Characterizing Nodal Gamma-Delta T-Cell Lymphoma: Clinicopathological and Molecular Insights.

in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc by Ming Liang Oon, Jing Quan Lim, Jan Bosch-Schips, Fina Climent, Rex K H Au-Yeung, Bailey Hutchison, Aliyah R Sohani, Ozgur Can Eren, Jyoti Kumar, Ahmet Dogan, Choon-Kiat Ong, Leticia Quintanilla-Martinez, Siok-Bian Ng

TLDR

  • The study presents a series of 12 cases of EBV-negative nodal gamma-delta T-cell lymphomas, highlighting their clinical, histopathological and molecular features, and emphasizes the need for further research to better characterize this rare entity.

Abstract

Peripheral T-cell lymphomas with gamma-delta phenotype (GDTCL) are rare lymphoid malignancies. Beyond the well-recognized entities of extranodal lymphomas with gamma-delta phenotype as defined by the 5th edition of the WHO Classification of Hematolymphoid Tumors and 2022 International Consensus Classification, there is a group of poorly-defined gamma-delta T-cell lymphomas with predominantly nodal presentation, termed as nodal GDTCL (nGDTCL). In this study, we present a series of 12 cases of EBV-negative nGDTCL, highlighting the clinical, histopathological and molecular features of this rare entity. Seven cases reported in the literature were included for the analysis. Of the 12 cases, nGDTCL shows an increased incidence in elderly males with a median age of 65.5 years. All cases presented primarily with enlarged lymph nodes and 4 cases (4/12; 33.3%) showed involvement of extranodal sites, including skin, liver, spleen and bone marrow. Histologically, 9 cases showed a diffuse and monomorphic proliferation of mostly medium to large lymphoid cells while 3 cases demonstrated a lymphoepithelioid morphology. All cases (12/12, 100%) were positive for CD3 and TCRγδ. CD4, CD8 and CD56 were positive in 66.7% (8/12), 25% (3/12) and 8.3% (1/11) of cases, respectively. Most cases (8/12, 66.7%) showed a non-cytotoxic phenotype. Using immunohistochemistry, the majority of cases (6/8, 75.0%) belonged to the PTCL-GATA3 subtype with GATA3 and/or CCR4 expression and a non-cytotoxic CD4-positive phenotype. Two cases (2/8, 25%) belonged to the PTCL-TBX21 subtype, of which 1 displayed a cytotoxic CD8-positive phenotype. Next-generation sequencing was performed on 9 cases and TP53 mutation was detected in 66.7% (6/9) of cases. Mutations of ATM and KSR2 were identified in 2 cases each. It remains uncertain if nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.

Overview

  • This study presents a series of 12 cases of EBV-negative nodal gamma-delta T-cell lymphomas (nGDTCL), highlighting their clinical, histopathological and molecular features.
  • The study aimed to better define the characteristics of this rare entity, which lacks a clear classification in the current WHO Classification of Hematolymphoid Tumors.
  • The research focuses on the diagnosis and management of nGDTCL, a group of poorly-defined gamma-delta T-cell lymphomas with predominantly nodal presentation.

Comparative Analysis & Findings

  • The study found an increased incidence of nGDTCL in elderly males, with a median age of 65.5 years and predominantly nodal presentation.
  • Histopathologically, 9 cases showed a diffuse and monomorphic proliferation of mostly medium to large lymphoid cells, while 3 cases demonstrated a lymphoepithelioid morphology.
  • Immunohistochemically, all cases were positive for CD3 and TCRγδ, and 75% of cases belonged to the PTCL-GATA3 subtype with GATA3 and/or CCR4 expression and a non-cytotoxic CD4-positive phenotype.

Implications and Future Directions

  • The study suggests that nGDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.
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