Cutaneous Plasmacytomas Secondary to Nonsecretory Multiple Myeloma

Introduction: Multiple myelomais characterized by neoplastic prolife ration of plasma cells in bone marrow. Cutaneous involvement occurs in only5 to 10% of patients and includes specific rare lesions such as multiple cutaneous plasmacytomas in advanced stages of disease. Case report: Male patient, 44years-old, diagnosed with nonsecretory multiple myeloma (Durie-Salmon stage III, International Staging System Stage I) for about18 months. No chromosomal or cytological characteristics of poor prognosis were found. Complete response was achieved after conventional chemotherapy, followed by intensive chemotherapy and autologous transplant of stem cells. Ten months after treatment, some erythemato-violaceous nodules and tumors with 2 to 7cmin diameter appeared, with elastic consistency and smooth surface with well-defined limits, slightly painful, localized in lower back, right leg and right forearm. The pathological examination of a nodule was consistent with metastatic cutaneous plasmacytoma, with intense and diffuse expression of CD138and cyclinD1 and frequent expressionforCD79a. Patient was treated with interferon-alpha and subsequently radiotherapy. At the third week of radiotherapy the patient suffered sudden death at his home (autopsy was inconclusive). Discussion: We present this case because it has occurred in a young adult, with the rare association to the nonsecretory multiple myeloma and for the presentation of exuberant cutaneous metastatic lesions after systemic chemotherapy and autologous transplant of stem cells. These lesions are a sign of poor prognosis and, in this case, the first sign of disease progression, exclusively cutaneous, without bone marrow involvement. INTRODUCTION Multiple Myeloma (MM) is a malignant hematologic disorder characterized by monoclonal proliferation of plasma cells. This entity affects men more often than women and tends to occur in older adults (mean age of 68 years) [1]. Cutaneous involvement associated with multiple myeloma occurs in a percentage that varies from 5 to 10% of cases and the lesions are classified in nonspecific and specific [2,3]. The nonspecific cutaneous manifestations of multiple myeloma are shown in table 1. The specific cutaneous lesions related to multiple myeloma are the extramedullary cutaneous plasmacytomas, which was first reported by Hedinger in 1911 [4]. They can occur by lymphatic or vascular spread or, more frequently, by direct extension to the skin, from underlying bone lesions. In some cases, cutaneous extra medullary plasmacytom as has been described as the presenting sign of multiple myeloma [5]. Any area of the skin can be involved, but it has been reported most frequently on the trunk and abdomen followed by face, scalp, neck and extremities [6-12]. Unusual localizations have been described, including eyelid, tongue, and scrotum and perianal region [13]. Multiple lesions are the rule, although solitary lesions have also been recorded. Morphologically, cutaneous plasmacytomas usually consist of erythematous nodules that may ulcerate or dome-shaped and smooth-surfaced plaques ranging from 1 to 5cm in diameter. Histopathological examination of the cutaneous plasmacytomas in MM revealed two patterns: nodular or diffuse interstitial infiltration [6]. The typical pattern represented by a dense monomorphic dermal plasmacytic infiltrate which is usually separated from the overlying epidermis. Cutaneous plasmacytomas in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Usually indicates aggressive behavior and short survival, coursing to death within 12 months after diagnosis [14]. Araújo et al. (2014) Email: J Dermatolog Clin Res 2(3): 1022 (2014) 2/5 Central This patient was diagnosed with an unusual nonsecretory multiple myeloma (Durie-Salmon stage III, International Staging System I), who ten months after complete response with conventional chemotherapy, intensive chemotherapy and autologous transplant of stem cells, presented cutaneous plasmocytomas. CASE PRESENTATION A 44years old man, caucasian, presented with lumbago with eight month of evolution. In July 2010 was diagnosed as having nonsecretory multiple myeloma initially presented with osteolytic lesions and vertebral plasmacytoma. There was no relevant personal or family history of malignancy or chronic pharmacologic therapy. Initial radiological exam was performed, which showed a pathologic fracture over the L3 vertebral body and multiple mild osteolytic lesions over the ribs, C2, C3, D2, L1 e L4. At that time, he was submitted to corrective surgery. Complaints of progressive malaise, loss of appetite, weight loss (more than 10Kg in 6 months) and generalized bone pain subsequently developed. Initial analytic characteristics are shown in table 2. In immunelectrophoresis, no monoclonal bands were observed. Bence-Jones protein was undetectable. There was no renal insufficiency. Examination of bone marrow from the iliac spine revealed a cellularity proportional to patient age without relevant morphologic alterations and < 10% plasma cells (CD 138+, MUM+ and kappa+). Histopathologic exam showed bone tissue partly substituted by large aggregates of neo plastic cells with scarce and poorly defined cytoplasm and irregular, hipercromatic and multi lobular nuclei. Immunohistochemical study revealed neo plastic cells with intense and diffuse expression of CD 138 (Figure 1) and cycline D1 and also frequent expression of CD 79a. No expression to CD45, CD3, CD 20 or mieloperoxidase. There weren’t found chromosomal or cytological characteristics of poor prognosis by Fluorescence In Situ Hybridization (FISH). After clinical staging, it was concluded to be nonsecretory multiple myeloma (Durie-Salmon stage III, International Staging System I) and chemotherapy was initiated with cyclophosphamide, bortezomib and dexamethasone between 08/2010 and 11/2010 followed by intensive chemotherapy and autologous transplant of stem cells in 01/2011 with complete response. A reassessment of bone marrow showed plasma cells < 10% and serial evaluation of protein electrophoresis was negative. Ten month safter treatment, some erythemato-violaceous nodules and tumors with 2 to 7cmin diameter appeared, with elastic consistency and smooth surface with well-defined limits, slightly painful, localized in lower back, right leg andright forearm (Figure 2). The pathological examination of a nodule was consistent with metastatic cutaneous plasmacytoma, with intense and diffuse expression of neo plastic cells for CD138 and cyclinD1 and frequent expression for CD79a. Some lesions underwent spontaneous remission and some appeared in other locations. No medullary plasmacytosis or serum immunoelectrophoretic changes were observed; urine immunofixation was also negative. Analytic characteristics at time of tumor recurrence are shown in table 3. A further skeletal survey revealed enlargement of some osteolytic lesions in D7, L5, sacrum and iliac crests. Patient was submitted to interferon-alpha and subsequently radiotherapy. At the third week of radiotherapy the patient suffered sudden death at his home (autopsy was inconclusive for the cause of death). Amyloidosis Purpura, Alopecia Ichthyosiform dermatitis Raynaud's phenomenon, Cold urticarial Pyodermagangrenosum Leukocytoclastic vasculitis Anhydrosis Sclerodermiform lesions Subcornealpustulardermatosis Scleromyxedema S.Sweet POEMS (polyneuropathy, organomegaly, M-protein and skin lesions) Angioedema with C1 inhibitor deficiency Plane xanthomas Necrobioticxanthogranuloma Follicular hyperkeratosis Table 1: Nonspecific cutaneous manifestations of multiple myeloma. Hemoglobin 15g/dl (13.5-17.0) Leucocytes 7.7x103/uL (4-10.5) Platelets 332x103/uL (166-308) PTH <2.5 pg/ml (14-72) Ca2+ 11.3 mg/dl (8.4-10.2) Lactic dehydrogenase 411 U/L (240-488) B2-microglobulin 1760 ng/mL (800-2200) C reactive protein 10.30 mg/L (<5) Alkaline phosphatase 137 U/L (40-130) Total protein 7.6 g/dL (6.4-8.7) Albumin 4.9 g/dL (3.5-5.2) A/G ratio 1.6 Immunoglobulin G (IgG) 685 mg/dl (700-1600) IgM 24 mg/dl (40-230) IgA 147 mg/dl (70-400) Table 2: Initialanalytical characteristics. Araújo et al. (2014) Email: J Dermatolog Clin Res 2(3): 1022 (2014) 3/5 Central Figure 1 Neoplastic cells with intense and diffuse expression of CD 138 in bone marrow biopsy. Figure 2 Metastatic cutaneous plasmacytoma localized in lower back, right leg and right forearm. Hemoglobin 13.8g/dl (13.5-17.0) Leucocytes 4.7x103/uL (4-10.5) Platelets 252x103/uL (166-308) Ca2+ 8.6 mg/dl (8.4-10.2) Lactic dehydrogenase 204 U/L (240-488) B2-microglobulin 2143ng/mL (800-2200) Total protein 6.7 g/dL (6.4-8.7) Albumin 3.9 g/dL (3.5-5.2)