Abstract

We present the case of a 77-year-old man with MPL, IDH1, and SRSF2-mutated primary myelofibrosis who presented with multiple subcutaneous nodules on his thighs while receiving the ALK2-inhibitor INCB000928. After termination of this treatment and initiation of luspatercept, an activin receptor ligand trap which reduces SMAD signaling and promotes erythropoiesis, the nodules became more tender over several weeks. There was no improvement with topical betamethasone. Punch biopsy revealed a neutrophil and histiocyte-rich septal and lobular panniculitic infiltrate. Immunohistochemistry showed IDH1 R132H expression in lesional cells, as well as MPO-positive mononuclear cells. Definitive blasts were not identified by morphology or by CD34 and CD117 immunostains. No erythroid precursors or megakaryocytes were noted with CD117 and CD61, respectively, providing no support for extramedullary hematopoiesis. Overall, the findings indicated cutaneous involvement by the patient's primary myelofibrosis. The possibility of secondary cutaneous involvement driven by a separate process was considered. Stains for bacterial, mycobacterial, and fungal organisms were negative, and the patient was afebrile, providing no support for infection. To our knowledge, panniculitis has not been reported as a cutaneous adverse event in association with luspatercept or INCB000928. Furthermore, the onset of the nodules preceded the initiation of INCB000928 and worsened after cessation of luspatercept, arguing against a drug culprit. The patient did not have a history of autoimmune disease. Ultimately, these lesions were interpreted to represent primary involvement by his myeloid neoplasm. This case highlights the utility of IDH1 R132H immunohistochemistry to quickly confirm cutaneous involvement by myeloid neoplasia harboring this specific mutation.