Duodenal Neoplasms of Gastric Phenotype: An Immunohistochemical and Genetic Study with a Practical Approach to the Classification

Risa Hida, Hidetaka Yamamoto, Minako Hirahashi, Reiko Kumagai, Kenichi Nishiyama, Toshihiro Gi, Motohiro Esaki, Takanari Kitazono, Yoshinao Oda

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.

元の言語英語
ページ(範囲)343-353
ページ数11
ジャーナルAmerican Journal of Surgical Pathology
41
発行部数3
DOI
出版物ステータス出版済み - 1 1 2017

Fingerprint

Duodenal Neoplasms
Adenoma
Stomach
Phenotype
Adenocarcinoma
Mutation
Gastric Mucosa
Stomach Neoplasms
Gastric Mucins
Pepsinogen A
Neoplasms
Proton-Translocating ATPases
Mucins
Oncogenes
Duodenum
Genes
Cytoplasm
Epithelial Cells
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

これを引用

Duodenal Neoplasms of Gastric Phenotype : An Immunohistochemical and Genetic Study with a Practical Approach to the Classification. / Hida, Risa; Yamamoto, Hidetaka; Hirahashi, Minako; Kumagai, Reiko; Nishiyama, Kenichi; Gi, Toshihiro; Esaki, Motohiro; Kitazono, Takanari; Oda, Yoshinao.

:: American Journal of Surgical Pathology, 巻 41, 番号 3, 01.01.2017, p. 343-353.

研究成果: ジャーナルへの寄稿記事

Hida, Risa ; Yamamoto, Hidetaka ; Hirahashi, Minako ; Kumagai, Reiko ; Nishiyama, Kenichi ; Gi, Toshihiro ; Esaki, Motohiro ; Kitazono, Takanari ; Oda, Yoshinao. / Duodenal Neoplasms of Gastric Phenotype : An Immunohistochemical and Genetic Study with a Practical Approach to the Classification. :: American Journal of Surgical Pathology. 2017 ; 巻 41, 番号 3. pp. 343-353.
@article{141fbac05a9f4810b42c5aa466c5291d,
title = "Duodenal Neoplasms of Gastric Phenotype: An Immunohistochemical and Genetic Study with a Practical Approach to the Classification",
abstract = "Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38{\%}) of 16 DNGPs (4 [57{\%}] adenomas, 1 [16{\%}] NUMP, and 1 [33{\%}] invasive adenocarcinoma) and APC in 4 of 15 (27{\%}) DNGPs: no adenomas, 2 (33{\%}) NUMPs, and 2 (67{\%}) invasive adenocarcinomas. BRAF mutation was present in only 1 (16{\%}) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term {"}NUMP{"} as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.",
author = "Risa Hida and Hidetaka Yamamoto and Minako Hirahashi and Reiko Kumagai and Kenichi Nishiyama and Toshihiro Gi and Motohiro Esaki and Takanari Kitazono and Yoshinao Oda",
year = "2017",
month = "1",
day = "1",
doi = "10.1097/PAS.0000000000000785",
language = "English",
volume = "41",
pages = "343--353",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Duodenal Neoplasms of Gastric Phenotype

T2 - An Immunohistochemical and Genetic Study with a Practical Approach to the Classification

AU - Hida, Risa

AU - Yamamoto, Hidetaka

AU - Hirahashi, Minako

AU - Kumagai, Reiko

AU - Nishiyama, Kenichi

AU - Gi, Toshihiro

AU - Esaki, Motohiro

AU - Kitazono, Takanari

AU - Oda, Yoshinao

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.

AB - Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.

UR - http://www.scopus.com/inward/record.url?scp=85006275629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006275629&partnerID=8YFLogxK

U2 - 10.1097/PAS.0000000000000785

DO - 10.1097/PAS.0000000000000785

M3 - Article

C2 - 27984236

AN - SCOPUS:85006275629

VL - 41

SP - 343

EP - 353

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 3

ER -