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

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

Publikationsverlauf

Artikel online veröffentlicht:
17. August 2023

• References

• 1 Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med 2000; 343 (02) 108-117
• 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
• 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
• 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
• 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
• 6 de Leval L. Approach to nodal-based T-cell lymphomas. Pathology 2020; 52 (01) 78-99
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 26 Xie Y, Jaffe ES. How I diagnose angioimmunoblastic T-cell lymphoma. Am J Clin Pathol 2021; 156 (01) 1-14
• 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
• 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
• 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
• 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
• 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
• 32 Gaulard P, de Leval L. Follicular helper T cells: implications in neoplastic hematopathology. Semin Diagn Pathol 2011; 28 (03) 202-213
• 33 Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr Opin Hematol 2007; 14 (04) 348-353
• 34 Odejide O, Weigert O, Lane AA. et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 2014; 123 (09) 1293-1296
• 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
• 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
• 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
• 38 Steinhilber J, Mederake M, Bonzheim I. et al. The pathological features of angioimmunoblastic T-cell lymphomas with IDH2^R172 mutations. Mod Pathol 2019; 32 (08) 1123-1134
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 46 You MJ, Medeiros LJ, Hsi ED. T-lymphoblastic leukemia/lymphoma. Am J Clin Pathol 2015; 144 (03) 411-422
• 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
• 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
• 49 Matson DR, Yang DT. Autoimmune lymphoproliferative syndrome: an overview. Arch Pathol Lab Med 2020; 144 (02) 245-251