Histopathology SBAs

Question 1

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 1

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 2

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 2

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 3

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 3

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 4

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 4

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 5

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 5

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 6

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 6

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 7

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 7

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 8

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 8

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 9

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 9

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 10

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 10

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 11

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 11

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 12

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 12

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 13

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 13

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 14

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 14

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 15

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 15

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 16

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 16

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 17

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 17

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 18

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 18

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 19

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 19

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 20

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 20

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 21

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 21

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 22

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 22

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 23

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 23

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

Question 24

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 24

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 25

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 25

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 26

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 26

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 27

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 27

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 28

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 28

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 29

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 29

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 30

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 30

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 31

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 31

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 32

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 32

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 33

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 33

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 34

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 34

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 35

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 35

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 36

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 36

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 37

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 37

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 38

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 38

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 39

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 39

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 40

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 40

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 41

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 41

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 42

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 42

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 43

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 43

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 44

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 44

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 45

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 45

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 46

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 46

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 47

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 47

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 48

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 48

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 49

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 49

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 50

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 50

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.