Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient

Abstract

Elevated peripheral blood (PB) cell counts, such as leukocytosis, thrombocytosis, and polycythemia, are often the presenting symptom in patients with myeloproliferative neoplasms (MPN). Because cythemias are nonspecific and may reflect either a reactive or neoplastic process, diagnostic workup of these patients is complicated and requires integration of numerous diagnostic modalities. Careful morphologic evaluation of the PB smear may provide insights into the underlying cause of the abnormal counts (such as the presence of teardrop erythrocytes in myelofibrosis or granulocytic dysplasia with left shift in atypical chronic myeloid leukemia). However, these morphologic findings need to be interpreted in concert with clinical findings and other laboratory results. In recent years, there has been a wealth of new genetic data in the field of MPN and many recurrent mutations have been identified, especially in cases lacking Philadelphia chromosome. Many of these genes impact the diagnosis and/or prognosis. Although certain mutations are preferentially enriched in specific MPN types, none of these mutations are disease defining; therefore, a thorough workup should always include a bone marrow biopsy for morphologic evaluation and diagnosis. This review will describe a comprehensive approach to the diagnosis of various MPN, with an emphasis on the diagnostic and prognostic implications of recurrent mutations in MPN.

Myeloproliferative neoplasms: Classifications and an approach to diagnosis

“…THE MYELOPROLIFERATIVE NEOPLASMS (MPNs) are a group of disorders that share overlapping clinical, pathological and genetic features that result in abnormal proliferation of mature myeloid cell lineages and a predisposition to developing bone marrow fibrosis and acute myeloid leukaemia. 1,2 MPNs are uncommon, with incidence rates quoted as 2-6 per 100,000 per year. 3,4 The four classic MPNs, which will be discussed in this article, include polycythaemia vera, essential thrombocytosis, primary myelofibrosis (PMF) and chronic myeloid leukaemia (CML).…”

“…Uncommonly, patients may present with leucostasis manifesting as pulmonary (dyspnoea, hypoxia) or neurological (visual changes, headaches, dizziness) symptoms. 1,10 In polycythaemia vera, microvascularrelated symptoms such as headaches, dizziness, visual disturbances, plethora, erythromelalgia and aquagenic pruritus may be evident. Erythromelalgia can be described as episodic intense erythema and burning pain in response to heat stimuli.…”

“…Symptoms, if present, are similar to polycythaemia vera and may include headaches, visual disturbances, dizziness and erythromelalgia. 1,13 PMF is a presentation of myelofibrosis without a preceding diagnosis of polycythaemia vera or essential thrombocytosis, in contrast to secondary myelofibrosis, in which there is a transformation of disease. Constitutional symptoms, such as fatigue, fevers, weight loss and night sweats, are common.…”

Designing a Scoring System for Differential Diagnosis From Reactive Thrombocytosis and Essential Thrombocytosis

“…In contrast, essential thrombocytosis is associated with the myeloproliferative neoplasms and results from unregulated abnormal platelet production from the bone marrow progenitor cells. The abnormal proliferation of mature bone marrow cells is observed in all three lineages: leukocytes, erythrocytes, and megakaryocytes ( 6 ).…”

Automated diagnostic support system with deep learning algorithms for distinction of Philadelphia chromosome-negative myeloproliferative neoplasms using peripheral blood specimen

“…Since various non-hematologic disorders can also cause leukocytosis, thrombocytosis, and polycythemia, careful evaluation of the morphology in PB cells is critical for accurate initial diagnoses of Ph-negative MPNs, especially for detecting abnormalities in the cells. For example, immature granulocytes and nucleated RBCs are known to be observed in MF, including overt PMFs and secondary MFs 6,7 .…”