Type II Enteropathy-Associated T-Cell Lymphoma: A Distinct Aggressive Lymphoma With Frequent gamma delta T-cell Receptor Expression

Department of Pathology, Queen Elizabeth Hospital, Hong Kong, SAR China.
The American journal of surgical pathology (Impact Factor: 5.15). 09/2011; 35(10):1557-69. DOI: 10.1097/PAS.0b013e318222dfcd
Source: PubMed


Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αβ T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."

15 Reads
  • Source
    • "Primary T/NK-cell lymphomas of the intestine are associated with a poor prognosis and a high risk of bowel perforation.[6]–[8] However, rare cases of primary GI indolent lymphoproliferative disorders of CD8+ and CD4+ T-cell lineages have been described, mostly as sporadic case reports.[12]–[18] "
    [Show abstract] [Hide abstract]
    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.
    PLoS ONE 07/2013; 8(7):e68343. DOI:10.1371/journal.pone.0068343 · 3.23 Impact Factor

  • Journal of clinical pathology 02/2012; 65(6):575-6. DOI:10.1136/jclinpath-2011-200618 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.
    The American journal of surgical pathology 02/2012; 36(4):481-99. DOI:10.1097/PAS.0b013e31824433d8 · 5.15 Impact Factor
Show more