myelofibrosis

Question 1

definition of myelofibrosis

Answer 1

Disorder of haematopoietic stem cells characterized by progressive marrow fibrosis in association with extramedullary haematopoiesis and splenomegaly.

Question 2

aetiology of myelofibrosis

Answer 2

primary stem cell defect not known = increased numbers of abnormal megakaryocytes (platelet precursors) with stromal proliferation as a secondary reactive phenomenon to growth factors from the megakaryocytes

30% of patients have previous history of polycythaemia rubra vera or essential thrombocythaemia

Question 3

pathology of myelofibrosis

Answer 3

hyperplasia of megakaryocytes

abnormal megakaryocytes release cytokines (eg PDGF and PF4) which stimulate fibroblast proliferation and collagen deposition in bone marrow ie fibrosis in marrow, = extramedullary hematopoiesis in liver and spleen

gain-of-function V617Fmutation in the JAK2 gene is associated with disease progression.

Question 4

epidemiology of myelofibrosis

Answer 4

Rare. Annual incidence 0.4 in 100 000.

50-70yrs

Question 5

sx of myelofibrosis

Answer 5

asymptomatic - diagnosed after abnormal blood count

systemic symptoms due to hypermetabolism:

common

• weight loss
• anorexia
• fever and night sweats
• pruritus

uncommon

• LUQ pain - splenomegaly
• indigestion - caused by massive splenomegaly

due to bone marrow failure - infections, bleeding

bleeding, bone pain and gout - less common complaints

Question 6

signs of myelofibrosis

Answer 6

splenomegaly (massive in 10%) is the main physical finding,

hepatomegaly present in 50–60%.

Question 7

Ix for myelofibrosis

Answer 7

blood

blood film

bone marrow aspirate or trephine biopsy

Question 8

blood results in myelofibrosis

Answer 8

FBC (variable Hb, WCC and platelets initially, but later anaemia, leukopaenia and thrombocytopaenia).

LFT abnormal

Question 9

blood film in myelofibrosis

Answer 9

leucoerythroblastic changes - circulating red and white cell precursors,

with characteristic ‘tear drop’ poikilocyte red cells.

Question 10

bone marrow aspirate or biopsy for myelofibrosis

Answer 10

Aspiration usually unsuccessful (‘dry tap’).

Trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining.

Question 11

bone marrow aspirate

Answer 11

diagnostic info where abnormalities in the peripheral blood

take from anterior iliac crest or sternum

provides a film that is examined by a microscope