Indolent T-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract (iTLPD-GI): A Review.

Francesca Sanguedolce,Cecilia Caprera,Stefano Luminari,Giovanni Martino,Maurizio Zizzo,Magda Zanelli,Alessandra Soriano,Linda Ricci,Stefano Ascani

doi:10.3390/cancers13112790

Abstract

Simple SummaryThis review aims to better define the clinical, pathological, and molecular features of the novel lymphoproliferative disease termed “indolent T-cell lymphoproliferative disorder of the gastro-intestinal tract (iTLPD-GI)”, to discuss potential pitfalls in differentiating this entity from other neoplastic and non-neoplastic disorders arising at the same site, and to point out a biomarker-based approach to the diagnosis.iTLPD-GI is a low-grade clonal T-cell lymphoproliferative disease arising in GI organs. It is an uncommon disease, and only recently has it been enlisted as a distinct provisional entity in the current WHO Classification. Data from the literature disclose high heterogeneity in terms of pathological and molecular features; on the other hand, establishing an accurate diagnosis of iTLPD-GI is of pivotal importance, since treatment options are different from that of other, more frequent lymphomas that arise in the gastrointestinal tract. In this review, we aimed to better define this novel entity, and to identify useful diagnostic biomarkers; moreover, we provide a biomarker-based approach to the diagnosis and describe the most common issues in differentiating iTLPD-GI from other neoplastic and non-neoplastic disorders.

Highlights

Indolent T-cell lymphoproliferative disorder of the gastro-intestinal tractis a low-grade, clonal, non-epitheliotropic T-cell lymphoproliferative disease, consisting of small lymphocytes, which can affect any site in the GI tract, most commonly the small bowel and colon [1,2]
A literature search was conducted using PubMed, Scopus, and Google Scholar databases with the following keywords: “indolent T-cell lymphoproliferative disorder AND gastrointestinal tract”, “iTLPD-GI”
A recent study demonstrated recurrent STAT3-JAK2 rearrangements by FISH in four out of five patients with CD4+ iTLPD-GIs, with evidence of STAT5 activation on staining for pY694-STAT5 [17]; three of their cases showed STAT3-JAK2 fusion with identical breakpoint. In keeping with these findings, one out of three CD4+ cases reported by Montes-Moreno et al [24] demonstrated JAK2 breaks and STAT3-JAK2 fusion, and mutations in the JAK-STAT signalling pathway genes were observed in 75% of the CD4+ cases and in the CD4+/CD8+ and CD4−/CD8− cases reported by Soderquist et al [21]

Summary

Introduction

Is a low-grade, clonal, non-epitheliotropic T-cell lymphoproliferative disease, consisting of small lymphocytes, which can affect any site in the GI tract, most commonly the small bowel and colon [1,2]. It probably arises from lamina propria lymphocytes [2]. In order to better define this novel entity, and to identify useful diagnostic biomarkers, we performed a systematic review of the literature and presented its results in three sections: first, we detail the clinical and pathological updated features of iTLPD-GI, we provide a biomarker-based approach to the diagnosis, and we describe the most common issues in its differential diagnosis

Objectives

Methods

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Conclusion