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American Journal of Pathology, Vol 134, 761-785, Copyright © 1989 by American Society for Investigative Pathology

REVIEWS

Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia

DM Knowles
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.

The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non- neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR- beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS)

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