Acta Dermato-Venereologica 99-7CompleteContent | Page 17

683 Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder Resembling B-cell Pseudo­ lymphoma on the Lip and Conjunctivae Fumi MIYAGAWA 1 , Yuki AOKI 1 , Aya HAYASHINO 2 , Chie SOTOZONO 3 and Hideo ASADA 1 Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo, Kashihara, Nara 634-8522, Japan, 2 Department of Surgical Pathology, and 3 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. E-mail: [email protected] 1 Accepted Mar 13, 2019; E-published Mar 14, 2019 Iatrogenic immunodeficiency-associated lymphoprolifera- tive disorders (LPD) are lymphoid proliferations or lym­ phomas that arise after treatment with immunosuppressive drugs (e.g. methotrexate) (1). LPD are strongly associated with Epstein-Barr virus (EBV) infections, probably due to defective immunosurveillance. Pseudolymphoma is characterized as a benign reactive polyclonal T- or B-cell lymphoproliferative process, which clinically and histologically simulates cutaneous lym­ phoma (2, 3). We describe here an unusual case, in which cutaneous B-cell pseudolymphoma-like lesions arose on 2 different organs, the lip and conjunctivae, in a patient who received long-term treatment with cyclosporine for pru- rigo. As histological examinations of both sites revealed follicular hyperplasia with scattered EBV-positive cells, it might be appropriate to refer to these lesions as iatroge- nic immunodeficiency-associated LPD, although they do not fit into any of the immunodeficiency-associated LPD categories listed in the 2017 World Health Organization (WHO) classification (1). CASE REPORT A 72-year-old woman presented with swelling of the lower lip, which had evolved over a 5-month period. Her medical history included diabetes mellitus and prurigo nodularis. She had been treated with 100 mg cyclosporine per day for approximately 10 years for intractable generalized prurigo, which often recurred when the dose of cyclosporine was reduced. Clinical examina- tion revealed an elastic, soft, red-coloured tumour, which covered almost the entire lower lip (Fig. 1a). Laboratory investigations detected the following abnormal values: white blood cell count 95×10 2 /µl (reference range 33–86×10 2 /µl), lactate dehydrogenase 318 U/l (124–222 U/l), creatinine kinase 186 U/l (41–153 U/l), alkaline phosphatase 460 U/l (106–322 U/l), blood urea nitrogen 22 mg/dl (8–20 mg/dl), creatinine 0.93 mg/dl (0.46–0.79 mg/dl), soluble interleukin-2 receptor 563 U/ml (145–519 U/ml) and IgG4 188 mg/dl (4.5–117 mg/dl). Tests for anti-SS-A and anti-SS-B anti- bodies were negative. A skin biopsy demonstrated dense nodular lymphocytic infiltrates with germinal centres (GC) surrounded by dense infiltrates of small round lymphocytes admixed with plasma cells and eosinophils (Figs. 1b, c). Most of the cells in the infiltrates were positive for CD20 (Fig. 1d), and a small number were positive for CD3. The cells in the GC were positive for CD20 (Fig. 1d), CD10, and bcl-6 (Fig. 1e), and negative for bcl-2 (Fig. 1f). The networks of CD21 + follicular dendritic cells were confi- ned to the GC (Fig. 1g). Ki-67 staining showed high proliferation rates in the GC (Fig. 1h). In situ hybridization for EBV-encoded small RNA (EBER) showed scattered positive cells (Fig. 1i). Few IgG4 + plasma cells were present. In situ hybridization and gene rearrangement studies confirmed that light-chain restriction and immunoglobulin heavy chain rearrangement, respectively, were absent. Positron emission tomography/computed tomography did not show any extracutaneous lesions. The patient was diagnosed with cutaneous B-cell pseudolymphoma (2). Three months prior to the appearance of the tumour on her lip, the patient had developed a salmon-coloured nodule on her right conjunctiva (Fig. S1a 1 ). She was referred to the ophthalmology department and underwent an excisional biopsy, followed by topi- SHORT COMMUNICATION Fig. 1. Clinical and histopatho­ logical findings of the lip lesion. (a) A reddish tumour on the lower lip. (b) Skin biopsy revealed a dense infiltrate of small lymphocytes in the dermis, admixed with plasma cells and eosinophils (haematoxylin and eosin; ×20). (c) A higher magnification image of (b) (×200). (d) Immunohistochemistry showed that the dense infiltrate of lymphocytes was positive for CD20 (×40). (e–h) Immunohistochemistry showed that the cells in the follicles expressed bcl-6 (e), but were negative for bcl-2 (f). CD21 + follicular dendritic cells were restricted to the germinal centres (GC) (g). Ki-67 staining showed high proliferation rates in the GC (h) (×40). (i) In situ hybridization for EBV-encoded small RNA (EBER) showed scattered positive cells (×200). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3172 Acta Derm Venereol 2019; 99: 683–684