Cooperation between pathologists and clinicians allows a better diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms

Abstract

As no specific genetic lesions have yet been identified, the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms is based on a simultaneous evaluation of the clinical, morphological and molecular features defined by the updated WHO classification, which allow most cases of full-blown disease to be classified. Nevertheless, about 10–15% of the patients have unclassifiable myeloproliferative neoplasms, most of whom are in the prodromal (early) phase of disease and identified by the presence of the JAK2 mutation, but lack the complete phenotype required by the WHO classification. The detection of these prodromal phases is extremely important in order to prevent dramatic thrombo-hemorrhagic complications and improve prognosis.

Keywords::

• bone marrow
• essential thrombocythemia
• megakaryocyte
• myelofibrosis
• myeloproliferative neoplasms
• polycythemia vera
• primary myelofibrosis

Financial & competing interests disclosure

The authors wish to thank Fondazione Matarelli per lo Studio e la Cura delle Malattie del Sangue and the Beat Leukemia Foundation – ONLUS (www.beat-leukemia.org) for granting funding support. G Lambertenghi Deliliers is the president of Fondazione Matarelli per lo Studio e la Cura delle Malattie del Sangue. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are characterized by hematopoietic stem cell-derived clonal myeloproliferation, progressive stromal alterations and possible evolution to acute myeloid leukemia.

• Approximately 97% of all polycythemia vera patients have the JAK2 V617F-acquired activating somatic mutation, which can be identified in about 50–60% of all essential thrombocythemia and primary myelofibrosis patients.

• Clinicians are aware that identifying the JAK2 V617F or other activating mutations is helpful in distinguishing reactive and neoplastic conditions although a positive result cannot differentiate the three Ph-MPNs.

• Because of the lack of specificity of the JAK2 V617F mutation, the diagnosis of Ph-MPNs is still based on the simultaneous evaluation of their clinical, morphological and genetic features as defined by the updated WHO classification.

• Ph-MPNs are characterized by a stepwise evolution that starts with a prodromal ‘early’ phase that cannot be identified using the current WHO diagnostic criteria, develops into full-blown disease and subsequently reaches an advanced myelofibrotic terminal phase.

• Identifying the prodromal phase is extremely important in preventing dramatic thrombotic and hemorrhagic events such as cerebral and splanchnic vein thrombosis or Budd–Chiari syndrome.

• Identification of the prodromal phase is currently based on evaluations of the JAK2 V617F mutation and the morphological features of a bone marrow biopsy.

Notes

A diagnosis of essential thrombocythemia requires the presence of all four criteria.

CML: Chronic myelogenous leukemia; MDS: Myelodysplastic syndrome; PMF: Primary myelofibrosis; PV: Polycythemia vera.

Adapted with permission from [42].