FRCPath Haem Part 1 EMQs- Oncology 72 and 73

Theme: Diagnosis, Risk Stratification and Management of ET

Options

A. Reactive thrombocytosis secondary to iron deficiency

B. Triple-negative ET

C. CALR-mutated ET

D. JAK2 V617F-positive ET

E. MPL-mutated ET

F. Hydroxycarbamide

G. Pegylated interferon-alpha

H. Anagrelide

I. Aspirin alone with observation

J. Bone marrow biopsy and extended molecular testing

K. Busulfan

L. Essential thrombocythaemia in pregnancy requiring LMWH and interferon

M. Idiopathic thrombocytosis of undetermined significance (ITUS)

N. Clonal thrombocytosis of undetermined significance (CTUS)

O. Post-ET myelofibrotic transformation

Questions

Question 1

A 33-year-old woman is referred with persistent thrombocytosis identified during investigation for headaches and erythromelalgia. Platelet count is 980 ×10⁹/L, Hb 118 g/L and WBC 7.5 ×10⁹/L. She has no cardiovascular risk factors and no previous thrombosis. Ferritin and CRP are normal. JAK2 V617F mutation is absent. Bone marrow examination demonstrates marked megakaryocytic proliferation with large hyperlobated “staghorn” megakaryocytes and minimal reticulin fibrosis. Molecular analysis reveals a type 1 CALR mutation.

Which is the SINGLE most likely diagnosis?

Question 2

A 71-year-old man with hypertension, diabetes mellitus and prior NSTEMI is found to have a platelet count of 670 ×10⁹/L. Hb is 152 g/L and WBC 14 ×10⁹/L. He reports aquagenic pruritus and transient visual disturbance. JAK2 V617F mutation is detected. Bone marrow demonstrates megakaryocytic proliferation without significant fibrosis.

Which molecular subtype is MOST associated with increased thrombotic risk and later transformation to polycythaemia vera?

Question 3

A 42-year-old female presents with platelet count 520 ×10⁹/L discovered incidentally during pre-operative assessment. Hb 82 g/L, MCV 68 fL and ferritin 5 µg/L. CRP normal. Blood film shows hypochromic microcytic red cells and thrombocytosis. JAK2, CALR and MPL mutations are negative.

What is the MOST likely explanation for the thrombocytosis?

Question 4

A 29-year-old woman with known ET presents at 10 weeks’ gestation. She has a prior history of first trimester miscarriage and a previous splanchnic vein thrombosis. Platelet count is 850 ×10⁹/L. She is currently taking hydroxycarbamide.

What is the MOST appropriate management?

Question 5

A 58-year-old man with ET was commenced on hydroxycarbamide 4 years ago after an ischaemic stroke. Platelet count is now well controlled at 390 ×10⁹/L. However, he develops painful non-healing ulcers over both ankles. There is no evidence of venous insufficiency or vasculitis.

What is the MOST appropriate next treatment?

Question 6

A 76-year-old frail woman with ET has progressive thrombocytosis despite intolerance to hydroxycarbamide and pegylated interferon. She has severe osteoarthritis, limited mobility and mild dementia. Platelet count is 1450 ×10⁹/L. Bone marrow shows no transformation.

Which cytoreductive therapy is MOST appropriate?

Question 7

A 36-year-old woman has persistent platelet counts between 470–520 ×10⁹/L for 4 years. She is asymptomatic. No cardiovascular risk factors are present. Ferritin, CRP and autoimmune screen are normal. JAK2/CALR/MPL testing and extended myeloid NGS panel are negative. Bone marrow demonstrates no megakaryocyte atypia and no fibrosis.

According to proposed BSH terminology, what is the MOST appropriate classification?

Question 8

A 64-year-old man presents with constitutional symptoms, drenching night sweats and weight loss. He has longstanding ET diagnosed 15 years previously. Examination reveals splenomegaly 8 cm below the costal margin. Hb 89 g/L, WBC 22 ×10⁹/L and platelets 210 ×10⁹/L. Blood film demonstrates tear drop poikilocytes and a leucoerythroblastic picture. Bone marrow aspirate is dry tap.

What is the MOST likely diagnosis?

Question 9

A 47-year-old female with ET is commenced on second-line therapy after hydroxycarbamide intolerance. Two years later, repeat marrow biopsy demonstrates progressive reticulin fibrosis. She remains on aspirin. The treating haematologist notes that the chosen agent is recognised to increase risk of myelofibrotic transformation compared with hydroxycarbamide.

Which treatment was MOST likely prescribed?

Question 10

A 52-year-old woman has platelet count persistently around 780 ×10⁹/L. JAK2/CALR/MPL testing is negative. Bone marrow shows atypical megakaryocytic proliferation consistent with ET morphology. Extended molecular testing demonstrates a pathogenic ASXL1 mutation. She has no thrombosis history but does have hypertension and hypercholesterolaemia.

According to proposed BSH terminology, which category BEST fits this patient?