Subcutaneous angiocentric T‐cell lymphoma associated with fatal hemophagocytic syndrome

A 70‐year‐old woman was admitted in November 1991 for Internal fixation of a left pertrochanteric fracture. On admission, several indurated plaques and nodules were noted. Two days later she developed an acute and severe episode of rectal bleeding. The patient had a 7‐month history of recurrent painful erythematous plaques and nodules on the lower extremities associated with fever and malaise. In September 1991, she was admitted to another institution for evaluation and treatment. At that time, a skin biopsy specimen from a nodular lesion showed a lobular panniculitis. She was diagnosed as having Weber‐Christian disease and treatment with prednjsone, 1 mg/kg, was prescribed. In spite of this therapy, new skin nodules appeared. On admission to our institution, physical examination revealed a febrile (38.5 °C) woman, with six to 10 tender erythematous plaques and nodules, 1–3 cm in diameter, distributed over the legs, anterior chest, arms, and abdomen. Some of the nodules were ulcerated in the centers (Fig. 1). A nontender splenomegaly was present, but no enlarged lymph nodes were noted. Laboratory tests showed anemia (hemoglobin 7.9 g/dL), a platelet count of 105×10 9 /L, and a normal leukocyte count and differential. Subsequent laboratory studies showed progressive thrombocytopenia (platelet count, 26×10 9 /L) and leukopenia (leukocyte count, 3.5×10 9 /L), mild hepatic dysfunction (serum glutamate oxalacetic transaminase (SGOT), 68 U/L; serum glutamate pyruvate transaminase (SGPT), 68 U/L; 31 U/L), and lactic dehydrogenase (LDH) (2365 U/L). The rest of the laboratory data, including coagulation studies, urinalysis, screening for connective tissue disorders, pancreatic enzyme levels, VORL, and serologic tests for hepatitis B and C, were normal or negative/nonreactive. Blood cultures, cerebrospinal fluid examination, and chest roentgenogram were also normal. Abdominal computed tomographic (CT) scan revealed only an enlarged spleen. The patient's general condition markedly deteriorated and extensive hemorrhages from venpuncture sites, epistaxis, and rectal bleeding developed. Further treatment with 6‐methyl‐prednisolone, 160 mg/day, and an i.v. pulse of 1 g cyclophosphamide was initiated, but marked leucopenia ensued. The patient died 23 days after admission. Histopathologic, immunohistochemical, and genotypic studies Skin biopsy specimens from two nodules showed a dense mononuclear, mainly perivascular, infiltrate in the mid‐ and deep dermis extending into the subcutis (Fig. 2). No epidermotropism was seen. The infiltrate consisted of atypical, small and medium‐sized lymphoid cells with irregular nuclei, prominent nucleoli, and frequent mitotic figures. Angioinvasion in the deep skin dermis and subcutaneous septa was noted (Fig. 3). In the subcutaneous tissue, large histiocyte‐appearing cells with pale‐staining cytoplasm filled with cellular debris (bean‐bag cells) were seen admixed within the infiltrate (Fig. 4). The lymphoid cells stained strongly with T‐cell markers (UCHL‐1, CD3) and the larger histiocytic cells were positive with Mac‐387 (++), a‐antitrypsin, a‐antichymotrypsin (+++), and lysozyme (+). Some of these macrophages also stained weakly positive with T‐cell and B‐cell markers (L26, CD45RA). Scattered CD30+ cells were also observed within the infiltrate. No frozen material was available for immunohistochemical studies. Immunohistochemical staining with monoclonal antibody anti‐Epstein‐Barr virus directed against latent membrane protein (LMP‐1) (Dako‐EVB, CS 1‐4) revealed cytoplasmic staining with peripheral reinforcement of scattered atypical lymphoid cells. Studies to defect Epstein‐Barr virus DNA were not performed. A postmortem skin biopsy specimen from a nodular lesion showed extensive necrosis of the subcutaneous tissue with some atypical lymphocytes still present in the septa. The bone marrow showed cellular hyperplasia with no evidence of lymphoma. Occasional phagocytic cells with hemophagocyfosis were observed. Genotypic analysis (Southern blot, C‐beta probe) from a postmortem skin biopsy failed to demonstrate a clonal T‐cell receptor gene rearrangement.