Histopathology SBAs+EMQs

Question 1

A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 36-year-old man presents to accident and emergency with a 1-day history of a fever of 39.2°C and night sweats. A new heart murmur is detected by the oncall cardiologist. The patient admits to being an intravenous drug user.

Answer 1

B Infective endocarditis Infective endocarditis (IE; B) results from bacterial-vegetation of heart valves. Acute IE has a time course of days and is usually caused by Staphylococcus aureus in intravenous drug users; both sides of the heart can be affected, but the right heart is most commonly affected, because the lungs filter out many organisms, so that the left side of the heart gets less exposure to organisms. Subacute IE has a time course of weeks/months and is generally secondary to Streptococcus viridans infection after dental procedures; only abnormal valves are affected and hence these are more likely to be on the left side of the heart because those valves are more commonly damaged as they are on the high pressure side of the heart. Perforation of the valve leaflets and rupture of papillary muscles may lead to aortic or mitral regurgitation.

Question 2

A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 64-year-old man presents to accident and emergency due to a collapse at home. An ejection systolic murmur is heard at the upper-left sternal edge.

Answer 2

H Aortic stenosis Aortic stenosis (H) occurs when there is an opening defect in the aortic valve. Causes include age-related degenerative calcification, rheumatic heart disease and congenital malformations (bicuspid valve). Calcification is confined to the cusps. Clinical presentation includes syncope, angina and dyspnoea. On examination an ejection systolic murmur, narrow pulse pressure and/or slow rising pulse may be detected. If due to a bicuspid valve an ejection systolic click may be heard. Left ventricular hypertrophy may develop as a consequence of chronic pressure overload.

Question 3

A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A widowed 72-year-old woman who has passed away at home is sent for autopsy due to unknown cause of death. Post-mortem examination reveals a nutmeg liver and haemosiderin-laden macrophages in the lungs.

Answer 3

F Left heart failure Left heart failure (F) results in the inability of the heart to meet the demands of the body. It is either due to increased demand (high output failure) or reduced supply (low output failure) of blood. Causes of high output failure include severe anaemia and hyperthyroidism, while low output failure occurs due to ischaemic heart disease, hypertension and aortic/mitral valve defects. Clinical features include dyspnoea, orthopnoea and paroxysmal nocturnal dyspnoea. Histological findings include dilated ventricles, thin walls, nutmeg liver and haemosiderin macrophages in the lungs.

Question 4

A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 54-year-old man presents to accident and emergency with fever and pleuritic chest pain. It is noted that the patient suffered a myocardial infarction 4 weeks previously.

Answer 4

C Dressler’s syndrome Dressler’s syndrome (C) is an autoimmune complication of myocardial infarction (MI) that occurs approximately 4 weeks after the episode. It is characterized by chest pain, fever and a pericardial rub. The complications of MI can be classified according to how they present temporally. Complications of MI that may occur within 1 week include arrhythmias (most commonly ventricular fibrillation and ventricular tachycardia), myocardial rupture, valve incompetence (causing regurgitation) and cardiogenic shock. Later developments include ventricular aneurysm, pericarditis and the aforementioned Dressler’s syndrome.

Question 5

A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 46-year-old man is referred to the cardiology outpatient clinic. On investigation he is found to have mitral regurgitation and has a past history of St Vitus Dance when he was in school and a mild pericarditis.

Answer 5

E Rheumatic heart disease Rheumatic heart disease (E) is an inflammatory condition most commonly affecting the connective tissue of the heart (but also joints and central nervous system). It occurs several weeks after throat infection with group A β-haemolytic streptococci usually under the age of 10 years. Cardiac complications include endocarditis (causing verroucous lesions of the heart valves); myocarditis (containing Aschkoff-bodies and Anitschow cells causing dilatation of the mitral ring, hence mitral regurgitation); pericarditis (fibrous exudate causing friction rub). Any layer of the heart can be affected, potentially leading to pancarditis. Many years after recovery from acute rheumatic fever, chronic rheumatic heart disease occurs, with fibrosis of the mitral and aortic valves that can occur. The history of St Vitus Dance Suggests Sydenham’s chorea, a well known feature of acute rheumatic fever

Question 6

A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 40-year-old male presents to his GP with chronic cough with copious amounts of purulent mucus production. High resolution CT scans demonstrate dilated bronchi.

Answer 6

D Bronchiectasis Bronchiectasis (D) is defined as the permanent dilatation of bronchi and bronchioles secondary to chronic inflammation. Causes are numerous, and include chronic pneumonia, for example due to Staphylococcus aureus or Haemophilus influenzae infection, obstructing tumours and cystic fibrosis. Histopathological findings include bronchial wall destruction and transmural inflammation. High-resolution computed tomography (CT) is the diagnostic modality of choice. Abscess formation, haemoptysis and pulmonary hypertension are complications that may arise as a result of bronchiectasis.

Question 7

A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 14-year-old girl is admitted to hospital after suffering her third bout of pneumonia caused by Pseudomonas aeruginosa infection. She also has a previous admission for pancreatitis.

Answer 7

H Cystic fibrosis Cystic fibrosis (CF; H) is an autosomal recessive condition caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein that primarily affects the exocrine glands. There are several mutations responsible for CF, the most common being ΔF508 mutation. Defective CFTR causes reduced secretion of chloride ions across epithelial cell membranes, resulting in increased sodium and hence water reabsorption into these cells. The result is viscous secretions from exocrine glands affecting multiple organs including the lungs (recurrent infections and bronchiectasis), gastrointestinal tract (distal intestinal obstruction syndrome) and pancreas (pancreatitis).

Question 8

A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 58-year-old man presents to his GP with haemoptysis and weight loss. He has a 30 pack–year history of smoking. He is referred to the oncologist for a biopsy, who determines ‘oat-shaped’ cells on microscopy.

Answer 8

B Small cell carcinoma Small cell carcinoma (B) is also known as ‘oat-cell’ carcinoma due to the appearance of the malignant cells under the microscope. They appear as nests of small round hyper-chromatic cells that are fragile (chromatin smudging) and possess nuclear moulding. Small cell carcinomas are very aggressive with approximately 80 per cent of cases having metastasized at the time of diagnosis. Small cell carcinomas also express neuroendocrine markers and can cause paraneoplastic syndromes such as Lambert–Eaton myasthenic syndrome. On chest X-rays, the cancer may be seen arising centrally.

Question 9

A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 62-year-old man presents to his GP with shortness of breath, lethargy and weight loss. The patient’s chest X-ray reveals a peripheral focal lesion in the left lung field.

Answer 9

E Non-small cell carcinoma Non-small cell carcinomas (E) comprise adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Adenocarcinomas are gland forming and therefore will have mucin vacuoles within. This sub-type of non-small cell carcinoma may lead to atypical adenohyperplasia whereby atypical cells are seen to line the alveolar walls; hence adenocarcinoma is usually a peripheral lung cancer. Squamous cell carcinomas are histologically characterized by keratinization and intracellular ‘prickle’ desmosomes. Large cell carcinomas are undifferentiated forms of adenocarcinoma or squamous cell carcinoma.

Question 10

A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 53-year-old woman with a history of rheumatic fever presents to accident and emergency with severe shortness of breath, and has been coughing up pink frothy sputum for the past 2 days.

Answer 10

G Pulmonary oedema Pulmonary oedema (G) is defined as fluid collections in the alveoli which impairs gas exchange that can potentially lead to respiratory failure. Increased hydrostatic pressure causes of pulmonary oedema include heart failure, mitral stenosis, fluid overload and renal failure. Increased capillary permeability can also cause pulmonary oedema, for example due to pneumonia. Chest X-rays can distinguish between cardiac and non-cardiac causes of pulmonary oedema; the former will demonstrate alveolar oedema (bat’s wing appearance), Kerley B-lines, cardiomegaly, upper lobe diversion of blood vessels and effusions.

Question 11

A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 35-year-old woman is referred to the rheumatology clinic due to recent onset dysphagia. The patient also reports that her fingers have turned very pale and cold. One examination she is found to have tightening of the skin near her finger tips and small dilated vessels on her skin.

Answer 11

G CREST syndrome CREST syndrome (G), also known as limited scleroderma, represents a combination of conditions: calcinosis (calcium deposition in the skin), Raynaud’s disease (vasospasm of blood vessels in response to triggers such as cold), oesophageal dysmotility, sclerodactyly (thickening and tightening of skin surrounding fingers/hands) and telangiectasia (dilation of blood capillaries causing red marks on the surface of the skin). The pathogenesis relates to excessive release of PDGF causing widespread fibroblast activation and multi-organ fibrosis. Chronic fibrosis leads to initimal thickening of the microvasculature known as ‘onion skinning.’

Question 12

A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 35-year-old woman with a history of recurrent miscarriages presents to her GP with joint pains. Blood tests reveal she is anti-double stranded DNA antibody positive.

Answer 12

A Systemic lupus erythematosus Systemic lupus erythematosus (SLE; A) is a multi-system connective tissue disease that is antinuclear antibody (ANA) positive. The underlying pathology of SLE relates to failure in the regulatory mechanisms of selftolerance. Autoantibodies form against nuclear components such as DNA, RNA and histones. This leads to complement activation and complex formation, which are deposited in organs. Cytology of tissues reveals haematoxylin bodies which are denatured nuclei that are produced when ANA bind to exposed nuclei. LE cells are also visible on microscopy; these are macrophages that have phagocytosed a haematoxylin body.

Question 13

A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 68-year-old man presents to accident and emergency with symptoms suggestive of heart failure. All initial investigations do not determine an underlying cause. However, a tongue biopsy sample gains an apple-green birefringence under polarized light using Congo red stain.

Answer 13

D Amyloidosis Amyloidosis (D) occurs due to the extracellular deposition of fibrillar proteins that accumulate in tissues and organs. Amyloid proteins arise due to dysfunctional folding resulting in non-branching fibrils. Proteins aggregate into insoluble crossed beta-pleated sheet tertiary conformation. Amyloid proteins contain P-component which causes biopsy samples to characteristically gain an apple-green birefringence using polarized light and Congo red stain. Four major amyloid proteins exist: AA, derived from serum amyloid assisted protein and associated with inflammation; AL, derived from IgG light chains and associated with myeloma; αβ2, linked with Alzheimer’s disease; β2 microglobulin, associated with patients undergoing dialysis treatment.

Question 14

A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 45-year-old woman presents to accident and emergency with signs suggestive of renal failure. She is found to be p-ANCA positive.

Answer 14

I Microscopic polyangitis Microscopic polyangitis (I) is a small vessel vasculitis affecting the arterioles, venules and capillaries. The pathology involves a trigger factor such as microorganisms and drugs causing immune complex formation in a previously sensitized host. These immune complexes deposit in small vessels leading to neutrophil-related inflammation. Microscopic polyangitis affects the skin, heart, brain and kidneys. Histopathological features of affected vessels include fibrinoid necrosis that leads to fragmented neutrophilic nuclei within vessel walls. Microscopic polyangitis is associated with p-ANCA.

Question 15

A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 52-year-old man presents to his GP with limb weakness and shortness of breath. A distinctive rash is noted around both eyes as well as plaques on the joints of his hands.

Answer 15

F Dermatomyositis Dermatomyositis (F) is an inflammatory myopathy that involves skeletal and thoracic muscles. Skeletal muscle involvement will lead to proximal muscle fatigue, especially in the hips and shoulders. Thoracic muscle involvement can affect the lungs (dyspnoea), heart (arrhythmia) and oesophagus (dysmotility). There is, however, sparing of the ocular muscles which differentiates dermatomyositis from myasthenia gravis. Dermatomyositis is also defined by a heliotrope rash (violet erythema around the periorbital region) and Gottron papules (violet scaly plaques over hand joints). Muscle inflammation will also cause an increased blood creatine kinase level.

Question 16

A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 54-year-old man is seen in the neurology clinic due to tremor and rigidity. A DAT scan reveals reduced uptake in the substantia nigra.

Answer 16

B Parkinson’s disease Parkinson’s disease (B) is a degenerative disorder associated with basal ganglia dysfunction. Clinical features can be remembered by the mnemonic SMART: shuffling gait, mask-like-face, akinesia, rigidity and tremor. Degeneration of the substantia nigra and locus coeruleus of the basal ganglia leads to reduced production of dopamine. At the microscopic level, inclusion bodies known as Lewy bodies are deposited in the cytoplasm of neurons that are made up of α-synuclein. Parkinson’s disease may be associated with Lewy body dementia.

Question 17

A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 74-year-old man presents to accident and emergency with increasing headache and confusion. The man’s wife suggests her husband may have tripped and fallen 3 days previously.

Answer 17

E Subdural haemorrhage Subdural haemorrhage (E) occurs between the dura and arachnoid due to an acute tear in bridging veins. This tends to occur after a clear history of trauma. Bleeding results in features of raised intracranial pressure. As the bleeding is venous in nature, haematoma development is slow (usually taking 48 hours) and as a result raised intracranial pressure takes time to become apparent. Chronic subdural haemorrhage refers to a re-bleed of a previous bridging vein subdural haemorrhage. Patients will usually present with an altered mental state.

Question 18

A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 45-year-old woman presents to accident and emergency with the worst headache she has ever experienced. She is noted to have polycystic kidney disease.

Answer 18

A Subarachnoid haemorrhage Subarachnoid haemorrhage (A) occurs in the subarachnoid space. Potential causes include a saccular ‘berry’ aneurysm (most commonly occurring at artery bifurcations of the anterior circulation), hypertension, trauma, arteriovenous malformations and coagulation disorders. Clinical features include a severe ‘thunder clap’ headache radiating to the occiput; this may be preceded by a warning bleed causing a sentinel bleed. Subarachnoid haemorrhages are more commonly associated with polycystic kidney disease, coarctation of the aorta and fibromuscular dysplasia.

Question 19

A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 35-year-old woman presents to the neurology clinic with weakness of her left side. On examination she is found to have nystagmus and an intention tremor. The patient complains of blurred vision for the past month.

Answer 19

G Multiple sclerosis Multiple sclerosis (MS; G) is a demyelinating disease of the upper motor system which follows a relapsing and remitting course. Histological features along the central nervous system include active (contain lymphocytes and macrophages) and inactive plaques (reduced nuclei and myelin). Clinical features include optic neuritis, intranuclear opthalmoplegia (disruption of medial longitudinal fasciculus) and cerebellar signs, as well as spasticity and weakness of limbs. Variants of MS include Devic disease (a more aggressive form) and Marburg MS (a fulminant form).

Question 20

A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 42-year-old man who suffers from Down syndrome is brought to see his GP by his carer. The carer describes how the patient has been wandering out of the house with increased frequency as well as becoming uncharacteristically aggressive, especially in the evening.

Answer 20

I Alzheimer’s disease Alzheimer’s disease (I) is a progressive degenerative disease which mainly occurs in patients over the age of 50 years and the condition is most commonly sporadic. In some instances, there may be a genetic component such as the amyloid precursor protein as well as presenelins 1 and 2 mutations associated with Down syndrome. Inheritance of the ε4 allele of apolipoprotein E increases risk of developing Alzheimer’s disease. Histological features include vascular wall deposition of β-amyloid (amyloid angiopathy), neurofibrillary tangles and neuritic plaques.

Question 21

A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 35-year-old man has a 3-week history of bloody stools without mucus with associated weight loss. A biopsy of the gastrointestinal tract reveals non-caseating granulomas with transmural inflammation.

Answer 21

H Crohn’s disease Crohn’s disease (H) is an inflammatory bowel disease which can affect any section of the gastrointestinal system. Characteristics include transmural inflammation (full intestinal wall thickness), skip lesions and fistulae. Biospy of the gastrointestinal wall will reveal non-caseating granulomas in approximately 60 per cent of cases. Complications include thickening of the bowel wall (also known as a ‘rubber hose wall’) which can lead to bowel obstruction. Extra-intestinal manifestations of Crohn’s disease include arthritis, ankylosing spondylosis, stomatitis and uveitis, as well as dermatological lesions (pyoderma gangrenosum and erythema nodosum).

Question 22

A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 24-year-old woman presents to her GP with a 2-week history of diarrhoea, weight loss and fatigue. Biopsy of the gastrointestinal tract reveals villous atrophy with crypt hyperplasia.

Answer 22

D Coeliac disease Coeliac disease (D) is an autoimmune disease that occurs due to gluten sensitivity, specifically gliadin found in wheat, barley and rye. It affects primarily the duodenum and jejunum. CD8+ cells are sensitized to gliadin; they accumulate in the gut and attack enterocytes and as a result villi disappear. As a compensatory mechanism immature enterocytes in the crypts proliferate causing deeper crypts. Therefore, features of gut biopsy samples include intraepithelial lymphocytes, villous atrophy and crypt hyperplasia. Clinical features include steatorrhoea, bloating, weight loss and fatigue (anaemia secondary to malabsorption).

Question 23

A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 54-year-old man presents to his GP with a 2-week history of worsening dysphagia. The patient’s past medical history reveals severe gastro-oesophageal reflux disease. A duodenoscopy suggests metaplastic transformation of the lower oesophageal region.

Answer 23

F Barrett’s oesophagus Barrett’s oesophagus (F) occurs as a result of chronic gastro-oesophageal reflux disease. At the squamo-columnar junction between the lower oesophagus and stomach, squamous epithelial cells usually exist. Acidity causes transformation of squamous epithelial cells to columnar epithelial cells, a metaplastic change. The metaplastic columnar epithelial cells include goblet cells that produce intestinal mucin; hence the process is termed intestinal metaplasia. The major complication of Barrett’s oesophagus is an increased risk of adenocarcinoma of the oesophagus.

Question 24

A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 45-year-old man is referred to the gastroenterology outpatient clinic due to severe epigastric pain and an episode of haematemesis. Further testing reveals he is Helicobacter pylori positive and has a 20 pack–year history of smoking.

Answer 24

I Peptic ulcer disease Peptic ulcer disease (I) can either be duodenal or gastric. Ulcers differ from erosions as they extend to the submucosa (sometimes to the muscularis mucosa) and take weeks to heal, whereas erosions breach the mucosa only and take days to heal. The main causes of peptic ulcers are Helicobacter pylori, NSAIDs, Zollinger–Ellison syndrome and smoking. These factors disrupt the balance between protective (mucus layer and bicarbonate secretion) and damaging (acid and enzymes) elements leading to ulceration.

Question 25

A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 56-year-old man presents to his GP with abdominal pain, weight loss and fatigue. A duodenoscopy allows a biopsy of a gastric lesion to be taken, which demonstrates signet ring cells and linitis plastica.

Answer 25

E Gastric carcinoma Gastric carcinoma (E) is usually a consequence of chronic gastritis and hence Helicobacter pylori is implicated in the pathogenesis. H. pylori causes intestinal metaplasia leading to gastric atrophy which becomes dysplasia and eventually carcinoma. On histology the carcinoma can be ulcer-like, but differs from peptic ulcers as they have irregular borders and raised edges. Features of gastric carcinoma are the presence of signet ring cells (cells with compressed nuclei) and linitis plastica (the stomach becomes thick and rigid resembling a leather bottle).

Question 26

A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 56-year-old man with previous history of hepatitis C infection presents to accident and emergency with jaundice. His wife notes that he has recently been bruising very easily. Ultrasound of the patient’s liver reveals irregular echogenicity demonstrating nodules.

Answer 26

B Cirrhosis Cirrhosis (B) is defined as the diffuse fibrosis of the liver with abnormal architecture characterized by nodules secondary to chronic hepatic disease. This can be sub-classified as macronodular (3 mm; usually viral aetiology). Fibrosis results from stellate cell activation, which deposit collagen. Nodules represent proliferating hepatocytes that lack normal acinar structure and hence have a haphazard blood supply; this leads to shunt formation and portal hypertension. Causes of cirrhosis include alcohol, hepatitis B and C, primary biliary cirrhosis, haemochromatosis, Wilson’s disease and α1-antitrypsin deficiency.

Question 27

A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 35-year-old man presents to his GP with his mother with signs of Parkinsonism (tremor, rigidity and slow movement) as well as recent changes in his behaviour.

Answer 27

I Wilson’s disease Wilson’s disease (I) is an autosomal recessive condition that results from a mutation in the ATP7B gene leading to multi-organ copper accumulation. ATP7B is a protein that facilitates the transport of copper across cell membranes. Liver involvement will lead to cirrhosis, most commonly in children, whilst accumulation in the brain can lead to Parkinsonism, seizures and dementia. Psychological features include behavioural changes, depression and psychosis. Other organs affected include the eyes (Kayser–Fleischer rings), kidneys (renal tubular acidosis) and heart (cardiomyopathy).

Question 28

A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 56-year-old woman is investigated by the hepatology team for decompensated liver disease. A liver biopsy sample stains blue with Perl’s Prussian blue stain.

Answer 28

F Haemochromatosis Haemochromatosis (F) is an autosomal recessive condition that is due to a mutation in the HFE gene. The HFE protein regulates iron absorption that is stored as haemosiderin. Histological features of haemochromatosis include a golden-brown haemosiderin deposition in the parenchyma of many organs. Haemosiderin eventually leads to inflammation and subsequent fibrosis. Histological samples of affected tissue will stain blue with Perl’s Prussian blue. Organs affected include the liver (cirrhosis), pancreas (diabetes), skin (bronzed pigmentation), heart (cardiomyopathy) and gonads (atrophy and impotence).

Question 29

A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 53-year-old man who has recently emigrated from sub-Saharan Africa is referred to the hepatology department due to recent onset weight loss, jaundice and ascites. There is history of previous aflatoxin exposure.

Answer 29

G Hepatocellular carcinoma Hepatocellular carcinoma (HCC; G) is the most prevalent primary liver malignancy. Most commonly HCC occurs secondary to cirrhosis. The risk factors for HCC are therefore the numerous causes of cirrhosis. However, carcinogens such as aflatoxin, produced by the fungal genus Aspergillus can directly cause HCC; aflatoxin contaminates many crops in the developing world, notably cereals and nuts. α-Fetoprotein is a marker that may suggest the presence of HCC. There is also evidence that the metabolic syndrome contributes to risk of developing HCC.

Question 30

A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 45-year-old woman presents to accident and emergency with jaundice and pruritis. Xanthelasma are noted on examination. The patient is found to be antimitochondrial antibody positive.

Answer 30

E Primary biliary cirrhosis Primary biliary cirrhosis (PBC; E) is an autoimmune disease of the liver, affecting the small and medium-sized intra-hepatic ducts. The primary histological feature is the dense accumulation of lymphocytes around bile ducts creating granulomas and total destruction of the ducts. This results in an obstructive cholestasis causing the triad of jaundice, xanthelasma (cholesterol is normally excreted in bile) and pruritis. Biochemically PBC is linked with anti-mitochondrial antibodies, as well as raised ALP, GGT, IgM and cholesterol. PBC is also strongly associated with Sjögren’s syndrome.

Question 31

A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 65-year-old man presents to his GP with blisters along his left arm that are about 1.0 cm in diameter. Gentle rubbing of the affected area does not lead to skin exfoliation.

Answer 31

A Pemphigoid Pemphigoid (A) is an autoimmune deep bullous (blisters \>0.5 cm) condition that occurs in the elderly. Bullae are fluid filled and therefore do not rupture easily; pemphigoid is Nikolsky sign negative. The underlying pathology involves IgG binding to hemi-desmosomes. This causes activation of eosinophils that are recruited to the area. Pemphigoid should not be confused with pemphigus (option J), also an autoimmune bullous disease that affects middle-aged patients, causing superficial bullae on the skin (Nikolsky positive). IgG bind to desmosomes in the intra-epidermal region resulting in acantholysis.

Question 32

A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 38-year-old man on the respiratory ward has been diagnosed with Mycoplasma pneumoniae and develops a number of target shaped rashes on his body.

Answer 32

H Erythema multiforme Erythema multiforme (H) is a hypersensitivity reaction secondary to infections (herpes simplex, mycoplasmas and fungi) and drugs (penicillin, phenytoin and barbiturates). The pathogenesis is unclear but is thought to be due to immune-complex deposition in the microvasculature of the skin and oral mucous membranes. Most commonly the rash is self-limiting and target shaped as well as being maculo-papular with sub-epidermal bullae in the centre. In severe cases, the rash may involve mucosal surfaces leading to Steven–Johnson’s syndrome, characterized by epidermal necrosis with minimal inflammatory cell infiltrate.

Question 33

A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 45-year-old woman presents to her GP with salmon-pink plaques with a silver– white scale on the extensor surfaces of her elbows.

Answer 33

F Psoriasis Psoriasis (F) is an autoimmune condition primarily affecting the extensor surfaces of the skin. Histological features include parakeratosis (corneum nuclei mixed with keratin to form a thick keratin layer creating ‘silvery scales’); Munro-abscesses (white blood cells entering the corneum); loss of the granular layer leading to pin-point bleeding (Auspitz sign); clubbing of the rete ridges, whereby they grow downwards leading to a ‘test-tubes in a rack’ appearance. Clinical features include salmon-pink plaques with a silver–white scale on the skin and onycholysis.

Question 34

A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 54-year-old man is referred to the dermatologist with a brown warty lesion on his nose which has a rough consistency. Biopsy of the lesion reveals solar elastosis.

Answer 34

E Actinic keratosis Actinic keratosis (solar keratosis; E) is defined as epidermal dysplasia that occurs secondary to sunlight and presents as a brown–red warty lesion with a sandpaper-like consistency. Histological features include solar elastosis, focal parakeratosis, atypical cells and inflammatory cell infiltrates. Actinic keratosis does not affect the full thickness of the epidermis. It is a premalignant condition that may progress to squamous cell carcinoma in approximately 20 per cent of cases.

Question 35

A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 59-year-old woman presents to her dermatologist with a 3 cm black irregular lesion on her cheek. Over the next month the lesion spreads to cover 6 cm with new onset pain.

Answer 35

I Malignant melanoma Malignant melanoma (I) is a malignant tumour of melanocytes. The characteristic features can be remembered by the mnemonic ABCDE: asymmetry, border irregularity, colour (usually black; sometimes demonstrate colours of the French flag), diameter \>5 cm and evolution (change in size, colour and/or new onset itchiness/pain). Malignant melanomas initially grow radially in situ within the epidermis; over time there is growth vertically into the dermis, eventually leading to metastases. Sub-types include lentigomaligna (LM), acrallentigious (AL), superficial spreading (SS) and nodular (N).

Question 36

A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 45-year-old man presents to accident and emergency with haematuria and admits to passing less urine than previously. He is found to be hypertensive. Microscopy of the patient’s urine reveals red and white cell casts.

Answer 36

A Nephritic syndrome Nephritic syndrome (A) involves the following: haematuria, red cell and white cell casts, dysmorphic red cells, oliguria and hypertension. The pathogenesis begins with inflammation of glomerular vessels allowing red blood cells to enter the renal tubule; as they enter they are damaged. The body compensates for the inflammation by slowing renal blood flow causing oliguria, which leads to water retention and hence hypertension. Cellular casts form as a result of Tamm–Horsefall secretions in the distal collecting duct and collecting duct that ‘glue’ cells together, hence forming a cast.

Question 37

A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 42-year-old man presents to accident and emergency with an episode of haemoptysis and haematuria. Blood tests reveal he is in acute renal failure. Once the patient is stable a renal biopsy demonstrates a crescent morphology on immunofluorescence.

Answer 37

F Goodpasture’s syndrome Goodpasture’s syndrome (F) is an anti-glomerular basement membrane disease that causes rapidly progressive glomerulonephritis (RPGN). RPGN all demonstrate a crescent sign on biopsy, which represents the proliferation of macrophages and parietal cells in the Bowman’s space. There are numerous causes of RPGN; these can be differentiated by looking at the IgG and C3 deposition pattern on immunofluorescence. Goodpasture’s syndrome occurs due to IgG against the A3 chain of type-4 collagen, creating a linear pattern on immunofluorescence.

Question 38

A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 64-year-old man on the Care of the Elderly ward is found to be in acute renal failure secondary to statin-related rhabdomyolysis. Urinalysis reveals the presence of ‘muddy’ casts.

Answer 38

D Acute tubular necrosis Acute tubular necrosis (D) is defined as damage to the tubular epithelium leading to acute renal failure. Ischaemic or toxic injury reduces GFR in three ways: 1) Loss of polarity (loss of membrane channels reduces sodium reabsorption; more sodium reaches macula densa constricting afferent arteriole, hence reducing GFR); 2) Glomerular backpressure (formation of casts in distal convoluted tubule creates backpressure reducing GFR); and 3) Interstitial leakage (back-pressure forces fluid into interstitium causing swelling and compression of tubules).

Question 39

A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis An 8-year-old girl presents to accident and emergency with frank haematuria. Her parents state that she had just recovered from a throat infection 2 days previously.

Answer 39

G IgA nephropathy IgA nephropathy (Berger’s disease; G) usually occurs 1–4 days after a respiratory or gastrointestinal infection (mucosal defence is primarily IgA). IgA is deposited in the mesangium which may lead to RPGN. On immunofluorescence a granular staining of IgG and C3 will demonstrate IgA nephropathy (other conditions causing this pattern are SLE, Henoch–Schlönein purpura, post-streptococcal infection and Alport’s syndrome). There is frank haematuria in 50 per cent of cases and microscopic haematuria in 50 per cent of patients.

Question 40

A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 62-year-old woman on the Care of the Elderly ward is found to have new onset ankle swelling. A urine dipstick demonstrates proteinuria

Answer 40

H Nephrotic syndrome Nephrotic syndrome (H) is the combination of proteinuria, hypoalbuminaemia and oedema (with associated hyperlipidaemia and lipiduria). Primary causes such as IgA nephropathy are most common in children, whereas systemic causes such as diabetes and SLE are more common in adults. Damage to the glomerulus causes increased permeability and hence proteins pass into the tubules leading to proteinuria and hypoalbuminaemia. A reduced oncotic pressure therefore causes oedema. The liver compensates by producing increased amounts of lipids which are then excreted via the damaged kidneys causing lipiduria.

Question 41

A Mastitis B Phylloides tumour C Fibroadenoma D Duct ectasia E Ductal carcinoma in situ F Gynaecomastia G Fibrocystic disease H Fat necrosis I Infiltrating ductal carcinoma A 55-year-old parous woman presents to her GP with a 2-week history of green discharge from her right nipple.

Answer 41

D Duct ectasia Duct ectasia (D) is defined as the chronic ductal inflammation due to acini secretions that become clogged in the ducts causing them to dilate and rupture. This leads to a green/white discharge being produced. Duct ectasia occurs in women older than 40 who have had children. It is an important diagnosis to make as it mimics breast cancer; the presentation may be nipple retraction due to fibrosis and bloody discharge secondary to rupture of the ducts.

Question 42

A Mastitis B Phylloides tumour C Fibroadenoma D Duct ectasia E Ductal carcinoma in situ F Gynaecomastia G Fibrocystic disease H Fat necrosis I Infiltrating ductal carcinoma A 35-year-old woman presents to her GP with a soft 3 cm mobile mass in her left breast. The patient suggests the size of the lump fluctuates with her menstrual cycle.

Answer 42

C Fibroadenoma Fibroadenoma (C) is the most common benign breast tumour. Fibroadenomas arise from stroma as well as lobules and hence are mixed tumours. They characteristically grow rapidly in pregnancy and during the menstrual cycle as lobules are oestrogen driven; conversely, fibroadenomas regress at menopause due to the lack of oestrogen. On examination, fibroadenomas are very mobile (sometimes known as a breast mouse), well circumscribed, discrete and usually less than 5 cm. They tend to be soft in a young female and firm in elderly women (as stroma becomes more fibrous).

Question 43

A Mastitis B Phylloides tumour C Fibroadenoma D Duct ectasia E Ductal carcinoma in situ F Gynaecomastia G Fibrocystic disease H Fat necrosis I Infiltrating ductal carcinoma A 54-year-old woman presents to her GP with a single lump in her left breast. A mammogram reveals a focal area of calcification.

Answer 43

E Ductal carcinoma in situ Ductal carcinomas in situ (DCIS; E) occur in pre- or post-menopausal women. They are usually unilateral and unifocal. On mammogram, microcalcification may be visible secondary to central necrosis. Microscopic features include the presence of central necrosis and pleomorphic nuclei. In contrast, lobular carcinoma in situ (LCIS) usually occurs mainly in pre-menopausal women and is bilateral and multifocal. No calcification occurs and hence there is no detection on mammogram. Histologically there is no necrosis and uniform nuclei are present.

Question 44

A Mastitis B Phylloides tumour C Fibroadenoma D Duct ectasia E Ductal carcinoma in situ F Gynaecomastia G Fibrocystic disease H Fat necrosis I Infiltrating ductal carcinoma A 60-year-old woman presents to her GP with a 5.5 cm mobile lump in her right breast. Biopsy reveals an ‘artichoke-like’ appearance.

Answer 44

B Phylloides tumour Phylloides tumours (B) are similar to fibroadenomas as they are mixed; they arise from stroma and duct epithelium. They are also similar to fibroadenomas as they are discrete, well-circumscribed and mobile. They differ in that they are usually greater than 5 cm, occur in women over the age of 40 years and can be malignant. Histological investigation reveals an ‘artichoke-like’ appearance as the stroma pushes up on the epithelium to form clubs.

Question 45

A Mastitis B Phylloides tumour C Fibroadenoma D Duct ectasia E Ductal carcinoma in situ F Gynaecomastia G Fibrocystic disease H Fat necrosis I Infiltrating ductal carcinoma A 58-year-old woman presents to her GP with a painful lump in her right breast. On examination there is also evidence of peau d’orange.

Answer 45

I Infiltrating ductal carcinoma Infiltrating ductal carcinoma (IDC; I) is an invasive cancer and therefore penetrates the basement membrane. IDC is also called no special type and usually results from DCIS. Macroscopically IDC has a scirrhous look whereby the centre is very fibrous giving a dense white appearance. IDC has the worst prognosis compared to all other invasive carcinomas (medullary, mucinous, tubular and papillary carcinoma). Features of invasive carcinoma also include peau d’orange, Paget’s disease of the breast, tethering, nipple retraction, lymphadenopathy, ulceration of the mass and pain.

Question 46

A Osteoporosis B Fibrous dysplasia C Paget’s disease D Osteomalacia E Osteochondroma F Osteoid osteoma G Renal osteodytrophy H Enchondroma I Giant cell tumour A 35-year-old man with pain and difficulty bending his left knee. X-ray reveals many lytic lesions in the epiphysis of the patient’s left knee.

Answer 46

I Giant cell tumour Giant cell tumour (GCT; I) is a borderline malignant tumour of giant osteoclast cells. The cells are similar to those found in Paget’s disease as they have multiple nuclei (\>20). The osteoclastic cells cause lytic lesions in the epiphyses (especially around the knee) that are visible on X-ray and may give a characteristic ‘soap bubble’ appearance. Histological features include multinucleated giant osteoclasts with surrounding ovoid and spindle cells.

Question 47

A Osteoporosis B Fibrous dysplasia C Paget’s disease D Osteomalacia E Osteochondroma F Osteoid osteoma G Renal osteodytrophy H Enchondroma I Giant cell tumour A 38-year-old woman presents to her GP with generalized bone pain. X-ray reveals areas of pseudofracture, especially in the ribs.

Answer 47

D Osteomalacia Osteomalacia (D) is defined as the insufficient mineralization of bone due to vitamin D deficiency. Reduced intake, malabsorptive conditions, phenytoin and chronic liver disease can cause vitamin D deficiency. A low vitamin D level causes hypocalcaemia resulting in increased PTH release (normalizing calcium). PTH stimulates osteoclastic activity causing bones to be soft and epiphyses to widen. Clinical features include craniotabes, bone pain, proximal weakness and pseudo-fractures (looser zones). Craniotabes is the descriptive term for the soft and elastic occipitoparietal bones causing an elastic recoil sensation when pushed.

Question 48

A Osteoporosis B Fibrous dysplasia C Paget’s disease D Osteomalacia E Osteochondroma F Osteoid osteoma G Renal osteodytrophy H Enchondroma I Giant cell tumour A 65-year-old woman is referred to the rheumatologist after suffering recurrent falls. Blood tests are all unremarkable but a DEXA scan reveals a T-score of 2.8.

Answer 48

A Osteoporosis Osteoporosis (A) is defined by reduced bone density (reduced quantity) but normal quality. Reduced circulating oestrogen concentration causes IL-1 and IL-6 levels to rise causing osteoclastic activity. Osteoporosis primarily affects the vertebrae and hips. Primary osteoporosis occurs in post-menopausal women. Secondary causes include lifestyle choices (smoking, alcohol, inactivity), drugs (steroid, goserelin), low BMI as well as thyroid and parathyroid disease. Diagnosis is made using a DEXA scan; a T-score of

Question 49

A Osteoporosis B Fibrous dysplasia C Paget’s disease D Osteomalacia E Osteochondroma F Osteoid osteoma G Renal osteodytrophy H Enchondroma I Giant cell tumour An 8-year-old boy has been diagnosed with precocious puberty. A routine examination by the paediatrician reveals café-au-lait spots on the child’s back. The boy has had numerous fractures of his femur and tibia bilaterally after falls.

Answer 49

B Fibrous dysplasia Fibrous dysplasia (B) occurs due to the developmental arrest of normal bone structures secondary to an osteoblast maturation defect. The most common sites affected are the proximal femur and ribs. On X-ray, fibrous dysplasia may cause a ground-glass or soap bubble appearance. Histological investigation reveals trabeculae that lack osteoblastic rimming. Two possible syndromes can arise: 1) Mono-ostotic (70 per cent) affecting femurs more than ribs occurring in patients under 30 years of age, and 2) McCune–Albright syndrome (30 per cent) that is poly-ostotic and causes café-au-lait spots and precocious puberty.

Question 50

A Osteoporosis B Fibrous dysplasia C Paget’s disease D Osteomalacia E Osteochondroma F Osteoid osteoma G Renal osteodytrophy H Enchondroma I Giant cell tumour A 50-year-old man presents to his GP with pain in his arms and legs. The patient also complains of shooting pains down his left leg as well as worsening shortness of breath.

Answer 50

C Paget’s disease Paget’s disease (C) is a disease of bone remodelling whereby new bone is larger but weaker and prone to fracture. During the initial lytic phase giant osteoclasts with multiple nuclei rapidly resorb bone. In the mixed phase, osteoblast activity leads to increased bone mass. In the final osteosclerotic phase, bone formation continues but is woven and weak, with collagen arranged haphazardly resulting in a mosaic pattern. Complications can arise from deformities that cause impingement of nerves. Bone marrow infiltration of weak woven bone can lead to high output heart failure.

Question 51

A 65-year-old patient with advanced breast malignancy and a history of multiple systemic emboli suffers a stroke. On examination, there are no cardiac murmurs but an echocardiogram reveals small bland vegetations on the mitral valve. Blood cultures are negative. What is the most likely diagnosis? A Infective endocarditis B Acute rheumatic fever C Non-bacterial thrombotic endocarditis D Chronic rheumatic valvular disease E Libman–Sacks endocarditis

Answer 51

C Non-bacterial thrombotic endocarditis Non-bacterial thrombotic endocarditis (NBTE; C) commonly affects patients over 40 years of age and is often characterized by the absence of inflammation or bacteria. Sterile fibrin and platelet vegetations are present on cardiac valves, more commonly affecting left-sided heart valves (mitral \> aortic) and are also associated with numerous diseases, especially advanced stage malignancy. NBTE is a source of thromboembolism to the brain, heart, kidneys, and recurrent emboli are a hallmark feature.

Question 52

A 41-year-old man presents with severe central chest pain which he describes as ‘tearing’ in nature and radiating to the back. He is tall, with long limbs and long thin fingers. He also has an aortic regurgitation murmur. Histologically there is cystic medial necrosis in the aortic wall. In which syndrome are these findings most likely? A Ortner’s syndrome B Ehlers–Danlos syndrome C Down syndrome D Turner syndrome E Marfan syndrome

Answer 52

E Marfan syndrome Cystic medial necrosis is a disorder particularly affecting the aorta, causing focal degeneration of the elastic tissue and muscle fibres in the media, with accumulation of basophilic ground substance. This leads to cyst-like pools between the fibres disrupting the normally parallel arrays. Clinically, aneurysm formation becomes more likely. It is more frequent after 40 years of age and is twice as common in males. There is evidence that links cystic medial necrosis to aortic dissection in patients with a variety of syndromes, the most common of which is Marfan’s syndrome (E). These patients are characteristically tall with long limbs and long thin fingers

Question 53

A 57-year-old overweight patient suffers an acute myocardial infarction and subsequently dies. A post-morterm examination of the infarcted area shows extensive cell infiltration including polymorphs and macrophages. There is also extensive debris post necrosis and the cytoplasm is homogeneous making it difficult to see the outlines of the myocardial fibres. There is no evidence of collagenization or a scar. How long after the initial attack did the patient die? A At the time of the attack (0–6 hours) B Hours after the attack (6–24 hours) C Days after the attack (1–4 days) D Within the first 2 weeks of the attack (4–14 days) E Weeks and months after (14 days +)

Answer 53

C Days after the attack (1–4 days) At 1–4 days (C) following an acute MI, the start of an extensive acute inflammatory response takes place with cell infiltration. Debris is left by the necrosis in the previous stage and the cytoplasm is homogeneous so that it is difficult to see the outlines of the myocardial fibres. Infiltration of polymorphs, and later macrophages, takes place. Removal of the debris takes place at about 5–10 days.

Question 54

A 35-year-old woman presents to accident and emergency with nausea, severe malaise, swelling and stiffness of the fingers. On examination, her blood pressure is 155/95 mmHg and she has Raynaud’s phenomenon. Blood tests reveal positive anti-topoisomerase antibodies and deranged serum creatinine and urea. A biopsy result of her small arteries reveals an onion skin appearance. What is the most likely diagnosis? A Systemic lupus erythematosus B Diffuse scleroderma C Kawasaki’s disease D Polyarteritis nodosa E Limited scleroderma/CREST

Answer 54

B Diffuse scleroderma Scleroderma exists as limited and diffuse forms. This patient has internal involvement with the evidence of renal failure, which is consistent with diffuse scleroderma (B), which is a rapidly progressing condition that affects a large area of skin and one or more internal organs such as the kidneys, oesophagus and heart.

Question 55

A 46-year-old woman presents with gradual muscle weakness in her neck and upper arms over the past 3 weeks. She is also said to have a purple ‘heliotrope’ rash on her upper eyelids, an erythematous scaling rash on her face and red patches on the knees. She has also experienced some weight loss. Blood tests reveal elevated skeletal muscle enzymes but electromyogram results were negative. What is the most likely diagnosis? A Polymyositis B Henoch–Schönlein purpura C Dermatomyositis D Kawasaki disease E Sarcoidosis

Answer 55

C Dermatomyositis Dermatomyositis (C) has the muscle components involved in polymyositis but in addition it is accompanied by periorbital oedema and a characteristic purple ‘heliotrope’ rash on the upper eyelids. Heliotrope is a pink/ purple colour that one only hears about in reference to dermatomyositis, but is actually the colour of the heliotrope flaver. It is also commonly present with an erythematous, scaling rash on the face, shoulders, upper arms and chest, with red patches over the knuckles, elbows and knees. Weight loss and arthralgia may also present

Question 56

A 43-year-old man presents with a rest tremor, slowness of voluntary movement and rigidity. It is reported that he has a mutation of the alpha-synuclein protein and he is free of Lewy bodies on histological examination. What is the most likely diagnosis? A Familial Parkinson’s disease B Alzheimer’s disease C Multiple system atrophy D Multiple sclerosis E Idiopathic Parkinson’s disease

Answer 56

A Familial Parkinson’s disease The alpha-synuclein protein is a major component of Lewy bodies. Its true function is unknown but its accumulation has a toxic effect on plasma membranes. In the rare cases of familial forms of Parkinson’s disease (A), there is a mutation in the gene coding for alpha-synuclein and this condition is free of Lewy bodies. Patients with these mutations have a worse prognosis with earlier onset and non-responsiveness to levodopa.

Question 57

The activity of the plaques in a 25-year-old multiple sclerosis patient is described with the presence of oedema and macrophages, and some myelin breakdown. Which ICDNS (International Classification of Diseases of the Nervous System) plaque type classification best fits the description? A Acute plaque B Early chronic active plaque C Late chronic active plaque D Chronic inactive plaque E Shadow plaque

Answer 57

B Early chronic active plaque Early chronic active plaque (B): Oedema and macrophages, indicative of an inflammatory disorder of the central nervous system, with some myelin breakdown. Reactive astrocytosis is present

Question 58

A 72-year-old woman is diagnosed with a disease that accounts for 50–75 per cent of all cases of dementia. The four characteristic pathological features for her diagnosis are severe brain atrophy, loss of neurons, senile plaques and neurofibllirary tangles. What is the most likely diagnosis? A Huntington’s disease B Alzheimer’s disease C Multiple system atrophy D Dementia with Lewy bodies E Parkinson’s disease

Answer 58

B Alzheimer’s disease Alzheimer’s disease (AD) (B) accounts for 50–75 per cent of all cases of dementia in Western countries. Dementia is the progressive loss of cognitive function due to degeneration of the cerebral cortex. There is severe brain atrophy particularly prominent in the hippocampus and the frontal lobes and the brain weight is reduced to 1000 grams or less (normal average being 1400 grams). Histological hallmarks of the disease include senile plaques, which are complex spherical structures involving the grey matter and the aggregation of beta-amyloid appears to play a central role in developing the senile plaques. Neurofibrillary tangles are abnormal tangles in neuronal cell bodies of insoluble cytoskeletal-like tau protein. It is believed that the major antigenic component is the phosphorylated tau.

Question 59

A 32-year-old man has a past medical history of severe gastro-oesophageal reflux disease. His most recent oesophageal biopsy shows a columnar epithelium with goblet cells suggestive of a diagnosis of Barrett’s oesophagus. What form of cell change is this also known as? A Anaplasia B Hyperplasia C Metaplasia D Dysplasia E Neoplasia

Answer 59

C Metaplasia The normal oesophagus is lined by stratified squamous epithelium and the squamo-columnar junction lies 2 cm above the gastro-oesophageal junction and is recognized by an irregular white line known as the Z line. Barrett’s oesophagus occurs due to long standing reflux, and is the re-epithelialization by metaplastic columnar epithelium with goblet cells replacing normal squamous epithelium. This is known as metaplasia (C), which is the conversion from one type of differentiated tissue to another. It is reversible and often represents an adaptive response to environmental stress. Surveillance is crucial with repeated biopsy to detect a potential adenocarcinoma early, which is becoming more common than squamous cell carcinomas.

Question 60

A 38-year-old man is a known gastritis patient. The most recent endoscopy and biopsy has detected that the area most severely affected is the pyloric antrum. He also has susceptibility for developing a gastric MALT lymphoma in the future. What is the most likely diagnosis? A Menetrier’s disease (hyperplastic hypersecretory gastropathy) B Acute gastritis C Helicobacter-associated chronic gastritis D Autoimmune chronic gastritis E Reactive/reflux chronic gastritis

Answer 60

C Helicobacter-associated chronic gastritis Helicobacter pylori-associated gastritis (C) is the most common form of chronic gastritis, accounting for 90 per cent of cases, and it is known that the pyloric antrum is the most severely affected area. An immune response is established and the infection may potentially persist for years. Around three-quarters of MALT (mucosa-associated lymphoid tissue) lymphoma or MALToma cases are associated with H. pylori infection. MALT is a system of small lymphoid tissue that regulates mucosal immunity and is present in a variety of organs in the body.

Question 61

A 50-year-old known alcoholic man has persistent severe epigastric pain radiating to the back and has experienced weight loss of 5 kg in 2 months. On initial presentation, the patient is not jaundiced. On contrast enhanced CT scan there are multiple calcific densities along the line of the main pancreatic duct. On histological examination, there is evidence of parenchymal fibrosis and large ducts containing insipissated secretions. What is the most likely diagnosis? A Chronic pancreatitis B Carcinoma in the head of the pancreas C Diabetes mellitus type 2 D Acute pancreatitis E Pseudocysts

Answer 61

A Chronic pancreatitis Chronic pancreatitis (A) causes irreversible loss of function. Histology shows chronic inflammation with parenchymal fibrosis, loss of pancreatic parenchymal elements and duct strictures with formation of intrapancreatic calculi. Jaundice may occur; it is a presenting feature in only a small proportion of patients and would be secondary to common bile duct obstruction during its course through the fibrosed head of the pancreas. Grossly, the pancreas is replaced by firm fibrous tissue within which are dilated ducts and areas of calcification

Question 62

A 22-year-old man presents with polyuria and polydipsia. His fasting plasma glucose is 7.3 mmol/L. He is Glutamic Acid Decarboxylase (GAD) antibody positive. What is the most likely diagnosis? A Diabetes mellitus type 1 B Diabetes insipidus C Psychogenic polydipsia D Diabetes mellitus type 2 E Zollinger–Ellison syndrome

Answer 62

A Diabetes mellitus type 1 Diabetes mellitus type (1) (A) is an autoimmune disorder of childhood/ adolescent onset that is characterized by antibody-mediated destruction of beta-cells of the islets of Langerhans. Ninety to ninety-five per cent of patients are HLA DR3 and HLA DR4 positive. Type 1 diabetes can present with polyuria as in this case, or, if the polyuria is ignored, with diabetic ketoacidosis. The peak incidence of type 1 diabetes is 12–14 years, so the patient being young also makes this type 1 diabetes

Question 63

A 37-year-old man, while abroad, was involved in a road traffic accident and required a blood transfusion. He had an episode of acute hepatitis with the contraction of a DNA virus of the Hepadna group. There is a small chance this may progress to chronic hepatitis. What is the most likely viral hepatitis type? A Hepatitis A B Hepatitis B C Hepatitis C D Hepatitis D E Hepatitis E

Answer 63

B Hepatitis B Hepatitis B (B) is a DNA virus of the Hepadna group. Transmission is commonly blood-borne but these can also be sexual and vertical transmission from mother to child. Most commonly, the infection can be asymptomatic with complete recovery, but also patients can develop acute or chronic hepatitis B infection. These patients always have a risk of developing chronic hepatitis. Hepatitis A (A) infection never causes chronic hepatitis.

Question 64

A 42-year-old woman, who has a history of joint and skin symptoms, presents with jaundice. Anti-mitochondrial antibodies are present and histologically there is evidence of a progressive, chronic granulomatous inflammation of the bile duct. What is the most likely diagnosis? A Primary sclerosing cholangitis B Autoimmune hepatitis C Primary biliary cirrhosis D α-1 Antitrypsin deficiency E Alcoholic liver disease

Answer 64

C Primary biliary cirrhosis Primary biliary cirrhosis (C) is the destruction of the intrahepatic bile duct, often associated with an immune component, with anti-mitochondrial antibodies present in 90 per cent of cases and associations with other autoimmune diseases such as rheumatoid arthritis or scleroderma. Primary sclerosing cholangitis (A) also presents with obstructive jaundice and probably has an autoimmune element to it, but is very unlikely to show any autoantibodies. Sixty per cent of cases are associated with ulcerative colitis.

Question 65

A 23-year-old patient has an autosomal recessive disorder. The patient has demonstrated parkinsonian symptoms such as a hand tremor and has developed chronic hepatitis. On examination, he is found to have Kayser–Fleischer rings. Blood levels of serum ceruloplasmin are low. What is the most likely diagnosis? A Wilson’s disease B Genetic haemochromatosis C α-1 Antitrypsin deficiency D Reye’s syndrome E Budd–Chiari syndrome

Answer 65

A Wilson’s disease Wilson’s disease (A) is an autosomal recessive metabolic disorder that is caused by a mutation in the copper transport ATPase gene on chromosome 13. It results in failure of the liver to secrete the copper–ceruloplasmin complex into the plasma. This creates an overspill of copper into the blood that typically causes liver disease, central nervous system disease resembling Parkinson’s disease and the characteristic development of brown discolouration around the cornea (Kayser–Fleischer rings).

Question 66

An 8-year-old Down syndrome boy presents with constipation, distended abdomen, vomiting and overflow diarrhoea. The cause is believed to be absence of ganglion cells in the myenteric plexus causing the failure of the dilation of the distal colon. What is the most likely diagnosis? A Stenosis B Hirschsprung’s disease C Atresia D Intussusception E Volvulus

Answer 66

B Hirschsprung’s disease Congenital aganglionic megacolon, also known as Hirschsprung’s disease (B), is believed to be due to the absence of ganglion cells in the myenteric plexus causing the failure of the dilation of the distal colon. Macroscopically, there is narrowing of an abnormally innervated bowel segment yet dilation and muscular hypertrophy of the bowel segment proximal to this. Microscopically, there is an absence of normal myenteric and submucosal plexus ganglion cells. The condition often presents in early childhood with symptoms of colonic obstruction. There has been a reported association of this condition with Down syndrome.

Question 67

A 25-year-old white man is experiencing bloody diarrhoea and mucous discharge. Macroscopic analysis shows abnormality in the colon and rectum only and is continuous with a normal bowel wall thickness. The pattern of inflammation is confined to the mucosa of the bowel wall and no evidence of granulomas exists. What is the most likely diagnosis? A Crohn’s disease B Ulcerative colitis C Ischaemic colitis D Pseudomembranous colitis E Viral gastroenteritis

Answer 67

B Ulcerative colitis Ulcerative colitis (B) is inflammation affecting the rectum and colon only in a contiguous fashion. There are many extra-intestinal manifestations including arthritis, myositis, uveitis/iritis, erythema nodosum, pyoderma gangrenosum and primary sclerosing cholangitis

Question 68

A 39-year-old man is diagnosed with a colon cancer proximal to the splenic flexure that is poorly differentiated and highly aggressive. There are no associated adenomata. It is an autosomal dominant condition that involves gene mutations of DNA mismatch repair genes. What is the most likely diagnosis? A Familial adenomatous polyposis B Gardner’s syndrome C Colorectal carcinoma D Hereditary non-polyposis colorectal cancer E Hamartomatous polyps

Answer 68

D Hereditary non-polyposis colorectal cancer Hereditary non-polyposis colorectal cancer (HNPCC) (D) is an uncommon autosomal dominant disease but the cancers are poorly differentiated and highly aggressive, therefore screening for identification of carriers for surveillance is necessary.

Question 69

A 25-year-old woman presents to clinic with an inability to conceive and a past history of Chlamydia trachomatis infection. On ultrasonography, she is diagnosed with hydrosalpinx. Hydrosalpinx is the most likely complication of which of the below options? A Endometriosis B Adenomyosis C Cervical intraepithelial neoplasia D Salpingitis E Human papillomavirus

Answer 69

D Salpingitis Salpingitis (pelvic inflammatory disease; D) is inflammation of the fallopian tubes that is almost always caused by infection, in particular sexually transmitted infections including chlamydia, mycoplasma and gonococcus. Other related infections, such as an actinomyces infection, are associated with intrauterine contraceptive device use. Hydrosalpinx, a complication of salpingitis, is the dilation of the fallopian tube that is thin-walled and contains clear fluid. This is believed to be a sequel to previous inflammatory damage to the tube. The scarring sequelae are believed to include plical fusion, adhesions to the ovary, tubo-ovarian abscess, peritonitis, hydrosalpinx, infertility and ectopic pregnancy.

Question 70

A 42-year-old Afro-Caribbean woman is nulliparous and trying to conceive. She has been experiencing dysmenorrhoea. Ultrasound scan shows multiple rounded nodules within the myometrium. What is the most likely diagnosis? A Cervical intraepithelial neoplasia B Vulval carcinoma C Leiomyoma D Endometrial carcinoma E CGIN (endocervical glandular dysplasia)

Answer 70

C Leiomyoma Leiomyoma (C), also called fibroids, is a benign smooth muscle tumour arising in the myometrium. They are the most common of all pelvic tumours, presenting often in women over 30 years of age and are more common in nulliparous and Afro-Caribbean women. The presentation often involves multiple large rounded nodules. They are well circumscribed with a pseudocapsule that may become pedunculated forming polyps.

Question 71

A 20-year-old woman presents to accident and emergency with a distended abdomen resembling a pregnancy. She later develops acute onset of severe abdominal pain. An ultrasound identified a mass in her right ovary. Her abdomen is rigid and she is admitted for emergency surgery. It is believed that three embryonic germ cell layers are present. What is the most likely diagnosis? A Teratoma of the ovary B Serous tumour of the ovary C Mucinous tumour of the ovary D Endometrioid tumour of the ovary E Clear cell carcinoma

Answer 71

A Teratoma of the ovary Teratoma (A) is a common benign cyst that contains all three embryonic germ cell layers and this is a torsion presentation which is the most common complication of teratomas. In mature cases there have been reports of teratomas containing features such as hair, teeth, bone and eyes. As they are encapsulated, teratomas are usually benign but may rarely undergo malignant change in postmenopausal women. Serous, mucinous and endometrioid tumours (B, C, D) are epithelial ovarian tumours where serous tumours differentiate to mimic tubal epithelium, mucinous tumours differentiate to mimic endocervical or intestinal wall and endometrioid tumours mimic the endometrium.

Question 72

A 32-year-old woman presents with generalized fatigue. Full blood count shows a reduced haemoglobin level and reduced mean corpuscular volume. A peripheral blood film has revealed iron deficiency anaemia. What features are most likely to be seen on her peripheral blood film? A Hypochromic and microcytic red blood cells with anisopoikilocytosis and acanthocytes B Hypochromic and microcytic red blood cells with hypersegmented neutrophils C Hypochromic and microcytic red blood cells with anisopoikilocytosis and no evidence of basophilic stippling D Hypochromic and microcytic red blood cells with Howell–Jolly bodies and basophilic stippling E Hypochromic and macrocytic red blood cells with target cells, acanthocytes and Howell–Jolly bodies

Answer 72

C Hypochromic and microcytic red blood cells with anisopoikilocytosis and no evidence of basophilic stippling Features of iron deficiency anaemia are hypochromic (pale) and microcytic (small) red blood cells. Poikilocytes are red blood cells that are abnormally shaped. When there are variations in shape and size, it is known as anisopoikilocytosis. Basophilic stippling (aggregation of ribosomal material) is absent in iron deficiency and present in b- thalassaemia trait and lead poisoning. In megaloblastic anaemia, there is impaired DNA synthesis and this can be caused by B12 deficiency, folate deficiency and drugs. Here the features are the characteristic hypersegmented neutrophils and macrocytic red blood cells. In hyposplenism, there is presence of target cells known as codocytes (red blood cells that have a high surface area:volume ratio). Acanthocytes (spiculated blood cells/spur cells) and Howell–Jolly bodies (nuclear remnants visible in red cells) are also present in the hyposplenism picture.

Question 73

A 26-year-old woman presents with fatigue ‘all the time’. She has a family history of coeliac disease and blood tests reveal hypochromic, microcytic anaemia. She is referred to the gastroenterology clinic for tests. The gold standard investigation is the duodenal biopsy, which is carried out after positive serological testing. Which current serological testing and histopathology findings in the options below are most consistent with a coeliac disease diagnosis? A Anti-reticulin antibodies only/villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes B Anti-gliadin antibodies only/no villous atrophy, crypt hyperplasia, decreased intraepithelial lymphocytes C Anti-endomysial antibodies only/villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes D Anti-endomysial antibodies and anti-tissue transglutaminase antibodies/ villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes E Anti-endomysial antibodies and anti-tissue transglutaminase antibodies/villous atrophy, no evidence of crypt hyperplasia, increased intraepithelial lymphocytes

Answer 73

D Anti-endomysial antibodies and anti-tissue transglutaminase antibodies/ villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes

Question 74

A 27-year-old woman has developed pain in her right proximal femur. She has a history of intermittent hip pain since childhood. An X-ray has demonstrated a ‘soap bubble’ appearance indicative of osteolysis and a characteristic shepherd’s crook deformity. The biopsy would show irregular trabeculae of woven bone said to resemble Chinese letters. What is the most likely diagnosis? A Non-ossifying fibroma B Fibrous dysplasia C Giant cell reparative granuloma D Ossifying fibroma E Simple bone cyst

Answer 74

B Fibrous dysplasia Fibrous dysplasia (B) is a benign disorder of children and young adults, whereby lesions composed of fibrous and bony tissue develop usually in the ribs, femur, tibia or skull. It mostly presents as bone pain and weakness in female patients under 30 years of age and results from congenital dysplasia of bone, consistent with the patient’s history. There are three forms: the more common monostotic form (lesions localized to only one bone), polyostotic (multiple lesions) and McCune–Albright syndrome, which also has endocrine manifestations. Shepherd’s crook deformity refers to a varus angulation of the proximal femur commonly seen in the femoral involvement of polyostotic fibrous dysplasia. Histologically, it is characterized by loose fibrous tissue with metaplastic immature or woven bone trabeculae arranged in a ‘Chinese letters’ formation.

Question 75

A 36-year-old man presents with swelling of his middle finger and subsequently a fracture. His X-ray shows cotton wool calcification and histopathology shows evidence of a tumour composed of benign hyaline cartilage. It is believed that he has only a very slight risk of malignant transformation. What is the most likely diagnosis? A Osteochondroma B Multiple myeloma C Osteoid osteoma D Giant cell tumour E Enchondroma

Answer 75

E Enchondroma Enchondroma (E) is a benign intramedullary cartilage tumour usually found in the central mature hyaline cartilage of the short tubular bones of the hands and feet. It may present at any age (average is 40 years) and is often asymptomatic, but some patients present with pain, fracture or swelling of the affected area. There are lytic lesions on X-rays that usually contain variably calcified chondriod matrix and histopathological findings showing bluish-grey lobules of hyaline cartilege. There may be a thin layer of lamellar bone surrounding the cartilage nodules but no permeation of pre-existing host bone which is a positive sign that the lesion is benign. Each potential enchondroma needs to be evaluated on imaging and histology to distinguish it from low-grade chondrosarcoma

Question 76

An 18-year-old man presents with pain and a mass in his right knee. His X-ray shows an ill defined mass in the metaphyseal region of the distal femur that is sclerotic and lytic. There is also an elevated periosteum (known as a Codman’s triangle). Prognosis is said to be poor and the treatment required is multi-disciplinary involving intensive chemotherapy and surgery. In cytology, these tumour cells will be positive for alkaline phosphatase. What is the most likely diagnosis? A Osteosarcoma B Chondrosarcoma C Fibrosarcoma D Malignant fibrous histiocytoma E Ewing’s sarcoma

Answer 76

A Osteosarcoma Osteosarcoma (A) is the most common primary bone malignancy that is aggressive with poor prognosis (60 per cent of patients with 5-year survival). The vast majority of these tumours occur in teenagers and young adults. The most common presentation is pain and a mass, which occurs near a joint such as the knee, with the distal femur and proximal tibia being the most common sites. X-rays show a mixed sclerotic and lytic lesion in the metaphysis that may permeate the bone causing a soft tissue mass and a periosteal reaction. Bone formation within the tumour is characteristic of osteosarcoma and is usually visible on X-rays. Bone alkaline phosphatase has significant value in diagnosing osteosarcoma, also indicating chemotherapy effectiveness and prognosis.

Question 77

A 25-year-old woman is due for her cervical smear test. Which method of cytopathology is going to be used? A FNA B Ultrasound guided FNA C Washings D Brushings E Liquid based cytology

Answer 77

E Liquid based cytology Liquid based cytology (E) is an important method of preparing cervical samples for examination under the microscope. The sample is collected in the standard brushings method using a spatula but rather than smearing the sample onto a microscope slide as before, the head of the spatula is broken off into a small glass vial containing preservative fluid. This is then sent to the laboratory and obscuring material, e.g. mucus and pus, is removed and a representative sample of cells is deposited onto a slide for examination

Question 78

A 57-year-old man who is a heavy smoker presents to his GP with gradually worsening dyspnoea and cough productive of green sputum. On examination, he is cyanosed, tachypnoeic and wheezing. What is the most likely diagnosis? A Chronic bronchitis B Pulmonary embolus C Asthma D Bronchiolitis E Emphysema

Answer 78

A Chronic bronchitis Obstructive lung disease is characterized by airway obstruction and a decreased FEV1/FVC ratio. Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis (A) and emphysema (E). While the two often coexist, a predominantly chronic bronchitis cough produces copious amounts of sputum, and infection is consistent with this patient, while sputum and infection are only occasional in emphysema. Chronic bronchitis is the damage caused to the airways/bronchi and the clinical definition is productive cough for at least 3 months per year for 2 consecutive years. Histopathology shows hypertrophy of mucous glands and goblet cell hyperplasia. Emphysema is alveolar parenchymal damage by activation of proteases (elastase) that are in turn activated by neutrophil/macrophage action secondary to cigarette smoking. Emphysema patients only have dyspnoea and no associated cough with no mucus excess.

Question 79

A 57-year-old man presents to accident and emergency with dyspnoea, fever, cough and purulent sputum. Histopathology confirms widespread fibrinosuppurative consolidation on the left lower lobe and the top differential diagnosis is lobar pneumonia. Which organism is the most likely cause? A Streptococcus pneumoniae B Staphylococcus aureus C Haemophilus influenzae D Streptococcus pyogenes E Mycobacterium tuberculosis

Answer 79

A Streptococcus pneumoniae Lobar pneumonia is one of two anatomical classifications of pneumonia, the other being bronchopneumonia. In up to 95 per cent of cases, the causative organism for lobar pneumonia is Streptococcus pneumoniae (A) type 1, 2, 3, and 7. The stages of pneumonia start with congestion in the first 24 hours; lobes are heavy, red and boggy due to hyperaemia, intra-alveolar fluid with scattered neutrophils and many bacteria. The second stage is red hepatization, with the lobe’s transformation to a liver-like mass, characteristic of lobar pneumonia. The red hepatization is blood-stained pulmonary exudate with many intra-alveolar neutrophils. Grey hepatization is when the lung is dry and firm because the red cells disintegrate and fibrinosuppurative exudates persist within the alveoli. Finally, the resolution stage involves the enzymatic digestion of the exudates in the alveoli and normal architecture remerges.

Question 80

A 27-year-old man with severe second degree burns is admitted to the ITU and develops severe shortness of breath and tachypnoea the next day. Diffuse alveolar damage is indicated in the histopathology report. What is the most likely diagnosis? A Pulmonary oedema B Acute respiratory distress syndrome C Cryptogenic fibrosing alveolitis D Bronchiectasis E Chronic bronchitis

Answer 80

B Acute respiratory distress syndrome Squamous cell carcinoma (B) is one type of lung cancer within the non-small cell lung carcinoma (NSCLC) group. This type of cancer is most closely associated with a history of tobacco smoking and is more common in men. These tumours, if well-differentiated, show keratin pearls and cell junctions (or desmosomes), which form the characteristic intercellular ‘prickles’

Question 81

A 47-year-old construction worker presents with a 6-month history of cough, haemoptysis and 5 kg weight loss. He is a heavy smoker and a centrally located lesion is found on his chest X-ray. Histology showed keratinization and intercellular ‘prickles’. What is the most likely diagnosis? A Tuberculosis B Squamous cell carcinoma C Mesothelioma D Emphysema E Large cell carcinoma

Answer 81

B Squamous cell carcinoma Squamous cell carcinoma (B) is one type of lung cancer within the non-small cell lung carcinoma (NSCLC) group. This type of cancer is most closely associated with a history of tobacco smoking and is more common in men. These tumours, if well-differentiated, show keratin pearls and cell junctions (or desmosomes), which form the characteristic intercellular ‘prickles'

Question 82

A 55-year-old non-smoking woman presents to her GP with a 6-month history of cough, haemoptysis and 5 kg weight loss. A chest X-ray showed the lesion is in the periphery and histopathology showed evidence of glandular differentiation and cytology showed mucin vacuoles. Mode of treatment most suitable is surgical. What is the most likely diagnosis? A Small cell carcinoma B Adenocarcinoma C Large cell carcinoma D Sarcoidosis E Pneuomoconiosis

Answer 82

B Adenocarcinoma Adenocarcinoma (B) is the most common type of lung cancer in nonsmokers and is usually seen in the periphery in the lungs, as opposed to small cell lung carcinoma (A) and squamous cell lung cancer, which both tend to be more centrally located. Adenocarcinomas often metastasize and are not as responsive to chemotherapy as small cell lung carcinomas

Question 83

A 27-year-old man presents with fever, fatigue and a rash. He has also noted a few painful ulcers in his mouth. The rash is described as numerous round lesions about an inch in diameter on the face, trunk, arms and legs, diagnosed as erythema multiforme. What is the most likely diagnosis for this patient? A Systemic lupus erythematosus B Stevens–Johnson syndrome C Pemphigoid D Pityriasis rosea E Contact dermatitis

Answer 83

B Stevens–Johnson syndrome Erythema multiforme is a pleomorphic skin eruption, with macules, papules, urticarial weals, vesicles and bullae. Its severest life-threatening form is related to Stevens–Johnson syndrome (B), believed to be mediated by the deposition of immune complexes in the microvasculature of the skin and oral mucous membranes following certain drugs, foods or infections

Question 84

A 55-year-old Australian man presents with a flat black lesion on his back that appears asymmetrical with an irregular border and 6 mm in diameter. Breslow’s depth is 0.4 mm. What is the most likely diagnosis? A Malignant melanoma B Basal cell carcinoma C Squamous cell carcinoma D Keratoacanthoma E Bowen’s disease

Answer 84

A Malignant melanoma Malignant melanoma (A) is the most life-threatening and aggressive form of skin tumour and must be monitored closely and treated assertively. It is key to examine for the ‘ABCDE’: asymmetry, border irregularity, colour, diameter and environment. The BRESLOW scale is used to quantify the tumour thickness and determine prognosis.

Question 85

A 23-year-old Irish man presents with an itchy blistering eruption on his buttocks and elbows. He also has diarrhoea and abdominal pain. Histopathology reveals papillary microabscesses and a neutrophilic infiltrate. He has a family history of gluten sensitivity. Which rash is most often associated with his presentation? A Psoriasis B Atopic eczema C Dermatitis herpetiformis D Lichen planus E Seborrhoeic dermatitis

Answer 85

C Dermatitis herpetiformis Dermatitis herpetiformis (C) is a chronic blistering skin condition associated with gluten intolerance or coeliac disease. The itchy papulovesicular eruptions are distributed symmetrically on extensor surfaces. Gluten intake will exacerbate the symptoms

Question 86

A 26-year-old man presents to accident and emergency having fallen off his skateboard and landed with a big impact on his right side. His X-ray shows a fracture in the midshaft of his right humerus that appears splintered although the soft tissue is intact. What type of fracture is this? A Greenstick fracture B Transverse fracture C Compound fracture D Impacted fracture E Comminuted fracture

Answer 86

E Comminuted fracture Comminuted fractures (E) are also known as segmental fractures whereby the bone is splintered and a number of pieces are visible but with intact soft tissue. A greenstick fracture (A) is specifically a paediatric problem where the fracture is transverse, but only partially, and therefore the bone bends away from the long axis but remains attached. A transverse fracture (B) is a fracture that is at right angles to the bone’s long axis and may be partial or complete (cortex to cortex). It is often a simple clean break with intact soft tissue.

Question 87

An 80-year-old woman presents complaining of pain on movement and stiffness after inactivity in her legs, most notably in her hips and knees. She also complains of pain in her hands and marked symmetrical swelling is noted in her distal interphalangeal joints. The X-ray of her right knee shows subchondral sclerosis, subchondral cyst formation, joint space narrowing and osteophytes. What is the most likely diagnosis? A Osteoarthritis B Rheumatoid arthritis C Ankylosing spondylitis D Psoriatic arthritis E Osteoporosis

Answer 87

A Osteoarthritis Osteoathritis (A) affects mainly the vertebrae, hips, knees, distal interphalangeal joints, carpometacarpal and metatarsophalangeal joints. The presentation of this patient is typical of osteoarthritis. Rheumatoid arthritis (B) is severe chronic relapsing synovitis that often presents in a younger population than this patient (30–40 years of age). Eighty per cent of patients are rheumatoid factor positive and characteristic deformities include ulnar deviation of the fingers, swan-neck and Boutonniere deformity of the fingers and a ‘Z’-shaped thumb. It characteristically spares the distal interphalangeal joint and affects symmetrically the small joints in the hands and feet, wrists, elbows, ankles and knees. Histopathology shows proliferative synovitis with thickening of the synovial membranes, hyperplasia of surface synoviocytes, intense inflammatory cell infiltrate and fibrin deposition and necrosis. Ankylosing spondylitis (C) is a chronic inflammatory arthritis with strong HLA B27 association affecting the spine and sacroilium that can cause eventual fusion of the spine (bamboo spine). It commonly presents in a male aged 20–40 with stiffness of the spine. In addition to joint involvement, psoriatic arthritis (D) will commonly present with psoriatic nail lesions (pitting, onycholysis), dactylitis and tendinitis. X-rays will show ‘new fluffy’ bone. Osteoporosis (E) would show osteopenia, cortical thinning and increased radiolucency in the X-rays.

Question 88

A 59-year-old man presents to accident and emergency with a painful, swollen and hot big toe. The joint aspirate shows negatively birefringent crystals under polarized red light. The crystals are needle shaped. What is the most likely diagnosis? A Pseudogout B Lyme disease C Reiter’s sydrome D Gout E Osteomyelitis

Answer 88

D Gout Only two conditions out of the five cause crystal-induced arthritis: gout and pseudogout. Gout (D) affects the big toe in 90 per cent of cases and needle-shaped crystals occur in the joint causing very severe pain. One might also see tophi, which are of monosodium glutamate precipitate in pathognoic for gout where monosodium urate crystals are deposited under the skin. Monosodium urate crystals are negatively bi-refringent when viewed using a polarising microscope.

Question 89

A 23-year-old man presents to accident and emergency with a 2-day history of left-sided loin pain, fever, rigors and vomiting. Urine analysis reveals microscopic haematuria and white cell casts. What is the most likely diagnosis? A Cystitis B Prostatitis C Urolithiasis D Acute pyelonephritis E Hydronephrosis

Answer 89

D Acute pyelonephritis Acute pyelonephritis (D) is strongly indicated if white cell casts are present. Red cell casts are strongly suggestive of glomerulonephritis. Eosinophiluria is strongly suggestive of tubulointerstitial nephritis.

Question 90

A 4-year-old boy presents with a large abdominal mass and haematuria. His blood pressure is 165/120 mmHg. The mass has a large necrotic solid tumour with extrarenal invasion. Microscopically, there are immature-looking glomerular structures. Aggressive therapy with surgery, chemotherapy and radiotherapy is indicated. What is the most likely diagnosis? A Teratoma B Wilm’s tumour C Oncocytoma D Spermatocytic seminoma E Bowen’s disease

Answer 90

B Wilm’s tumour Wilm’s tumour (B) (nephroblastoma) is a malignant embryonic tumour derived from the primitive metanephros. It is the most common childhood urological malignancy and involves mutations of the tumour suppressor gene WT1 located on chromosome 11. Macroscopically, the kidney is replaced by rounded masses of solid, fleshy, white lesions with vast amounts of necrosis. Microscopically, it is composed of four elements: immature-looking glomerular structures, primitive small cell blastaematous tissue, epithelial tubules and stroma composed of spindle cells and striated muscle.

Question 91

A 79-year-old man has hesitancy and terminal dribbling urinary symptoms secondary to a tumour growth. No other symptoms are present. On rectal examination, the prostate is reported as hard and craggy. The patient has been given a Gleason’s score of 8; a primary grade of 3, describing that the tissue has recognizable glands and these cells are beginning to invade the surrounding tissue. There is also a secondary grade of pattern 5 suggesting poorly differentiated cells. What is the most likely diagnosis? A Prostatic adenocarcinoma B Seminoma C Prostatic intraepithelial neoplasia D Benign prostatic hyperplasia E Transitional cell carcinoma

Answer 91

A Prostatic adenocarcinoma Prostatic adenocarcinoma (A) is rare in men under 50 years of age. The gross histopathology involves the peripheral portion of prostate, posteriorly. It is poorly demarcated, firm and yellow and there may be urinary bladder, seminal vesicle and rectal invasion. The Gleason’s scoring system is used to help evaluate the prognosis of men with prostate cancer. The pathologist assigns a grade to the most common tumour pattern and a second grade to the worst pattern, then the two grades are added together to get the Gleason score.

Question 92

A 27-year-old lactating mother presents with a painful red left breast. On closer examination, there are cracks and fissures on the left nipple. What is the most likely diagnosis? A Fat necrosis B Acute mastitis C Duct ectasia D Simple fibrocystic change E Epithelial hyperplasia

Answer 92

B Acute mastitis Acute mastitis (B) is the acute inflammation of the breast that often affects lactating women. The usual causative organism is Staphylococcus aureus. An abscess may develop and drainage and antibiotics are curative.

Question 93

A 56-year-old woman presents with blood stained nipple discharge and a solitary mass located just superior to the nipple in her left breast. A histopathology analysis shows that a papillary mass is lined by epithelium and myoepithelium. It is believed that there is no increased risk of malignancy. What is the most likely diagnosis? A Intraductal papilloma B Phylloides tumour C Fibroadenoma D Radial scar E Ductal carcinoma in situ

Answer 93

A Intraductal papilloma Intraductal papilloma (A) is a benign papillary tumour arising within the duct system of the breast. The two forms are peripheral (arise within small terminal ductules) and central (arise in larger lactiferous ducts). Only central papillomas can present with nipple discharge that is blood stained, while peripheral papillomas can remain clinically silent.

Question 94

A 53-year-old overweight woman with a positive family history of breast cancer attends her appointment for the NHS Breast Screening Programme. She is one of the 5 per cent of women who have an abnormal mammogram and are called for a core biopsy. She has been given a B code of B5b. What is the most likely diagnosis? A Benign abnormality B Lesion of uncertain malignant potential C Ductal carcinoma in situ D Invasive carcinoma E Suspicious of malignancy

Answer 94

D Invasive carcinoma Invasive breast carcinomas (D) are a group of malignant epithelial tumours which infiltrate within the breast and have capacity to spread to distant sites. The risk factors include: early menarche, late menopause, increased weight, high alcohol consumption, oral contraceptive use and a positive family history. BRCA mutations are known to cause a lifetime risk of invasive breast carcinoma of up to 85 per cent. The types of invasive carcinomas include: invasive ductal carcinoma, invasive lobular carcinoma, mucinous, tubular, medullary and papillary. Ductal carcinoma in situ (DCIS) is a form of non-invasive breast carcinoma.

Question 95

A 44-year-old man has developed end stage renal failure over the past 5 years with numerous episodes of macroscopic haematuria. He was asymptomatic previously. Ultrasound scan has shown numerous asymmetrical large cysts bilaterally. The patient’s mother had a similar condition. What is the most likely diagnosis? A Acquired cystic disease B Medullary sponge disease C Adult polycystic kidney disease D Cystic renal dysplasia E Simple renal cysts

Answer 95

C Adult polycystic kidney disease Adult polycystic kidney disease (C) is an autosomal dominant condition, believed to involve two genes: PKD1 and PKD2. Both kidneys are replaced by fluid-filled cysts. It is asymptomatic initially, but in the fourth decade or later, the patient presents with a large lobulated abdominal mass, pain or haematuria. It is managed by blood pressure control and eventually dialysis or transplantation.

Question 96

A 48-year-old man presents with oliguria and a vasculitic rash on his legs. Investigations indicate that he has a reduced glomerular filtration rate and urinalysis finds urine casts containing red and white blood cells. Histopathology shows scanty deposits of immunoglobulins and complement present with associated anti-neutrophil cytoplasm antibodies (ANCA). What is the most likely diagnosis? A IgA nephropathy B Thrombotic microangiopathy C Anti-GBM crescentic glomerulonephritis disease D Pauci-immune crescentic glomerulonephritis disease E Amyloidosis

Answer 96

D Pauci-immune crescentic glomerulonephritis disease Pauci-immune crescent glomerulonephritis (D) is associated with antineutrophil cytoplasm antibodies (ANCA) and vasculitis in other systems such as the skin and lungs. This patient has glomerulonephritis that is sufficient to cause acute renal failure and therefore is almost certain to be associated with glomerular crescents.

Question 97

A 35-year-old oedematous woman is found to have urinary protein loss of 5.1 g daily. Further tests show a low albumin level and significant interference with podocyte function. No glomerular crescents were detected. What is the most likely diagnosis? A Acute glomerulonephritis B Nephritic syndrome C Nephrotic syndrome D Acute tubular necrosis E Acquired cystic disease

Answer 97

C Nephrotic syndrome Nephrotic syndrome (C) is the breakdown of selectivity of the glomerular filtration barrier leading to massive protein leak. There is proteinuria at least of 3.5 g/day, hypoalbuminaemia, oedema and hyperlipidaemia. There are systemic and primary glomerular diseases. The latter interferes with podocyte function and can be one of three types: minimal change disease, focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis.

Question 98

A 58-year-old woman is known to have a Berry aneurysm in the basilar artery. She develops sudden onset severe headache, nausea and loss of consciousness. There was evidence of a ‘warning bleed’ but no history of brain trauma. What is the most likely fatal diagnosis caused by the ruptured Berry aneurysm? A Intracerebral haemorrhage B Subarachnoid haemorrhage C ‘Watershed’ strokes D Transient ischaemic attack E Tonsillar brain herniation

Answer 98

B Subarachnoid haemorrhage Subarachnoid haemorrhage (B) is usually non-traumatic and due to rupture of a Berry aneurysm, which are present in 1 per cent of the general population. They occur on the circle of Willis, mostly at the arterial bifurcations of the internal carotid artery and within the vertebrobasilar circulation. The Berry aneurysms enlarge with time and pose the greatest risk of rupture when at 6–10 mm diameter. They are more common in females than males and in 20 per cent of cases the patients have a ‘warning bleed’, which will lead to a rupture and poses a much worse prognosis than without a ‘warning bleed’.

Question 99

A 9-year-old boy presents with fever, headache, stiff neck and altered mental state. His cerebrospinal fluid is turbid and contains mostly neutrophils. The meninges appear congested and there is purulent material in the subarachnoid space. What is the most likely causative organism? A Coxsackie virus B Treponema pallidum C Staphylococcus aureus D Streptococcus pneumoniae E Haemophilus influenzae

Answer 99

D Streptococcus pneumoniae The diagnosis is acute purulent meningitis. It is a major cause of morbidity and mortality in all ages, but in children older than 6 years, Streptococcus pneumoniae (D) is the most common cause.

Question 100

A 22-year-old HIV-infected woman is pregnant with her second child. HIV has been transmitted perinatally to her first child. One of the most successful interventions to reduce vertical transmission of HIV during pregnancy to less than 1 per cent is the use of combination anti-retroviral treatment, which ideally should reduce the viral load to? A 50 copies/mL B 800 copies/mL C 1000 copies/mL D 5000 copies/mL E 10 000 copies/mL

Answer 100

A 50 copies/mL Almost all new childhood HIV infections are due to mother-to-child (vertical) transmission; before (in utero), during childbirth (intra partum) or through breastfeeding. HIV viral load tests are reported as the number of HIV copies in a millilitre (copies/mL) of blood. A high viral load can be anywhere from 5000 to 10 000 copies/mL. Initial, untreated and uncontrolled HIV viral loads can range as high as one million or more copies/mL. A low viral load is usually between 40 and 500 copies/mL and this result indicates that HIV is not actively reproducing and that the risk of disease progression is low.