Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype

Abstract

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8(+)CD56(+) (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαβ over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8(+) cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

“…[1][2][3][4][5][6] In the present study, a high proportion of cases expressed γδ-TCR (10/20, 50%), and six cases were negative for both αβ and γδ-TCR, a finding that differs from the description in the WHO classification, which states that EATL Type II cases express αβ-TCR. Tan et al 7 reported predominant expression of αβ-TCR over γδ-TCR, and Chan et al 8 reported that 78% of Type II EATL cases expressed γδ-TCR. Our results confirm that the expression of γδ-TCR is frequently associated to the EATL Type II in Asia.…”

“…5,6 Prevalence of the HLA-DQ2 and DQ8 haplotypes that are frequently found in celiac disease was reported to be low in the Eastern Hemisphere. 7 In Asia, almost all EATL cases are classified as Type II, [6][7][8][9] and because of its low incidence, its pathological mechanism and immunohistological findings remain undefined and poorly understood. However, the association of Type II EATL with autoimmune hemolytic anemia is suggestive of a yet unidentified immunological background.…”

Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior

“…Absence of TCR expression might be a common phenomenon in T-cell lymphoma and was also reported in EATL. 28 Although the mechanism for TCR downregulation remains to be elucidated, lack of TCR in a significant proportion of T-cell type ENKTLs suggests that it might play a role in the pathogenesis of this tumor type. Cytotoxic T(Tc)-cells are key factors in the defense against viral infections.…”

Peripheral T cell lymphoma in Asia

“…In keeping with the normal ratio of IEL subsets, CD8? cases showed predominant CD8aa homodimer expression (77 %), regardless of TCR lineage [61].…”

“…In a recent Asian collaborative study, patients with EATL were mostly adult males (median age 58 years, male:female ratio 2.6:1), presenting with abdominal pain (60 %), intestinal perforation (40 %), and weight loss (28 %). None had a history of celiac disease, and the median survival was only 7 months [61]. EATL is a neoplasm of intraepithelial T lymphocytes (IEL) [56].…”