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C.
D.
PATHOLOGY: Skin biopsy revealed a diffuse and perivascular infiltrate of atypical lymphocytes with enlarged, hyperchromatic, and monotonous appearance consistent with the previous diagnosis of T-cell leukemia.
DISCUSSION: The patient's presentation with splenomegaly, leukocytosis, and resistance to the first two chemotherapeutic lines of therapy, CHOP and fludarabine, prompted re-evaluation of the initial diagnosis. His clinical presentation was most consistent with T-cell prolymphocytic leukemia (TPLL).
T-PLL is a rare variant of chronic lymphocytic leukemia that usually occurs in elderly patients. The clinical manifestations of T-PLL include splenomegaly, lymphadenopathy, hepatomegaly, and serous effusions, as well as skin lesions in 27% of patients (1). Hematologic abnormalities include a high leukocyte count with over 90% prolymphocytes in the peripheral blood. Anemia and thrombocytosis are also common in this disease (1). The most common type of skin involvement in T-PLL is a diffuse, infiltrated maculo-papular erythema, usually present at the time of diagnosis. Patients may also have localized maculopapular eruptions, or nodules. Occasionally patients present with generalized erythroderma. The lesions are usually distributed on the torso, arms, and face (2, 3).
The etiology of T-PLL is not yet known. There is conflicting evidence as to whether infection with HTLV- I may contribute to the pathogenesis of disease in some patients (2). Ataxia telangiectasia, caused by mutation of the ATM gene, is one condition that predisposes patients to developing T-PLL. Chromosome rearrangements involving mutations of two other genes, MTCP I and TCL I, have also been associated with T-PLL (2).
T-PLL can be diagnosed by light microscopic examination of peripheral blood or skin biopsy, showing numerous prolymphocytes with characteristic atypical features. Immunohistochernistry and flow cytometry are consistent with a mature T-cell phenotype.
T-PLL has a progressive course, with a poor prognosis. In one series, the median survival was 7.5 months (1). The disease is usually unresponsive to alkylating agents, although some studies show response to pentostatin and deoxyadenosine analogs. (2) If patients fail to respond to these treatment options, they may benefit from a new monoclonal antibody. Several studies have shown that Campath- I H (alemtuzumab), a monoclonal antibody directed against the CD52 antigen, may be useful in the treatment of this disease. (2, 4).
This patient was started on Campath- I H and noted improvement of his
rash after the first few initial infusions.
REFERENCES:
REFERENCES
1. Matutes, E., Brito-Babapulle, V., Swansbury, J., Ellis, J., Morilla, R., Dearden, C., Sempere, A., and Catovsky, D. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 1991, 78(12): 3269-3274.
2. Kipps, T. Chronic lymphocytic leukemia and related disorders. In Williams Hematology, 6th Ed, 2001, p 1181-1182.
3. Mallett, R., Matutes, E., Catovsky, D., Maclennan, K., Mortimer, P., and Holden, C. Cutaneous infiltration in T-cell prolymphocytic leukaemia. British Journal of Dermatology 1995,132: 263266.
4. Flynn, J., and Byrd, J. Campath- I H monoclonal antibody therapy. Current Opinion in Oncology 2000, 12: 574-58 1.
5. Tsai, L. et al.: T-cell prolymphocytic leukemia with helper-cell phenotype and a review of the literature. Cancer 1984, 54: 463-470.
My thanks to Drs. Alison Klenk, Jaeyoung Yoon, Anne Lind, and Pui-yan Kwok for their assistance in the preparation of this case.
