Hematopathology / AUTOIMMUNE MYELOFIBROSIS Pathology of Autoimmune Myelofibrosis A Report of Three Cases and a Review of the Literature

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or lowgrade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis. Bone marrow fibrosis is associated with numerous causes including myeloproliferative disease, other hematologic and nonhematologic malignant neoplasms, autoimmune disorders, and endocrine disorders.1 Cases reported as autoimmune myelofibrosis (AM) have been associated with collagen vascular disease, in particular, systemic lupus erythematosus (SLE).2-14 This rare bone marrow failure syndrome may predate the diagnosis of SLE or SLE-like disease or develop during the course of documented disease. Rare cases of AM have been described in patients with Sjögren syndrome and progressive systemic sclerosis.15,16 In addition, 1 case of AM has been described with a positive direct Coombs test result, splenomegaly, and bone marrow lymphoid infiltrate mimicking hairy cell leukemia.17 AM typically occurs in females, with most cases developing before the age of 40 years.2-17 Laboratory features of AM include anemia, thrombocytopenia, left-shifted granulocytes, rare circulating nucleated RBCs, serologic evidence of autoimmune disease, hypocomplementemia, and a positive direct Coombs test result.2 Physical examination may demonstrate splenomegaly or hepatosplenomegaly and arthralgias or, less commonly, oral ulcers, gingival bleeding, petechiae, pleuritis, pericarditis, lymphadenopathy, and malar rash.2 We describe 3 new cases of AM in order to further define the morphologic and immunohistochemical features characteristic of this entity and to review the clinical and pathologic features of cases reported in the literature.