103701940 Clinical Haematology 1 50

7/28/2019 103701940 Clinical Haematology 1 50

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Clinical Haematology/oncology - Pastest

1. A 73-year-old man with chronic lymphocytic leukaemia (CLL) is followed up in clinic.

He has become increasingly breathless over the last three months but has no othersymptoms and is on no medication. On examination, he is pale and has bilateral cervicaland inguinal lymphadenopathy and a firm 5-cm splenomegaly. FBC shows:

Hb 7.4 g/dl; WCC 25 103/mm3; platelets 117 103/mm3; urea 15 mmol/l; creatinine 203

mmol/l; bilirubin 49 mmol/l.

Which investigation is most appropriate to demonstrate the likely cause of anaemia?

Bone marrow aspirate

Autoantibody profileErythropoietin level

Antiglobulin test Your answer

Urinary haemosiderin

Anaemia in CLL has several causes including marrow infiltration, marrow suppression

from chemotherapeutic agents, hypersplenism and haemolysis (which is extravascular andmediated by IgG antibodies against the erythrocyte membrane). A disproportionately low

haemoglobin compared to the platelet count is more likely to reflect a red cell problem

alone; and the raised bilirubin level suggests that haemolysis is occurring, rather than theanaemia being due to marrow failure. Autoimmune haemolysis is demonstrated by the

antiglobulin test, either indirectly (patients serum incubated with human red cells andantiglobulin antibodies) or directly (patients cells and serum incubated with antiglobulin

antibody). The haemolysis is extravascular and so there will be no increase in urinaryhaemosiderin.

2. Which one of the following is the MOST common cause of aplastic crisis in apatient with sickle cell disease?

Dehydration

Respiratory syncytial virus infection

Human parvovirus B19 infection

Your answer


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Repeated blood transfusion

Haemophilus influenzae septicaemia

Aplastic anaemic crises occur more frequently in children with a parvovirusinfection, which is characterised by mild fever, dyspnoea on exertion, anorexia,and pallor. Recovery from aplastic crisis typically requires a week, but thepatient may need to be transfused with packed erythrocytes until marrowrecovery. However, well-known precipitants of vaso-occlusive pain crises (VPC)include cold weather, relative high haemoglobin concentration, dehydration,infection, exercise, dampness, poor diet, hypoxia, acidosis, emotional stress,and fatigue.

3. A 38-year-old woman presents with painful swelling of her left arm. Venography shows

occlusion of her left subclavian vein. Her only previous medical history is of threespontaneous miscarriages. Her haematological investigations before treatment were as

follows:

Hb 13.2 g/dl, WCC 7.4 109/l, with a normal differential, platelets 123 109/l, PT 16 s

(normal range 1217), APTT 44 s (normal range 2438), TT 17 s (normal range 1422) andfibrinogen 2.4 g/l (normal range 25).

What is the most likely cause of her thrombotic problem?

Factor V Leiden mutation

von Willebrands disease

Primary thrombocythaemia

Antiphospholipid syndrome Your answer

Autoimmune thrombocytopenia

The antiphospholipid syndrome (APS) may be diagnosed when arterial or venous

thrombosis or recurrent miscarriage occurs in a patient with positive laboratory tests forantiphospholipid antibody. Patients may also have thrombocytopenia and livedo reticularis,but APS can be detected incidentally in healthy subjects. On laboratory screening the

APTT is prolonged and does not correct to normal when mixed with normal plasma,

showing the presence of an inhibitor. This can be confirmed on further coagulation testingand immunoassays for anticardiolipin antibodies. Patients require anticoagulation, the

duration and intensity of which depends on the clinical scenario. Antiphospholipid


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antibodies can also be detected in association with certain drugs, eg chlorpromazine, and

with chronic infection, eg syphilis and hepatitis C.

4. A 72-year-old woman presents with worsening back pain. She also feels generally weak.

An X-ray of her back shows multiple vertebral collapses and lytic lesions. What is the most

likely diagnosis?

Osteoporosis

Osteosarcoma

Bone metastases

Multiple myeloma Your answer

Chronic myeloblastic leukaemia

Bone pain, frequently in the back or chest, is present at diagnosis in more than two-thirdsof patients with myeloma. Loss of height from multiple vertebral collapses may occur. The

most common symptoms are weakness and fatigue, which are often due to anaemia. Fever

is rare and, when present, is usually due to an infection. An acute infection, renal failure,hypercalcaemia or amyloidosis may be the presenting feature. The liver is palpable in about

20% of patients, and the spleen in 5%. Extramedullary plasmacytomas are uncommon and

are usually observed late in the course of the disease as large, purplish, subcutaneousmasses.

5. A 50-year-old man, who has a history of excess alcohol intake, presents complaining ofarthralgia. On examination he has pigmented skin and 2 cm of hepatomegaly. On

investigation his Hb is 14.5 g/dl (1318), WCC 8.3 109/l (411 109) with a normal

differential, platelets 164 109/l (150400 109); urea 6.0 mmol/l (2.57.5), Na 140

mmol/l (137144), K 4.2 mmol/l (3.54.9), creatinine 95 mol/l (60110), AST 65 U/l (131), ALT 82 U/l (535), ALP 135 U/l (45105), bilirubin 23 mmol/l (122), LDH 326 U/l

(10250), serum iron 45 mol/l (1429), total iron-binding capacity 82 mol/l (4572),

ferritin 623 g/l (15200). What is the most likely diagnosis?

Wilsons disease

Alcoholic cirrhosis

Acute viral hepatitis

Excess iron ingestion

Haemochromatosis Your answer

Hereditary haemochromatosis is an autosomal-recessive disorder of iron metabolism,

resulting in excess intestinal absorption and the cellular deposition of iron. It is relatively

common in people of northern European origin. The disease was found to be associated with


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theHLA-A3 allele, and theHFEgene (located on chromosome 6) has now been discovered

to be mutated in over 83% of patients.

The disorder presents with non-specific complaints such as malaise, fatigue, arthralgia,

sexual dysfunction and abdominal pain. The classical bronze diabetes with hepatic fibrosisand cirrhosis, cardiomyopathy, endocrine dysfunction and liver cancer presents after

prolonged iron loading when the diagnosis is made late. Transferrin saturation (serumiron/total iron-binding capacity) is the most sensitive biochemical marker of iron overload. Atransferrin saturation of > 55% in men or > 50% in women merits investigation for

haemochromatosis.

Treatment is with venesection. It is recommended that weekly phlebotomy is carried out

until the serum ferritin level is between 10 and 20 g/l, followed by maintenance

phlebotomy three or four times a year to maintain the serum ferritin level at 50g/l.

Liver biopsy should be considered in patients with a serum ferritin level greater than 400

mg/l in men and 200 g/l in women to determine the amount of stainable iron and to assessfor liver injury.

6. A 47-year-old alcoholic was brought into the accident and emergency departmentunconscious. He had multiple bruises over his trunk and had suffered a nosebleed from

which he was still oozing. His spleen was palpably enlarged. What is the most likely

vitamin deficiency?

Vitamin A

Vitamin B

Vitamin C

Vitamin D

Vitamin K Your answer

Vitamin K is required for the post-translational modification of six haemostatic factors,four with procoagulant activity (factors II, VII, IX, and X), and two with anticoagulant

activity (protein C, protein S). The enzyme, vitamin K-dependent -glutamylcarboxylaseadds a carboxyl group to each member of a cluster of glutamyl residues, thereby forming

the -carboxyglutamyl residues crucial to enabling these six haemostatic factors to interact

with phospholipid membranes in a calcium-dependent fashion. During this -carboxylation

reaction, the reduced form of vitamin K (vitamin KH2) is oxidised to vitamin K epoxide;oral anticoagulants inhibit the two enzymes vitamin K epoxide reductase and vitamin K

reductase, respectively, which act in sequence to regenerate the reduced form of vitamin K.


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7. A relative of a patient of yours who has metastatic cancer asks your opinion about a new

experimental cancer treatment that works by cutting off the tumour blood supply. He is

referring to which group of drugs?

Angiogenesis inhibitors Your answer

InterferonsMonoclonal antibodies

Taxanes

Matrix metalloproteinase inhibitors

Angiogenesis inhibitors have been shown to treat cancer in mice by halting tumour growth

and stopping the formation of new blood vessels in these tumours. For a tumour to grow it

must first induce the creation of new blood vessels by a process called angiogenesis, and ifthis is halted then the tumour cannot grow. Trials of this type of drug are currently underway

in humans.

Interferons are used in immunotherapy for certain cancers such as kidney cancer and

myeloma. The main side-effects are malaise and flu-like symptoms.Monoclonal antibodies are artificial antibodies against a particular target (the antigen) andare produced in the laboratory. Monoclonal antibodies are used in cancer diagnosis and

therapy. A monoclonal antibody called rituximab (MabThera) can be useful in the treatment

of non-Hodgkins lymphoma, while trastuzumab (Herceptin) is useful against certain breastcancers.

Taxanes, well-established chemotherapeutic agents that block cell division by inhibiting

formation of the mitotic spindle, are used extensively in the treatment of breast and ovarian

cancer.

Matrix metalloproteinases inhibit the proteases that cancer cells produce to facilitatedetachment from the primary tumour, invasion of the bloodstream and growth at distant

sites. They are currently being tested in clinical trials.

8. A 26-year-old woman who has suffered her third spontaneous abortion is referred by theobstetricians for review. Past history of note includes a deep vein thrombosis that was

thought to have been related to a long-haul flight. VDRL testing (used as a syphilis screen)

is positive, and IgG anticardiolipin antibodies are positive. What diagnosis fits best withthis clinical picture?

SLEAntiphospholipid syndrome Your answer

Protein C deficiency

Protein S deficiency

Syphilis

The antiphospholipid syndrome has a varied presentation, but may present with recurrent

spontaneous abortion in women. Often patients with multiple deep venous thromboses are


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investigated for coagulopathy and the condition is then discovered.

Associated neurological presentations may include stroke, transient ischaemic attacks (TIA),

migraine, multi-infarct dementia, epilepsy, chorea, movement disorders, transverse

myelopathy and dysarthria. The condition may be associated with systemic lupuserythematosus (SLE), Sjgrens syndrome, but is rarely associated with rheumatoid arthritis.

Patients with multiple small pulmonary emboli may present with symptoms of pulmonaryhypertension, there may be associations with renal vein thrombosis or Addisons disease.Gut ischaemia, hepatic vein thrombosis and the BuddChiari syndrome are also associated.

Skin presentations may include livedo reticularis and recurrent skin ulceration.

Laboratory antibody testing may reveal a false-positive VDRL result, circulating lupus

anticoagulant, prolonged activated partial thromboplastin time (APTT) and positive IgGanticardiolipin. Management of recurrent thromboses involves life-long anticoagulation.

9. A 68-year-old with known small-cell lung carcinoma presents with a history ofincreasing confusion and seizures over a period of several weeks. There are no focal

neurological signs and haematological and biochemical investigations are normal. A brain

CT and MRI are normal. What underlying cause do you suspect?

Septicaemia

Cerebral metastases

Senile dementia

Paraneoplastic disorder Your answer

Steroid related

Paraneoplastic neurological disorders (PNDs) are rare syndromes that are caused by, or

associated with, an underlying malignancy. PNDs do not occur by direct tumour

involvement in neural tissue, but are thought to be caused by crossed antigenicity or tumour-peptide release. PNDs can affect many parts of the nervous system and, unlike most gradual

neurodegenerative disorders, PNDs typically exhibit a rapid onset of symptoms. Although

PNDs most often occur in small-cell lung cancer, they can also be caused by a variety of

other cancers including breast, colon and testicular cancers. Clinical manifestations includeencephalitis, myelopathy, neuropathy, myopathy, cerebellar degeneration and the Eaton

Lambert syndrome (myasthenic syndrome, resulting from an inappropriate immune response

to the neuromuscular junction).

Sepsis is an important differential diagnosis and needs to be excluded. The normal CT/MRImakes cerebral metastases unlikely. The time scale is too short for senile dementia. Steroids

in high doses can cause a psychosis but are unlikely to cause seizures given the normal

biochemistry.


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10. A 62-year-old woman is sent to you for review. There is a history of long-standing

rheumatoid arthritis for which she takes NSAIDs and Salazopyrin. Examination reveals

changes consistent with rheumatoid arthritis and a palpable spleen. Her blood picturereveals mild anaemia, neutropenia and a platelet count of 74 10 9 (150400). Bone

marrow biopsy reveals an excess of immature granulocyte precursors. Autoimmune screen

reveals a raised ESR, positive rheumatoid factor, positive ANA and antihistone antibody.What diagnosis fits best with this clinical picture?

Portal hypertension with splenomegaly

Lymphoma

Amyloidosis

Feltys syndrome Your answer

Myelofibrosis

Feltys syndrome is defined as the triad of rheumatoid arthritis, splenomegaly and

leucopenia. It is considered an extra-articular manifestation of rheumatoid arthritis, andoccurs more frequently in patients suffering from other extra-articular manifestations such as

Sjgrens syndrome.

Feltys syndrome is said to occur in less than 1% of patients with rheumatoid arthritis, there

is a female preponderance (60%70%); cases are usually recognised from the fifth decade oflife, patients having suffered from rheumatoid arthritis for around 10 years. The blood

picture is as seen in this case, ultrasonography or CT scanning may be useful in confirming

splenomegaly.

Splenectomy has been standard therapy for Feltys syndrome since 1932, although this isusually reserved for patients with severe neutropenia and recurrent infections. A few studies

have suggested that the short-term use of lithium may be useful in stimulating

granulopoiesis.

11. A 46-year-old patient has been referred because of pyrexia of unknown origin. He has

had pyrexia for the last month interrupted by short afebrile episodes. Blood cultures and aninfection screen were both negative. On examination his temperature is 38 C and he has

palpable, non-tender neck lymph nodes. What is the most important step in obtaining the

diagnosis?

Erythrocyte sedimentation rate

C-reactive protein

Bone marrow biopsy

Blood cultures

Lymph node biopsy Your answer

The diagnosis of Hodgkins disease is based on a review of an adequate biopsy by anexpert haematopathologist. Subsequent evaluation should include a careful history and


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examination, complete blood count, erythrocyte sedimentation rate determination, serum

chemistry studies (including serum lactate dehydrogenase), chest X-ray, computer

tomography of the chest, abdomen and pelvis, and bone marrow biopsy. Gallium scans canbe performed to document radioisotope uptake by the tumour, which can then be repeated

at the completion of therapy to document remission. Bipedal lymphangiograms can be

useful if radiologists expert in carrying out the procedure are available. Staginglaparotomies are now rarely indicated.

12. Which one of the following bone sites is the MOST common site involved in bonemetastases from carcinomata?

Ribs

Pelvis

Spine Your answerSkull

Long bones

The sites most usually involved in bone metastasis are, in order of frequency, the spine,

pelvis, ribs, skull and proximal long bones.

13. You are reviewing a 35-year-old patient who presented to the Emergency department

with bleeding. His blood picture in Emergency suggested disseminated intravascularcoagulation, and unfortunately acute promyelocytic leukaemia (APML) was confirmedsoon after his admission. He begins treatment with all-trans retinoic acid (ATRA). Which

of the following descriptions best fits with the features of ATRA therapy?

ATRA should only be used during the acute period of DIC

ATRA worsens the DIC picture

ATRA promotes the differentiation of APML cells into mature

granulocytes

Your

answer

ATRA is usually given as maintenance therapy for 6 months after

postremission therapy is completed

APML carries a worse prognosis where remission is achieved compared

with other types of AML

APML is associated with the chromosome translocation t(15;17), and is specifically

associated with disseminated intravascular coagulation (DIC). Patients may present withsevere bleeding, which may worsen with chemotherapy as leukaemic blast cells break down

leading to the consumption of platelets and clotting factors.


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ATRA promotes the differentiation of leukaemic blast cells into mature granulocytes and

ameliorates both DIC and the bone marrow failure associated with ATRA. ATRA is usually

continued for 1 year after postremission chemotherapy has been completed. If remission isachieved, then the long-term prognosis is better overall compared to other subtypes of AML.

14. A 72-year-old woman presents with worsening back pain. She also feels generally

weak. An X-ray of her back shows multiple vertebral collapses and lytic lesions. What is

the next investigation to confirm the diagnosis?

Magnetic resonance imaging

Muscle biopsy

Serum electrophoresis Your answer

Bone biopsy

CT scan

The serum protein electrophoretic pattern shows a spike or localised band in 80% of cases,

hypogammaglobulinaemia is present in 10%, while no apparent abnormality is found in the

remainder. The paraprotein is IgG in about 50% of patients, IgA in 20% and Bence Jones

proteinaemia in almost 20%. IgD occurs in 2%, and biclonal paraproteinaemias are foundin 1%, whereas no serum M-protein is present at diagnosis in the remainder of the patients.

15. You are asked to provide advice on a 35-year-old woman who is admitted under the

maxillofacial surgeons for the extraction of wisdom teeth. The only concern was that shehad developed prolonged bleeding after a tooth extraction 10 years previously and had

required suturing. Besides this, she gave no other history of bleeding. What is the most

likely diagnosis?

Factor IX deficiency

Factor V LeidenFactor XII deficiency

Primary antiphospholipid syndrome

Von Willebrands disease (vWD) Your answer

Von Willebrand factor (deficient in vWD) plays a role in platelet adhesion to damagedsubendothelium and in the stabilisation of factor VIII:C in plasma. The gene is situated on

chromosome 12 and three phenotypes of vWD have been identified. Type 1 is autosomal


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dominant and characterised by a mild reduction in vWF. Type 2 is caused by a decrease in

high molecular weight multimers and is also inherited in autosomal dominant fashion.

Type 3 has recessive inheritance and has barely detectable levels of vWF. Type 1 and 2patients generally have very mild clinical features, such as bleeding after trauma or minor

surgery and menorrhagia in women. Type 3 is associated with a more severe bleeding

tendency. Treatment is often unnecessary in Types 1 and 2, although major surgery may becovered with intermediate purity factor VIII or vWF concentrates. Desmopressin acetate

(DDAVP) may also be useful.

16. You are asked to review a postmenopausal 57-year-old woman who has attended the

oncology clinic for review. She has recently had a left mastectomy with axillary lymph

node clearance, nine lymph nodes contained evidence of tumour infiltration. The tumour

cells are oestrogen and progesterone receptor-positive. You are considering starting her onthe drug treatment anastrozole. Which of the following options most accurately describes

the mode of action of anastrozole?

It blocks the ovarian production of oestrogens

It blocks the peripheral tissue conversion of androgens to oestrogens Your answer

It blocks the production of progesterone

It is an oestrogen-receptor antagonist

It is a progesterone-receptor antagonist

Anastrozole is indicated as adjuvant treatment of oestrogen receptor-positive early breast

cancer. It is contraindicated in patients with severe hepatic or renal disease. Its mode of

action is to block the action of aromatase, which is responsible for the peripheral conversionof androgens to oestrogens. Two non-steroidal aromatase inhibitors are currently marketed in

the UK, anastrozole and letrozole. Side-effects include hot flushes, vaginal dryness, vaginal

bleeding, anorexia, hair thinning, anorexia, nausea and vomiting.

Where it is in doubt as to whether a patient has passed the point of menopause, laboratorytesting to establish menopause is recommended before therapy is commenced. In

premenopausal women the use of a gonadorelin analogue or consideration of ovarian

ablation is recommended.

17. A 46-year-old patient has been referred because of pyrexia of unknown origin. He has

had pyrexia for the last month interrupted by short afebrile episodes. Blood cultures and aninfection screen were both negative. On examination his temperature is 38 C, and he has

palpable, non-tender neck lymph nodes. What is the most likely diagnosis?

Malaria


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Hodgkins disease Your answer

Chronic myeloid leukaemia

Acute myeloblastic leukaemia

Infectious mononucleosis

Patients with classical Hodgkins disease usually present with palpable non-tenderlymphadenopathy. In most patients, lymph nodes are discovered in the cervical,

supraclavicular and axillary regions. More than half the patients have mediastinallymphadenopathy at diagnosis, and symptoms from a large mediastinal mass are often the

initial presentation. Approximately one-third of patients with classical Hodgkins disease

present with fevers, night sweats and/or weight loss.

Hodgkins disease can present as a pyrexia of unknown origin. This presentation is morecommon in older patients who have mixed-cellularity or lymphocyte-depletion Hodgkins

disease and who present with disease in abdominal nodes. Pyrexia associated with

Hodgkins disease occasionally persists for days to weeks, followed by afebrile intervals,

and then re-occurrence of the pyrexia. This pattern is known as PelEbstein fever.

18. An 82-year-old man is reviewed in a medical clinic for weight loss and headaches. He

has had trouble reading and there are no other neurological symptoms. He is an ex-smokerand has cardiac failure controlled with furosemide (frusemide) and captopril. On

examination, he has axillary lymphadenopathy and splenomegaly. FBC shows Hb 10.1

g/dl, WCC 6.2 103/mm3, platelets 118 103/mm3, ESR 98, and his renal and boneprofiles are normal. What is the likely diagnosis?

Multiple myeloma

Temporal arteritis

Hodgkins lymphoma

Lymphoplasmacytoid lymphoma Your answer

Systemic lupus erythematosus (SLE)

This man has symptoms of hyperviscosity (headaches and visual disturbance) with a high

ESR and lymph node enlargement. Lymphoplasmacytoid lymphoma (or Waldenstroms

macroglobulinaemia) is due to infiltration of the marrow and reticular system withlymphoplasmacytoid cells that secrete IgM, which accumulates in the serum and, as it

forms a pentamer in solution, increases the viscosity of the blood. Myeloma can present

with hyperviscosity, but this is rarer as the immunoglobulin subclasses are G, A and D;these form smaller molecules, and myeloma does not tend to present with lymph node and

spleen enlargement. Hodgkins lymphoma can present with weight loss and adenopathy

with a raised ESR, but not with hyperviscosity. Temporal arteritis can present with visualdisturbance and headache and raised inflammatory markers, but is not associated with

adenopathy and splenomegaly.


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19. A 45-year-old man presents to A&E with a 1-day history of dark-colouredurine. He returned from a holiday in Kenya 1 week ago. On examination he is

anaemic and mildly confused.His Hb is 8.6 g/dl, MCV 87 fl, MCH 29 pg, MCHC 32 g/dl, WCC 15 109/l andplatelets 81 109/l. A coagulation screen shows a PT of 19 s (normal range1217), APTT 45 s (normal range 2438), TT 23 s (normal range 1422),

fibrinogen 1.2 g/l (normal range 25) F.D.P. 35 g/ml (normal range < 10).The laboratory reports the presence of red cell inclusions.

What is the most likely cause of his illness?

Bartonella bacilliformis

Plasmodium falciparum

Your answer

Plasmodium vivax

Plasmodium ovale

Trypanosoma brucei gambiense

Plasmodium falciparum is the most common form of malaria in Africa and South-East Asia. It presents with an acute illness that is associated with cerebral,pulmonary and renal complications and may be fatal. One of the most serioushaematological manifestations is the acute intravascular haemolytic anaemia,blackwater fever. Anaemia is frequently present and thrombocytopenia ispresent in two-thirds of cases. Disseminated intravascular coagulation is oftenpresent in severe cases. All travellers to endemic areas should takechemoprophylaxis in line with current guidelines for the area of travel.


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20. A 16-year-old Italian girl presents with anaemia. Serum haemoglobin is 70 g/l (120

160 g/l). Her blood film shows marked hypochromia and variation in cell shape and size.

Nucleated red cells are also found. What is the most likely diagnosis?

Aplastic anaemia

Thalassaemia Your answerSickle-cell anaemia

Acute myeloblastic leukaemia


This patients presents with thalassaemia and severe anaemia. The haemoglobin values on

presentation range from 20 to 80 g/l. The appearance of the stained peripheral blood film is

grossly abnormal. The red cells show marked hypochromia and variation in shape and size.There are many hypochromic macrocytes and microcytes, some of which are mere fragments

of cells. There is a moderate degree of anisochromia and basophilic stippling. There are

always some nucleated red cells in the peripheral blood.

The thalassaemias occur widely through the Mediterranean region, parts of West Africa, theMiddle East, parts of the Indian subcontinent and throughout Southeast Asia in a line

stretching from southern China through Thailand, the Malay peninsula and Indonesia to the

Pacific island populations. The thalassaemias are inherited in a simple mendelian fashion.

21. You review a 68-year-old heavy smoker who has laryngeal carcinoma. He is not keento have surgical intervention and wants to consider radiotherapy. For which of the

following tumours can radiotherapy alone be best considered a potentially curativeintervention?

Lung cancer

Breast cancer

Laryngeal carcinoma Your answer

Gastric carcinoma

Colonic carcinoma

Radiotherapy may be curative in certain types of retinal, CNS, skin, oropharynx, larynx,

oesophageal, cervical, vaginal and prostatic tumours. It may also be curative when used as

the sole treatment for certain types of lymphoma. Radiotherapy can be curative when used asan adjuvant to primary surgery for lung, breast, uterine, bladder, rectal, seminomatous, andsarcomatous tumours.

The palliative benefits of radiotherapy include pain relief, relief of headache and vomiting

when used for CNS tumours, relief of GI, bladder or lymphatic obstruction, preservation of

skeletal integrity from bony metastases, and temporary reverse of neurological impairmentassociated with spinal cord impingement.


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22. A 72-year-old heavy smoker presents with shortness of breath andhaemoptysis. On examination you notice some facial swelling. You suspect a

bronchial neoplasm. What other clinical sign would it be particularly importantto look for?

Venous dilatation over the anterior chest wall

Your answer

Supraclavicular or cervical lymphadenopathy

Finger clubbing

Cranial nerve palsy

Central cyanosis

It seems very likely that there is an underlying bronchial neoplasm, but the facialswelling should alert you to the possibility of a superior vena cava obstruction(SVCO). In this respect, venous dilatation over the anterior chest wall is anothersign that might be present. SVCO is an oncological emergency and needs to betreated rapidly with steroids once the diagnosis is confirmed. Thereafter,treatment depends on the underlying cause. About 70% of cases of SVCO are dueto lung cancer, but other malignant causes include lymphomas, leukaemias andgerm-cell tumours.

The other answers describe clinical signs that might all occur in patients withlung cancer, but they would be less useful in deciding whether or not an SVCOwas present.

23. A 37-year-old man noticed some mild nose bleeds followed by a small patchy

reddening on both legs associated with bruising. His treatment for chronic polyarthritis was

switched 2 weeks ago. Haematology laboratory results reveal a thrombocyte count of 9 109 /l, otherwise his blood counts were normal.


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What is the next step in identifying the cause?

Cytological bone marrow examination

Histological bone marrow examination

Identification of the new medication Your answer

Therapeutic trial with prednisoloneAbdominal ultrasound with spleen measurement

A variety of haematological changes are due to drug therapy for rheumatoid arthritis and

related disorders. The administration of gold occasionally causes marked thrombocytopeniaor pancytopenia. Salicylates may produce chronic blood loss, while drugs containing

phenacetin produce methaemoglobinaemia and Heinz-body haemolytic anaemia that may

sometimes be preceded by a marked eosinophilia. Phenylbutazone produces pancytopenia,which may be severe and irreversible; this drug has now been discontinued for use in the

United Kingdom. Oxyphenylbutazone and penicillamine may also cause severe marrow

depression.

24. An 18-year-old woman is referred to the haematology out-patients department by the

gynaecologists who cant find a structural or hormonal cause for her severe menorrhagia.

Clinical examination is unremarkable apart from her pallor, and she is on no medication. Afull blood count shows:

Hb 8.4 g/l; MCV 71 fl; RDW 21%; WCC 7.2 103/mm3; platelets 501 103/mm3.

Her liver function and renal function are normal, as is her prothrombin time. Which is the

most useful investigation to perform next?

Factor VIII:C level


Serum ferritin

Activated partial thromboplastin time

von Willebrand factor level Your answer

This young woman most likely has an iron deficiency anaemia and reactive

thrombocytosis. Her prothrombin time is normal, so an acquired coagulation disorder isunlikely as they typically affect both the prothrombin time (PT) and activated partial

thromboplastin time (APTT). With a normal platelet count (hence a bone marrow

differential is less helpful) the defect either lies in the level of factors that affect the APTTor in platelet function. Platelet dysfunction is more commonly acquired due to renal or liver

disease, drugs and myeloproliferative disease. Inherited causes include Glanzmanns

thrombaesthenia (lack of glycoprotein (gp) IIb/IIIa expression) and BernardSoulier

syndrome (lack of binding to intact von Willebrand factor (vWF) ). von Willebrands


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disease (vWD) causes reduced platelet function (as vWF mediates platelet binding to

exposed subendothelial cells) as well as a reduced factor VIII:C level as vWF also

stabilises factor VIII. Haemophilia A causes a reduced circulating level of factor VIII:Cdue to the reduced production of factor VIII. Hence the APTT will be prolonged in both

these conditions and will not differentiate von Willebrands disease from a coagulation-

factor deficiency. Furthermore, severe menorrhagia is a typical presentation of vWD as itreflects the reduced platelet function exacerbating mucosal bleeding.

25. A 45-year-old patient with recently diagnosed acute myeloblastic leukaemia presents

with right-sided weakness. A CT scan of his brain shows an intracerebral haemorrhage.

What is the most likely cause?

Hyperleucocytosis Your answerDisseminated intravascular coagulation

Metastases

Chemotherapy

Anaemia

Patients with hyperleucocytic leukaemia (WBC count of more than 75 109/l) can sufferearly death with central nervous system (CNS) haemorrhage and pulmonary capillary

leakage, sometimes due to a delay in treatment. These patients are at great risk of vessel

rupture.

Clinically, high leukaemia blast-cell counts in acute myeloblastic leukaemia (AML) and

chronic myelocytic leukaemia (CML) are associated with fever and evidence of functionalimpairment of the lungs and brain. The most predictive sign of ongoing vascular rupture is a

target purpura with a single, deep central nodule. The rigidity of the myeloblast causes stasiswith expanding aggregates, arteriole infarction and bleeding. Increased viscosity is offset by

a concurrent anaemia. The combined haematocrit and leucocrit at presentation is usually no

more than 45%. Because this critical level is not exceeded unless iatrogenically increased byred blood cell transfusions, the incidence of clinical leucostasis in patients with WBC counts

less than 75 109/l is low.

In a high percentage of patients CNS damage can be prevented with a continuous infusion of

high-dose cytarabine. Hydroxycarbamide (hydroxyurea) (6 g/m2) and cyclophosphamide (3g/m2) are also of value in rapidly reducing the WBC count.

26. Which brain tumour typically manifests bilaterally in patients with neurofibromatosis

type 2?

Capillary haemangioma

Giant-cell astrocytoma


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Acoustic neurinoma Your answer

Medulloblastoma

Ependymoma of the ventricles

The gene for neurofibromatosis type 2 (central neurofibromatosis) has been mapped to

chromosome 22q12.2. This disorder is characterised in particular by bilateral acousticneurinomas, but tumours may occur on other cranial nerves or spinal roots and also

paraspinally. Meningiomas and gliomas may develop. A further feature is the occurrence ofjuvenile posterior subcapsular lenticular opacities.

27. You review a 48-year-old man who has a diagnosis of colorectal carcinoma. You are

considering oxaliplatin therapy for his case. Which of the following descriptions best fitswith the use of oxaliplatin therapy?

It is commonly used as monotherapy

Concomitant folinic acid is usually prescribed Your answer

Ototoxicity is not seen with this platinum derivative

Renal function monitoring is only advised in severe renal impairment

Motor neuropathy is a common side-effect

Oxaliplatin is licensed for the treatment of metastatic colorectal carcinoma in combination

with fluorouracil and folinic acid. It is given by intravenous infusion. The dose is limited byneurotoxicity (usually sensory polyneuropathy). Other side-effects include GI toxicity,

ototoxicity and myelosuppression. Renal function monitoring is advised in cases of moderate

renal impairment.Current NICE guidance (from March 2002) recommends that oxaliplatin use be confined tothose patients who have liver metastases only, and which might be amenable to surgical

resection after chemotherapy. Irinotecan therapy may be considered in patients who have

failed to respond to a platinum-containing therapy.

28. A 38-year-old patient is being investigated for his anaemia. A bone marrow biopsy

shows a reduction of haematopoietic cells and a trephine biopsy shows mainly fatty bone

marrow. What is the most likely diagnosis?

Vitamin B12 deficiency

Folate deficiency

Aplastic anaemia Your answer

Erythropoietin deficiency



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Bone marrow aspiration is usually easy, fatty fragments are obtained and there is a

reduction of haematopoietic cells in the trails. The cellularity of the marrow may be judged

to some extent from the marrow aspirate, but a so-called dry-tap (no material obtainedfrom an aspirate) or blood-tap (no fragments obtained) does not allow an assessment of

bone marrow activity. In aplastic anaemia, there may be a patchy loss of cellularity

throughout the marrow so that an aspirate may yield relatively normal-looking marrow.The diagnosis cannot therefore be made on a bone marrow aspirate alone. Assessment of

cellularity is made on a trephine biopsy, which shows replacement of the normal cellular

marrow by fatty marrow.

29. What does the R2 classification stand for in cancer therapy?

Tumour size 2 cm

The tumour was macroscopically visible but could not be removedcompletely

Youranswer

Metastases present

Lymph node involvement

Good differentiated tumour

The following residual tumour (R) classification exists in addition to the TNMclassification and the histological grade (G):

RX Presence of residual tumour cannot be assessed

R0 No residual tumourR1 Microscopic residual tumour

R2 Macroscopic residual tumour

30. A 37-year-old man has a lump in his testicle, a mass on chest X-ray and a raised b-HCG.

What would be the most appropriate next step in his management?

Testicular biopsy

Orchidectomy

Staging computed tomography (CT) scan Your answer

Testicular ultrasound

CT-guided biopsy of the chest lesion


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The triad of a testicular lump, a mass on chest X-ray and a raised b-HCG are suggestive of

testicular seminoma. A raised b-HCG is found in around 15% of seminomas.

Orchidectomy with chemotherapy is curative in 90% of cases. Beta-Human chorionicgonadotrophin levels may be a useful correlate with response to treatment.

31. A woman is found to have ilio-femoral thrombosis during her pregnancy. Her mother

had deep vein thrombosis (DVT) as well when she was pregnant. Her thrombophilia screenis normal. Which of the following should be done?

She should be advised that she has a thrombotic state

Repeat thrombophilia screen in one month

Start low molecular weight heparin for subsequent pregnancy

Screen her sister for thrombophiliaShe may be reassured that the risks of DVT in subsequent pregnancy are

lowYour answer

A study by Edwards et al, Safety of withholding heparin in pregnant women with a historyof venous thromboembolism. N Engl J Med 2000; 343:14391444 suggests that risks of

recurrent thromboembolic disease in subsequent pregnancy are low. This study put the

risks as low as 2.4% in patients without a thrombophilic disorder. Patients with recurrent

deep vein thrombosis in pregnancy should be managed with low-molecular-weight heparin,as should those with a disorder resulting in thrombophilia.

32. A 60-year-old woman presents to her general practitioner complaining oftiredness. She is a vague about her symptoms. On examination she is clinicallyanaemic. There is a history of abdominal surgery some years previously. Somelaboratory investigations are carried out, the results of which are as follows: Hb5.6 g/dl (11.516.5), MCV 117 fl (8096), MCH 31 pg (2832), MCHC 35 g/dl (3235), WCC 2.5 109/l (411 109), platelets 132 109/l (150400 109); urea 5.0mmol/l (2.57.5), Na 139 mmol/l (137144), K 4.0 mmol/l (3.54.9), creatinine65 mmol/l (60110), AST 25 U/l (131), ALT 41 U/l (535), ALP 90 U/l (45105),

bilirubin 35 mmol/l (122), LDH 850 U/l (10250), serum vitamin B12 56 ng/l(140650), serum folate 2.5 m g/l (> 1.8).

Which of the following is most likely to be the cause of her macrocytic anaemia?

Autoimmune haemolytic anaemia

Ileal resection Your answer


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Myelodysplastic syndrome

Congenital lack of intrinsic factor

Sideroblastic anaemia

This woman has macrocytic anaemia with a markedly low serum vitamin B12level. There are some signs of haemolysis (increased bilirubin and LDH), inkeeping with the associated ineffective erythropoiesis.

Vitamin B12 is synthesised by microorganisms, and humans acquire this vitaminby eating other animals and foods contaminated by microorganisms. VitaminB12 combines in the stomach with intrinsic factor (which is produced by thegastric parietal cells) and the complex is absorbed from the terminal ileum.

Vitamin B12 deficiency can be due to dietary deficiency especially in strictvegans, or to gastric causes (pernicious anaemia, congenital lack of intrinsicfactor and gastric resection) or to intestinal causes (intestinal stagnant loop,tropical sprue, ileal resection and Crohns disease and to infection with thefish tapeworm, Diphyllobothrium latum).

33. A patient underwent an 80-cm ileum resection for Crohns disease 4 yearsago, he now presents with anaemia. His haemoglobin is 68 g/l and MCH 38 pg.What is the most likely cause?

Impaired vitamin B12 absorption

Your answer

Impaired iron absorption

Chronic bleeding after surgery

Haemolysis


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Bacterial infection

Vitamin B12 is synthesised by micro-organisms; animals obtain it by eating partsof other animals or animal produce (milk, cheese, eggs, etc), or vegetable foodscontaminated by bacteria. Malabsorption of vitamin B12 is frequent in patientswith Crohns disease, but severe vitamin B12 deficiency is unusual unless an ilealresection, fistula or stagnant loop occurs. Vitamin B12 anaemia is associated withabnormal nuclear maturation, megaloblastic erythropoiesis and macrocytic redcells.

34. A 50-year-old woman presents with acute chest pain and dyspnoea. Examination

reveals bilateral ankle oedema, with 24 hour urine protein assessment showing 8 g/d (


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109) and platelets 130 109/l (150400 109). Which haemopoietic growth factor is most

likely to lead to improvement in her neutrophil count?

Thrombopoietin

G-CSF Your answer

ErythropoietinSCF (stem-cell factor)

IL-3

Stem-cell factor (SCF) and Flt ligand (Flt-L; Flt, fms (feline McDonough sarcoma, nowknown as CSF-1 receptor)-like tyrosine kinase) act at the earliest stage of pluripotent stem-

cell development. Interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating

factor (GM-CSF) are multipotential growth factors that act on the earliest marrowmultipotential progenitors, and have overlapping activities. With cooperation from other

growth factors, SCF, Flt-L, IL-3 and GM-CSF effect the survival and differentiation of early

haemopoietic cells, so maintaining the pool of stem cells.

A series of growth factors act on committed progenitor cell to produce cells in response tothe bodys needs: G-CSF on neutrophils, M-CSF on monocytes, IL-5 (an eosinophil growth

factor) on eosinophils, erythropoietin on red cells and thrombopoietin on platelets.

Throughout the system there is considerable redundancy and overlap in function.

36. A 19-year-old man presents with a 1-week history of shortness of breath and tiredness.

There is no past medical history of note. On examination he is clinically anaemic. There isa petechial rash on his lower limbs but nothing else of note on examination. His Hb is 7.2

g/dl (1318), WCC 1.8 109

/l (411 109

), neutrophils 0.2 109

/l (1.57.0 109

) andplatelets 10 109/l (150400 109). Coagulation screen, urea and creatinine and liverfunction tests are all normal. What is the most likely diagnosis?

Acute myeloid leukaemia

Aplastic anaemia Your answer

Acute folic acid deficiency

Lymphoma

Paroxysmal nocturnal haemoglobinuria

Aplastic anaemia causes pancytopenia resulting from failure of the bone marrow. It can be

congenital (eg Fanconis anaemia) or acquired. The acquired form can be idiopathic orsecondary to ionising radiation, chemicals, drugs or infections (eg viral hepatitis). The resultis a reduction in the number of pluripotential stem cells, either due to their destruction or an

immune reaction against them. The peak age of incidence of the acquired form is 30 years

and the patients present with symptoms and signs of anaemia, neutropenia andthrombocytopenia.

Treatment initially involves removal of the cause and providing supportive treatment.

Specific treatment includes immune suppression with antilymphocyte globulin, ciclosporin


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and methylprednisolone. Bone marrow transplantation may be curative if a suitable donor is

available. Androgens and haemopoietic growth factors may also have a role to play.

37. A 35-year-old man with Christmas disease and associated arthropathy presents with a

large swollen knee joint after playing football with his young son. He is unable to weight

bear. What is the most appropriate treatment?

Aspiration of the joint

Intravenous infusion of cryoprecipitate

Intravenous DDAVP (desmopressin)

Intravenous factor IX concentrate Your answer

Bedrest and analgesia

Christmas disease, or haemophilia B, is deficiency of factor IX and is inherited in an X-

linked recessive pattern. The factor IX level dictates the disease severity and established

arthropathy is usually seen in those with severe disease (factor IX level < 1%). The historyis consistent with the development of a haemarthrosis. Joint aspiration is not recommended.

Cryoprecipitate is rich in fibrinogen, factor VIII, and von Willebrand factor and was an

established treatment for haemophilia A before the availability of plasma-derived clotting

factor concentrates. DDAVP (desmopressin) can increase factor VIII levels transiently inthose with mild haemophilia A and is useful prior to minor surgical procedures in these

patients. It is not helpful in those with severe haemophilia A or in those with haemophilia

B. The treatment of haemarthrosis is intravenous replacement of the deficient clotting

factor in this case with plasma-derived factor IX concentrate.

38. A 35-year-old man attends the haematology clinic having found a lump in his neck. He

feels generally unwell but has no past history. There is axillary lymphadenopathy and

splenomegaly. FBC shows:

WCC 16 103/mm3; Hb 8.3 g/dl; platelets 106 103/mm3

and the blood film and bone marrow aspirate show lymphoblasts. What is the most useful

test to make a definitive diagnosis?

Cytogenetic analysis

Lymph node biopsy

Total-body computed tomography (CT) scan


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Total-body positron-emission tomography (PET) scan

Immunophenotyping Your answer

Differentiating acute lymphoblastic leukaemias is most simply achieved with

immunophenotyping. B-cell lineage leukaemias are all CD10- and CD19-positive, whereas

T-cell lineage cells are CD7- and TdT (terminal deoxynucleotidyl transferase) -positive(although pre-B cells are TdT+ve, but if more mature B cells are present they are TdTve).

Cytogenetic analysis is more useful in differentiating myeloid leukaemias and inmyelodysplastic syndrome. Staging and disease progression can be monitored

radiologically.

39. Where is the chromosomal translocation in acute promyelocytic leukaemia located?

t(15:17) Your answert(9:22)

t(13:18)

t(10:19)

t(16:18)

Acute promyelocytic leukaemia (APML) almost always involves a chromosomal

translocation t(15:17) that results in the fusion of the retinoic acid receptor alpha (RAR

alpha) gene with a transcription factor gene called PML.

40. You review a 67-year-old man who has suffered from severe weight loss over the past

few weeks. He also has epigastric pain that radiates to his back. On examination he isjaundiced and you wonder about a mass in the epigastrium. Your laboratory is able to

check his tumour marker status, and you find a raised CA-19-9 result. What is the most

likely source of his cancer?

Lung

Liver

StomachPancreas Your answer

Colon

CA-19-9 is particularly raised in pancreatic cancer, although it may be raised in othergastrointestinal neoplasms. Given this patients history, the most likely primary source in

this case appears to be a pancreatic tumour.

Other tumour markers include alpha-fetoprotein (associated with hepatocellular carcinoma


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and non-seminomatous germ-cell tumours), beta-HCG (associated with choriocarcinomas,

germ-cell tumours and lung cancers), prostate-specific antigen (associated with prostatic

carcinoma), CEA (associated with gastrointestinal cancers), CA-125 (associated with ovariancancer) and CA-15-3 (associated with breast cancer). It should be noted that none of these

markers have 100% specificity for cancer, and are normally used as an adjunct to monitoring

of cancer status, rather than for diagnosis.

41. A 49-year-old man returns from working abroad with a recent diagnosis of chronic

myeloid leukaemia. You are considering a trial of the drug imatinib. Which of thefollowing statements best fits the advice and information to be given regarding the use of

imatinib?

Constipation is a common side-effect

It is recommended by NICE for Philadelphia chromosome-negativepatients

Nausea is common in patients taking imatinibYour

answer

NICE recommends its continued use after transformation from thechronic to acute phase

Gynaecomastia never occurs in patients taking imatinib

Imatinib, a protein-tyrosine kinase inhibitor, has brought great improvements in thetreatment of chronic myeloid leukaemia (CML). It is licensed for the treatment of newlydiagnosed CML where bone marrow transplantation is not considered first-line therapy, and

for CML in the chronic phase after failure of interferon-alpha, or in the accelerated phase, or

in blast crisis. Imatinib is also licensed for the treatment of gastrointestinal stromal (GIST)tumours.

Side-effects of imatinib include nausea, vomiting, diarrhoea, oedema, abdominal pain,

fatigue, myalgia, headache and rash. Gynaecomastia is reported, and is related to decreased

testosterone levels.

The National Institute for Clinical Excellence (NICE) has recommended imatinib as the first-line treatment for patients with Philadelphia chromosome-positive CML in the chronic phase

and as an option for patients presenting in the accelerated phase or with blast crisis, provided

the drug has not been used previously. In patients who progress despite the drug, itscontinued use is only recommended by NICE as part of an ongoing clinical trial.


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42. You are asked to review a patient with metastatic lung cancer who has a potassium

level of 6.5 mmol/l. He has been generally well, although he has recently complained of

tiredness and malaise. Clinically examination is unremarkable and he has normal renalfunction. He is currently on no medication. A repeat measurement shows his potassium

level to be 6.6 mmol/l. What might be the cause of his hyperkalaemia?

Tumour-lysis syndrome

Septicaemia

Bilateral uteric obstruction

Bilateral adrenal metastases Your answer

Haemolysed blood sample

The adrenal glands are the fourth most common site of metastasis after the lungs, liver andbone. The most common primary sites are lung, breast, skin (melanoma), kidney, thyroid and

colon. Adrenal metastases may be unilateral or bilateral and the tumours vary in size. Most

often, the lesions are clinically silent but hypoadrenalism does occasionally occur, as in thiscase.

Tumour-lysis syndrome is another cause of hyperkalaemia but there would be no clinical

reason to suspect it in this case. Septicaemia and bilateral uteric obstruction can lead to

hyperkalaemia by causing renal failure, but renal function is normal in this case. The factthat a repeat blood sample also shows hyperkalaemia makes haemolysis of the blood sample

unlikely.

43. A 35-year-old man of Northern European origin underwent a routine medical

examination and was found to have a 10-cm splenomegaly. He works as anadministrator and has never travelled outside Europe. He is otherwise well andhas no other physical findings. A blood test shows:

Hb is 12.3 g/dl; WCC 62 109/l; platelets 542 109/l.

What is the most likely cause of his splenomegaly?

-Thalassaemia intermedia

Malaria

Cirrhosis

Systemic lupus erythematosus


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Your answer

Splenomegaly can be classified as:

Haematological malignant Chronic myeloid leukaemia, chronic lymphocyticleukaemia, acute leukaemia, lymphoma,myelofibrosis, polycythaemia vera

Haemolysis Sickle-cell disease, autoimmune haemolyticanaemia, megaloblastic anaemia

Portal hypertension Cirrhosis, portal vein thrombosis

Storage diseases Gauchers disease, NiemannPick disease,

histiocyt-Thalassaemia intermediaosis XSystemic diseases Sarcoidosis, amyloidosis, systemic lupus

erythematosus, rheumatoid arthritis

Acute infections Bacterial endocarditis, typhoid, infectiousmononucleosis

Chronic infections Tuberculosis, brucellosis, syphilis, malaria,leishmaniasis, schistosomiasis

44. Which one of the following malignant tumours has the highest predilectionfor dissemination to bone?

Breast

Prostate

Your answer

Kidney

Lung

Thyroid


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Tumours that have a predilection for dissemination to bone are those of theprostate (32%), breast (22%), and kidney (16%) followed by the lung and the

thyroid

45. A 32-year-old Asian woman is referred to the haematology clinic with anaemia. Shehas rheumatoid arthritis and is currently taking prednisolone but has recently taken

NSAIDs for analgesia. She has a palpable splenomegaly. FBC shows Hb 8.1 g/dl, MCV 69

fl, platelets 154 103/mm3, WCC 5.2 103/mm3. A bone marrow trephine is stained for

iron and shows that iron is present in the developing erythroblasts. What is the likely causefor her anaemia?

Right medial medulla

Anaemia of chronic disease

Sideroblastic anaemia

Haemoglobinopathy Your answer

Myelodysplasia

Although there are less invasive tests to distinguish the cause of microcytic anaemia, the

presence of iron in erythroblasts effectively rules out iron deficiency and also makesanaemia of chronic disease less likely (as it involves reduced iron transport within the

marrow). A diagnosis of sideroblastic anaemia requires that the iron be specifically in a

ring form (in the mitochondria around the nucleus) in the erythroblast. Her racial origin

combined with iron in the erythroblasts makes thalassaemia the likely diagnosis where

there are reduced globin chains of adult haemoglobin A (either- or -chains). Red cellsurvival is reduced due to the imbalance of globin-chain production, as the correctly

synthesised chain precipitates and lyses the cell. Microcytosis with very mild anaemia can

be caused by small reductions in either- or -globin chain production so-called

thalassaemia trait. If no -chains are produced then thalassaemia major results, which

presents in the first year of life when haemoglobin synthesis switches from Hb F (- and -

chains) to adult Hb A (- or-chains). If no -chains are produced this causes death in

utero or very shortly after delivery (as the only Hb formed is made out of four-chains and

this form of haemoglobin cant carry oxygen). However, other forms of- or-

thalassaemia can cause an anaemia with a Hb level in the range of 7 to 10 g/dl. Four genesare needed for normal -chain production, and if three genes are deleted then anaemia can

result with splenomegaly. -Thalassaemia can result in a picture less severe than the infantpresentation if the free a-chains can be mopped up in some way either with coexistent

-thalassaemia (which will reduce the severity of the anaemia as there will be fewer free -chains to precipitate) or with the persistence of fetal haemoglobin, Hb F, which will

combine the excess - chains with -chains.


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46. An HIV-1-positive man develops raised purple lesions on his legs. His CD4 count is 96cells/mm3 (> 600 mm3) and his viral load measures greater than 500 000 copies/ml. What is

the most likely diagnosis?

Cryoglobulinaemia

Basal-cell carcinomas

Kaposis sarcoma Your answer

Fixed drug eruption

Melanoma

Kaposis sarcoma is the commonest tumour in HIV-1-positive individuals and a leading

cause of death in these patients. It is an AIDS-defining illness in 15% of patients.

Other common tumours in HIV-1 include non-Hodgkins lymphoma, Hodgkins lymphomaand those caused by human papillomavirus, including cervical and anal cancers. Kaposis

sarcoma most commonly occurs with a CD4 count of less than 200. It has a particularly

bad prognosis when it spreads to the lungs.

47. A 30-year-old man completed adjuvant chemotherapy for a stage-I testicular teratoma

one month ago. He now presents with increasing shortness of breath and a dry cough. Yoususpect an adverse drug reaction related to one of his chemotherapeutic agents. What

would be the most likely drug responsible?

Bleomycin Your answer

Cisplatin

Etoposide

Methotrexate

Vincristine

Bleomycin can cause pulmonary toxicity, which typically occurs during or shortly after

completing treatment. Classical symptoms are shortness of breath, dry cough and fever

(particularly in the acute setting). It can result in permanent damage and pulmonaryfibrosis. While methotrexate can cause pulmonary fibrosis, it is rarely seen and is not used

in the treatment of teratoma. Cisplatin and etoposide are both used to treat testicularteratoma but do not cause pulmonary toxicity. Vincristine does not cause pulmonary

toxicity the common side-effects of this agent are sensory neuropathy and alopecia.


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48. A 70-year-old woman is investigated for recurrent chest infections and bleeding.

Routine investigations show a WCC 32 103/mm3, Hb 9.1 g/dl, platelets 37 103/mm3,with a blood film showing cells of the myeloid series at various stages of maturation. What

further investigation will be most helpful in terms of diagnosis?

Cytogenetic analysis

Neutrophil LAP score

Bone marrow trephine Your answer

Immunophenotyping


Marrow failure with a large number of circulating myeloid series cells is either due to

chronic myelogenous leukaemia (CML) or myelofibrosis the clinical presentation androutine investigations are often the same in both conditions. The demonstration of marrow

fibrosis requires a trephine biopsy as the aspirate is often dry. Cytogenetic analysis can behelpful as the Philadelphia chromosome is negative in myelofibrosis, but is also negative in5% of cases of CML. The neutrophil leucocyte alkaline phosphatase (LAP) score is normal

or high in myelofibrosis and low in CML, but this is not diagnostic. The trephine

appearance in CML is of a marrow full of myeloid precursors.

49. The determination of the carcinoembryonic antigen (CEA) in patients with carcinoma

of the colon is most useful for which of the following?

The detection of an early state

As a parameter for operability

For staging

For postoperative follow-up Your answer

As a screening method

Serological tests such as carcinoembryonic antigen (CEA) levels are of some value in

postoperative management and in the detection of tumour recurrence, but are secondary to

accurate histological staging.

50. A 58-year-old Greek man is found to have a microcytic anaemia on routine screening at

his daughters general practitioner. Red cells have low mean corpuscular volume (MCV)


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and mean corpuscular haemoglobin (MCH). Serum ferritin is normal. What would be the

next management step?

Barium enema

Iron therapy

Upper and/or lower endoscopyHaemoglobin electrophoresis Your answer

Labelled red-cell scan

Given the mans ethnic origin, the most likely diagnosis is heterozygous beta-thalassaemia(thalassaemia minor). He has not presented to the medical service with any symptoms, so

any underlying blood loss is unlikely. Anaemia is mild or absent in thalassaemia minor, red

cells are hypochromic and microcytic with low mean corpuscular volume (MCV) and meancorpuscular haemoglobin (MCH), which may give rise to confusion with iron-deficiency

anaemia. Haemoglobin electrophoresis usually demonstrates a raised Hb A2 and often a

raised Hb F. Iron should not be given to these patients unless they have co-existent iron-

deficiency anaemia.

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