EXTRAORDINARY CASE REPORT Rare Presentation of Secondary Cutaneous Involvement by Splenic Marginal Zone Lymphoma: Report of a Case and Review of the Literature Jeffrey M. Cohen, BA,* Rosalynn M. Nazarian, MD,† Judith A. Ferry, MD,† Ronald W. Takvorian, MD,‡ and Joi B. Carter, MD§ Abstract: Cutaneous lymphomas encompass a broad spectrum of malignancies, including both primary and secondary cutaneous lymphomas. Determining the exact subtype of cutaneous lymphoma offers prognostic importance and directs therapeutic decisions. We describe the case of a 67-year-old woman with cutaneous involvement of splenic marginal zone lymphoma successfully treated with rituximab and bendamustine. We discuss the diagnostic work-up, including the histopathologic findings and treatment of this disease. Key Words: B-cell lymphoma, cutaneous lymphoma, splenic marginal zone lymphoma, chemotherapy (Am J Dermatopathol 2015;37:e1–e4) INTRODUCTION Splenic marginal zone lymphoma (SMZL) is a rare and generally indolent B-cell lymphoma. 1 Standard treatment is with rituximab, and chemotherapy has been added with reported increased rates of maintenance and prevention of disease progression. 2,3 SMZL metastasizes infrequently, and spread to the skin is quite rare. 1 Here, we describe the case of a 67-year-old woman with SMZL involving the skin. Her disease has been successfully managed with rituximab and bendamustine. CASE REPORT A 67-year-old woman was referred to the hematology–oncology clinic by her primary care physician for the evaluation of splenomegaly. This was accompanied by a 1-year history of weight loss and fatigue, despite a good appetite. The patient denied bleeding, easy bruising, and constitutional complaints. She did note a feeling of fullness in the right and left upper quadrants of her abdomen. Physical examination revealed a firm, nontender, palpable spleen (2 fingerbreadths) below the umbilicus on quiet breathing. The liver was palpable approximately 2–3 fingerbreadths below the costal margin. No palpable peripheral lymphadenopathy and no cutaneous lesions were identified. Complete blood count revealed thrombocytopenia (73,000/mm 3 ). The hematocrit was 36.9, the white blood cell count was 5600 per cubic millimeter (32% neutrophils, 65% lymphocytes, 3% monocytes), and the peripheral blood smear showed occasional lymphocytes with villous projections. The b-2–microglobulin level was elevated at 5.1 mg/mL (normal, 0.70–1.80). Abdominal CT scan revealed splenomegaly. A bone marrow biopsy was performed. The bone marrow biopsy was found to have lymphoid aggregates suspicious for involvement by lymphoma. Immunohis- tochemistry revealed that the aggregates were composed of CD20 + B cells with scattered admixed CD3 + T cells. CD21 staining showed dendritic meshworks in the lymphoid aggregates. The aggregates stained positively for Bcl-2 and negatively for Bcl-6. In situ, hybrid- ization for kappa and lambda immunoglobulin light chains revealed monotypic kappa-positive plasma cells in a small background of polytypic plasma cells. Flow cytometric analysis performed on the marrow aspirate showed a population of CD19 + , CD20 + , CD5 2 , CD10 2 , CD23 +/2 , CD43 2/+ B cells expressing monotypic kappa immunoglobulin light chain (31% of all cells). These findings were consistent with a low grade B-cell lymphoma with plasmacytic differentiation. In a patient with marked splenomegaly and circulating villous lymphocytes, the findings in the bone marrow were most consistent with involvement by SMZL. The patient was treated initially with rituximab. The spleno- megaly responded to this therapy, and the patient was feeling well. Approximately 6 months after initiating rituximab, the patient reported new skin lesions. Physical examination showed a 3 · 4 cm fairly flat erythematous plaque on the left back, midway between the cervical spine and scapula, and a newly discovered left breast mass. The patient was referred for mammography, which revealed bilateral breast masses (left greater than right). Left breast biopsy revealed atypical ductal hyperplasia and a dense patchy lymphoid infiltrate consistent with involvement by the patient’s previously diagnosed SMZL. Cutaneous and breast lesions both decreased in size in response to rituximab maintenance therapy. Approximately 14 months into the rituximab therapy, the patient presented to the cutaneous oncology clinic with a 1-week history of new red patches and nodules distributed on the chest, shoulders, and upper back. A total body skin and lymph node examination demonstrated numerous 2–5 cm pink patches and indu- rated smooth plaques on the chest and upper back with overlying telangiectasias (Figs. 1A, B). Additionally, there was palpable lymphadenopathy in the right axilla. Punch biopsy from the skin on the left chest revealed a dense dermal “bottom-heavy” lymphoid infiltrate without epidermotropism composed of numerous small- and medium-sized CD20 + B cells with a scant to moderate quantity of pale cytoplasm, irregular nuclear contours, and coarse chromatin (Fig. 2) that were variably Bcl-2+. The infiltrate showed a perivascular and periadnexal distribution in From the *Harvard Medical School, Boston, MA; Departments of †Pathology, ‡Medicine, Division of Hematology-Oncology, and §Dermatology, Mas- sachusetts General Hospital, Harvard Medical School, Boston, MA. Mr. J. M. Cohen and Drs. J. A. Ferry, R. W. Takvorian, J. B. Carter, and R. M. Nazarian contributed to the writing and editing of this article. The authors declare no conflicts of interest. Reprints: Joi B. Carter, MD, Department of Dermatology, 2nd Floor, 50 Staniford Sreet, Massachusetts General Hospital, Boston, MA 02114 (e-mail: jcarter9@partners.org). © 2013 Lippincott Williams & Wilkins Am J Dermatopathol  Volume 37, Number 1, January 2015 www.amjdermatopathology.com | e1