Splenic marginal zone lymphoma with Evans’ syndrome, autoimmunity, and peripheral gamma/delta T cells

Abstract

Dear Editor, Several theories have tried to explain the occurrence of autoantibodies in lymphoid malignancies. Autoimmune phenomena like Evans’ syndrome, lupus anticoagulants, autoimmune thrombocytopenia, and autoimmune hemolytic anemias are frequently associated with lymphomas [4, 5]. Recently, systemic lupus erythematosus (SLE) was associated with an increased risk of diffuse large B cell and marginal zone lymphomas [3]. Splenic marginal zone lymphoma (SMZL) is an indolent B cell lymphoma, which generally presents splenomegaly and involvement of both bone marrow and peripheral blood. In this report, we describe a patient with autoimmunity and bone marrow infiltration that probably broke the mechanisms of central tolerance in bone marrow producing the emergency of new auto-reactive clones and autoantibodies. A 60-year-old man had a 12-month history of B symptoms. Physical examination was unremarkable, except for the presence of massive splenomegaly. A computerized tomograhpy (CT) scan of the abdomen confirmed splenomegaly and visualized enlarged lymph nodes in retroperitoneum (Fig. 1). Blood smear and peripheral blood immunophenotype suggest SMZL with villous lymphocytes. The patient underwent laparotomy for splenectomy, lymph node, and bone marrow biopsies. Histology corresponds to SMZL. Follow-up studies detected the persistence of lymphoid neoplastic cells (1.4%) and a γδ T cell population (TCR γδ CD2+, CD3+, CD5 low+, CD7+, CD8 low+/−, CD16 −/+ CD56+, CD57 +/−) that represented 12% of the cells in peripheral blood. Five months after diagnosis, the patient presented with abdominal discomfort. On a CT scan, abdominal adenopatic progression was observed and the two populations (3.4% of SMZL and 4.9% of γδ T cells) persisted in peripheral blood. The patient received eight cycles of chemotherapy with cyclophosphamide–doxorubicin–vincristin–prednisone regime, resulting in radiological remission. At this moment, flow cytometry of peripheral blood revealed 0.0026% of tumor cells and 13.75% of γδ T cells. Four months after chemotherapy, the patient was admitted to the hospital with a recurrence of SZML. He showed, besides, respiratory insufficiency and Evans’ syndrome, associated with high titers of antiphospholipid antibodies, lupus anticoagulant and prolonged partial tromboplastin time, high levels of immune complexes, and low levels of both immunoglobulins and C3 and C4 fractions of complement. Antinuclear, antineutrophil cytoplasmic, anticardiolipin, antiplatelets, anti-HLA I, and antiEPCR antibodies were also detected. CT scan ascertained the presence of pulmonary emphysema and hepatomegaly, without associated enlarged lymph nodes. Peripheral blood flow-cytometry indicated an increase in the neoplastic B cell population (50%) and a decrease of γδ T cells (5%). The bone marrow biopsy confirmed lymphoid infiltration (SMZL 35% and γδ T cells 4%) by immunophenotype. Ann Hematol (2009) 88:177–178 DOI 10.1007/s00277-008-0555-z