Triple-negative Primary Myelofibrosis: A Diagnostic Challenge

Abstract

Primary myelofibrosis (PMF) is a BCR-ABL1-negative myeloproliferative neoplasm that may be diagnostically difficult when canonical driver mutations are absent. We report a male in his 30s with treated hypothyroidism who presented with low-grade intermittent fever and left-sided dragging abdominal pain for one week, with loss of appetite for two months, weight loss for one month and easy fatigability for one month. Examination showed pallor and massive splenomegaly extending beyond the umbilicus into the right iliac fossa. Complete blood count demonstrated pancytopenia, with haemoglobin 5.6 g/dL, total count 1.1 x 10^3/microL and platelet count 55 x 10^3/microL. Peripheral smear showed dimorphic anaemia, nucleated red blood cells, leucopenia, thrombocytopenia and a leucoerythroblastic blood picture, without circulating blasts or dysplastic cells. Imaging confirmed massive splenomegaly without lymphadenopathy. Bone marrow biopsy showed hypercellular marrow with trilineage haematopoiesis, dimorphic erythropoiesis, megakaryocytic atypia with hypolobulated and dwarf forms, and grade 2 marrow fibrosis. BCR-ABL1 fluorescence in situ hybridisation was negative, and JAK2, CALR and MPL testing did not identify clinically significant variants. Positron emission tomography-computed tomography, flow cytometry, autoimmune tests, viral serology and infectious work-up did not support lymphoma or reactive marrow fibrosis. Next-generation sequencing did not detect high-risk or prognostically adverse mutations. On clinicopathological correlation, the diagnosis favoured triple-negative overt fibrotic PMF. The patient was risk stratified as clinically intermediate risk and treated with ruxolitinib and thalidomide, with improvement in cytopenias, constitutional symptoms and spleen size. The case highlights the importance of integrating marrow morphology, exclusion of secondary causes and molecular testing in triple-negative PMF.