#00066468

A 12-year-old girl with persistent bone pains, muscle weakness, and severe thrombocytopenia presented to hematology with a negative autoimmune workup. Recent complete blood count revealed a leukocyte count of 11.89 × 10⁹/L, hemoglobin of 10.6 g/dL, and a platelet count of 40 × 10⁹/L, with 2.9% immature granulocytes. Peripheral smear demonstrated normocytic, normochromic anemia, rare dacrocytes (panel A, Giemsa-Wright stain; original magnification ×1000). Bone marrow biopsy showed >95% cellularity with orderly granulopoiesis and erythropoiesis and a myeloid-to-erythroid ratio of 4:1. Megakaryocytes were markedly increased, showing a spectrum of cytomorphology, forming frequent, variably tight clusters (panel B-C, hematoxylin and eosin stain, original magnification ×100; panel D, CD61, original magnification ×200). A diffuse increase in type 3 collagen fibers with frequent dense, intersecting fibers and coarse bundles was seen (panel E, original magnification ×100; panel F, original magnification ×200). CD20 (panel G, original magnification ×200) and CD3 (panel H, original magnification ×200) highlighted increased interstitial B- and T-lymphocytes, respectively. Flow cytometry showed no abnormal populations. The patient was diagnosed with World Health Organization grade MF-2 myelofibrosis. Following additional workup for infectious and metabolic disorders, genetic testing was pursued. Microarray analysis identified a 15.3-Mbp region copy-neutral loss of heterozygosity on 6p22.2–p21.1, encompassing MPIG6B (megakaryocyte and platelet inhibitory receptor G6b). Subsequent exome sequencing detected a pathogenic variant, MPIG6B c.30del, p.(L11Cfs∗21). MPIG6B-related myelofibrosis is a rare, autosomal recessive primary myelofibrotic disorder.

This case demonstrates the high level of clinical suspicion required to identify pediatric cases of primary myelofibrotic conditions.

For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit https://imagebank.hematology.org.