Clinical manifestations, pathologic features, and diagnosis of peripheral T cell lymphoma, not otherwise specified
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
The peripheral T cell lymphomas are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas in adults [1,2]. (See "Classification of the hematopoietic neoplasms".)
Among these, in decreasing frequency of occurrence, are:
●Peripheral T cell lymphoma, not otherwise specified
●Anaplastic large cell lymphoma, primary systemic type
●Angioimmunoblastic T cell lymphomaTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998; 16:2780.
- Medeiros LJ, Lardelli P, Stetler-Stevenson M, et al. Genotypic analysis of diffuse, mixed cell lymphomas. Comparison with morphologic and immunophenotypic findings. Am J Clin Pathol 1991; 95:547.
- A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997; 89:3909.
- Abramson JS, Feldman T, Kroll-Desrosiers AR, et al. Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. Ann Oncol 2014; 25:2211.
- Ellin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 2014; 124:1570.
- Abouyabis AN, Shenoy PJ, Lechowicz MJ, Flowers CR. Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States. Leuk Lymphoma 2008; 49:2099.
- Vose J, Armitage J, Weisenburger D, International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26:4124.
- Adams SV, Newcomb PA, Shustov AR. Racial Patterns of Peripheral T-Cell Lymphoma Incidence and Survival in the United States. J Clin Oncol 2016; 34:963.
- Weisenburger DD, Savage KJ, Harris NL, et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood 2011; 117:3402.
- Dogan A, Morice WG. Bone marrow histopathology in peripheral T-cell lymphomas. Br J Haematol 2004; 127:140.
- Falini B, Pileri S, De Solas I, et al. Peripheral T-cell lymphoma associated with hemophagocytic syndrome. Blood 1990; 75:434.
- Chott A, Dragosics B, Radaszkiewicz T. Peripheral T-cell lymphomas of the intestine. Am J Pathol 1992; 141:1361.
- Gonzalez CL, Medeiros LJ, Braziel RM, Jaffe ES. T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol 1991; 15:17.
- Bekkenk MW, Vermeer MH, Jansen PM, et al. Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients. Blood 2003; 102:2213.
- Suchi T, Lennert K, Tu LY, et al. Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification. J Clin Pathol 1987; 40:995.
- Weiss LM, Crabtree GS, Rouse RV, Warnke RA. Morphologic and immunologic characterization of 50 peripheral T-cell lymphomas. Am J Pathol 1985; 118:316.
- Patsouris E, Noël H, Lennert K. Histological and immunohistological findings in lymphoepithelioid cell lymphoma (Lennert's lymphoma). Am J Surg Pathol 1988; 12:341.
- Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84:1361.
- Borowitz MJ, Reichert TA, Brynes RK, et al. The phenotypic diversity of peripheral T-cell lymphomas: the Southeastern Cancer Study Group experience. Hum Pathol 1986; 17:567.
- Rahemtullah A, Longtine JA, Harris NL, et al. CD20+ T-cell lymphoma: clinicopathologic analysis of 9 cases and a review of the literature. Am J Surg Pathol 2008; 32:1593.
- Weiss LM, Trela MJ, Cleary ML, et al. Frequent immunoglobulin and T-cell receptor gene rearrangements in "histiocytic" neoplasms. Am J Pathol 1985; 121:369.
- Weiss LM, Picker LJ, Grogan TM, et al. Absence of clonal beta and gamma T-cell receptor gene rearrangements in a subset of peripheral T-cell lymphomas. Am J Pathol 1988; 130:436.
- Boehm T, Baer R, Lavenir I, et al. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J 1988; 7:385.
- Caccia N, Bruns GA, Kirsch IR, et al. T cell receptor alpha chain genes are located on chromosome 14 at 14q11-14q12 in humans. J Exp Med 1985; 161:1255.
- Caccia N, Kronenberg M, Saxe D, et al. The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans. Cell 1984; 37:1091.
- Hecht F, Morgan R, Hecht BK, Smith SD. Common region on chromosome 14 in T-cell leukemia and lymphoma. Science 1984; 226:1445.
- Kaneko Y, Maseki N, Homma C, et al. Chromosome translocations involving band 7q35 or 7p15 in childhood T-cell leukemia/lymphoma. Blood 1988; 72:534.
- Schlegelberger B, Himmler A, Gödde E, et al. Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas. Blood 1994; 83:505.
- Ong ST, Le Beau MM. Chromosomal abnormalities and molecular genetics of non-Hodgkin's lymphoma. Semin Oncol 1998; 25:447.
- Hartmann S, Gesk S, Scholtysik R, et al. High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus. Br J Haematol 2010; 148:402.
- Agostinelli C, Piccaluga PP, Went P, et al. Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies. J Clin Pathol 2008; 61:1160.
- Iqbal J, Weisenburger DD, Greiner TC, et al. Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood 2010; 115:1026.
- Vasmatzis G, Johnson SH, Knudson RA, et al. Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas. Blood 2012; 120:2280.
- Piccaluga PP, Agostinelli C, Califano A, et al. Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. J Clin Invest 2007; 117:823.
- Wang T, Feldman AL, Wada DA, et al. GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood 2014; 123:3007.
- Iqbal J, Wright G, Wang C, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 2014; 123:2915.
- de Leval L, Rickman DS, Thielen C, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 2007; 109:4952.
- Piccaluga PP, Fuligni F, De Leo A, et al. Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study. J Clin Oncol 2013; 31:3019.
- Hastrup N, Ralfkiaer E, Pallesen G. Aberrant phenotypes in peripheral T cell lymphomas. J Clin Pathol 1989; 42:398.
- Pinkus GS, O'Hara CJ, Said JW. Peripheral/post-thymic T-cell lymphomas: a spectrum of disease. Clinical, pathologic, and immunologic features of 78 cases. Cancer 1990; 65:971.
- Palomero T, Couronné L, Khiabanian H, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet 2014; 46:166.
- Parrilla Castellar ER, Jaffe ES, Said JW, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 2014; 124:1473.
- Weisenburger DD, Linder J, Armitage JO. Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases. Hematol Oncol 1987; 5:175.
- Coiffier B, Brousse N, Peuchmaur M, et al. Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d'Etude des Lymphomes Agressives). Ann Oncol 1990; 1:45.
- Armitage JO, Greer JP, Levine AM, et al. Peripheral T-cell lymphoma. Cancer 1989; 63:158.
- Lippman SM, Miller TP, Spier CM, et al. The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype. Blood 1988; 72:436.
- Schmitz N, Trümper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood 2010; 116:3418.
- Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Blood 1998; 92:76.
- Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood 2004; 103:2474.
- Lee Y, Uhm JE, Lee HY, et al. Clinical features and prognostic factors of patients with "peripheral T cell lymphoma, unspecified". Ann Hematol 2009; 88:111.
- Gutiérrez-García G, García-Herrera A, Cardesa T, et al. Comparison of four prognostic scores in peripheral T-cell lymphoma. Ann Oncol 2011; 22:397.
- Went P, Agostinelli C, Gallamini A, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol 2006; 24:2472.
- Dupuis J, Emile JF, Mounier N, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study. Blood 2006; 108:4163.
- Chihara D, Oki Y, Ine S, et al. Analysis of prognostic factors in peripheral T-cell lymphoma: prognostic value of serum albumin and mediastinal lymphadenopathy. Leuk Lymphoma 2009; 50:1999.
- Cuadros M, Dave SS, Jaffe ES, et al. Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas. J Clin Oncol 2007; 25:3321.
- Valleron W, Ysebaert L, Berquet L, et al. Small nucleolar RNA expression profiling identifies potential prognostic markers in peripheral T-cell lymphoma. Blood 2012; 120:3997.
- CLINICAL FEATURES
- Genetic features
- DIFFERENTIAL DIAGNOSIS
- Angioimmunoblastic T cell lymphoma
- Anaplastic large cell lymphoma
- Hodgkin lymphoma
- Adult T cell leukemia-lymphoma
- T cell histiocyte rich large B cell lymphoma
- Granulomatous lymphadenitis
- Paracortical hyperplasia