Myasthenia gravis is a B-cell-mediated autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The underlying defect is an autoantibody-mediated attack on the acetylcholine receptors (AchRs) at the neuromuscular junction. Rituximab is a genetically engineered chimeric murine/human monoclonal antibody indicated for treatment of patients with low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Based on its potential for elimination of auto-reactive B-cell clones, rituximab may have a role in the management of some autoimmune disorders. We report a patient with B-cell, follicular non-Hodgkin lymphoma and a long-standing history of myasthenia gravis and the favorable impact of rituximab on both disorders. Am.

An 84-year-old female was admitted to the State University of New York University Hospital (Syracuse, NY) with complaints of persistent right hip pain for longer than 1 month. Her past medical history was significant for Wolff-Parkinson-White syndrome and osteoarthritis. The physical exam was unremarkable except for some decreased range of motion of the right hip. Computed tomography scan of the abdomen and pelvis showed a massive (8.5 ϫ 7.0 cm), asymmetric, and heterogeneous mass in the right psoas muscle (Fig 1). Radiologically, the mass appeared to be a well-circumscribed hematoma. Biopsy showed a diffuse infiltrate of large neoplastic cells with plasmablastic (cells with rounded nuclei, coarser chromatin, and smaller two to three nucleoli) and immunoblastic morphology (cells with vesicular enlarged nuclei and single prominent nucleolus, Fig 2A). High proliferative index, frequent apoptosis, and focal necrosis were seen. The neoplastic cells were essentially CD20 negative ( Fig 2B) and showed strong positivity with CD138 ( Fig 2C) and CD79a ( Fig 2D). Additionally kappa light chain restriction was noted by in situ hybridization (Figs 3A, kappa; 3B, lambda). Multiple myeloma oncogene-1 (Fig 3C) showed diffuse strong nuclear positivity and paired box gene-5 (PAX-5; Fig 3D) was positive in more than 50% of the tumor cells. Pancytokeratin, markers for breast carcinoma (GCDFP-15 and mammoglobulin), lung malignancy (TTF-1 and CK-7), melanoma (S-100 and MART-1) and other lymphoid markers (CD10, CD3, CD4, CD8, CD56, CD68, Bcl-6, ALK, and CD30) were all negative. Staining for Epstein-Barr virus (EBV) both by immunohistochemistry (EBV latent member protein 1) and in situ hybridization (EBV-encoded RNA) was also negative. Further staging work-up including computed tomography of the thorax and bone scan were

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Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. Am.