganglioma
Pancreas – may be the earliest manifestation
- Pancreatic cysts ~40%
- Pancreatic neuroendocrine tumours
- ~12.5% of patients
- Usually non-functional
- Frequently multiple
- Pancreatic serous cystadenomas: ~12.5% of patients
- Pancreatic adenocarcinomas
Liver
Liver cysts
Urogenital
- Epididymal cysts
- Papillary cystadenoma of the epididymis
- Broad ligament cystadenomas
CNS
Haemangioblastomas ~70%
- Cerebellar ~60%
- Spinal cord ~30% - most commonly in the cervical and thoracic cord
- brainstem
Choroid plexus papilloma
Head and neck
Retinal haemangioblastoma
- Most common presenting feature
- Vision loss
Endolymphatic sac tumours
- Bilateral in 30%, pathognomonic for vHL
ANGIOMYELOLIPOMA is./path/assox
Sporadic, or as part of a phakomatosis 80:20% respectively
Also associated with:
TS – predominantely
Von Hippel-Lindau syndrome
Neurofibromatosis type 1
These usually larger, earlier and more numerous
More likely to be fat-poor
Often incidentally found
Symptomatic presentaiton is with spontaneous retroperitoneal haemorrhage
Pathology:
- Perivascular epithelioid cells tumour group (PEComas) and are composed of variable amount of three components:
- blood vessels lacking elastic tissue,
- Plump spindle cells, and
- Adipose tissue
Variants:
- Typical – triphasic
- Atypical – monophasic or epithelioid
- Epithelioid AML often with nuclear atypia – may mimic RCC
Larger AMLs resect of embolise.
ONCOCYTOMA is and path
Relatively benign renal tumours
6th-7th decade presentation, with a 2:1 male predilection
Pathology:
Macroscopic:
= Macroscopically tan in colour, similar to renal cortex, or dark brown
= A rim of compressed normal renal parenchyma is sometimes seen, forming a pseudocapsule
Microscopic
= Thought to originate from the intercalated tubular cells of the collecting tubules
= Composed of large, swollen eosinophilic cells of protuberant mitochondrial components
= Necrosis is usually absent
Associations:
Birt-Hogg-Dube
Tuberous sclerosis
CLEAR CELL RCC is and path
The most common type of RCC
Usually ~60yo, but younger onset with von-Hippel Lindau.
Pathology:
- 75-80% of RCC cases.
- Sporadic in >95%, but 5% are familial - VHL
- Loss of sequences on the short arm of chromosome 3, usually by deletion or unbalanced translocation resulting in loss of 3p12-3p26
- The region containing the sequence for the VHL gene (a tumour suppressor gene)
- The gene increases expression of proteins of the ubiquitin ligase complex
- Ubiquitin ligase complex normally identifies and tags proteins for destruction
- Ubiquitin mediated degradation of hypoxia inducible factor 1 (HIF-1) - A proangiogenic factor normally expressed in hypoxic environments
- So, the loss of the VHL allele results in increased levels of HIF-1 and resulting increase in pro-angiogenic factors such as VEGF, PDGF, TGF-alpha, TGF-beta, leading to cellular dysplasia and ultimately neoplasia
Macroscopic: yellowish, golden appearance due to high lipid content
Microscopic: characterised by -
- Large cells with uniform appearance
- Abundant clear cytoplasm rich in glycogen and lipid
- High vascularity
Compared to other forms of RCC, it is said to have:
- An exophytic appearance
- A greater degree of enhancement on the corticomedullary and nephrographic phases on multiphasic CT (compared to papillary cell carcinoma)
- A more heterogenous appearance (due to multiple areas of internal necrosis, cystic change or haemorrhage
PAPILLARY RCC is and path
The second most common histological subtype of RCC
May account for 13-20% of all RCC - slightly increased male predilection
Associations:
- Hereditary leiomyomatosis and RCC
- Hereditary papillary renal cell cancer type 1
Two subtypes:
Type 1
- Papillae covered by a single layer of cuboidal or low columnar cells with scanty cytoplasm and low grade nuclei
- Carry a better prognosis than type II tumours
Type 2
- higher nuclear grade and contain more than one layer of cells with abundant eosinophilic cytoplasm
- Mostly unilateral, the subtype is considered most common to result in bilateral RCCs
Less vascular than the more common clear cell subtype, showing overall hypoenhancement compared to the adjacent normal renal cortex - particularly in the corticomedullary phase
Can be difficult to differentiate from hyper-attenuating cysts
CHROMOPHOBE RCC is
One of the less common subtypes of renal cell carcinoma
The least common major subtype of RCC, occurring 5% of the time
Arises from intercalated cells of collecting ducts - called chromophobe because the tumour cells are less translucent than clear cell renal cell carcinomas during staining
Similar origin to oncocytomas.
“spoke wheel pattern of enhancement”
MEDULLARY RCC
Rare and highly aggressive variant
Centered in the renal medulla
Occurs almost exclusively in adolescent and young adult blacks with sickle cell trait or haemoglobin SC disease
- But not with homozygous haemoglobin SS sickle cell disease
Typically affects patients around the age of 20yo, range of 10-39yo
Pathology:
- Epithelial origin
- Thought to arise at the renal pelvic-mucosal interface
- The tumour quickly grows to fill the renal pelvis, and invade vascular and lymphatic structures
BLADDER ADENOCARCINOMA (?bladeno?) is and path
Rare, accounts for ~1% of bladder cancers. 90% are TCC
Metaplasia of the urinary bladder induced by chronic irritation or infection can lead to adenocarcinoma
Pathological types of adenocarcinoma of the urinary bladder:
- Mucinous adenocarcinoma
- Signet-ring types
- Papillary adenocarcinoma
- Not otherwise specified (NOS)
Can be subclassified as primary (2/3 are non-urachal, 1/3 is urachal) or secondary (metastases)
Aetiology:
- Persistent urachal remnant is most common
- Cystitis glandularis (secondary to bladder outlet obstruction, chronic infection and/or bladder calculi
- Schistosomiasis,
- Associated with bladder exstophy
Appearance:
- Non-urachal: diffuse bladder wall thickening
- Urachal: midline, infraumbilical soft tissue mass with peripheral calcification
BLADDER SCHISTOSOMIASIS (schistosomiapiss?) is and path
An infection caused by the Schistosoma flukeworm
Predisposes individuals to bladder SCC
Very common, particularly in Africa
Pathology:
- 5 species of the blood fluke that cause disease in humans
- Larvae are released from snails into water and penetrate human skin exposed to the infected water
- These travel to the lungs and liver of the human host, where they reside until they mature
- After maturation, the adult worms travels to the pelvic veins.
- Eggs are deposited in the bladder wall vessels and incite a granulomatous response that results in polypoid lesions
- The eggs may go on to incite a chronic inflammatory response and fibrosis, which is an important predisposing factor for SCC
Features:
- Acute - nodular, bladder wall thickening is observed
- Chronic - contracted, fibrotic, thick-walled bladder with calcifications
- Calcifications are typically curvilinear and represent the large numbers of calcified eggs in the bladder wall
- A mass may be secondary to inflammation or complicating carcinoma, typically SCC
- Calcifications can extend to the ureters
BLADDER SCC is
Rare, accounts for only 3-8% of all bladder cancers
The most common type of non-TCC bladder cancer
Most commonly seen in the setting of chronic irritation, e.g. from bladder stones
Tend to be solitary and large at the time of detection, with muscular wall invasion reported
Risk factors:
- Antecedent infection with Schistosomiasis
- Chronic irritation e.g. indwelling catheter, bladder calculi
- Chronic infection
- Intravesical BCG
BLADDER TCC is n path
The most common primary malignancy of the urinary tract
May be found along its entire length, from renal pelvis to the bladder
Urothelial cell carcinoma can be used to described malignant bladder carcinomas of epithelial origin, since 25-37% of transitional cell carcinomas contain a mixture of histologic tissue types
Typically a tumour of older patients, with the average age being ~65 and typically >60
Strong male predilection
Chemical compounds implicated:
- Smoking
- Azo dye/pigment manufacturing
- Cyclophosphamide - also haemorrhagic cystitis and bladder fibrosis
- Thorotrast
- Phenacetin
- Aristolochic acid - typically results in upper urinary tract tumours
- Heavy caffeine consumption and artificial sweeteners
Additionally, stasis acts to prolong exposure of the urothelium to any carcinogens in the urine - so horseshoe kidney/calculi/ureteral pseudodiverticulosis/ureteritis cystica
Distribution:
- Renal pelvis - uncommon ~2-3%
- Ureter - least common ~1%
- Bladder - most common ~97%
Pathology:
Two main morphological patterns:
Papillary
- Broad base with many frond-like papillary projections
- Tend to be low grade and invasion beyond the mucosa is a late feature
Non-papillary
- Sessile or nodular tumours
- Tend to be high grade with early invasion beyond the mucosa
BLADDER RHABDOMYOSARCOMA is n path
Uncommon tumours occuring in pelvic organs
A disease nearly exclusive to the paediatric population
Peak incidence is 3-6yo, with a slight male predominance 2-3:1
Prostatic origin is the most common in males, and the bladder is most frequent in both
Vagina, cervix and uterus ma all be involved in females
The vagina is the most prevalent
Paratesticular tumours are the only GIT rhabdomyosarcomas that tend to occur in older children - typically adolescents
Pathology:
As with other rhabdomyosarcomas, there are 4 major subtypes:
- Embryonal
- Most common
- Botryoid variant of embryonal type
- Most frequent to affect the bladder
- Alveolar
- Undifferentiated
Barrett’s oesophagus:
Distal stratified squamous mucosa is replaced by metaplastic specialised (intestinalised columnar epithelium)
30x risk of developing oesophageal adenocarcinoma
The annual risk of developing adenocarcinoma depends on the degree of histological dysplasia
OESOPHAGEAL VARICES are
Dilated submucosal veins of the oesophagus
An important portosystemic collateral pathway
Epidemiology:
- Present in ~50% of pts with portal hypertension
- Occur with greater frequency in pts with more severe cirrhosis
- ~40% Child Pugh A patients
- ~85% Child Pugh C patients
Presentation:
- Asymptomatic until a variceal heamorrhage - yearly rate of 5-15%
- Present with upper GI haemorrhage: haematemesis, melaena
- The primary predictor is variceal wall tension: diameter and pressure
- Patients will have stigmata of portal hypertension and cirrhosis
Treatment:
- Primary prevention is the mainstay - pharmacological (beta blockers) or endoscopic variceal ligation
OESOPHAGEAL VARICES path
Uphill varices - the most common form
- Typically from portal hypertension, as a collateral between the portal vein and SVC
- Typically occur in the lower third of the oesophagus
- Commonly co-occur with gastric varices (less common)
- There is extension of the oesophageal varices along the lesser curvature
- Can also have paraoesophageal varices - varices of the adventitial oesophageal veins
Aetiology:
- Cirrhosis
- Budd-Chiari syndrome
- Primary biliary cholangitis
- Primary sclerosing cholangitis
Downhill varices - relatively rare
- Due to SVC obstruction, as part of the superior vena cava syndrome
- Typically in the upper 1/3, although can span the entire oesophagus
- Do not co-occur with gastric varices due to a different pathophys
- Relatively lower bleeding risk
OESOPHAGEAL WEB is, path and assoc
An oesophageal constriction caused by a thin mucosal membrane projecting into the lumen
Tend to affect middle-aged females
Pathology:
- More commonly occur in the cervical esophagus near cricopharyngeus muscle than in the thoracic oesopahgus
- Anterior wall, never posterior wall
Associations:
- Plummer-Vinson syndrome
- Graft-vs-Host disease
- GORD
Treatment:
- Balloon dilatation
- Bougienage during endoscopy
BARRETS OESOPHAGUS is and path
A term for intestinal metaplasia of the oesophagus
Considered a precursor lesion for adenocarcinoma
Epidemiology:
- Thought to have a prevalence of 3-15% in patients with reflux oesophagitis
- Mean age at diagnosis 55y
Risk factors:
- Male
- Tobacco intake
- Central obesity
- White race
- Scleroderma - ~37% of patients
Asymptomatic, discovered in the workup for GORD
Pathology:
- Progressive metaplasia of oesophageal stratified squamous cell epithelium to columnar epithelium
- 90-100% of adenocarcinomas are thought to arise from the metaplasia
- 30x risk of developing oesophageal adenocarcinoma, but the annual risk depends on the degree of histological dysplasia
Management:
- Considered a premalignant lesion - upper endoscopy and biopsy is warranted
- If confirmed, aggressive therapy for GORD +/- endoscopic surveillance
MALToma is and path
An extranodal marginal zone B-cell lymphoma
Represents 7% of non-Hodgkin lymphoma
Average age of presentation is 60yo, with slight female predominance
Pathology:
- Arise in epithelial tissues where lymphoid cells are not usually found
- Chronic infection/inflammation has been implicated in the pathogenesis
- Less than 10% transform from low-grade to high-grade disease
MEN 1
Pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumour
MEN 2A
medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia
MEN 2B
Medullary thyroid cancer, pheochromocytoma, mucosal neuromas/gangliomas, marfanoid habitus
OESOPHAGEAL CARCINOMA is and risk factors
Relatively uncommon, tends to present with increasing dysphagia, initially to solids and progresses with obstruction of the lumen
Epidemiology:
- <1% of all cancers, 4-10% of all GI malignancies
- Male preponderance 4: 1F
Predisposing factors:
- Alcohol and smoking - for squamous cell carcinoma and adenocarcinoma
- Achalasia
- Asbestosis
- Barrett oesophagus - for adenocarcinoma
- Coeliac disease
- Ionising radiation
- Obesity - adenocarcinoma
- Plummer-Vinson syndrome
- HPV
Treatment/outcome
- Localised disease ~40% 5yr survival
- Distant metastasis ~5% 5yr survival
Complications:
- Fistula formation to the trachea 5-10%, bronchi or mediastinum
OESOPHAGEAL CARCINOMA path
Histological subtypes
- Squamous cell carcinoma of the oesophagus 81-95%
- Adenocarcinoma of the oesophagus 4-19%
- Arising from the mucosal/submucosal glands, heterotopic gastric mucosa or columnar-lined epithelium
- >90% relate to Barrett oesophagus
- Tend to occur at the GOJ
- In the western world, adenocarcinoma is as common, or slightly more common than squamous cell carcinoma
Macroscopic appearance
- Polypoid/fungating (most common)
- Sessile/pedunculated
- Lobulated surface protruding
- Irregular, polycyclic, overhanging
- Ulcerating - large ulcer niche in a bulging mass
- Infiltrating - gradual narrowing with a smooth transition
- Superficial spreading carcinoma
OESOPHAGEAL CARCINOMA staging
Tumour
0 No evidence of primary tumour, Tis: high grade dysplasia
1 - Tumour invades the lamina propria, muscularis mucosae or submucosa
2 - Tumour invades the muscularis propria
3 - Tumour invades the adventitia
4 - Tumour invades adjacent structures
Nodes
0- No lymph nodes
1- 1-2 regional lymph nodes
2- 3-6 regional lymph nodes
3 - >7 regional lymph nodes
Stage of disease:
1 - T1 N0 M0
2 - 3: Any combination of T and N that adds up to the stage
4: M1
Metastases:
Haematogenous: lung, liver, adrenal glands
GASTRIC CANCER is and path
Adenocarcinoma, the most common gastric malignancy
Third most common GI malignancy following colon and pancreatic cancer
Epidemiology:
- Rare before age 40. Climbs and peaks in the 7th decade of life
- 2:1 male predominance
Non-specific symptoms
Nodal metastases:
- Sister Mary Joseph’s node - umbilical
- Virchow’s node - left supraclavicular
- Drains the thoracic duct
- Krukenberg’s tumour - ovary
- Irish node - enlarged axillary lymph node
Aetiology:
- Association with H-pylori
- Most are sporadic in occurrence, 8-10% have an inherited gastric component
Risk factors:
- Pernicious anaemia
- Adenomatous gastric polyps
- Atrophic gastritis
- Bilroth II partial gastrectomy for benign disease
- Type A blood group
- Smoking
Prognosis:
- 20% 5yr survival rate
Differentials:
- Gastric lymphoma
- Gastric metastases
- GIST
GIST - GASTROINTESTINAL STROMAL TUMOUR is and assoc
The most common mesenchymal tumour of the GIT
Account for ~5% of all sarcomas
Most frequently found within the stomach and mid-distal small bowel
Used to be called Leiomyomas/etc but differentiated by an expression of c-KIT and CD34 antigens
Epidemiology:
- Uncommon compared to gastric carcinoma
- Age ~40+
- Possible slight male predilection
Location:
- Oesophagus - uncommon (vs leiomyomas)
- Stomach - most common, 70%
- Small bowel - #2, 20-25%
- Colon/rectum - most common rectal sarcoma - 7% at the rectum, then colon
- Can also occur in the mesentery, omentum and retroperitoneum
Associations:
Majority are sporadic, but can also occur with:
- Carney triad - extra-adrenal paraganglioma, GIST, pulmonary chondroma
- NF1
- Carney-Stratakis syndrome - autosomal dominant condition comprising of familial paragangliomas and gastric stromal sarcoma
Treatment
- Resection
- 50% will have metastasized at the time of presentation
- Adjuvant chemotherapy is given
GIST - GASTROINTESTINAL STROMAL TUMOUR path
Typically submucosal tumours
Often the overlying mucosa remains intact on pathological and imaging assessment
Arise from the Interstitial cells of Cajal
95% stain positive for cd117 (C-KIT) and 70% for CD34 - a tyrosin kinase growth factor receptor and target of ST-571
Grading requires assessment of both tumour size and mitotic index
- Smaller lesions have less aggressive biological behaviour, as do stomach GISTs compared to tumours elsewhere
Macroscopic:
- Rounded with frequent haemorrhage
- Larger tumours may demonstrate necrosis and cystic change
- Size is variable, 1-30cm
Histology:
- A relatively cellular tumour composed of spindle cells 70-80% and plump epithelioid cells 20-30%
- They appear to arise from the muscularis propria layer
LEIOMYOMA is and light path
A benign smooth muscle neoplasm of the oesophagus, the most common benign tumour of the oesophagus
Epidemiology: most frequently presents in young and middle aged groups 20-50yo
Pathology: like other leiomyomas, they comprise of smooth muscle overgrowth
Location: mid-distal oesophagus
No treatment necessary if <5cm and asymptomatic, otherwise resected
MALTOMA is and light path
Extranodal marginal zone B-cell lymphoma, low grade
Represents ~7.5% of non-Hodgkin lymphomas
Average age ~60yo with female predominance
Pathology:
- Arise in the epithelial tissues where lymphoid cells aren’t usually found
- Chronic infection/inflammation has been implicated in the pathogenesis - e.g. H pylori in gastric MALT, Sjogren syndrome in salivary gland MALT
Less than 10% transform from low-grade to high grade disease
Considered indolent disease with good prognosis. Treatment is tailored to the affected organ, and may consist of: surgery, chemotherapy and/or radiation therapy
- Antibiotics are used to treat gastric MALToma
SMALL BOWEL CARCINOMA path
50% less common than colonic carcinoma
Pathology:
Almost 50% are found in the duodenum, especially near the ampulla. Of the remaining, the jejunum is more commonly involved than the ileum
Risk factors:
- Crohn disease
- Sprue
- Peutz-Jeghers syndrome
- Lynch syndrome II
- Congenital bowel duplication
- Ileostomy or duodenal or jejunal bypass surgery
More distal adenocarcinomas tend to be annular, duodenal adenocarcinomas tend to be papillary/polypoid
MUCINOUS NEOPLASM OF THE APPENDIX is and light path
Epithelial tumours of the appendix that produce mucin
Represent a spectrum of malignant potential, and the most common cause of pseudomyxoma peritonei
Pathology:
- Classified as premalignant, uncertain malignant potential or malignant
Defined as mucinous when extracellular mucin corresponds to more than 50% of the lesion
COLORECTAL CARCINOMA is, risk factors and assoc
The most common cancer of the GIT, tends to be a disease of the elderly, with median age of diagnosis between 60-80yo
Slight male predilection
Risk factors:
- Low fibre/high fat/animal protein diet
- Obesity
- IBD
- Asbestos exposure
- Family history of benign/malignant colorectal tumours
Associations:
- Seen in 6% of CRC
- Familial adenomatous polyposis syndrome
- Gardner and Turcot syndrome variants
- Peutz-Jeghers syndrome
- Hereditary non-polyposis colon cancer syndrome
- Juvenile polyposis syndrome
- MUTYH-associated polyposis
Location:
- Rectosigmoid 55%
- Caecum and ascending colon ~20%
- Ileocaecal valve 2%
- Transverse colon ~10%
- Descending colon ~5%
Treatment/prognosis:
- Local resection for all
- Adjuvant chemotherapy for stage III
- 40-50% 5yr survival, with stage at operation the single most important factor affecting prognosis
- BRAF-mutated CRC has a poorer prognosis with a median survival of <12mo
- Recurrence is common
- Local recurrence - 80% within 2yrs
- CEA is used for detecting early recurrence - inappropriate for screening
- Higher levels are associated with higher grade tumours, higher stage of disease and visceral metastases
COLORECTAL CARCINOMA path
Most arise from pre-existing colonic adenomas (neoplastic polyps) which undergo malignant transformation as they accumulate additional mutations
Morphology can be anything
Rarely will there be wide invasion of the submucosa (e.g. like linitis plastica of the stomach)
These are typically scirrhous adenocarcinomas
RECTAL CA IS AND STAGIGN
Shares many features with CRC
Requires an MRI for local staging
Epidemiology: >50yo, and male predilection
Similar path to other adenocarcinomas
T stage
- Confined to or extends through the muscularis propria
- Extent of extramural spread and whether the peritoneum or other organs are invaded
N stage
- Size isn’t a reliable indicator of nodal involvement
- Number of nodes, irregular or spiculated margin and heterogenous signal intensity
Surgical resection with either radiotherapy alone or combined chemo/ray in T3 and/or N1 disease
A circumferential resection margin of <1-2mm confers a poorer prognosis
Staging:
T1: invades the submucosa
T2: invades muscularis propria
T3: invades through the muscularis propria into the subserosa or non-peritonealised perirectal tissues without reaching the mesorectal fascia or adjacent organs
- A - <1mm, b 1-5mm, C 5-15mm, D >15mm
T4: invades directly into other organs or structures and/or perforates visceral peritoneum
ANAL CANCER IS
Relatively uncommon, <2% of large bowel malignancies
Most are SCC
Typically originates between the anorectal junction above and the anal verge below
POLYPOSIS LOCATION
Stomach - cronkite-canada
Small bowel - Peutz Jegher
Large bowel - Juvenile polyposis, Lynch, Cowden, Turcot, FAP, cronkite-canada
CRONKITE-CANADA IS AND PATH
Non neoplastic, non-hereditary hamartomatous polyposis syndrome
Characterized by rash, alopecia and watery diarrhoea
Epidemiology:
- 3 male : 2 female
- Patients are typically middle age 50-60yo
Clinical presentation:
- Watery diarrhoea and a protein-losing enteropathy with associated nail atrophy, brownish skin pigmentation and alopecia
Pathology:
- Numerous hamartomatous polyps in the digestive tract
- Predominant involvement of the stomach, large intestine and to a lesser extent, small bowel
- The exact etiology is unknown
- Polyps are similar to those of juvenile polyposis syndrome, except the mucosa in CCS polyps is oedematous and inflammation of the lamina propria is usually present
- In juvenile polyposis syndrome, the mucosa between polyps is normal
PEUTZ-JEGHER IS AND PATH
Autosomal dominant polyposis syndrome
Characterized by:
- Multiple hamartomatous polyps
- Mucocutaneous melanin pigmentation involving the mouth, fingers and toes
Locations:
- Small intestines, predominantly the ileum
- Colon and stomach
- Mouth and esophagus are spared
Pathology:
- Non-neoplastic hamartomas due to the proliferation of all three layers of the mucosa,
- Polyps have a characteristic feature of a smooth muscle core continuous with muscularis mucosa in a tree-like branching pattern
- Distinguishes them from the hamartomatous polyps of CCS, JP and cowden disease
- Patients are at increased risk of intussusception
- GI tract adenocarcinoma, although the polyps aren’t premalignant
Stomach 29% lifetime risk
Small intestines 13% lifetime risk
Extraintestinal malignancy:
Adenomal malignum (subtype of the cervix)
Breast 45-50%, usually ductal
Pancreas 11-36%
Ovary 18-21%
uterus
Cervix
Testes
Lung
Genetics:
- Attributed to mutations in tumour suppressor genes, most commonly STK11
Due to the increased risk of malignancy, screening is generally recommended
TURCOT IS AND PATH
A variation in polyposis syndromes
Characterized by multiple colonic polyps and an increased risk of colon and primary brain cancers
Epidemiology:
- A rare disease
- Typically presents by the second decade
Pathology:
- Intestinal polyposis
- CNS: typically glioblastoma or medulloblastoma
Genetics:
- Autosomal recessive inheritance
- 2/3 of patients have mutations in the APC gene, the same genetic defect as in FAP - these patients have multiple colonic adenomas and virtually all develop colorectal carcinoma by age 40
- The common intracranial tumour in this subtype is medulloblastoma
- The other 1/3 have mutations in the HNPCC genes
- Colonic malignancy is not as common in this type, but tends to develop at a younger age
- Most develop glioblastomas
GARDNER SYNDROME is and path
One of the polyposis syndromes, characterized by:
- Familial adenopolyposis
- Multiple osteomas - especially of the mandible, skull and long bones
- Epidermal cyst
- Fibromatoses
- Desmoid tumours of mesentery and anterior abdominal wall
Other abnormalities include:
- Supranumerary teeth, odontomas, dentigerous cysts
- Duodenal tumours/ampullary carcinoma
- Papillary thyroid carcinoma
Autosomal dominant inheritance in the FAP gene (chromosome 5q) in a majority of patients, but with 20% of cases resulting from new mutations
Extracolonic features often precede the diagnosis of colonic polyps
FAMILIAL ADENOMATOUS POLYPOSIS is and path
Characterized by the presence of hundreds of adenomatous polyps in the colon
The most common of the polyposis syndromes
Familial polyposis coli, attenuated familial adenomatous polyposis and Gardner syndrome are all variants of the same disease and FAPS is used to describe the entire spectrum
The average age of presentation is 16yo
Associations:
- Colorectal carcinomas
- Hepatoblastoma
- Extracolonic polyps - stomach, duodenum
- Desmoid tumours
- Osteomas
- Dental anomalies
- Congenital hypertrophy of the retinal pigment epithelium
- Papillary thyroid carcinoma
Pathology:
- Hundreds/thousands of colonic adenomatous polyps, usually tubular or tubulovillous
- The rectum is occasionally spared
- Less commonly they affect the small bowel and stomach
Genetics:
- Due to a mutation of the tumour suppressor adenomatous polyposis coli gene (APC) located on chromosome 5q21-2.
- 1/3 are thought to be sporadic, 2/3 familial
- MUTYH gene has been associated with APC-negative FAPS: this has autosomal recessive inheritance
Total colectomy with ileoanal anastomosis is generally considered the surgical treatment of choice
COWDEN SYNDROME is and path
Multiple hamartoma syndrome - characterized by multiple hamartomas throughout the body, and increased risk of several cancers
Type 2 segmental Cowden syndrome is the association of Cowden syndrome with a Cowden naevus when it is considered a type of epidermal naevus syndrome
Pathology:
Characterized by:
- Mucocutaneous lesions - present in >90%
- GI hamartomatous polyps (small and large bowel)
- Glycogenic acanthosis
- Thyroid abnormalities
- Thyroid adenomas
- Multinodular goitre
- Fibrocystic disease of the breast
Increased risk for cancers:
- Breast 30%
- Thyroid 5%, usually follicular
- CNS dysplastic cerebellar gangliocytoma, occurs when in association with Lhermitte-Duclos disease
Syndromic associations
- PTEN-related diseases:
- Lhermitte-Duclos disease
- Bannayan-Riley-Ruvalcaba syndrome
Genetics:
Autosomal dominant inheritance, with -variable penetrance
A gene locus for the disease has been identified on chromosome 10q22-23, a mutation of the pTEN gene
LYNCH is and path
Hereditary non-polyposis colorectal cancer
Autosomal dominant condition which predisposes to a host of malignancies, including colorectal carcinoma
Epidemiology:
- Typically presents age 40-50 with colorectal cancer or an associated malignancy
- 5x more common than familial adenomatous polyposis syndromes
- The most common hereditary cause of endometrial cancer
Pathology:
- Mutation in DNA mismatch repair (MMR) genes, resulting most frequently in colorectal carcinoma as well as extracolonic malignancies
GU
- Endometrial carcinoma 15-60%, most often endometrioid type
- Ovarian tumour 4-12%
- Prostate cancer 30%
- Urothelial tract cancer 1-7%
Small bowel cancer ~5%
- Duodenum 45%
- Jejunum 29%
- Ileum 12%
- Gastric cancer 6-13%
Hepatobiliary tract malignancy 1-4%
Pancreatic malignancy 1-6%
CNS tumours: most often glioblastomas
Variants:
- Muir-Torre syndrome: HNPCC-variant with sebaceous tumours and keratoacanthocytomas
Radiographic features
- Related to underlying conditions:
- Colorectal cancer - more frequently right sided, 70% proximal to the splenic flexure
- Arise from adenomatous polyps
- Diffuse polyposis is characteristically absent
- Small bowel adenocarcinoma: most commonly duodenal
- Endometrial carcinoma
- Ovarian tumours
- urinary tract malignancy
Frequent screening +/- colectomy
JUVENILE POLYPOSIS SYNDROME is and path
Consists of hundreds of juvenile polyps
Presentation is in the second decade
Present with rectal bleeding, bowel obstruction and intussusception
Hundreds of hamartomatous polyps containing fluid/mucous
Both the tumour suppressor gene SMAD4 on chromosome 10q and BMPR1A gene have been implicated
Associations:
- Intestinal malrotation
- Meckel diverticulum
- Hydrocephalus
- Congenital heart disease
- Mesenteric lymphangioma
- Pulmonary AVM
H-PYLORI/PEPTIC ULCER DISEASE IS
More common in males 3:1, and usually the older population
Risk factors:
- Helicobacter pylori infection
- Confirmed on biopsies obtained at endoscopy and urea breath test
- NSAIDS
- Corticosteroids
- Stress
- Zollinger-Ellison syndrome
- Hypercalcaemia
Ulceration is the end point, after acid resulting in inflammation, superficial erosions and eventually frank ulceration
H Pylori: a spiral gram-negative bacterium has been identified as the leading cause of duodenal ulceration
Graft vs host disease is and GI facts
frequent complication, often involving the GIT, skin and liver.
A disease of allogenic bone marrow transplant or haematopoietic stem cell transplantation
Can present early/acute (<100 days) or late/chronic (>100 days) post allogeneic haematopoietic stem cell transplantation and is one of the major complications of this treatment
The skin, GIT (esp small bowel) and liver are the principal affected organs
End organ damage is the result of the recipient’s immune system (mainly antigen presenting cells) interacting with donor T-cell, leading to the latters activation with a resultant cell-mediated and inflammatory cascade
Bowel: “ribbon” appearance, with fold thickening
- Oedema of the mucosal folds in the ileum and jejunum
- Effacement of the folds towards the ileum: can give featureless (atrophic) loops
- Thickening of the bowel walls
- Spasms and stenosis with prestenotic dilatation
- In the active phase, the bowel can appear shortened
CT:
- Bowel wall thickening, small/large or both (most common)
- Bowel dilatation
- Engorgement of the vasa recta adjacent to the affected bowel segments
- Mucosal enhancement
- Mesenteric stranding ~60%
- Ascites
- Biliary abnormalities
PERIANAL FISTULA is and path
The presence of a fistulous tract across/between/adjacent to the anal sphincter
Usually an inflammatory condition
Male predilection 2-4:1
Associations:
Spontaneous:
- Diverticulitis
- Crohn disease
- Other bowel or pelvic infections
- Tuberculosis
Iatrogenic
- Post surgical complication
Pathology:
- Cryptoglandular hypothesis: obstruction of the deep submucosal glands results in infection and abscess formation in the inter-sphincteric space, which consequently drains inferiorly between the sphincters opening onto the skin surface or, less commonly, erodes through both the internal and external sphincters into the ischiorectal space, then onto the skin surface
- Transsphincteric fistulae are secondary to ischiorectal abscesses with a resultant extension of the tract through the external sphincter
- Intersphincteric fistulae are due to perianal abscesses
- Suprasphincteric fistulae are due to supralevator abscesses
PERIANAL FISTULA grading
Radiological grading: based on landmarks in the axial plane and incorporates abscesses and secondary extensions
Grade 1 - simple linear intersphincteric
Grade 2 - intersphincteric with abscess or secondary tract
Grade 3 - transsphincteric
Grade 4 - transsphincteric with abscess or secondary tract within the ischiorectal fossa
Grade 5 - supralevator and translevator extension
APPENDICITIS is and path
Acute inflammation of the vermiform appendix
Pathology:
Typically caused by obstruction of the appendiceal lumen, with resultant build-up of fluid, suppurative inflammation, secondary infection, venous congestion, ischaemia and necrosis
Obstruction may be caused by:
- Lymphoid hyperplasia ~60%
- Appendicolith ~33%
- Foreign body ~4%
- Crohn disease
MUCOCOELE is and path
When there is abnormal accumulation of mucin causing abnormal distention of the vermiform appendix due to various neoplastic or non-neoplastic causes
Benign or malignant lesions, categorised into 4 histologic types:
- Mucous retention cyst due to obstruction - usually appendicolith
- Mucosal hyperplasia
- Mucinous cystadenoma of the appendix (most common)
- Mucinous adenocarcinoma of the appendix
Curvilinear mural calcification suggests the diagnosis
Intraluminal bubbles of gas, or a gas-fluid level within a mucocoele indicates the presence of superinfection
Mural nodularity and irregular mall thickening are suggestive of a malignant process
PYLORIC STENOSIS is
Idiopathic thickening of the gastric pyloric musculature which then results in progressive gastric outlet obstruction
Relatively common, male predilection 4:1
Risk factor: first born, maternal history of pyloric stenosis
Typically manifests 6-12 weeks of age
Pathology:
- The result of both hyperplasia and hypertrophy of the pyloric circular muscle fibres
Four theories:
- Immunohistochemical abnormalities
- Genetic abnormalities
- Infectious cause
- Hyperacidity theory
Associations:
- Turner syndrome
- Tracheo-oesophageal fistula
- Oesophageal atresia
- Trisomy 18
HIRSCHPRUNGS is and path
The most common cause of neonatal colonic obstruction 15-20%
Commonly characterized by a short segment of colonic aganglionosis affecting neonates, esp boys
In short segment disease there is a male predilection, which reduces with increasing length of involvement
Almost never seen in premature infants
Characterised by aganglionosis in the distal colon and rectum
Thought to occur from either a failure of neuroblasts in neural crest cells to migrate into bowel segments or degeneration of already migrated neuroblasts
Affects cells in the myenteric and submucosal plexuses
Functional obstruction develops as a result of a spasm in the denervated colon
Anatomically divided into four types according to the length of the aganglionic segment:
- Short segment ~75%: rectal and distal sigmoid colon only
- Long segment ~15%: typically extends to the splenic flexure/transverse colon
- Total colonic aganglionosis ~7.5%
- Also known as Zuezler-Wilson syndrome
- Occasional extension of aganglionosis into the small bowel
- Ultrashort segment disease
- 3-4cm of internal anal sphincter only
Associations:
- Down syndrome ~10%
- Neurocristopathy syndromes
- Waardenburg-Shah syndrome
- MEN Iia
- Neuroblastoma
NEC is and path
The most common gastrointestinal condition in premature neonates
Characterized by inflammation, ischemia and permeability of the neonatal bowel wall to bacteria
Potentially life threatening with significant associated morbidity
Usually develops 2-3 days after birth, 90% within the first 10 days
Pathology:
- Usually idiopathic and multi-factorial
- A combination of ischaemic and infective aetiology with contributive factors e.g. immature immunity
- No causative organ has been isolated
- Inflammation starts from the mucosal surface and progresses to haemorrhagic and coagulative necrosis
- There is ensuing loss of mucosal integrity, transmural necrosis and perforation
- Can affect any part of the large or small bowel, but most commonly involves the terminal ileum
- The right colon is occasionally involved
Management:
- Medically and surgically
- Medical: supportive measures and cessation of oral feeding, broad spectrum antibiotics and gastric aspiration
- Surgery: reserved for patients with evidence of perforation, entails resection of the necrotic bowel
High mortality, and surviving patients often go on to develop a stricture
MESENCHYMAL HAMARTOMA is
Uncommon benign hepatic lesions mostly seen in children under 2
Considered to be developmental anomalies rather than cystic neoplasia
Lesions are characterised by an admixture of ductal structures (blood vessels, small groups of hepatocytes and bile ducts) within a copious loose/oedematous connective tissue stroma
Rarely calcify
Typically there are multiple cysts in an oedematous stroma
The cysts vary in size
Histologically: a series of histologic modifications including progressive loss of hepatocytes, degeneration of bile duct epithelium and cystic changes of the mesenchymal component
Genetics: attributed to abnormal expression of the chromosome 19 microRNA cluster
Autoimmune gastritis: is
loss of parietal cells and intrinsic factor disables ileal vitamin B12 absorption
Typically spares the antrum and induces hypergastrinaemia (compared to H-pylori)
Characterized by antibodies to parietal cells and intrinsic factor that can be detected in serum and gastric secretions
Reduced serum pepsinogen levels
Antral endocrine cell hyperplasia
B12 deficiency (pernicious anaemia/megaloblastic)
Defective gastric acid secretions (achlorydia)
Associated with Hashimotos and addisons disease
WHIPPLES DISEASE is and GI features
A rare infectious multi-system disorder caused by the actinobacteria Tropheryma Whipplei
Incidence is unknown
Peak age for presentation is the 5th decade of life, men 8: 1 women
More common in farmers/those who work with soil and livestock
Pathology:
- Periodic acid-Schiff-positive granular foamy macrophages in a sampled tissue
Location:
- Small bowel classically, as well as a multitude of other organ systems with or without small bowel involvement:
- Skin
- Joints,
- CNS
- Mediastinum
GIT:
- Extensive infiltration of the lamina propria with large macrophages infected by intracellular T-whipplei causes marked swelling of intestinal villi and thickened irregular mucosal folds primarily in the duodenum and proximal jejunum
- When they become large enough to be macroscopically visible, they may appear as innumerable small filling defects superimposed on irregularly thickened folds “sand-like nodules”
Imaging:
- Diffuse 1-2mm micronodules in the jejunum
- Thickened mucosal folds: esp jejunum
- Small bowel calibre: normal or slightly dilated
- Mesenteric lymphadenopathy: nodes of very low (near fat) density
COLITIS locations and causes
Infectious:
- Preferentially right colon, appendix and ileum: yersinia, salmonella
- Diffuse colon: CMV, E-coli
- Most severe at the left colon: Shigella, schistosomiasis
- Rectosigmoid: gonorrhoea, herpes, C-trachomatis
Ischaemia:
Location relates to the anatomy
- SMA: right colon to splenic flexure
- IMA: left colon from splenic flexure
Watershed areas:
- Splenic flexure - Griffiths point
- Rectosigmoid junction - Sudeck point
Pathology:
- Diminished/absent blood flow > bowel wall ischaemia and secondary inflammation
- Bacterial contamination may produce superimposed pseudomembranous inflammation
- If necrosis develops, then ulceration or perforation can occur
- Fibrosis may lead to stricture
Aetiology:
- Arterial occlusion - arteriosclerosis, vasculitis, emboli
- Venous thrombosis
- Low flow states
- Others - sickle cell disease,
ATROPHIC GASTRITIS is/path
A chronic condition of autoimmune and non-autoimmune aetiology
Two types:
A - Autoimmune
- Gastric body and fundus atrophy secondary to antiparietal cell antibodies
- Decreased secretion of acid and intrinsic factor, with the latter leading to vitamin B12 deficiency
B - non-autoimmune (more common)
- Gastric antrum atrophy secondary to H-pylori infection (most common), alcohol, NSAIDs
Associations:
- Vitamin B12 deficiency
- Pernicinous anaemia- megaloblastic
- Subacute combined degeneration of the cord
- Gastric carcinoid tumours
ULCERATIVE COLITIS is, path, clinical, assoc
Predominantly affects the colon, with extraintestinal manifestations
Typically manifests in young adults, age 15-40yo
Pathology:
- Limited to the mucosa and submucosa
- Crohns is a transmural disease
Associations:
- Primary sclerosing cholangitis (PSC) 70-80% of patients with PSC develop IBD 87% UC
- Moya moya phenomenon
- Ankylosing spondylitis
- Colorectal carcinoma
Extraintestinal manifestations:
-Uveitis, iritis
- Thrombotic complications
- Fatty liver
- Seronegative spondyloarthropathy
- Chronic active hepatitis
CROHNS is, path, clinical, assoc
An idiopathic inflammatory bowel disease characterised by widespread discontinuous GIT inflammation
The terminal ileum and proximal colon are most often affected
Epidemiology: typically diagnosed age 15-25yo
Pathology:
- Idiopathic
- Higher incidence in people with first degree relatives with IBD
- Initially the disease is limited to the mucosa, with neutrophilic cryptitis and lymphoid hyperplasia, lymphoedema and shallow aphthoid ulceration
- The entire bowel wall becomes involved as the disease progresses, with linear longitudinal and circumferential ulcers extending into the mesentery
- Chronic fibrotic change occurs over time, with stricture formation
- Inflammation can occur anywhere along the digestive tract
Extraintestinal manifestations:
- Enterocutaneous fistulas
- Joints: sacroiliitis, seronegative spondyloarthritides
- Eyes: episcerlitis, iritis, uveitis
- Liver: pericholangitis, PSC, autoimmune hepatitis, cirrhosis, gallstones, hepatic abscess,
- Renal: renal calculi,
- Lung: bronchiectasis, mosaic perfusion, chronic bronchitis, COP
COELIAC DISEASE is and light path
A chronic autoimmune disease
Small bowel mucosa is primarily affected, resulting in progressive degrees of villous inflammation nad destruction
Tends to start in the duodenum and extend towards ileum, resulting in induction crypt hyperplasia
Loss of villi, which absorb fluid, and hypertrophy of crypts which produce fluid, resulting in excess fluid in the small bowel lumen
Associations:
- Idiopathic pulmonary haemosiderosis
- iGa Deficinecy
- Small bowel lymphoma
WILSONS is and path
Autosomal recessive disorder of copper metabolism affecting multiple systems.
Pathology:
A disorder that results from abnormal caeruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene
Total body copper is elevated - has toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs e.g. liver and brain
Three pathways are most affected:
- Dentatorubrothalamic tract
- Pontocerebellar tract
- Corticospinal tract
Markers:
- Serum caeruloplasmin reduced
- Serum copper reduced
- Free serum copper increased
Urinary copper increased
Hepatobiliary manifestations vary, from fatty changes to cirrhosis and occasionally fulminant hepatic necrosis
- Due to the accumulation of copper in the liver
- Usually the presentation at 10-13yo
NB: cant be seen on MR, so the commonest change is contour/cirrhotic abnormalities
HAEMOCHROMATOSIS is and types
An iron overload disorder, characterised by a progressive increase in total body iron stores and deposition of iron in some non-reticuloendothelial system (RES) body organs which results in some organ dysfunction
Primary haemochromatosis:
90% due to an abnormal HFE gene - the protein product of which regulates iron absorption from the GIT
- The two most common HFE gene mutations are c282y AND h63d
Equally distributed incidence between men and women, but menstruation is protective and presentation is delayed until after menopause.
Secondary haemochromatosis
Rare and seen in association with disease that chiefly cause hemosiderosis
The distribution of iron in RES and non-RES tissue can aid differentiation
Aetiology:
- Frequent transfusion
- High erythrogenic requirements
Radiographic features:
Primary haemochromatosis: Predominant liver involvement without spleen/bone marrow deposition - non-RES iron deposition
Secondary haemochromatosis: spleen and bone marrow, and liver - RES deposition, most likely from haemosiderosis
BUDD CHIARI is and causes
Hepatic venous outflow obstruction, where there is partial or complete obstruction of the hepatic veins
The acute presentation:
- Ascites
- Hepatomegaly
- Abdominal pain
The acute form results from an acute thrombosis of the main hepatic veins, or IVC
The chronic form is related to fibrosis of the intrahepatic veins, presumably related to inflammation
Aetiology:
Majority result from thrombosis within the hepatic veins
25% arise from external compression that results in obstruction
May be associated with concurrent portal vein thrombosis
Idiopathic
Congenital
- Hepatic vein or IVC webbing
- Interruption of the diaphragm
Venous thrombosis secondary to:
- Dehydration
- Sepsis
- Polycythemia rubra vera
- Antiphospholipid syndrome
- Sickle cell disease
Injury and/or inflammation:
- Phlebitis: bone marrow transplant and chemotherapy
- Behcets disease
- Tumour invasion
ALPHA-1-ANTITYPSIN is and path
A hereditary metabolic disorder
The most common genetic cause of emphysema and metabolic liver disease in children
Accumulation of altered alpha-1-antitrypsin in hepatocytes incites an inflammatory response and chronic liver disease
Pathology:
- Alpha-1-antitrypsin is a protein that prevents enzymes e.g. elastase from degrading normal host tissue
- 90% of the alpha-1-antitrypsin protein is produced in hepatocytes by codominant gene expression on chromosome 14
- Alpha-1-antitrypsin protein inhibits neutrophil elastase
- The neutrophil elastase acts unopposed resulting in damage to the lower respiratory tract - the damage distribution is predominantly basal due to gravitational distribution of pulmonary blood flow
Associations:
- Asthma
- Pancreatitis
- Aneurysms
Hepatic manifestation: cirrhosis, and increased risk of HCC
PRIMARY SCLEROSING CHOLANGITIS is and path
Multiple strictures of the biliary tree, liver damage and eventual cirrhosis
Strongly associated with IBD, especially ulcerative colitis
Associations:
- Ulcerative colitis
- Autoimmune hepatitis
- Sjogren syndrome
- Retroperitoneal fibrosis
- Mediastinal fibrosis
- Riedel thyroiditis
- Orbital pseudotumour
Pathology:
- No histological findings are pathognomonic
Frequent findings include:
- Periductal fibrosis
- Periportal eosinophilic infiltrate
- Paucity of ducts
Markers: antibody titres are usually absent or low
LFTs will have a cholestatic pattern with elevated ALP and bilirubin
Intra and extra hepatic involvement
- In 20% only the intrahepatic and proximal extrahepatic bile ducts are involved
- Cirrhosis of the whole liver, with the exception of the caudate lobe
- Other causes of cirrhosis will often involve hypertrophy of the left lobe
A risk factor for gallbladder cancer, so polyps should be considered malignant until proven otherwise
Complications:
- Hepatic osteodystrophy
- Cholangiocarcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Gallbladder carcinoma
PRIMARY BILIARY CHOLANGITIS is and path
A chronic progressive cholestatic liver disease that is the cause of 1-2% of deaths from cirrhosis and constitutes the third most common indication for liver transplantation in adults
Typically middle aged women with symptoms of fatigue and pruritis
Associations:
- Cholelithiasis ~40%
- Other autoimmune diseases: Sjogren syndrome 75%, autoimmune thyroiditis 25%, systemic sclerosis 10%
- Interstitial lung disease 15%
- Hepatocellular carcinoma ~5%
- Hepatic osteodystrophy
Characterised by the destruction of small intrahepatic bile ducts, portal inflammation and progressive scarring
The cause is unknown
Serum anti-mitochondrial antibody (AMA) tests are highly sensitive and specific for PBC
TODANI CLASSIFICATION
1 - fusiform dilation of the extrahepatic bile duct
2 - saccular outpouchings from the supraduodenal extrahepatic bile duct or intrahepatic bile duct
3 - focal dilation of the distal common bile duct into the duodenum (choledochocele)
4 - multiple communicating intra- and extra-hepatic duct cysts
5 - caroli disease
BILIARY ATRESIA
Absence or severe deficiency of the extrahepatic biliary tree. Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3mo of life.
HEPATIC ADENOMA is and path
Benign, generally hormone-induced, liver tumours
Usually solitary, with a predilection for haemorrhage
Epidemiology:
- OCP
- Anabolic steroids - typically young men
- Glycogen storage diseases
- Type 1 - Von Gierke disease
- Type 3 - Cori or Forbes disease
- Obesity
Pathology:
Usually solitary 70-80% of cases, and large at the time of diagnosis 5-15cm
Most frequently seen at the subscapular location in the right lobe of the liver and are often round, well-defined pseudo-encapsulated masses
May have dystrophic calcification
Hepatic adenomatosis - the presence of numerous (10+) hepatic adenomas
Patients often have an associated risk factor, like glycogen storage disease type 1
Histologically characterized by proliferation of pleomorphic hepatocytes without normal lobular architecture
- Frequently have abundant glycogen
Described as being devoid of bile ducts and Kupffer cells
HEPATIC ADENOMA subtypes
Inflammatory hepatic adenoma
- Most common
- Highest bleed rate
- Different appearance from the other subtypes
- The most common subtype 40-50%
- Occur in OCP setting, or older patients with hepatic steatosis or metabolic syndrome
- Clinical presentation: fever, leucocytosis, elevated CRP, elevated LFTs
- MRI
- Unlike the others, these can show enhancement after PRIMOVIST (HB contrast) since they express the hepatospecific receptor
- No drop out on the out of phase
HNF-1 alpha mutated hepatic adenoma
- Second most common subtype 30-35%
- Only in female with history of OCP use
- Often multiple (50%)
- MRI
- T1 iso/hyper relative to liver
- Moderate arterial enhancement
- No continuity of enhancement
- Drop out on out of phase
- Iso – mildly high T2
Beta catenin-mutated hepatic adenoma
- Least common subtype 10-15%
- Highest risk in men on anabolic steroids and patients with glycogen storage disease, familial adenomatous polyposis
- Usually regresses with ceasation of hormone administration
Unclassified hepatic adenoma
- Lack known genetic abnormalities
FNH is, assoc and path
A regenerative mass lesion of the liver and the second most common benign liver lesion
Most frequently found in young-middle-aged adults, with a strong female predilection
Usually isolated occurrence is the commonest, but up to 20% may be multiple
Associations:
- Hepatic haemangiomas
- Hereditary haemorrhagic telangiectasia
- Arteriovenous malformations (AVM)
- Anomalous venous drainage
- Hepatic adenoma
- Budd-Chiari syndrome
Pathology:
- Thought to be due to a hyperplastic growth of normal hepatocytes with a malformed biliary drainage system, possibly in response to a pre-existent AVM
- Arterial supply - hepatic artery
- Venous drainage - hepatic veins
- No portal venous supply
Two types:
Typical 80%
Atypical 20%
- Lacks a central scar and central artery
HCC is and path
The most common primary malignancy of the liver
Strongly associated with cirrhosis, of both alcoholic and viral aetiologies
Risk factors:
Hepatitis B, C
Biliary cholangitis
Congenital biliary atresia
Inborn errors of metabolism
- Haemochromatosis
- Alpha-1-antitrypsin deficiency
- Type 1 glycogen storage disease
- Wilson disease
- Tyrosinaemia type 1
- Porphyrias
Obesity and diabetes
Pathology:
- The origin is believed to be related to repeated cycles of necrosis and regeneration, irrespective of the cause
- HBV/HCV may contain genetic material that may predispose cells to accumulate mutations or disrupt growth control
Three types of macroscopic growth:
- Nodular
- Massive
- Infiltrative
Markers: AFP are elevated in 50-75%
Fl-HCC is and path
A distinct histological variant of HCC
Characterized on microscopy by laminated fibrous layers between tumour cells
Typically occur in young adults 20-40yo
Not associated with cirrhosis, alcoholism or hepatitis B/C infection
Pathology:
- Well differentiated and well circumscribed, with a dense fibrotic background
- The tumour cells are arranged in cords that are separated by sheetlike fibrous bands arranged in a parallel or lamellar distribution
Often these don’t produce AFP
The central scar is typically low on all sequences, can be T2 bright, mimicking FNH
GALLBLADDER CANCER is and path
A primary epithelial malignancy arising from the gallbladder, in which the majority (90%) are adenocarcinomas and the remainder are squamous cell carcinomas
More prevalent in elderly women, and in most cases are only symptomatic when in advanced stages
Risk factors:
- Chronic cholecystitis
- Gallstones are present in 70-90% of cases
- FAP
- IBD
- Porcelain gallbladder
- Gallbladder polyps >1cm
- Primary sclerosing cholangitis
Majority are related to chronic inflammatory metaplasia and dysplasia
Three morphologies:
- Intraluminal mass
- Diffuse mural thickening
- Mass replacing the gallbladder
CHOLANGIOCARCINOMA path
Risk factors:
- Caroli disease/choledochal cysts
- Choledocholithiasis
- Primary sclerosing cholangitis
- Recurrent pyogenic cholangitis
- Cirrhosis
- Toxins
- Viral infection
- IBD
- Fibropolycystic liver disease
- Hepatolithiasis
Location
-Intrahepatic - 10%
- Extrahepatic
- Perihilar 70%
- Klatskin tumour
- Distal 20% (Distal to the cystic duct insertion )
Typically sclerotic masses without haemorrhage or macroscopic necrosis
The active tumour is at the periphery, with central portions replaced by fibrosis: accounting for the capsular retraction
Three macroscopic descriptions are used:
- Mass-forming: definite mass in the liver parenchyma
- Periductal-infiltrating: extends longitudinally along the bile duct, often causing peripheral bile duct dilatation
- Intraductal growth - proliferates in the lumen of the bile duct like a papilla or tumour thrombus
- Characterised by alterations in duct calibre, usually duct ectasia with or without a visible mass
- If the mass is visible, it may be mural or polypoid in shape
- The duct dilatation is thought to be due to abundant mucin production - similar to IPMN
Histologically divided into well, moderately and poorly differentiated adenocarcinomas.
- Biliary intraepithelial neoplasia is a common finding, considered to be a precursor lesion of cholangiocarcinoma
- Typically a microscopic lesion with a flat or micropapillary dysplastic epithelium
- Synonymous with carcinoma in situ.
CHOLANGIOCARC IMAGING
Mass-forming:
- Non contrast: Homogenously low in attenuation
- Arterial - heterogenous minor peripheral enhancement with gradual centripetal enhancement
- The rate and extent depends on the degree of central fibrosis
- Capsular retraction may be evident
- The distal bile ducts are typically dilated
- Narrowing of the portal veins, less frequently hepatic veins, can also be seen, but cholangiocarcinoma rarely forms a tumour thrombus
- Lobar or segmental hepatic atrophy is usually associated with vascular invasion
Periductal infiltrating
- Intrahepatic tumours appear as regions of duct wall thickening or of the periductal parenchyma, with altered calibre of the involved duct (usually narrowed)
- These are most common at the hepatic hilum
- Tend to be longer than benign strictures (approximately 20mm in length), and show contrast enhancement
- There is usually some proximal (peripheral) dilatation of the biliary tree
Intraductal tumours
- Characterised by alterations in duct calibre, usually duct ectasia with or without a visible mass
HEPATOLITHIASIS is
The presence of bile duct stones within the intra-hepatic bile ducts, specifically proximal to the confluence of the right and left hepatic ducts
Associations:
- Primary sclerosing cholangitis
- Post-operative biliary strictures
- Caroli disease
Pathology:
- Can occur with or without the concomitant presence of cholelithiasis or choledocholithiasis
PRE-ECLAMPSIA is and path
A disorder of pregnancy involving new-onset hypertension (systolic BP >140 or diastolic >90) and involvement of one other organ system
Affects up to 8% of pregnancies
Risk factors:
- Diabetes mellitus
- Chronic hypertension
- Family history
- Nulliparity
- Advanced maternal age (>40yo)
- Obesity
- Anti-phospholipid syndrome (9x)
- Pre-eclampsia in prior pregnancy (7x)
After 20 weeks with:
- Proteinuria
- Thrombocytopenia
- Renal impairment (doubling of creatinine)
- Liver impairment (doubling of hepatic transaminases)
- Pulmonary oedema
- Headache or visual disturbance
- If they seizure = eclampsia
Pathology: incompletely understood
Defective development of spiral placental arteries and subsequent placental ischaemia is thought to be key
PANCREATITIS is and path
An acute inflammation of the pancreas
Two subtypes:
Interstitial oedematous pancreatitis 90-95%
Necrotising pancreatitis
Pathology:
Debate over the precipitating factor leading to acute pancreatitis
Duct occlusion is an important factor, but not necessary or sufficient
Activation of pancreatic enzymes in the pancreas rather than the bowel leads to inflammation of the pancreatic tissue, disruption of small pancreatic ducts and leakage of pancreatic secretions
The pancreas lacks a capsule, so the juices have ready access to surrounding tissues
Pancreatic enzymes digest fascial layers, spreading the inflammatory process to multiple anatomic compartments
Aetiology:
- Gallstone passage/impaction - most common
- Idiopathic 20%, most are associated with congenital duct abnormalities
- Alcohol abuse – most common cause of chronic pancreatitis
- Metabolic disorders – hypertriglyceridaemia-induced
- Most common cause in pregnancy
- Hypercalcaemia
- Autoimmune pancreatitis
- Penetrating peptic ulcer
- Trauma – most common in children
- Blunt abdominal trauma
- Surgery
- Malignancy
- Pancreatic adenocarcinoma
- Lymphoma
- Hereditary pancreatitis
- Malnutrition
- Infection
- Viral – mumps, Coxsackievirus, hepatitis, i- fectious mononucleosis, HIV/AIDS
- Parasitic – ascariasis, clonorchiasis
- Structural – not a cause,
IgG4 PANCREATITIS is and path
A form of chronic pancreatitis associated with autoimmune manifestations
Rare, incidence is ~5-11% of chronic pancreatitis cases
Variable age of presentation, male predilection
Clinical presentation:
- Jaundice, weight loss
- New onset diabetes mellitus
- Extra-pancreatic manifestations with lymphocytic infiltration:
- Inflammatory bowel disease
- Pulmonary involvement
- Renal involvement
- Biliary tree
- Salivary glands
- Elevated IgG and antinuclear antibody levels >50% of cases
- Abdominal pain and acute pancreatitis
- Serum amylase and lipase can also be raised
Characterised by a heterogenous autoimmune inflammatory process where prominent lymphocytic infiltration with associated fibrosis of the pancreas causes organ dysfunction
The cause is unknown, though an autoimmune process with antibody reaction to carbonic anhydrase and lactoferrin has been postulated
Macroscopic appearance: diffusely indurated and firm pancreas, with some demonstrating a focal mass
Microscopic:
- Collar-like periductal infiltrates composed of lymphocytes and plasma cells, with the lymphocytes being CD8+ and CD4+ T lymphocytes
- Clusters of inflammatory cells are also seen in the walls of small veins and nerves, as well as medium and large-sized vessels
- Interlobular septa are thickened by a proliferation of myofibroblasts and infiltrated by lymphocytes and plasma cells
- Other organs can be involved with a lymphocyte infiltrate: gallbladder, biliary tree, kidney, lung and salivary gland
Associations:
- IgG4- related sclerosing disease
- Rheumatoid arthritis
- Sjogren syndrome
- Inflammatory bowel disease
- IgG4-related sclerosing cholangitis
Pancreatic NET is and syndromes
Arise from the pancreatic islet cells and include some distinct tumours that match the cell type of origin
Overall have an incidence of 0.001%, and account for 1-2% of pancreatic neoplasms
They occur most commonly at ages 30-60, with no clear gender predilection
Associations
- Most are isolated
- 1-2% are associated with multiple endocrine neoplasia type I (MEN I) which is characterised by the triad of parathyroid, pituitary and pancreatic lesions
- Pancreatic endocrine tumours
- Von Hippel-Lindau disease
- Tuberous sclerosis
Syndromes:
Insulinoma: Whipple triad
- Fasting hypoglycaemia
- Symptoms of hypoglycaemia
- Immediate relief with administration of glucose
Gastrinoma: Zollinger-Ellison syndrome
- Diarrhoea
- Gastritis
- Severe GORD
- Peptic ulcer disease
Glucagonoma: 4D syndrome
- D - dermatitis
- D - mild diabetes mellitus
- D - deep vein thrombosis
- D - depression
Non-functioning: tend to present late and often larger in size
Pancreatic NET path
Insulinoma
- Most common
- Develop from ductal pluripotent cells into unregulated cells secreting insulin
- The beta cells of the islet of Langerhans normally secrete insulin
-10% of insulinomas are multiple, and 10% malignant
- Equally distributed throughout the pancreas
Gastrinomas
- Usually multiple
- Typically located in the duodenum (more commonly) or pancreas (less commonly)
- Secrete gastrin that results in hypersecretion of gastric acid
- Marker: Chromogranin A levels may be elevated
Glucagonoma
- Most are malignant
- Most are large and have metastasised at the time of diagnosis
- Most are located in the distal pancreas and tend to demonstrate significant hypervascularity
IPMN is
Epithelial pancreatic cystic tumours of mucin-producing cells that arise from the pancreatic ducts
Most commonly seen in elderly patients
Characterised by single or multiple unilocular or septated pancreatic cystic lesions communicating with the pancreatic ducts
Typically 50-60yo
can be main or side branch
Main duct lesions present a decade earlier than branch type
Can be further divided histologically with respect to their macroscopic appearances
Uncommon ductal epithelial tumours comprising of 10-15% of cystic pancreatic neoplasms
IPMN path
Main duct
- Reminiscent of chronic pancreatitis
- Segmental or diffuse distribution
- Highest malignant potential ~60%
Branch type
- Most seen in the head and uncinate process
- More localised and mass-like
- Multi-focal
- May be macro or microcystic in appearance
- Typically indolent behaviour ~5% are malignant
Divided into:
- Adenoma
- Borderline-malignant
- Intraductal papillary mucinous adenocarcinoma
Markers: Abnormal pancreatic enzyme markers (amylase/lipase) are associated with malignant IPMN
SEROUS CYSTADENOMA OF THE PANCREAS is and path
An uncommon type of benign cystic pancreatic neoplasm
Strong female predilection, and usually present in middle age to elderly patients >60yo
Association:
- Von hippel lindau - can be multiple or diffuse and present at a younger age
Pathology:
- Benign neoplasms composed of numerous small cysts arrayed in a honeycomb-like formation
- Can be significant variation in locule size 1-20mm
- Most are typically <10mm
- Three morphological patterns:
- Polycystic 70%
- Honeycomb 20%
- Oligocystic <10%
- Cysts are lined by glycogen-rich flat or cuboidal epithelium separated by fibrous septa that radiate from a central scar and may by calcified
- Tend to be large at presentation
Location:
- Head/uncinate process 40%, body 34% and tail 26%
MUCINOUS CYSTADENOMA OF THE PANCREAS is and path
The most common pancreatic cystic lesion
Middle aged females exclusively
Pathology:
- A large uni/multilocular cystic pancreatic neoplasm lined by columnar mucinous epithelium
- Infrequently communicate with the pancreatic duct, but can cause partial pancreatic ductal obstruction
- Considered premalignant/malignant: usually with an elevated CEA and CA19-9
Cant differentiate on CT between adenoma and adenocarcinoma
SPEN is and path
Rare, account for 1-2% of exocrine pancreatic lesions
Tend to present in young non-Caucasian females ~2nd-3rd decades of life
Associations: pancreatic dorsal agenesis
Pathology:
- Frequently contain varying amounts of necrosis, haemorrhage and cystic change
- Can be large at the time of diagnosis
Greater predilection to occur at the tail
PANCREATIC ADENOCARCINOMA is and path
Risk factors:
- Cigarette smoking
- Chronic pancreatitis
- Obesity
- Diabetes mellitus
- Family history
- Hereditary syndromes:
- BRCA2 mutations are the most frequent cause of familial pancreatic cancer
- HNPCC
- Familial breast cancer
- Familial atypical multiple mole melanoma
- Hereditary pancreatitis
- Ataxia-telangiectasia
- Peutz-jegher syndrome
Serum markers:
- CEA
- CA19-9
Pathology:
Precursors:
- Pancreatic intraepithelial neoplasia - 90%
- Intraductal papillary mucinous neoplasm (IPMN)
- Mucinous cystic neoplasm
Pathogensis:
- The most prevalent molecular changes responsible are:
- KRAS - the most commonly mutated oncogene 90%
- TP53 70-75%
- SMAD4 - inactive 55%
- CKN2A altered 30%
HERPES ENCEPHALITIS is and path
Most common cause of fatal sporadic fulminant necrotising viral encephalitis
Two subgroups:
- Neonatal - typically HSV2
- Childhood and adult – typically HSV 1 (90%)
There is no particular age, sex or seasonal predilection
Diagnosis: PCR of CSF – pleocytosis and elevated protein
Pathology:
- Obligatory intracellular virus
- Enters via infecting nasopharyngeal cells into the sensory branch of the lingual nerve, ascending to trigeminal ganglion where it remains latent for a lifetime
- Reactivation occurs with immunosuppression, trauma, or other stressors
- Can result in fulminant hemorrhagic necrotising encephalitis
- High affinity for limbic systems with bilateral but asymmetric involvement
Micro:
- Perivascular cuffs of lymphocytes, large inclusions in neurones and glial cells - “owl eyes”
CNS CRYPTOCOCCUS is and path
An infection of the CNS with the yeast-like fungus Cryptococcus neoformans
The most common fungal infection
Predominantly immunocompromised patients,
Pathology:
- Typically haematogenous spread from the lungs - usually the primary site
- In HIV/AIDs patients, the infection occurs when the CD4+ count drops below 100 cells/uL
- Can have either meningeal or parenchymal involvement, meningeal being the primary manifestation
- Grey mucinous exudate accumulates over the involved brain surface
Three forms:
- Meninges = meningitis
- Parenchyma = cryptococcomas
- Perivascular spaces = gelatinous pseudocysts. Usually only immunocompromised
CNS TOXOPLASMOSIS is and path
An opportunistic infection caused by the parasite Toxoplasma gondii
Typically affects patients with HIV/AIDs, and is the most common cause of cerebral abscess in these patients
An intracellular parasite that infects birds and mammals
Transferred via excrements into food, leading to infection
Pathologically, the lesions have three distinct zones:
- A central avascular zone of coagulative necrosis
- An intermediate vascular zone containing numerous organisms
- An outermost zone of encysted organisms
These lesions don’t have a capsule
Manifest as multiple lesions, with a predilection for the basal ganglia, thalami and corticomedullary junction
CJD is and path
A transmissible spongiform encephalopathy resulting in rapidly progressive dementia and death, usually within a year of onset
The vast majority are sporadic, but familial and acquired forms are occasionally encountered
Four types:
- Sporadic - 85-90% of cases
- Variant - bovine transmission
- Familial - 10%
-PRPc mutation
- Iatrogenic
Diagnostic markers
- EEG
- S100
- CSF 14-3-3 protein - a positive marker
Pathology:
- Mediated via prions, a type of protein
- Considered infectious, in that they can alter the structure of neighbouring proteins
- Leads to spongiform degeneration of the brain
- Caused by the conversion of normal prion protein to proteinaceous infectious particles that accumulate in and around neurones and lead to cell death
CNS TB is and path
Can result from either haematogenous spread from distant infection or direct extension from local infection
Protean infection, can affect all compartments
Extra-axial
- TB meningitis : leptomeningitis - pachy is rare
Intra
- Tuberculoma (tuberculous granuloma)
- Focal tuberculous cerebritis
- Intracranial TB abscess
- TB rhombencephalitis
- TB encephalopathy
Seen in all age groups, with a predilection for younger patients
Haematogenous spread from the lungs or GIT is most common, leading to small subpial or subependymal infective foci
These are called Rich foci and form a reservoir from which intracranial manifestations may arise
Either during primary infection (uncommon) or reactivated later
NEUROCYSTERICOSIS is and path
A parasitic infection caused by ingestion of tapeworm eggs through faecal-oral transmission
A pork tapeworm: Taenia solium
No gender or race predilection, most symptomatic patients are aged 15-40yo
Pathology:
- Infection by contaminated food/water
Four stages:
- Vesicular - variable parasite with intact membrane, and no host reaction
- Cyst with a dot sign
- Colloidal vesicular - parasite dies within 4-5yrs untreated, or earlier with treatment and the cyst fluid becomes turbid
- As the membrane becomes leaky oedema surrounds the cyst
- Oedema, cyst and the wall become thickened and brightly enhance
- Granular nodular - oedema decreases as the cyst retracts further, enhancement persists
- Oedema decreases, cyst retracts and becomes a small enhancing nodule
- Nodular calcified - end stage quiescent calcified cyst remnant, no oedema
Location can be both intra and extra-axial. The most common locations are:
- Subarachnoid space over the cerebral hemispheres
- Parenchyma - most frequent
- Basal cisterns
- ‘grape-like’ “racemose”
- Ventricles
- Usually a solitary cyst
- 4th ventricle is most common
- Spinal forms
- Concomitant intracranial involvement
- Subarachnoid and interventricular cysts don’t typically have a visible scolex
- Look for ventriculitis
CADASIL is and path
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
An autosomal dominant microvasculopathy characterised by recurrent lacunar and subcortical white matter ischaemic strokes and vascular dementia in young and middle-aged patients without known vascular risk factors
Typically symptomatic in adulthood, 30-50yo
Present with TIA/strokes in multiple areas
Mutation of chromosome 19p13.12, involving the NOTCH3 gene
Results in small vessel and arteriole stenosis secondary to fibrotic thickening of the basement membrane of the vessels
- The pathological hallmark is the deposition of granular osmiophilic material in close relation to the vascular smooth muscle cells
Anterior temporal lobe and external capsule
Relative sparing of subcortical U-fibres and the cortex, as well as occipital/ orbitofrontal subcortical white matter
AMYLOID ANGIOPATHY is and path
Cerebrovascular disorder caused by the accumulation of cerebral amyloid-B in the tunica media and adventitia of the leptomeningeal and cortical vessels of the brain
The resultant fragility manifests in normotensive elderly patients as lobar intracerebral hemorrhage
Can be sporadic or familial
- Sporadic - higher rates in Alzheimers
- Familial - rare, autosomal dominant conditions
Pathology
- Deposition of amyloid in the tunica media and/or tunica adventitia of small and medium-sized arteries of the cerebral cortex and leptomeninges
- There is associated fibrinoid degeneration with separation of the tunica media and tunica intima and microaneurysm formation
- Different proteins can lead to intravascular amyloid deposition
Associations
- Alzheimer disease
- Down syndrome
- Chronic traumatic encephalopathy
- Spongiform encephalitis
Imaging
- Intracerebral haemorrhage - usually cortico-subcortical
- Micro-haemorrhage
- Tend to spare the basal ganglia and pons
- Convexity SAH
- Cortical superficial siderosis
Cerebellar superficial siderosis
Ischemia
GLOBAL HYPOXIC INJURY is/pattern
Primarily affects the grey matter structures
- Basal ganglia
- Thalami
- Cerebral cortex - esp sensorimotor and viscual cortices
- Cerebellum
- Hippocampi
Grey matter involvement due to high metabolic requirement for oxygen and glucose to supply a large number of synapses
- Makes the grey matter more susceptible to hypoxic-ischaemic injury
MRI: DWI is the first to change
WERNICKES is and path
Thiamine (vitamin B1) deficiency
Typically seen in alcoholics
Triad of presentation:
- Acute confusion
- Ataxia
- Ophthalmoplegia
Can evolve into a chronic form: korsakoff psychosis
- Memory loss
- Confabulation
Aetiology:
- Malnutrition and malabsorption, which can occur for a number of reasons
- Alcohol abuse
- Starvation/fasting
- Chronic dialysis
- GI malignancy
Acutely: haemorrhage, necrosis and oedema may be present
Chronic: atrophy, especially involving the mamillary bodies
MRI
Symmetrically increased signal intensity in the:
- Mamillary bodies
- Dorsomedial thalami
- Tectal plate
- Periaqueductal grey matter
- Around the third ventricle
- Can have contrast enhancement in the same region
- Restricted diffusion may be seen
Differential:
- Leigh syndrome - child
CO poisoning is and path
May result in anoxic-ischaemic encephalopathy, with acute as well as delayed effects
Acute: headache, dizziness, altered conscious state, seizure
Cardiac arrest may occur
Chronic: cognitive decline, abnormal gait, faecal incontinence
Pathology:
Two fold pathophysiology:
- CO binds strongly to haemoglobin and the resultant carboxyhaemoglobin in the bloodstream can cause profound hypoxic/anoxic injury
- A respiratory chain metabolism toxin that interferes with mitochondrial oxidative phosphorylation and activates polymorphonuclear leucocytes > delayed brain lipid peroxidation
Tend to be bilateral, with the globus pallidus most affected
LEIGHS DISEASE is and path
Subacute necrotising encephalomyelopathy
A mitochondrial disorder with progressive neurodegeneration leading to death, usually in childhood
Symptoms are evident by age 2
- Psychomotor delay/regression
- Superimposed signs of basal ganglia and brainstem dysfunction
- Ataxia
- Ophthalmoplegia
- CN palsies
Pathology
- One of many mitochondrial disorders, due to a broad range of genetic mutations in either nuclear or mitochondrial DNA
- Nuclear DNA mutations are more common - AR, and X-linked
Chronic energy deprivation leads to histological features such as:
- Spongiform degeneration
- Capillary proliferation
- Demyelination
- Neuronal loss
- Gliosis
Markers: CSF lactate may be elevated
MRI
- Brainstem
- Periaqueductal grey matter
- Medulla
- Midbrain
- Putamen
WILSON DISEASE CNS is and path and imaging
Autosomal recessive disorder of copper metabolism
Abnormal caeruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene
Total body copper is elevated - toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs e.g. liver and brain
Three pathways are most affected:
- Dentatorubrothalamic tract
- Pontocerebellar tract
- Corticospinal tract
Basal ganglia - especially putamen, followed by midbrain, pons and thalamus
Distribution is bilateral and symmetric
CT
- May see atrophic changes in the basal ganglia, cortical and cerebellar regions
- Non-enhanced: copper deposition doesn’t increase density on CT
- Post contrast: lesions don’t enhance
MRI
- Abnormal T2 high signal in the putamen
- Predominantly the deep grey nuclei
- “face of the giant panda sign” - midbrain tegmentum involvement
PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION imaging
“eye of the tiger sign”: symmetrical bilateral abnormal low signal on T2
Accumulation of iron in the globus pallidus with central high signal
PHTHISIS BULBI is and path
end stage eye
An atrophic scarred and disorganised non-functioning globe, that may result from a variety of occular insults
Typicaly elderly patients
Small globe with thickened/folded posterior sclera
Dysmorphic calcification is common, osseous metaplasia may occur
Aetiology
- Trauma
- Infection
- Other inflammatory process’
- Radiation
- Chronic retinal detachment
- retinoblastoma
DIABETES INSIPIDIS is and path
Deficiency or resistance to the hormone vasopressin (antidiuretic hormone) which results in polyuria and polydipsia
Central/neurogenic/hypothalamic - vasopressin deficient (most common)
Peripheral/nephrogenic - vasopressin resistant
Aetiology:
Central - reduced secretion
- Trauma, NSx
- Malignancy - craniopharyngioma, germinoma, mets
- Autoimmune - lymphocytic hypophysitis
- Inflammatory disease - sarcoid, LCH, IgG4
- Infection - TB
- Pregnancy
- Familial,
- Idiopathic
Peripheral - increased end-organ resistance to vasopressin
- Congenital renal insensitivity to vasopressin (rare)
- Long term lithium use (~15% of patients)
- Metabolic - hypokalaemia, hypercalcaemia
- Chronic kidney disease
- pregnancy
HUNTINGTONSis and path
An autosomal dominant trinucleotide repeat neurodegenerative disease
Characterised by a loss of GABAergic neurones of the basal ganglia, especially atrophy of the caudate nucleus and putamen
- Atrophic caudate nucleus > concomitant enlargement of the frontal horns of the lateral ventricles
Typically diagnosed age 30-50yo, equal incidence in both genders
Presentation is progressive rigidity, choreoathetosis, dementia, psychosis and emotional lability
Genetics: autosomal dominant with complete penetrance and genetic anticipation
- The next generation with have more repeats of CAG and a more severe course of the disease/earlier symptoms
- Chromosome 4p16:3, a CAG trinucleotide repeat
- Microscopically: Huntington nuclear inclusion bodies
Both deep grey matter, and white matter (to a lesser degree) are involved
PICK DISEASE = FRONTOTEMPORAL LOBAR DEGERENATION is and path
A neurodegenerative disease and one of the tauopathies characterised by the accumulation of Pick bodies
Typically manifests between age 40-60, with a male predilection
Characteristic features:
- Pick bodies
- Swollen chromatolytic neurones
- Loss of large pyramidal neurones
- Astrocytic gliosis
Imaging: cortical atrophy of the frontal and temporal lobes
- Can be markedly asymmetrical and affect one area more than another
- Caudate head volume can also be reduced
Differential:
- Other varieties of frontotemporal lobar degeneration
- Alzheimer disease - parietal lobe is more pronounced
ALZHEIMERS is and path
A common neurodegenerative disease, responsible for 60-80% of all dementias
A result of accumulation and deposition of cerebral amyloid-B, the most common cerebral amyloid deposition disease
Typically 85-90yo
Risk factors:
- Advanced age
- Female gender
- Current smoker
- Family history
- Down syndrome
- Psoriatic arthritis - chronic inflammation etc.
The accumulation of cerebral amyloid-beta forms neuritic plaques, neurofibrillary tangles and eventually progressive loss of neurones
Increasing evidence suggests that chronic inflammation is at least partially responsible
Imaging:
- Diagnosis should be made based on two features:
- Mesial temporal lobe atrophy - particularly the hippocampus, entorhinal cortex and perirhinal cortex
- Assessment of volumes should be done accurately, not by eyeballing
- Additionally often have white matter high T2 signal - chronic small vessel ischaemic changes
- SPECT/PET: detect regional hypoperfusion/hypometabolism in a biparietal and bitemporal distribution, while amyloid and tau accumulate in the grey matter and medial temporal lobes respectively
PARKINSONS is and path
A neurodegenerative disease and movement disorder characterised by resting tremor, rigidity and hypokinesia due to progressive degeneration of dopaminergic neurones in the substantia nigra
The most common cause of the parkinsonian syndrome - accounts for 80% of cases
The remainder are others, e.g. Lewy body dementia
The most common form s in elderly patients, and usually sporadic
Clinically:
-Resting pill rolling tremor
- Cog-wheel rigidity
- Bradykinesia
- Postural instability
Pathology:
- The dopaminergic tract is predominantly affected
- Nigrostriatal dopaminergic degeneration > neuronal loss in the substantia nigra pars compacta
- Other areas: basal ganglia, brainstem, autonomic nervous system and cerebral cortex
Imaging:
Loss of the normal swallow tail appearance of susceptibility signal pattern in the substantia nigra on axial imaging
PIT ADENOMA is and path
Primary neuroendocrine tumours that occur in the pituitary gland, one of the most common intracranial neoplasms
Classified into micro (<10mm) and macro (>10mm)
Associations:
A small number are associated with:
- MEN 1
- MEN 4
- Carney complex
- McCune-Albright syndrome
Presentation: either hormonal imbalance or mass effect - esp the optic chiasm
ADAMANTINOUS CRANIOPHARYNGIOMAis and path
Cystic masses with peripheral calcification
Far more common than papillary, and identified in all age groups with peaks in child hood and age 40-60
Primarily suprasellar, with a small intrasellar component present in 20-25%
Purely intrasella is uncommon
Presentation:
- Headache and raised ICP
- Visual symptoms
- Hormonal imbalances
- Short stature and delayed puberty
- Amenorrhoea
- Diabetes insipidus
- Behavioural change due to frontal or temporal extension
Pathology:
- Palisading peripheral columnar epithelium, wet keratin and stellate reticulum that have appearances reminiscent of the enamel pulp of developing teeth - similar to ameloblastomas
- May be a single or multiple cysts filled with thick oily fluid, rich in protein, blood products and/or cholesterol
- Calcification is usually present ~90%
PAPILLARY CRANIOPHARYNGIOMA is and path
WHO grade 1, typically presenting as mostly solid masses
Far less common than adamantinomas, and rare before middle age
Most commonly between 40-60yo
No race or sex has been identified
Primarily suprasella, with a small intrasellar component present in a minority
Purely intrasellar is uncommon
Occasionally appear as masses within the third ventricle
Presentation:
- Headache, raised ICP
- Visual symptoms
- Hormonal imbalances:
- Decreased libido
- Amenorrhoea
- Diabetes insipidus
Formed of mases of monomorphic squamous epithelium with a fibrovascular core and scattered immune cells
“wet keratin” and calcifications are absent - seen in adamantinomatous
Usually solid
DEMYELINATION is and causes
Loss of normal myelin around axons in the CNS
Different from dysmyelination: where the formation of normal myelin is absent
Primary demyelinating disorders:
- Clinically isolated syndrome: may not progress to MS
- Multiple sclerosis
- Variants:
- Tumefactive
- Acute malignant Marburg type
- Neuromyelitis optica (Devic disease)
- Schilder type (diffuse cerebral sclerosis)
- Balo concentric sclerosis
- Acute disseminated encephalomyelitis (ADEM)
- Transverse myelitis
- Chronic inflammatory demyelinating polyneuropathy
- Guillain-Barre syndrome
Infective:
- Progressive multifocal leukoencephalopathy
- HIV encephalitis
Toxic:
- Osmotic demyelination syndrome
- Posterior reversible encephalopathy syndrome
Metabolic/genetic
- Leukodystrophies
MULTIPLE SCLEROSIS is and path
An acquired chronic relapsing demyelinating disease involving the CNS
Disseminated in space and time
Presents between adolescence and the 6th decade, with a peak around 35yo
Strong female predilection
Presentation depends on the area of involvement
- Common - optic neuritis, internuclear ophthalmoplegia
Several patterns of longitudinal disease
- Relapsing-remitting ~70%
- Secondary progressive
- 85% of those with RR MS eventually enter this phase
- Primary progressive 10%
- Progressive with relapses
- Benign 15-50%
Investigations
- History
- Oligoclonal bands in CSF
- Immunoglobulin G in serum
- Abnormal visual evoked potential
Pathology:
- Poorly known
- An infectious agent is suspected
- A cell mediated autoimmune response against one’s own myelin components, with loss of oligodendrocytes, with little or no axonal degeneration in the acute phase
- In the later stage, loss of oligodendrocytes results in axonal degeneration
- Each lesion/plaque undergoes three stages:
Early acute - active
- Active myelin breakdown
- Plaques are pink and swollen
Subacute
- Abundant macrophages
- Plaques are paler in colour
Chronic stage - inactive plaques/gliosis
- Little or no myelin breakdown
- Gliosis with associated volume loss
- Appear grey/translucent
NEUROMYELITIS OPTICA is and path
A severe demyelinating disease caused by an autoantibody to the aquaporin-4 water channel
The classic presentation is: optic neuritis, longitudinally extensive myelitis and positive anti-AQP4 antibody
Slightly older group than MS
BALO CONCENTRIC RING MS is
A rounded lesion with alternating layers of high and low signal intensity on MRI
“bulls-eye or onion-bulb” appearance
T1/2: irregular concentric areas
ADEM is and path
A monophasic acute inflammation and demyelination of white matter, typically 1-2weeks following a viral infection or vaccination
Grey matter, especially basal ganglia, is often involved.
Spinal cord to a lesser extent
Thought to occur from a cross-reactivity in immunity to viral antigens, triggering a subsequent autoimmune attack on the CNS
Half of the confirmed cases have anti-MOG (myelin oligodendrocyte glycoprotein)
Markers
- CSF pleocytosis
- CSF may show increase in myelin basic protein
- Anti-MOG antibodies
Involvement of the callososeptal interface is unusual
TRANSVERSE MYELITIS is
An inflammatory condition affecting both halves of the spinal cord
Typically long segment of greater than 2/3rds of the cross-sectional area of the cord with variable enhancement and no diffusion restriction
CSF: need to demonstrate inflammation = pleocytosis or increased IgG index or enhancement
Aetiology:
- Acute infection - most commonly viral
- Post infection
- Autoimmune
- Post vaccination
- Systemic malignancy
- Atopy and allergy
CENTRAL PONTINE MYELINOLYSIS is
Acute demyelination in the setting of osmotic changes - typically the rapid correction of hyponatraemia
Classic trident shaped appearance. Can also involve the basal ganlia
The peripheral fibres (corticospinal tracts, ventrolateral longitudinal fibres) as well as periventricular and subpial regions are typically spared
CHIARI I is and path
The most common Chiari variant
Characterised by the caudal descent of the cerebellar tonsils through foramen magnum
Underlying cause: a mismatch between size and content of the posterior fossa
Four groups:
- Abnormal skull base - e.g. short clivus
- Cervical segmentation anomalies e.g. Klippel-Feil syndrome
- Small cranial vault and/or posterior fossa and consequent overcrowding
- Excessive brain tissue
Has to protrude >5mm to count
Associations:
- Cervical cord syrinx ~35%
- Hydrocephalus
- Skeletal anomalies
- Platybasia/basilar invagination
- Atlanto-occipital assimilation
- Sprengal deformity
- Syndrome associations:
- Klippel-Feil syndrome
- Crouzon syndrome
- Hajdu-Cheney syndrome
Look for features of intracranial hypertension as a differential
Perform CSF flow studies
CHIARI II is and path
Myelomeningocele (lumbosacral spina bifida aperta) with a small posterior fossa, with descent of the brainstem and cerebellar tonsils and vermis
Due to in utero malformation of the spine and cranial structures resulting in characteristic displacement of the medulla, 4th ventricle and cerebellum through foramen magnum
Thought to be due to open spinal dysraphism
Associations
Spinal
- Syrinx
- Scoliosis
- Segmentational anomalies 50%
- Klippel-Feil syndrome
- Diastematomyelia
Cerebral
- Corpus callosum dysgenesis
- Absent septum pellucidum
- Obstructive hydrocephalus
Skeletal
- Club foot
DANDY WALKER MALFORMATION is
A spectrum of posterior fossa malformation, characterised by:
- Hypoplasia of the vermis and cephalad rotation of the vermian remnant
- Cystic dilatation of the 4th ventricle, extending posteriorly
- Enlarged posterior fossa with trocular-lambdoid inversion
CAVERNOMA is and path
Cerebral cavernous venous malformations
A slow flow venous malformation
Typically presents ~40-60yo, most with a single lesion
Multiple lesions may be familial - familial cavernous malformation syndrome
Risk of haemorrhage is 1% per patient year for familial, lower for sporadic
“mulberry-like’ clusters of hyalinised dilated thin-walled capillaries with surrounding haemosiderin
- These vessels are thrombosed to varying degrees
- There is no normal brain between the interstices of these lesions - unlike AVMs
Associations:
- Developmental venous anomaly
Tend to be supratentorial ~80% of cases, but can be found anywhere, including the brainstem
DAI is and classification
Diffuse axonal injury is characterised by multiple focal lesions with a characteristic distribution: typically located at the grey-white matter junction, in the corpus callosum and in more severe cases in the brainstem.
A classification :
Grade 1: microscopic-only evidence of axonal damage in the white matter of the cerebral hemispheres including corpus callosum, in the brainstem, and, occasionally, in the cerebellum
Grade 2: focal lesion in the corpus callosum, in addition to diffuse axonal damage
Grade 3: focal lesions in both the corpus callosum and dorsolateral quadrant of the rostral brainstem, in addition to diffuse axonal damage
WARTHINS is and path
Common tumour of parotid gland with double layer of epithelial cells resting on dense lymphoid stroma
2nd most common benign salivary gland tumour
Almost always is the parotid gland, 10% of parotid tumours. Often in the tail
70% of bilateral salivary glands are warthin tumours
Usually male smokers age 40+
Associations:
- Smoking, irradiation, TB
May occur synchronous with pleomorphic adenoma and salivary duct carcinoma
Malignant change 1% - to lymphoma, Merkel cell carcinoma, adenocarcinoma etc.
Pathology:
Encapsulated, lobulated, mulitcystic with mucinous/serous secretions
Presence of a mural nodule is highly suggestive. solid cystic.
PLEOMORPHIC ADENOMA is and path
Benign mixed tumours
Well-circumscribed rounded masses, most commonly within the parotid gland
70-80% of benign salivary gland tumours
Mixed histology
Contain both epithelial and myoepithelial (mesenchymal) tissues, with mixed histology
Appear encapsulated, well circumscribed, however the pseudocapsule is incomplete
MUCOEPIDERMOID CARCINOMA is and path
A malignant glandular epithelial neoplasm characterised by mucous, intermediate and epidermoid cells, with columnar, clear cell or oncocytoid features
Most common salivary gland neoplasm in adults and children
Occurs in major > minor salivary glands
Possibly associated with ionising radiation
Pathology:
A mixture of:
- Mucous secreting cells
- Squamous cells
- Lymphoid infiltrate
Histology:
- Clear mucin-containing cells, which stain reddish pink with the mucicarmine stain
Histologically classified as:
- Low – well differentiated with little cellular atypia
- High proportion of mucous cells
- Prominent cyst formation
- Intermediate
- High – poorly differentiated with cellular pleomorphoism
- High proportion of squamous cells
- Solid with few, if any, cysts
heterogenous enhancement
ADENOID CYSTIC CARCINOMA is and path
A carcinoma of the primary salivary glands characterised by its biphasic ductal and myoepithelial differentiation
May occur in major and minor salivary glands
- Most commonly the parotid
Grows in tubular, cribriform and/or solid patterns
Epidemiology:
- M=F
- Mean age ~57
Locally aggressive, propensity for perineural spread
homogenous enhancement
ACINAR CELL CARCINOMA is and path
A histological subtype of adenocarcinoma
Generally considered low grade,
Characterised by serous acinar cell differentiation in at least some of the neoplastic cells
Essential features:
- Parotid is the most common
- Favourable prognosis – low local recurrence, distant mets
10-17% of primary salivary gland malignancies
2nd most common in children, 3rd in adults: mucoepidermoid carcinoma > adenoid cystic carcinoma
THYROGLOSSAL DUCT is/apath
Epithelium-lined connection between the foramen caecum and the thyroid that forms during the descent of the thyroid during embryological development
Arises from the proximal primitive foregut between the first and second pharyngeal pouches
Passes anterior to the body of the hyoid bone, curving backwards and superiorly to reach behind the bone, before turning inferiorly and continuing to the isthmus of the thyroid
The pyramidal lobe, if present marks this point
The tip of the duct bifurcates, forming the two lobes of the gland
HASHIMOTOS is and path
Autoimmune disease with goiter, elevated circulating antithyroid peroxidase and antithyroglobulin antibodies
90-95% in women, usually 45-65yo
May coexist with other conditions – SLE, RA, Sjogren syndrome, MALT lymphoma etc.
Associated with well differentiated thyroid cancer, and may evolve into thyroid lymphoma
Autoantibodies include:
- Anti-TSH: specific for hashimoto’s and grave’s disease
- Antithyroglobulin
- Antithyroid peroxidase
Pathology:
- Diffuse enlargement of the thyroid gland with intact capsule
- May have adhesions, but easily separated from other structures
- Surface resembled lymph nodes with tannish yellow colour
- May have increased interlobular fibrosis, or be fibrotic
- Occasionally gland in nodular or asymmetric
- No necrosis of calcification
- Histologically, extensive lymphocytic infiltrate with germinal centre formation
PAPILLARY THYROID CA is and path
The most common thyroid malignancy
Typically middle ages, ~3-4th decades
More common in women
Associations:
- Gardner syndrome
- Cowden syndrome
- FAP
Tendency to metastasise early to local lymph nodes - check ipsilateral jugular chain, level III + IV
Distal haematogenous dissemination is less common than with follicular cancer
Lymphatic spread is more common
Histopath:
- Delicate stalks of epithelial cells
- Characteristic orphan annie eye nuclear inclusions and psammoma bodies
FOLLICULAR THYROID CA is and path
Typically occurs in women, and an older age group than papillary
It metastasises late to lymph nodes, but only 5-10% have nodal mets at the time of diagnosis
- Haematogenous spread is more common – 20% at the time of presentation
Genetics: RAS oncogene is positive
Variants:
- Classic follicular thyroid carcinoma
- Insular variant
Cytology required, FNA can’t differentiate between follicular thyroid adenoma and follicular thyroid carcinoma
MEDULLARY THYROID CA is and path
Non-familial case – typically peaks in the 3rd - 4th decades
Associations:
- MEN 2 – both A and B
- VHL
- NF1
Arises from the parafollicular C cells of the thyroid
Amyloid components are seen on histology
Characterised by consistent production of a hormonal marker (calcitonin), calcification of both primary and metastatic sites
Mets up to 50% of the time
ANAPLASTIC THYROID CA is and path
A highly aggressive form of thyroid cancer
Typically occurs in the elderly, with peak incidence in the 6th-7th decades
A significant proportion may have a history of concurrent multinodular goitre
Tend to present late with symptoms of neighbouring structure compression
US – may show microcalcifications
Highly infiltrative mass
DEQUERVAINS THYROIDITIS is and path
A subacute granulomatous thyroiditis – self limited, subacute thyroiditis
Inflammation of the thyroid gland that includes granulomas
75% in women, usually 30-50yo
- Associated with HLA-B35
Aetiology may be systemic viral infection,
Self-limited, usually resolves in 6-8 wks, with only 1% having permanent hypothyroidism
- May have transient hypothyroidism at 2-8 wks
Focal – diffuse enlargement of the thyroid gland >2x normal size
- May be asymmetric with nodules of variable size,
- May be firm, but does not adhere to surrounding structures
Microscopic
- Early – neutrophils and destruction of follicles with colloid depletion
- Later – non-caseating granulomas surrounding follicles and engulf colloid
PARATHYROID HYPERPLASIA is and path
Diffuse enlargement of the parathyroid glands
A less common cause of primary HPTH
Female predilection
~50% have asymmetric enlargement of the parathyroid glands
Aetiology:
primary
- Sporadic 80% - radiation and lithium exposure
- Familial 20% - MEN 1 and 2a
Secondary
- Renal failure
HYPERPARATHYROIDISM is and path
Increased parathyroid hormone leads to increased osteoclastic activity
Results in bone resorption and cortical thinning + osteopenia
subtypes
Primary
- Parathyroid adenoma 80%
- Parathyroid hyperplasia 10-15%
- Parathyroid carcinoma 1-5%
Secondary
- Chronic hypocalcaemia with renal osteodystrophy being the most common cause
- Results in parathyroid hyperplasia
RETINOBLASTOMA is and path
The most common intraocular neoplasm found in childhood
Characterised by a heterogenous retinal mass with calcifications, necrotic components and increased vascularisation
May be sporadic or secondary to a germline mutation of the retinoblastoma protein tumour suppressor gene (RB), which is usually inherited
Can be:
Bilateral (30-40%) = definitely have a germline mutation
Unilateral 60-70% of cases, 15% of these have a germline mutation
So around 55%
The mutation is inherited in an autosomal dominant fashion, with 90% penetrance
Most cases are diagnosed within the first 4yrs of life, typically ~18-24yo
A germline mutation also means increased risk of developing trilateral retinoblastoma (unilateral or bilateral retinoblastoma and pineoblastomas
Also osteosarcoma
Pathology:
Three patterns of growth:
- Endophytic
- Growth occurs inwards into the vitreous
- Cell clusters may detach and float in the vitreous
- Exophytic
- Growth occurs outwards
- Associated with non-hematogenous retinal detachment
- Combined endophytic and exophytic
May metastasise via direct spread into the orbit, along the optic nerve into the brain, or into the subarachnoid space = leptomeningeal metastases
It can also haematogenously metastasise preferentially to the bone, bone marrow and liver
Rarely it will spread to regional lymph nodes
Histology:
- A small round-cell tumour of neuroepithelial origin
- Flexner-Wintersteiner rosettes (relatively specific for retinoblastoma) and Homer-Wright pseudo-rosettes (also found in other PNETs)
ONDONTOGENIC KERATOCYST is and path and imaging why not
Rare benign cystic lesions involving the mandible or maxilla
Locally aggressive and tend to recur after excision
Predominantly in younger patients (2nd and 3rd decades)
May be seen in either the body or ramus of the mandible (~70%) or maxilla
May be a male predilection
Typically incidental
Pathology:
- Thin walled, friable cyst containing fluid and debris
- Viscosity of the contents ranges
- They originate from epithelial cell rests found along the dental lamina and periodontal margin of the alveolus of the mandible
- Inflammation may impede histologic characterisation
Associations
- Basal cell naevus syndrome - strong association - Gorlin syndrome
- Marfan syndrome
- Noonan syndrome
OPG
- Solitary, radiolucent, unilocular, expansile with smooth, corticated borders
- Often scalloped around the roots of the teeth
- In the maxilla, they expand into the maxillary sinus
- Appearance and location can vary
MRI
- T1 - high
- T2 - heterogenous
- DWI - restricts, due to presence of keratin
- Peripheral enhancement, no nodular component
Differentials:
- Dentigerous cyst - both can be positioned pericoronally/ Tend to attach to the cemento-enamal junction of teeth
- Radicular cyst - doesn’t scallop, septate and is more expansile
- Ameloblastoma - multilocular, more expansile with a soap-bubble appearance. Tends to be more aggressive with more significant tooth resorption
DENTIGEROUS CYST is and path and imaging
Slow growing benign and non-inflammatory odontogenic cysts
Well-defined and unilocular radiolucency surrounding the crown of an unerupted or impacted tooth within the mandible
Second most common odontogenic cyst
- After periapical
Typically seen in the 2nd-4th decades of life
Formed by the hydrostatic force exerted by the accumulation of fluid between reduced enamel epithelium and the tooth crown of unerupted teeth
The cyst encloses the crown and is attached to the neck at the cementoenamel junction
Almost exclusively occur in permanent dentition
Stratified squamous non-keratinising epithelium lines the cyst
Over 75% of all cases are located in the mandible
Associations
- Mucopolysaccharidoses
- Basal cell naevus syndrome
Imaging:
- a cystic expansile pericoronal lesion
- Contains the crown of an impacted tooth projecting into a cystic cavity
- No further imaging is required
- Thin regular sclerotic margin
- Expand the overlying cortex without breach
- The roots of the teeth are often outside the cyst
MRI
- T1 low
- T2 high
- No solid component or enhancement
AMELOBLASTOMA is and path and imaging
Locally aggressive benign tumours that arise from the mandible, less commonly the maxilla
Usually present as a slowly but continuously growing lesion near the angle of the mandible in the 3rd - 5th decade
Second most common tumour - odontoma is the most common
Arise from ameloblasts, which are part of the odontogenic epithelium, responsible for enamel production and eventual crown formation
Four forms are described:
- Unicystic
- Solid (multi-cystic)
- Desmoplastic
- Peripheral (extra-osseous)
There are no histo features to differentiate between craniopharyngiomas
Imaging:
- Multicytic, expansile “soap bubble” lesions, with well-demarcated borders and no matrix calcifications
- Resorption of adjacent teeth and root blunting is often a feature
MRI - mixed solid and cystic pattern, with thick irregular wallls
Differential:
- ABC
- Other odontogenic cysts
ODONTOMA is and path and imaging
Most common odontogenic tumour
Can occur at any age, typically diagnosed ~2nd decade of life
“tooth hamartoma” - consists of various tooth components
Complex - irregular calcified lesions with no distinct tooth components
Compound - identifiable tooth components
Associations:
- 1/2 will be associated with an unerupted tooth
- A feature of Gardner syndrome
Imaging:
- Initially lucent, develops small calcifications which eventually coalesces to form a radiodense lesion with a lucent rim
- Epithelial components may occasionally give rise to a dentigerous cyst
PERIAPICAL CYST is and path
The most frequent cystic lesion related to teeth and result from infection of the tooth
Typically seen in middle to older 3rd-6th
Results from infection of the tooth, which spreads to the apex
Usually <1cm in diameter and bordered by a thin rim of cortical bone
Differentials:
- Periapical abscess
- Periapical granuloma
- Dentigerous cyst
- Keratocystic odontogenic tumour
JUVENILE NASOPHARANGEAL ANGIOFIBROMA is and path
Rare benign, but locally aggressive, vascular tumours
Occur almost exclusively in males, typically adolescence
Benign but highly vascular tumours
May be locally aggressive
Exact site is variable, but thought to arise from the posterior choanal tissues in the region of the sphenopalatine foramen
Imaging:
- Arise in the region of the sphenopalatine foramen, usually sizeable at diagnosis and frequently extend medially into the nasopharynx, laterally into the pterygopalatine fossa, eventually going into the orbit, paranasal sinuses, intracranial cavity and infratemporal fossa
- Bony remodelling/resorption rather than destruction
- Majority are supplied by the ECA, ICA less common
MRI
- T1 intermediate
- T2 heterogenous – dark flow voids
- Prominent enhancement
PELVIC INFLAMMATORY DISEASE is and path
A spectrum of infection and inflammation of the upper female genital tract, resulting in a range of abnormalities
Highest incidence is sexually active women, 75% < 25yo
Presentation:
- Acute pelvic pain, cervical motion tenderness, vaginal discharge, fever, dyspareunia and leucocytosis
- Right upper quadrant pain - perihepatitis in Fitz-Hugh-Curtis syndrome
Pathology:
- Ascending spread of micro-organisms, unrelated to pregnancy or surgery
- Generally ascends from the vagina/cervix to the endometrium, then fallopian tubes +/- contiguous structures e.g. tubo-ovarian abscess, peritonitis
- Can result from a number of causative organisms
Common:
- Chlamydia trachomatis - pelvic chlamydial infection
- Neisseria gonorrhoeae - pelvic gonococcal infection
- Polymicrobial infection ~35%
- Less common: TB, actinomyces
Usually bilateral, except when caused by the direct extension of an adjacent inflammatory process e.g. appendiceal, diverticular or post-surgical abscesses
Often non-specific features, but disproportionate to what may be apparent from the symptoms
Complications:
- Tubo-ovarian abscess
- Pyosalpinx
- Infertility due to tubal adhesions
- Ectopic pregnancy
- Chronic pelvic pain
- Peritonitis
- Ovarian vein thrombosis
- Peritoneal adhesion formation causing bowel obstruction
- Fitz-Hugh-Curtis syndrome
MULLERIAN DUCT ANOMALIES
Congenital abnormalities that occur when the Mullerian ducts don’t develop correctly
May be as a result of complete agenesis, defective vertical or lateral fusion or resorption failure
Occur in 1-5% of women
Majority are asymptomatic
Subtypes:
- Uterine agenesis 10%
- Arcuate uterus ~7%
- Unicornuate uterus ~15%
- Uterine duplication anomalies
- Uterus didelphys ~7.5%
- Bicornuate uterus ~25%
- Septate uterus ~45%
- Subseptate uterus
The shape of the external uterine contour is crucial to differentiate a septate uterus from a bicornuate uterus
ADENOMYOSIS is and path
A common uterine condition of ectopic endometrial tissue in the myometrium
Classically, affects multiparous women of reproductive age
Most patients are asymptomatic, but can cause dysmenorrhoea, menorrhagia, dysparenunia etc.
Histologically defined as the presence of ectopic endometrial tissue within the myometrium
The exact cause is unknown, but thought that the endometrial glands directly invade the myometrium resulting in spiral vessel angiogenesis and adjacent smooth muscle hyperplasia and hypertrophy
Postulated that the dysfunctional hypertrophied muscular tissue surrounding the ectopic endometrial glands prevents uterine contractions from tamponading bleeding myometrial arterioles, hence these patients frequently present with dysfunctional uterine bleeding or menorrhagia
Associations:
- Co-existent endometriosis 20%
- Leiomyomas 50%
- Endometrial hyperplasia
- Endometrial polyps
Three forms:
- Diffuse adenomyosis - most common
- Focal adenomyosis and adenomyoma (term used for focal adenomyosis)
- Cystic adenomyosis and adenomyotic cyst
Typically relatively generalised, affecting large portions of the uterus, but sparing the cervix
ENDOMETRIAL HYPERPLASIA is and path
Endometrial hyperplasia
- Defined as diffuse smooth thickening >15mm premenopause, >5mm post menopause.
- An increased proliferation of the endometrial glands relative to the stroma, resulting in an increased gland-to-stroma ratio when compared with normal proliferative endometrium.
Now classified as non-atypical hyperplasia and atypical hyperplasia
- Non atypical rarely progress to adenocarcinoma 1-3%
- Atypical hyperplasia - have a lot of overlap with well-differentiated endometrioid adenocarcinoma and accurate distinction without hysterectomy isn’t possible. 23-48% are found to have carcinoma when a hysterectomy is performed
Associations:
- Obesity
- PCOS
- Pregnancy - including ectopic
- Oestrogen-secreting ovarian tumours - granulosa cell tumour of the ovary
- Tamoxifen
ENDOMETRIAL CARCINOMA is and path
he most common gynecological malignancy, with peak incidence ~6th decade
Risk factors:
Anything that leads to increased oestrogen exposure
- Oestrogen replacement therapy
- PCOS
- Tamoxifen
- Obesity
- Early menarche or late menopause
- Nulliparity
- Oestrogen producing tumours e.g. g-ranulosa cell cancer
= Diabetes mellitus
Smoking may be protective
Associations:
= HNPCC, 30-50x increased lifetime risk
Two subtypes
Type 1: 80%
= In the setting of unopposed hyperoestrogenism and endometrial hyperplasia
= Most commonly obese women, age 55-65
= Tamoxifen
= Well differentiated tumour with relatively slow progression, and a more favourable outcome
= PTEN gene mutation occurs in 30-80%
Type 2: 20%
= In the setting of endometrial atrophy, females 65-75
= P53 mutation occurs in up to 50%
= Tend to be less differentiated and spread early via lymphatics or through Fallopian tubes into the peritoneum = poorer prognosis
ENDOMETRIAL CARCINOMA staging
FIGO
1. confined to uterus
a;less than half myome
b; outer half myomet
- extends to cervical stroma
- beyond uterys
a; serosa or adneza
b; vagina or parametrium
c pelic or paraaortic nodes
c1 pelvic c2 parasortic - bladder/rectal or distant
a; bladder/bowel
b; distant mets
UTERINE LEIOMYOMAS are and path
Benign tumours of myometrial origin, and the most common solid benign uterine neoplasm
Commonly an incidental finding on imaging
Occur in ~25% of women of reproductive age, particularly common in the African population
Responsive to hormones e.g. stimulated by oestrogen, so growth is accelerated during pregnancy and involution occurs with menopause
Pathology
- Benign monoclonal tumours, predominantly composed of smooth muscle cells with variable amounts of fibrous connective tissue
- Commonly multiple ~85%, and range significantly in size
Numerous locations
Intrauterine
- Intramural - most common
- Subserosal - may be pedunculated and simulate an adnexal mass
- Submucosal - least common, 10-15%
Extrauterine
- Broad ligament leiomyoma
- Cervical leiomyoma
- Parasitic leiomyoma
- Diffuse uterine leiomyomatosis
Can undergo
- Hyaline degeneration
- Cystic degeneration ~5%
- Myxoid degeneration
- Red degeneration - due to haemorrhagic infarction, esp in pregnancy
UTERINE LEIOMYOSARCOMA are and path
The most common location for a leiomyosarcoma
Irregular margins of a uterine leiomyoma on MRI is suggestive of sarcomatous transformation, but not specific
Mostly arise de novo from uterine musculature or the connective tissue of uterine blood vessels, but can rarely arise from a pre-existing leiomyoma
The pattern of tumour spread is myometrium > pelvic blood vessels and lymphatics > contiguous pelvic structures, abdomen, and distantly often to the lungs
Differentiated histologically from a leiomyoma by the presence of infiltrative margins, nuclear atypia and increased mitotic figures
PCOS is and path
A chronic anovulation syndrome associated with androgen excess
The Rotterdam criteria is used to make the diagnosis and requires any two of the following three criteria for the diagnosis
- Ovulatory dysfunction (oligo- and/or anovulation)
- Clinical and/or biochemical signs of hyperandrogenism
- Polycystic ovarian morphology on US
The classic triad is:
- Oligomenorrhoea and/or anovulation
- Hirsutism
- Obesity
Pathology
Markers
- Anti-Mullerian hormone (AMH) levels are generally increased
- Measure free testosterone, free androgen index, or calculated bioavailable testosterone, androstenedione
Associations:
- Subfertility and recurrent pregnancy loss
Long term increased risk of:
- T2DM
- Dyslipidaemia
- Cardiovascular disease
- Endometrial cancer
- High prevalence of anxiety and depression
- Increased risk of OHSS when undergoing IVF
US criteria:
- In patients >8yrs post menarche, with transvaginal images:
- Follicle number >20 per ovary and/or
- Ovarian volume >10ml
- No corpora lutea, cysts or dominant follicles are present
Not part of the criteria:
- Hyperechoic central stroma
- Peripheral location of follicles
- Follicles of similar size, 2-9mm
OVARIAN SEROUS IS AND PATH
The commonest of the epithelial ovarian tumours
More prevalent than mucinous
Subdivided into benign 60%, borderline 15% and malignant 25%
- Malignant tend to be older
- Benign: no cellular proliferation
- Borderline: cellular proliferation + minor nuclear atypia without invasion
- Malignant: cellular proliferation + nuclear atypia + stromal invasion
Pathology:
- Defined by a histological resemblance to normal fallopian tubal epithelium
Imaging:
- Typically smaller than mucinous
- Typically unilocular and homogenous
- Often bilateral, esp if maligannt
- Psammoamtous calcification is a feature, not seen in mucinous
Features favouring malignant:
- Large cystic mass
- Thick irregular walls and septa
- Papillary projections
- Large soft tissue component
- Ascites
- Evidence of invasive spread or adenopathy
Differentials:
- Functional cyst - tend to change or resolve in the next menstrual cycle
- Paraovarian cyst - ovary is separate from the cyst
- Mucinous cyst - tend to be multiseptated, often larger than serous tumours
- Monolateral rather than bilateral
- Cystic loculi with variable signal intensities on MR
OVARIAN MUCINOUS
A subgroup of epithelial tumours
Represent 10-15% of all ovarian tumours, 10% of malignant ovarian tumours
Typically women 20-40yo (benign)
Borderline and malignant tumours tend to be an older age range
Pathology
- Multiple cysts lined by mucinous epithelium, often resembling gastrointestinal-type epithelium
- KRAS mutations are a common feature
Subtypes:
- Cystadenoma 80%
- Borderline 10-15
- Cystadenocarcinoma 5-10%
Imaging:
- Often larger than serous counterparts
- Tend to be more multilocular with small cystic components +/- honeycomb-like locules
- Calcification is comparatively rare, and tends to be linear
- Usually unilateral
- Peritoneal carcinomatosis is less common compared with serous tumours
- May have accompanying pseudomyxoma peritonei
MRI
- T1 - depends on the mucin concentration
- T2 - high
Differentials:
Serous tumour
- Calcification
- Smaller
- More frequently bilateral
Haemorrhagic cyst
- Smaller
- Unilocular
Endometrioma
- High signal on T1, with T2 shading
Which is true regarding ovarian teratomas? (March 2016)
Ovarian teratomas are associated with limbic encephalitis
Immature teratomas are associated with carcinoid syndrome
Ovarian teratomas are associated with limbic encephalitis
True - paraneoplastic limbic encephalitis.
Mature (benign) teratomas - cystic and often referred to as dermoid cysts. Usually found in young women during the active reproductive years.
1% of dermoids undergo malignant transformation, most commonly to SCC
Specialised/monodermal teratomas - struma ovarii and carcinoid. Always unilateral. Carcinoid can cause carcinoid syndrome. They usually arise from intestinal tissue found in teratomas. Metastatic intestinal carcinoid is virtually always bilateral. Primary ovarian carcinoid is not.
Immature malignant teratomas - rare. Grow rapidly and frequently penetrate the capsule, spread either locally or distally.
TERATOMA is and path
The most common group of ovarian germ cell tumours
Can be divided into 3 main subtypes
Mature
- Also called a dermoid cyst
- Slow growing elements from multiple germ cell layers
- Dermoid: only dermal and epidermal elements (both ectodermal)
- Teratoma: mesodermal and endodermal
- Encapsulated tumours with mature tissue or organ components
- Composed of well-differentiated derivations from at least 2 of 3 germ cell layers
- Typically smaller than 10cm
- Bilateral in 10-15%
- US:
- Tip of iceberg sign
- Rokitansky nodule
- Don’t metastasise
Immature
- Uncommon, differ histologically and clinically - more malignant
- Affect a younger age group, usually in the first two decades of life
- The proportion of immature tissue elements correlates with the tumour grade
- Large, encapsulated masses with a prominent solid component
- May have features of a mature teratoma - hair/cartilage/bone/calc
- Associations:
- Ipsilateral mature cystic teratoma 25%
- Contralateral immature teratoma 10%
- Markers
- Doesn’t produce b-HCG
- Serum AFP elevation in 50%
- Imaging
- A large, heterogenous mass with a prominent solid component
- Tend to be larger than mature cystic teratomas
Specialised
- Struma ovarii
MEIGS SYNDROME is and path
Defined as the presence of ascites and pleural effusion in associated with a benign, usually solid ovarian tumour
In the vast majority of cases, the primary tumour is an ovarian fibroma
Less than 1% present with this syndrome
Other primary tumours:
- Fibrothecoma
- Thecoma
- Granulosa cell tumour
- Brenner - rare
Usually ~7th decade of life, rare <30yo
Speculative pathophysiology of ascites
Plural fluid tends to be right sided
Benign and resolves after resection of the primary tumour
GESTATIONAL TROPHOBLASTIC DISEASE is and path
Results from the abnormal proliferation of trophoblastic tissue, and encompasses a spectrum of diseases
Hydatidiform mole: complete/partial/coexistent
Gestational trophoblastic neoplasia
- Invasive mole ~10%
- Choriocarcinoma 1%
- Placental site trophoblastic tumour
- Epithelioid trophoblastic tumour
Typically women >40, and <20 are at higher risk
Presentation:
- Uterus larger than pregnancy age
- Abnormally high B-HCG
- Hyperemesis
- Hypertension
- Theca-lutein cysts
Pathology: all characteristically are an abnormal proliferation of trophoblasts, but different components predominate in different tumours
Hydatidiform mole
Complete - commonest ~80%
- 46 XX or 46 XY: paternal chromosomes only
- No fetus
- BHCG markedly elevated
- Atypia of cells present
- May progress to an invasive mole ~15%, or choriocarcinoma ~5%
Partial
- 69XXX or 69XXY: paternal and maternal chromosomes
- May have fetus or fetal components
- BHCG moderately elevated
- No cellular atypia
Gestational trophoblastic neoplasia
Invasive mole
- Distorts uterine zonal structures
- Boundaries between a tumour and myometrium are irregular and indistinct
- May invade parametrial tissue and blood vessels
Gestational choriocarcinoma
- May look identical to a hydatidiform mole
- Arises following:
- Molar pregnancy 50%
- Miscarriage 30%
- Normal pregnancy 20%
- Can appear less vascular than a complete mole
- Tends to invade myometrium through venous plexuses
- Patients often present with multiple metastases without an easily identified primary
BRENNER TUMOUR is and path
An uncommon surface epithelial tumour of the ovary
Account for ~3% of ovarian epithelial neoplasms
Typically women in their 5th-7th decades of life
Pathology: transitional cells covered by fibrous stroma, similar to neoplasms of the urothelium
Associations:
- Another epithelial ovarian neoplasm of either the ipsilateral or contralateral ovary in ~30% of cases
- Bilateral in 6-7%
ENDOMETRIOID tumour is and path
A subtype of epithelial ovarian tumours
Majority are malignant and invasive
Usually characterised as complex non-specific solid-cystic masses and found associated with endometriosis
The second commonest malignant ovarian neoplasm
Similar path to other tumours, with variable solid and cystic components
Benign is rare
Associations:
- Synchronous endometrial carcinoma or endometrial hyperplasia may be present in up to 1/3 of cases
- Endometrioid carcinoma is the most common malignant neoplasm arising within an endometioma
Bilateral in 25-40%
Look for endometrial thickening, evidence of endometriosis or a contralateral mass
CHORIOCARCINOMA IS AND PATH
A rare subtype of ovarian germ cell tumour
Account for <1%
Occur in prepubertal girls and post menopausal women
May occur during or outside of pregnancy
Can represent metastasis from uterine choriocarcinoma, or arise from an ectopic pregnancy
Serum BHCG is elevated
A vascular solid tumour with cystic, haemorrhagic and necrotic areas
MIXED MULLERIAN TUMOUR OF THE OVARY IS AND PATH
A rare type of mixed ovarian tumour with both epithelial and stromal components
Biphasic tumours with both carcinomatous (epithelial) and sarcomatous (stromal) elements
JUVENILE GRANULOSA CELL is and path
Classified as ovarian sex cord/stromal tumours
Typically occur in premenarchal girls and young women, ~13yo
Precocious puberty as a consequence of oestrogen secretion
Associations:
- Maffucci syndrome
- Ollier disease
Vary varied appearance.
SERTOLI - LEYDIG is and path
A subtype of ovarian sex cord stromal tumour
Rare, typically <30yo
Most are unilateral and confined to the ovaries
Characterized by the presence of testicular structures that produce androgens
Only 30% are hormonally active
Typically a solid/cystic mass
THECOMA is and path
Benign sex cord/stromal origin tuours
Secrete oestrogen = described as functional ovarian tumours
Typically present in older women, >80% post menopausal
Pathology:
- Same histopath spectrum as fibroma/fibrothecoma
Associations:
- Most have a mixture of fibroma and thecoma components
- More than 20% have concurrent endometrial carcinoma
MYOSITIS us
A form of myopathy: a broad range of diseases which lead to dysfunction of skeletal muscle
Wide range of differentials:
- Inflammatory
- Infectious
- Drug related
- Trauma
MRI is the gold standard, demonstrating oedema in the affected muscle
Inflamed muscles demonstrate contrast enhancement
If chronic, T1 will show fat replacement and atrophy
INCLUSION BODY MYOSITIS is and path
An inflammatory myositis, often considered the most common acquired myopathy in patients > 50yo
Tends to present in older individuals, with greater occurrence in males 3:1
Clinical onset is gradual: months - years.
- Weakness peripherally of the wrist and fingers
- Dysphagia in approximately 50%
Pathology:
- Chronic, progressive muscle inflammation accompanied by muscle weakness
- Inflammation isn’t considered a dominant component of the disease
- Pathognomonic is the presence of inclusion bodies in the nucleus and cytoplasm of affected muscle cells
Can affect both proximal and distal muscles, usually bilateral, although weakness may affect only one side of the body
Recognized associations:
- Diabetes mellitus ~20%
- Other autoimmune conditions ~15%
No response to steroids etc. Mangagement is essentially suportive
FIBROMATOSIS is
A wide range of soft tissue lesions that share an underlying histopathologic pattern of fibrous tissue proliferation
They occur in a variety of anatomic sites, and also vary in their behaviour
Ranging from indolent/benign lesions to metastatic/malignant
NODULAR FASCIITIS is and path
A rapidly growing non-neoplastic soft tissue lesion which is frequently located in the deep subcut region or in the fascia
The most common locations are the volar aspect of the forearm, the lower extremity (16%), chest and back (20%), head and neck (18%)
Typically manifests as a rapidly growing mass
Often in patients 20-40yo, but children may also be affected
Pathogenesis is poorly understood, possible reaction to trauma
Location:
Three subtypes based on involvement location
- Subcutaneous
- Intramuscular
- Fascial
Microscopic:
- Benign proliferation of fibroblasts and myofibroblasts, typically mistaken for a sarcomatous lesion due to rapid growth, abundant spindle-shaped cells and mitotic activity
Imaging:
- Tend to be small
- Categorized as myxoid/cellular or fibrous
Verify with an excisional biopsy
UNDIFFERENTIATED PLEOMORPHIC SARCOMA is and path
Previously malignant fibrous histiocytoma
The most common type of soft tissue sarcoma
Aggressive biological behaviour and poor prognosis
Usually affects the extremities, but can involve the retroperitoneum
Typically in adults, age 32-80 with a slight male predominance
The most frequent soft tissue sarcoma to occur as a result of radiotherapy, and also seen on a background of Paget disease
Secondary transformation has been reported in fibrous dysplasia, giant cell tumour, enchondroma, chronic myelitis and osteonecrosis
Usually confined to the soft tissue but occasionally may arise in or from bone
Macroscopically: typically large, well circumscribed but unencapsulated with a grey firm heterogenous cut surface, sometimes with areas of necrosis
Histopath:
- Heterogenous fibroblastic tumours made up of poorly differentiated fibroblasts, myofibroblasts, histocyte-like cells with significant cellular pleomorphism, storiform architecture and bizarre multi-nucleated giant cells
High grade and aggressive
Frequently metastasis (30-50% at diagnosis), and locally recur. Survival 25-70% over 5yrs
Prognostic factors:
- Tumour size - smaller is better
- Location - superficial is better
- Histological grade: myxoid is better than stooriform-pleomorphic
LYMPHANGIOSARCOMA is and path
Rare malignant soft tissue neoplasms representing a vascular tumour which occurs in patients with chronic lymphoedema
Affects females > males
- Esp post-mastectomy lymphoedema
Arises from the vascular channels, pathogenesis is unclear
Look for enhancing vascular nodular soft tissue tumour involving soft tissue and skin of the involved limbs associated with signs of oedema within the subcutaneous tissue
LEIOMYOSARCOMA is and path
Originate from smooth muscle cells
Can potentially occur anywhere with smooth muscle
Uterus = 1/3, retroperitoneum = most common non-uterus site
These tend to be large, with central necrosis and no calcification
LIPOSARCOMA is and path
Malignant counterpart to lipoma
Second most common type of soft-tissue sarcoma
Found in adults, age 40-60
Presentation varies according to the tumour location
Histological subtypes:
- Well differentiated liposarcoma, most common 50%
- Myxoid liposarcoma - 2nd most common, chromosomal translocation t(12,16)
- Dedifferentiated liposarcoma - high grade, aggressive
- Pleomorphic liposarcoma - least common, high grade, frequent mets
- Mixed
Usually seen in the extremities, most commonly the thigh. Less common in the retroperitoneum
SYNOVIAL SARCOMA is and path
Common intermediate-to-high grade malignant soft tissue tumours
Most commonly involving the soft tissue surrounding the knee
Typically adolescents - young adults, age 15-40
May be a mild male predilection
Pathology:
- Resembles normal synovium, but stains for epithelial markers (e.g. epithelial membrane antigen and cytokeratin) which synovium does not
- Can be found in locations without synovium
- Most commonly near large joints e.g. popliteal fossa.
Four subtypes:
- Biphasic 20-30%
- Monophasic fibrous 50-60%
- Monophasic epithelial: very rare
- Poorly differentiated 15-25%
Cytogenetic aberation of t(X; 18) translocation is highly specific, seen in >90% of cases
Very suspicious if dystrophic calcification is present - non specific within the periphery of the lesion
Very heterogenous “triple sign” on T2
ANGIOSARCOMA is
Arise from vascular structures
Difficult to differentiate
Tend to be multicentric tumours with haemorrhage and necrosis
RHEUMATOID ARTHRITIS is and path
Chronic autoimmune multisystemic inflammatory disease that affects many organs, but predominantly attacks the synovial tissues and joints
Overall prevalence, 0.5-1%, and 2-3x more common in women
Onset is generally ~4th-5th decades
Risk factors:
- Smoking - seropositive RA
- Obesity
- Low socioeconomic status
Aetiology is probably multifactorial
Thought to be a genetic predisposition (HLA-DR B1), with an environmental trigger e.g. EBV, leading to an autoimmune response against synovial structures
Activation of B cell lymphocytes to produce antibodies, including rheumatoid factor, which makes immune complexes that deposit in different tissues and contribute to further injury
Activation of endothelial cells > increased adhesion and accumulation of inflammatory cells
Produce RANKL which in turn activates osteoclasts causing subchondral bone destruction
The inflammatory response leads to pannus formation
- Pannus: oedematous thickened hyperplastic synovium infiltrated by lymphocytes, plasmocytes, macrophages and osteoclasts
- Pannus will gradually erode bare areas, followed by articular cartilage
- It causes fibrous ankylosis which eventually ossifies
Markers:
Rheumatoid factor: an IgM antibody against the FC portion of the IgG antibodies
- A traditional marker, but non-specific
- Associated with several autoimmune and chronic infectious diseases
Anti-cyclic citrullinated peptide (Anti-CCP)/ACPA)
- More than 80% sensitive, more than 95% specific
Elevated CRP or ESR
RA extra articular manifestations
Pulmonary
- Interstitial lung disease
- Pulmonary nodules
- Pleural effusion
- Caplan syndrome - rheumatoid arthritis and pneumoconiosis
Cardiovascular involvement
- Accelerated/premature coronary artery atherosclerosis
- Pericarditis
Cutaneous involvement
- Rheumatoid nodules - usually in pressure areas, in RF-positive patients
- Rheumatoid vasculitis - classically deep cutaneous ulcers in the lower limbs
Haematological involvement
- Anaemia of chronic disease
- Felty syndrome - syndrome characterised by the triad of rheumatoid arthritis, splenomegaly and neutropenia
- Large granular lymphocyte leukaemia
Ocular involvement
- Episcleritis
- Keratoconjunctivitis sicca
JUVENILE IDIOPATHIC ARTHRITIS is and apth
The most common chronic arthritic disease of childhood
By definition, symptoms must start before 16 years of age
Females are more affected 2:1
Oligoarticular or polyarticular arthritis of a duration of 6wks +
Can present with systemic onset (Still disease)
- Intermittent spiking fevers are typically noted, which helps distinguish JIA from other diseases e.g. infection, other inflammatory diseases and malignancy
Pathology:
Several subtypes:
- Oligoarticular
- Polyarticular
- Systemic onset
OSTEOARTHRITIS is and path
The most common form of arthritis, affecting ~25% of adults
Prevalence increases with age – more in men <50yo, more in women >50yo
Pain, instability and stiffness – worsened by activity and decreases at rest
Pathology:
- Incompletely understood
- Emphasis is placed on articular cartilage degeneration, but the remainder of the joint is involved
Classification:
- Primary – idiopathic
- No antecedent insult
- Strong genetic component
- Secondary – abnormal mechanical forces e.g. occupational stress, obesity
- Previous joint injury
- Post-traumatic OA
- Prior surgery
- Crystal deposition e.g. gout, CPPD
- Inflammatory arthritis e.g. RA, seronegative spondyloarthritis
- Haemochromatosis
Risk factors:
- Obesity
- Increasing age
- Female sex, esp age 50-80
CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION | PSEUDOGOUT is and path
The cooccurrence of arthritis with evidence of CPPD deposition within the articular cartilage
CPPD: occurrence of calcium pyrophosphate crystals +/- symptoms
Asymptomatic CPPD: chondrocalcinosis +/- changes of osteoarthritis, but clinically asymptomatic
Acute CPPD crystal arthritis (pseudogout): self limiting synovitis in the setting of CPPD
OA with CPPD – typical changes of OA in the setting of CPPD
Commonest in patients >50yo, and equally men and women
Presentation resembles a gout attack, but commonly involves the knee and upper joints, or pubic symphysis
Pathology:
- Weakly positively birefringent on polarised microscopy
- Rhomboid or rod shape
Aetiology:
- Idiopathic
- Hereditary – AD, ANKH gene
Secondary
- Haemochromatosis
- Hyperparathyroidism
- Hypothyroidism
- Hypomagnesemia
- Previous joint injury
- Ochronosis
CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION | PSEUDOGOUT imaging
Features of OA with an unusual distribution e.g. symmetrical, non-weightbearing joints
OA in joints not commonly affected:
- Wrist: radiocarpal and scapholunate joints
- SLAC wrist in advanced cases
- Metacarpophalangeal joints
- 2nd and 3rd preferentially
- Hook like osteophytes
- Patellofemoral joint
- Shoulder and elbow
Chondrocalcinosis in many locations:
- Knee – medial meniscus and patellofemoral joint
- Wrist – TFCC, lunotriquetral
- Pubic symphysis
- Spine
- Chronic retro-odontoid pseudotumour
- Crowned dens syndrome
- Intervertebral discs
GOUT is and path
A crystal arthropathy due to deposition of monosodium urate crystals in and around the joints
Typically occur in those 40+yo, with a strong male predilection 20:1
- The male predilection is more pronounced in younger and middle-aged adults
- Estradiol has a urate-lowering effect = uncommon in premenopausal women
Pathology:
- Characterised by monosodium urate crystal deposition in periarticular soft tissues
- Needle-shaped and strongly negative birefringent in plane-polarised light
- The synovial fluid is a poor solven for monosodium urate, and therefore crystallisation occurs at low temperatures
- Crystals are chemotactic and active complement
There are 5 recognised stages:
- Asymptomatic hyperuricaemia
- Acute gouty arthritis
- Intercritical gout – between attacks
- Chronic tophaceous gout
- Gouty nephropathy
The primary risk factor is hyperuricaemia, but only a small proportion of patients with hyperuricaemia develop gout – often taking 20-30yrs to develop
Aetiology:
Primary RF is hyperuricaemia, only a small proportion of whom develop gout. often taking 20-30ys.
Undersecretion of uric acid by the kidneys 90%
- Chronic kidney disease
- Hypertension
- Hyperparathyroidism
- Alcohol
- Drugs
- Lead poisoning
- Obesity
Overproduction of uric acid 10%
- Myeloproliferative disorders
- Haemolysis
- Extreme exercise
- Lesch-Nyhan syndrome
Location:
- Usually asymmetrical polyarticular distribution
- 1st MTP joint, hands and feet
- Less common: bones, tendons and bursae
- Chondrocalcinosis is present in ~5%
Tophi:
- T1 iso, T2 variable, characteristically heterogenously hypointense
- Often enhance
- Hyperdense heterogenous on US, with poorly defined contours
Look for synovial thickening
Management:
- NSAIDs acutely
- Xanthine oxidase inhibitors e.g. allopurinol, to reduced urate levels and prevent further acute flares
HYDROXYAPATITE DEPOSITION is and path
A disease of uncertain aetiology, characterised by periarticular and intra-articular deposition of hydroxyapatite crystals
The shoulder is the most frequently involved site
Most commonly found in middle-aged individuals
Pathology:
- Believed that HADD will begin to accumulate in damaged tendons (secondary to trauma) via fibrocartilaginous metaplasia
- Characterised by calcium apatite crystal deposition in periarticular soft tissues – esp in the tendons
- Most frequently involves the shoulder joint, where crystal deposition occurs in the supraspinatus tendon, but can affect numerous other sites as well
- Calcific enthesitisis the most appropriate term
- Can involve other sites e.g. gluteus medius tendon, or femur etc.
- Variable size and shape of calcifications,
- Mono- or polyarticular
Three phases:
- Formative, resting and resorptive
- Formative and resting – round –to-ovoid calcification in the soft tissue with well-defined borders
- Resorptive – ill-defined with a comet tail-like appearance
- May mimic a periosteal reaction
Treatment: NSAIDs,
When intra-articular, crystals can cause joint destruction
- Milwaukee shoulder
- Advanced articular surface destruction
- Intra-articular loose bodies
- Subchondral sclerosis
- Soft tissue swelling
- Rotator cuff disruption
ANKYLOSING SPONDYLITIS is and path
Seronegative spondyloarthropathy resulting in fusion of the spine and sacroiliac joints
Thought to be male predominant 3:1, manifesting in young adults by the 3rd decade
Associations:
- Anterior uveitis 25-40%
- Psoriasis
- Inflammatory bowel disease
- Osteopenia
- Cardiovascular disease
- Apical/UL predominant ILD with small cystic spaces
- Aortic valve disease/aortitis
Pathology:
- Rheumatoid factor negative
- HLA-B27 is the gene with the strongest association : 90%
- 5% of people with the gene develop ankspon
REACTIVE ARTHRITIS is and path
Sterile, inflammatory, monoarticular or oligoarticular arthritis that follows an infection at a different site – typically enteric or urogenital
A type of seronegative spondyloarthropathy
Formerly known as Reiter syndrome – urethritis, arthritis and conjunctivitis
Most commonly occurs in males ages 15-35yo
- 1 in 100 following enteric infections
Usually transient and involving one or two large joints
Other extra-articular manifestations: cardiac conduction abnormalities and aortic regurgitation
Pathology:
- Joint inflammation, bone proliferation, periostitis and enthesitis
Aetiology:
- Enteric – yersinia, salmonella, shigella, campylobacter and less commonly E-COLI
- Sexually transmitted – chlamydia
- Other – brucellosis
Markers:
- HLA-B27 positive in ~80% of patients
- A proportion have serum rheumatoid factor
SLE ARTHRITIS is and path
Symmetrical polyarthritis, varying degrees
Deforming non-erosive arthropathy, due to ligamentous laxity (not articular destruction)
Classically seen on Norgaard views, but absent on PA views = reducible deformities
- Deformity without erosion differentiates if from rheumatoid
Hands and feet:
- Symmetrical interphalangeal joint involvement: swan neck and boutonniere deformity, subluxation with ulnar deviation of the 1st MCP joint, a widened forefoot and hallux valgus
- Joint space narrowing is uncommon
- Can develop hook erosions of the MCP heads, more on the radial side
PSORIATIC ARTHRITIS is and path and imaging
An inflammatory arthritis associated with psoriasis
Usually negative for rheumatoid factor
Affects up to ~25% of patients with psoriasis – median age of diagnosis 48yo
Associations:
- Obesity
- Hypertension
- T2DM
- Hyperlipidaemia
- Dermatological features precede arthritis in ~65%
- Asymmetrical oligoarthritis with spondylitis
Pathology:
- Up to 60% are HLA-B27 positive
- A proportion have a positive serum RF
Extra-articular manifestations are common:
- Ocular – uveitis, conjunctivitis
- GI – IBD
- Cardiac – rhythm disturbances: LBBB
- Urogenital – urethritis, prostatitis, cervicitis, vaginitis
Imaging:
- Combined erosion and bone proliferation, predominantely distal distribution
- Hands and feet: symmetric polyarthropathy, or asymmetric oligoarthropathy with distal predominance
- Enthesitis and marginal bone erosions: “pencil-in-cup” deformities
- Bone proliferation results in an irregular “fuzzy” appearance of the bone
- Periostitis – rregular thickening of the cortex
- Dactylitis – sausage digit
- Acro-osteolysis
- Arthritis mutilans – osteolysis and articular collapse
- Ivory phalanx
- Sacroiliitis – often asymmetrical
SEPTIC ARTHRITIS is and path
Destructive arthropathy caused by intra-articular infection that is usually related to severe symptoms and reduced range of motion
Risk factors:
- Bacteraemia, advanced age, immunocompromised, RA, itra-articular injection, prosthetic joint
- Usually secondary to haematogenous seeding
- Staph aureus is most common
- Gonococcal is not uncommon
Large joints are most prone, IVDU: sternovclavicular and SIJ are more frequently affected
HAEMOPHLIC ARTHROPATHY is and path
Permanent joint disease as a long-term consequence of repeated haemarthrosis
Around50% of haemophilia will develop this
Haemophilia: X-linked recessive disease, mainly affecting males
- Haemarthroses are usually in the same joint, age 2+ to adolescence
- Less common in adulthood
- Proliferative chronically-inflammed synovium results in the development of haemophiliac arthropathy
Haemarthrosis results in iron deposition in the synovium > neoangiogenesis and ultimately damage to both the articular cartilage and subchondral bone
Arthropathy:
- Synovial hyperplasia, chronic inflammation, fibrosis and haemosiderosis
- The synovium mass erodes cartilage and subchondral bone leading to subarticular cyst formation
Location:
- Knee > elbow > ankle > hip > shoulder
HAEMOPHLIC ARTHROPATHY imaging
Joint effusion
Periarticular osteoporosis – from hyperaemia
Epiphyseal enlargement with gracile diaphysis – from hyperaemia
Symmetrical degenerative changes
Knee:
- Widened intercondylar notch
- Squared inferior margin of patella
- Bulbous femoral condyles
- Flattened condylar surfaces
Elbow:
- Enlarged radial head
- Widened trochlear notch
Ankle:
- Talar tilt
PVNS is and path
Benign proliferative condition affecting synovial membranes of the joints, bursae or tendons resulting from possible neoplastic synovial proliferation with villous and nodular projections and haemosiderin deposition
Most commonly monoarticular ~70% knee
Can be oligoarticular
Predominantely early – middle age
No gender predilection for intra-articular disease, extra-articular disease has a slight female predilection.
Associations:
- Cherubism
- Extremity lymphedema
- Mandibular lesion
- Noonan syndrome
- Vascular lesions
Synovium is diffusely thickened, dark brown/heterogenous with areas of yellow discolouration
OSTEITIS CONDENSANS ILII is
Benign sclerosis of the ilium, adjacent to the SIJ, typically bilateral and triangular in shape
More common in women, primarily pregnancy and puerperium
Usually asymptomatic
Unknown aetiology
Lack of sacral or joint space involvement is diagnostic
SYNOVIAL CHONDROMATOSIS IS
aka reichel syndrome
disorder characterised by loose cartilaginous bodies which may be calcified/ossified
can be primary or secondary
- priary; monoarticular, unknown aetiology
- secondary; loose bodies from trauma, OA, neuropathic arthropathy
in secondary, articular nodules are large, vary in size and frequently ossify
in primary smaller and more uniform.
ALVEOLAR PROTEINOSIS ios and path
Lung disease characterised by abnormal intra-alveolar accumulation of surfactant-derived lipoprotienaceous material
Rare, usually presents in young and middle aged adults 20-50yo
Smoking is strongly associated
When it presents before the age of 1yo there is an association with thymic alymphoplasia
Pathology:
Multiple causes:
Autoimmune - 90%
- Adult/acquired
- IgG antibodies to GM-CSF
Secondary 5-10% presents in individuals with other precipitating illness
- Hematological malignancies - most commonly myeloid origin - CML > AML
- Inhalational lung disease
- Silica
- Titanium oxide
- Immunosuppression
Congenital 2%
- Presents in the neonatal period in term babies
- Poor prognosis if left untreated
Histopath: amorphous periodic acid-Schiff (PAS) stain lipoproteinaceous material filling the alveoli with relatively normal background lung architecture
Markers:
- Elevated acute inflammatory markers e.g. lactate dehydrogenase
- + BAL or serum anti-GM-CSF antibodies
Complications:
- Superimposed infection
- Pulmonary fibrosis in 30%
HYPERSENSITIVITY PNEUMONITIS is and path
A group of immune-mediate pulmonary disorders characterised by an inflammatory and/or fibrotic reaction affecting the lung parenchyma and small airways
Aetiology: more than 200 different antigens are involved
The triggering particles are usually in the range of 1-5micrometres in size. In ~40% the inciting agent may not be identified
Histopathology:
- Chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli
- Fibrosis and emphysema may develop later on
- Most cases involve 4 histologic features in variable amounts and combinations:
- Cellular bronchiolitis
- Diffuse chronic interstitial inflammatory infiltrates
- Poorly circumscribed interstitial non-necrotising granulomas
- Individual giant cells in the alveoli or interstitium
Smoking is protective
Subtypes:
- Non-fibrotic - purely inflammatory
- Fibrotic - mixed inflammatory/fibrotic or purely fibrotic
SOLITARY FIBROUS TUMOUR OF THE PLEURA is and path
Rare benign pleural-based tumours that account for <5%
Usually presents are 6th-7th decades, with no gender predilection
Associations:
- Hypoglycaemia 2-4%: thought to be due to the production of insulin-like growth factor 2
- Hypertrophic pulmonary osteoarthropathy ~20% - due to abnormal production of hyaluronic acid
- Asbestos exposure is not an association
Irregularly arranged fascicles consisting of spindle cells separated by collagen
80% arise from the visceral pleura
Myxoid or cystic degeneration can occur
Approximately 30% are malignant
Location:
- Predilection for the mid-lower zones of the chest
Variants:
- Lipomatous haemangiopericytoma - a fat-forming variant
Imaging:
- Pleural based, may be pedunculated
- Calcification, rib destruction and pleural effusions aren’t typically associated
- Tends to have soft tissue attenuation
MRI:
- T1 typically low - intermediate
- T2 typically low
CHRONIC BRONCHITIS is and path
Defined as the presence of a productive cough for 3mo in two successive years in a patient in whom other causes of a chronic cough has been excluded
Often results from overproduction and hypersecretion of mucous by goblet cells
The mechanism isn’t entirely clear, but linked to both hypertrophy of submucosal glands and increased number of goblet cells which are thought to be the protective reaction to tobacco smoke or other pollutants
It can lead to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodelling and alteration of airway surface tension predisposing to collapse
EMPHYSEMA is and path
Abnormal and permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of the alveolar wall and without obvious fibrosis
Predominantly a disease of middle - late life, owing to the cumulative effect of lifelong tobacco smoking
Risk factors:
- Smoking ~90% of cases
- Alpha-1-antitypsin deficiency
- Ritalin lung
Clinical: pink puffers, often hypocapnic
Pathology:
- A heterogenous group of pathological processes forming COPD
Morphological subtypes
- Centrilobular emphysema
- Panlobular emphysema
- Paraseptal emphysema
- Paracicatricial emphysema
ALPHA 1 ANTITRYPSIN is
A hereditary metabolic disorder, the most common genetic cause of emphysema and metabolic liver disease in children
Results in the un-opposed action of the neutrophil elastase
SILICOSIS is and path
A fibrotic pneumoconiosis caused by the inhalation of fine particles of crystalline silicon dioxide
Occurs in two forms, subdivided by their temporal relationship to the exposure to silica
- Acute - alveolar silicoproteinosis
- Classic - chronic interstitial reticulonodular disease
Imaging:
- Nodules 1-10mm in diameter
- Predominately upper lobe and posterior
- Calcification of nodules, eggshell calcification of node
- Perilymphatic distribution
CWP is and path
Three main effects from carbon on the lungs:
- Anthracosis - harmless deposition of carbon dust
- Simple CWP
- Complicated CWP
Along with silicosis, asbestosis, berylliosis and talcosis, CWP is a fibrotic pneumoniosis
Not easily distinguished on imaging from silicosis
Imaging:
- Nodules tend to be less well-defined and more granulated
- Increased risk of tuberculosis
MESOTHELIOMA is and path
An aggressive malignant tumour of the mesothelium
Most tumours arise from the pleura ~90%
Accounts for 5-28% of all malignancies that involve the pleura
There is a strong association between asbestos fibre exposure and mesothelioma
- Crocidolite is the most causative fibre type
Increased risk for those with household exposure
Clinically:
- Pleural effusions are seen in the vast majority of patients at some stage
- 25% are metastatic at presentation
Aetiology:
- Asbestos fibre exposure
- Erionite fibre exposure
- Simian virus 40
- Radiation exposure
Histology:
Three types:
- Epithelial ~60%
- Mixed ~25%
- Sarcomatoid 15%
The cytological and histological diagnosis can be difficult, with mesothelial hyperplasia and metastatic adenocarcinoma appearing similar
Specific markers:
- Calretinin
- Epithelial membrane antigen
- Cytokeratin
- Mesothelin
Subtypes e.g. multicystic/cystic are rarer and less aggressive
PULMONARY ASPERGILLOSIS is and path
A collective term for conditions caused by infection with a fungus of the Aspergillus species
Multiple forms:
- Aspergilloma
- Allergic bronchopulmonary aspergillosis
- Invasive aspergillosis
- Obstructive bronchopulmonary aspergillosis
There are a variety of species. If the lungs are normal and host immunity is intact, this shouldn’t cause pathology
Both heightened (hypersensitivity) and reduced immunity predisposes
Aspergilloma is and path
Mass-like fungal balls: mycetoma is an incorrect term
Underlying conditions:
- Pulmonary TB
- Sarcoidosis
- Bronchiectasis
- Pulmonary cavities:
- Bronchogenic cyst
- Pulmonary sequestration
- Pneumocystis pneumonia associated pneumatoceles
Haemoptysis may be present due to the surrounding reactive vascular granulation tissue
An eroded bronchial artery can lead to life-threatening haemoptysis
Pathology: a mass-like collection of fungal hyphae, mixed with mucous and cellular debris within a cavity, the walls of which demonstrate vascular granulation tissue
Commonly in the posterior upper lobes and superior lower lobes
Monod sign. can have calcs. bronchial arteries can be enlarged. pleura can be thickened
ABPA is and path
Mostly patients with longstanding asthma, occasionally with cystic fibrosis
Generally patients are young and diagnosed before the age of 40
Major and minor criteria:
Major
- Clinical - asthma
- Radiographic:
- Pulmonary opacities
- Central bronchiectasis
- Immune system
- Blood eosinophilia
- Elevated IgG and/or IgE against A.fumigatus
- Increased serum IgE
Minor criteria
- Fungal elements in the sputum
- Expectoration of brown plugs/flecks
- Delayed skin reaction to fungal antigens
Pathology:
A hypersensitivity reaction towards aspergillus spp. Which grows in the lumen of the bronchi without invasion
The hypersensitivity initially causes bronchospasm and bronchial wall oedema - IgE mediated
Ultimately there is bronchial wall damage with loss of muscle and bronchial wall cartilage resulting in bronchiectasis (typically central bronchiectasis)
Both types I and III allergic reactions have been implicated
Bronchocentric granulomatosis often occurs - characterised by necrotising granulomatous inflammation that destroys the walls of the small bronchi
Angio invasive aspergillosis is and path
A life threatening condition, seen in patients who are profoundly immunosuppressed
Pathology:
Spores of Aspergillus spp are inhaled and proliferate in the alveoli
The hyphae are able to invade the pulmonary arteries resulting in pulmonary necrosis and haemorrhage
May gain access to the systemic circulation and disseminate
If the neutrophil count recovers the central necrotic area of lung demarcates, shrinks and separates from the adjacent viable tissue = the air crescent sign
CARCINOID TUMOURS are and path
Can be divided into two groups depending on location:
- Bronchial carcinoid tumours: central lesion
- Peripheral pulmonary carcinoid tumours: peripheral lesions
Can also be divided into typical and atypical by histology
Bronchial:
- Occur in relation to a bronchus - usually segmental or larger
- Typically affects patients from the 3rd-7th decades, with a mean age ~45
- Most are central
- Associations:
- Multiple endocrine neoplasia type 1
- Cushing syndrome - ACTH producing carcinoid tumour types
Peripheral:
- A subtype, less common than centrally-located bronchial carcinoids
- Most are discovered incidentally
- Many have a lobulated margin
PLEURAL EFFUSION is and path and causes
Abnormal accumulation of fluid within the pleural space
Pathology: transudate vs exudate
Transudate - when there is an increase in hydrostatic pressure or a decrease of capillary oncotic pressure
- cardiac failure
- Cirrhosis
- Nephrotic syndrome
- Dressler syndrome
- Biochemical analysis:
- Protein concentration <30
- Lactate dehydrogenase <20
Exudate - occurs due to the increase in permeability of the microcirculation or alteration in the pleural space drainage to lymph nodes
- bronchial carcinoma
- Pulmonary embolism and infarction
- Pneumonia
- Tuberculosis
- Biochemical analysis
- Protein >30
- Lactate dehydrogenase >20
PNEUMOCYSTIS JIROVECI is and path
Virtually never present in immunocompetent individuals
Typically occurs at CD4 counts <200 cells/mm
An atypical yeast-like fungus of the genus Pneumocystits, previously thought to be a protozoan
Ground glass pattern, predominantly perihilar or mid zones
Reticular opacities or septal thickening
Pneumatoceles
Differentials:
- Viral pneumonia - similar, but cysts are absent
- Mycobacterium TB when upper zone cysts are prominent
- Angio invasive aspergillosis
PULMONARY LCH is and path
May be seen as part of widespread involvement or distinct entity in young adult smokers
Usually young adults, 20-40yo
A history of current or previous cigarette smoking is identified in up to 95% of cases
Associations:
- Haematopoietic neoplasms
- ALL
- AML
Can present with a pneumothorax
Proliferate in the bronchiolar and bronchial epithelium, forming granulomas
These evolve, peripheral fibrosis forms, resulting in traction on the central bronchiole which becomes cyst-like
So evolution nodule > cyst
Electron microscopy: Birbeck granules
SARCOIDOSIS IS
Non caseating granulomatous multisystem disease with a wide range of clinical and radiographic manifestations
Most commonly presents in the 2nd-4th decades of life
No significant gender predominance
Pathology:
- A multisystem disorder of unknown aetiology characterized by the formation of inflammatory non-caseating granulomas within affected tissues
- Histologically, the lesions characteristically demonstrate an absence of a necrotic component, except in rare cases
- The granulomas may resolve spontaneously or progress to fibrosis
- Thought to represent a disorder of immune regulation, particularly of cell-mediated immunity
- Mycobacterium and propionibacterium RNA and DNA have been detected in sarcoidosis lesions - raising the possibility of an infectious trigger
Microscopic:
- Non-caseating granulomas
- Schaumann bodies
- Asteroid bodies
- Necrosis is atypical and may suggest another aetiology
Biochemical markers
- Elevated ACE
- Hypercalcaemia, hypercalciuria
- A positive Kveim-Siltzbach skin test helps to confirm the diagnosis
ASBESTOS RELATED BENIGN PLEURAL DISEASE includes
Benign asbestos - induced pleural effusions: 20%, exudative
- Usually occur within 10yrs of exposure
Pleural plaques
- Almost always involve the parietal pleura
Visceral pleural involvement is usually at the lower and lateral aspect
- May be calcified, non-calcified or mixed
- Tend to spare the apices and costophrenic angles
Diffuse pleural thickening ~15%
LUNG CA is and path
The leading type of cancer in the world, accounting for ~20% of deaths
Major risk factor is smoking, and increased risk can be divided by histological subtypes
Other risk factors:
- Asbestos
- Occupational exposure
- Diffuse lung fibrosis
- Chronic obstructive pulmonary disease
Associations:
Paraneoplastic:
Endocrine/metabolic
- SIADH causing hyponatreamia
- ACTH secretion (cushing syndrome)
- Carcinoid syndrome
- Gynaecomastia
- Adrenal insufficiency (addison) - from bilateral metastases
- Hyperparathyroidism
- Hypocalcaemia
- PTH-related peptide causing hypercalcaemia
Neurological
- Polyneuropathy
- Myelopathy
- Limbic encephalitis
- Cerebellar degeneration
- Lambert-Eaton myasthenia syndrome
Other
- Finger clubbing
- Hypertrophic pulmonary osteoarthropathy - squamous cell carcinoma
- Nephrotic syndrome
- Polymyositis
- Dermatomyositis
- Eosinophilia
Pathology:
Non-small cell lung cancer 80%
- Adenocarcinoma 35%
- Most common, especially women, peripheral
- Squamous cell cancer 30%
- Smoking, most common to cavitate, poor prognosis
- Large cell carcinoma 15%
- Peripheral, large, usually >4cm
Small cell lung cancer 20%
- Almost always in smoking, metastasizes early
- Most common primary lung malignancy to cause paraneoplastic syndromes and SVC obstruction
- Worst prognosis
Markers
- PDL1
- TTF-1: expressed in most except squamous cell cancer
Genetics
- ROS1 mutation
- ALK mutation
SMALL CELL is and path
Staging:
- Limited
- Confined to one hemithorax
- Inclusive of hilar/supraclavicular lymph nodes
- Suitable for radiotherapy and chemotherapy
- Extensive
- Extends beyond one hemithorax
- Only chemotherapy
- 70% of cases
90-95% occur centrally, arising adjacent to a lobar or main bronchus
Serology:
- Lactate dehydrogenase is a non-specific marker of survival
The most common cause of SVC obstruction
SQUAMOUS CELL is and path
Second only to adenocarcinoma as the most commonly encountered
~30-35% of cancers
Associated with smoking, more common in male smokers, adenocarcinoma is more common in female smokers
Presentation depends on location of the tumour
- Central > invasion and obstruction of the bronchi
- Peripheral > invade the chest wall e.g. pancoast tumour
Pathology:
- Invade the surrounding parenchyma and extend into the chest wall
- Have a tendency to undergo central necrosis
- Characterised by intercellular bridging and/or keratinisation of the individual cells or squamous pearls
Degree of differentiation classifies it into 4 subtypes:
- Papillary
- Clear cell
- Small cell
- Basaloid
Immunohistochemistry:
- P63, negative for TTF1
LUNG ADENOCARCINOMA is and path
The most common histologic type of lung cancer
Pathology:
Preinvasive
- Atypical adenomatous hyperplasia
- Adenocarcinoma in situ
Minimally invasive
- Lepidic growth pattern
Invasive >5mm invasion
AAH <5mm.
adeno in situ <3cm, lepic pattern. absence of stromal vascular or pleural invasion
minimally invasive described small solitary adenocarcinomas with either pure lepidic or lepidic preominant and <5mm stromal invasion.
invasive >5mm invasion. further subcat according to dominant histo pattern.
EGFR and KRAS are becoming increasingly important for consideration of therapy
THYMOMA IS
rare thymic epithelial lesion.
Over 30 conditions are associated with a thymoma
- Myasthenia gravis - most common
- Pure cell aplasia
- Hypogammaglobinaemia
SLE
Pathology:
- Macroscopically of variable shape - typically rounded with a bosselated outer surface
- Both non-invasive and invasive thymomas may appear to have an intact capsule
- Larger tumours are more likely to demonstrate cystic changes as well as haemorrhage and calcification
Imaging:
- Calcification is frequently seen in thymic carcinoma
Rheumatoid lung disease patterns
Rheumatoid nodules tend to be located in the periphery of the upper and middle zones.”
Most commonly UIP, with peripheral and basilar predominance of fibrosis, indistinguishable from idiopathic pulmonary fibrosis
Can have bronchiectasis
Bronchiolitis may be due to chronic infection or constrictive bronchiolitis
Rheumatoid nodes are rare. May be single or multiple, can become large and cavitate
Rheumatoid nodules may be complicated by bronchopleural fistula
PULMONARY HAEMOSIDEROSIS is
Surplus iron deposition in the lungs
can be primary or secondary
- primary
- goodpastures
- heiners
- idiopathic
- secondary; usually MS
Characterised by:
- Small, ill-defined pulmonary nodules or
- Coarse reticular areas of increased opacity with a bias for middle and lower lung regions
- Not actually calcified, tend to be large nodular opacities
- Pulmonary ossification - dense nodules with a tenduancy for confluence
PULMONARY ALVEOLAR MICROLITHIASIS is
A rare idiopathic condition characterised by widespread intra-alveolar deposition of spherical calcium phosphate microliths
Slight female predilection
Associations: testicular microlithiasis
Pulmonary alveolar microlithiasis is believed to be due to a mutation in the SLC34A2 gene that causes inactivation of a sodium-dependent phosphate cotransporter, which is found mainly in alveolar type II cells. This cotransporter normally clears phosphate from degraded surfactant, and when inactivated there is accumulation of phosphate in the alveolus, and calcium phosphate microliths are then thought to form 9.
An autosomal recessive inheritance pattern has been proposed given familial occurrence in a majority of cases 2,3,9. Usually, there is no abnormal calcium metabolism.
PULMONARY HAMARTOMA is and path
Benign neoplasms composed of cartilage, connective tissue, muscle, fat and bone
May be chondromatous (most common), leiomyomatous or a mixture
Usually found in the 4th-5th decade, uncommon in children
Majority are located peripherally within the lungs (>90%), endobronchial hamartomas represent 5% of lesions
60% have fat, 20-30% have calcification - popcorn like
Pulmonary carcinoid:
- Higher attenuation
- More lobulation
- More distal nodularity
- Distal hyperlucency
- Atelectasis
- More bronchial extension and involvement
- Marked homogenous contrast enhancement
TUBERCULOSIS is and path
A wide disease spectrum, predominantly caused by the organism mycobacterium tuberculosis
ulmonary manifestations depend on whether the infection is primary or post-primary
Primary:
- Usually asymptomatic
- Although a small number go on to have symptomatic haematological dissemination = miliary TB
- 5%, usually with impaired immunity, go on to have progressive primary tuberculosis
- May present with a chronic dry cough +/- haemoptysis
- ghon lesion; clacified fdocus
- ranke complex; focus and calcified node
post primary
- recurs years latyer, decreased immaune status
Location:
- Primary - anywhere in children, upper or lower zone predilection in adults
- Post primary - strong predilection for the upper zones
- Miliary - evenly distributed
CYSTIC FIBROSIS IS
An autosomal recessive genetic disease that affects the exocrine function of the lungs, liver, pancreas, small bowel, sweat glands and male genital system
Due to homozygous defect of the CFTR gene located on chromosome 7q31.2
- Encodes for the transmembrane protein “cystic fibrosis transmembrane regulator” responsible for regulating chloride passage across cell membranes
- Also encodes for the indlux of chloride and increases the sodium channel activity in the skin = increase in salt content in the skin of pts with CF
Atleast 6 classes of mutations
TWIN PREGNANCIES class, complications, imaging
Broadly categorised into:
- Dizygotic 70%
- Monozygotic 30%
DIZYGOTIC
- Independent fertilisation of two ova, and always results in dichorionic-diamniotic pregnancies
- 20% of monozygotic pregnancies will be dichorionic-diamniotic
- Documentation of different sex fetus’ is the most reliable sign of dizygotic
Risk factors:
- IVF
- Advanced maternal age
- Advanced parity
- Maternal family history
- Ethnicity
MONOZYGOTIC
- Due to fertilisation of a single ovum that then separates into two
- Unlike dizygotic pregnancy, monozygotic pregnancies do not have maternal age, family history or ethnic predisposition
- The time of separation determines the chorionicity and amnionicity of the pregnancy
- 1-2 days: DCDA
- 4-8 days: MCDA
- 1-2 weeks: MCMA
- >2 weeks: conjoined twins
Complications
- The risk depends on chorionicity - prognosis is worse for mono-mono and best for di-di
- Mono-mono: >50% perinatal mortality
Monochorionic complications
- ~30% of pregnancy related complications
- Share a single placenta, so prone to haemodynamic complications e.g.
- Twin-twin transfusion
- Twin anaemia polycythaemia sequence
- Twin reversed arterial perfusion sequence
- Acardiac twin
- Demise of co-twin
- Twin embolisation syndrome
Monoamniotic complications
- Share the amniotic sac
- Prone to entangled cords, as well as all the monochorionic complications
- Conjoined twins can only occur in monoamniotic pregnancies
US
Dichorionic
- Separate gestational sacs with chorion extending between them <10 wks
- Twin-peak sign
- Separate placental masses
- May be of different genders
Monochorionic diamniotic
- Single gestational sac
- Two yolk sacs
- T sign: thin intertwin membrane
- Single placental mass
Monoamniotic
- No intertwin membrane
- Usually one yolk sac
- Entangled cords are common
TWIN-TWIN-TRANSFUSION SYNDROME is
A potential complication that can occur in a monochorionic twin pregnancy
Results from unbalanced vascular (arteriovenous and arterioarterial) anastomoses in the placenta
So the placental circulation is directed predominantly towards one twin and away from the other
The resultant hypovolaemia and hypoperfusion in one twin and hypervolaemia and hypertension in the other create a cascade of hormonal changes including the renin-angiotensin system
Leads to chronic tubulopathy and oliguria in the hypovolaemia twin, with consequent oligohydramnios, and polyuria and subsequent polydramnios in the hypervolaemic twin
TRAPS is
twin reversed arterial perfusion
rare comp of MC preganncies
lack of a well formed heart in one twin “acardiac”.
superficial artery to artery placental anatomosis providing perfusion of the acardiac twin by the “donor” twin
reversel of the acardiac twin umbilical artery doppler; flow toward fetus
TRAPs imaging
acardiac
- severely abnormal
- morph types; acardius, anceps, amorphus, acormus
- heart absent or abnormal
- head and upper extremities underdeveloped due to perfusion to iliacs
- severe anasarca and cystic hydromas
- single UA common
pump
- often normal, but can have anomalies
- ridk of high output heart failure
- complications
= HOCF
= cerebral ischaemia
= preterm
= FDIU
SHEEHAN SYNDROME is and path
A rare cause of pituitary apoplexy and hypopituitarism
Only occurs in postpartum females who experience large volume haemorrhage and hypovolaemic shock, either during delivery or afterwards with resultant necrosis of the anterior pituitary cells
Clinical presentation:
Pituitary failure
- Can be silent, with delayed hypopituitarism
- Agalactorrhoea
- Amenorrhoea
- Oligomenorrhoea
- Adrenal insufficiency
Optic chiasm compression
- Visual field loss
- Headache
- Ophthalmoplegia
Pathology
Hyperplasia of pituitary cells occurs in the weeks preceding delivery resulting in increased metabolic demand, without a concomitant increase in blood supply
The anterior pituitary blood supply is under relatively low pressure, making these cells susceptible to ischaemia
The posterior pituitary has its blood supply under higher pressure, not usually affected
HYDROPS is and path
Excessive extravasation of fluid into the third space in a fetus which could be due to heart failure, volume overload, decreased oncotic pressure, or increased vascular permeability
Defined as the accumulation of fluid +/- oedema involving at least two fetal components, which may manifest as:
- Pleural effusion
- Pericardial effusion
- Ascites
- Generalised body oedema:
- Fetal anasarca - Subcutaneous skin thikening to more than 5mm
- Nuchal oedema - swollen neck >3mm up to the 14th week, >4-6mm later. No septations
- Cystic hydroma
- Placental enlargement
- Polyhydramnios
- Hepatomegaly
Considered a prenatal form of cardiac failure
Divided into two broad groups:
Immune hydrops
- Minority ~10%
- Fetomateral blood group incompatibility
Non-immune hydrops
- Chromosomal anomalies
- Turner syndrome
- Trisomies - 13, 18, 21
- Cardiac - tachyarrhythmias
- Twin pregnancy complications
- In-utero infections
- Parvovirus B19 is most common infectious cause, secondary to anaemia
- Fetal tumours capable of producing AV shunts
PLACENTA ACCRETA is and path
A general term applied to abnormal placental adherence
The placental villi extend beyond the confines of the endometrium and attach to the superficial aspect of the myometrium, but without deep invasion
Risk factors:
- Placenta previa
- Prior caesarean section
- Uterine anomalies
- Previous uterine surgery
- Dilation and curettage
- Myomectomy
- Maternal age >35
- Multiparity
Abnormal implantation is thought to result from a deficiency in the decidua basalis, where the decidua is partially or completely replaced by loose connective tissue
Chorionic villi directly attach to the myometrium with little or no intervening decidua
Lab investigations:
= Elevated alpha-fetoprotein
= Elevated BHCG
INCRETA is
Intermediate level, with placental villi extending beyond the confines of the endometrium and invading the myometrium
PERCRETA is
Transmural extension of placental tissue across the myometrium with a serosal breach
PLACENTA PREVIA is and path
Low lying placenta - close to, or covering the internal cervical os
The most common cause of antepartum haemorrhage
Cant make the diagnosis before 20 weeks
Classification:
1 - low lying placenta
Lies in the lower uterine segment, but lower edge 0.5 - 2.0cm from the internal os
2 - marginal placenta
Tissue reaches the margins of the internal cervical os, but doesn’t cover it
3 - partial previa
Partially covers the internal cervical os
4 - complete previa
Placenta completely covers the internal cervical os
PLACENTAL ABRUPTION is and path
Premature separation of the normally implanted placenta after the 20th week of gestation, and before the 3rd stage of labour
Risk factors
- Pre-eclampsia and maternal hypertension
- Previous placental abruption
- Prolonged rupture of membranes
- Maternal age
- Maternal trauma
- Cigarette smoking
Clinical presentation
- Increased abdominal tone, contractions
- Pathology - unknown, likely rupture of a spiral artery with haemorrhage into the decidua basalis leading to separation of the placenta
- The small vessel disease seen in abruptio placentae may also result in placental infarction
Can be classified as:
- Marginal placental abruption
- Retroplacental abruption
- Preplacental abruption
PRE-ECLAMPSIA is and path
A disorder of pregnancy involving new-onset hypertension and involvement of one or more other organ systems
- Systolic >140, diastolic >90
Affect up to 8% of pregnancies
Risk factors:
- DM
- Chronic hypertension
- Family history
- Nulliparity
- Advanced maternal age
- Obesity
- Antiphospholipid syndrome
- Pre-eclampsia in prior pregnancy
Occurs after 20wks gestation, and up to 4-6 wks postpartum, with one or more of:
- Proteinuria
- Thrombocytopenia
- Renal impairment
- Liver impairment
- Pulmonary oedema
- Headache or visual disturbance
The addition of tonic-clonic seizures = eclampsia
US may demonstrate IUGR, and mean UA PI >95th centile
OSTEOPOROSIS is and path
A metabolic bone disease characterised by decreased bone mass and skeletal fragility
Defined as:
- BMD T-score < -2.5 SD
- Measured in post menopausal women and men at least 50yo
- Reference standard is the femoral neck, but other sites e.g. lumbar spine can be used
Essentially decreased bony tissue per unit volume of bone
There is no microstructural or biochemical change - as in osteomalacia or rickets
So the mineral-to-osteoid ratio is normal
- Decreased in osteomalacia
Can be localised or diffuse:
Primary - no cause identified
- Post menopausal (type 1): occurs in 50-65yo females,
- Disproportionate loss of cancellous bone as compared to cortical bone
- So more involvement of cancellous bone-rich areas e.g. vertebrae and ends of long bones
- Senile (type 2): in the elderly
- Proportionate loss of cortical and cancellous bones affecting long bones
Secondary (type 3): due to a range of causes, including:
- Endocrine disease - cushings, hyperthyroidism, hyperparathyroidism, DM
- Chronic illness - COPD, chronic liver disease, multiple sclerosis, coeliac disease
- Inflammation
- Medications - steroids, phenytoin
- Thalassaemia major
- Nutritional disturbances - malnutrition, anorexia
- Muscular dystrophies - duchenne muscular dystrophy
HYPERPARATHYROIDISM is and path
Excess parathyroid hormone in the body
Can be primary, secondary or tertiary
Supported biochemically by either an elevated serum parathyroid hormone level or an inappropriately normal level in the setting of hypercalcaemia
Associations:
- MEN 1, 2A
Pathology:
- Increased levels of parathyroid hormone lead to increased osteoclastic activity
- The resultant bone resorption produces cortical thinning (subperiosteal resorption) and osteopenia
Subtypes:
Primary hyperparathyroidism
- Parathyroid adenoma ~80%
- Parathyroid hyperplasia 10-15%
- Parathyroid carcinoma 1-5%
Secondary hyperparathyroidism
- Caused by chronic hypocalcaemia with renal osteodystrophy being the most common cause
- Others - malnutrition, vitamin D deficiency
- Results in parathyroid hyperplasia
Tertiary hyperparathyroidism
- Autonomous parathyroid adenoma, caused by the chronic overstimulation of hyperplastic glands in renal insufficiency
HYPERPARATHYROIDISM imaging
Subperiosteal bone resorption
- Radial aspect of the proximal and middle phalanges of the 2nd and 3rd fingers
- Medial aspect of the tibia/femur/humerus
Subchondral resorption
- Lateral end of the clavicles
- Symphysis pubis
- Sacroiliac joints
Subligamentous resorption
- Ischial tuberosity
- Trochanters
Intracortical resorption - cigar/oval shaped or tunnel shaped radiolucency in the cortex
Terminal tuft erosion
Rugger-jersey spine
Osteopenia
Brown tumours
Salt and pepper sign in the skull
Chondrocalcinosis
OSTEOMALACIA is and path
Bone softening due to insufficient mineralisation of the osteoid secondary to any process that results in vitamin D deficiency or defects in phosphate metabolism
- High remodelling rate - excessive osteoid formation with normal/little mineralisation
- Low remodelling rate - normal osteoid production with diminished mineralisation
Aetiology:
Vitamin D deficiency - most common
- Inadequate intake or absorption
- Dietary deficiency, lack of sunlight exposure, gastric surgery, small bowel disease - crohns/coeliac, or pancreatic insufficiency
- Deficiency of vitamin d metabolism
- Cirrhosis
- Chronic kidney disease
- Cytochrome P450 inducers
Phosphate deficiency
- Inadequate intake or absorption
- Renal phosphate wasting
- Hereditary hypophosphataemic rickets
- Fanconi syndrome
- Tumour induced osteomalacia - due to phsphaturic mesenchymal tumour
Decreased deposition of calcium in bone
- Bisphosphonates
Markers:
- 25(OH)D decreased
- Serum calcium - slightly decreased/normal
- Urinary calcium - decreased
- Serum phosphorus - decreased
- Serum alkaline phosphatase - elevated
- Serum parathyroid hormone - elevated
OSTEOPETROSIS is and path
An uncommon hereditary disorder that results from defective osteoclasts
Bones become sclerotic and thick, but abnormal structure causes them to be weak and brittle
Clinical:
- Present with fractures, often with multiple areas of callous formation
- Crowding of the marrow > bone marrow function is affected, resulting in myelopthisic anaemia, extramedullary haematopoiesis and splenomegaly
- May terminate in acute leukaemia
Pathology:
- Localised chromosomal defects which result in defective osteoclasts and overgrowth of bone
- Disordered architecture results in weak and brittle bones
- Osteoclasts lack carbonic anhydrase, which may play a role in the pathophysiology
Types:
- Infantile autosomal recessive osteopetrosis
- Benign adults autosomal dominant osteopetrosis
Treatment:
- Bone marrow transplant
OSTEOGENESIS IMPERFECTA is and path
A heterogenous group of congenital, non sex-linked, genetic disorders of collagen type I production, involving connective tissues and bones
The hallmark is osteoporosis and fragile bones which fracture easily, as well as, blue sclera, dental fragility and hearing loss
Occurs with equal frequency between males and females, races and ethnic groups
Associations:
- Congenital cataracts
Pathology:
- Disturbance in the synthesis of type I collagen, which is the predominant protein of the extracellular matrix of most tissues
- In bone, it results in osteoporosis
- It’s a major constituent of dentine sclerae, ligaments, blood vessels and skin
Genetics:
- A mutation in one of the two genes which carry instructions for making type 1 collagen
- COL1A1 and COL1A2 genes which encode the alpha2 polypeptide chains, and are responsible for >90% of all cases
- Depending on the type, the inheritance can be autosomal dominant (>95%), autosomal recessive (<10%) or by sporadic mutation
Types
- 1 - mild
- 2 - perinatal lethal
- 3 - progressive deforming
- 4 - 8 vary in severity, these are uncommon
FIBROUS DYSPLASIA is and path
Non neoplastic, tumour like congenital process, manifested as a localised defect in osteoblastic differentiation and maturation, with replacement of the normal bone with large fibrous stroma and islands of immature woven bone
4 subtypes:
- Monostotic - single bone
- Polyostotic - multiple bones
- Craniofacial fibrous dysplasia - skull and facial bones alone
- Cherubism - mandible and maxilla alone - not true fibrous dysplasia
75% occur before the age of 30yo. The polyostotic form usually presents by age 10
Usually sporadic, but has a number of associations:
- McCune-Albright syndrome: 2-3% of cases with the polyostotic form
- Isolated endocrinopathy without the full McCune-Albright syndrome precocious puberty in girls
- Mazabraud syndrome
Pathology:
- Due to developmental dysplasia and focal arrest in normal osteoblastic activity secondary to a non-hereditary mutation which results in the presence of all of the components of normal bone with a lack of normal differentiation into their mature structures
Mono-ostotic: 70-80% of cases
- Becomes inactive after puberty, and the monostotic form does not progress to polyostotic form
- Location:
- Ribs - 30%, most common
- Proximal femur 25%
- Tibia > craniofacial bones > humerus
Polyostotic:
- Often unilateral and monomelic: one limb
- Femur 90%, tibia 80%, pelvis 80%, foot etc.
Sarcomatous dedifferentiation:
- Osteosarcoma - most common
- Fibrosarcoma
- Malignant fibrous histiocytoma
- Rarely chondrosarcoma
- More common in the polyostotic form
mccune albright
cafe au lait
polyostotic fd
endocrinopathy
mazabraud
polyostotic fd
intramuscular myxomas
PAGET DISEASE is and path
A common chronic bone disorder characterised by excessive abnormal bone remodelling
Relatively common, may be male predilection
Pathology:
- The aetiology is not entirely known, but a disease of osteoclasts
- Viral infection in association with genetic susceptibility has been postulated
Three classically described stages, part of a continuous spectrum:
- Early destructive stages (incipient active, lytic): predominanted by osteoclastic activity
- Intermediate stages (active, mixed): osteoblastic as well as osteoclastic activity
- Late stage (inactive, sclerotic/blastic)
Markers:
- Elevated serum alkaline phosphatase
- Normal calcium and phosphorus levels
- Increased urine hydroxyproline
Complications:
- Osseous weakening resulting in deformity and pathological fractures
- Increased risk of osteoarthritis
- Hearing loss
- Sensorineural hearing loss
- Conductive hearing loss
- Neural compression
- Basilar invagination may occur in advanced cases with hydrocephalus or brainstem compression
- Secondary development of tumours
- Osteosarcoma ~1% of cases, highly resistant to treatment
- GCT of the skull
- High output congestive cardiac failure
- Hyperparathyroidism ~10%
- Extramedullary haematopoiesis
OSTEONECROSIS is and path
A generic term referring to the ischemic death of the constituents of the bone
A wide variety of causes, and can affect any bone in the body
Historically
- Subchondral (epiphyseal) ON was called ischaemic and AVN
- Bone infarct - medullary (metaphyseal) ON
- ON is a general, more inclusive term
Pathology:
- Infarction begins when the blood supply to a section of bone is interrupted
- Once established, there is a central necrotic core surrounded by an ischaemic zone - with the inner portion being ‘almost dead’ and the outer portion being hyperaemic
- Beyond this is normal viable marrow
- Between the normal and ischaemic zone that demarcation occurs with the development of viable granulation separating dead tissue = double line sign on MRI
- Double line: T2 low outer sclerosis, with T2 bright inner (granulation tissue) line
- When the infarct is subcortical, a wedge of tissue is typically affected, the apex of which points towards the centre of the bone
Aetiology
- Trauma
- Caisson disease
- Haemoglobinopathies - sickle cell disease
- Pregnancy related
- Radiotherapy
- Connective tissue disorders
- Renal transplantation
- Corticosteroid excess
- Pancreatitis
- Gaucher disease
- Alcohol
- Cirrhosis
- Freiberg disease
- Chemotherapy
OSTEOMYELITIS is and path
Inflammation of the bone due to infection, typically bacterial
Can occur at any age, particularly common age 2-12 and in males
Pathology:
- Results from haematogenous spread, or direct from trauma/ulcers etc.
- Bacteria multiple, localised inflammatory reaction results in localised cell death
- With time, the infection becomes demarcated by a rim of granulation tissue and new bone deposition
- No organisms are recovered in up to 50% of cases
- Staph Aureus is the most common
Other scenarios:
- E coli - IVDU and GIT infection
- Pseudomonas - IVDU
- Klebsiella
- HIB - neonate, and GB step
Location:
- Lower limb most common
- Vertebrae: lumbar > thoracic > cervical
- Radial styloid
- SI joints
- Neonates: metaphysis and/or epiphysis
- Children: metaphysis
- Adults: epiphyses and subchondral regions
TB SPONDYLITIS is and path
Vertberal body osteomyelitis and IV discitis
Pathology: haematogenous spread via arteries and veins
Anterior involvement: spread through the anterior arterial arcade that richly supplies the subchaondral paradiscal bone, resulting in infection anterosuperiorly and anteroinferior - adjacent to the disc
- The disc is conspiciously spared due to sparse vascularity
- Subligamentous spread
- Gradual anterior collapse = acute kyphotic/gibbus deformity
Central involvement: spread via the venous plexus of Batson, typically resulting in infection arising centrally within the vertebral body
- More common in older patients
Posterior involvement - appendiceal pattern due to venous haematogenous spread via the posterior venous plexus
Cold abscess: large paraspinal abscess’ can develop without severe pain or frank pus, prominent inflammatory signs and symptoms
MECONIUM ASPIRATION us and imaging
Small airways obstruction and a chemical pneumonitis
XRAY
Increased lung volumes
- Hyperinflated lungs with flattened hemidiaphragms
- Secondary to distal small airway obstruction and gas trapping
Asymmetric patchy pulmonary opacities
- Due to subsegmental atelectasis
Pleural effusions
Pneumothorax and pneumomediastinum
SEQUESTRATION is and path
Refers to the aberrant formation of segmental lung tissue with no connection to the bronchial tree or pulmonary arteries
A bronchopulmonary foregut malformation
Extralobular more commonly presents in newborns as respiratory distress, cyanosis, or infection
- Venous drainage into systemic veins
- Separated from any surrounding lung by its own pleura
Intralobular presents in late childhood or adolescence with recurrent pulmonary infections
- Majority
- Venous drainage commonly occurs via the pulmonary veins, but can be through the azygos-hemiazygos system
- Closely connected to adjacent normal lung, doesn’t have a separate pleura
Prefer the lower lobes
- 60% affect the LLL, 40% the RLL
- Extralobar is always the LLL, and 10% can be subdiaphragmatic
Associations
- CPAM
- Congenital heart disease
- Congenital diaphragmatic hernia
- Scimitar syndrome
May show cystic spaces if infected
A triangular opacity in the affected segment
HYALINE MEMBRANE DISEASE is and path
Results form insufficient production of surfactant in preterm neonates
- Uncommon after 36wks gestation
The lack of surfactant increases the surface tension in alveoli causing collapse.
A diffuse type of adhesive atelectasis
Reduced lung volumes are key on imaging.
- Diffuse ground glass changes - bilateral and symmetrical +/- air bronchograms
Treated with exogenous surfactant administration and supportive oxygen therapy
There is deposition of a layer of hyaline proteinaceous material in the peripheral airspaces of infants who succumb to this condition
Associations: male gender, maternal diabetes, and delivery by caesarean section
Fundamentally a deficiency of pulmonary surfactant
- Responsible for the reduction of surface tension
- Surfactant is produced by type II alveolar cells, accelerated after the 35th week of gestation
- Synthesis is modulated by a variety of hormones and growth factors.
Prophylactic surfactant treatments are given, as well as antenatal glucocorticoid therapy
CONGENITAL PULMONARY AIRWAY MALFORMATION is and path
Multicystic mass of segmental lung tissue with abnormal bronchial proliferation
Part of a spectrum of bronchopulmonary foregut malformations
If large, can cause pulmonary hypoplasia with resultant poor prognosis
Pathology:
- Results from failure of normal bronchoalvoelar development with a hamartomatous proliferation of terminal respiratory units in a gland-like pattern (adenomatoid) without proper alveolar formation
- Histologically characterised by adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands
- These have intracystic communications and, unlike bronchogenic cysts, can also have a connection to the tracheobronchial tree
Subtypes
1 - 4
Type 1 is most common
- 70% of cases
- Large cysts, one or more dominant cyst 2-10cm in size
2 - 15-20% of cases
- Cysts are <2cm in diameter
- Associated with other abnormalities
- Renal agenesis or dysgenesis
- Pulmonary sequestration
- Congenital cardiac anomalies
3 ~10%
- Microcysts, typically involve an entire lobe
4 - unlined cyst, typically affects a single lobe
0 - rare, lethal
Location
- Unilateral, involve a single lobe, and less frequently in the middle lobe
Associations:
- Hybrid lesions - CPAM and sequestration
- Renal agenesis
- Polyhydramnios
- Hydrops fetalis
CONGENITAL DIAPHRAGMATIC HERNIA is and path
84% left sided, 13% right sided, 2% bilateral
Mortality is determined by the development of pulmonary hypoplasia due to mass effect on the developing lung
Diaphragm development is complete ~9th week of gestation
Pathology:
- Bochdalek - most common
- Posterolateral
- Morgagni
- Less common, anterior, presents later
Associations:
- Pulmonary hypoplasia
- LV hypoplasia
- Intestinal malrotation
- Bronchopulmonary sequestration
PRUNE BELLY SYNDROME is and path
Eagle Barrett syndrome or triad syndrome
A rare anomy comprising of three major findings:
- Gross pelvicalyceal and ureteric dilatation with renal dysplasia
- Anterior abdominal wall underdevelopment
- Bilateral undescended testes in males
Associations:
Aneuploidic syndromic associations
- Trisomy 18, 13
Congenital cardiac anomalies
- VSD
- ASD
- TOF
Intestinal malrotation
Imperforate anus
Talipes equinovarus
Urinary tract abnormalities include:
- Bilateral hydroutereronephrosis - extremely dilated, tortuous ureters
- Varying degrees of renal dysplasia
- Enlarged urinary bladder, often with urachal diverticulum
- VUR is common
- Poor bladder contractility
- Dilated posterior urethra without urethral obstruction
WILMS TUMOUR is and path
A malignant paediatric renal tumour
The most common renal mass, typically occurs in childhood 1-11yrs, with peak incidence 3-4yrs
Associations:
Overgrowth syndromes - WT2 gene
- Beckwith-Wiedemann syndrome
- Perlman syndrome
- Sotos syndrome
Non-overgrowth - WT1 gene
- WAGR syndrome
- Denys-Drash syndrome
- Fasier syndrome
- Bloom syndrome
Isolated abnormalities
- Cryptorchidism
- Hemihypertropy
- Hypospadias
- Sporadic aniridia
Risk factors: nephroblastomatosis
Pathology:
- Typically arises from mesodermal precursors of the renal parenchyma
- Implicated genes on chromosome 11
NEC is and path
Risk factors:
- Prematurity 50-80%
- Congenital heart disease
- Perinatal asphyxia
- Decreased umbilical flow in utero
Pathology:
- Usually idiopathic and multi-factorial
- A combination of ischaemic and infective aetiology
- Inflammation starts from the mucosal surface and progresses to haemorrhagic and coagulative necrosis
- Ensuing loss of mucosal integrity, transmural necrosis and perforation
- Can affect any part of the large or small bowel, most commonly the terminal ileum
TESTICULAR GERM CELL TUMOUR general
These account for 90% of primary testicular tumours
The most common non-haematologic malignancy in men age 15-49yo
Divided into:
Testicular seminoma – 40%
Non-seminomatous – 60%
- Embryonal cell carcinoma
- Choriocarcinoma
- Yolk sac tumour
- Testicular teratoma
- Mixed germ cell tumour 15%
Testicular non-germ cell tumours – 10%
- leydig
- sertoli
SEMINOMA is and path
Age 15-49
Risk factors
- Undescended testis 10-40x increased risk
- Previous tumour in the contralateral testis
- Family history
Bilateral are rare ~2% and almost always asynchronous
Pathology: pure seminoma on histo, and not associated with an elevated AFP
Otherwise classified as non-seminomatous
Three subtypes:
Classic: 85%,
- infrequent mitoses; monotonous sheet of large cells with abundant cytoplasm and round hyperchromatic nuclei, prominent nucleoli
Anaplastic: 10%,
- ≥3 mitotic figures per high-power field
Spermatocytic: 5%,
- older male patients above 60 years old, rarely metastasise; well-differentiated with cells resembling secondary spermatids
On gross examination, these are pale grey – yellow nodules that are uniform or slightly lobulated and often bulge form the cut surface
NON SEMINOMATOUS germ cell tumours are and path (including types)
Occur in younger patients, late teens - twenties
The most common primary testicular malignancy
Tend to be more aggressive than seminomas, and frequently metastasise
Markers:
70% produce hormone markers
- AFP – elevated in yolk sac
- BHCG – elevated in choriocarcinoma
- Lactate dehydrogenase
Tend to be more heterogenous on US, and T2 – frequent cystic areas or calcification
Subtypes:
Embryonal cell carcinoma - rare
- Age 25-30yo
Choriocarcinoma
- Age 20-30yo
- Most commonly detected as a component of a mixed malignant germ cell tumour
- The pure form is rare
- BHCG elevated
Yolk sac tumour
- Most common childhood tumour 80%, most before 2yo
- Pure is rare in adults, but mixed GCT is commonly seen
- Aetiology: totipotent cells which later form extraembryonic fetal membranes give rise to yolk sac tumours
- Markers: AFP elevated in >90%
- Macroscopically, the testis is replaced by a gelatinous mass
- US: diffusely enlarged, heterogenous testis
- MRI: heterogenous testicular mass with post-contrast heterogenous enhancement, areas of haemorrhage/necrosis
Teratoma
- Often aggressive in its biological behaviour
- Often exists as part of a testicular mixed GCT
- Divided by the age of the patient and degree of differentiation
- Mature – well-differentiated, biologically indolent
- Consider aggressive in post-pubertal males
- Prepubertal are usually benign
- Immature are more common in the testis
- US Cystic, heterogenous, mixed mucinous or sebaceous material, with or without hair follicles
Mixed
- Consist of two+ types of GCT
TESTICULAR SEX CORD/STROMAL TUMOURS are and path
~90% are benign, but cannot be differentiated from testicular malignancies on imaging
LEYDIG
- Most common, ~30% hormonally active
- Non-specific imaging, but serum hormone levels are abnormal
- Hypoestrogenism + gynaecomastia
- Virilisation
- Tend to be bimodal, one peak in paeds ~5-10yo, and one in adults ~20-30yo.
- Malignancy in ~10% of tumours
Pathology
- Arise from the interstitial cells of Leydig, adjacent to the seminiferous tubules
SERTOLI
- Less common than Leydig cell tumour
Pathology
- Large-cell calcifying - paeds
- Intratubular large cell hyalinising sertoli cell neoplasia
- Associated with paediatric males with Peutz-Jegher syndrome
- Sclerosing Sertoli cell tumour - adults
- Less likely to be hormonally active
- Associated with the Carney complex
BILATERAL TESTICULAR NEOPLASTIC LESIONS
Lymphoblastic leukaemia (acute or chronic)
Lymphoma (Non-hodgkins)
- Primary testicular lymphoma is rare
Metastases
PROSTATE CANCER is and path
The most common primary malignant tumour in men
Adenocarcinoma is the most common histological type
Primarily a disease of elderly men
PSA >1-4ng/dL is abnormal
Pathology
- 95% develop from the acini of the prostatic ducts
- Arise in the posterior/peripheral (70%) prostate gland more commonly than in the anterior gland and central zone (30%)
- Can spread by local invasion – bladder and seminal vesicles, lymphatic (pelvic > para-aortic > inguinal), or haematogenous
- Bone > lung > liver > pleura > adrenal glands
Histology
- Grading is using the Gleason score – the sum of the most prevalent and second most prevalent types of dysplasia, each on a scale of 1-5
- 5 is the most dysplastic
PROSTATITIS is
Infection or inflammation of the prostate gland
A clinical diagnosis, but imaging is used for abscess formation
Subtypes:
- Acute bacterial
- Chronic bacterial
- Chronic prostatitis/chronic pelvic pain syndrome
- Granulomatous
ADENOMATOID TUMOUR OF THE SCROTUM is and path
Benign, solid extratesticular lesions that can originate from the epididymis, tunica vaginalis or spermatic cord
3rd - 5th decade
Mesothelial origin
Most common extra testicular neoplasm, and the most common tumour of the epididymis
- Occur more often in the lower pole than the upper pole – 4:1
Usually an incidental finding, manifest as a small (<2cm) scrotal mass
- More frequently on the left
BENIGN PROSTATIC HYPERTROPHY is and path
Hyperplasia of stromal and glandular components
Predominantly located in the transitional zone of the prostate
50% prevalence in men age 51-60, increasing incidence with age
Location: transition (periurethral) zone of the prostate
Pathophysiology
- Proliferation of both stromal and epithelial cells, leading to new glandular budding and branching, with formation of nodules
- Central role of sex steroids and growth factors
- Aetiology unknown
Markers:
- Prostate specific antigen (PSA): Elevated but non-specific
SCROTAL TUBERCULOSIS is
A rare manifestation of extrapulmonary tuberculosis
Infection usually affects the epididymis first, then can affect the testis if not treated
Believed to occur due to retrograde extension from the prostate and seminal vesicles, as well as haematogenous spread
CRYPTORCHIDISM is and path
Absence of a testis in the scrotal sac
Testes develop in the abdomen, at 21 wks migrating towards the inguinal canal through the deep inguinal ring
The migration is complete ~30wks
The gubernaculum is the ligament which connects the testes to the scrotum
Under hormonal influence, the gubernaculum contracts, and the testes descend into the scrotum
Causes:
- Premature birth
- Intrauterine growth restriction
- Associations with smoking, alcohol intake during pregnancy
- Androgen insensitive syndrome
- Congenital syndrome
- Noonan syndrome
- Prune belly syndrome
- Gestational diabetes
MELANOMA is and path
The most common subtype of malignant melanoma, a malignant neoplasm that arises from melanocytes
Melanocytes predominantly occur in the basal layer of the epidermis, but do occur elsewhere in the body
While a less common skin cancer, it causes majority of the skin cancer related deaths due to tendency to metastasise
Risk factors:
- Exposure to high level UV
- Genetic predisposition
- More than 50 naevi
- Immunosuppression, sun sensitivity and freckles may also confer a predisposition to development of malignant melanoma
Pathology:
- Melanocytes produce melanin - the pigment responsible for skin colour
- Arise from the neural crest in the embryo and migrate throughout the body.
- Majority end up in the dermo-epidermal junction of the skin, providing melanin for the epidermal keratinocytes
- Those that undergo malignant change show varied architectural patterns of growth
Metastatic melanoma:
- The most frequent site of involvement of metastatic disease is the lymphatic system, particularly the local and regional nodes surrounding the primary.
- Further LN involvement typically progresses in a contiguous fashion
- Detection of spread in the LN is the most important predictor of survival
NF1 is and path, incl dx criteria and manifestaions
The most common phakomatosis
Autosomal dominant disorder
1:2500 – 3000, half are inherited the other are de novo mutation
Variable expression, but 100% penetrance by 5yo
Diagnostic criteria:
- >6 café au lait spots evident during one year
- 2+ neurofibromas or 1 plexiform neurofibroma
- Optic nerve glioma
- Distinctive osseous lesion – e.g. sphenoid wing dysplasia or thinning of long bone cortex +/- pseudoarthrosis
- 2+ iris hamartomas (Lisch nodules)
- Axillary or inguinal freckling
- A primary relative with NF1 with the above criteria
45% have learning disabilities
1% have hypertension due to renal artery stenosis
NF1 onset is earlier than schwannomatosis and NF2
Pathology:
- NF1 gene locus on chromosome 17q11.2. The gene product is neurofibromin – acts as a tumour suppressor of the RAS/MAPK pathway
- Inactivation of the gene predisposes to tumour development
- Primarily the disease is a hamartomatous disorder that involves the ectoderm and mesoderm
Three types:
- Localised - most common, dermis and subcut skin
- Diffuse - subcutaneous, usually head and neck
- Plexiform - considered pathognomonic, often neck, pelvis and extremities
Inactivation of a tumour suppressor gene > increased incidence of numerous tumours:
- Pheochromocytoma
- Malignant peripheral nerve sheath tumour
- Wilms tumour
- Rhabdomyosarcoma
- Renal AML
- Glioma:
- Juvenile pilocytic astrocytoma ~20%
- Optic nerve glioma
- Diffuse brainstem glioma
- Spinal astrocytoma, spinal pilocytic astrocytoma
- Carcinoid tumours
- Leiomyomas
- Leiomyosarcoma
- Ganglioglioma
- Leukaemia
Other manifestations
CNS
- FASI
- Optic nerve glioma
- Sphenoid wing dysplasia
- Lambdoid suture defects
- Dural calcification at the vertex
- Moya-moya phenomenon
- Buphthlamos
Skeletal
- Kyphoscoliosis
- Posterior vertebral scalloping
- Hypoplastic posterior elements
- Enlarged neural foramina
- Ribbon rib deformity, rib notching and dysplasia
- Dural ectasia
- Tibial pseudoarthrosis, or ulnar pseudoarthrosis
- Bony dysplasia’s - esp of the tibia
- Severe bowing, gracile bones
- Multiple non-ossifying fibromas
- Limb hemihypertrophy
Thoracic
- Mediastinal masses
- Neurofibroma
- Lateral thoracic meningocele - typically on the convex side of scoliosis
NF2 is and path
Autosomal dominant neurocutaneous disorder manifesting as a development of multiple CNS tumours
Rare, prevalence ~1:50 000, usually presents in young adults, age 18-24
50% of patients have an affected parent, and 50% have a de novo mutation
Pathology:
- NF2 gene is located on the long arm of chromosome 22 (22q12) and encodes the merlin protein - schwannomin
- Plays a role in contact inhibition of growth, with partial tumour suppressor function
Associations:
- Syringohydromyelia with lesions in the spine and cataracts
Imaging:
- Meningioma
- Schwannoma
- Usually from the inferior vestibular division of the vestibulocochlear nerve
- Can also be the facial nerve
- Ependymoma - usually spinal intramedullary
TURNERS SYNDROME is and path
45XO, the most common of the sex chromosome abnormalities in females
Associations:
- Hypertension
- Glucose intolerance
- Inflammatory bowel disease
- Hypothyroidism
- Horseshoe kidney
- Gonodal dysgenesis
Pathology:
- Absence of one X chromosome (45 XO), with the missing chromosome most frequently (2/3) being the paternal one
- Most occur spontaneously
Three main subtypes:
- Complete monosomy ~60% - most will spontaneously abort: ~70% at 16+ weeks
- Partial monosomy ~15%
- Mosaicism ~30%
There is no association with maternal age
Markers
- Serum AFP decreased
- Beta HCG Elevated if hydrops is present, decreased if no hydrops
- Serum inhibin Elevated if hydrops is present, absent if hydrops is absent
Complications
- In utero development of hydrops fetalis - usually secondary to lymphatic failure
TURNERS SYNDROME imaging
Antenatal
- Cystic hygroma - may appear septate
- Increased nuchal thickness, increased nuchal translucency
- Coarctation of the aorta 15-20%
- Bicuspid aortic valve
- Pelvic kidney
- Mild IUGR
- Short fetal limbs
Postpartum
MSK
- Scoliosis
- Short 4th MCP
- Narrowed scapholunate angle - positive carpal sign
- Abnormal medial femoral condyle
- Decreased carpal angle - madelung deformity
- Valgus deformity of the elbow
Pelvis:
- Streaky uterus
- Streaky ovary
Cardiovascular:
- Aortic dissection
GI
- Pyloric stenosis
TRISOMY 21 is and path (incl manifestations)
The most common trisomy, and commonest chromosomal disorder
Risk factors:
- Increased incidence with increasing maternal age
- Translocation down syndrome gene carriers
- Previous pregnancy with Down syndrome
Often diagnosed antenatally
Classic phenotype:
- Depressed nasal bridge
- Epicanthal folds
- Abundant nasal skin
- Macroglossia
Pathology:
- Chromosomal abnormality is trisomy of chromosome 21 due to meiotic non-disjunction (failure of a chromosome pair to separate)
- So the total chromosome count is 47 - maternal non-disjunction accounts for ~95% of cases
Neurology:
- Cerebellar and vermian hypoplasia
- Moyamoya syndrome
- Alzheimer disease
- Hippocampal volume loss
- Hearing loss: semicircular canal dysplasia and dehiscence, narrowed IAC, cochlear nerve canal stenosis, enlarged vestibular aqueduct
Cardiovascular:
- Congenital heart disease in 40%
- AVSD - most common
- Secundum ASD
- VSD
Respiratory
- Pulmonary hypoplasia
- Pulmonary cyst
- Pig bronchus
GI
- Anal, duodenal atresia
- Coeliac disease
- Hirschsprung disease
- Omphalocele
- Diaphragmatic herniation
MSK
- Eleven ribs
- Hypersegmented sternum
- Joint laxity/dislocations
- DDH
- Atlantoaxial subluxation and atlanto-occipital instability
- Hypoplastic posterior arch of C1
- “mickey mouse” pelvis with flaring of iliac wings
Endocrine
- Thyroid dysfunction - mostly hypothyroidism
Increased incidence of leukaemia
TUBEROUS SCLEROSIS is and path
Phakomatosis characterized by the development of multiple benign tumours of the embryonic ectoderm
Most are sporadic
The pathognomonic triad – only seen in 30%
- Seizures: absent in ¼ of individuals
- Intellectual disability: up to half have normal intelligence
- Adenoma sebaceum: only present in ~¾ of patients
Pathology:
- Spontaneous mutations account for 50-66%, the rest are inherited as an autosomal dominant condition
Two tumour suppressor genes are involved:
- TSC1 – encoding hamartin, on chromosome 9q32-34
- TSC2 – encoding tuberin, on chromosome 16p13.3
TS manifestations
Neurology:
- Cortical/subcortical tubers: 50% in the frontal lobe
- High T2, low T1 – 10% enhance, frequently calcify
- Subependymal hamartomas – 88% associated with calcification
- Variable signal, high T1, iso-high T2
- Variable enhancement
- Only serial growth is reliable to differentiate from SEGA
- Subependymal giant cell astrocytomas
- Peak occurrence 8-18yo
- White matter abnormalities
- Radial bands – specific for TS
- Variable appearance – nodular, ill-defined, cystic and band-like lesions seen
- Retinal phakomas
Rarer findings:
- Cerebellar atrophy
- Infarcts
- Arachnoid cysts
- Chordoma
Abdominal
- Renal angiomyolipomas
- TS accounts for 20%
- Seen in 55-75% of patients with TS
- Tend to be multiple, large and bilateral
- Fat may not be visible in up to 4.5%
- Renal cysts: TSC2 gene is located adjacent to the PCKD1 gene
- 18-53% of patients with TS
- Renal cell carcinoma and oncocytomas
- RCC tends to occur earlier
- Retroperitoneal lymphangiomyomatosis
- Histologically identical to pulmonary LAM
- Retroperitoneal cystic lesions
- Chylous ascites, enlarged lymph nodes, dilataton of the thoracic duct
- GI polyps
- Pancreatic neuroendocrine tumours
- Hepatic angiomyolipomas
Thoracic
- Lymphangioleiomyomatosis (LAM)
- Rare
- 25-40% of female pts with TS
- Indistinguishable from sporadic LAM
- Pneumothorax and chylous pleural effusions are common
- ~80% 10yr survival
- Multifocal micronodular pneumocyte hyperplasia (MMPH)
- Rare
- Multicentric, well-demarcated nodular proliferation of type II pneumocytes
- Benign, non-progressive
- Differentials: miliary opacities
Cardiac rhabdomyomas
- Benign striated muscle tumour characterised by the presence of spider cells
- Seen in 50-65% of pts with TS
- 40-80% of patients with cardiac rhabdomyomas have TS
- Multiple or single
- Typically involve the ventricular septum
- Occur before the age of 1yo (75%)
- Spontaneous regression in 70% of children by age 4
Thoracic duct and aortic/pulmonary artery aneurysm
Myocardial fatty foci
MSK
- Sclerotic bone lesions 46-66%
- Hyperostosis of the inner table of the calvaria
- Periosteal new bone
- Scoliosis
- Bone cyst
Skin
- Cutaneous lesions in ~95% of cases
- Facial angiofibromas
- Hypopigmented macules – ash leaf spots
- Fibrous plaques on forehead
- Confetti lesions
VHL is and path including manifestations
Numerous benign and malignant tumours in different organs, due to mutations in the VHL tumour suppressor gene on chromosome 3
Most are diagnosed with their first tumour in early adulthood
Abdominal:
Renal cell carcinomas
- Usually clear cell and bilateral
- 70% lifetime risk
- Present earlier in pts with VHL
Renal cysts
- Often bilateral and multiple
- Can be simple, complex or cystic RCC
Renal angiomyolipomas
Adrenal:
- Phaeochromocytomas 25-30%
- Extra-adrenal phaeochromocytoma/paraganglioma
Pancreas – may be the earliest manifestation
- Pancreatic cysts ~40%
- Pancreatic neuroendocrine tumours
- ~12.5% of patients
- Usually non-functional
- Frequently multiple
- Pancreatic serous cystadenomas: ~12.5% of patients
- Pancreatic adenocarcinomas
Liver
- Liver cysts
Urogenital
- Epididymal cysts
- Papillary cystadenoma of the epididymis
- Broad ligament cystadenomas
CNS
Haemangioblastomas ~70%
- Cerebellar ~60%
- Spinal cord ~30% - most commonly in the cervical and thoracic cord
- brainstem
Choroid plexus papilloma
Head and neck
- Retinal haemangioblastoma
- Most common presenting feature
- Vision loss
- Endolymphatic sac tumours
- Bilateral in 30%, pathognomonic for vHL
Endocarditis is and path
Acute endocarditis
- High virulent organisms (e.g. staph aureus)
- Typically seeds a previously normal valve
- Necrotizing, ulcerating and invasive infections
- Clinical: rapid onset fever and constitutional symptoms
Morphology:
- Right heart valves more commonly affected than left valves in IV drug users
- Bulky vegetations with underlying valve destruction
- Invasion into adjacent myocardium or aorta can occur
- Distal embolization with septic infarcts and mycotic aneurysms can occur
Subacute endocarditis:
- Moderate to low virulence organisms
- Streptococcus viridans most common (50-60%)
- Enterococci
- HACEK group of oral comsensals:
- Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella
- Seeding of a previously abnormal or damaged valve
- Less valvular destruction
- Nonspecific clinical course, lower mortality rate than acute infective endocarditis
Morphology:
- Smaller vegetations
- Less likely to cause distal embolic phenomena due to their small size
Duke Criteria for infective endocarditis:
For diagnosis require:
2 major and 1 minor criteria
1 major and 3 minor criteria
5 minor criteria
Major criteria:
- Positive blood cultures
- Typical micro-organism cultured
- Persistently positive cultures: 2 blood cultures greater than 12 hours apart
- Evidence of endocardial involvement:
- Positive echocardiogram
- Oscillating intracardiac mass
- Abscess
- New partial dehiscence of a prosthetic valve
- New valvular regurgitation
Minor criteria:
- Predisposing heart condition or IV drug use
- Fever >38 degrees
Vascular phenomena:
- Major arterial emboli
- Septic pulmonary infarcts
- Mycotic aneurysm
- Intracranial haemorrhage
- Conjunctival haemorrhage
- Janeway lesions
Immunologic phenomena:
- Glomerulonephritis
- Osler nodes
- Roth spots
- Rheumatoid factore
Microbiologic evidence:
- Positive blood culture which does not meet major criteria
- Serological evidence of active infection with consistent organism
- Echocardiography findings consistent with infective endocarditis but not meeting major criteria
Indian ink stain demonstrates
cryptococci with their thick gelatinous capsules
May show encapsulated yeasts of Cryptococci on India Ink or Cryptococcal antigen, or in tissue
sections by PAS, mucicarmine and silver stains (esp. frequent in debilitated or
immunocompromised patients)
Schwannoma path
Focal growth, encapsulated
Cystic degeneration,
haemorrhage,
xanthomatous change common
Arise eccentrically from parent
nerve
Nerve fibres do not run through
tumour
Spindle cells (Antoni A) &
looser myxoid stroma (Antoni B)
schwann cells. nf2. common. cnviii and spinal nerves. no malignant degen.
Neurofibroma path
Infiltrating growth
Unencapsulated
Necrosis & cystic change
uncommon
Nerve fibres run through tumour
Spindle cells, with intercellular
collagen fibrils in myxomatous
matrix
nf1. cutaneous and spinal. 5-10% malignant degen.
CMV encephalitis path
Neurologic manifestations of CMV thus include acute or chronic meningoencephalitis, cranial neuropathy, vasculitis, retinitis, myelitis, brachial plexus neuropathy, and peripheral neuropathy
The pathologic hallmark of CMV is the “owl’s eye,” an enlarged cell with a distended nucleus containing eosinophilic viral inclusions, surrounded by a halo, resulting in the characteristic appearance
The owl’s eye appearance can be seen in ependymal cells, subependymal astrocytes,
oligodendroglia, endothelial cells, and neurons.
Ependymal involvement is quite common.
Infrequently, CMV infection may result in extensive destruction of gray and white matter
Other typical histopathologic findings in the CNS include well-circumscribed microglial nodules,
