Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease...

Area of Science:

• Hematopathology
• Oncology
• Molecular Diagnostics

Background:

• The diagnostic criteria for essential thrombocythemia (ET) remain controversial, particularly regarding the role of histopathology.
• Quantifying interobserver variability in the histopathological assessment of ET is crucial for diagnostic accuracy.

Purpose of the Study:

• To assess interobserver variability in the histopathological diagnosis of essential thrombocythemia (ET) using World Health Organization (WHO) classification criteria.
• To identify key morphologic features and their association with molecular markers and clinical outcomes in ET.

Main Methods:

• Bone marrow trephine biopsy specimens from 370 ET patients (diagnosed by Polycythemia Vera Study Group criteria) were reviewed by 3 hematopathologists.
• Hematopathologists assessed 16 morphologic features and provided an overall diagnosis according to WHO classification.
• Statistical analyses, including factor analysis and association with JAK2 V617F status, were performed.

Main Results:

• Substantial interobserver variability was observed in the overall diagnosis and specific cellular characteristics, including megakaryocyte morphology.
• Reticulin grade emerged as the primary independent predictor of the WHO diagnostic category across all pathologists.
• Three independent factors were identified: cellularity (associated with JAK2 V617F), megakaryocyte clustering, and fibrotic process.

Conclusions:

• The histopathological criteria in the WHO classification for ET are challenging to apply reproducibly.
• Distinguishing between "true ET" and "prefibrotic myelofibrosis" based on subjective morphologic criteria is questionable.
• Further refinement of diagnostic criteria integrating histopathology and molecular findings is warranted for essential thrombocythemia.