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Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review

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Abstract

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 − /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 − . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 − /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 − , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.

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Abbreviations

CD:

Crohn disease

CHOP:

Cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone

CISH:

Chromogenic in situ hybridization

EATL–II:

Type II enteropathy-associated T-cell lymphoma

EBER:

Epstein-Barr virus–encoded RNA

FFPE:

Formalin-fixed, paraffin-embedded

FISH:

Fluorescence in situ hybridization

HPF:

High-power field; H&E, Hematoxylin and eosin

IHC:

Immunohistochemistry

iTLPD-GI:

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract

IBD:

Inflammatory bowel disease

ITCL NOS:

Intestinal T-cell lymphoma, not otherwise specified

LI:

Labeling index

MEITL:

Monomorphic epitheliotropic intestinal T-cell lymphoma

NGS:

Next-generation sequencing

PCR:

Polymerase chain reaction

PTCL NOS:

Peripheral T-cell lymphoma, not otherwise specified

TCR:

T-cell receptor

UC:

Ulcerative colitis

VAF:

Variant allele frequency

WHO:

World Health Organization

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Acknowledgements

Part of this study had been presented as a poster at the 11th Asia Pacific International Academy of Pathology Congress on October 9 to 14, 2019 in Hefei, China. We thank Dr. Qinglong Hu (Pathology Associates, Clovis, CA, USA) for his critical discussion and revision on the manuscript. We thank Dr. Shu-Yuan Xiao (Department of Pathology, The University of Chicago, Chicago, IL, USA) for his polishing the manuscript. We thank all investigators at Zhongnan Hospital of Wuhan University for participating in this study.

Funding

This study was supported by Zhongnan Hospital of Wuhan University, Science, Technology and Innovation Seed Fund (Project number: znpy2019067).

Author information

Authors and Affiliations

  1. Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Wei Fan, Li Niu, Jian Xu & Qiongrong Chen

  2. Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China

    Huihua He & Jingping Yuan

  3. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China

    Fei Yuan

  4. Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Beijing, China

    Xueying Shi

  5. Department of Gastroenterology, Peking University Third Hospital, Beijing, China

    Ye Wang

  6. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Min Chen & Meifang Huang

  7. Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Fuling Zhou

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  1. Wei Fan
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Contributions

All authors contributed to the study conception and design.

Wei Fan carried out the testing of FISH, TCR, NGS, and analyzed the data. Li Niu carried out immunohistochemical staining. Huihua He and Jingping Yuan contributed case 2 (surgical resected specimen). Xueying Shi and Ye Wang contributed case 4, and Fei Yuan contributed case 5. Qiongrong Chen, Jingping Yuan, Xueying Shi, and Fei Yuan reviewed and analyzed all the 6 cases. Min Chen, Meifang Huang, Fuling Zhou, and Ye Wang collected and organized the clinical and endoscopic data. Jian Xu carried out the H&E staining and EBER. Qiongrong Chen coordinated the study and wrote the manuscript.

Corresponding author

Correspondence to Qiongrong Chen.

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Ethics approval

The study has been conducted according to the guidelines of the local ethical committee (the clinical research ethics certificate number was 2021052 K).

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Fig. S1

Single nucleotide variants tested by NGS on resected sample of patient 1. a TET2 mutation: T was inserted at codon 2482 in exon 3 of the TET2 gene (TET2 c.2482dupT); b Another point mutation of TET2: T was deleted at codon 2647 in exon 3 of the TET2 gene (TET2 c.2649delT). c Missense mutation [c.664G > C (p.A222P)] was detected in exon 7 of DDX3X gene (DDX3X c.664G > C) (PNG 385 KB).

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Fan, W., Niu, L., He, H. et al. Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review. Virchows Arch 482, 729–743 (2023). https://doi.org/10.1007/s00428-022-03467-5

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