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

Abstract

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2 + (60%), CD3e + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR)β + (10%), TCRγ + (35%), TCRγδ + (50%), and double negative for TCR (six cases, 30%). All cases were EBER − . The genomic profile showed recurrent copy number gains of 1q32. 3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8 + CD56 + phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.

T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: review and update

“…21,52 Epidemiology MEITL occurs worldwide with predominance in Asia, and is less common in Western populations. 7,26,[52][53][54][55][56][57][58] Whereas examples of MEITL have been reported in patients with coeliac disease, 7 several well-characterised European and Asian series have shown no clear association with coeliac disease. 26,53,55,56 MEITL occurs over a wide age range (23-89 years), 55,56 with a median age of 58 years in the largest series reported to date.…”

“…[53][54][55][56][57][58] Clinical features and course More than half of patients present acutely with bowel perforation or obstruction, while others present more insidiously with abdominal pain, diarrhoea and weight loss. 53,55,56,58 The small bowel, particularly the jejunum, is involved in most cases, 26,[53][54][55][56][57][58] although the large bowel [53][54][55][56][57][58] and sometimes the stomach 55,58 can also be involved. Spread to mesenteric lymph nodes is common, 53 and disease can disseminate to extra-GI sites, including peripheral lymph nodes, lungs, liver and the central nervous system.…”

“…3A,B) of the tumour is characterised by transmural infiltration by lymphoma cells, 53,56,58 which are generally medium-sized with inconspicuous nucleoli and a rim of pale or clear cytoplasm. 26,[52][53][54][55][56][57] The infiltrate typically has a monotonous appearance on low power magnification, though there may be some variation in cell size between patients (small to large). 2,54,57 In contrast to EATL, an inflammatory background, 26,53,56,57 coagulative necrosis 26,52,53,[56][57][58] and angioinvasion 53 are absent.…”

Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms

“…MEITL is associated with frequent gains of the 8q24 locus involving the MYC oncogene [47,48]. The majority of MEITLs express γδ TCR, though there are αβ TCR variants [49].…”

The 2016 revision of the World Health Organization classification of lymphoid neoplasms

“…131 Gains in chromosome 8q24 involving MYC are seen in a high proportion of cases. 132 Many cases of MEITL are derived from gd T cells, but exceptions exist; some cases are T-cell receptor (TCR) silent and some cases express TCR ab. 133 Likewise, most cases of EATL express TCR ab, but gd variants exist.…”