Diagnostic Challenges in Myelofibrosis: Distinguishing Prefibrotic Disease_
Panelists discuss how distinguishing pre-fibrotic myelofibrosis from other myeloproliferative neoplasms like essential thrombocythemia remains challenging due to overlapping clinical and molecular features, subjective histopathologic interpretation, and variable application of diagnostic criteria, underscoring the need for expert pathology review and multidisciplinary evaluation to guide accurate diagnosis and management.
Summary for Physicians:
Challenges in Distinguishing Pre-Fibrotic Myelofibrosis from Other MPNs:
Prefibrotic myelofibrosis (pre-MF) presents several diagnostic challenges, particularly in differentiating it from other Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) such as essential thrombocythemia (ET) and early-phase primary myelofibrosis (PMF). These challenges include:
- Overlapping Clinical Features:
- Pre-MF and ET often share similar presentations—such as thrombocytosis, mild leukocytosis, and minimal symptoms—making them difficult to distinguish based on clinical features alone.
- Splenomegaly and constitutional symptoms may be mild or absent in early stages of both conditions.
- Histopathologic Complexity:
- Accurate diagnosis requires expert bone marrow histopathology review. Pre-MF is characterized by increased megakaryocyte proliferation and atypia without significant reticulin fibrosis (grade 0-1).
- Distinguishing these subtle histologic features from ET—where megakaryocytes are more mature and clustered differently—can be subjective and requires experienced hematopathology interpretation.
- Prognostic Implications:
- Misclassification has important consequences, as pre-MF carries a higher risk of progression to overt myelofibrosis or leukemic transformation compared to ET.
- Therefore, precise diagnosis impacts risk stratification, treatment planning, and surveillance intensity.
- Molecular Similarities:
- Both pre-MF and ET can harbor similar driver mutations (eg, JAK2, CALR, MPL), which do not definitively differentiate between the entities.
- Non–driver mutations (eg, ASXL1, SRSF2) may provide prognostic value but are not routinely used to distinguish between MPN subtypes.
- Lack of Uniform Awareness or Criteria Application:
- Variability in how the 2016 World Health Organization criteria are applied across institutions may lead to inconsistent diagnoses.
- Increased awareness and standardization in using the diagnostic criteria are needed to improve diagnostic accuracy.
In summary, distinguishing prefibrotic MF from other MPNs like ET is complex due to overlapping features, subjective histologic interpretation, and limited discriminative value of molecular findings. A multidisciplinary approach involving experienced hematopathologists, molecular profiling, and clinical correlation is essential for accurate diagnosis and appropriate management.
