Myeloproliferative neoplasm

Myeloproliferative neoplasms are a diverse group of conditions that are characterised by an excess of terminally differentiated myeloid cells (red cells, white cells, and/or platelets) in the peripheral blood. Under WHO classification of haematolymphoid tumours, myeloproliferative neoplasms are categorised under the myeloid, mature categories ⁶.

Pathology

Classification

The classic four types of myeloproliferative neoplasms are the following ⁴:

• primary myelofibrosis

• polycythaemia vera

• essential thrombocythaemia

• chronic myeloid leukaemia

According to the World Health Organisation classification, there are additional entities categorised under myeloproliferative neoplasms ⁶:

• chronic eosinophilic leukaemia

• juvenile myelomonocytic leukaemia

• chronic neutrophilic leukaemia⁷

• myeloproliferative neoplasm, NOS

There is another separately defined category of "myeloid/lymphoid neoplasms" associated with eosinophilia characterised by specific gene arrangements ⁶.

Some additional conditions demonstrate overlap of features of myeloproliferative neoplasms and myelodysplastic syndromes ⁶.

Genetics

Chronic myeloid leukaemia is caused by a reciprocal translocation between chromosomes 9 and 22, creating the fusion gene BCR-ABL1⁷. The shortened chromosome 22 containing the fusion gene is called the Philadelphia chromosome.

All patients with polycythaemia vera and a majority of patients with primary myelofibrosis and essential thrombocytopenia have a gain-of-function mutation in JAK2, which encodes a tyrosine kinase. The most common mutation in patients with polycythaemia vera results in substitution of valine for phenylalanine in a negative regulatory domain (V617F). Most of the remaining minority of patients with primary myelofibrosis and essential thrombocythaemia have a mutation in the CALR or MPL genes.

Known gene rearrangements associated with myeloproliferative causes of hypereosinophiliamyeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions involve PDGFRA, PDGFRB, FGFR1,or PCM1-JAK2 JAK2 ⁷.

Radiographic features

Patients may present radiologically with thrombosis or bleeding ⁴. Unexplained splanchnic vein thrombosis, involving the hepatic veins (Budd-Chiari syndrome) or portal vein, is quite commonly associated with myeloproliferative neoplasms (particularly polycythaemia vera and essential thrombocythaemia) and should prompt testing for JAK2 V617F ⁵. 

Osseous changes are particularly seen in primary myelofibrosis secondary to marrow infiltration, manifest on MRI as abnormally low T1 signal, on radiographs as osteosclerosis, and on bone scintigraphy as diffusely increased skeletal uptake (superscan)

Splenomegaly is common but non-specific. As peripheral blood count abnormalities may sometimes be masked by hypersplenism, other secondary radiologic findings may be the only clue to an occult myeloproliferative neoplasm. 

The most common solid lesion is extramedullary haematopoiesis, which can appear as masses in the spleen, liver, or paravertebral tissues.