T-cell lymphoma involving subcutaneous tissue: A clinicopathologic entity commonly associated with hemophagocytic syndrome

Eight cases of T-cell lymphoma localized primarily to the subcutaneous adipose tissue are described, five of which were referred in consultation with a benign diagnosis having been made or suggested. All patients presented with 1-12-cm-diameter subcutaneous nodules, which preferentially involved the extremities in six individuals. Histologically, the lesions were reminiscent of panniculitis and were composed of a mixture of small and large atypical lymphoid cells (large cells predominated in four cases) infiltrating between adipocytes. Focally, sheets of tumor cells were found. Karyorrhexis, fat necrosis, and benign histiocytes were present in all cases. Involvement of small blood vessels was found in seven cases, but the infiltrates were not primarily angiocentric, and angiodestruction was minimal or absent. Immunophenotypic analysis (paraffin or frozen sections) in all cases showed that the atypical cells were of T-cell phenotype. Frozen-section studies demonstrated a mature T-cell phenotype with evidence of pan-T-cell antigen loss in two of five lesions. Genotypic analysis demonstrated a rearrangement of the T-cell receptor β-chain gene in one (possibly two) biopsies of three cases studied. All patients had some evidence of hemophagocytosis during their clinical course. Six patients developed a florid hemophagocytic syndrome, fatal in five patients. Autopsies were done in all of the expired patients, and all had residual subcutaneous lymphoma and a hemophagocytic syndrome. Dissemination to nonsubcutaneous sites did not occur. Three patients are currently alive without evidence of lymphoma after aggressive chemotherapy (mean follow-up, 12 months). These results suggest that T-cell lymphomas that are primarily localized to the subcutaneous tissue may represent a distinct clinicopathologic entity. Initial biopsy findings may be misinterpreted as benign. A hemophagocytic syndrome commonly supervenes that may be secondary to lymphokine production by the malignant cells or related to the destruction of normal cells at subcutaneous sites.