A systematic review of 47 published cases of extramedullary hematopoiesis in myelofibrosis: clinical patterns, treatment responses, and prognostic implications

Extramedullary hematopoiesis (EMH) in myelofibrosis manifests beyond classical splenomegaly, causing life-threatening complications, yet lacks systematic characterization in the JAK inhibitor era. We systematically reviewed 36 publications (2011–2025), available on PubMed database, reporting 47 unique myelofibrosis-associated EMH cases, analyzing demographics, anatomic distribution, presentations, diagnostics, treatments, and outcomes. Median age was 68 years (range 43–82; M: F 26:21); primary myelofibrosis predominated (64%). EMH favored atypical sites: abdominopelvic (28%), thoracic (26%; pulmonary/pleural), serosal (17%), cutaneous (13%). Symptomatic onset occurred in 75% (dyspnea 28%, abdominal pain 21%). CT/MRI revealed characteristic lobulated masses with T2 hypointensity; biopsy confirmed trilineage hematopoiesis with atypical megakaryocytes (CD61+). Ruxolitinib-based regimens, administered in 19 patients (40%) as EMH-directed therapy, yielded rapid palliation (dyspnea/ascites resolution), complemented by radiotherapy (11%) and splenectomy; HSCT achieved complete remission in one case. Mortality reached 38% (median follow-up 5 months), driven by EMH-related organ failure or AML transformation. Atypical EMH signals advanced myelofibrosis with dismal prognosis, responsive to JAK inhibitors/locoregional therapies but highlighting sanctuary biology. Systematic surveillance and transplant referral are imperative; prospective registries are needed to refine risk models and test novel antifibrotics.