Histopathology Flashcards
Where do non-traumatic intraparenchymal haemorrhages tend to occur most frequently?
Basal ganglia
Define cavernous angioma.
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
What is the biggest cause of death in people < 45 years?
Traumatic brain injury
Describe the Braak stages of Alzheimer’s disease.
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
What is the diagnostic gold standard for Parkinson’s disease?
Alpha-synuclein immunostaining
What are three important differentials to consider in a patient with Parkinson’s disease?
Multiple system atrophy
Corticobasal degeneration
Progressive supranuclear palsy
What is multisystem atrophy?
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
What are the main histological features of Pick’s disease?
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
Which gene encodes tau?
17q21
Describe how the types of tau present in Alzheimer’s disease is different from CBD, PSP and Pick’s disease.
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
What is a characteristic feature of frontotemporal dementia associated with progranulin mutations?
Atrophy tends to be unilateral
Which other protein is thought to be implicated in some types of fronto-temporal dementia?
TDP-43 (trafficking protein)
On a cellular level, what insult results in ARDS?
Acute damage to the endothelium and/or alveolar epithelium
The basic pathology is the same regardless of cause: diffuse alveolar damage
Outline the pathophysiology of ARDS.
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
Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency.
Smoking – centrilobular damage
Alpha-1 antitrypsin deficiency – panacinar (throughout the lungs)
Where is the CFTR gene found?
7q31.2
What are the histopathological stages of lobar pneumonia?
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)
Describe the histological appearance of atypical pneumonia.
Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells
NOTE: causes include Mycoplasma, viruses, Coxiella and Chlamydia
Where do squamous cell carcinomas tend to arise?
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)
What is the precursor lesion for adenocarcinoma of the lung?
Atypical adenomatous hyperplasia (proliferation of atypical cells lining the alveolar walls)
Which mutations are associated with adenocarcinoma in smokers?
Kras
Issues with DNA methylation
P53
Which mutations are associated with adenocarcinoma in non-smokers?
EGFR
EML4-ALK
List some common mutations seen in small cell lung cancer.
P53
RB1
Which molecular changes are important to test for in adenocarcinoma?
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
Which stain is used for melanin?
Fontana stain
Which stain is used for amyloid?
Congo Red
When viewed under polarised light, it produces apple green birefringence
What is a key immunological lymphoid marker?
CD45
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
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
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
Which mutation causes fibrous dysplasia?
GNAS mutation Chr 20 q13 (mutation in a G-protein)
Describe the histological appearance of fibrous dysplasia.
The marrow is replaced by fibrous stroma with rounded trabecular bone (‘Chinese letters’)
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
Which cancers in children tend to spread to the bone?
Neuroblastoma
Wilm’s tumour
Osteosarcoma
Ewing’s sarcoma
Rhabdomyosarcoma
Describe the X-ray appearance of osteosarcoma.
Usually metaphyseal
Lytic
Elevated periosteum (Codman’s triangle)
Sunburst appearance
Describe the X-ray appearance of chondrosarcoma.
Lytic with fluffy calcification
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
What is an Ewing’s sarcoma?
Highly malignant small blue round cell tumour
Occurs in people < 20 years old
MIC2 (CD99) antibody
Which genetic abnormality is associated with Ewing’s sarcoma?
Chromosomal translocation 11:22 (EWSR1/FLI1) (q24:q12)
List three types of soft tissue tumour.
Liposarcoma
Spindle cell sarcoma
Pleomorphic sarcoma
Outline the coding used by cytopathologists when assessing breast aspirates.
C1 = inadequate
C2 = benign
C3 = atypia, probably benign
C4 = suspicious of malignancy
C5 = malignant
Describe the histology of fibroadenoma.
Consists of lots of glandular and stromal cells
What are the two different types of intraductal papilloma
Peripheral papilloma – arises in small terminal ductules
Central papilloma – arises in large lactiferous ductules
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
fDescribe the histological appearance of radial scars.
Central stellate area with proliferation of ducts and acini in the periphery
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
What is ductal carcinoma in situ?
A neoplastic intraductal epithelial proliferation in the breast that has not breached the basement membrane
What is in situ lobular neoplasia?
A solid proliferation of cells within the acinus
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
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
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
Describe the histological appearance of Basal-like carcinoma.
Sheets of markedly atypical cells with a prominent lymphocytic infiltrate
Central necrosis is common
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
Which histological grading system is used for invasive breast carcinoma?
Nottingham modification of the Bloom-Richardson system
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)
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
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
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)
List the four types of thyroid cancer in order of decreasing prevalence.
Papillary (80%)
Follicular (15%)
Medullary (5%)
Anaplastic
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)
Where does follicular thyroid cancer tend to metastasise?
Lungs, bone and liver (via the bloodstream)
What are the parathyroid glands derived from?
Developing pharyngeal pouches
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
List three causes of acute primary adrenal failure.
Haemorrhage
DIC associated with sepsis (Waterhouse-Friderichson syndrome)
Sudden withdrawal of corticosteroid treatment
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
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)
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
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
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
What is the name of non-infective endocarditis associated with SLE?
Libman-Sacks endocarditis
What is the localised form of scleroderma called?
Morphoea
What pattern of ANA immunofluorescence is seen in scleroderma?
Nucleolar
What ANA immunofluorescence pattern is seen in mixed connective tissue disease?
Speckled
What criteria is used to classify vasculitides based on the size of the vessel?
Chapel Hill Criteria
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
Which antibody is associated with granulomatosis with polyangiitis?
cANCA – against proteinase 3
Which antibody is associated with Churg-Strauss syndrome?
pANCA – against myeloperoxidase
List some gynaecological infections that cause serious complications.
Chlamydia (infertility)
Gonorrhoea (infertility)
Mycoplasma (spontaneous abortion and chorioamnionitis)
HPV (cancer)
What feature of high risk HPV viruses are responsible for the carcinogenic effects of HPV?
E6 protein – inactivates p53
E7 protein – inactivates retinoblastoma
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)
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
List some causes of endometrial hyperplasia.
Persistent anovulation (due to persistently raised oestrogen)
PCOS
Granuloma cell tumour of the ovary
Oestrogen therapy
List some risk factors for endometrial carcinoma.
Nulliparity
Obesity
Diabetes mellitus
Excessive oestrogen stimulation
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
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
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
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
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)
List two types of non-neoplastic functional cysts.
Follicular and luteal cysts
Endometriotic cyst
List three types of primary specific ovarian tumour.
Surface epithelial tumours
Sex cord stromal tumours
Germ cell tumours
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
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
List some benign ovarian tumours.
Serous cystadenoma
Cystadenofibroma
Mucinous cystadenoma
Brenner tumour
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
Which type of ovarian tumour has a strong association with endometriosis?
Clear cell tumours
NOTE: endometrioid tumours are associated about 20% of the time
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)
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
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
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
List three familial syndromes associated with ovarian cancer.
Familial breast-ovarian cancer syndrome
Site-specific ovarian cancer
Cancer family syndrome (Lynch type II)
List some specific genetic associations for serous, mucinous and endometrioid carcinoma.
Serous – BRCA
Mucinous and endometrioid - HNPCC
Name a benign tumour of the vulva.
Papillary hidradenoma
Which arteries tend to be involved in myocardial infarction (in order of most to least frequent)?
LAD – 50%
RCA – 40%
LCx – 10%
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
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
What is hibernating myocardium?
Chronic sublethal ischaemia leads to lower metabolism in myocytes which can be reversed with vascularisation
Outline the histology of heart failure.
Dilated heart
Scarring and thinning of the walls
Fibrosis and replacement of ventricular myocardium
What is dilated cardiomyopathy?
Caused by progressive loss of myocytes leading to a dilated heart
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
Which valve is most commonly affected in rheumatic valvular disease?
Left-sided valves (almost always mitral)
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)
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)
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
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
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
What is a common histological feature of all acute hepatitis?
Spotty necrosis
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
List some histological features of alcohol hepatitis.
Ballooning – cell swelling
Mallory Denk bodies/Mallory hyaline - pink intracellular material
Apoptosis
Pericellular fibrosis
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
What is primary biliary cholangitis?
Autoimmune conditions characterised by bile duct loss associated with chronic inflammation (with granulomas)
What is the diagnostic test for PBC?
Anti-mitochondrial antibodies (AMA)
What is the histological appearance of PBC?
Bile ducts surrounded by epithelioid macrophages, suggestive of chronic granulomatous destruction of bile ducts
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
What is the diagnostic test for PSC?
Bile duct imaging
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
What is haemosiderosis?
Type of iron overload characterised by the accumulation of iron in macrophages
Usually occurs as a result of receiving blood transfusions
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)
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
Which precursor lesion has the highest risk of developing into breast cancer?
In situ lobular neoplasia
Which gene is mutated in Wilson disease?
ATP7B on chromosome 13
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.
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
Which antibody is associated with drug-induced lupus?
Anti-histone
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
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
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
List some complications of acute pancreatitis.
Pseudocyst formation, abscesses
Shock
Hypoglycaemia
Hypocalcaemia
List some complications of chronic pancreatitis.
Malabsorption
Diabetes mellitus
Pseudocysts
Pancreatic carcinoma
What is the characteristic feature of autoimmune pancreatitis?
Large numbers of IgG4 positive plasma cells typically found around the ducts
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)
Name two types of cystic neoplasm of the pancreas.
Serous cystadenoma
Mucinous cystadenoma
Name two types of dysplastic precursor lesion that ductal carcinoma can arise from.
Pancreatic intraductal neoplasia (PanIN)
Intraductal mucinous papillary neoplasm
Which mutation is very common in pancreatic cancer?
K-ras (95%)
Describe the microscopic appearance of ductal carcinoma.
Adenocarcinomas (secrete mucin and form glands)
Mucin-secreting glands are set in desmoplastic stroma
By what mechanism does pancreatic cancer cause migratory thrombophlebitis?
Circulating pancreatic cancer cells release mucous which activates the clotting cascade
What can be measured as a screening test for neuroendocrine tumours?
Chromogranin
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
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
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)
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)
How does acute tubular injury lead to reduced GFR?
Blockage of tubules by casts
Leakage from tubules into interstitial space
Secondary haemodynamic changes
Describe the histological appearance of acute tubulo-interstitial nephritis.
Heavy interstitial infiltration with eosinophils and granulomas
Clinical features include oliguria, fever and a rash
What causes crescents to appear in acute glomerulonephritis?
Occurs in severe glomerulonephritis due to proliferation of cells within Bowman’s capsule
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
List some causes of immune complex-associated crescentic glomerulonephritis.
SLE
IgA nephropathy
Post-infectious glomerulonephritis
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
What are the main features of pauci-immune crescentic glomerulonephritis?
Scanty glomerular immunoglobulin deposits
Usually associated with ANCA
Triggers neutrophil activation and glomerular necrosis
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
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
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
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
Which antibodies are often found in primary membranous glomerulonephritis?
Antibodies against phospholipase A2 type M receptor (PLA2R)
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