Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics

Abstract

The diagnosis of a myeloid neoplasm relies on a combination of clinical, morphological, immunophenotypic and genetic features, and an integrated, multimodality approach is needed for precise classification. The basic diagnostics of myeloid neoplasms still rely on cell counts and morphology of peripheral blood and bone marrow aspirate, flow cytometry, cytogenetics and bone marrow trephine biopsy, but particularly in the setting of Ph− myeloproliferative neoplasms (MPN), the trephine biopsy has a crucial role. Nowadays, molecular studies are of great importance in confirming or refining a diagnosis and providing prognostic information. All myeloid neoplasms of chronic evolution included in this review, nowadays feature the presence or absence of specific genetic markers in their diagnostic criteria according to the current WHO classification, underlining the importance of molecular studies. Crucial differential diagnoses of Ph− MPN are the category of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This review focuses on morphological, immunophenotypical and molecular features of BCR-ABL1-negative MPN and their differential diagnoses. Furthermore, areas of difficulties and open questions in their classification are addressed, and the persistent role of morphology in the area of molecular medicine is discussed.

CSF3R T618I mutant myelodysplastic/myeloproliferative neoplasm in the elderly: An age-related disease with unfavorable prognosis

“…Sometimes, it became challenging to definitively classify these cases. Due to the overlapping mutational and expression profile of CNL and aCML, and to a lesser extent CMML and MDS/MPN-U, and their association with clonal hematopoiesis, it has recently been suggested that these entities might represent a continuum of closely related hematological disorders rather than discrete entities [ 19 , 20 ]. The findings in our patients supported this model, which suggested that it might be appropriate to collectively classify these cases as CSF3R positive myeloid neoplasm.…”

Cytological Diagnosis of Classic Myeloproliferative Neoplasms at the Age of Molecular Biology

“…Reticulin staining is normal in 80% of cases but increased reticulin or mild to moderate collagen fibrosis can be observed, depending on the stage of disease [ 31 ]. At the diagnosis, the discovery of fibrosis grade 1 has a negative prognostic impact with the rapid evolution of the disease [ 32 , 33 ]. Therefore, BM biopsy should be realized whatever the levels of Hb, Hct and EPO for establishing the initial diagnosis.…”

“…Transformation into myelofibrosis can occur in 4.9–6% of PV at 10 years [ 33 , 34 ]. This stage is generally associated with cytopenia, extra-medullary hematopoiesis and hypersplenism.…”

“…The BM biopsy shows lower cellularity: erythropoiesis and granulopoiesis are decreased with possible fibrosis of grade 2–3. Dystrophic megakaryocytic clusters with hyperchromatic and very dysmorphic nuclei (hypolobulation) are prominent and an elevation of blast count is observed [ 33 ]. Osteosclerosis and the transformation into MDS or AL (more than 20% blast count in PB or BM) are around 10% [ 20 ].…”

“…Finally, no MPL mutation is observed in PV and only very rare CALR mutation type I can be observed [ 50 ]. In these two described cases, erythropoiesis is elevated with irregular MKs but without clustering [ 33 ].…”