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

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 an...

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Veröffentlicht in:Modern pathology 2015-10, Vol.28 (10), p.1286-1296
Hauptverfasser: Tomita, Sakura, Kikuti, Yara Y, Carreras, Joaquim, Kojima, Minoru, Ando, Kiyoshi, Takasaki, Hirotaka, Sakai, Rika, Takata, Katsuyoshi, Yoshino, Tadashi, Bea, Silvia, Campo, Elias, Nakamura, Naoya
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container_end_page 1296
container_issue 10
container_start_page 1286
container_title Modern pathology
container_volume 28
creator Tomita, Sakura
Kikuti, Yara Y
Carreras, Joaquim
Kojima, Minoru
Ando, Kiyoshi
Takasaki, Hirotaka
Sakai, Rika
Takata, Katsuyoshi
Yoshino, Tadashi
Bea, Silvia
Campo, Elias
Nakamura, Naoya
description 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%), CD3 ɛ + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR) β + (10%), TCR γ + (35%), TCR γδ + (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.
doi_str_mv 10.1038/modpathol.2015.85
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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%), CD3 ɛ + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR) β + (10%), TCR γ + (35%), TCR γδ + (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 ). 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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%), CD3 ɛ + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR) β + (10%), TCR γ + (35%), TCR γδ + (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 ). 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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%), CD3 ɛ + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR) β + (10%), TCR γ + (35%), TCR γδ + (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 ). 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subjects 692/699/1541/1990/291/1621/1916
82/51
Adult
Aged
Comparative Genomic Hybridization
Enteropathy-Associated T-Cell Lymphoma - genetics
Enteropathy-Associated T-Cell Lymphoma - immunology
Enteropathy-Associated T-Cell Lymphoma - pathology
Female
Genome, Human
Humans
Immunohistochemistry
Immunophenotyping
In Situ Hybridization, Fluorescence
Japan
Laboratory Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
Oligonucleotide Array Sequence Analysis
original-article
Pathology
title Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan
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