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Pathobiology of Peripheral T-cell Lymphomas

Correspondence: Elaine Jaffe, MD, NCI, NIH; Bldg. 10, Rm. 2N202, MSC 1500, Bethesda MD 20891-1500; Phone 301-496-0183; Fax 301-402-2415; Email elainejaffe{at}nih.gov

Abstract

Peripheral T-cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas, and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification, clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities.

Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK cells and T cells of the innate immune system recognize antigen in the absence of MHC antigens and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of T-cell origin. In contrast, most nodal T-cell lymphomas belong to the adaptive immune system.

Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (T_FH), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts.

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