Download PDF
CC BY 4.0 · Indian J Med Paediatr Oncol 2023; 44(05): 534-542
DOI: 10.1055/s-0043-1772192
Review Article

An Approach to Nodal T- and NK-Cell Lymphomas—A Systemic Review

Mayur Parkhi 
1   Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India
,
Amanjit Bal 
1   Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

T-cell lymphomas are rare neoplasms that have complex pathology. The multiparameter approach has been recommended by World Health Organization (WHO) for the classification of T-cell lymphomas taking into account morphology, immunophenotype, genetics, and clinical features. This also includes division established on the possible cell-of-origin (COO) from T regulatory or T-follicular helper (TFH) cells. The recent WHO-HAEM5 has classified entities as precursor T-lymphoblastic neoplasms, mature T-cell neoplasms, Epstein-Barr virus (EBV)-related T- and NK/T-cell lymphomas, and tumor-like lesions with T-cells predominance. Distinct entities have been recognized within the anaplastic large cell lymphoma (ALCL) family founded on the status of anaplastic lymphoma kinase (ALK) gene rearrangement: ALK-positive and molecularly heterogeneous ALK-negative. The family of lymphomas arising from TFH cells consists of three distinct nodal TFH cell lymphoma entities: angioimmunoblastic-type, follicular-type, and not otherwise specified. These three entities show significant clinical and immunophenotypic overlap. The cases that do not qualify for ALCL or nodal TFH cell lymphomas are labelled as peripheral T-cell lymphomas-not otherwise specified after ruling out nodal EBV-positive T- and NK- cell lymphoma. The new category termed tumor-like lesions with T cell predominance has a high chance to be misdiagnosed as lymphoma. This category includes entities such as Kikuchi-Fujimoto disease, indolent T-lymphoblastic proliferation, and autoimmune lymphoproliferative syndrome. For pathologists, diagnosing nodal T-cell lymphomas may be thought-provoking due to their broad histopathologic spectrum that mimics reactive as well as other neoplastic processes. This review provides a comprehensive diagnostic criterion of the most commonly encountered nodal T-cell and NK cell lymphomas in day-to-day training and an algorithmic approach.

Keywords

pathology - T-cell lymphoma - NK cell lymphomas - T-follicular helper cells - WHO-HAEM5


Publication History

Article published online:
17 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med 2000; 343 (02) 108-117
    CrossrefPubMedGoogle Scholar
  • 2 Jaffe ES, Nicolae A, Pittaluga S. Peripheral T-cell and NK-cell lymphomas in the WHO classification: pearls and pitfalls. Mod Pathol 2013; 26 (Suppl. 01) S71-87
    CrossrefPubMedGoogle Scholar
  • 3 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 (11) 3909-3918
    CrossrefPubMedGoogle Scholar
  • 4 Alaggio R, Amador C, Anagnostopoulos I. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia 2022; 36 (07) 1720-1748
    CrossrefPubMedGoogle Scholar
  • 5 Stein H, Foss HD, Dürkop H. et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 2000; 96 (12) 3681-3695
    CrossrefPubMedGoogle Scholar
  • 6 de Leval L. Approach to nodal-based T-cell lymphomas. Pathology 2020; 52 (01) 78-99
    CrossrefPubMedGoogle Scholar
  • 7 Pinkerton R, Cairo MS, Cotter FE. Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science. Br J Haematol 2016; 173 (04) 503-504
    CrossrefPubMedGoogle Scholar
  • 8 Savage KJ, Harris NL, Vose JM. et al; International Peripheral T-Cell Lymphoma Project. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood 2008; 111 (12) 5496-5504
    CrossrefPubMedGoogle Scholar
  • 9 Werner MT, Zhao C, Zhang Q, Wasik MA. Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target. Blood 2017; 129 (07) 823-831
    CrossrefPubMedGoogle Scholar
  • 10 Lamant L, Dastugue N, Pulford K, Delsol G, Mariamé B. A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 1999; 93 (09) 3088-3095
    CrossrefPubMedGoogle Scholar
  • 11 Shustov A, Cabrera ME, Civallero M. et al. ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project. Blood Adv 2021; 5 (03) 640-648
    CrossrefPubMedGoogle Scholar
  • 12 Yoon SE, Cho J, Kim YJ. et al. Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas. Exp Hematol Oncol 2021; 10 (01) 33
    CrossrefPubMedGoogle Scholar
  • 13 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 (09) 1473-1480
    CrossrefPubMedGoogle Scholar
  • 14 Pedersen MB, Hamilton-Dutoit SJ, Bendix K. et al. DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study. Blood 2017; 130 (04) 554-557
    CrossrefPubMedGoogle Scholar
  • 15 Waldmann TA, Chen J. Disorders of the JAK/STAT pathway in t cell lymphoma pathogenesis: implications for immunotherapy. Annu Rev Immunol 2017; 35: 533-550
    CrossrefPubMedGoogle Scholar
  • 16 Parkhi M, Bal A, Das A. et al. ALK-negative anaplastic large cell lymphoma (ALCL): prognostic implications of molecular subtyping and JAK-STAT pathway. Appl Immunohistochem Mol Morphol 2021; 29 (09) 648-656
    CrossrefPubMedGoogle Scholar
  • 17 Oishi N, Brody GS, Ketterling RP. et al. Genetic subtyping of breast implant-associated anaplastic large cell lymphoma. Blood 2018; 132 (05) 544-547
    CrossrefPubMedGoogle Scholar
  • 18 Woo DK, Jones CR, Vanoli-Storz MN. et al. Prognostic factors in primary cutaneous anaplastic large cell lymphoma: characterization of clinical subset with worse outcome. Arch Dermatol 2009; 145 (06) 667-674
    PubMedGoogle Scholar
  • 19 Breitfeld D, Ohl L, Kremmer E. et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 2000; 192 (11) 1545-1552
    CrossrefPubMedGoogle Scholar
  • 20 Kim CH, Lim HW, Kim JR, Rott L, Hillsamer P, Butcher EC. Unique gene expression program of human germinal center T helper cells. Blood 2004; 104 (07) 1952-1960
    CrossrefPubMedGoogle Scholar
  • 21 Petrich AM, Helenowski IB, Bryan LJ, Rozell SA, Galamaga R, Nabhan C. Factors predicting survival in peripheral T-cell lymphoma in the USA: a population-based analysis of 8802 patients in the modern era. Br J Haematol 2015; 168 (05) 708-718
    CrossrefPubMedGoogle Scholar
  • 22 de Leval L, Parrens M, Le Bras F. et al. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets. Haematologica 2015; 100 (09) e361-e364
    CrossrefPubMedGoogle Scholar
  • 23 Federico M, Rudiger T, Bellei M. et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol 2013; 31 (02) 240-246
    CrossrefPubMedGoogle Scholar
  • 24 Alizadeh AA, Advani RH. Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies. Clin Adv Hematol Oncol 2008; 6 (12) 899-909
    PubMedGoogle Scholar
  • 25 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 (25) 4124-4130
    CrossrefPubMedGoogle Scholar
  • 26 Xie Y, Jaffe ES. How I diagnose angioimmunoblastic T-cell lymphoma. Am J Clin Pathol 2021; 156 (01) 1-14
    CrossrefPubMedGoogle Scholar
  • 27 Nicolae A, Pittaluga S, Venkataraman G. et al. Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: both EBV-positive and EBV-negative variants exist. Am J Surg Pathol 2013; 37 (06) 816-826
    CrossrefPubMedGoogle Scholar
  • 28 Rodriguez-Justo M, Attygalle AD, Munson P, Roncador G, Marafioti T, Piris MA. Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers. Mod Pathol 2009; 22 (06) 753-761
    CrossrefPubMedGoogle Scholar
  • 29 Mourad N, Mounier N, Brière J. et al; Groupe d'Etude des Lymphomes de l'Adulte. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Blood 2008; 111 (09) 4463-4470
    CrossrefPubMedGoogle Scholar
  • 30 Swerdlow SH, Campo E, Pileri SA. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127 (20) 2375-2390
    CrossrefPubMedGoogle Scholar
  • 31 Basha BM, Bryant SC, Rech KL. et al. Application of a 5 marker panel to the routine diagnosis of peripheral T-cell lymphoma with T-follicular helper phenotype. Am J Surg Pathol 2019; 43 (09) 1282-1290
    CrossrefPubMedGoogle Scholar
  • 32 Gaulard P, de Leval L. Follicular helper T cells: implications in neoplastic hematopathology. Semin Diagn Pathol 2011; 28 (03) 202-213
    CrossrefPubMedGoogle Scholar
  • 33 Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr Opin Hematol 2007; 14 (04) 348-353
    CrossrefPubMedGoogle Scholar
  • 34 Odejide O, Weigert O, Lane AA. et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 2014; 123 (09) 1293-1296
    CrossrefPubMedGoogle Scholar
  • 35 Lemonnier F, Cairns RA, Inoue S. et al. The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development. Proc Natl Acad Sci U S A 2016; 113 (52) 15084-15089
    CrossrefPubMedGoogle Scholar
  • 36 Ondrejka SL, Grzywacz B, Bodo J. et al. Angioimmunoblastic T-cell lymphomas with the RHOA p.Gly17Val mutation have classic clinical and pathologic features. Am J Surg Pathol 2016; 40 (03) 335-341
    CrossrefPubMedGoogle Scholar
  • 37 Dobson R, Du PY, Rásó-Barnett L. et al. Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis. Haematologica 2022; 107 (02) 489-499
    CrossrefPubMedGoogle Scholar
  • 38 Steinhilber J, Mederake M, Bonzheim I. et al. The pathological features of angioimmunoblastic T-cell lymphomas with IDH2R172 mutations. Mod Pathol 2019; 32 (08) 1123-1134
    CrossrefPubMedGoogle Scholar
  • 39 Dobay MP, Lemonnier F, Missiaglia E. et al. Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin. Haematologica 2017; 102 (04) e148-e151
    CrossrefPubMedGoogle Scholar
  • 40 Weisenburger DD, Savage KJ, Harris NL. et al; International Peripheral T-cell Lymphoma Project. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood 2011; 117 (12) 3402-3408
    CrossrefPubMedGoogle Scholar
  • 41 Kurita D, Miyoshi H, Yoshida N. et al. A clinicopathologic study of Lennert lymphoma and possible prognostic factors: the importance of follicular helper T-cell markers and the association with angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 2016; 40 (09) 1249-1260
    CrossrefPubMedGoogle Scholar
  • 42 Heavican TB, Bouska A, Yu J. et al. Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma. Blood 2019; 133 (15) 1664-1676
    CrossrefPubMedGoogle Scholar
  • 43 Iqbal J, Wright G, Wang C. et al; Lymphoma Leukemia Molecular Profiling Project and the International Peripheral T-cell Lymphoma Project. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 2014; 123 (19) 2915-2923
    CrossrefPubMedGoogle Scholar
  • 44 Sakata-Yanagimoto M, Fukumoto K, Karube K, Chiba S. Molecular understanding of peripheral T-cell lymphomas, not otherwise specified (PTCL, NOS): a complex disease category. J Clin Exp Hematop 2021; 61 (02) 61-70
    CrossrefPubMedGoogle Scholar
  • 45 Jeon YK, Kim JH, Sung JY, Han JH, Ko YH. Hematopathology Study Group of the Korean Society of Pathologists. Epstein-Barr virus-positive nodal T/NK-cell lymphoma: an analysis of 15 cases with distinct clinicopathological features. Hum Pathol 2015; 46 (07) 981-990
    CrossrefPubMedGoogle Scholar
  • 46 You MJ, Medeiros LJ, Hsi ED. T-lymphoblastic leukemia/lymphoma. Am J Clin Pathol 2015; 144 (03) 411-422
    CrossrefPubMedGoogle Scholar
  • 47 Dumas G, Prendki V, Haroche J. et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. [published correction appears in Medicine (Baltimore). 2014 Nov;93(24):414] Medicine (Baltimore) 2014; 93 (24) 372-382
    CrossrefPubMedGoogle Scholar
  • 48 Saglam A, Singh K, Gollapudi S. et al. Indolent T-lymphoblastic proliferation: a systematic review of the literature analyzing the epidemiologic, clinical, and pathologic features of 45 cases. Int J Lab Hematol 2022; 44 (04) 700-711
    CrossrefPubMedGoogle Scholar
  • 49 Matson DR, Yang DT. Autoimmune lymphoproliferative syndrome: an overview. Arch Pathol Lab Med 2020; 144 (02) 245-251
    CrossrefPubMedGoogle Scholar