Histopathology Flashcards

1
Q

Where do non-traumatic intraparenchymal haemorrhages tend to occur most frequently?

A

Basal ganglia

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2
Q

Define cavernous angioma.

A

Well-defined malformative lesion composed of closely-packed vessels with no parenchyma interposed between vascular spaces
NOTE: it is similar to an arteriovenous malformation but there is no brain substance wrapped up amongst the vessels
NOTE: these tend to bleed at lower pressure causing recurrent small bleeds
NOTE: shows target sign on MRI

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3
Q

What is the biggest cause of death in people < 45 years?

A

Traumatic brain injury

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4
Q

Describe the Braak stages of Alzheimer’s disease.

A

Stage 1: tau pathology in the transentorhinal cortex
Stage 2: posterior hippocampus
Stage 3: immunostaining is visible by eye, affects substantia nigra
Stage 4: superior temporal gyrus
Stage 5: peristriate cortex
Stage 6: striate cortex
NOTE: clinically, symptoms tend to arise in stage 3 or 4

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5
Q

What is the diagnostic gold standard for Parkinson’s disease?

A

Alpha-synuclein immunostaining

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6
Q

What are three important differentials to consider in a patient with Parkinson’s disease?

A

Multiple system atrophy
Corticobasal degeneration
Progressive supranuclear palsy

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7
Q

What is multisystem atrophy?

A

It is an alpha-synucleinopathy like Parkinson’s disease which targets glial cells
It presents similarly to Parkinson’s disease
It mainly affects the cerebellum so the patients are more likely to present with falls

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8
Q

What are the main histological features of Pick’s disease?

A

Marked gliosis and neuronal loss
Balloon neurones
Tau-positive Pick bodies
NOTE: mutations in tau are associated with a fronto-temporal dementia phenotype often associated with Parkinson’s disease
NOTE: there are 17 autosomal dominant syndromes resulting from mutations in tau

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9
Q

Which gene encodes tau?

A

17q21

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10
Q

Describe how the types of tau present in Alzheimer’s disease is different from CBD, PSP and Pick’s disease.

A

Alzheimer’s – when the tau is put through a Western blot, it will form 3 dense bands. If this is dephosphorylated it will show all 6 isoforms of tau
CBD and PSP – produces 2 dense bands which, when dephosphorylated, are shown to be made up of only 4R tau (i.e. it is a 4R tauopathy)
Pick’s disease – it is a 3R tauopathy

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11
Q

What is a characteristic feature of frontotemporal dementia associated with progranulin mutations?

A

Atrophy tends to be unilateral

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12
Q

Which other protein is thought to be implicated in some types of fronto-temporal dementia?

A

TDP-43 (trafficking protein)

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13
Q

On a cellular level, what insult results in ARDS?

A

Acute damage to the endothelium and/or alveolar epithelium

The basic pathology is the same regardless of cause: diffuse alveolar damage

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14
Q

Outline the pathophysiology of ARDS.

A

Exudative phase – the lungs become congested and leaky
Hyaline membranes – form when serum protein that is leaked out of vessels end up lining the alveoli
Organising phase – organisation of the exudates to form granulation tissue sitting within the alveolar spaces

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15
Q

Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency.

A

Smoking – centrilobular damage

Alpha-1 antitrypsin deficiency – panacinar (throughout the lungs)

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16
Q

Where is the CFTR gene found?

A

7q31.2

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17
Q

What are the histopathological stages of lobar pneumonia?

A

Stage 1: congestion (hyperaemia and intra-alveolar fluid)
Stage 2: red hepatisation (hyperaemia, intra-alveolar neutrophils)
Stage 3: grey hepatisation (intra-alveolar connective tissue)
Stage 4: resolution (restoration of normal tissue architecture)

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18
Q

Describe the histological appearance of atypical pneumonia.

A
Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells 
NOTE: causes include Mycoplasma, viruses, Coxiella and Chlamydia
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19
Q

Where do squamous cell carcinomas tend to arise?

A

Centrally – arising from the bronchial epithelium
NOTE: there is an increasing incidence of peripheral squamous cell carcinomas (possibly due to deeper inhalation of modern cigarette smoke)

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20
Q

What is the precursor lesion for adenocarcinoma of the lung?

A

Atypical adenomatous hyperplasia (proliferation of atypical cells lining the alveolar walls)

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21
Q

Which mutations are associated with adenocarcinoma in smokers?

A

Kras
Issues with DNA methylation
P53

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22
Q

Which mutations are associated with adenocarcinoma in non-smokers?

A

EGFR

EML4-ALK

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23
Q

List some common mutations seen in small cell lung cancer.

A

P53

RB1

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24
Q

Which molecular changes are important to test for in adenocarcinoma?

A

EGFR (responder or resistance)
ALK translocation
Ros1 translocation

NOTE: it is important to correctly identify the type of lung cancer because of treatment implications. E.g. bevacizumab can cause fatal pulmonary haemorrhage in squamous cell carcinoma

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25
Which stain is used for melanin?
Fontana stain
26
Which stain is used for amyloid?
Congo Red | When viewed under polarised light, it produces apple green birefringence
27
What is a key immunological lymphoid marker?
CD45
28
List some tumour-like conditions of the bone.
``` Fibrous dysplasia Metaphyseal fibrous cortical defect/non-ossifying fibroma Reparative giant cell granuloma Ossifying fibroma Simple bone cyst ```
29
What is fibrous dysplasia?
Condition in which fibrous tissue develops in place of normal bone tissue Can occur in any bone but ribs and proximal femur is most common Tends to affect patients < 30 years Causes soap bubble osteolysis on X-ray NOTE: giant cell tumours can also have a soap bubble appearance on X-ray but tend to affect the bones around the knee
30
Which eponymous syndrome is characterised by polyostotic fibrous dysplasia?
McCune Albright Syndrome – polyostotic fibrous dysplasia + endocrine problems (precocious puberty) + rough border café-au-lait spots
31
Which mutation causes fibrous dysplasia?
GNAS mutation Chr 20 q13 (mutation in a G-protein)
32
Describe the histological appearance of fibrous dysplasia.
The marrow is replaced by fibrous stroma with rounded trabecular bone (‘Chinese letters’)
33
What is an enchondroma and which bones tend to be affected?
A cartilaginous proliferation within the bone Most tend to be found in the hands and can cause pathological fractures X-ray may show popcorn calcification Associated with Ollier's syndrome and Maffuci syndrome
34
Which cancers in children tend to spread to the bone?
``` Neuroblastoma Wilm’s tumour Osteosarcoma Ewing’s sarcoma Rhabdomyosarcoma ```
35
Describe the X-ray appearance of osteosarcoma.
Usually metaphyseal Lytic Elevated periosteum (Codman’s triangle) Sunburst appearance
36
Describe the X-ray appearance of chondrosarcoma.
Lytic with fluffy calcification
37
List the histological subtypes of chondrosarcoma.
``` Conventional (myxoid or hyaline) Clear cell (low grade) Dedifferentiated (high grade) Mesenchymal NOTE: myxoid = composed of clear, mucoid substance ```
38
What is an Ewing’s sarcoma?
Highly malignant small round cell tumour Occurs in people < 20 years old MIC2 (CD99) antibody
39
Which genetic abnormality is associated with Ewing’s sarcoma?
Chromosomal translocation 11:22 (EWSR1/FLI1) (q24:q12)
40
List three types of soft tissue tumour.
Liposarcoma Spindle cell sarcoma Pleomorphic sarcoma
41
Outline the coding used by cytopathologists when assessing breast aspirates.
``` C1 = inadequate C2 = benign C3 = atypia, probably benign C4 = suspicious of malignancy C5 = malignant ```
42
Describe the histology of fibroadenoma.
Consists of lots of glandular and stromal cells
43
What are the two different types of intraductal papilloma
Peripheral papilloma – arises in small terminal ductules | Central papilloma – arises in large lactiferous ductules
44
What is a radial scar?
A benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue
45
fDescribe the histological appearance of radial scars.
Central stellate area with proliferation of ducts and acini in the periphery
46
What is flat epithelial atypia/atypical ductal hyperplasia?
May be the earliest precursor to low grade DCIS | There are multiple layers of epithelial cells and the lumens become more regular
47
What is ductal carcinoma in situ?
A neoplastic intraductal epithelial proliferation in the breast that has not breached the basement membrane
48
What is in situ lobular neoplasia?
A solid proliferation of cells within the acinus
49
Describe the histological appearance of low grade DCIS.
Lumens are compact and regular (cribriform (punched out) appearance) Rapid death and proliferation of cells leads to calcification
50
Describe the two genetic pathways that result in DCIS.
Low grade – arise from low grade DCIS or in situ lobular neoplasia and show 16q loss High grade – arise from high grade DCIS and show complex karyotypes with unbalanced chromosomal aberrations
51
Describe the histological appearance of: a. Invasive ductal carcinoma b. Invasive lobular carcinoma c. Invasive tubular carcinoma d. Invasive mucinous carcinoma
a. Invasive ductal carcinoma Cells are pleomorphic and have large nuclei b. Invasive lobular carcinoma Cells have a linear arrangement and are monomorphic NOTE: cords of cells are sometimes referred to as ‘Indian File’ pattern c. Invasive tubular carcinoma Elongated tubules of cancer cells invade the stroma d. Invasive mucinous carcinoma Lots of ‘empty’ spaces containing mucin
52
Describe the histological appearance of Basal-like carcinoma.
Sheets of markedly atypical cells with a prominent lymphocytic infiltrate Central necrosis is common
53
Describe the immunohistochemistry findings in Basal-like carcinoma.
Positive for basal cytokeratins - CK5/6 and CK14 NOTE: basal-like carcinoma is associated with BRCA mutations
54
Which histological grading system is used for invasive breast carcinoma?
Nottingham modification of the Bloom-Richardson system
55
Outline the coding of biopsies for suspicious breast lumps.
``` B1 = normal breast tissue B2 = benign abnormality B3 = lesion of uncertain malignant potential B4 = suspicious of malignancy B5 = malignancy (a = DCIS; b = invasive carcinoma) ```
56
Describe the histology of gynaecomastia.
Epithelial hyperplasia with finger-like projections extending into the duct lumen Periductal stroma is often cellular and oedematous Similar to fibroadenoma
57
List some causes of thyrotoxicosis that are not associated with the thyroid gland.
Struma ovarii – ovarian teratoma with ectopic thyroid hormone production Factitious thyrotoxicosis – exogenous thyroid hormone intake
58
Describe the histology of Hashimoto’s thyroiditis.
There are lots of lymphoid cells with germinal centres | The epithelial cells become large with lots of eosinophilic cytoplasm (Hurthle cells)
59
List the four types of thyroid cancer in order of decreasing prevalence.
Papillary (80%) Follicular (15%) Medullary (5%) Anaplastic
60
What is the diagnosis of papillary thyroid cancer based on?
Nuclear features • Optically clear nuclei • Intranuclear inclusions (Orphan Annie eye) There may also be psammoma bodies (little foci of calcification) Usually non-functional On histology, they have a papillary structure (central connective tissue stalk with surrounding epithelium)
61
Where does follicular thyroid cancer tend to metastasise?
Lungs, bone and liver (via the bloodstream)
62
What are the parathyroid glands derived from?
Developing pharyngeal pouches
63
What are the causes of hyperaldosteronism?
35% adenoma (Conn’s syndrome) 60% bilateral adrenal hyperplasia NOTE: Meeran's website says Conn's is more common but this may have changed recently
64
List three causes of acute primary adrenal failure.
Haemorrhage DIC associated with sepsis (Waterhouse-Friderichson syndrome) Sudden withdrawal of corticosteroid treatment
65
Which tumours are associated with the different types of MEN?
``` MEN1 = pituitary + parathyroid + pancreatic islet cell MEN2 = parathyroid + medullary thyroid cancer + phaeochromocytoma 2B = + marfanoid appearance + mucosal neuromas ```
66
List three autoantibodies found in SLE. Which is most specific?
Anti-dsDNA Anti-smith (against ribonucleoproteins) – most specific but low sensitivity Anti-histone – drug-related (e.g. hydralazine)
67
How is anti-dsDNA measured?
Incubate the patient’s serum with Crithidia Luciliae (protozoan) It has a big organism with dsDNA (kinetoplast) so if the patient has anti-dsDNA antibodies it will bind to the dsDNA in the kinetoplast NOTE: it can also be measured with ELISA
68
Describe the appearance of skin histology in SLE.
Lymphocytic infiltration of the dermis Vacuolisation (dissolution of the cells) of the basal epidermis Extravasation of blood causes a rash Immunofluorescence will show immune complex deposition at the epidermis-dermis junction
69
Describe the appearance of renal histology in SLE.
Glomerular capillaries are thickened (wire-loop capillaries) due to immune complex deposition NOTE: this can be visualised by immunofluorescence
70
What is the name of non-infective endocarditis associated with SLE?
Libman-Sacks endocarditis
71
What is the localised form of scleroderma called?
Morphoea
72
What pattern of ANA immunofluorescence is seen in scleroderma?
Nucleolar
73
What ANA immunofluorescence pattern is seen in mixed connective tissue disease?
Speckled
74
What criteria is used to classify vasculitides based on the size of the vessel?
Chapel Hill Criteria
75
What is polyarteritis nodosa? What are its main features?
A necrotising arteritis which is focal and sharply demarcated It heals by fibrosis and mainly affects the renal and mesenteric vessels May present with gut ischaemia or renal impairment It produces a rosary beads appearance on angiography due to multiple aneurysms Associated with hepatitis B
76
Which antibody is associated with granulomatosis with polyangiitis?
cANCA – against proteinase 3
77
Which antibody is associated with Churg-Strauss syndrome?
pANCA – against myeloperoxidase
78
List some gynaecological infections that cause serious complications.
Chlamydia (infertility) Gonorrhoea (infertility) Mycoplasma (spontaneous abortion and chorioamnionitis) HPV (cancer)
79
What feature of high risk HPV viruses are responsible for the carcinogenic effects of HPV?
E6 protein – inactivates p53 | E7 protein – inactivates retinoblastoma
80
What are the two types of HPV infection? Describe them.
Latent (non-productive) • HPV DNA continues to reside within basal cells • Infectious virions are not produced • Replication of viral DNA is coupled to replication of epithelial cells • This means that complete viral particles are not produced • Cellular effects of HPV are not seen Productive • Viral DNA replication occur independently of host chromosomal DNA synthesis • Large amount of viral DNA and infectious virions are produced • Characteristic cytological and histological features are seen (halo around the nucleus – koilocyte)
81
Other than CIN, what else is screened for in some centres?
High risk HPV using molecular genetic analysis Hybrid capture II (HC2) HPV DNA Test – smear is mixed with fluid containing RNA probes that match 5 low-risk and 13 high-risk types of HPV
82
List some causes of endometrial hyperplasia.
Persistent anovulation (due to persistently raised oestrogen) PCOS Granuloma cell tumour of the ovary Oestrogen therapy
83
List some risk factors for endometrial carcinoma.
Nulliparity Obesity Diabetes mellitus Excessive oestrogen stimulation
84
What are the subtypes of type I endometrial carcinoma?
Endometrioid adenocarcinoma Mucinous adenocarcinoma Secretory adenocarcinoma NOTE: tends to occur in younger patients, low grade and oestrogen-dependent, arises from atypical endometrial hyperplasia
85
What are the subtypes of type II endometrial carcinoma?
Serous and clear cell tumours | NOTE: occurs in older patients, less oestrogen-dependent and arises in atrophic endometrium
86
Which genetic mutations are associated with the two types of type II endometrial carcinoma?
``` Endometrial Serous Carcinoma • P53 (90%) • P13KCA (15%) Her2 amplification Clear Cell Carcinoma • PTEN • CTNNB1 • Her2 amplification ```
87
What are the chances of moles progressing to malignancy?
NO partial moles progress to malignancy 2.5% of complete moles progress to malignancy 10% of complete moles develop into locally destructive invasive moles
88
Describe how complete and partial moles form.
Complete mole • Occurs when you get fertilisaiton of an EMPTY egg • Reduplication of the 23X from sperm results in a homozygous diploid 46XX genome • Can also occur due to fertilisation of an empty egg by 2 sperms with 2 independent sets of 23X or 23Y Partial mole • A normal ovum containing 23X gets fertilised by TWO sperm leading to the presence of 3 sets of chromosomes (2 paternal + 1 maternal) • Dispermia  diandry • Overdose of male chromosomes drive proliferation • Can also occur due to fertilisation of a normal egg by a sperm carrying unreduced paternal genome (46XY)
89
List two types of non-neoplastic functional cysts.
Follicular and luteal cysts | Endometriotic cyst
90
List three types of primary specific ovarian tumour.
Surface epithelial tumours Sex cord stromal tumours Germ cell tumours
91
Outline the classification of epithelial ovarian tumours.
``` Type 1 • Low grade • Relatively indolent and arise from well characterised precursors (benign tumours) and endometriosis • Mutations: K-Ras, BRAF, P13KCA, Her2, PTEN, beta-catenin Type 2 • HIGH GRADE • Aggressive • P53 mutation in 75% of cases • NO precursor lesion ```
92
Give examples of Type 1 and Type 2 ovarian tumours.
Type 1 = low grade serous, endometrioid, mucinous and clear cell Type 2 = mostly serous NOTE: endometrioid has a better prognosis than mucinous or serous
93
List some benign ovarian tumours.
Serous cystadenoma Cystadenofibroma Mucinous cystadenoma Brenner tumour
94
What are the key features of serous tumours?
MOST COMMON type of ovarian tumour Usually cystic 30-50% bilateral Benign tumours are lined by bland epithelium Borderline tumours have a more complex, atypical epithelial lining with papillae but no invasion through the basement membrane Malignant tumours are invasive with a poor prognosis
95
Which type of ovarian tumour has a strong association with endometriosis?
Clear cell tumours | NOTE: endometrioid tumours are associated about 20% of the time
96
List four types of sex cord stromal tumours and the hormones that they may produce.
Fibroma (no hormone production) Granulosa cell tumour (may produce oestrogen) Thecoma (may produce oestrogen (rarely androgens)) Sertoli-Leydig cell tumour (may be androgenic)
97
What are the four main types of germ cell tumour?
Dysgerminoma – no differentiation Teratoma – from embryonic tissues Endodermal sinus tumour – from extraembryonic tissue (e.g. yolk sac) Choriocarcinoma – from trophoblastic cells which would form the placenta
98
What are the key features of an immature teratoma?
Indicates presence of embryonic elements (most commonly neural tissue) Malignant tumour that grows rapidly, penetrates the capsule and forms adhesions Spreads within peritoneal cavity and metastasises to the lymph nodes, lungs, liver and other organs
99
Name two secondary ovarian tumours.
Krukenberg Tumour – bilateral metastases composed of mucin-producing signet ring cells (usually from breast or gastric cancer) Metastatic colorectal cancer
100
List three familial syndromes associated with ovarian cancer.
Familial breast-ovarian cancer syndrome Site-specific ovarian cancer Cancer family syndrome (Lynch type II)
101
List some specific genetic associations for serous, mucinous and endometrioid carcinoma.
Serous – BRCA | Mucinous and endometrioid - HNPCC
102
Name a benign tumour of the vulva.
Papillary hidradenoma
103
Which arteries tend to be involved in myocardial infarction (in order of most to least frequent)?
LAD – 50% RCA – 40% LCx – 10%
104
Describe the microscopic changes that take place in myocardial infarction.
Under 6 hours – normal histology 6-24 hours – loss of nuclei, homogenous cytoplasm, necrotic cell death 1-4 days – infiltration of polymorphs then macrophages 5-10 days – removal of debris 1-2 weeks – granulation tissue, new blood vessels, myofibroblasts, collagen synthesis Weeks to months – strengthening and decellularising the scar
105
What is reperfusion injury?
Consequence of letting blood go back into the area of myocardial necrosis Oxidative stress, calcium overload and inflammation cause further injury Arrhythmias are common It can cause stunned myocardium – reversible cardiac failure lasting several days
106
What is hibernating myocardium?
Chronic sublethal ischaemia leads to lower metabolism in myocytes which can be reversed with vascularisation
107
Outline the histology of heart failure.
Dilated heart Scarring and thinning of the walls Fibrosis and replacement of ventricular myocardium
108
What is dilated cardiomyopathy?
Caused by progressive loss of myocytes leading to a dilated heart
109
What is hypertrophic cardiomyopathy?
Thickening of the heart muscle Family history in 50% of cases Some are associated with a specific abnormality in the beta-myosin heavy chain NOTE: other mutations include myosin binding protein-C and troponin T
110
Which valve is most commonly affected in rheumatic valvular disease?
Left-sided valves (almost always mitral)
111
How is the arrangement of endothelial cells in the liver different from other parts of the body?
The endothelial cells do not sit on a basement membrane and the endothelium is discontinuous (there are no tight junctions)
112
What is the role of stellate cells and what could happen to them when activated?
Storage of vitamin A | When activated, they become myofibroblasts that lay down collagen (this is responsible for scarring in liver disease)
113
Outline the arrangement of structures within a normal liver.
There will be portal tracts consisting of a branch of the hepatic artery, a branch of the portal vein and a bile duct Blood will flow from the portal tract to the central vein There is a ring of collagen around the portal tract called the limiting plate There are three zones of hepatocytes in between the portal tract and the central vein Zone 3 is closest to the central vein and contains the most metabolically active enzymes
114
Describe the arrangement of hepatocytes, endothelial cells, stellate cells and Kupffer cells in a normal liver.
There are spaces in between endothelial cells and there is a gap in between the endothelial cells and the hepatocytes (space of Disse) Stellate cells sit within the space of Disse Kupffer cells are found within the sinusoids Blood can easily get through the spaces in the endothelial cells into the space of Disse where they are exposed to hepatocytes
115
Describe how the arrangement of cells changes in liver disease.
Kupffer cells become activated (inflammatory response) Endothelial cells stick together so blood finds it more difficult to get into the space of Disse Stellate cells become activated and secrete basement membrane-type collagens into the space of Disse Hepatocytes lose their microvilli All these changes make it difficult for blood to be exposed to hepatocytes
116
What is a common histological feature of all acute hepatitis?
Spotty necrosis
117
What is interface hepatitis?
Aka piecemeal hepatitis Inflammation crosses the limiting plate making it difficult to distinguish where the portal tract ends and the hepatocytes begin Characteristically seen in chronic viral hepatitis and autoimmune hepatitis Portal inflammation = inflammation confined within limiting place Lobular inflammation = inflammation across entire lobule
118
List some histological features of alcohol hepatitis.
Ballooning – cell swelling Mallory Denk bodies/Mallory hyaline - pink intracellular material Apoptosis Pericellular fibrosis
119
In which part of the liver do the histological features of alcoholic hepatitis tend to be seen and why?
Zone 3 Alcohol is not toxic, but acetaldehyde is toxic Zone 3 cells contain the most alcohol dehydrogenase thereby producing the most acetaldehyde Furthermore, by the time blood reaches zone 3 (after passing zones 1 and 2) it is relatively hypoxic making the cells in zone 3 even more vulnerable to damage
120
What is primary biliary cholangitis?
Autoimmune conditions characterised by bile duct loss associated with chronic inflammation (with granulomas)
121
What is the diagnostic test for PBC?
Anti-mitochondrial antibodies (AMA)
122
What is the histological appearance of PBC?
Bile ducts surrounded by epithelioid macrophages, suggestive of chronic granulomatous destruction of bile ducts
123
What is primary sclerosing cholangitis?
Autoimmune condition characterised by periductal bile duct fibrosis leading to loss of bile ducts NOTE: in PBC, bile duct loss is caused by inflammation, whereas in PSC it is caused by fibrosis NOTE: PSC is associated with ulcerative colitis and is associated with an increased risk of cholangiocarcinoma
124
What is the diagnostic test for PSC?
Bile duct imaging
125
What causes haemochromatosis and which gene is implicated?
Caused by increased gut iron absorption HFe gene on chromosome 6 NOTE: women tend to present later because they have naturally lower iron levels
126
What is haemosiderosis?
Type of iron overload characterised by the accumulation of iron in macrophages Usually occurs as a result of receiving blood transfusions
127
What is Wilson’s disease?
Characterised by an accumulation of copper due to the failure of excretion of copper by hepatocytes into the bile Low serum copper, low caeruloplasmin, high urine copper Rhodanine stain NOTE: treated with penicillamine (copper chelator)
128
How is autoimmune hepatitis diagnosed?
Type 1: Anti-smooth muscle antibodies (ASMA), anti-soluble liver antigen, ANA Type 2: anti-LKM, associated with IgA deficiency NOTE: type 2 tends to present at a younger age (paediatrics) and has a poor response to steroids
129
Which precursor lesion has the highest risk of developing into breast cancer?
In situ lobular neoplasia
130
Which gene is mutated in Wilson disease?
ATP7B on chromosome 13
131
What are the stages of lupus nephritis?
Class I: minimal mesangial lupus nephritis with immune complexes but no structural alteration Class II: mesangial proliferative lupus nephritis with immune complexes and mild/mod increase in mesangial matrix and cellularity Class III: focal lupus nephritis with active swelling and proliferation in less than half the glomeruli Class IV: diffuse lupus nephritis with involvement of more than half the glomeruli Class V: membranous lupus nephritis with subepithelial immune complex deposition Class VI: advanced scleroising with complete sclerosis of >90% of the glomeruli.
132
What are some common associations of polycystic kidney disease?
``` Hepatic cysts (and cirrhosis with PKD1) Berry aneurysms) Mitral valve prolapse Aortic root dilatation Abdominal wall hernias ```
133
Which antibody is associated with drug-induced lupus?
Anti-histone
134
What is the most common type of lung cancer?
Adenocarcinoma | NOTE: this is the most common cause of lung cancer in both smokers and non-smokers
135
Describe how alcohol can cause acute pancreatitis.
It leads to spasm/oedema of the sphincter of Oddi and the formation of protein-rich pancreatic fluid which is thick and causes an obstruction NOTE: most other causes of acute pancreatitis will do so via direct acinar injury
136
Describe the three main patterns of injury in acute pancreatitis and describe what they result from.
Periductal – necrosis of acinar cells near ducts (usually secondary to obstruction) Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply) Panlobular – results from worsening periductal or perilobular inflammation
137
List some complications of acute pancreatitis.
Pseudocyst formation, abscesses Shock Hypoglycaemia Hypocalcaemia
138
List some complications of chronic pancreatitis.
Malabsorption Diabetes mellitus Pseudocysts Pancreatic carcinoma
139
What is the characteristic feature of autoimmune pancreatitis?
Large numbers of IgG4 positive plasma cells typically found around the ducts
140
What are the two types of pancreatic cancer and which is more common?
Ductal (85%) Acinar (15%) NOTE: many ductal carcinomas may actually arise from acini after a process called acini-ductal metaplasia (these ductal carcinomas have a different natural history to truly ductal carciomas)
141
Name two types of cystic neoplasm of the pancreas.
Serous cystadenoma | Mucinous cystadenoma
142
Name two types of dysplastic precursor lesion that ductal carcinoma can arise from.
Pancreatic intraductal neoplasia (PanIN) | Intraductal mucinous papillary neoplasm
143
Which mutation is very common in pancreatic cancer?
K-ras (95%)
144
Describe the microscopic appearance of ductal carcinoma.
Adenocarcinomas (secrete mucin and form glands) | Mucin-secreting glands are set in desmoplastic stroma
145
By what mechanism does pancreatic cancer cause migratory thrombophlebitis?
Circulating pancreatic cancer cells release mucous which activates the clotting cascade
146
What can be measured as a screening test for neuroendocrine tumours?
Chromogranin
147
What are the two types of gallstone and what are their distinguishing features?
``` Cholesterol • May be single • Mostly radiolucent (NOT seen on AXR) Pigment • Often multiple • Contain calcium salts of unconjugated bilirubin • Mostly radio-opaque ```
148
What is the term used to describe diverticula of the gallbladder? How do they form?
Rokitansky-Aschoff sinuses – form as a result of the gallbladder contracting against an obstruction
149
Describe the role of the following parts of the nephron: a. Proximal convoluted tubule b. Loop of Henle c. Distal convoluted tubule d. Collecting duct
a. Proximal convoluted tubule Actively absorbs sodium Carriers out hydrogen exchange to allow carbonate resorption Co-transport of amino acids, phosphate and glucose Reabsorption of potassium b. Loop of Henle Descending limb and thin ascending limb: permeable to water, impermeable to ions and urea Ascending limb: actively resorbs sodium and chloride This creates a counter-current multiplier that is aligned with the vasa recta c. Distal convoluted tubule Impermeable to water Regulates pH by active transport of protons and bicarbonate Regulates sodium and potassium by active transport (aldosterone) Regulates calcium (PTH, 1,25-dihydroxy vitamin D) d. Collecting duct Reabsorb water (principal cells, ADH) Regulates pH (intercalated cells, proton excretion)
150
What is the inheritance pattern of polycystic kidney disease and which genes are implicated?
Autosomal dominant (most of the time) Genes: PKD1 (Chr16) and PKD2 (Chr4) NOTE: PKD is associated with an increased risk of berry aneurysms (and subarachnoid haemorrhage)
151
How does acute tubular injury lead to reduced GFR?
Blockage of tubules by casts Leakage from tubules into interstitial space Secondary haemodynamic changes
152
Describe the histological appearance of acute tubulo-interstitial nephritis.
Heavy interstitial infiltration with eosinophils and granulomas Clinical features include oliguria, fever and a rash
153
What causes crescents to appear in acute glomerulonephritis?
Occurs in severe glomerulonephritis due to proliferation of cells within Bowman’s capsule
154
List some causes of acute crescentic glomerulonephritis.
Immune complex deposition Anti-GBM disease (Goodpasture’s) Pauci-immune (ANCA) NOTE: these can rapidly lead to irreversible renal failure
155
List some causes of immune complex-associated crescentic glomerulonephritis.
SLE IgA nephropathy Post-infectious glomerulonephritis
156
What are the antibodies directed against in anti-GBM disease?
Against the alpha 3 subunit of type IV collagen NOTE: these antibodies can cross-react with the alveolar basement membrane leading to pulmonary haemorrhage and haemoptysis
157
What are the main features of pauci-immune crescentic glomerulonephritis?
Scanty glomerular immunoglobulin deposits Usually associated with ANCA Triggers neutrophil activation and glomerular necrosis
158
What is thrombotic microangiopathy?
Damage to the endothelium in glomeruli, arterioles and arteries resulting in thrombosis Red cells can be damaged by fibrin causing MAHA or HUS Causes include E. coli, ADAMTS13 deficiency, drugs, scleroderma, antiphospholipid syndrome
159
List some causes of nephrotic syndrome.
``` Primary glomerular disease (non-immune complex mediated) • Minimal change disease • Focal segmental glomerulosclerosis Primary renal disease (immune complex mediated) • Membranous glomerulonephritis Systemic disease • SLE • Amyloidosis • Diabetes mellitus ```
160
Describe the histological appearance of focal segmental glomerulosclerois.
Some glomeruli are partially scarred This responds less well to immunosuppression Associated with sickle cell disease, HIV and heroin use Most common cause of nephrotic syndrome in Afro-Caribbeans
161
What is membranous glomerulonephritis?
Common cause of nephrotic syndrome in adults Characterised by immune deposits outside the glomerular basement membrane (subepithelial) Primary disease is autoimmune It can occur secondary to epithelial malignancy, SLE, drugs and infections Thickening of basement membrane shows 'spike and dome' pattern
162
Which antibodies are often found in primary membranous glomerulonephritis?
Antibodies against phospholipase A2 type M receptor (PLA2R)
163
List and describe the stages of diabetic nephropathy.
Stage 1: thickening of the basement membrane on electron microscopy Stage 2: increase in mesangial matrix, without nodules Stage 3: nodular lesions/Kimmelstein-Wilson nodules Stage 4: advanced glomerulosclerosis
164
What is amyloidosis?
Deposition of extracellular proteinaceous material exhibiting beta-pleated sheet structure
165
Name two causes of isolated microscopy haematuria.
Thin basement membrane | IgA nephropathy
166
What is thin basement membrane disease and what causes it?
Basement membrane < 250 nm thickness Caused by a hereditary defect in type IV collagen synthesis Microscopic haematuria is the only consequence in most cases
167
What is Alport syndrome?
X-linked disease caused by a mutation in the alpha-5 subunit of type IV collagen (some forms affect alpha-3 and alpha-4) Leads to progressive damage resulting in renal failure in middle-age Often accompanied by deafness and ocular disease
168
What is IgA nephropathy?
Most common cause of glomerulonephritis Caused by mesangial IgA immune complex deposition NOTE: Henoch-Schonlein purpura is a type of IgA nephropathy 30% will progress to end-stage renal failure
169
What are some diseases associated with chronic kidney disease?
Ischaemic heart disease | Calcium and phosphate derangement (due to resulting hyperparathyroidism, osteomalacia and osteoporosis)
170
What are consequences of hypertensive nephropathy?
Shrunken kidneys with granular cortices Nephrosclerosis on histology (arterial hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis)
171
What system is used to classify lupus nephritis?
ISI/RPS classification
172
What is a key histological feature of the oesophageal mucosa?
Presence of submucosal glands
173
What does the body and fundus of the stomach have in abundance?
Specialised glands responsible for producing acid and enzymes E.g. chief cells (pepsinogen) and parietal cells (acid)
174
What are the three layers of the gastric mucosa?
Columnar epithelium Lamina propria Muscularis mucosa
175
What does the presence of goblet cells in the stomach signify?
Intestinal metaplasia | NOTE: goblet cells are not normally seen in the stomach
176
Define dysplasia.
Changes showing some of the cytological and histological features of malignancy but with no invasion through the basement membrane
177
What are the main histological features of squamous cell carcinoma of the oesophagus?
Cells produce keratin (normal oesophageal squamous epithelium is non-keratinised) Intercellular bridges
178
What is mucosa-associated lymphoid tissue and what is their presence indicative of?
Chronic gastritis caused by H. pylori infection induces lymphoid tissue in the stomach The presence of lymphoid follicles in a stomach biopsy, is highly suggestive of H. pylori infection This is important because it is associated with an increased risk of lymphoma
179
Name a key virulence factor that enables H. pylori to cause chronic infection.
Cag-A positive H. pylori has a needle-like appendage that injects toxins into intercellular junctions allowing bacteria to attach more easily Hydrogenase - produces energy by oxidising molecular H2
180
Define gastric ulcer.
The depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa)
181
What are the two main morphological subtypes of gastric adenocarcinoma? What are their key features?
Intestinal: well-differentiated, presence of big gland containing mucin Diffuse: poorly differentiated, composed of single cells with no attempt at gland formation
182
Name two types of diffuse adenocarcinoma of the stomach.
Linitis plastica | Signet ring cell carcinoma
183
List some other pathogens that affect the duodenum.
CMV Cryptosporidium Giardiasis Whipple’s disease (Tropheryma whippelii)
184
What is lymphocytic duodenitis?
When you get the inflammatory changes (increased intraepithelial lymphocytes) without architectural changes Many people with this condition either have coeliac disease or will go on to develop coeliac disease
185
What is a classic histological feature of HSV infection?
Cells with multiple nuclei
186
What are giant cell tumours? Where do they tend to be found and what is their histological appearance?
Benign tumour of the bone characterised by the presence of lots of osteoclasts (giant cells) They tend to be found at the ends of long bones It has a lytic appearance on X-ray Histology shows many osteoclasts on a background of spindle/ovoid cells
187
Describe the X-ray appearance of Ewing’s sarcoma.
Onion skinning of the periosteum | Lytic with or without sclerosis
188
Describe the histology of intraductal papillomas.
Histology will show a large dilated duct with a polypoid mass in the middle The mass tends to have a fibrovascular core
189
Describe the appearance of usual epithelial hyperplasia.
Irregular lumens
190
Describe the histological appearance of high grade DCIS.
Cells are large and few lumens left | Cells are pleomorphic and occlude the duct
191
What is histological grading of breast cancer dependent on?
Tubule formation Nuclear pleomorphism Mitotic activity Each factor gets a score out of 3
192
What is the most important prognostic factor in invasive breast cancer?
Status of axillary lymph nodes
193
What is the most common cause of non-toxic goitre?
Iodine deficiency NOTE: brassicas (e.g. cabbages) interfere with thyroid hormone synthesis It may also be caused by a hereditary enzyme deficiency
194
What is the most common cause of secondary hyperparathyroidism?
Renal failure
195
Describe the vascular histology in scleroderma.
Intimal proliferation gives an onion skin appearance
196
Which type of lung cancer is most likely to: A) Spread to the bone B) Arise in the periphery
A) squamous cell carcinoma | B) adenocarcinoma
197
What is a nutmeg liver suggestive of?
Congestive hepatopathy - liver failure due to venous congestion (usually resulting from heart failure)
198
Outline the pathophysiology of bullous pemphigoid.
Autoimmune disorder driven by IgG and C3 which attack the basement membrane (hemidesmosomes) They recruit eosinophils which release elastase which further damages anchoring proteins (anchoring lower keratinocytes to the basement membrane) Linear deposition of IgG can be seen along BM
199
What is acantholysis?
Loss of intercellular connections leading to loss of cohesion between keratinocytes NOTE: this can occur due to a lot of dermatological conditions so immunofluorescence is needed to identify where the immune-mediated attack is taking place
200
What can neutrophil recruitment to the epidermis in plaque psoriasis cause?
Formation of Munro’s microabscesses
201
What is lichen planus and what are its main features?
Lichenoid reaction pattern Pruritic, purple, papules and plaques Presents with papules and plaques that are slightly purplish in colour on the wrists and arms In the mouth it presents as white lines (Wickham striae)
202
Which histological feature is classic of seborrhoeic keratosis?
Horn cysts – entrapped keratin surrounded by proliferating epidermis NOTE: the epidermis is proliferating in an orderly manner
203
List some different types of inflammatory reactions patterns in the skin.
``` Vesiculobullous – forms bullae Spongiotic – becomes oedematous Psoriasiform – becomes thickened Lichenoid – forms a sheeny plaque Vasculitic – associated with vasculitis Granulomatous – associated with granulomas ```
204
Outline the pathophysiology of pemphigus vulgaris.
IgG-mediated disease where the damage is occurring within the keratinocyte layers (intraepidermal bullae) IgG antibodies target desmosomal proteins Shows netlike pattern of intercellular IgG deposits
205
Outline the pathophysiology of pemphigus foliaceus.
IgG-mediated attack on the outer layer of keratinocytes (where the stratum corneum is found)
206
What is hyperparakeratosis?
Thickening of the skin on the surface where the patient has been scratching The epidermis gets thicker
207
Which layer of the epidermis disappears in plaque psoriasis and why?
Stratum granulosum – there is not enough time to form it NOTE: psoriasis skin turnover time is around 7 days (as opposed to 50 days in normal skin)
208
Describe the histological appearance of lichen planus.
Distinction between dermis and epidermis is difficult to see due to lymphocyte-mediated destruction of the bottom layer of keratinocytes Saw-tooth rete ridges Hyperparakeratosis There is band-like lymphocytic infiltration just under the epidermis NOTE: this is also seen in mycosis fungoides
209
Describe the histological appearance of malignant melanoma.
Melanocytes start migrating upwards through the epidermis (pagetoid spread) They become active and lose the ability to differentiate Melanoma thickness > 4 mm has a > 50% mortality
210
List some underlying conditions that can lead to the formation of calcium oxalate stones.
Absorptive hypercalciuria – excessive calcium absorption from the gut Renal hypercalciuria – impaired absorption of calcium in the proximal renal tubule Hypercalcaemia (e.g. hyperparathyroidism)
211
Define papillary adenoma.
Benign epithelial kidney tumour composed of papillae and/or tubules They must be < 15 mm in size They tend to be well circumscribed
212
What are the genetic associations of papillary adenomas?
Trisomy 7 and 17 | Loss of Y chromosome
213
What is a renal oncocytoma?
Benign epithelial kidney tumour composed of oncocytic cells They are usually well-circumscribed and usually sporadic Often an incidental finding NOTE: an oncocyte is an epithelial cell that has a lot of mitochondria giving it acidophilic, granular cytoplasm
214
Describe the histological appearance of oncocytes.
Large cells with pink granular cytoplasm and a prominent nucleolus
215
What is an angiomyolipoma?
Benign mesenchymal kidney tumour composed of thick-walled blood vessels, smooth muscle and fat Derived from perivascular epithelioid cells NOTE: often an incidental finding but may cause flank pain, haemorrhage and shock (if > 4 cm)
216
Name the subtypes of renal cell carcinoma in order of prevalence.
Clear cell renal carcinoma (70%) Papillary renal cell carcinoma (15%) Chromophobe renal cell carcinoma (5%) NOTE: papillary renal cell carcinoma is associated with dialysis
217
What is a common genetic finding in clear cell renal carcinoma?
Loss of chromosome 3p
218
Describe the histological appearance of the two types of papillary renal cell carcinoma.
Type 1: composed of a single layer of small and flat cells. You see a lot of islands of cells. Type 2: there is stratification (multi-layering) of the cells NOTE: type 2 tends to have a worse prognosis than type 1
219
Define chromophobe renal cell carcinoma.
Epithelial kidney tumour composed of sheets of large cells that display distinct cell borders, reticular cytoplasm and a thick-walled vascular network The cells are pale and eosinophilic NOTE: grossly appears as a well-circumscribed solid brown tumour
220
What grading system is used for clear cell and papillary renal cell carcinoma?
ISUP Nuclear Grade
221
What risk progression index is used for clear cell carcinoma?
Leibovich risk model
222
What is Nephroblastoma (Wilm’s tumour)?
Malignant triphasic kidney tumour of childhood: • Blastema (small round blue cells) • Epithelial • Stromal Typically present with an abdominal mass in children aged 2-5 years NOTE: 95% have an excellent prognosis
223
What are the three main subtypes of urothelial carcinoma?
Non-invasive papillary urothelial carcinoma Invasive urothelial carcinoma Flat urothelial carcinoma in situ
224
Describe the macroscopic appearance of non-invasive papillary urothelial carcinoma.
Appears as frond-like growths Can be divided into low or high grade dependent on nuclear atypia NOTE: high grade tumours have many genetic aberrations (e.g. RB, TB53)
225
What is a possible mechanism for the onset of BPH?
Increased oestrogen with ageing induces androgen receptors and stimulates hyperplasia
226
List some mutations that are implicated in prostate cancer.
PTEN AMACR P27 GST-pi
227
Which genetic factor is associated with testicular germ cell tumours?
Amplification of i12p
228
List the five histological subtypes of testicular germ cell tumours.
``` Seminoma Embryonal carcinoma Post-pubertal teratoma Yolk sac tumour Choriocarcinoma ```
229
Describe the histological appearance of a. Seminoma b. Embryonal carcinoma c. Post-pubertal teratoma d. Yolk sac tumour e. Choriocarcinoma
a. Seminoma Mostly made up of clear cells with a prominent lymphocytic infiltrate b. Embryonal carcinoma High-grade appearance with prominent nucleoli c. Post-pubertal teratoma The tumour is trying to produce a variety of tissues (e.g. keratin, cartilage, glands) This is malignant – any component of the tumour can become malignant d. Yolk sac tumour Smaller cells Lace-like pattern Some pink inclusions e. Choriocarcinoma Made up of two cell types: cytotrophoblasts (clear looking cells) and syncytiotrophoblasts (multinucleated cell) NOTE: both components are needed to define choriocarcinoma
230
What is an adenomatoid tumour?
Benign tumour consisting of small tubules lined by mesothelial cells
231
List some describe a few types of benign penile diseases.
Lichen sclerosus/balanitis xerotica obliterans – inflammatory condition that causes phimosis Zoon’s balanitis – inflammatory condition that causes red areas Condylomas – HPV 6 and 11 Peyronie’ disease – scarring, inflammation and thickening of the corpus cavernosa
232
List and describe some benign diseases of the urethra.
Urethritis Prostatic urethral polyp – papillary lesion in the prostatic urethra Urethral caruncle – common lesion at the urethral meatus in women NOTE: malignant diseases include urethral carcinoma (squamous cell carcinoma) and malignant melanoma
233
List and describe some diseases of the scrotum.
Epidermoid cyst (common) Scrotal calcinosis Angiokeratomas (benign vascular lesions) Fournier’s gangrene – necrotising fasciitis of the scrotum and perineum Scrotal squamous cell carcinoma
234
List three types of benign renal neoplasm.
Papillary adenoma Renal oncocytoma Angiomyolipoma
235
Name a syndrome that is associated with renal oncocytoma.
Birt-Hogg-Dubé syndrome
236
Which hereditary condition is associated with angiomyolipoma?
Tuberous sclerosis
237
Define clear cell renal carcinoma.
Epithelial kidney tumour composed of nests of clear cells set in a delicate capillary vascular network Grossly appears golden-yellow with haemorrhagic areas
238
Define papillary renal cell carcinoma.
Epithelial kidney tumour composed of papillae and/or tubules By definition > 15 mm in size NOTE: this is the malignant counter part of papillary adenoma. They appear grossly as a fragile, friable brown tumour
239
Describe the histological appearance of chromophobe renal cell carcinoma.
Sharply defined cell borders and a thick vascular network
240
What scoring system is used for prostate cancer? Explain how it is calculated.
Gleason score Expressed as x + y = z Calculated by adding the top two most common patterns/grades seen on histological grading Higher scores are associated with a poorer prognosis
241
Name three types of testicular non-germ cell tumours.
Lymphoma – more in older men, poor prognosis Leydig cell tumour – may cause precocious puberty (if pre-pubertal) Sertoli cell tumour – 90% benign
242
Describe the microanatomy of bone.
Made up of several micro-columns Haversian canals are found at the middle of the micro-columns Volkmann canals are canals that connect the Haversian canals Around the Haversian canals are concentric lamellae and in between these units will be interstitial lamellae Around the entire bone you will find circumferential lamellae In the middle the bone will be trabecular lamellae
243
Which static parameters are measured in the histological analysis of bone in metabolic bone disease?
Cortical thickness Trabecular bone volume Thickness, number and separation of trabeculae
244
Which technique is used to measure histodynamic parameters when investigating metabolic bone disease?
Tetracycline labelling
245
What are the effects of long-term steroid use on bone?
Affects all three bone cell types Leads to decrease in bone quality Ultimately results in osteonecrosis and fracture
246
Define renal osteodystrophy.
Term used to describe all the skeletal changes of chronic renal disease: • Increased bone resorption (osteitis fibrosa cystica) • Osteomalacia • Osteosclerosis • Osteoporosis • Growth retardation
247
Describe the histological appearance of Paget’s disease.
Lines will be seen between areas of new bone formation so it looks like a mosaic/jigsaw puzzle
248
Which virus is associated with Paget’s disease?
Parvomyxovirus
249
What are the four stages of fracture repair?
Organisation of a haematoma at the site of the fracture (pro-callus) Formation of a fibrocartilaginous callus Mineralisation of the fibrocartilaginous callus Remodelling of the bone along weight-bearing lines
250
Which sites are most commonly affected by osteomyelitis?
Vertebra Jaw (secondary to dental caries) Toe Long bones (usually metaphysis)
251
Describe the X-ray changes seen in osteomyelitis.
Usually appear about 10 days after onset Mottled rarefaction and lifting of periosteum First week changes – irregular sub-periosteal new bone formation (involucrum – layer of new bone that forms around dead bone) Later changes – irregular lytic destruction Some areas of the necrotic cortex may become detached (sequestra). This takes 3-6 weeks
252
What congenital skeletal lesions are associated with syphilis?
Osteochondritis Osteoperiostitis Diaphyseal osteomyelitis
253
List some acquired skeletal lesions that are associated with syphilis.
Non-gummatous periostitis Gummatous inflammation of joints and bones Neuropathic joints (tabes dorsalis) Neuropathic shaft fractures
254
What are the HLA associations of rheumatoid arthritis?
HLA DR4 and HLA DR1 (Chr6p21) | Other alleles: TFNA1P3, STAT4
255
Which type of multinucleate giant cell may be seen in rheumatoid arthritis?
Grimley-Sokoloff cell (like a Langerhans cell but does not have horshoe nuclei)
256
What are the key clinical and radiological features of osteosarcoma?
Peak in adolescence 60% around the knee X-ray: usually metaphysial, lytic, permeative, elevated periosteum (Codman’s triangle)
257
What are the main clinical, radiological and histological features of chondrosarcoma?
Malignant cartilage producing tumour Affects axial skeleton, proximal femur and proximal tibia X-ray: lytic with fluffy calcification Histology: malignant chondrocytes with or without chondroid matrix
258
What histological feature is typically seen in hyperparathyroidism?
Brown cell tumour – several multinucleated giant cells on a background of fibrous stroma with haemorrhage
259
List some genetic associations of Hirschsprung disease.
Down syndrome | RET proto-oncogene Cr10
260
List three types of non-neoplastic polyp.
Hyperplastic Inflammatory (pseudopolyp) Haemartomatous (juvenile polyposis syndrome, Peutz-Jeghers (LKB1))
261
Which gene is mutated in FAP?
APC gene – chromosome 5q21 | NOTE: almost 100% will develop cancer in 10-15 years
262
What is Gardner’s syndrome?
Same features of FAP but with extra-intestinal manifestations: multiple osteomas of the skull and mandible, epidermoid cysts, desmoid tumours and supernumerary teeth
263
Which gene mutation is associated with HNPCC?
1 of 4 DNA mismatch repair genes is mutated
264
List some features of an adenoma of the colon that are associated with increased risk of becoming a carcinoma.
Size of polyp (> 4 cm = 45%) Proportion of villous component Degree of dysplastic change within a polyp
265
Which stains are used during colposcopy?
``` Lugol's iodine (looks at glycogen content within cells - cancerous cells don't have much glycogen) Acetic acid (acetowhite appearance is associated with HPV) ```
266
Where are the genes that cause neurofibromatosis located?
NF1 – 17q11 | NF2 – 22q12
267
Which genetic mutations are associated with gliomas in adults and in children?
``` Diffuse infiltration (adults) – IDH1/2 Circumscribed gliomas (children) – MAPK (BRAF) ```
268
List some examples of circumscribed gliomas.
Pilocytic astrocytoma (MOST COMMON) Pleiomorphic xanthoastrocytoma Subependymal giant cell astrocytoma
269
What is the hallmark histological feature of pilocytic astrocytoma?
Piloid (hairy) cell Often see Rosenthal fibres and granular bodies Slow-growing with low mitotic activity
270
List some key features of astrocytoma.
Usually Grade II-IV Cerebral hemispheres are the most common site in adults Can progress to become a higher grade (malignant progression) IDH2 mutation in 80% of cases Mitotic activity and vascular proliferation is absent
271
List some key features of glioblastoma multiforme.
Grade IV Most patients > 50 years High cellularity and high mitotic activity Microvascular proliferation and necrosis 90% occur de novo with wildtype IDH 10% occur secondary to astrocytoma and have IDH mutation
272
List some key features of oligodendrogliomas.
Grade II-III Tends to present with a long history of neurological signs (usually seizures) Slow-growing Better prognosis than astrocytoma (better response to chemotherapy and radiotherapy)
273
Which gene mutations are associated with oligodendroglioma?
IDH1/2 | Co-deletion of 1p/19q
274
What is a medulloblastoma?
Embryonal tumour originating from neuroepithelial precursors of the cerebellum and dorsal brainstem They are always found in the cerebellum
275
Describe the histological appearance of medulloblastoma.
Small blue round cell tumour with expression of neuronal markers (very little differentiation) NOTE: synaptophysin is an example of a neuronal marker
276
What histological feature is suggestive of partial neuronal differentiation?
Homer-Wright rosettes
277
Outline the molecular classification of medulloblastoma.
WNT-associated SHH-associated Non-WNT/non-SHH
278
List some key features of pilocytic astrocytoma.
``` Usually grade I Mainly occurs in children Associated with NF1 Often cerebellar BRAF mutation in 70% of cases ```
279
What is a characteristic histological feature of oligodendroglioma?
Round cells with clear cytoplasm (fried egg)
280
Which histological feature of a meningioma is important in determining grade?
Mitotic activity (number of mitoses per 10 high power fields) Grade 1 < 4 Grade 2: 4-20 Grade 3 > 20 NOTE: brain invasion is also an important thing to assess (presence of brain invasion makes it grade II) Grade 2 and 3 will require radiotherapy as well as surgery
281
Which tumours most commonly metastasise to the brain?
Lung Breast Melanoma
282
What are the two types of cerebral oedema?
Vasogenic – due to disruption of blood-brain barrier Cytotoxic – secondary to cellular injury (e.g. hypoxia, ischaemia). This is usually due to damage to astrocyte end feet NOTE: AQP4 is the water transporter in the brain
283
Where is CSF produced and where does it drain to?
Produced: choroid plexus Drained: via arachnoid granulations into the superior sagittal sinus
284
ƒWhat is the normal range for ICP?
7-15 mm Hg
285
Which diseases are excluded by this definition of ‘stroke’?
Subdural and epidural haemorrhage | Infarction due to infection or tumour
286
Which part of the cerebral vascular tends to be affected by infarcts resulting from emboli?
Middle cerebral artery branches
287
List and describe the main neuropathological features of Alzheimer’s disease.
Extracellular plaques – extracellular accumulations of amyloid beta Neurofibrilliary tangles – intra-neuronal pathology caused by disruption of the cytoskeleton of neurones Cerebral amyloid angiopathy – deposits of protein in blood vessel walls which impairs normal vascular function
288
Outline the main histological features of Parkinson’s disease.
Characterised by the presence of Lewy bodies which are intracellular accumulations of alpha-synuclein Parkinson’s disease is caused by abhorrent metabolism of alpha-synuclein NOTE: this was discovered because mutations in the alpha-synuclein gene are associated with rare familial forms of Parkinson’s disease
289
Describe the main histological features of asthma.
Lots of eosinophils and mast cells Goblet cell hyperplasia Mucus plugs within airways Thickening of bronchial smooth muscle and dilatation of blood vessels Whorls of shed epithelium (Curschman spirals) Charcot-Leyden crystals
290
List some histological features of chronic bronchitis.
Dilated airways Mucus gland hyperplasia Goblet cell hyperplasia Mild inflammation
291
What is bronchopneumonia?
Infection is centred around the airways Tends to be associated with compromised host defence (mainly the elderly) and is caused by low virulence organisms (e.g. Staphylococcus, Haemophilus, Pneumococcus) It will show patchy bronchial and peribronchial distribution often involving the lower lobes
292
What is lobar pneumonia?
Infection is focused in a lobe of the lung 90-95% caused by S. pneumoniae Widespread fibrinosuppurative consolidation
293
What is large cell carcinoma of the lung?
Poorly differentiated tumour composed of large cells There is no evidence of squamous or glandular differentiation It has a poor prognosis
294
Outline the changes that give rise to atherosclerosis.
1 - endothelial injury 2 - LDL enters the intima and becomes oxidised 3- macrophages take up oxidised LDL via scavanger receptors and become foam cells 4 - apoptosis of foam cells causes inflammation and cholesterol core of plaque 5 - increase in adhesion molecules on endothelium leads to more macrophages and T cells entering the plaque 6 - vascular smooth muscle cells form the fibrous cap
295
How long does it take for ischaemia to lead to irreversible injury to the myocardium and myocyte death?
20-40 mins if severe
296
What signs might be picked up on examination of a patient with papillary muscle rupture as a result of an MI?
Mitral regurgitation
297
What is arrhythmogenic right ventricular cardiomyopathy?
Myocyte loss with fibrofatty replacement typically affecting the right ventricle
298
What are the diagnostic criteria for rheumatic heart disease?
Develops 2-4 weeks after a group A strep infection + 2 major criteria OR 1 major + 2 minor
299
What are the major criteria for rheumatic heart disease?
``` Carditis Arthritis Sydenham's chorea Erythema marginatum Subcutaneous nodules ``` NOTE: minor criteria include fever, raised ESR/CRP, migratory arthralgia, previous rheumatic fever, malaise
300
Describe some histological features that may be seen in acute acute rheumatic fever.
Verrucae - beady fibrous vegetations Aschoff bodies - small giant-cell granulomas Anitschkov myocytes - regenerating myocytes
301
What is non-bacterial thrombotic endocarditis?
Aka marantic endocarditis Formed by thrombi in hypercoagulable states or DIC Small, bland vegetations formed of thrombi occur at the lines of closure
302
How is acute rheumatic fever treated?
Benzylpenicillin Alternative: erythromycin
303
Which organisms cause acute bacterial endocarditis?
Staphylococcus aureus | Streptococcus pyogenes
304
Which organisms subacute bacterial endocarditis?
``` Streptococcus viridans Staphylococcus epidermidis Coxiella Mycoplasma Candida Haemophilus ```
305
Which murmurs are usually heard in infective endocardtiis?
Mitral regurgitation or aortic regurgitation
306
Describe the presentation of mitral valve prolapse.
Shortness of breath Chest pain Mid-systolic click and late systolic murmur (Barlow murmur)
307
List some types of pericarditis.
``` Fibrinous (MI, uraemia) Purulent (staphylococcus) Granulomatous (TB) Haemorrhagic (tumour, TB, uraemia) Fibrous (constrictive) ```
308
Describe the CT appearance of interstitial lung disease.
Honeycomb lung NOTE: a key clinical sign of interstitial lung disease is end-inspiratory crackles
309
List the types of interstitial lung disease.
Fibrosing Granulomatous Eosinophilic Smoking related
310
List some causes of fibrosing interstitial lung disease.
``` Cryptogenic fibrosing alveolitis (idiopathic pulmonary fibrosis) Pneumoconiosis Cryptogenic organising pneumonia Connective tissuedisease Drug-induced Radiation pneumonitis ```
311
List some causes of granulomatous interstitial lung disease.
Sarcoid Extrinsic allergic alveolitis Vasculitides
312
Describe the key pathological features and progression of idiopathic pulmonary fibrosis.
Histological pattern of fibrosis = usual interstitial pneumonia Progressive patchy interstitial fibrosis with honeycomb change, beginning at the periphery of the lobule Hyperplasia of type II pneumocytes causing cyst formation (honeycomb fibrosis) Treated with steroids and immunosuppressants
313
What is pneumoconiosis and which part of the lungs are affected?
Occupational lung disease due to inhalation of mineral dusts and inorganic particles Most affect the upper lobes NOTE: asbestosis is similar but caused by asbestos exposure and tends to affect the lower lobes
314
What is extrinsic allergic alveolitis?
Group of immune-mediated lung disorders caused by intense or prolonged exposure to inhaled organic antigens --> widespread ALVEOLAR inflammation
315
Outline the histological features of extrinsic allergic alveolitis.
Presence of polypoid plugs of loose connective tissue within alveoli/bronchioles - granuloma formation and organising pneumonia
316
Which type of cell does small cell lung carcinoma arise from?
Neuroendocrine cell
317
Which gene mutation in non-small cell lung cancer is associated with a poor response to cisplatin?
ERCC1
318
What pulmonary artery pressure would be considered pulmonary hypertension?
> 25 mm Hg
319
List the classes of pulmonary hypertension.
``` Class 1: idiopathic Class 2: associated with left heart disease Class 3: due to lung disease Class 4: due to chronic VTE Class 5: mulifactorial ```
320
Which cells do carcinoid tumours arise from?
Enterochromaffin cells | They produce 5HT
321
Describe the symptoms of carcinoid syndrome.
Bronchoconstriction Flushing Diarrhoea
322
List some features of a carcinoid crisis.
``` Life-threatening vasodilation Hypotension Tachycardia Bronchoconstriction Hyperglycaemia ```
323
Which test is used for carcinoid syndrome?
Urine 5-HIAA | NOTE: treated with ocreotide (somatostatin analogue)
324
What metabolic complication is associated with villous adenomas?
Hypoproteinamic hypokalaemia (due to leakage of large amounts of protein and potassium)
325
What are the roles of secretin and CCK?
Secretin: made by S-cells in the duodenum, controls gastric acid secretion and buffering with HCO3- CCK: made by I-cells in the duodenum. Causes release of digestive enzymes
326
What do the alpha, beta and delta cells in the pancreas secrete?
Alpha - glucagon Beta - insulin Delta - somatostatin Others: D1 is a peptide that stimulates the secretion in water, pancreatic polypeptide (PP) self-regulates secretory activities
327
What are the consequences of a gastrinoma?
Aka Zollinger-Ellison syndrome Recurrent ulceration NOTE: VIPoma will cause diarrhoea/metabolic acidosis/hypokalaemia, glucagonoma causes necrolytic migrating erythema
328
Which scoring system is used to indicate the prognosis of liver cirrhosis?
Modified Child-Pugh score Based on ascites, encephalopathy, bilirubin, albumin and PT NOTE: < 7 = A, 7-9 = B, 10+ = C
329
Which type of bladder cancer is associated with schistosomiasis?
Squamous cell carcinoma NOTE: most bladder cancer will be transitional cell (urothelial) carcinoma
330
Describe the presentation of Whipple's disease.
``` Steatorrhoea Abdominal pain Weight loss Arthritis Periodic acid-Schiff positive macrophages on jejunal biopsy ```
331
What are the two main types of vulval intraepithelial neoplasia?
Usual Type: younger women, warty/basaloid SCC | Differentiated Type: older women, keratinising SCC, higher risk of malignant transformation
332
What type of cancer are most vulval carcinomas?
Squamous cell carcinoma
333
What is a distinguishing histological feature of serous cystadenoma of the ovary?
Psammoma bodies | From columnar epithelium
334
List some risk factors for cervical cancer.
``` Early age at first intercourse Multiple partners Multiparity Smoking HIV Immunosuppression NOTE: it is a squamous cell carcinoma (less commonly it can be adenocarcinoma) ```
335
Which cancers does BRCA increase the risk of?
Breast Ovarian Prostate Pancreatic
336
Why is lobular carcinoma in situ (LCIS) always an incidental finding?
No microcalcifications or stromal reactions so can't be seen on mammography Cells do NOT have the adhesion protein E-cadherin
337
Describe the consequences of a stroke in the territory of ACA.
Contralateral leg paralysis Sensory loss Cognitive defects (apathy, confusion, poor judgment)
338
Describe the consequences of a stroke in the territory of MCA.
Contralateral weakness and sensory loss of face and arm Cortical sensory loss May have contralateral homonymous hemianopia Aphasia if dominant hemisphere Neglect if non-dominant hemisphere
339
Describe the consequences of a stroke in the territory of PCA.
Contralateral hemianopia Midbrain: CN 3 and 4 palsy Thalamic: sensory loss, amnesia, decreased consciousness Bilateral: cortical blindness
340
Describe the consequences of a stroke in the territory of the basilar artery.
Proximal: impaired eye movement, nystagmus, dysarthria Distal: somnolence, memory and behavioural
341
Describe the consequences of a stroke in the territory of PICA.
``` Ataxia (ipsilateral) Horner's (ipsilateral) Facial sensory loss (ipsilateral) Contralateral limb impairment of pain and temperature Nystagmus ```
342
Describe the consequences of a stroke in the territory of lacunar infarcts.
Pure motor hemiparesis Pure sensory loss Ataxic hemiparesis Depends on the part of hte brain affected)
343
Which artery is most commonly affected in extradural haemorrhage?
Middle meningeal artery NOTE: subdural haemorrhages are caused by venous bleeding from damaged bridging veins
344
Which types of brain tumour are associated with NF1 and NF2?
NF1: optic glioma, neurofibroma NF2: vestibular schwannoma, meningioma, ependyoma, astrocytoma
345
Name a familial syndrome that is associated with glioblastoma multiforme and medulloblastoma.
Turcot syndrome
346
What is Li Fraumeni syndrome associated with?
Astrocytoma PNET Non-brain tumours such as sarcomas, breast cancer and leukaemia
347
What are the two main forms of multiple sclerosis?
Primary progressive | Relapsing remitting
348
What are some X-ray features of osteoarthritis?
Loss of joint space Osteophytes Subchondral sclerosis Subchondral cysts
349
Describe the typical presentation of osteoid osteoma.
Small benign bone forming lesion typically at the tibial diaphysis/proximal femur Causes night pain relieved by aspirin X-ray shows radiolucent nidus with surrounding sclerotic bone (Bull's eye)
350
What is the most common type of benign bone tumour?
Osteochondroma (aka exostosis) It appears as a cartilage capped bony spur (mushroom) on X-ray Tends to occur at the site of a previous fracture (several years before)
351
What is the difference between hyperkeratosis and acanthosis?
Hyperkeratosis: increase in stratum corneum Acathosis: increase in stratum spinosum WARNING: dont get confused with acantholysis
352
Which clinical signs can be elicited in psoriasis?
Auspitz - rubbing the lesions causes pin-point bleeding | Koebner phenomenon - lesions form at sites of trauma
353
List some causes of erythema multiforme.
Infections: HSV, mycoplasma Drugs: sulphonamides, NSAIDs, penicillin, phenytoin, allopurinol
354
What is the main histological feature of dermatitis herpetiformis?
Subepidermal bullae | Caused by IgA antibodies bind to basement membrane
355
List some subtypes of malignant melanoma.
Lentigo maligna - occurs on sun exposed areas of elderly Caucasians, flat, slow growing Superficial spreading - irregular borders with variation in colour Nodular - younger age group, more aggressive Acral lentiginous - occurs on palms, soles and subungual areas
356
What is Nikolsky sign?
Rubbing the skin leads to exfoliation of the outermost layer of skin This is seen in TEN and SJS
357
Describe the clinical presentation of pityriasis rosea.
Salmon pink rash appears first (herald patch) followed by oval macules in a christmas tree distribution Usually appears after viral illness and remits spontaneously
358
Which HLA alleles are associated with scleroderma?
HLA DR5 and DR8
359
What is Buerger's disease?
Inflammation and thrombosis of arteries in the extremities (usually legs) occurring in young, heavy smokers Corkscrew appearance on angiogram
360
List the key features of microscopic polyangiitis.
Pulmonary haemorrhage Glomerulonephritis pANCA (anti-myeloperoxidase)
361
Which proteins are implicated in haemodialysis-associated amyloidosis?
Deposition of beta-2 microglobulin
362
Outline the clinical features of amyloidosis.
``` Kidney: nephrotic syndrome (MOST COMMON) Heart: conduction defect, heart failure Hepatosplenomegaly Macroglossia Neuropathies (e.g. carpel tunnel) ```
363
What is the pathognomonic histological feature of sarcoidosis?
Non-caseating granulomas Also get Schaumann bodies and asteroid bodies (inclusions of protein and clacium)
364
List the circumstances in which a death needs to be reported to the coroner.
Cause of death is unknown Death was violent or unnatural Death was sudden and unexplained Person who died was not visited by a medical practitioner during their final illness Medical certificate is not available Person who died was not seen by the doctor who signed the medical certificate within 14 days before death or after they died Death occurred during an operation or before the person came out of anaesthetic Medical certificate suggests the death may have been caused by an industrial disease or industrial poisoning Death in custody
365
How can the histology in chronic hepatitis be used to grade and stage the disease?
Severity of inflammation = grade (how bad does it look) | Severity of fibrosis = stage (how far has it spread)
366
Which type of bone is considered immature and is usually pathological?
Woven bone
367
How does primary hyperparathyroidism affect urine calcium levels?
Increases urine calcium NOTE: it causes increased reabsorption of calcium in the kidneys, but the hypercalcaemia means that more calcium is filtered in the first place
368
Which type of ovarian neoplasm typically causes the largest tumours?
Mucinous tumour
369
What is a key distinguishing feature between mucinous and serous ovarian neoplasms?
Mucinous - tends to be unilateral and can be very large | Serous - often bilateral
370
Describe the histological differences between fibromas and thecomas.
Fibroma - intersecting bundles of spindle cells | Thecoma - fibrous tissue containing spindle cells and lipids
371
What are some key features of embryonal carcinoma?
Very aggressive tumour Produces hCG and AFP Neoplastic cells are anaplastic
372
What is a key difference between seminomatous and non-seminomatous germ cell tumours?
Seminomatous - radiosensitive, present in the 30s, 15% produce hCG, do not produce AFP Non-seminomatous - radioresistant, presents in the 20s, may secrete AFP or hCG
373
Describe the smear findings of a syphilitic ulcer.
Necrotic centre Periarteritis and endarteritis obliterans Pericellular infiltrate of mononuclear cells and giant cells
374
What metaplasia occurs at the transformation zone of the cervix?
Columnar to squamous
375
What is the best investigation to confirm the benign status of ovarian cyst?
Fine needle aspiration
376
What is a key difference between the presentation of subdural haemorrhage and extradural haemorrhage?
Subdural: venous blood loss, takes longer, may take days or weeks to cause neurological changes (e.g. headache, confusion) Extradural: arterial blood loss, initial lucid interval is followed by rapid development of neurological signs
377
Which parts of the brain tend to be affected by lacunar infarcts?
Basal ganglia Internal capsule Thalamus Pons
378
What is the most common cause of nephrotic syndrome in adults?
Focal segmental glomerulosclerosis
379
Define microalbuminuria.
Excretion of 30-300 mg of protein in the urine per day
380
Which test is done to determine whether a breast cancer is lobular or ductal?
``` Ductal = E-cadherin positive Lobular = E-cadherin negative ```
381
Which stain is used to detect alpha-1 antitrypsin?
Periodic acid-Schiff stain
382
ST depression in a patient presenting with chest pain at rest is suggestive of damage to which part of the heart?
Subendocardial necrosis due to ischaemia of the inner 1/3 of the heart muscle ST elevation is seen in transmural infarction
383
What percentage stenosis of a coronary artery is required to cause chest pain at rest?
> 90%
384
Define 'erosion'.
Loss of surface epithelium with or without lamina propria (muscularis mucosa is intact)
385
What is a key difference between the histological appearance of chronic ulcers compared to acute ulcers?
Chronic ulcers have an element of fibrosis
386
What is the point at which the oesophageal mucosa transitions from squamous to columnar epithelium called?
Z-line
387
What is a key difference between the potential complications of anterior and posterior duodenal ulcers?
Anterior --> perforation --> peritonitis | Posterior --> gastroduodenal ulcer --> haemorrhage
388
List some causes of chronic pancreatitis.
``` Alcohol (80%) Gallstones Haemochromatosis Idiopathic Autoimmune (IgG4) ```
389
What are the stages of sarcoidosis?
Stage 1: BHL only Stage 2: BHL with pulmonary infiltrates Stage 3: pulmonary infiltrates without BHL Stage 4: pulmonary fibrosis
390
What are that main features of lateral medullary syndrome?
Characterised by sensory deficits that affect the trunk and extremities contralaterally (opposite to the lesion), and sensory deficits of the face and cranial nerves ipsilaterally (same side as the lesion)
391
Name and describe a few different types of fracture.
Transverse: fracture is at right angles to the bone's long axis Comminuted: bone is splintered into a number of small pieces Greenstick: occurs in children, the fracture is transverse but only partial, the bone bends away from the long axis but remains attached Compound: when the fracture penetrates the skin surface (aka open fracture) Oblique: fracture axis is oblique to the long axis of the bone Spiral: tends to be due to rotational injury, leaves sharp points, similar appearance to oblique
392
Name two causes of gastritis in immunocompromised patients.
CMV | Strongyloides
393
Which type of breast cancer is sometimes referred to as 'no special type'?
Invasive ductal carcinoma
394
Which type of bladder cancer is associated with schistosomiasis?
Squamous cell carcinoma
395
Which oncogene is associated with medullary thyroid cancer?
RET proto-oncogene
396
Which antigens are targeted in: Pemphigus foliaceus Pemphigus vulgaris Bullous pemphigoid
Pemphigus foliaceus - desmoglein 1 Pemphigus vulgaris - desmosomes (desmoglein 1 and 3) Bullous pemphigoid - hemidesmosomes
397
Which type of cancer classically has 'oat cells'?
Small cell lung cancer
398
Where are osteoclasts found within the bone?
Within Howship's lacunae
399
Which type of mastitis affects young women who smoke?
Periductal mastitis
400
What is the most common type of endometrial cancer?
Endometrioid (80%)
401
Which type of glomerulonephritis is associated with hepatitis B and C viruses?
Membranous glomerulonephritis AND membranoproliferative glomerulonephritis
402
What is a key difference between the pattern of immune complex deposition in membranous and membranoproliferative glomerulonephritis?
Membranous - subepithelial (spike and dome) | Membranoproliferative - subendothelial (tram track)
403
What is Young syndrome?
Congenital cause of bronchiectasis characterised by rhinosinusitis, azoospermia and bronchiectasis
404
Which cells might be found in the lungs of a patient with pulmonary oedema due to heart failure?
Haemosiderin-containing macrophages | NOTE: aka heart failure cells
405
What might be the first presentation of Crohn's disease?
Aphthous ulcers Also characterised by cobblestone mucosa and skip lesions
406
Describe the histological appearance of acinar cell carcinoma of the pancreas.
Neoplastic epithelial cells with eosinophilic granular cytoplasm Positive for lipase, trypsin and chymotrypsin
407
Which commonly used medication is associated with hepatic adenoma?
OCP May present with abdominal pain and intraperitoneal bleeding (may shrink if the OCP is stopped)
408
Which inborn errors of metabolism can cause cirrhosis?
Galactosaemia | Glycogen storage disease