Cutaneous involvement by multiple myeloma
Authors: Agnieszka W. Kubica, David A. Wetter, Julia S. Lehman
Journal: American Journal of Hematology (2014)

A 59-year-old Caucasian male presented with 1 month of asymptomatic cutaneous lesions on his chest. He had a one-and-a-half year history of multiple myeloma, with a predominance of lambda (5.09 mg/dL) over kappa (0.12 mg/dL) light chains and an alpha heavy chain phenotype (i.e., IgA lambda multiple myeloma). The malignant plasma cells from the bone marrow stained positively for CD45, CD38, and CD138 but did not express CD19 or CD20. His disease course had been progressive, despite treatment with lenalidomide, autologous stem cell transplantation, and combination chemotherapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD). Due to the new onset of the cutaneous eruption in the setting of progressive multiple myeloma, he was evaluated by dermatology. On physical examination, scattered erythematous macules and papules were noted (Image 1). Biopsies were obtained from representative lesions, and histopathological examination was performed. A dermal and periadnexal infiltrate of atypical, pleomorphic plasma cells was identified. Russell bodies, which are eosinophilic inclusions usually found in a plasma cell undergoing excessive synthesis of immunoglobulin, were also noted. The cells expressed CD138, were negative for CD20, and showed a predominance of lambda over kappa light chains by in situ hybridization (Image 1), confirming cutaneous involvement of the patient's underlying multiple myeloma. Although IgG4-related skin disease can show a dense population of dermal plasma cells, these plasma cells typically do not manifest cytomorphologic atypia. Moreover, the lymphoplasmacytic infiltrate of IgG4-related skin disease is accompanied by storiform fibrosis and obliterative phlebitis, neither of which were present in the case reported herein 1. Left—Hematoxylin and eosin stain at high and low magnification showing a dermal and periadnexal atypical plasma cell infiltrate, with scattered Russell bodies (see arrows). Center—Erythematous macules and papules distributed across the patient's chest. Right—CD138 immunohistochemical stain shows positivity (top); lambda immunohistochemical staining predominates (middle) over kappa (bottom). Together with the positron emission tomography/computed tomography results of widespread and metastatic multiple myeloma involving the bones, lungs, and soft tissue, the results of the biopsy confirmed progression of the patient's malignancy. The patient ultimately died 5 months later. The evaluation of the skin allowed for rapid and accurate ascertainment of the severity of multiple myeloma in this case, as cutaneous involvement of multiple myeloma is rare. Multiple myeloma is associated with varied cutaneous eruptions, including paraneoplastic processes (e.g., scleredema, scleromyxedema, necrobiotic xanthogranuloma, Sweet syndrome, pyoderma gangrenosum, leukocytoclastic vasculitis, erythema elevatum diutinum, subcorneal pustular dermatosis, and plane xanthomas); skin manifestations of associated hematologic abnormalities (e.g., anemia, thrombocytopenia, and leukopenia); cutaneous complications of the proteins the malignant plasma cells produce (e.g., amyloidosis, cryoglobulinemia [particularly type 1]); and direct involvement of the skin by malignant plasma cells (e.g., plasmacytomas) 2. This patient's case is best categorized as extramedullary plasmacytoma, which is a rare cutaneous presentation of multiple myeloma. Cutaneous variants of plasmacytomas can be subdivided into primary or secondary plasmacytomas 3, 4. Primary plasmacytomas are a controversial entity and can be an initial manifestation of underlying multiple myeloma 2, 3. Alternatively, some authors posit that plasmacytomas may exist without any underlying systemic disease, although this is disputed 2, 3. Secondary plasmacytomas can exist as extensions from underlying bony foci of disease 2-4. Most rarely, as in the case of our patient, cutaneous plasmacytomas develop from metastases of multiple myeloma or “overflow” of malignant cells into the dermis, generally in the cases of advanced disease 2-4. Microscopically, the malignant plasma cell infiltrate can demonstrate a nodular or interstitial pattern 4. Cutaneous involvement by multiple myeloma reflects a high tumor burden and generally portends a poor prognosis 2, 4-6. Treatment of cutaneous plasmacytomas is generally guided by treatment of the underlying multiple myeloma 5. In patients with underlying multiple myeloma, the onset of new skin lesions warrants further investigation to assess for potential progression of systemic disease. Along with additional hematologic studies, skin biopsy can assist in diagnosis and may have prognostic significance for patients with multiple myeloma.