Histopath Flashcards
1
Q
Give 3 types of potential complication after a myocardial infarction and an example of each.
A
1) Mechanical e.g. loss of muscle, ventricular dysfunction, papillary muscle injury (+ mitral regurgitation), ventricular aneurysm
2) Arrythmias e.g. ventricular fibrillation (presenting in first 24h)
3) Pericardial e.g. early pericarditis (see dusky haemorrhagic tissue), pericardial effusion, Dressler’s, fibrinous pericarditis
2
Q
What is Dressler’s syndrome?
A
Patient with fever, chest pain and pericardial effusion more than 4 weeks after a myocardial infarction.
3
Q
A 70 year old man with known ischaemic heart disease is admitted to hospital with shortness of breath and swelling legs. What is the pathophysiology of the condition he has developed?
A
Heart failure
Reduction in cardiac output leads to activation of the renin-angiotensin system and increased retention of salt and water.
Reduced stroke volume stimulates baroreceptors, therefore increasing feedback from the sympathetic nervous system and leading to vasoconstriction. The increased peripheral resistance leads an increased afterload and dilation of the left ventricle.
4
Q
Name the type of cardiomyopathy described below:
Causes systolic dysfunction. May have an idiopathic cause or be due to alcohol, sarcoidosis or iron deposition. Associated with ischaemic heart disease, hypertension and congenital heart disease.
A
Dilated cardiomyopathy
5
Q
Name the type of cardiomyopathy described below:
Causes diastolic dysfunction, usually secondary to a genetic cause or storage disease. Associated with hypertension.
A
Hypertrophic cardiomyopathy
Hypertrophy occurs without ventricular dilation, which can leads to arrythmias (AF, VF), obstructed blood flow and mitral regurgitation. Histology shows a disarray of monocytes.
In HOCM, there is septal hypertrophy which leads to an outflow obstruction and eventual dilated cardiomyopathy.
Occurs due to mutation in genes for sarcomeric proteins e.g. betaMHC, MYBP-C, Troponin T
6
Q
Name the type of cardiomyopathy described below:
Causes diastolic dysfunction, secondary to sarcoidosis, amyloidosis or radiation-induced fibrosis. Associated with pericardial constriction.
A
Restrictive cardiomyopathy
7
Q
A 10 year old boy presents to A&E with stiffness in his joints and jerky movements. Two weeks ago he had a sore throat. What is the likely diagnosis and what would be the associated findings on histology?
A
Acute rheumatic fever - there is antigenic mimicry between Lancefield group A streptococcus and myocardial antigens.
Histology shows:
- beady, fibrous vegetations
- Aschoff bodies: small giant cell granulomas
- Anitschkow myocytes: regenerating myocytes which show a ‘caterpillar pattern’ of chromatin
Mx - benzylpenicillin/erythromycin
8
Q
Pick the most appropriate option from those below:
A 62 year old woman with known systemic lupus erythematosus is suffering from increasing shortness of breath, fatigue on exertion and angina.
a) Rheumatic heart disease
b) Acute infective endocarditis
c) Subacute infective endocarditis
d) Non-bacterial thrombotic (marantic) endocarditis
e) Libman-Sacks
A
e) Libman-Sacks
Endocarditis associated with underlying SLE or anti-phospholipid syndrome. On post-mortem, clusters of small (<2mm), wart-like, platelet rich vegetations may be seen on the mitral valve leaflet and elsewhere. The leaflet and the chordae tendinae are often adherent to the endocardium of the ventricular wall. This is easily missed on echocardiogram.
Most cases of Libman-Sacks are asymptomatic but patients may eventually suffer from mitral or aortic valve disease.
9
Q
Pick the most appropriate option from those below:
A 75 year old man with known mitral valve dysfunction is admitted to hospital with a fever. He has painful red lesions on the tips of his fingers. An echocardiogram does not show any obvious vegetations, but blood cultures are positive for Streptococcus viridans.
a) Rheumatic heart disease
b) Acute infective endocarditis
c) Subacute infective endocarditis
d) Non-bacterial thrombotic (marantic) endocarditis
e) Libman-Sacks
A
c) Subacute infective endocarditis
This is caused by low virulence bacteria such as streptococcus viridans, staphylococcus epidermidis, HACEK organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), coxiella, mycoplasma and candida.
It leads to friable, soft, small thrombi forming on the chordae. This is in contrast to acute infective endocarditis, where there a larger, more localised vegetations.
10
Q
Pick the most appropriate option from those below:
A 33 year old female with known Factor V Leiden and a history of recurrent episodes of VTE is found to have small bland vegetations of thrombi on the lines of closure of the heart valves.
a) Rheumatic heart disease
b) Acute infective endocarditis
c) Subacute infective endocarditis
d) Non-bacterial thrombotic (marantic) endocarditis
e) Libman-Sacks
A
d) Non-bacterial thrombotic (marantic) endocarditis
Occurs in people with DIC or hypercoagulable states e.g. Factor V Leiden. Small bland vegetations of thrombi are found on the heart valves but it is asymptomatic. Symptoms come from thromboemboli circulating to other organs.
11
Q
A 28 year old IVDU is diagnosed with acute infective endocarditis, secondary to streptococcus pyogenes. What criteria are used to diagnose infective endocarditis?
A
Duke criteria - diagnosed using 2 major or 1 major and 3 minor or 5 minor criteria
Major criteria:
- positive blood culture with known infective endocarditis causing organism or 2 +ve cultures over 12h apart
- vegetation of abscess on echo or new regurgitation murmur
Minor:
- risk factors: IVDU, prosthetic valve, congenital valve
- fever >38 degrees
- thromboembolic phenomena
- immune phenomena
- positive blood culture with atypicals
12
Q
Compare the treatment of subacute and acute infective endocarditis.
A
Subacute - benzylpenicillin with gentamicin or vancomycin 4/52
Acute - flucloxacillin if MSSA
- rifampicin, vancomycin and gentamicin if MRSA
13
Q
Name the murmur given the information below:
Mid-systolic click with a late systolic murmur in a middle aged female with shortness of breath and chest pain.
a) Aortic stenosis
b) Aortic regurgitation
c) Mitral stenosis
d) Mitral regurgitation
e) Mitral valve prolapse
A
e) Mitral valve prolapse
14
Q
Name the murmur given the information below:
Rumbling early diastolic murmur with backflow into the left ventricle.
a) Aortic stenosis
b) Aortic regurgitation
c) Mitral stenosis
d) Mitral regurgitation
e) Mitral valve prolapse
A
b) Aortic regurgitation
Secondary to infective endocarditis, dissecting aortic aneurysm, left ventricular dilation, connective tissue disease
15
Q
Name the murmur given the information below:
Diastolic decrescendo murmur with opening snap after the second heart sound.
a) Aortic stenosis
b) Aortic regurgitation
c) Mitral stenosis
d) Mitral regurgitation
e) Mitral valve prolapse
A
c) Mitral stenosis
Backflow into the left atrium; often secondary to rheumatic fever
16
Q
Name 5 different types of pericarditis.
A
Fibrinous - associated with MI and uraemia
Granulomatous - associated with TB
Fibrous (constrictive)
Purulent - associated with Staph
Haemorrhage - associated with tumour or TB
17
Q
Name the type of obstructive lung disease in the patient below:
A 30 year old patient with a recent infectious exacerbation of asthma has permanent dilation of the bronchi, scarring and a cough with purulent sputum.
a) Chronic bronchitis
b) Bronchiectasis
c) Emphysema
d) Asthma
e) Bronchiolitis
A
b) Bronchiectasis
Causes include infection, reduced host defence, post inflammation, asthma or fibrosis.
Hx - cough, purulent sputum, fever associated with permanent dilation of airways and scarring.
Complications include recurrent infection, haemoptysis, pulmonary hypertension and amyloidosis.
18
Q
Name the type of obstructive lung disease in the patient below:
A 12 year old boy with an episodic cough, brought on by exercise and cold air. Histology shows Curschmann spirals of shed epithelium, eosinophils and Charcot-Leyden crystals.
a) Chronic bronchitis
b) Bronchiectasis
c) Emphysema
d) Asthma
e) Bronchiolitis
A
d) Asthma
Charcot Leyden crystals - hexagonal bipyramidal microscopic crystals found int the cytoplasm of eosinophils and basophils.
19
Q
Name the type of obstructive lung disease in the patient below:
A 32 year old man with shortness of breath associated with a cough who has recently been diagnosed with macronodular liver cirrhosis.
a) Chronic bronchitis
b) Bronchiectasis
c) Emphysema
d) Asthma
e) Bronchiolitis
A
c) Emphysema
Occurs secondary to smoking or alpha-1 antitrypsin deficiency. Histology shows a reduction in alveolar parenchyma distal to the terminal bronchioles, with airspace enlargement and wall destruction.
Complications include pneumothorax, respiratory failure and pulmonary hypertension.
20
Q
Definition of chronic bronchitis.
A
Cough associated with sputum which is present on most days for 3 months over a period of 2 years.
Histology - dilation of airways, goblet cell hyperplasia, hypertrophy of mucous glands
21
Q
What is yellow nail syndrome?
A
A rare condition which causes yellow dystrophic nails associated with pulmonary emboli, lymphoedema and bronchiectasis.
22
Q
What is Young’s syndrome?
A
Rhinosinusitis, azoospermia and bronchiectasis.
23
Q
What is the process that leads to the development of ‘honeycomb lung’ in cryptogenic fibrosing alveolitis?
A
There is progressive patchy interstitial fibrosis with the loss of normal lung architecture peripherally, associated with an increased number of type 2 pneumocytes and cyst formation.
24
Q
Outline the presentation of pneumoconiosis.
A
Fibrotic, non-neoplastic reaction to the inhalation of mineral dust and inorganic particles leads to either upper lobe (coal, silicosis) or lower lobe (asbestosis) fibrotic disease.
25
Name 3 potential causes of cryptogenic organising pneumonia.
Radiation pneumonitis
Drug-induced
Connective tissue disease
26
Outline the acute and chronic presentations of extrinsic allergic alveolitis.
Acute - inhalation of antigen dust in a sensitised individual leads to systemic symptoms e.g. fever, chills, SOB, cough
Chronic - progressive persistent productive cough, SOB, clubbing, severe weight loss
Histology - polypoid plugs of loose connective tissue in the alveoli and bronchioles
27
Name the type of EAA described:
A type of EAA caused by thermactinomyces spp., found in heated reservoirs.
Humidifier's lung
28
Name the organisms associated with:
Cheese washer's lung
Aspergillus clavatus and penicillium casei
Aspergillus clavatus is also associated with malt worker's lung
29
Name the type of EAA described:
Caused by mouldy hay, grain or silage
Farmer's lung - saccharopolyspora rectivirgula
30
Name the lung tumour described:
Associated with smoking, which leads to c-Myc and p53 mutations. There is local spread with late metastasis. Histology shows keratinisation and IC prickles.
Squamous cell carcinoma (30-50%)
Subtypes include papillary, basaloid (associated with cavitation) and hypercalcaemia caused by PTHrP secretion or calcitonin release from small cell lung cancer. SCC progresses from angiosquamous dysplasia.
31
A female non-smoker presents to her GP with 2 months of cough, fever and weight loss. A chest X-ray shows a primary tumour that has spread to the other lung and lymph nodes. What will the findings be on histology?
Adenocarcinoma (20-30%)
Found in female, non-smokers and associated with EGFR mutation.
Epithelial tumour with glandular differentiation and mucin production (cells contain mucin vacuoles). There is early metastasis from the primary site.
32
What type of lung tumour is associated with p53 and RB1 mutations?
Small cell carcinoma (20-25% of lung Ca) - it is associated with smoking and forms from neuroendocrine tissue.
Small cell tumours are found in the proximal bronchi and may lead to ectopic ACTH production, Lambert Eaton syndrome (proximal myopathy with autonomic dysfunction) and cerebellar degeneration.
These tumours are highly malignant with early metastasis to bone, adrenals, liver and brain but they are very chemosensitive.
33
Which type of lung tumour is a poorly differentiated epithelial cell tumour with large cells and prominent nucleoli?
Large cell carcinoma (10-15% of lung Ca)
Poorly differentiated malignant epithelial tumour with large cells, nuclei and prominent nucleoi, without glandular or squamous differentiation.
34
What is carcinoid syndrome and what does the tumour produce?
Flushing, diarrhoea and bronchoconstriction secondary to serotonin release.
35
Name 3 mutations that lead to a poor response to chemotherapy in lung cancers.
ERCC1 - in non-small cell lung cancer, poor response to cisplatin
Kras - in adenocarcinoma and squamous cell cancer; poor prognosis
EML4-ALK - in adenocarcinoma; non benefit from tyrosine kinase inhibitors
36
What is the definition of pulmonary hypertension?
Mean pressure >25mmHg at rest
37
Outline the 5 classes of pulmonary hypertension.
1 - F aged 20-40y, secondary to idiopathic, hereditary, toxins, CHD
2 - secondary to left HD e.g. systolic or diastolic dysfunction
3 - due to lung disease
4 - chronic thromboembolic pulmonary HTN
5 - multifactorial e.g. metabolic, systemic
38
What histology findings are associated with diffuse alveolar damage?
Expanded, firm, plum-coloured, airless lung
39
What layer of the body of the stomach wall contains specialised glands?
Lamina propria
In antral stomach, gastric pits of non-specialised glands are found in the lamina propria.
40
A 50 year old Afro-Caribbean male presents with difficulty swallowing. He admits to drinking 50cl of rum a day since he was 25 and smokes 5 cigarettes a day. On questioning, he reports that it is now difficult to swallow solid food and it is painful to swallow. He has lost 4kg in the past month. What is his diagnosis?
Squamous cell carcinoma of the oesophagus
Epidemiology - associated with smoking, alcohol, higher incidence in Afro-Caribbeans (6x) and males, Plummer Vinson, achalasia, nutritional deficiencies, nitrosamines and HPV. 50% occur in the middle third of the oesophagus.
Presents with a progressive dysphagia from solids to liquids, odynophagia, anorexia and severe weight loss. There is rapid growth and metastasis to the lymph nodes, liver and through the oesophageal wall.
Achalasia = impaired relaxation of the lower esophageal sphincter in response to swallowing and loss of peristalsis.
41
Why does cag A positive H.Pylori lead to a higher incidence of gastric cancer?
Toxin allows easy bacterial attachment to the gastric mucosa.
42
A 78 year old woman presents to her GP complaining of epigastric pain. She says that the pain is worse after she eats. She takes ibuprofen daily for arthralgia and smokes 15 cigarettes a day. What is her diagnosis and what might be visualised on OGD?
Gastric ulcer
These ulcers are mostly found in the elderly and breach through the muscularis mucosa to the submucosa, causing punched out lesions with rolled margins. Risk factor include Helicobacter infection, smoking, NSAIDs, stress and delayed gastric emptying.
Complications include iron deficiency anaemia, perforation (presenting with peritonitis) and malignancy.
43
What is the treatment for MALT caused by chronic Helicobacter infection?
Triple therapy - PPI e.g. omeprazole, clarithromycin and amoxicillin/metronidazole.
44
What antibodies may be found in active coeliac disease?
Anti-endomysial antibodies, anti-tissue transglutaminase antibodies, anti-gliadin antibodies
Histological findings - villous atrophy, crypt hyperplasia, lymphocyte infiltration
45
A 6 month old male has suffered from chronic constipation from birth, with occasional diarrhoea and vomiting. His mother says that there was delayed passage of meconium after birth but he has been otherwise fit and well. What findings would be expected on a distal colon biopsy and what is the definite treatment for this condition?
Hirschsprung's disease
80% of cases are found in males. Associated with Down's syndrome, but Hirschsprung's may occur in as few as 2% of all children with Down's. There is also an association with positive RET protooncogene Cr10+.
An absence of ganglion cells in the myenteric plexus leads to a failure of the distal colon to dilate, which therefore leads to obstruction with constipation and overflow diarrhoea or vomiting. The abdomen may also be distended.
Biopsy of the affected area will show the absence of ganglia and hypertrophy of nerve fibres. The only definitive management is to resect the affected segment.
46
A 6 month old child presents to A&E with his mother. He says that for the past 24h he has been very difficult to settle and sometimes vomits after feeds. He will cry inconsolably for 20-30 minutes then quieten, but only briefly. On examination, there is a sausage-shaped mass in the right upper quadrant and no bowel in the right lower quadrant (Dance's sign). How would you confirm the diagnosis and what are some potential causes?
Intussusception - can confirm on barium enema which will show a 'crescent sign'. Air insufflation may be tried to inflate the bowel and therefore correct the area of telescoping. If there are severe complications then laparotomy may be required.
The disruption of peristalsis in the bowel is causing colicky abdominal pain (inconsolable crying) and vomiting. 50% of cases are related to a viral infection e.g. rotavirus, adenovirus or HHV-6.
47
What is the 'hygiene hypothesis' of the aetiology of Crohn's disease?
Reduced food contamination leads to reduced rates of infection and therefore reduced development of a mucosal immune response.
48
Describe the appearance of the gastrointestinal mucosa in Crohn's disease.
Lesions may be 'from mouth to anus'.
- skip lesions: patchy, transmural inflammation
- cobblestone appearance: healthy mucosa overlying diseased mucosa
- apthous ulcer first lesion (painful shallow ulcer) with deep 'rosethorn' ulcers
- ulcers may coalesce to form serpentine ulcers
- may also see non-caseating granulomas and fistulas/fissures
49
Name 3 extra-intestinal conditions associated with Crohn's disease.
```
Angular stomatitis
Erythema nodosum
Erythema multiforme
Sacroilitis
Uveitis/conjuncitivits
Pyoderma gangrenosum
Polyarthropathy of large joints
Primary sclerosing cholangitis
```
50
What drugs are used to treat Crohn's disease?
Mild - prednisolone
Severe - IV hydrocortisone
Metronidazole with or without azathioprine/methotrexate/infliximab
51
Describe the appearance of the mucosa in ulcerative colitis.
Extends from the rectum in continuous fashion
- backwash ileitis: small bowel inflammation in severe pancolitis
- extensive, superficial, broad ulcers with superficial inflammation which is confined to the mucosa
- no granulomas, fissures, fistulae or strictures
- pseudopolyps: islands of regenerating mucosa which bulge into the lumen
52
What is toxic megacolon?
Damage to the muscularis propria in inflammatory disease with disruption of neuromuscular function, leading to 'paralysis' (loss of tone, function and motility). It presents as a very dilated colon with associated abdominal distension and sometimes fever, abdominal pain and shock. It is more commonly associated with UC than Crohn's.
53
What treatments are used for UC?
Prednisolone with mesalazine +/- steroid enema
| If severe flare up, admit, give IV fluids and hydrocortisone aswell as rectal steroids.
54
What are the 3 types of neoplastic polyp found in the colon?
1) Tubular (most common - 70-85%) = rounded neoplastic glands
2) Villous (rare) = epithelial projections, which are associated with leakage of potassium and protein
3) Tuberovillous (10-25%) = mixture of straight/branched tubules of dysplastic tissue and finger-like dysplastic epithelial projections
The higher the villous component, the higher the likelihood of malignancy!
55
Describe the pathophysiology of Familial Adenomatous Polyposis.
Autosomal dominant condition which has an onset of about 25 years old.
Mutation in the APC tumour suppressor gene (5q21) leads to the formation of 1000s of polyps. Nearly all patients develop cancer (adenocarcinoma) within 10-15 years.
56
How does Gardner's syndrome differ from Familial Adenomatous Polyposis?
Lots of polyps but also has extra-intestinal manifestations such as:
- multiple osteomas of the skull and mandible
- epidermoid cysts
- desmoid tumours
- dental caries
- mesenteric fibromas
57
A 35 year old female presents to her GP with a change in bowel habits and some mucous in the stool. Her dad died of colon cancer aged 51. A colonoscopy shows a mass close to the splenic flexure and a biopsy is taken. The biopsy shows a poorly differentiated mucinous carcinoma.
What type of genes are affected in the condition described above?
Hereditary non-polyposis colorectal cancer
Autosomal dominant inheritance; accounts for 3-5% of all colorectal cancer. Mutations occur in DNA mismatch repair genes which leading to errors in DNA repair and increased risk of cancer. Also associated with extracolonic cancer of the endometrium, prostate, breast and stomach.
58
A 4 year old boy who presented to his GP with rectal bleeding is found to have focal malformations of the mucosa and lamina propria. What is the likely underlying diagnosis and management of this condition?
Juvenile polyposis - autosomal dominant
Presents with bleeding polyps, mostly found in the rectum. The only definitive way to stop the bleeding in major haemorrhage is with a colectomy.
59
A 3 year old girl who has previously had to go to A&E because of intussusception is admitted to hospital for investigation of multiple polyps in her colon. It is also noted that she has high levels of mucocutaneous pigmentation and freckles around her mouth and on the soles of her feet. What is the likely underlying diagnosis and the associated gene mutation?
Peutz Jegher's - autosomal dominant, associated with LKB1 (or STK11). Presentation is of benign hamartamous polyps in the gastrointestinal tract with hyperpigmented macules on the lips and oral mucosa.
Complications include intussusception and malignancy.
60
What hormones regulate the function of the pancreas?
Secretin, from s-cells of the duodenum: controls gastric acid secretion and bicarbonate ion buffering from epithelial duct cells.
CCK, from l-cells of the duodenum: controls release of digestive enzymes from acinar cells.
Together they lead to the production of enzyme and bicarbonate rich fluid.
61
What are the causes of acute pancreatitis?
```
I GET SMASHED
Idiopathic
Gallstones (50%)
Ethanol (33%)
Trauma
Steroids
Mumps
Autoimmune
Scorpion venom
Hyperlipidaemia
ERCP
Drugs e.g. thiazides
```
62
A 45 year old woman with a history of gallstones presents to A+E with severe epigastric pain which radiates to her back and is worse on lying down. She has vomiting 5 times in the past 12 hours. What findings would you expect on histology?
Fat necrosis due to the release of lipases - yellow-white foci due to calcium binding to free fatty acids. There is a progression from stromal oedema to haemorrhagic necrosis (direct acinar injury).
Ix - transient increased in amylase and increase in serum lipase in 48h
Complications include abscess, shock, hypoglycaemia and hypocalcaemia.
63
How does chronic pancreatitis develop from acute pancreatitis?
Persistent inflammation with parenchymal fibrosis leads to loss of parenchyma, duct strictures with calcified stones and secondary dilatations.
On histology - fibrosis, loss of exocrine tissue, duct dilation with thick secretions, calcification
Symptoms are of acute pancreatitis with malabsorption, weight loss, develop of diabetes and steatorrhea. Pseudocysts may also form; fibrous tissue lined spaces containing enzyme rich fluid and necrotic material.
64
What is IgG4 disease?
Autoimmune pancreatitis - characterised by large numbers of IgG4 positive plasma cells. May also involve bile ducts and other parts of the body.
65
Name the type of pancreatic tumour described below:
A 65 year old diabetic man with a BMI of 32 goes to his GP complaining of fatigue and back pain. On questioning he has noticed that his stools are pale and foul-smelling. Courvoisier's sign in positive. On blood tests his bilirubin is 60 and a Ca19.9 is 105IU/ml.
Ductal carcinoma (85% of pancreatic cancers)
Risk factors are increased age, smoking, BMI and diet, chronic pancreatitis and diabetes. 95% have K-Ras mutation. It presents with cachexia, anorexia, epigastric pain radiating to the back, jaundice, pruritis, steatorrhea and ascites.
```
Courvoisier's = enlarged non-tender gall bladder with jaundice unlikely to be gallstones.
Trousseau's = recurrent superficial thrombophlebitis
```
Macroscopic findings = gritty, grey
Microscopic findings = mucin secreting glands in desmoplastic stroma
66
Name the pancreatic tumour described below:
Usually benign and multilocular, with serous or mucin secreting epithelium.
Cystic tumour
67
A pancreatic tumour is positive for lipase, trypsin and chymotrypsin. What is the likely diagnosis and underlying histopathology?
Acinar cell carcinoma - rare pancreatic cancer mostly found in the elderly. Histology shows neoplastic epithelial cells with eosinophilic granular cytoplasm.
68
Name three types of neuroendocrine pancreatic tumour and describe how they present.
Insulinoma - hypoglycaemic attacks
Gastrinoma - Zollinger Ellison syndrome and recurrent ulcers
Glucagonoma - necrolytic migrating erythema
69
What tumours are associated with:
a) MEN 1
b) MEN 2A
c) MEN 2B
a) Parathyroid adenoma, pancreatic endocrine tumours, phaeochromocytoma, pituitary adenoma
b) Parathyroid, thyroid, phaeochromocytoma
c) Medullary thyroid, phaeochromocytoma, neuroma (associated with Marfan's)
70
What are Rokitansky-Aschoff sinuses?
Pseudodiverticula of the muscle layer of the gallbladder, which may be microscopic or macroscopic. Associated with chronic cholecystitis.
71
How is cirrhosis of the liver classified as either micronodular or macronodular?
Micronodular - nodules < 3mm, uniform involvement of the liver, secondary to alcohol or biliary tract disease
Macronodular - nodules > 3mm, variable size, secondary to viruses, Wilson's or alpha-1 antitrypsin deficiency
72
What are the criteria for calculating the Child Pugh score?
1) Ascites - none to severe
2) Encephalopathy - none to marked
3) Bilirubin - <34, 34-50, >50
4) Albumin - >35, 28-35, <28
5) PT - <4 to >6
73
Define portal hypertension and outline the main causes.
Definition = increased portal pressure secondary to increased vascular resistance within the liver, hyperdynamic circulation or increased circulating volume.
Aetiology:
1) Prehepatic - portal vein thrombosis e.g. secondary to FV Leiden
2) Hepatic - presinusoidal, sinusoidal or post-sinusoidal; causes include schistosomiasis, PBC, sarcodiosis, cirrhosis and venous occlusion
3) Post-hepatic - Budd Chiari (i.e. hepatic vein occlusion), thrombophilia, leukaemia, renal tumours, HCC
74
What causes:
a) Spotty necrosis of the liver
b) Piecemeal necrosis?
a) Acute hepatitis, caused by viruses and drugs
| b) Inflammatory chronic hepatitis (portal, interface or lobular causes)
75
Outline the histological progression from hepatitic steatosis to alcohol cirrhosis in alcoholic liver disease.
1) Fatty liver
- macroscopic: large, pale, yellow, greasy liver
- microscopic: accumulation of fat droplets in hepatocytes (chronic exposure leads to fibrosis)
2) Alcoholic hepatitis
- macroscopic: large, fibrotic liver
- microscopic: hepatocyte ballooning and necrosis secondary to the accumulation of fat, water and proteins (mallory bodies - damaged intermediate filaments within hepatocytes)
3) Alcoholic cirrhosis
- macroscopic: shrunken, non-fatty, brown liver
- microscopic: micronodular cirrhosis with bands of fibrous tissue
76
What are the antibodies associated with:
a) Type 1 autoimmune hepatitis
b) Type 2 autoimmune hepatitis?
a) ANA, anti-Sm, anti-actin, anti-soluble liver antigen
| b) Anti-LKM
77
A 48 year old woman presents with a 3 week history of fatigue, pruritis and abdominal discomfort. She has a raised ALP, cholesterol and bilirubin on blood tests. Anti-mitochondrial antibodies are also detected. What will be seen on USS?
Primary biliary cirrhosis
- autoimmune destruction of medium-sized intrahepatic bile ducts leads to cholestasis and slow development of liver cirrhosis
USS will not show bile duct dilatation, like it would with gallstones. This is because there is progressive bile duct destruction and granuloma formation. Treatment is with ursodeoxycholic acid - if used early enough this leads to remission in 25%.
78
A 42 year old male with a history of ulcerative colitis presents with jaundice, RUQ pain and a fever. His ALP is raised and pANCA is found on analysis for auto-antibodies. What findings will be visible on USS?
Primary sclerosing cholangitis
- inflammation and obliterative fibrosis of extra and intrahepatic bile ducts leads to multifocal stricture formation.
May be seen as bile duct dilation or 'beading' on USS, due to the alternating strictures and preserved segments (visualisation and diagnosis better on ERCP).
79
Name the condition described below:
Autosomal recessive condition due to ATP7B mutation on chromosome 13 which presents in teenagers. A blue Rhodamine stain shows brown spots with mallory bodies and fibrosis on microscopy. Treatment is with lifelong penicillamine.
Wilson's disease
A failure of copper transportation leads to excretion of copper by hepatocytes into the bile and subsequent deposition in the liver, CNS and iris. There is hepatolenticular degeneration.
Presentation is with acute hepatitis (eventually progressing to fulminant liver failure), Parkinsonism, psychosis, dementia, Kayser-Fleischer rings in Descemet's membrane of the cornea.
Ix - decreased serum caeruloplasmin, decreased serum copper and increased urinary copper.
80
A 50 year old Caucasian male has just been diagnosed with T2DM. On a diabetes check up, the doctor notes that he also has hepatomegaly and a nice dark tan. He does blood tests which show high levels of iron, ferritin and a transferrin saturation of 60% with a low TIBC. He refers him for an echocardiogram. What is the treatment for this condition?
Haemochromatosis - autosomal recessive, mutated HFE gene at 6p21.3
Mx - venesection, desferrioxamine
Increased absorption of iron in the gut leads to deposition in the liver, heart and pancreas. Deposits can be stained with Prussian blue stain.
81
What is haemosiderosis?
Iron accumulation in macrophages. Treat with blood transfusion.
82
What investigations are used to diagnose the accumulation of alpha-1 antitrypsin in the cytoplasm of hepatocytes in alpha-1 antitrypsin deficiency?
Periodic acid Schiff stain; absent alpha globulin band on electrophoresis
Lungs have lack of enzyme therefore protease destruction of alveoli leading to emphysema.
Deficiency is also a cause of neonatal jaundice.
83
Name the 3 main types of bladder cancer and their associated risk factors.
1) Transitional cell tumours (90%) - more in males, 50-80y; risk factors are smoking, exposure to aromatic amines and previous TCT
2) Squamous cell carcinoma - risk factor = schistosomiasis infection
3) Adenocarcinoma - risk factors = post extensive intestinal metaplasia, from urachal remnants
84
What are the risk factors for the development of germ cell testicular tumours?
Germ cell tumours = seminoma (most common, peak in 30s, radiosensitive) and teratoma (at any age, chemosensitive)
RFs - cryptoorchidism, testicular dysgenesis, Kleinfelters
85
Name the condition described by the case below:
A 14 year old boy who has had a cough and a sore throat for the past two days begins to have frank haematuria. He has no other symptoms.
a) Diabetic glomerulosclerosis
b) Amyloidosis
c) Minimal change disease
d) Focal segmental glomerulosclerosis
e) Membranous glomerular disease
f) Post-streptococcal glomerulonephritis
g) IgA nephropathy (Berger)
h) Rapidly progressive crescentic nephritic syndrome
i) Alport's syndrome
j) Thin basement membrane disease
g) IgA nephropathy
Most common glomerulonephritis - there is deposition of IgA immune complexes in the mesangium of the glomeruli. It usually presents for the first time with episodes of frank haematuria, often 1-2 days after an upper respiratory tract infection. The disease may eventually progress to early end stage renal failure.
86
Name the condition described by the case below:
A 45 year old Caucasian woman with hepatitis B presents with swelling of her legs and frothy urine. A urine dipstick shows significant proteinuria. A kidney biopsy viewed under microscopy with immunofluorescence shows immunoglobulin deposits and complement in granular deposits within the glomerular basement membrane.
a) Diabetic glomerulosclerosis
b) Amyloidosis
c) Minimal change disease
d) Focal segmental glomerulosclerosis
e) Membranous glomerular disease
f) Post-streptococcal glomerulonephritis
g) IgA nephropathy (Berger)
h) Rapidly progressive crescentic nephritic syndrome
i) Alport's syndrome
j) Thin basement membrane disease
e) Membranous glomerular disease
This may be idiopathic or secondary to SLE, infection (hepatitis B/C, malaria), drugs (penicillamine, NSAIDs) or malignancy (solid tumours of lung and colon).
There is diffuse glomerular basement membrane thickening with a loss of podocyte processes and spikey subepithelial deposits. Tissue from a renal biopsy view under light or electron microscopy (Jones' stain) may identify these features, or added immunofluorescence will show immunoglobulin and complement deposits in the GBM.
There is a poor response to steroids. 40% progress to end stage renal failure in the following 2-20 years.
87
Name the condition described by the case below:
A 55 year old woman with known SLE presents with oliguria. Her urine dipstick shows microscopic haematuria and proteinuria. Red cell casts are found in the urine. Her serum urea and creatinine are both very high. Renal biopsy shows granular lumpy bumpy immune complex deposition. Two weeks later, she is put on dialysis.
a) Diabetic glomerulosclerosis
b) Amyloidosis
c) Minimal change disease
d) Focal segmental glomerulosclerosis
e) Membranous glomerular disease
f) Post-streptococcal glomerulonephritis
g) IgA nephropathy (Berger)
h) Rapidly progressive crescentic nephritic syndrome
i) Alport's syndrome
j) Thin basement membrane disease
h) Rapidly progressive nephritis
There are many types, which are classified by their immunological findings. All present with nephritic syndrome inclusive of oliguria and may progress to renal failure within a few weeks.
Type 1 - anti-GBM antibodies; associated with Goodpasture's (HLA DRB1), with linear IgG deposition in the GBM. May also find anti-COL4-A3 antibodies. May lead to pulmonary haemorrhage.
Type 2 - immune complex deposition; as described in case. Associated with SLE, IgA nephropathy and post infectious glomerulonephritis.
Type 3 - ANCA; associated with Wegener's or microscopic polyangitis. Scanty immune complex deposition. May also lead to vasculitis.
88
Name the condition described by the case below:
A 60 year old man has progressive oedema in his legs and frothy urine. He was recently diagnosed with a restrictive cardiomyopathy.
a) Diabetic glomerulosclerosis
b) Amyloidosis
c) Minimal change disease
d) Focal segmental glomerulosclerosis
e) Membranous glomerular disease
f) Post-streptococcal glomerulonephritis
g) IgA nephropathy (Berger)
h) Rapidly progressive crescentic nephritic syndrome
i) Alport's syndrome
j) Thin basement membrane disease
b) Amyloidosis
The kidney is the most common site of deposition in amyloidosis. AL amyloidosis is the most common type and leads to progressive renal failure. It is also associated with multiple myeloma. The AL protein is from immunoglobulin light chains.
AA amyloidosis is from serum amyloid, which are acute phase proteins which increased during chronic inflammation e.g. with rheumatoid arthritis or TB.
Both show apple green birefringence on a congo red stain due to the deposition of extracellular proteinaceous material in organs.
89
What are Kimmelstiel Wilson nodules?
Mesangial matrix nodules found in diabetic glomerulosclerosis alongside diffuse GBM thickening.
90
Name the condition described by the case below:
A 66 year old woman with a BMI of 38 presents to her GP with swollen legs. A urine dipstick shows proteinuria and there are low levels of serum albumin on her LFTs. She is given a diagnosis by a nephrologist who says that 50% of patients with this condition progress to end stage renal failure within 10 years.
a) Diabetic glomerulosclerosis
b) Amyloidosis
c) Minimal change disease
d) Focal segmental glomerulosclerosis
e) Membranous glomerular disease
f) Post-streptococcal glomerulonephritis
g) IgA nephropathy (Berger)
h) Rapidly progressive crescentic nephritic syndrome
i) Alport's syndrome
j) Thin basement membrane disease
d) Focal segmental glomerulosclerosis
This is secondary to obesity and HIV. Histology shows focal and segmental glomerular consolidation with scarring, hyalinosis and loss of podocyte food processes. The scarred areas have immunoglobulin and complement deposition.
50% will respond to steroids and 50% progress to ESRF in 10 years.
91
What are Kimmelstiel Wilson nodules?
Mesangial matrix nodules found in diabetic glomerulosclerosis alongside diffuse GBM thickening.
92
What investigations are used to diagnosis post-streptococcal glomerulonephritis?
Increased ASOT titre (for streptococcus Dx) and decreased C3. C3 and IgG granular deposits are found in the glomeruli, along with subendothelial humps on electron microscopy.
93
What is the most common cause of acute renal failure and its pathophysiology?
Acute tubular injury
- damage to tubular epithelial cells leads to blockage of tubules by casts and therefore decreased flow and haemodynamic changes.
Aetiology - ischaemia due to burns or septicaemia or nephrotoxic drugs e.g. NSAIDs, gentamicin, contrast.
Histology shows necrosis of short tubule segments.
94
How do acute and chronic interstitial nephritis differ?
Basically the same except time frame - acute is due to drug hypersensitivity reaction whereas chronic is associated with long term use of analgesia.
Both present with haematuria and proteinuria.
- acute: + fever, skin rash, eosinophilia
- chronic: + hypertension and anaemia
95
What is the definition of a thrombotic microangiopathy?
Triad of thrombosis, MAHA and thrombocytopaenia. May lead to renal failure. There is widespread fibrin deposition in vessels, platelet fibrin thrombi and platelet and red blood cell destruction.
96
What are the findings on investigation of haemolytic uraemic syndrome?
Most commonly associated with E.Coli O157:H7 infection.
Thrombi to the kidneys with petechiae, haematemesis, melena, pallor and jaundice. Investigations show low Hb, low platelets, high biliurbin, high reticulocyte count, high LDH and negative Coomb's.
97
How does thrombotic thrombocytopaenic purpura differ in presentation from HUS?
Thrombi are throughout the circulation and many are deposited in the CNS. Therefore presents with neurological symptoms such as headache, altered consciousness, seizures and coma.
98
Name 3 types of renal cell carcinoma and how do they present?
Clear cell - well-differentiated
Papillary - associated with dialysis and cystic disease
Chromophobe - pale, eosinophilic cells
Clinical features of all - costovertebral pain, palpable mass, haematuria, paraneoplastic syndrome e.g. polycythaemia (high erythropoietin), hypercalcaemia (calcitonin), hypertension, Cushing's, amyloidosis.
99
What are the potentials complications from pelvic inflammatory disease?
- Infertility
- Fitz Hugh Curtis = RUQ pain from perihepatitis and adhesions
- Increased risk of ectopics
- Intestinal obstruction
- Tubo-ovarian abscess
- Chronic pelvic pain
- Peritonitis
100
What are the theories for the pathophysiology of endometriosis?
1) Retrograde menstrual flow leads to implantation
2) Metastatic transformation of coelomic epithelial cells
3) Vascular or lymphatic dissemination
101
How do fibroids present on histology?
Sharply circumscribed, discrete, round, firm, grey-white tumour. On microscopy, there are bundles of smooth muscle cells.
102
Compare endometrioid and non-endometrioid carcinomas.
Endometrioid (80%) - associated with oestrogen excess therefore risk factors include obesity, PCOS, nulliparity, early menarche, late menopause, tamoxifen, DM and hypertension
- mostly adenocarcinomas (85%) with look of normal glands
Non-endometrioid (20%)
- aggressive cancer which includes papillary, serous and clear cell tumours
- found in elderly females with endometrial atrophy
103
Pick the appropriate option from the conditions below:
An ovarian epithelial cell tumour with abundant clear cytoplasm, intracellular glycogen and a hobnail appearance. It has a poor prognosis.
a) Serous cystadenoma
b) Mucinous cystadenoma
c) Endometrioid
d) Clear cell carcinoma
e) Dysgerminoma
f) Teratoma
g) Choriocarcinoma
h) Fibroma
i) Granulosa-Theca cell tumour
j) Sertoli-Leydig cell tumour
d) Clear cell carcinoma
104
Pick the appropriate option from the conditions below:
A tumour that mimics tubal columnar epithelium and includes psammoma bodies (dystrophic calcification).
a) Serous cystadenoma
b) Mucinous cystadenoma
c) Endometrioid
d) Clear cell carcinoma
e) Dysgerminoma
f) Teratoma
g) Choriocarcinoma
h) Fibroma
i) Granulosa-Theca cell tumour
j) Sertoli-Leydig cell tumour
a) Serous cystadenoma
Most common type of epithelial ovarian tumour. Presents in females aged 30-40 years.
105
Pick the appropriate option from the conditions below:
50% of these type of tumours are associated with Meig's syndrome.
a) Serous cystadenoma
b) Mucinous cystadenoma
c) Endometrioid
d) Clear cell carcinoma
e) Dysgerminoma
f) Teratoma
g) Choriocarcinoma
h) Fibroma
i) Granulosa-Theca cell tumour
j) Sertoli-Leydig cell tumour
h) Fibroma - a stromal tumour
Meig's = ascites with pleural effusion
106
Pick the appropriate option from the conditions below:
A 45 year old female presents to her GP complaining of excessive hair growth and a deepened voice. On examination, the clitoris is enlarged.
a) Serous cystadenoma
b) Mucinous cystadenoma
c) Endometrioid
d) Clear cell carcinoma
e) Dysgerminoma
f) Teratoma
g) Choriocarcinoma
h) Fibroma
i) Granulosa-Theca cell tumour
j) Sertoli-Leydig cell tumour
j) Sertoli-Leydig tumour
Produces androgens which leads to virilising effects in female.
107
Pick the appropriate option from the conditions below:
A 13 year old girl presents with ovarian torsion. A CT abdomen scan shows a large solid mass on her right ovary. She has an elevated serum alpha-feto protein.
a) Serous cystadenoma
b) Mucinous cystadenoma
c) Endometrioid
d) Clear cell carcinoma
e) Dysgerminoma
f) Teratoma
g) Choriocarcinoma
h) Fibroma
i) Granulosa-Theca cell tumour
j) Sertoli-Leydig cell tumour
f) Teratoma
This is an immature teratoma which presents in young girls up to the age of 20. It is malignant and is usually a solid mass which secretes aFP.
Mature teratomas are usually bilateral and asymptomatic. 95% are formed from dermoid cysts and produce mature tissues e.g. skin, hair and teeth.
108
What is pseudomyxoma peritonei?
A condition caused by mucin-secreting cells which produce abundant mucin or gelatinous ascites. It may present with abdominal distension, pelvic pain and a change in bowel habit. Most cases are secondary to tumours which begin on the appendix but mucinous cystadenomas of the ovaries are also implicated.
109
What is the most common ovarian malignancy in young females?
Dysgerminoma - rare otherwise. These tumours are radiosensitive.
110
What are the risk factors for development of cervical cancer?
```
Anything that increases exposure to HPV 16 and 18 infection:
- early sexual intercourse
- multiple partners
- multiparity
Plus: smoking, HIV, immunosuppression
```
111
A 25 year old female who has just given birth has decided to breastfeed. 2 weeks later she goes to the GP with a painful, erythematous breast and a fever. What will the findings be histology and what advice should she be given?
Acute mastitis - staphylococcal infection post lactation.
Histology - necrotic breast tissue with neutrophil infiltration.
Advice - keep expressing milk, antibiotics, surgical drainage if does not improve
112
What type of mastitis is associated with smoking?
Periductal mastitis - histology shows keratinising squamous epithelium which infiltrates deep into nipple duct orifices.
113
How does mammary duct ectasia present?
Poorly defined palpable periareolar mass with thick white nipple secretions. Occurs due to granulomatous inflammation and dilation of breast ducts. It is associated with multiparity and women aged 40-60y.
Cytology shows proteinaceous material and inflammatory cells.
114
What breast cancer is described below?
A 32 year old comes to the breast clinic concerned about bloody discharge from her right nipple. On examination, no lump is palpated and mammogram does not detect any malignant changes.
Duct papilloma = benign papillary tumour within the duct system
- if in small terminal ductules = peripheral papilloma
- if in larger lactiferous ducts = central papilloma
Ix - galactogram
115
Which breast cancer is described below?
Usually an incidental finding on biopsy. Cells do not have E-cadherin adhesion protein. 20-40% present bilaterally.
Lobular carcinoma in-situ - neoplastic epithelial proliferation limited to lobules by basement membrane
116
Which breast cancer is described below?
Most common in 75-80y age group. Lifetime risk is 1/8. May have hard fixed lump, Paget's disease of the breast, peau d'orange skin changes and nipple retraction.
Breast carcinoma
Risk factors include BRCA 1/2, increased hormone exposure, advancing age, family history, Caucasian, obesity, tobacco and alcohol.
Screening - in females 43-73y every 3y; mammography
117
Describe the presentations of the 4 different types of invasive breast carcinoma.
1) Ductal - most common
2) Lobular - cells aligned in single file chains
3) Tubular - well formed tubules with low-grade nuclei
4) Mucinous - produce extracellular mucin
118
What is core needle biopsy of breast cancer used for?
To assess nuclear pleomorphism, tubule formation and mitotic activity.
119
Describe the presentation of basal-like carcinoma.
Sheets of atypical cells with lymphocytic infiltrate - positive for CK4/5/6
120
What is a Phyllodes tumour?
A tumour of the interlobular stroma which may arise within existing fibroadenomas. They have increased cellularity and mitoses.
121
What are Charcot-Bouchard microaneurysms?
Found in small penetrating blood vessels of the brainstem and midbrain. Associated with hypertension and most commonly occur in the lenticulostriate branch of the middle cerebral artery.
Most common cause of intraparenchymal haemorrhage. Presents with severe headache, vomiting, rapid loss of consciousness and focal neurological signs.
122
Name 3 causes of non-traumatic haemorrhage.
Intraparenchymal haemorrhage
Cavernous angioma = malformative lesions of closely packed vessels with lack of parenchyma between vascular spaces. Low pressure therefore present with recurrent bleeds, headache, seizures and focal deficits.
AVM - high pressure malformation leads to massive haemorrhage, seizures, headache and focal signs. 10-18% mortality rate.
Subarachnoid haemorrhage = rupture of berry aneurysm, most commonly at internal carotid artery bifurcation with 20% at vertebrobasilar junction. Risk factors - PKD, Ehler's Danlos, aortic coarctation
123
How can cerebral infarction be managed?
Aspirin +/- dipyridamole (inhibits platelet aggregation)
Thrombolytics may be used if less than 3h after initial symptoms
Carotid endarterectomy
Long-term: antihypertensives, treat dyslipidaemia, anticoagulants
124
How can you distinguish the causes of meningism on CSF analysis?
1) Pyogenic - turbid CSF, large increase in neutrophils, low glucose, raised protein (>0.4g/L)
2) TB - fibrin web in CSF, lymphocytes (50-1000), low glucose, high protein (1-5g/L)
3) Viral - clear CSF, lymphocytes (10-1000), normal glucose, normal or raised protein (0.4-1g/L)
125
What are the most common causes of meningitis in:
a) A neonate
b) An infant
c) A young adult
d) The elderly?
a) Group B strep, E.coli, listeria; viral - echovirus, coxsackie, mumps, HIV
b) Streptococcus pneumoniae, Haemophilus influenzar
c) Neisseria meningitidis, S.pneumoniae
d) S.pneumoniae gram negative bacteria
126
What brain tumour is being described below?
50-60% occur in the frontal lobe. They are associated with a long history of neurological signs e.g. seizures. Associated with IDH-1 and 1p19q deletion.
Oligodendroglioma - diffuse glial tumour
127
What brain tumour is being described below?
Presents in teenagers. On histology, the tumour shows marked nuclear atypia and vascular proliferation. There are Rosenthal fibres, granular bodies and piloid 'hairy' cells.
Pilocytic astrocytoma - grade 1 tumours usually found in the cerebellum and brainstem
128
Which primary tumours most commonly produce metastases in the brain?
Lung, melanoma, breast, renal and colon
129
What is multiple system atrophy and give 3 examples of presentations.
Neurodegeneration that may present similarly to Parkinson's (but will not respond to Parkinson's medications).
- Shy Drager; presents with autonomic dysfunction
- Striatonigral: movement difficulties
- Olivopontocerebellar: difficulties with balance and coordination
130
What is the rachitic rosary sign and what disease does it represent?
Osteomalacia in children i.e. rickets
| Rachitic rosary sign is the expansion of the anterior ends of the ribs ('rib beading')
131
What investigation findings are associated with hyperparathyroidism?
- Brown's tumours in fingers, pelvis and facial bones (marrow fibrosis and cysts)
- Osteitis fibrosa cystica: bone resorption in the long bones
- Salt and pepper skull on X-ray
- Subperiosteal bone resorption
- Biochemistry: high calcium, low phosphate, normal or high ALP
132
How does Paget's disease of bone present?
History - >40y, bone pain, microfractures, nerve compression (with possible medulla involvement), increased head size, deafness, high output heart failure
XR - osteoporosis circumscripta and cotton wool calcifications of skull, picture frame and ivory vertebrae, sclerosis, lucency in the pelvis
Histology - large osteoclasts with over 100 nuclei, mosaic/jigsaw pattern of lamellar bone
133
Outline the process of bone fracture repair.
- Pro-callus formation - organisation of haematoma
- Formation of fibrocartilagenous callus
- Mineralisation of fibrocartilagenous callus
- Remodelling of bone along weight-bearing lines
134
What are the most common organisms associated with osteomyelitis?
- Adults = S.aureus
- Children = H.influenza, GBS
- Sickle cell = salmonella
- IVDA = pseudomonas
- Immunocompromised = TB, syphilis
135
Describe the development of osteomyelitis.
Begins with mottled appearance of bone with periosteal lifting about 10 days after onset. There is then irregular new bone formation (involucrum). Finally there is detachment of the necrotic cortex after 3-6 weeks (sequestra).
136
Describe the findings on histology of rheumatoid arthritis.
Proliferative synovitis with thickened synovial membranes, intense inflammatory cell infiltrate, fibrin deposition and necrosis.
Associated with increase in IL-6, IL-1B, TNF-alpha and CRP. Antigen at synovial membrane leads to T cell proliferation associated with increase in B cells and angiogenesis, chronic inflammation, pannus formation and destruction.
137
Compare the presentation of gout and pseudogout.
Gout - associated with dietary purine, alcohol and diuretics
- 90% occur in MTP joint; hot swollen red painful joint with tophi
- Ix: needle shaped urate crystals, negatively birefringent
- Mx: acute - colchicine, chronic - allopurinol
Pseudogout - associated with hyperparathyroidism, diabetes, hypothyroidism and Wilson's
- Hx: hot swollen joint (knee, shoulder) with effusion
- Ix: positively birefringent rhomboid shaped calcium pyrophosphate crystals
- Mx: NSAIDs, intraarticular steroids
138
Name the bone malignancy described below:
A highly malignant, small, round cell tumour that presents as sheets of cells on histology. It is usually found in the diaphysis or metaphysis of long bones.
a) Fibrous dysplasia
b) Osteochondroma
c) Enchondroma
d) Osteoid osteoma
e) Osteoblastoma
f) Giant cell tumour
g) Metastases
h) Osteosarcoma
i) Chondrosarcoma
j) Ewing's sarcoma
j) Ewing's sarcoma - 80% occur in <20y, associated with t(11:22) and CD99
XR - onion skinning of periosteum with lytic +/- sclerotic lesions
139
Name the bone malignancy described below:
Locally aggressive tumour of the epiphysis, usually of the knee, with metaphyseal extension. There are osteoclast-type multinucleate giant cells on a background of spindle or ovoid cells.
a) Fibrous dysplasia
b) Osteochondroma
c) Enchondroma
d) Osteoid osteoma
e) Osteoblastoma
f) Giant cell tumour
g) Metastases
h) Osteosarcoma
i) Chondrosarcoma
j) Ewing's sarcoma
f) Giant cell tumour
Borderline malignant. XR shows lytic or lucent lesions up to the articular surface.
140
Name the bone malignancy described below:
Most commonly found in the ribs or proximal femur this may be present with café-au-lait spots and precocious puberty as part of McCune-Albright syndrome.
a) Fibrous dysplasia
b) Osteochondroma
c) Enchondroma
d) Osteoid osteoma
e) Osteoblastoma
f) Giant cell tumour
g) Metastases
h) Osteosarcoma
i) Chondrosarcoma
j) Ewing's sarcoma
a) Fibrous dysplasia
In McCune Albright, this is polyostotic dysplasia.
Ix - chinese letters on histology (misshapen bone trabeculae), soap bubble osteolysis and shepherd's crook deformity on XR.
141
Name the bone malignancy described below:
Found on XR as a radiolucent nidus with a sclerotic rim. Most common sites are the tibia and femur.
a) Fibrous dysplasia
b) Osteochondroma
c) Enchondroma
d) Osteoid osteoma
e) Osteoblastoma
f) Giant cell tumour
g) Metastases
h) Osteosarcoma
i) Chondrosarcoma
j) Ewing's sarcoma
d) Osteoid osteoma - in adolescents
Small benign bone forming lesion which presents with nighttime bone pain. Manage with aspirin.
142
Name the bone malignancy described below:
Histology of this malignancy shows malignant mesenchymal cells +/- bone and cartilage formation. XR shows an elevated periosteum with a lytic, permeative lesion in Codman's triangle and a sunburst appearance.
a) Fibrous dysplasia
b) Osteochondroma
c) Enchondroma
d) Osteoid osteoma
e) Osteoblastoma
f) Giant cell tumour
g) Metastases
h) Osteosarcoma
i) Chondrosarcoma
j) Ewing's sarcoma
h) Osteosarcoma - adolescents, M:F 2:1, 60% knee
Mx - chemotherapy and limb salvage surgery
143
What type of bone neoplasia is associated with Ollier's syndrome and Maffuci's syndrome?
Enchondroma - benign tumour of cartilage
Ix - expansile, cotton wool calcification, O ring sign
```
Ollier's = multiple enchondromas
Maffuci's = multiple enchondromas and hemangiomas
```
144
What is diaphyseal aclasis?
Also known as hereditary multiple exostoses, this is when osteochondromas (cartilage capped bony outgrowths) present alongside short stature and bone deformities.
145
How does osteoblastoma differ from osteoid osteoma?
Has speckled mineralisation on XR instead of radiolucent nidus with sclerotic rim.
146
What is Auspitz's sign of psoriasis?
Pinpoint bleeding occurs when psoriatic plaque is rubbed.
147
What are the histological findings of psoriasis?
Parakeratosis (nuclei found in the stratum corneum), loss of granular layer, 'test tubes in rack' appearance, Munro's microabscesses
148
What are Wickam's striae?
Fine white network found on the surface of lichen planus lesions. Histology = hyperkeratosis with saw toothing of rete ridges and basal cell degeneration.
149
Name 2 infectious and 2 iatrogenic causes of erythema multiforme.
Infectious - HSV, mycoplasma
| Drugs - sulphonamides, NSAIDs, allopurinol, penicillin, phenytoin
150
What is the pathophysiology of dermatitis herpetiformis?
IgA antibody binding to the basement membrane leading to the formation of subepidermal bullae on the extensor surfaces of the elbows and buttocks in individuals with coeliac disease.
Histology = coalescing microabscesses which develop into bullae; IgA and neutrophil deposits on dermal papillae.
151
How do the histological findings of pemphigus and pemphigoid differ?
Pemphigus - netlike pattern of intracellular IgG and acantholysis (IgG in desmosomes)
Pemphigoid - eosinophils and linear IgG on the basement membrane (IgG in hemidesmosomes of BM)
152
What are the histological findings associated with actinic keratosis?
```
SPAIN
Solar elastosis
Parakeratosis
Atypia
Inflammation
Not full thickness
```
153
How does Bowen's disease become squamous cell carcinoma of the skin?
Bowen's - full thickness atypia limited to the epidermis ('intraepidermal SCC in situ'); presents as flat, red, scaly patches on sun exposed sites.
SCC - invasion into the dermis; shows nuclear crowding on histology.
154
Name 4 types of melanoma.
1) Lentigo maligna - associated with sun exposure, flat and slow growing
2) Superficial spreading malignant melanoma - irregular borders and colour
3) Nodular
4) Acral lentiginous - on palms, soles and subungal
155
How is Steven Johnson syndrome distinguished from toxic epidermal necrolysis?
Both cause sheets of skin detachment and are Nikolsky skin positive with prominent mucosal involvement.
SJS covers less than 10% of skin surface; TEN is more than 30%.
156
Differences between polymyositis and dematomyositis on histology.
Poly - endomysial inflammatory infiltrates
| Dermato - 'drop out' of capillaries with associated perivascular myofibre damage
157
Name 3 different medium vessel vasculitides.
1) Polyarteritis nodosa - renal involvement with lung sparing; associated with underlying hepatitis B (30%)
2) Kawasaki's disease - fever >5 days, desquamating rash of palms and soles, inflammation of lips/mouth/tongue, cervical lympadenopathy, coronary artery aneurysm formation, conjunctivitis
3) Buerger's (thromboangitis obliterans) - found in heavy smokers, inflammation of arteries of extremities with pain and ulceration (toes, feet, fingers)
Ix - corkscrew appearance on angiogram associated with segmental occlusive lesions
158
What is the triad of symptoms in Wegener's granulomatosis?
Upper respiratory tract - sinusitis, epistaxis, saddle nose
Lower respiratory tract - cavitation, pulmonary haemorrhage
Kidneys - crescentic glomerulonephritis
159
Outline the causes of amyloidosis.
Primary - most common, AL protein, associated with plasma cell dyscrasias and paraproteins
Secondary - AA protein (acute phase protein), secondary to autoimmunity and chronic infections e.g. TB osteomyelitis, renal cell carcinoma, Hodgkin's
Haemodialysis - deposition of beta 2 microglobulin
Familial - increased IL-1 leads to fever, inflammation of pleura and peritoneum; gene associated with pyrin production
160
What are the possible presentations of amyloidosis?
1) Kidney - nephrotic syndrome
2) Heart - conduction defects, heart failure, cardiomegaly
3) Liver/spleen - hepatosplenomegaly
4) Tongue - macroglossia
5) Neuropathies - carpal tunnel
161
What are the possible presentations of sarcoidosis?
1) Lungs - insidious shortness of breath, cough, chest pain, night sweats
2) Skin - erythema nodosum, lupus pernio, skin nodules
3) Lymph nodes - painless rubbery lymphadenopathy
4) Eyes - anterior uveitis (misty vision, red eye), posterior uveitis, keratoconjunctivitis, lacrimal gland enlargement
5) Heerfordt's syndrome - parotid enlargement +/- facial nerve palsy
6) Hepatosplenomegaly
7) Leukopenia +/- anaemia
8) Hypercalcemia (renal calculi, nephrocalcinosis)
9) Heart - dysrhythmias, cardiomyopathy
10) CNS involvement
162
Investigations for sarcoidosis
CXR - bilateral hilar lymphadenopathy and pulmonary infiltrates (fine nodular shadowing)
Biochem - high calcium, high ESR, raised ACE
