title: Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features.
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.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Margolskee
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Lewis
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.forename: Peter H R
authors.initials: PH
authors.lastname: Green
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002446:Celiac Disease / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D003967:Diarrhea / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015431:Weight Loss
chemical_list: D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell