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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Enteropathy-associated T-cell lymphoma


Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 7 February 2012, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Enteropathy-associated T-cell lymphoma (EATL) is an intestinal tumor of intraepithelial T lymphocytes showing varying degrees of transformation but usually presenting as a tumor composed of large lymphoid cells, often with an inflammatory background (WHO, 2008)

Terminology
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● Also called intestinal T-cell lymphoma (with or without enteropathy), but many other T-cell lymphomas can present with intestinal involvement

Epidemiology
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● Rare aggressive disease associated with gluten-sensitive enteropathy (celiac disease)
● Higher frequency in areas with high prevalence of celiac disease (northern Europe)
● Monomorphic variant (type II EATL): 10-20% of cases of EATL, broader geographic distribution and sporadic occurrence in areas where celiac disease is rare (Asia)

Etiology
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● Lymphomas of small intestine may derive from various subsets of intestinal intraepithelial lymphocytes that are differentially activated by diverse antigenic stimuli
● Association with celiac disease: positive serology, HLA DQ2 or DQ8 expression, dermatitis herpetiformis, hyposplenism
● Monomorphic variant NOT associated with celiac disease, may represent a distinct entity
● EATL in situ: refractory celiac disease with intraepithelial lymphocytes showing immunophenotypic and genetic features similar to EATL
● Recent studies evaluating the risk of lymphoma in patients with celiac disease: Table

Sites
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● Typically affects jejunum or ileum (ulcers with possible perforation)
● May occur in duodenum, stomach, colon or outside the GI tract, but rare

Clinical features
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● Childhood onset celiac disease in a minority of patients
● Adult onset celiac disease or celiac disease diagnosed simultaneously with lymphoma in most patients
● Abdominal pain, often intestinal perforation, sometimes prodrome of refractory celiac disease accompanied by ulceration (ulcerative jejunitis - UJ)

Case reports
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● 23 year old woman presenting with acute renal failure (World J Gastroenterol 2006;12:2301)
● 36 year old man with NK-like T cell lymphoma involving ileum but without celiac disease (Arch Pathol Lab Med 2003;127:e142)
● 37 year old man with enteropathy but no celiac disease (Hum Pathol 2004;35:639)
● 47 year old man with tumor developing after intestinal diffuse large B-cell lymphoma (Am J Surg Pathol 2007;31:476)

Treatment and prognosis
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● Usually poor for both forms, with recurrences most frequently in the small intestine and death from abdominal complications superimposed on uncontrolled malabsorption
● Proposed management to avoid perforation (Case Rep Oncol 2009;2:36)

Postulated normal counterpart
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● Intraepithelial T-cells of the intestine

Gross description
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● Multiple ulcerated mucosal masses, also single/multiple ulcers or large exophytic mass

Gross images
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Well defined mural mass


Multiple patchy segmented lesions

Micro description
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● Variably sized cells with abundant intraepithelial T cells, often infiltrating the individual crypt epithelium; villous atrophy due to celiac disease may be present
● Most commonly: relatively monotonous medium to large cells with round/angulated vesicular nuclei, prominent nucleoli and moderate/abundant pale cytoplasm
● Less commonly: marked pleomorphism with multinucleated cells similar to anaplastic large cell lymphoma
● Infiltration by inflammatory cells with numerous histiocytes and eosinophils, sometimes obscuring the lymphoma
● Enteropathy in the adjacent mucosa: villous atrophy, crypt hyperplasia, lamina propria lymphoplasmacytic infiltrate, intraepithelial lymphocytosis
Monomorphic variant (type II EATL): medium-sized, round, dark nuclei, rim of pale cytoplasm, florid crypt intraepithelial infiltration, prominent intraepithelial lymphocytosis in the adjacent mucosa, no inflammatory background, less necrosis

Micro images
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Various images

Positive stains
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● CD3, CD7, CD103, cytotoxic proteins TIA-1, perforin, granzyme B
● Variable CD8 and TCRβ
● CD30 in a variable proportion of tumor cells but in almost all cases
● Monomorphic variant: CD3+, CD4-, CD8+, CD56+, TCRβ+

Negative stains
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● CD4, CD5, CD56

Genetics and Molecular
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● Clonal rearrangement of TRB@ and TRG@ genes
HLADQA1*0501, DQB1*0201 genotype (celiac disease)
● Complex segmental amplifications of the 9q31.3-qter region or del16q12.1 (58-70% of cases, both forms)
● Classical form: +1q, +5q
● Monomorphic form: 8q24 (MYC) amplifications
● TCR gene rearrangements studies for EATL (Fig.2) and UJ (Fig.3) (Am J Pathol 1997;151:493)

Differential diagnosis
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● B cell lymphoma, histiocytic neoplasms, anaplastic carcinoma, melanoma

Additional references
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Am J Clin Pathol 2007;127:701

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Enteropathy-associated T-cell lymphoma


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