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A Clinicopathologic, Immunohistochemical, and Cytogenetic Study of 8 Cases

Luis Requena, MD; Heinz Kutzner, MD; Gabriele Palmedo, PhD; Eduardo Calonje, MD; Celia Requena, MD; Gemma Pérez, MD; María Antonia Pastor, MD; Omar P. Sangueza, MD

Arch Dermatol. 2003;139:475-486.

Background  Specific cutaneous involvement in patients with multiple myeloma (MM) is very uncommon. It usually occurs in late stages of MM as a reflection of increased tumor cell burden. We studied 8 patients with cutaneous involvement of MM without underlying bony lesions and reviewed the literature on this rare dermatologic manifestation.

Design  We were particularly interested in the clinical course of patients with MM and cutaneous metastases, including survival once metastases were detected and the possible influence of various forms of therapy. Our goal was also to identify the immunoglobulin and the light-chain type in these cases, with emphasis on any possible association between a particular immunoglobulin class and cutaneous involvement, as well as the histopathologic, immunohistochemical, and cytogenetic features of the neoplastic plasma cells involving the skin.

Setting  University department of dermatology, university hospital, and private practice.

Patients  Medical records and biopsy specimens from 8 patients with MM and specific cutaneous lesions were reviewed.

Results  Cutaneous lesions consisted of multiple erythematous or violaceous nodules or plaques with a wide anatomical distribution. Histopathologically, 2 different patterns were identified: nodular and diffuse interstitial. Neoplastic plasma cells showed atypical features, and in 1 case they displayed a spindle shape, giving a sarcomatoid appearance to the lesion. Immunohistochemical studies demonstrated that neoplastic plasma cells were strongly positive for CD79a, CD138, and epithelial membrane antigen, and variably positive for VS38c and CD43. In each case the immunoglobulin profile and the light-chain type expression of the neoplastic cells were the same as those identified in the serum of the patients: 5 cases were IgA; 2 cases were IgG; and 1 case was IgA. In cases 2, 3, and 4, polymerase chain reaction investigations revealed monoclonal rearrangement for IgH genes, whereas the investigations for human herpesvirus 8 and Epstein-Barr virus yielded negative results. Fluorescent in situ hybridization investigations in these 3 cases demonstrated that the cutaneous neoplastic plasma cells showed the deletion of the rb-1 (retinoblastoma) gene. Despite aggressive chemotherapy, all 8 patients died a few months after the development of cutaneous involvement.

Conclusions  In our series, there was a perfect correlation of immunoglobulin and light-chain type between the serum electrophoresis and the cutaneous plasma cells. Patients with MM showed a short survival once cutaneous metastases appeared independently of the therapy. The deletion the rb-1 gene may provide prognostically relevant information to identify a high-risk subset of patients with MM.

From the Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain (Drs L. Requena and Pastor); Dermatopathologische Gemeinschaftspraxis, Friedrichshafen, Germany (Drs Kutzner and Palmedo); Dermatopathology Department, St John's Institute of Dermatology, St Thomas' Hospital, London, England (Dr Calonje); Department of Dermatology, Hospital General Universitario, Valencia, Spain (Drs C. Requena and Pérez); and Departments of Dermatology and Pathology, Wake Forest University, Winston-Salem, NC (Dr Sangueza). The authors have no relevant financial interest in this article.

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