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Journal of Clinical Oncology, Vol 23, No 13 (May 1), 2005: pp. 3138-3140 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.175
Plasma Cell ProblemsCASE 1. Disseminated Cutaneous Plasmacytomas Treated With Total Skin Electron RadiotherapyBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Yale University School of Medicine, New Haven, CT
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA A previously healthy 78-year-old man presented with a decrease in his exercise tolerance. Initial evaluation revealed a microcytic anemia (hemoglobin, 8.0g/dL) and thrombocytopenia (platelets, 38,000/uL). The patient required transfusion of 4 units of packed red cells and during the ensuing month, the anemia and thrombocytopenia spontaneously resolved. The patient returned for investigation of these abnormalities by bone marrow biopsy, at which time a small painless subcutaneous nodule above his right knee was detected. A biopsy of this lesion showed an anaplastic plasmacytoma comprised of monotypic plasmablasts with anaplastic features (Fig 1A). The lesion extended from the dermis through the subcutaneous tissue and infiltrated deep into the skeletal muscle (Fig 1B). The plasma cells were strongly immunoreactive for the plasma cell marker CD138, stained weakly with CD79a, demonstrated restricted expression for lambda light chain, and were negative for CD20, T-cell markers, CD30, and ALK-1. The proliferation index (Mib-1 labeling fraction) was estimated to be 80%. Laboratory studies showed serum immunoglobin (Ig) G levels of of 365 mg/dL (normal range, 60 to 1,500 mg/dL), elevated IgA levels of 1,333 mg/dL (normal range, 60 to 380 mg/dL), IgM levels of 68 mg/dL (normal range, 50 to 250 mg/dL) and beta-2 microglobulin levels of 2.1 mg/L (normal range, 0.7 to 1.8 mg/L). Serum protein electrophoresis identified a monoclonal band confirmed by immunofixation electrophoresis to be an IgA lambda M-protein. He had no Bence-Jones proteins in his urine. The bone marrow biopsy revealed no increase in plasma cells. Skeletal survey and whole body computed tomography scans were unremarkable. The patient rapidly developed multiple cutaneous lesions ranging in size from 1 to 8 cm in diameter over his trunk, arms, face, and genital areas (Fig 2A). One large lesion in the left supraclavicular region developed central ulceration (Fig 2B). The lesions remained painless, however lesions near the orbits impeded eyelid function. Initial therapy consisted of thalidomide and dexamethasone, which resulted in some improvement of his cutaneous lesions. Due to significant fatigue, he was only able to tolerate a reduced dose of 100 mg per day of thalidomide. His lesions continued to progress on therapy. Therefore, he was treated with dexamethasone and bortezomib at a dose of 1.3 mg/m2. The lesions responded initially to this therapy, but later progressed. Palliative total skin electron therapy was initiated. The patient was treated with a standard six-field technique using 6 mega-electronvolt electrons to deliver 2 Gy to the skin surface over the course of a two-day treatment cycle.1 The skin below the knees was shielded at 15 Gy and the skin below the iliac crests was shielded at 25 Gy. The skin above the iliac crests received a total dose of 30 Gy in 8 weeks. The right supraclavicular fossa, left supraclavicular fossa, perineum, and soles of feet received boost treatments of 10.5 Gy, 10.5 Gy, 9 Gy, and 7 Gy, respectively, with 120-kilovolt photons during the first 2 weeks of treatment. During the course of radiotherapy, the patient also received weekly bortezomib at a dose of 1.3 mg/m2. The patient tolerated combined radiotherapy and bortezomib well, developing predictable toxicities of skin hyperpigmentation, erythema, and a bullous lesion on his ankle. After treatment, nearly all of his skin lesions had completely resolved (Figs 2C and 2D), except for residual disease in the scrotum and right medial canthus. At a dose of 18 Gy, he developed marked unilateral lower extremity edema, erythema, and pain without fevers, chills, or signs of arterial insufficiency. Ultrasound was negative for deep venous thrombosis. A superficial skin biopsy of the medial thigh was unremarkable, but a deep biopsy at this site revealed extensive immature plasma cells consistent with plasmablastic plasmacytoma. On completion of total skin radiotherapy, synchronous positron emission tomography–computed tomography showed multiple lesions involving the right orbit, trunk, pelvis, perineum, scrotum, lower extremities, gallbladder, and peripancreatic area. Systemic therapy was reinitiated with melphalan, prednisone, vincristine, and liposomal doxorubicin 2 months after completion of total skin radiotherapy. The patient showed isolated progression of his disease in the right canthus/orbit 1 month into systemic therapy and received an additional 30 Gy of electron radiation to this site, achieving a complete response by the latter half of treatment.
The patient had progression of disease in the right canthus 3 months after completion of total skin electron therapy. This was treated with an additional 30 Gy of electron radiation, with a complete response. The patient subsequently developed progressive systemic and sporadic sites of cutaneous disease over the next year, while undergoing systemic therapy. His chemotherapy regimen was changed to cyclophosmamide, liposomal doxorubicin, bortezomib, and dexamethasone. Symptomatic sites of cutaneous and subcutaneous disease were effectively palliated with hypofractionated electron radiation treatments. A second course of skin electron treatment was undertaken for near confluent disease in the lower extremeties with good response. The patient, however, died of progressive systemic disease approximately 1 year after total skin electron therapy. Cutaneous involvement by extramedullary plasmacytomas in multiple myeloma is a rare entity, often associated with diffuse, systemic, late-stage disease and reflects high tumor burden.2 Primary cutaneous plasmacytoma, however, is a distinct rare clinical entity defined by the presence of plasmacytomas in the skin without evidence of systemic or bone marrow involvement. This disease has variable severity, clinical course, and response to treatment.3 The number of cutaneous lesions reported varies widely, ranging from a single lesion to greater than fifty. Interestingly, as observed in this case, previous reports of cutaneous plasmacytomas showed a similar coexistent IgA gammopathy.3,4,5 Total skin electron therapy is an established treatment for the cutaneous neoplastic disease mycosis fungoides.1,6 Experience with total skin electron therapy in other cutaneous malignancies is limited. To our knowledge, this is the first reported case of total skin electron therapy for cutaneous plasmacytoma. Bortezomib is known to be efficacious in the treatment of multiple myeloma.7,8 Additionally, bortezomib has radiosensitization properties in cultured cells.9 Here, we report novel and effective use of bortezomib together with radiotherapy in this case of cutaneous plasmacytomas. This case report illustrates the combination of total skin radiotherapy and bortezomib chemotherapy resulting in a dramatic palliative response for disseminated cutaneous plasmacytomas. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Jones GW, Kacinski BM, Wilson LD, et al: Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol 47:364-370, 2002[CrossRef][Medline]
2. Requena L, Kutzner H, Palmedo G, et al: Cutaneous involvement in multiple myeloma: A clinicopathologic, immunohistochemical, and cytogenetic study of 8 cases. Arch Dermatol 139:475-486, 2003 3. Kazakov DV, Belousova IE, Muller B, et al: Primary cutaneous plasmacytoma: A clinicopathological study of two cases with a long-term follow-up and review of the literature. J Cutan Pathol 29:244-248, 2002[Medline] 4. Ah-Weng A, Charles-Holmes R, Rose P, et al: Multiple cutaneous plasmacytomas following an autologous peripheral stem cell transplant. Clin Exp Dermatol 27:293-295, 2002[Medline] 5. Arico M, Bongiorno MR: Primary cutaneous plasmacytosis in a child: Is this a new entity? J Eur Acad Dermatol Venereol 16:164-167, 2002[Medline] 6. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sezary syndrome). Cancer 85:1985-1995, 1999[Medline]
7. Hideshima T, Richardson P, Chauhan D, et al: The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 61:3071-3076, 2001
8. Richardson PG, Barlogie B, Berenson J, et al: A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609-2617, 2003 9. Russo SM, Tepper JE, Baldwin AS Jr, et al: Enhancement of radiosensitivity by proteasome inhibition: Implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys 50:183-193, 2001[CrossRef][Medline]
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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