Histopathology Flashcards
- Cardiovascular pathology
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
1 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 on-call cardiologist. The patient admits to being an intravenous drug user.
1) B
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.
Monckeberg arteriosclerosis (A) involves focal calcification of the media of small medium-sized arteries. It usually presents in patients over 50 years of age and unlike atherosclerosis, there is no associated inflammation in the pathogenesis.
Dilated cardiomyopathy (D) occurs due to a progressive loss of myocytes resulting in a left ventricular ejection fraction of less than 40%. Causes include alcohol, chemotherapy (e.g. doxorubicin) and viral myocarditis.
Hypertrophic obstructive cardiomyopathy (G) is an autosomal dominant condition caused by a mutation in the Beta-myosin heavy chain. Histological features include myocyte hypertrophy and disarray.
Carcinoid syndrome (I) occurs due to 5-hydroxyindoleacetic acid producing tumours and is characterized by episodic flushing, abdominal cramps and diarrhoea. Right sided valve abnormalities may also result.
- Cardiovascular pathology
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
2 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.
2) H
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. LVH may develop as a consequence of chronic pressure overload.
Monckeberg arteriosclerosis (A) involves focal calcification of the media of small medium-sized arteries. It usually presents in patients over 50 years of age and unlike atherosclerosis, there is no associated inflammation in the pathogenesis.
Dilated cardiomyopathy (D) occurs due to a progressive loss of myocytes resulting in a left ventricular ejection fraction of less than 40%. Causes include alcohol, chemotherapy (e.g. doxorubicin) and viral myocarditis.
Hypertrophic obstructive cardiomyopathy (G) is an autosomal dominant condition caused by a mutation in the Beta-myosin heavy chain. Histological features include myocyte hypertrophy and disarray.
Carcinoid syndrome (I) occurs due to 5-hydroxyindoleacetic acid producing tumours and is characterized by episodic flushing, abdominal cramps and diarrhoea. Right sided valve abnormalities may also result.
- Cardiovascular pathology
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
3 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.
3) F
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.
Monckeberg arteriosclerosis (A) involves focal calcification of the media of small medium-sized arteries. It usually presents in patients over 50 years of age and unlike atherosclerosis, there is no associated inflammation in the pathogenesis.
Dilated cardiomyopathy (D) occurs due to a progressive loss of myocytes resulting in a left ventricular ejection fraction of less than 40%. Causes include alcohol, chemotherapy (e.g. doxorubicin) and viral myocarditis.
Hypertrophic obstructive cardiomyopathy (G) is an autosomal dominant condition caused by a mutation in the Beta-myosin heavy chain. Histological features include myocyte hypertrophy and disarray.
Carcinoid syndrome (I) occurs due to 5-hydroxyindoleacetic acid producing tumours and is characterized by episodic flushing, abdominal cramps and diarrhoea. Right sided valve abnormalities may also result.
- Cardiovascular pathology
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
4 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.
4) C
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.
Monckeberg arteriosclerosis (A) involves focal calcification of the media of small medium-sized arteries. It usually presents in patients over 50 years of age and unlike atherosclerosis, there is no associated inflammation in the pathogenesis.
Dilated cardiomyopathy (D) occurs due to a progressive loss of myocytes resulting in a left ventricular ejection fraction of less than 40%. Causes include alcohol, chemotherapy (e.g. doxorubicin) and viral myocarditis.
Hypertrophic obstructive cardiomyopathy (G) is an autosomal dominant condition caused by a mutation in the Beta-myosin heavy chain. Histological features include myocyte hypertrophy and disarray.
Carcinoid syndrome (I) occurs due to 5-hydroxyindoleacetic acid producing tumours and is characterized by episodic flushing, abdominal cramps and diarrhoea. Right sided valve abnormalities may also result.
- Cardiovascular pathology
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
5 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.
5) E
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 Beta-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.
Monckeberg arteriosclerosis (A) involves focal calcification of the media of small medium-sized arteries. It usually presents in patients over 50 years of age and unlike atherosclerosis, there is no associated inflammation in the pathogenesis.
Dilated cardiomyopathy (D) occurs due to a progressive loss of myocytes resulting in a left ventricular ejection fraction of less than 40%. Causes include alcohol, chemotherapy (e.g. doxorubicin) and viral myocarditis.
Hypertrophic obstructive cardiomyopathy (G) is an autosomal dominant condition caused by a mutation in the Beta-myosin heavy chain. Histological features include myocyte hypertrophy and disarray.
Carcinoid syndrome (I) occurs due to 5-hydroxyindoleacetic acid producing tumours and is characterized by episodic flushing, abdominal cramps and diarrhoea. Right sided valve abnormalities may also result.
- Mitral valve vegetation
65yo patient with advanced breast malignancy and a hx of multiple systemic emboli suffers a stroke. O/E: no cardiac murmurs but an echo 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
C
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 thrombo-embolism to the brain, heart, kidneys, and recurrent emboli are a hallmark feature.
Infective endocarditis (A) is unlikely in this case because of the absence of a persistent fever, no new or changing murmur and negative blood cultures. Other absent features of infective endocarditis include Roth’s spots, Janeway lesions and Osler’s nodes.
Acute rheumatic fever (B), mainly affecting children, commonly involves the endocardium and typically results in verruca formation on the left-sided heart valves. Vegetations are small as described, but they are much more likely to cause stenosis and are therefore inconsistent with this patient.
Chronic rheumatic valvular disease (D), mainly affecting adults, is a sequela of earlier rheumatic fever and causes thickening of valve leaflets, especially along lines of closure, and thickening, shortening and fusion of the chordate tendineae.
Libman–Sacks endocarditis (E) is very commonly assoc with SLE and rarely causes emboli.
- Bone pathology
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
1 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.
1) I
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.
Osteochondroma (E) is a bone neoplasm affecting those aged between 10 and 30 years. It targets the large joints and is a low malignancy risk.
Osteoid osteoma (F) is a painful bone neoplasm. X-ray investigation reveals central nidus (luscent) with sclerotic rim (opaque) pattern.
Renal osteodystrophy (G) is also known as secondary hyperparathyroidism. It occurs in patients with renal failure due to build-up of phosphate, damage to 1alpha-hydroxylase, osteosclerosis and aluminium toxicity.
Enchondroma (H) is a bone neoplasm most prevalent in patients aged between 10 and 40 years. It affects the small joints and has a high risk of malignant transformation.
- Bone pathology
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
2 A 38-year-old woman presents to her GP with generalized bone pain. X-ray reveals areas of pseudofracture, especially in the ribs.
2) D
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.
Osteochondroma (E) is a bone neoplasm affecting those aged between 10 and 30 years. It targets the large joints and is a low malignancy risk.
Osteoid osteoma (F) is a painful bone neoplasm. X-ray investigation reveals central nidus (luscent) with sclerotic rim (opaque) pattern.
Renal osteodystrophy (G) is also known as secondary hyperparathyroidism. It occurs in patients with renal failure due to build-up of phosphate, damage to 1alpha-hydroxylase, osteosclerosis and aluminium toxicity.
Enchondroma (H) is a bone neoplasm most prevalent in patients aged between 10 and 40 years. It affects the small joints and has a high risk of malignant transformation.
- Bone pathology
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
3 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.
3) A
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 <1 reflects osteopenia and a score of <2.5 suggests osteoporosis. All blood markers of metabolic bone disease are normal.
Osteochondroma (E) is a bone neoplasm affecting those aged between 10 and 30 years. It targets the large joints and is a low malignancy risk.
Osteoid osteoma (F) is a painful bone neoplasm. X-ray investigation reveals central nidus (luscent) with sclerotic rim (opaque) pattern.
Renal osteodystrophy (G) is also known as secondary hyperparathyroidism. It occurs in patients with renal failure due to build-up of phosphate, damage to 1alpha-hydroxylase, osteosclerosis and aluminium toxicity.
Enchondroma (H) is a bone neoplasm most prevalent in patients aged between 10 and 40 years. It affects the small joints and has a high risk of malignant transformation.
- Bone pathology
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
5 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.
5) C
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.
Osteochondroma (E) is a bone neoplasm affecting those aged between 10 and 30 years. It targets the large joints and is a low malignancy risk.
Osteoid osteoma (F) is a painful bone neoplasm. X-ray investigation reveals central nidus (luscent) with sclerotic rim (opaque) pattern.
Renal osteodystrophy (G) is also known as secondary hyperparathyroidism. It occurs in patients with renal failure due to build-up of phosphate, damage to 1alpha-hydroxylase, osteosclerosis and aluminium toxicity.
Enchondroma (H) is a bone neoplasm most prevalent in patients aged between 10 and 40 years. It affects the small joints and has a high risk of malignant transformation.
- Bone pathology
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
8yo 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.
4) B
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%) affecting femurs more than ribs occurring in patients under 30 years of age, and
2) McCune–Albright syndrome (30%) that is poly-ostotic and causes café-au-lait spots and precocious puberty.
Osteochondroma (E) is a bone neoplasm affecting those aged between 10 and 30 years. It targets the large joints and is a low malignancy risk.
Osteoid osteoma (F) is a painful bone neoplasm. X-ray investigation reveals central nidus (luscent) with sclerotic rim (opaque) pattern.
Renal osteodystrophy (G) is also known as secondary hyperparathyroidism. It occurs in patients with renal failure due to build-up of phosphate, damage to 1alpha-hydroxylase, osteosclerosis and aluminium toxicity.
Enchondroma (H) is a bone neoplasm most prevalent in patients aged between 10 and 40 years. It affects the small joints and has a high risk of malignant transformation.
- Gastritis
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
C
Helicobacter pylori-associated gastritis (C) is the most common form of chronic gastritis, accounting for 90% 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 75% 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.
In addition to the infectious cause of chronic gastritis, there are 2 other forms. The autoimmune chronic gastritis (D) is associated with pernicious anaemia in the elderly and typically affects the body of the stomach.
In reactive gastritis (E) the dominant feature is the epithelial change with minimal inflammation that can be idiopathic or due to reflux of bile-containing duodenal fluid or drugs.
Acute gastritis (B) is often a superficial form resulting from ingested chemicals and hypotension, unlikely in this patient who appears to have a more chronic presentation.
Menetrier’s disease (A) is a rare disease characterized by gross hyperplasia of gastric pits and a marked increase in mucosal thickness and typically affects the fundus and body of the stomach.
- Diseases of the exocrine pancreas
A 50-year-old known alcoholic man has persistent severe epigastric pain radiating to the back and has experienced weight loss of 5kg 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
A
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. The pathogenesis of acute pancreatitis (D) is similar but with a lack of permanent impairment and often resolves with supportive therapy. Histologically it would only show acute inflammation and necrotic changes.
Carcinoma in the head of the pancreas (B) presents early with obstructive jaundice, which this patient does not have, despite the history of weight loss and epigastric pain.
Diabetes mellitus type 2 (C) is a metabolic disorder, where patients may present with polyuria and polydipsia due to the chronic hyperglycaemia and not with severe epigastric pain.
Pseudocysts (E) are collections of fluid and necrotic inflammatory debris in the pancreas that may be associated with acute or chronic pancreatitis but often resolve spontaneously.
- Diseases of the endocrine pancreas
A 22-year-old man presents with polyuria and polydipsia. His fasting plasma glucose is 7.3mmol/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
A
DMT1 (A) is an autoimmune disorder of adolescent onset that is characterized by antibody-mediated destruction of beta-cells of the islets of Langerhans. 90-95% of patients are HLA DR3 and HLA DR4 positive. T1DM can present with polyuria or with DKA, if the polyuria is ignored. The peak incidence of T1DM is 12–14 years, so the patient being young also makes this T1DM.
DMT2 (D) is not an autoimmune disorder and has no HLA associations and the patient usually is a bit older. T2DM used to be called “maturity asset diabetes”, as it commonly affected people >50 years old, although with the increase in obesity, patients are beginning to present with T2DM at a younger age, and in some patients, further tests are required before one can easily distinguish T1DM from T2DM. Patients with T1DM are GAD (glutamic Acid Decarboxylase Autoantibodies test) antibody positive, and this test has superceded the HLA tissue type, which is not diagnostic. The diagnosis of diabetes mellitus is on the finding of hyperglycaemia. Diagnosis of DM = fasting venous plasma glucose levels of >7.0mmol/L or a random venous plasma glucose level of >11.1mmol/L.
Diabetes Insipidus (B) is a disorder of the pituitary where there is either a failure of ADH production (cranial DI) or the renal distal tubules are refractory to the water reabsorptiveaction of ADH (nephrogenic DI). While both present with polyuria and polydipsia, DI is not related to plasma glucose levels.
Psychogenic polydipsia (C) is excessive fluid intake with no organic pathology. Described in schizophrenics and young children with emotional difficulties.
Zollinger–Ellison syndrome (E) is where there is gastric hypersecretion, multiple peptic ulcers and diarrhoea caused by gastric-secreting tumour of the pancreatic G cells. This may be part of MEN1 syndrome, with adenomas present in other endocrine glands.
- Viral hepatitis
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
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.
Hepatitis C (C) is an RNA flavivirus that also shows predominantly blood-borne spread and is very common among intravenous drug abusers. A high percentage (70%) will develop chronic hepatitis, increasing the life-long risk of cirrhosis and hepatocellular carcinoma.
Hepatitis D (D) is an RNA virus that is incomplete and can only cause infection in the presence of hepatitis B virus.
Hepatitis E (E) is an RNA virus that behaves in a similar fashion in terms of transmission and clinical features to hepatitis A virus.
- Anti-mitochondrial antibodies
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 alpha-1 Antitrypsin deficiency E Alcoholic liver disease
C
Primary biliary cirrhosis (C) is the destruction of the intrahepatic bile duct, often assoc w. an immune component, with anti-mitochondrial antibodies present in 90% of cases and assoc w. other autoimmune diseases such as RA or scleroderma.
Primary sclerosing cholangitis (PSC) (A) also presents with obstructive jaundice and probably has an autoimmune element to it, but is very unlikely to show any autoantibodies. 60% cases assoc with UC.
Autoimmune hepatitis (B) is similar histologically to chronic viral hepatitis, and is associated with hyperglobulinaemia and anti-smooth muscle antibodies.
Alpha-1 antitrypsin deficiency (D) is an inherited condition, where individuals fail to produce protease inhibitor alpha-1 antitrypsin. This can cause hepatitis in adults due to the accumulation of abnormal alpha-1 antitrypsin globules in the liver.
Alcoholic liver disease (E) = history of alcohol abuse and the ethanol toxicity damages hepatocytes leading to fatty liver, acute hepatitis and cirrhosis.
- Congenital metabolic disorders
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 alpha-1 Antitrypsin deficiency D Reye’s syndrome E Budd–Chiari syndrome
A
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).
Genetic haemochromatosis (B) is excessive deposition of iron in tissues due to increased absorption of iron from the gut. Iron accumulates as haemosiderin in various organs giving them a rusty brown appearance, including hyperpigmentation of the skin. The diagnosis is based on the high saturation of transferrin in the blood, high serum iron and ferritin levels.
Alpha-1 antitrypsin deficiency (C) is not known to affect the central nervous system, but may cause chronic hepatitis and cirrhosis due to accumulation of the abnormal alpha-1 antitrypsin globules in the liver.
Reye’s syndrome (D) often occurs following an upper respiratory tract infection and was thought to occur in children exposed to aspirin. It is rare and presents with acute encephalopathy secondary to severe impairment of liver function.
Budd–Chiari syndrome (E) is the rare condition that is characterized by the occlusion of the main hepatic vein due to either local compression or thrombosis, or is idiopathic.
- Gastrointestinal diseases in children
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
B
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 = narrowing of an abnormally innervated bowel segment yet dilation and muscular hypertrophy of the bowel segment proximal to this.
Microscopically = absence of normal myenteric and submucosal plexus ganglion cells. often presents in early childhood with symptoms of colonic obstruction. reported association with Down syndrome.
Stenosis (A) implies incomplete obstruction, while atresia (C) implies complete obstruction. Both are rare in the colon but more commonly found in the duodenum and small intestine.
Intussusception (D) - when one portion of the bowel invaginates into the adjoining segment, most commonly at the ileoceacal valve. Bleeding takes place due to the venous congestion of the invaginated portion, which this patient does not have signs of.
Volvulus (E) is a type of mechanical disorder, where there is complete twisting of a loop of bowel at mesenteric base causing obstruction and infarction and severe pain on presentation.
- Colitis
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
B
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.
Crohn’s disease (A), on the other hand, can affect any region of the gastrointestinal tract with ‘skip lesions’. It is also associated with transmural inflammation and non-caseating granulomas, which this patient does not have evidence of. Wall is thickened and described as ‘rubber-hose’ and ‘cobblestone mucosa’. Ulcers tend to be linear and the lumen is narrowed. Extra-intestinal manifestations are also common in Crohn’s disease.
Ischaemic colitis (C) is the most common vascular disorder of the intesti- nal tract and usually occurs in segments in ‘watershed zones’ such as the splenic flexure or the rectosigmoid flexure. It may be transmural and may lead to perforation.
Pseudomembranous colitis (D) is a type of bacterial enterocolitis caused by the protein exotoxins of Clostridium difficile. The necrosis of the colonic mucosa characteristically causes the formation of a pseudomembrane. Patients develop fever, abdominal pain and diarrhoea.
Viral gastroenteritis (E) is the most common in children and infants and typically presents with cramps, vomiting and fever but no blood in stools.
- Neoplastic disease of the intestine
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
D
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.
Familial adenomatous polyposis (FAP) (A) is also a rare autosomal dominant condition that is caused by a mutation in the FAP gene on chromosome 5. It is characterized by the presence of adenomata in the large bowel, which this patient did not have, yet also carries a 90 per cent risk of developing into carcinoma by the age of 45.
Gardner’s syndrome (B) is similar clinically, pathologically and aetiologically to FAP and also carries a high carcinoma risk. However, there are very distinct extra-intestinal manifestations of Gardner’s syndrome, including multiple osteomas of the skull and mandible, epidermoid cysts and desmoid tumours.
Colorectal carcinoma (C) of the sporadic type is inconsistent with the history and age of the patient, as it is more commonly present in patients over the age of 60.
Hamartomatous polyps (E) often present in childhood or adolescence as part of Peutz–Jeghers syndrome and these carry a small risk of carcinomas. Patients also tend to have pigmented lesions around the mouth that are characteristic of this condition.
- Hydrosalpinx
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
D Salpingitis (pelvic inflammatory disease; D) is inflammation of the fal- lopian 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.
Endometriosis (A) occurs when endometrial glands develop outside the uterus and is associated with development of fibrous adhesions. It may develop in the Fallopian tube but will not cause a hydrosalpinx and is not often associated with a history of an infectious episode.
Adenomyosis (B) is a disorder of the uterus whereby the endometrium grows to develop deep within the myometrium.
Cervical intraepithelial neoplasia (C) is a pre-neoplastic (dysplastic) proliferation of epithelium of the transformation zone of the cervix. This is strongly associated with human papillomavirus (E) infection, particularly serotypes 16 and 18.
- Congenital causes of cardiovascular disease
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
E
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. All other syndromes are inconsistent with this patient.
The most common murmur in Ortner’s syndrome (A) is mitral stenosis, associated with an enlarged left atrium and recurrent laryngeal nerve palsy.
Turner’s syndrome (D) is only present in females. Congenital heart defects include: aortic coarctation, aortic stenosis, ventricular septal defect and atrial septal defect, but aortic dissection is uncommon.
In Ehlers–Danlos syndrome (B), cystic medial necrosis can cause fragile blood vessels but aortic regurgitation is not commonly present.
Down syndrome (C) patients may have congenital atrioventricular septal canal defects. Other causes of cystic medial necrosis in patients without Marfan’s syndrome are advanced age and chronic hypertension.
- Respiratory pathology
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
1 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.
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.
Hyaline membrane disease (A) is also known as respiratory distress syndrome. It occurs in premature neonates due to surfactant deficiency leading to hyaline deposition and hypoxia.
Extrinsic allergic alveolitis (C) occurs secondary to a type III hypersensitivity reaction. Long-term exposure to an inhaled allergen leads to pulmonary fibrosis.
Chronic bronchitis (F) is one end of the chronic obstructive pulmonary disease spectrum. Histological features include mucus gland hypertrophy, goblet cell hyperplasia/metaplasia and mucosal oedema.
Sarcoidosis (I) is a multisystem, non-caseating granulomatous disease. Inflammatory markers such as TNF-alpha , IFN-gamma and IL-12 play an important role in the inflammatory process.
- Respiratory pathology
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
2 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.
2) H
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 F508 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).
Hyaline membrane disease (A) is also known as respiratory distress syndrome. It occurs in premature neonates due to surfactant deficiency leading to hyaline deposition and hypoxia.
Extrinsic allergic alveolitis (C) occurs secondary to a type III hypersensitivity reaction. Long-term exposure to an inhaled allergen leads to pulmonary fibrosis.
Chronic bronchitis (F) is one end of the chronic obstructive pulmonary disease spectrum. Histological features include mucus gland hypertrophy, goblet cell hyperplasia/metaplasia and mucosal oedema.
Sarcoidosis (I) is a multisystem, non-caseating granulomatous disease. Inflammatory markers such as TNF-alpha , IFN-gamma and IL-12 play an important role in the inflammatory process.
- Respiratory pathology
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
3 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.
3) B
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 hyperchromatic cells that are fragile (chromatin smudging) and possess nuclear moulding. Small cell carcinomas are very aggressive with approximately 80% 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.
Hyaline membrane disease (A) is also known as respiratory distress syndrome. It occurs in premature neonates due to surfactant deficiency leading to hyaline deposition and hypoxia.
Extrinsic allergic alveolitis (C) occurs secondary to a type III hypersensitivity reaction. Long-term exposure to an inhaled allergen leads to pulmonary fibrosis.
Chronic bronchitis (F) is one end of the chronic obstructive pulmonary disease spectrum. Histological features include mucus gland hypertrophy, goblet cell hyperplasia/metaplasia and mucosal oedema.
Sarcoidosis (I) is a multisystem, non-caseating granulomatous disease. Inflammatory markers such as TNF-alpha, IFN-gamma and IL-12 play an important role in the inflammatory process.
- Respiratory pathology
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
4 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.
4) E
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.
Hyaline membrane disease (A) is also known as respiratory distress syndrome. It occurs in premature neonates due to surfactant deficiency leading to hyaline deposition and hypoxia.
Extrinsic allergic alveolitis (C) occurs secondary to a type III hypersensitivity reaction. Long-term exposure to an inhaled allergen leads to pulmonary fibrosis.
Chronic bronchitis (F) is one end of the chronic obstructive pulmonary disease spectrum. Histological features include mucus gland hypertrophy, goblet cell hyperplasia/metaplasia and mucosal oedema.
Sarcoidosis (I) is a multisystem, non-caseating granulomatous disease. Inflammatory markers such as TNF-alpha , IFN-gamma and IL-12 play an important role in the inflammatory process.
- Respiratory pathology
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
5 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.
5) G
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.
Hyaline membrane disease (A) is also known as respiratory distress syndrome. It occurs in premature neonates due to surfactant deficiency leading to hyaline deposition and hypoxia.
Extrinsic allergic alveolitis (C) occurs secondary to a type III hypersensitivity reaction. Long-term exposure to an inhaled allergen leads to pulmonary fibrosis.
Chronic bronchitis (F) is one end of the chronic obstructive pulmonary disease spectrum. Histological features include mucus gland hypertrophy, goblet cell hyperplasia/metaplasia and mucosal oedema.
Sarcoidosis (I) is a multisystem, non-caseating granulomatous disease. Inflammatory markers such as TNF-alpha , IFN-gamma and IL-12 play an important role in the inflammatory process.
- Gynaecological tumours
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)
C
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.
Cervical intraepithelial neoplasia (A) is a dysplastic transformation at the cervix; it is associated with HPV infection and does not present as nodules in the myometrium, nor with dysmenorrhoea.
Vulval carcinoma (B) is often squamous and associated with HPV 16 infection and does not present with internal symptoms such as dysmenorrhoea.
Endometrial carcinoma (D) is malignant and more common in postmenopausal women. There is a hyperoestrogenic form and a non-hyperoestrogenic form, with superficial invasion of the myometrium and deep invasion respectively. The condition classically presents with postmenopausal bleeding and not dysmenorrhoea.
CGIN (E) is a rare disorder of the cervix that is difficult to diagnose and manage and may compromise fertility of the patient but does not involve the myometrium.
- Ovarian tumours
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
A
Teratoma (A) is a common benign cyst that contains all three embry- onic 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. Pseudomyxoma peritonei, metastases from the appendix, are sometimes a characteristic feature of mucinous tumours.
Clear cell carcinomas (E) are uncommon and tend to be malignant with a poor prognosis. As the name suggest, they have a clear cytoplasm and are often associated with endometriosis.
- Nephritic disorders
A Minimal change disease B Wegener’s granulomatosis C Microscopic polyangitis D Lupus nephritis E IgA nephropathy F Membranoproliferative glomerulonephritis G Rapidly progressive glomerulonephritis H Post-streptococcal glomerulonephritis I Goodpasture’s syndrome
5 A 3-year-old boy is seen by the GP after his mother noticed swelling of his legs. A week previously the boy had been stung by a bee. Urine dipstick reveals the presence of proteinuria, while blood tests show hypoalbuminaemia and hyperlipidaemia.
5) A
Minimal change disease (A) is the most common cause of nephrotic syndrome in children. Triggers include a recent allergic reaction such as a bee sting (type I hypersensitivity reaction). Histological characteristics of renal biopsy specimens include a lack of structural change visible on light microscopy, while electron microscopy will demonstrate podocyte effacement. Steroids are the primary treatment modality, which lead to remission of disease in the vast majority of cases.
Microscopic polyangitis (C) is a small vessel vasculitis affecting the arterioles, venules and capillaries. This vasculitis is associated with focal necrotizing glomerulonephritis as well as the presence of perinuclear ANCA (p-ANCA) in the circulation directed towards cytoplasmic myeloperoxidase.
Lupus nephritis (D) is characterized by the deposition of IgG, IgM, IgA and C3 in the sub-endothelial segment of the glomerular basement membrane and in the mesangium.
Membranoproliferative glomerulonephritis (F) is defined by mesangial cell proliferation with thickening of the capillaries. Two types exist: type 1 in which there is classical and alternative complement pathway activation and type 2 that is associated with only alternative pathway activation.
Goodpasture’s syndrome (I) is characterized by the presence of anti-glomerular basement membrane proteins, specifically targeting type IV collagen. Pulmonary features include cough, dyspnoea and haemoptysis; renal features include haematuria, acute renal failure and nephrotic syndrome.
- Nephritic disorders
A Minimal change disease B Wegener’s granulomatosis C Microscopic polyangitis D Lupus nephritis E IgA nephropathy F Membranoproliferative glomerulonephritis G Rapidly progressive glomerulonephritis H Post-streptococcal glomerulonephritis I Goodpasture’s syndrome
4 A 65-year-old man with known renal failure is transferred to the renal team by the accident and emergency department with worsening renal function. A renal biopsy is taken which demonstrates the presence of crescents on histology; immunofluorescence staining of IgG/C3 reveals a granular pattern. The man is very ill with suggestions that he may require a renal transplant.
4) G
Rapidly progressive glomerulonephritis (RPGN; G) is the most aggressive of all glomerulonephritides, which may cause end-stage renal failure over a period of days. The three sub-types include immune complex disease, pauci-immune disease and anti-glomerular basement membrane disease, all of which demonstrate crescent formation on biopsy (proliferation of macrophages and parietal epithelial cells). Immunofluoresence of IgG/C3 distinguishes between the three sub-types: immune complex disease is characterized by granular staining, pauci-immune disease shows absent/scant staining, while anti-glomerular basement membrane disease demonstrates linear staining.
Microscopic polyangitis (C) is a small vessel vasculitis affecting the arterioles, venules and capillaries. This vasculitis is associated with focal necrotizing glomerulonephritis as well as the presence of perinuclear ANCA (p-ANCA) in the circulation directed towards cytoplasmic myeloperoxidase.
Lupus nephritis (D) is characterized by the deposition of IgG, IgM, IgA and C3 in the sub-endothelial segment of the glomerular basement membrane and in the mesangium.
Membranoproliferative glomerulonephritis (F) is defined by mesangial cell proliferation with thickening of the capillaries. Two types exist: type 1 in which there is classical and alternative complement pathway activation and type 2 that is associated with only alternative pathway activation.
Goodpasture’s syndrome (I) is characterized by the presence of anti-glomerular basement membrane proteins, specifically targeting type IV collagen. Pulmonary features include cough, dyspnoea and haemoptysis; renal features include haematuria, acute renal failure and nephrotic syndrome.
- Nephritic disorders
A Minimal change disease B Wegener’s granulomatosis C Microscopic polyangitis D Lupus nephritis E IgA nephropathy F Membranoproliferative glomerulonephritis G Rapidly progressive glomerulonephritis H Post-streptococcal glomerulonephritis I Goodpasture’s syndrome
3 A 25-year-old man presents to his GP with symptoms and signs of nephritic syndrome. The patient had a sore throat 2 weeks previously. Blood tests reveal anti-streptolysin titre is high, while IgA levels are normal.
3) H
Post-streptococcal glomerulonephritis (H) is usually caused by a preceding group A beta haemolytic streptococcus pharyngitis. Anti-streptolysin O titre (ASOT) will be raised. Pathological hallmarks of post-streptococcal glomerulonephritis include diffuse hypercellularity and diffuse swelling of the mesangium and glomerular capillaries. Influx of neutrophils and macrophages may reveal crescent formation on histology. Direct immunofluorescence reveals the sub-epithelial deposition of IgG and C3. The condition usually subsides with supportive treatment, including antibiotic therapy to combat the outstanding infection.
Microscopic polyangitis (C) is a small vessel vasculitis affecting the arterioles, venules and capillaries. This vasculitis is associated with focal necrotizing glomerulonephritis as well as the presence of perinuclear ANCA (p-ANCA) in the circulation directed towards cytoplasmic myeloperoxidase.
Lupus nephritis (D) is characterized by the deposition of IgG, IgM, IgA and C3 in the sub-endothelial segment of the glomerular basement membrane and in the mesangium.
Membranoproliferative glomerulonephritis (F) is defined by mesangial cell proliferation with thickening of the capillaries. Two types exist: type 1 in which there is classical and alternative complement pathway activation and type 2 that is associated with only alternative pathway activation.
Goodpasture’s syndrome (I) is characterized by the presence of anti-glomerular basement membrane proteins, specifically targeting type IV collagen. Pulmonary features include cough, dyspnoea and haemoptysis; renal features include haematuria, acute renal failure and nephrotic syndrome.
- Nephritic disorders
A Minimal change disease B Wegener’s granulomatosis C Microscopic polyangitis D Lupus nephritis E IgA nephropathy F Membranoproliferative glomerulonephritis G Rapidly progressive glomerulonephritis H Post-streptococcal glomerulonephritis I Goodpasture’s syndrome
2 A 24-year-old man presents to his GP with a few days’ history of blood in his urine. Urinary investigations reveal the presence of proteinuria, red and white cell casts and dysmorphic red cells. The patient’s notes state that he was diagnosed with pharyngitis in the previous week. Blood tests reveal a raised IgA level.
2) E
IgA nephropathy (Berger’s disease; E) is the most common cause of glomerunephritis in the developed world. The condition occurs after a gastrointestinal or upper respiratory infection; potential offenders are postulated to include Haemophilus influenzae, hepatitis B virus and cytomegalovirus. Antigenic targets for IgA are thought to include collagen, fibronectin and laminin. Characteristically there is mesangial proliferation with deposition of IgA together with alternative pathway factors C3 and properdin. Blood tests will reveal a raised IgA level. Henoch–Schonlein purpura has a similar pathogenesis to IgA nephropathy but presents in children and has extra-renal clinical features.
Microscopic polyangitis (C) is a small vessel vasculitis affecting the arterioles, venules and capillaries. This vasculitis is associated with focal necrotizing glomerulonephritis as well as the presence of perinuclear ANCA (p-ANCA) in the circulation directed towards cytoplasmic myeloperoxidase.
Lupus nephritis (D) is characterized by the deposition of IgG, IgM, IgA and C3 in the sub-endothelial segment of the glomerular basement membrane and in the mesangium.
Membranoproliferative glomerulonephritis (F) is defined by mesangial cell proliferation with thickening of the capillaries. Two types exist: type 1 in which there is classical and alternative complement pathway activation and type 2 that is associated with only alternative pathway activation.
Goodpasture’s syndrome (I) is characterized by the presence of anti-glomerular basement membrane proteins, specifically targeting type IV collagen. Pulmonary features include cough, dyspnoea and haemoptysis; renal features include haematuria, acute renal failure and nephrotic syndrome.
- Nephritic disorders
A Minimal change disease B Wegener’s granulomatosis C Microscopic polyangitis D Lupus nephritis E IgA nephropathy F Membranoproliferative glomerulonephritis G Rapidly progressive glomerulonephritis H Post-streptococcal glomerulonephritis I Goodpasture’s syndrome
1 A 50-year-old woman presents to accident and emergency with haematuria. Blood tests demonstrate deranged renal function and further tests reveal the presence of circulating cANCA antibodies. The patient is noted to have a saddle-shaped nose.
1) B
Wegener’s granulamatosis (B) is a systemic vasculitis characterized clinically by epistaxis, haemoptysis and haematuria. Wegener’s granulomatosis is defined by the presence of cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA). c-ANCA is directed towards proteinase 3 (PR3), an enzyme normally present within the cytoplasm of neutrophils. It is proposed that an infection is the trigger for the disease, which causes circulating neutrophils to become adherent to the endothelium and upregulation of PR3 on the cell surface. Vasculitis is mediated by both direct effect of PR3 on the endothelium as well as cANCA–PR3 immune complex deposition.
Microscopic polyangitis (C) is a small vessel vasculitis affecting the arterioles, venules and capillaries. This vasculitis is associated with focal necrotizing glomerulonephritis as well as the presence of perinuclear ANCA (p-ANCA) in the circulation directed towards cytoplasmic myeloperoxidase.
Lupus nephritis (D) is characterized by the deposition of IgG, IgM, IgA and C3 in the sub-endothelial segment of the glomerular basement membrane and in the mesangium.
Membranoproliferative glomerulonephritis (F) is defined by mesangial cell proliferation with thickening of the capillaries. Two types exist: type 1 in which there is classical and alternative complement pathway activation and type 2 that is associated with only alternative pathway activation.
Goodpasture’s syndrome (I) is characterized by the presence of anti-glomerular basement membrane proteins, specifically targeting type IV collagen. Pulmonary features include cough, dyspnoea and haemoptysis; renal features include haematuria, acute renal failure and nephrotic syndrome.
- Cell changes
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
C
The normal oesophagus is lined by stratified squamous epithelium and the squamo-columnar junction lies 2cm 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.
Metaplasia can lead to dysplasia (D), which is an abnormal pre-malignant disordered pattern of growth. The cells are altered in size, shape and organization.
If it leads to neoplasia (E), histologically there will be an abnormal proliferation and the process of tumour growth is detected.
Anaplasia (A) is defined as dedifferentiation or the reversion of differentiated cells and is characteristic of malignant neoplasms, implying loss of structure or function, which is not the case here.
Hyperplasia (B) is a physiological proliferation and increase in the number of cells in a tissue or organ, which is not consistent with Barrett’s oesophagus.
- Breast pathology
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
5 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.
5) I
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.
Mastitis (A) occurs in breast-feeding mothers. As a result of cracked nipples, bacteria such as Staphylococcus aureus are able to enter. On examination, the area is tender to touch, erythematous and oedematous.
Gynaecomastia (F) is defined as enlargement of male breasts due to epithelial hyperplasia. Causes include: malnutrition, spironolactone, ketoconazole and cirrhosis.
Fibrocystic disease (G) is usually a peri-menopausal disease that regresses after menopause. It occurs due to irregular menstrual cycles that result in unbalanced oestrogen.
Fat necrosis (H) occurs after trauma to the breast resulting in a tender lump consisting of necrosed fat surrounded by macrophages.
- Breast pathology
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
4 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.
4) B
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 5cm, 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.
Mastitis (A) occurs in breast-feeding mothers. As a result of cracked nipples, bacteria such as Staphylococcus aureus are able to enter. On examination, the area is tender to touch, erythematous and oedematous.
Gynaecomastia (F) is defined as enlargement of male breasts due to epithelial hyperplasia. Causes include: malnutrition, spironolactone, ketoconazole and cirrhosis.
Fibrocystic disease (G) is usually a peri-menopausal disease that regresses after menopause. It occurs due to irregular menstrual cycles that result in unbalanced oestrogen.
Fat necrosis (H) occurs after trauma to the breast resulting in a tender lump consisting of necrosed fat surrounded by macrophages.
- Breast pathology
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
3 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.
3) E
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 premenopausal 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.
Mastitis (A) occurs in breast-feeding mothers. As a result of cracked nipples, bacteria such as Staphylococcus aureus are able to enter. On examination, the area is tender to touch, erythematous and oedematous.
Gynaecomastia (F) is defined as enlargement of male breasts due to epithelial hyperplasia. Causes include: malnutrition, spironolactone, ketoconazole and cirrhosis.
Fibrocystic disease (G) is usually a peri-menopausal disease that regresses after menopause. It occurs due to irregular menstrual cycles that result in unbalanced oestrogen.
Fat necrosis (H) occurs after trauma to the breast resulting in a tender lump consisting of necrosed fat surrounded by macrophages.
- Breast pathology
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
2 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.
2) C
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 5cm. They tend to be soft in a young female and firm in elderly women (as stroma becomes more fibrous).
Mastitis (A) occurs in breast-feeding mothers. As a result of cracked nipples, bacteria such as Staphylococcus aureus are able to enter. On examination, the area is tender to touch, erythematous and oedematous.
Gynaecomastia (F) is defined as enlargement of male breasts due to epithelial hyperplasia. Causes include: malnutrition, spironolactone, ketoconazole and cirrhosis.
Fibrocystic disease (G) is usually a peri-menopausal disease that regresses after menopause. It occurs due to irregular menstrual cycles that result in unbalanced oestrogen.
Fat necrosis (H) occurs after trauma to the breast resulting in a tender lump consisting of necrosed fat surrounded by macrophages.
- Breast pathology
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
1 A 55-year-old parous woman presents to her GP with a 2-week history of green discharge from her right nipple.
1) D
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.
Mastitis (A) occurs in breast-feeding mothers. As a result of cracked nipples, bacteria such as Staphylococcus aureus are able to enter. On examination, the area is tender to touch, erythematous and oedematous.
Gynaecomastia (F) is defined as enlargement of male breasts due to epithelial hyperplasia. Causes include: malnutrition, spironolactone, ketoconazole and cirrhosis.
Fibrocystic disease (G) is usually a peri-menopausal disease that regresses after menopause. It occurs due to irregular menstrual cycles that result in unbalanced oestrogen.
Fat necrosis (H) occurs after trauma to the breast resulting in a tender lump consisting of necrosed fat surrounded by macrophages.
- Renal pathology
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulo-nephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulo-nephritis
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 and the only blood abnormality is a low albumin level.
H
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 hypo-albuminaemia. 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.
Wegener’s granulamatosis (B) is a c-ANCA mediated pauci-immune RPGN, creating an absent/scant pattern on IgG and C3 immunofluorescence staining.
Membranous glomerulonephritis (C) is defined on histological investigation as a thickened glomerular basement membrane, spike/dome protrusions, sub-epithelial immunoglobulin and a granular staining pattern.
Minimal change glomerulonephritis (E) appears normal with light microscopy but podocyte effacement is visible on electron microscopy. Most cases will respond to steroid treatment.
Focal segmental glomerulonephritis (I) appears with obliterated lumen and podocyte effacement on histological examination. Focal segmental glomerulonephritis is not responsive to steroids.
