On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.5 Rio de Janeiro Sept./Oct. 2004
Multiple myeloma with cutaneous plasmocytomas*
Daniella Abbruzzini Ferreira de SouzaI; Thais Helena Proença de FreitasII; Roberto Antonio Pinto PaesIII; Helena MüllerIV; Vânia T. M. HungriaV
IDoctor of the Advanced Course, Dermatology,
Service, Department of Clinical Medicine, Hospital da Santa Casa de Misericordia
de Sao Paulo
IIAssistant Doctor at the Dermatology Service, Department of Clinical Medicine, Hospital da Santa Casa de Misericordia de Sao Paulo
IIIAssistant Doctor at the Department of Pathologic Anatomy, Hospital da Santa Casa de Misericordia de Sao Paulo
IVDoctor, Head of the Adjunct Clinic, Pathologic Anatomy Service, Hospital da Santa Casa de Misericordia de Sao Paulo
VAssistant Doctor at the Hematology Service, Department of Clinical Medicine, Hospital da Santa Casa de Misericordia de Sao Paulo
Multiple myeloma is a malignant proliferation of plasma cells which infiltrate bone marrow; cutaneous involvement with plasma cell neoplasms is uncommon, and may be nonspecific or specific. The specific dermatologic lesions arise either as a direct extension from the underlying bone lesions or by metastatic accumulation in the form of nodules and plaques. The authors report the case of a 59-year-old male patient with multiple myeloma, who developed cutaneous plasmacytomas (violaceous nodules on the limbs) seven months after the disease diagnosis.
Key words: skin manifestations; multiple myeloma; plasmacytoma.
Multiple myeloma is characterized by the proliferation of neoplastic plasmocytes in the bone marrow; resulting in bone destruction, bone marrow insufficiency and monoclonal protein production.1
The criteria for the diagnosis of multiple myeloma consist of bone marrow biopsy with plasmocytes above 10% or a plasmocytoma and at least one of the following findings: 1) monoclonal protein in the serum; 2) monoclonal protein in the urine; 3) lytic bone lesions.1
The electrophoretic pattern of serum proteins shows a monoclonal peak in 80% of the cases; IgG is found in 50%; IgA in 20%; light chains (Bence Jones proteins) in 17%; IgD in 2%; biclonal gammopathy in 1%; and 10% do not secrete proteins (nonsecretor).1
Cutaneous involvement associated to multiple myeloma occurs in a percentile that varies from five to 10% of cases, the lesions are classified into nonspecific and specific.2
The nonspecific skin lesions include amyloidosis, purpura, alopecia, pruriginous ichthyosiform dermatitis, Raynaud's phenomenon, cold urticaria, pyoderma gangrenosum, xanthoma planum, anhydrosis, sclerodermiform lesions, subcorneal pustular dermatosis, lichen myxedematosus and necrobiotic xanthogranuloma.2,3
The specific cutaneous lesions related to multiple myeloma are the secondary plasmocytomas, that can occur by direct extension to the skin, from underlying bone lesions, or by hematogenic spread (distant from the bone tumor); the first type of lesions are more common, often soft at palpation and normochromic. The latter are represented by subcutaneous or intradermal violaceous nodules, with a hardened consistency, which occur late in the course of the disease. These lesions constitute a sign for poor prognostic, coursing to death within 12 months after diagnosis.3
Cutaneous plasmocytomas can appear in patients without evidence of multiple myeloma, and are then denominated primary cutaneous plasmocytomas. These tumors are rare, corresponding to three to 12% of the cases of extramedullary plasmocytomas; they have a variable prognostic, depending on whether or not there is dissemination of the disease.4
A patient was seen with diagnosis of multiple myeloma, who, after seven months of evolution, presented cutaneous plasmocytomas. In view of the fact that a search of the national literature dating back to the last twenty years found only one reference to cutaneous plasmocytomas associated to multiple myeloma, the authors decided to report the present case.
Male, 59-year-old patient, white, born and resident in Sao Paulo, sought the orthopedics service in October/98, complaining of pain in the left arm with onset one year previously. At physical exam, he presented tumoration of approximately 10 cm in diameter, painful on palpation, located in the lateral portion of the limb. Radiological exam was performed, which showed an area of bone reabsorption in the proximal third of the humerus, and a hypothesis of pathological fracture of the left humerus (Figure 1). Histopathologic exam showed bone tissue partly substituted by immature neoplasia characterized by dense proliferation of cells with ample cytoplasm and eccentric nuclei, characteristic of atypical plasmocytes, condensed in an irregular form that was compatible with a diagnosis of plasmocytoma.
Myelogram detected the presence of 79% plasmocytes, suggesting myeloma. Dosage of serum immunoglobulins presented an increase in immunoglobulin A (538 mg/dL), compatible with IgA multiple myeloma. After clinical staging, it was concluded to be a stage IIIA multiple myeloma, and chemotherapy was initiated with prednisone and melphalan. After two months of treatment, the patient presented an osteolytic lesion in the right femur, suggestive of plasmocytoma, though this was not confirmed by histopathologic exam.
After seven months, erythematous-violaceous nodules and plaques appeared in the right thigh and left forearm, the largest diameter measures varied from three to 7 cm, with precise borders and a hardened consistency (Figures 2 and 3). Histopathological exam of the nodule located in the right thigh showed diffuse infiltration of the dermis by immature neoplasia, compatible with plasmocytoma (Figures 4 and 5).
The patient died 40 days after diagnosis of the cutaneous lesions, as a consequence of extensive bronchopneumonia and septicemia.
Cutaneous plasmocytomas can occur primarily in the skin, without involvement of the bone marrow (primary cutaneous plasmocytoma), or, more frequently, resulting from dissemination of multiple myeloma or of plasma cell leukemia (secondary cutaneous plasmocytoma).5
Frequently, secondary plasmocytomas develop due to proximity with adjacent bone lesions; distant metastatic lesions are uncommon.6 In the present case, the cutaneous lesions were close to areas of bone fracture (bone plasmocytomas of the left humerus and right thigh), which probably indicates infiltration of the skin due to proximity.
Secondary cutaneous plasmocytoma usually represents dissemination of end-stage multiple myeloma, probably due to an alteration in the adhesion molecules.7 Alberts and Linch consider the size of the initial total tumoral mass is an important factor for the cutaneous dissemination of the disease, the prognosis being worse in cases in which it has a mass of over 2 kg.8,9
In the evolution of multiple myeloma, the neoplastic lesions are initially limited to the bone and bone marrow, with late extramedullary involvement; this behavior reflects the natural history of B cell neoplasias, with preliminary involvement of the lymph nodes and bone marrow with subsequent dissemination to other organs and the skin.8
The lesions are represented by cutaneous or subcutaneous nodules, with diameter between one and 5 cm; in relation to color, they can be erythematous-violaceous (more frequently) or normochromic; their surface is smooth and raised; they are usually multiple and more common in the trunk, extremities and face.10 In this case specifically, three nodular erythematous-violaceous lesions were observed, without ulceration, one in the right thigh and two in the left forearm.
The plasma cells in the plasmocytoma (primary and secondary) synthesized various amounts of monotypic cytoplasmatic light chain kappa, which can be identified by immunohistochemistry of the tissue; monoclonality is a characteristic finding generally in neoplastic plasmocytomas, with a prevalence of light chain kappa in relation to lambda chain greater than 10:1, according to the study by Torne and cols.11 This type of study is particularly useful for the diagnosis of multiple myeloma in cases in which cutaneous lesions constitute the first manifestation of the disease, before the appearance of abnormal serum proteins.6 Immunohistochemical analysis of the skin was not considered necessary, since the patient's multiple myeloma had already been diagnosed when the cutaneous nodules first appeared.
Cutaneous involvement in multiple myeloma has been recognized in association with the following proteins: IgG, IgM, IgA and IgD; heavy chains; and kappa and lambda light chains (separately or in association with an immunoglobulin class).6,12
The evidences suggest that any class of protein of the myeloma is capable of producing cutaneous dissemination and that IgG is probably the most common and is considered to be the most frequent immunoglobulin among the myelomas in general. However, some authors have mentioned a greater predominance of IgA in cases with cutaneous infiltration, as occurred in the patient presented here. Other authors have described the aggressive behavior of IgD myeloma, that, albeit rare, presents greater extra-medullary involvement, including cutaneous involvement.6,10,13
Secondary cutaneous plasmocytoma constitutes a sign of unfavorable prognostic for multiple myeloma, with 50% of the patients dying within six months after diagnosis.10,14 In the autopsy, most of the patients presented plasmocytic infiltration of several organs.15
The patient discussed here presented cutaneous plasmocytomas seven months after the diagnosis of multiple myeloma secretor of IgA and died only one month after diagnosis of the cutaneous lesions, corroborating the concept that cutaneous infiltration in cases of multiple myeloma dictates a poor prognostic for the patient.
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Daniella Abbruzzini Ferreira de Souza
Alameda Araguaia, 1293, cj 609 - Alphaville
06455-000 Barueri SP
Tel./Fax: (11) 4193-5034
Received on December 05, 2001.
Approved by the Consultive Council and accepted for publication on September 10, 2003.
* Work done at Dermatology Service of the Internal Medicine Department, Santa Casa de Misericordia de Sao Paulo (Charitable Hospital).