Essential thrombocythemia with MPL W515S mutation

An 81-year-old woman with multiple medical comorbidities presented with long-standing anemia and episodic thrombocytosis (857 × 10⁹/L at presentation). Initial laboratory testing was notable for low ferritin and negative genotyping for JAK2 exon 12, JAK2 V617F, calreticulin (exon 9), and MPL (W515L/K) gene mutations. A peripheral smear revealed frequent large platelets (panel A: Wright-Giemsa stain; 100× objective, original magnification ×1000). Bone marrow biopsy revealed megakaryocytic hyperplasia with large, atypical, hyperlobated forms (panel B: hematoxylin and eosin stain; 50× objective, original magnification ×500). An iron stain showed decreased iron stores. Although the episodic nature of her thrombocytosis, negative polymerase chain reaction (PCR) testing, and decreased iron stores favor a reactive thrombocytosis, suspicion for a myeloproliferative neoplasm remained high given the chronicity of her thrombocytosis (∼12 years) and bone marrow morphology. Therefore, next generation sequencing (NGS) was performed, revealing an MPL W515S mutation (panel C).

Although rare, activating mutations at codon W515 other than W515L/K have been reported in the literature, including W515S. Importantly, targeted PCR testing for MPL gene mutations may only identify the 2 most common amino acid substitutions (W515L/K). In patients with bone marrow biopsies that are suspicious for a myeloproliferative neoplasm but have negative PCR workups (so-called triple-negative myeloproliferative neoplasms), NGS should be considered.

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