Secondary cutaneous anaplastic large cell lymphoma treated with liposomal doxorubicin (Doxil) leading to complete remission.

A 46-year-old Caucasian woman presented with a right inguinal lymph node in April 1998. Biopsy showed anaplastic lymphoma kinase (ALK) protein-negative, CD30+ anaplastic large cell lymphoma (ALCL). Computed tomography (CT) scans showed only inguinal adenopathy. She was successfully treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for three cycles over 3 months, followed by radiation therapy. In November 1999, she relapsed with biopsy-proven liver involvement that manifested with ascites. This was treated with ifosfamide, cyclophosphamide, and etoposide chemotherapy over 3 months. This was followed by total body radiation and an autologous stem cell transplant. The post-transplant remission lasted 1 year. She relapsed in March 2001 with pain and swelling of the legs and progressive skin lesions without constitutional symptoms. Physical examination revealed multiple, violaceous nodules of varying size, the largest measuring 5 cm, in the pelvic and vulvar area, extending to both legs (Fig. 1). Both lower extremities had marked pitting edema, the left greater than the right. CT and positron emission tomography (PET) scans showed no systemic disease. Figure 1. Secondary cutaneous anaplastic large cell lymphoma of the pelvic area before doxorubicin treatment Download figure to PowerPoint Skin biopsy showed a dense dermal tumor composed of large mononuclear cells. The cells had an irregular nuclear contour and hyperchromasia with scant eosinophilic cytoplasm. There were numerous mitotic figures and apoptotic cells. Flow cytometry immunophenotyping demonstrated an abnormal T-cell population with the expression of cytoplasmic CD3+, CD30+, as well as a CD3+, CD52+ population. The abnormal T cells were CD5–, CD7–, CD25–. No B cells (CD19) were identified. Immunohistochemistry was ALK negative. Our diagnosis was secondary cutaneous ALCL, based on the World Health Organization (WHO) classification (Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology 2000; 36: 69–86). She was put on gemcitabine, 1000 mg/m2 for 1 month, with a minor clinical response. Chemotherapy was switched to polyethylene glycol-coated liposomal doxorubicin (Doxil®, Alza Corporation, Mountain View, CA, USA), 40 mg/m2 (70 mg per cycle); after one cycle, the patient showed a dramatic response, with the resolution of the majority of her skin lesions. After six cycles of liposomal doxorubicin every 3–4 weeks, there were multiple, atrophic, hyperpigmented patches with surrounding areas of erythema in the pelvic area, evidence of clinical complete remission (Fig. 2). The treatment was well tolerated. Pitting edema of the legs had mostly resolved. A biopsy was performed, which confirmed complete histologic remission. Serial cardiac-gated blood pool studies showed good left ventricular contractility. A follow-up skin biopsy and CT scan showed no evidence of residual lymphoma 4 months after the six cycles of chemotherapy had been completed. For the last 10 months, the patient has remained in complete remission as defined by the criteria of Cheson et al. (Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17: 1244–1253). Figure 2. The pelvic area 4 months after six cycles of doxorubicin Download figure to PowerPoint