Histopath Flashcards
Give 3 types of potential complication after a myocardial infarction and an example of each.
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
What is Dressler’s syndrome?
Patient with fever, chest pain and pericardial effusion more than 4 weeks after a myocardial infarction.
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?
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.
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.
Dilated cardiomyopathy
Name the type of cardiomyopathy described below:
Causes diastolic dysfunction, usually secondary to a genetic cause or storage disease. Associated with hypertension.
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
Name the type of cardiomyopathy described below:
Causes diastolic dysfunction, secondary to sarcoidosis, amyloidosis or radiation-induced fibrosis. Associated with pericardial constriction.
Restrictive cardiomyopathy
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?
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
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
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.
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
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.
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
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.
A 28 year old IVDU is diagnosed with acute infective endocarditis, secondary to streptococcus pyogenes. What criteria are used to diagnose infective endocarditis?
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
Compare the treatment of subacute and acute infective endocarditis.
Subacute - benzylpenicillin with gentamicin or vancomycin 4/52
Acute - flucloxacillin if MSSA
- rifampicin, vancomycin and gentamicin if MRSA
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
e) Mitral valve prolapse
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
b) Aortic regurgitation
Secondary to infective endocarditis, dissecting aortic aneurysm, left ventricular dilation, connective tissue disease
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
c) Mitral stenosis
Backflow into the left atrium; often secondary to rheumatic fever
Name 5 different types of pericarditis.
Fibrinous - associated with MI and uraemia
Granulomatous - associated with TB
Fibrous (constrictive)
Purulent - associated with Staph
Haemorrhage - associated with tumour or TB
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
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.
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
d) Asthma
Charcot Leyden crystals - hexagonal bipyramidal microscopic crystals found int the cytoplasm of eosinophils and basophils.
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
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.
Definition of chronic bronchitis.
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
What is yellow nail syndrome?
A rare condition which causes yellow dystrophic nails associated with pulmonary emboli, lymphoedema and bronchiectasis.
What is Young’s syndrome?
Rhinosinusitis, azoospermia and bronchiectasis.
What is the process that leads to the development of ‘honeycomb lung’ in cryptogenic fibrosing alveolitis?
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.
Outline the presentation of pneumoconiosis.
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.
Name 3 potential causes of cryptogenic organising pneumonia.
Radiation pneumonitis
Drug-induced
Connective tissue disease
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
Name the type of EAA described:
A type of EAA caused by thermactinomyces spp., found in heated reservoirs.
Humidifier’s lung
Name the organisms associated with:
Cheese washer’s lung
Aspergillus clavatus and penicillium casei
Aspergillus clavatus is also associated with malt worker’s lung
Name the type of EAA described:
Caused by mouldy hay, grain or silage
Farmer’s lung - saccharopolyspora rectivirgula
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.
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.
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.
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.
What is carcinoid syndrome and what does the tumour produce?
Flushing, diarrhoea and bronchoconstriction secondary to serotonin release.
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
What is the definition of pulmonary hypertension?
Mean pressure >25mmHg at rest
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
What histology findings are associated with diffuse alveolar damage?
Expanded, firm, plum-coloured, airless lung
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.
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.
Why does cag A positive H.Pylori lead to a higher incidence of gastric cancer?
Toxin allows easy bacterial attachment to the gastric mucosa.
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.
What is the treatment for MALT caused by chronic Helicobacter infection?
Triple therapy - PPI e.g. omeprazole, clarithromycin and amoxicillin/metronidazole.
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
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.
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.
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.
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
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
What drugs are used to treat Crohn’s disease?
Mild - prednisolone
Severe - IV hydrocortisone
Metronidazole with or without azathioprine/methotrexate/infliximab
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
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.
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.
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!
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.
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
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.
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.
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.
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.
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
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.
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.
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.
