Unusual lymphoma manifestations: case 1. Natural killer cell leukemia with dermal erythema and vascular epidermal growth factor production.

In 1996 we reported a 73-year-old man with natural killer cell (NK) leukemia complicated by severe dermal erythema secondary to vascular epidermal growth factor (VEGF) secretion by the leukemic cells [1]. He presented with fever, itching, splenomegaly, and profound dermal erythema, especially of his trunk and lower extremities (Figs 1A, 1B). Generalized adenopathy was not present. A computed tomography scan of the abdomen showed splenomegally without adenopathy. A skin biopsy showed an increased number of moderately dilated and irregular vascular channels in the superficial dermis (Fig 2). The white count was 11,300/ L with 13% neutrophils and 82% lymphocytes. The predominant cells in the peripheral blood and in the bone marrow were large granular lymphocytes (CD16, CD7, CD2 and CD3, CD4, and CD8 ; Fig 3). With treatment, splenomegaly disappeared. Slowly, over a period of months, the dermal erythema disappeared. The treatment consisted of lowdose oral cytoxan and low-dose oral prednisone. We tested the hypothesis that the dermal erythema was a manifestation of VEGF production by examining this patient’s peripheral leukocytes and leukocytes of six other patients for the production of VEGF by reverse transcriptase polymerase chain reaction. The cells from our NK leukemia patients expressed all forms of VEGF. VEGF was not identified in our control patients, including a patient with chronic lymphocytic leukemia, chronic myelocytic leukemia, and four normal volunteers. After treatment the VEGF completely disappeared, and the profound erythema slowly resolved. The patient continues in complete remission 6 years later, on therapy (low dose cytoxan and low dose prednisone). There are no NK cells in the peripheral blood. The spleen is not palpable, and his skin is perfectly normal. The morphology, cytochemistry, and surface markers of NK lymphocytes have been presented in considerable detail [2]. In addition, several publications during the last decade have outlined and discussed neoplastic diseases of NK cells [3-5]. To our knowledge, there has been no previous description of a patient with NK leukemia whose cells secreted VEGF, causing a dermal erythema that disappeared following resolution of the leukemia. Robin B. Gear, Sue Heffelfinger, and Herbert C. Flessa University of Cincinnati College of Medicine; Department of Internal Medicine, Division of Hematology-Oncology, Cincinnati, OH