Indolent Small Intestinal CD4+ T-cell Lymphoma Is a Distinct Entity with Unique Biologic and Clinical Features

Elizabeth Margolskee,Bachir Alobeid,Vaidehi Jobanputra,Govind Bhagat,Peter H R Green,Suzanne K Lewis,Dat Quoc Tran

doi:10.1371/journal.pone.0068343

Elizabeth Margolskee, Bachir Alobeid + Show 5 more

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https://doi.org/10.1371/journal.pone.0068343

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Journal: PloS one	Publication Date: Jul 4, 2013
Citations: 116	License type: CC BY 4.0

Affiliation: Columbia University Irving Medical Center

Abstract

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.

Highlights

Clinical Characteristics We identified 3 cases of primary small intestinal CD4+ T-cell lymphomas, which occurred in 2 males and 1 female, all of western European descent
All patients had prior evaluations at other institutions for diarrhea and weight loss and were diagnosed as having celiac disease. They were referred to our institution for further work-up and management of celiac disease ‘‘non-responsive’’ to a gluten free diet (GFD)
We describe a series of three cases of a rare subtype of primary small intestinal CD4+ T-cell lymphoma associated with a relatively indolent disease course

Summary

Introduction

The gastrointestinal (GI) tract is the most common extranodal site for the occurrence or presentation of lymphomas, the majority of which are of B-cell origin. [1,2] Peripheral T-cell lymphomas (PTCLs) account for approximately 15% of primary intestinal lymphomas. [3,4] Secondary involvement of the GI tract by different subtypes of T- and NK-lineage lymphomas can be seen in up to 46% of cases at autopsy. [5] Enteropathy associated T-cell lymphoma (EATL) types I and II and extranodal NK/T-cell lymphoma, nasal type, are the most frequent types of lymphomas presenting with intestinal involvement.[6,7,8] Rarely, other types of PTCL such as ALK+ anaplastic large cell lymphoma and gammadelta T-cell lymphoma can arise in the GI tract or involve it secondarily.[9,10,11].Primary T/NK-cell lymphomas of the intestine are associated with a poor prognosis and a high risk of bowel perforation.[6,7,8] rare cases of primary GI indolent lymphoproliferative disorders of CD8+ and CD4+ T-cell lineages have been described, mostly as sporadic case reports.[12,13,14,15,16,17,18] Recently, distinct phenotypic, biological and clinical features of indolent NK-cell lymphoproliferations of the GI tract were delineated in a series of cases. [19] morphologic and clinical features of indolent lymphomas of the T-cell lineage have been described, data regarding their immunophenotypic profiles and associated genomic abnormalities are limited.we evaluated the pathologic, genomic and clinical characteristics of three cases of indolent CD4+ T cell lymphomas, primarily involving the small intestine. Primary T/NK-cell lymphomas of the intestine are associated with a poor prognosis and a high risk of bowel perforation.[6,7,8] rare cases of primary GI indolent lymphoproliferative disorders of CD8+ and CD4+ T-cell lineages have been described, mostly as sporadic case reports.[12,13,14,15,16,17,18] Recently, distinct phenotypic, biological and clinical features of indolent NK-cell lymphoproliferations of the GI tract were delineated in a series of cases. [19] morphologic and clinical features of indolent lymphomas of the T-cell lineage have been described, data regarding their immunophenotypic profiles and associated genomic abnormalities are limited. Immunophenotypic and clinical features and manifested non recurrent genetic abnormalities, distinct from other types of primary enteric T-cell lymphomas. Immunophenotypic and clinical features and manifested non recurrent genetic abnormalities, distinct from other types of primary enteric T-cell lymphomas. [20] In conjunction with prior reports,[14,15,16,17] our findings suggest the existence of a unique and rare subtype of PTCL not recognized in the current WHO classification, which warrants greater awareness for correct diagnosis and optimal management. [20]

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