De Novo CD5 + Diffuse Large B-Cell Lymphoma With Cutaneous Involvement Dmitry V. Kazakov, MD, PhD,* Pavel Jindra, MD, PhD,† Werner Kempf, MD,‡ Boris Kreuzberg, MD, PhD,§ Ondrej Sebera, MD,‖ Marianne Tinguely, MD,‡ and Michal Michal, MD*¶ Abstract: De novo CD5 + diffuse large B-cell lymphoma (DLBCL) is rare but distinctive clinicopathologic variant of DLBCL mainly affecting elderly people, showing female predilection and characterized by poor survival and outcome with conventional therapy. The main differential di- agnoses include secondary CD5 + DLBCL (acquisition of CD5 expression during the progression of DLBCL or follicular lymphoma), large cell trans- formation in B-cell chronic lymphocytic leukemia (Richter syndrome), and mantle cell lymphoma. Extranodal involvement is often seen, but cutane- ous involvement in this lymphoma variant is unusual. Key Words: cutaneous lymphoma, diffuse large B-cell lymphoma, CD5, angiocentric (Pathology Case Reviews 2014;19: 200–203) D e novo CD5 + diffuse large B-cell lymphoma (DLBCL) is rare but distinctive clinicopathologic variant of DLBCL with ad- verse features, poor survival and outcome with conventional ther- apy. 1 This lymphoma subtype comprises about 5% to 10% of all cases of DLBCL. 2 The ratio between nodal to extranodal cases is approximately 2:1. The bone marrow, liver, and spleen are the most frequently involved extranodal anatomical sites. 3 Cutaneous involvement in this lymphoma variant is rare. CASE REPORT A 59-year-old female patient presented with multiple reddish 0.5- to 3-cm plaques and nodules on the face and occasional similar lesions on the neck that had been present, according to the patient, for about 1 month (Fig. 1). The patient complained of “stuffed” nose and had prior been treated in another hospital for chronic maxillary sinusitis with bilateral mucosectomy. The patient reported weight loss of 15 kg during the previous 3 months, malaise, and episodes of mild fever. Apart from the cutaneous le- sions, clinical examination revealed slightly enlarged submandib- ular lymph nodes. A biopsy from a lesion on the nose was taken, and the patient was referred to the ENT department where clinical examination disclosed infiltrations and erosions of the soft palate and defects of the oral alveolar mucosa. Sonography and com- puter tomography revealed multiple enlarged submandibular, cer- vical, supraclavicular, axillary, hilar, mediastinal, retroperitoneal, and inguinal lymph nodes. In addition, osteolytic lesions of the maxilla, mandibular, and the right orbit were detected (Fig. 2). Biopsies were taken endoscopically from the mucosa of the nasal cavity, nasopharynx, oral cavity, soft palate, and maxillary sinus. Based on the results of the skin and mucosal biopsies, the diagno- sis of de novo CD5 + DLBCL (vide infra). The patient denied bone marrow biopsy to complete staging investigations. The clinical stage was defined as IIIAE,IPI aa 2. The patient was administered Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisone (6 cycles), which resulted in partial regression of the skin lesions and reduction of peripheral lymphadenopathy, but the osteolytic lesions on the right maxilla and sinus progressed, and a newly developed mass in the left sphenoid sinus was identified. A new skin biopsy was sam- pled from a persistent skin lesion at the end of chemotherapy. Salvage chemotherapy consisting of Rituximab, Dexamethasone, Cytarabine, and Cisplatin. was immediately commenced; high-dose chemother- apy with autologous hematopoietic cell support is planned in case of patient’s response after 2 to 4 cycles. Histopathologically, the first skin biopsy revealed infiltrates in the dermis and subcutis with marked angiocentric features. The cells infiltrating vessel walls were medium-sized elements to large blasts immunoreactive for CD79a, CD20, CD5, and PAX5; occasional cells expressed bcl-6 and MUM-1 (Fig. 3). Cy- clin D1 and CD30 reacted negatively. Similar cells were found in the infiltrate in the dermis, but these were focally outnumbered by a small cell population expressing T-cell markers (CD3). Cyto- toxic and natural killer cell markers (CD8, granzyme B, perforin, TIA-1, CD56, CD57) were negative. Immunostaining for Epstein- Barr virus (EBV) was ambiguous, but polymerase chain reaction (PCR) for EBV proved negative. Molecular biology investigation using PCR showed no clonal rearrangement for T-cell receptor and immunoglobulin H, but there was monoclonal arrangement of the gene coding the κ light chain. The mucosal biopsies from the nasal cavity, nasopharynx, oral cavity, soft palate, and maxillary sinus (altogether 6 specimens) manifested a diffuse infiltrate composed mainly of large centroblasts showing identical immunophenotype (CD5 + , CD20 + , CD79a + ) to that seen in the skin specimen. (Fig. 4). In the second skin bi- opsy, there were no angiocentric features, and the infiltrate was predominantly composed of large centroblasts and occasional immunoblasts similar to the features in the mucosal specimens. DISCUSSION De novo CD5 + DLBCL is considered a rare clinicopatho- logic variant of DLBCL. The term “de novo CD5 + ” stresses the expression of CD5 in this neoplasm seen ab initio as opposed to CD5 expression that may appear in DLBCL during the course of disease, which is termed secondary CD5 + DLBCL. 1,2 CD5 is a glycoprotein expressed by a subset of normal naive B cells as well by T cells. 4 Clinical Features De novo CD5 + DLBCL mainly affects elderly people and shows a female predilection. Common is extranodal involvement (including central nervous system involvement) constitutional From the *Sikl’s Department of Pathology, Charles University in Prague, Med- ical Faculty in Pilsen; and †Department of Hematooncology, Charles Univer- sity Hospital, Pilsen, Czech Republic; ‡Kempf und Pfaltz, Histologische Diagnostik, Zürich, Switzerland; §Department of Radiology and ‖Ear, Nose, and Throat Clinic, Charles University in Prague, Medical Faculty in Pilsen; and ¶Bioptical Laboratory, Pilsen, Czech Republic. Reprints: Dmitry V. Kazakov, MD, Sikl’s Department of Pathology, Charles University Medical Faculty Hospital, Alej Svobody 80, 304 60, Pilsen, Czech Republic. E-mail: kazakov@medima.cz. The authors have no funding or conflicts of interest to declare. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 1082-9784 DOI: 10.1097/PCR.0000000000000046 CASE REVIEW 200 Pathology Case Reviews • Volume 19, Number 4, July/August 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.