Accepted Article
Article type
: Letters, techniques and images
Title: Adenocarcinoma of the colon, presenting as a submucosal tumor
Running title: Colon cancer presenting as an SMT
Authors: Hourin Cho,1, 2 Shigeki Sekine,2,3 Masau Sekiguchi,1, 4
Institutions: 1
Endoscopy Division, National Cancer Center Hospital, 2Division of Pathology and
Clinical Laboratories, National Cancer Center Hospital,
3
Division of Molecular
Pathology, National Cancer Center Research Institute, 4Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan
Addresses of the institutions: 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan1-4 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/den.12949 This article is protected by copyright. All rights reserved.
Accepted Article
Correspondence to:
Masau Sekiguchi, M.D., Ph.D.
Endoscopy Division, National Cancer Center Hospital,
5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
E-mail: [email protected]
Tel: +81-3-3542-2511; Fax: +81-3-3248-2463
A 64-year-old woman underwent colonoscopy for abdominal discomfort and a protruded lesion measuring approximately 10 mm was detected in the descending colon. The tumor was entirely covered by normal-appearing mucosa and was regarded as a submucosal tumor (SMT). A small adenomatous polyp was present beside the SMT (Figure 1). For precise histological assessment of the SMT and therapeutic purpose of the coexisted polyp, we performed complete resection of the lesions by endoscopic submucosal dissection. Pathological examination unexpectedly showed that the SMT was a moderately differentiated tubular adenocarcinoma confined to the submucosal layer (Figure 2A, 2B). The adenocarcinoma was completely covered by non-neoplastic mucosa (Figure 2C, 2D). The coexisted polyp was a tubular adenoma (Figure 2A). Histologically, the adenocarcinoma and adenoma had no continuity (Figure 2D) and no mucosal lesion
This article is protected by copyright. All rights reserved.
Accepted Article
was detected for the adenocarcinoma. Colectomy with lymphadenectomy was performed following the endoscopic resection (pT1b ≥1000 µm), and no metastatic or residual lesions were detected. Although the adenocarcinoma and adenoma were histologically separate, histogenetic relationship was suspected based on their proximity. A mutation analysis of APC using Sanger sequencing1 identified a frameshift mutation (c.4418delA) in both lesions. This mutation is reportedly very rare; only 1 tumor has been recorded to have this mutation among 6319 APC mutations in the COSMIC database2, suggesting that two lesions were derived from a single precursor lesion. Several literatures have described colorectal adenocarcinomas showed SMT-like appearance3-5. However, these previous cases invariably had a mucosal lesion, consistent with their epithelial origin. Our case is distinctive in that the adenocarcinoma was completely confined to the submucosal layer, having no contact with the epithelium even on pathological examination. The present case suggests that while rare, some colorectal cancers are hardly distinguishable from other SMTs.
Acknowledgement
We thank Ms. Sachiko Miura, Ms. Toshiko Sakaguchi and Ms. Chizu Kina for their skillful technical assistance. We also thank Dr. Mai Ego, Dr. Taku Sakamoto, Dr. Hiroyuki Takamaru, Dr. Masayoshi Yamada, Dr. Takahisa Matsuda, Dr. Hiroshi
This article is protected by copyright. All rights reserved.
Accepted Article
Yoshida, Dr. Hirokazu Taniguchi, and Dr. Yutaka Saito for their critical revision of the manuscript.
Conflict of Interest
The authors declare no conflicts of interest for this article.
References
1
Hashimoto T, Ogawa R, Matsubara A et al. Familial adenomatous polyposis-
associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features. Histopathology. 2015; 67: 689-698
2
COSMIC. Catalogue of somatic mutations in cancer [Internet]. England:
Welcome Trust Sanger Institute; c 2004-2017 [accessed on 2017 June 4]. Available from: http://cancer.sanger.ac.uk/cosmic/.
3
Nakajima T, Kamano T, Shibasaki K et al. Colonic carcinoma resembling
submucosal tumor. Int J Gastrointest Cancer. 2005; 36: 155-161.
This article is protected by copyright. All rights reserved.
Accepted Article
4
Shinagawa T, Ishihara S, Nozawa H et al (in press). Small colorectal cancers
resembling submucosal tumor with massive submucosal invasion and lymph node metastasis: A report of two cases and review of the literature. Clin Res Hepatol Gastroenterol. doi: 10. 1016/j.clinre.2016.07.007
5
Zenda T, Masunaga T, Shinozaki K et al. Primary minute invasive de novo
colonic adenocarcinoma appearing as submucosal tumor. Int J Gastrointest Cancer. 2005; 36: 177-181.
This article is protected by copyright. All rights reserved.
Accepted Article
Figure legends
Figure 1. Endoscopic findings of the protruded lesion and polyp
Colonoscopy revealed a protruded lesion measuring approximately 10 mm in the descending colon. The tumor was entirely covered by normal-appearing mucosa and considered to be a submucosal tumor (SMT). Some minute depressions were present on the surface. The small polyp measuring approximately 4 mm was closely located to the SMT.
Figure 2. Histological findings of the resected specimen
(A) Cross-sectional view of the lesion showing a well-demarcated SMT (asterisk) and a small polyp (arrowheads). The small polyp was a tubular adenoma. (B) The SMT was a moderately differentiated tubular adenocarcinoma [7x7mm, pSM2(3000
μ m),
ly0, v0, pHM0, pVM0]. (C) The adenocarcinoma was covered by non-
neoplastic mucosa. Note the intact muscularis mucosae (arrowheads). (D) An area of minute depression observed during the endoscopic examination showed granulomatous inflammation extending to the mucosal layer. The surface was covered by non-neoplastic epithelium (arrows). There was no continuity between the adenocarcinoma (asterisk) and the adenoma (arrowheads).
This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Article type
: Letters, techniques and images
Title: Adenocarcinoma of the colon, presenting as a submucosal tumor
Running title: Colon cancer presenting as an SMT
Authors: Hourin Cho,1, 2 Shigeki Sekine,2,3 Masau Sekiguchi,1, 4
Institutions: 1
Endoscopy Division, National Cancer Center Hospital, 2Division of Pathology and
Clinical Laboratories, National Cancer Center Hospital,
3
Division of Molecular
Pathology, National Cancer Center Research Institute, 4Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan
Addresses of the institutions: 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan1-4 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/den.12949 This article is protected by copyright. All rights reserved.
Accepted Article
Correspondence to:
Masau Sekiguchi, M.D., Ph.D.
Endoscopy Division, National Cancer Center Hospital,
5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
E-mail: [email protected]
Tel: +81-3-3542-2511; Fax: +81-3-3248-2463
A 64-year-old woman underwent colonoscopy for abdominal discomfort and a protruded lesion measuring approximately 10 mm was detected in the descending colon. The tumor was entirely covered by normal-appearing mucosa and was regarded as a submucosal tumor (SMT). A small adenomatous polyp was present beside the SMT (Figure 1). For precise histological assessment of the SMT and therapeutic purpose of the coexisted polyp, we performed complete resection of the lesions by endoscopic submucosal dissection. Pathological examination unexpectedly showed that the SMT was a moderately differentiated tubular adenocarcinoma confined to the submucosal layer (Figure 2A, 2B). The adenocarcinoma was completely covered by non-neoplastic mucosa (Figure 2C, 2D). The coexisted polyp was a tubular adenoma (Figure 2A). Histologically, the adenocarcinoma and adenoma had no continuity (Figure 2D) and no mucosal lesion
This article is protected by copyright. All rights reserved.
Accepted Article
was detected for the adenocarcinoma. Colectomy with lymphadenectomy was performed following the endoscopic resection (pT1b ≥1000 µm), and no metastatic or residual lesions were detected. Although the adenocarcinoma and adenoma were histologically separate, histogenetic relationship was suspected based on their proximity. A mutation analysis of APC using Sanger sequencing1 identified a frameshift mutation (c.4418delA) in both lesions. This mutation is reportedly very rare; only 1 tumor has been recorded to have this mutation among 6319 APC mutations in the COSMIC database2, suggesting that two lesions were derived from a single precursor lesion. Several literatures have described colorectal adenocarcinomas showed SMT-like appearance3-5. However, these previous cases invariably had a mucosal lesion, consistent with their epithelial origin. Our case is distinctive in that the adenocarcinoma was completely confined to the submucosal layer, having no contact with the epithelium even on pathological examination. The present case suggests that while rare, some colorectal cancers are hardly distinguishable from other SMTs.
Acknowledgement
We thank Ms. Sachiko Miura, Ms. Toshiko Sakaguchi and Ms. Chizu Kina for their skillful technical assistance. We also thank Dr. Mai Ego, Dr. Taku Sakamoto, Dr. Hiroyuki Takamaru, Dr. Masayoshi Yamada, Dr. Takahisa Matsuda, Dr. Hiroshi
This article is protected by copyright. All rights reserved.
Accepted Article
Yoshida, Dr. Hirokazu Taniguchi, and Dr. Yutaka Saito for their critical revision of the manuscript.
Conflict of Interest
The authors declare no conflicts of interest for this article.
References
1
Hashimoto T, Ogawa R, Matsubara A et al. Familial adenomatous polyposis-
associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features. Histopathology. 2015; 67: 689-698
2
COSMIC. Catalogue of somatic mutations in cancer [Internet]. England:
Welcome Trust Sanger Institute; c 2004-2017 [accessed on 2017 June 4]. Available from: http://cancer.sanger.ac.uk/cosmic/.
3
Nakajima T, Kamano T, Shibasaki K et al. Colonic carcinoma resembling
submucosal tumor. Int J Gastrointest Cancer. 2005; 36: 155-161.
This article is protected by copyright. All rights reserved.
Accepted Article
4
Shinagawa T, Ishihara S, Nozawa H et al (in press). Small colorectal cancers
resembling submucosal tumor with massive submucosal invasion and lymph node metastasis: A report of two cases and review of the literature. Clin Res Hepatol Gastroenterol. doi: 10. 1016/j.clinre.2016.07.007
5
Zenda T, Masunaga T, Shinozaki K et al. Primary minute invasive de novo
colonic adenocarcinoma appearing as submucosal tumor. Int J Gastrointest Cancer. 2005; 36: 177-181.
This article is protected by copyright. All rights reserved.
Accepted Article
Figure legends
Figure 1. Endoscopic findings of the protruded lesion and polyp
Colonoscopy revealed a protruded lesion measuring approximately 10 mm in the descending colon. The tumor was entirely covered by normal-appearing mucosa and considered to be a submucosal tumor (SMT). Some minute depressions were present on the surface. The small polyp measuring approximately 4 mm was closely located to the SMT.
Figure 2. Histological findings of the resected specimen
(A) Cross-sectional view of the lesion showing a well-demarcated SMT (asterisk) and a small polyp (arrowheads). The small polyp was a tubular adenoma. (B) The SMT was a moderately differentiated tubular adenocarcinoma [7x7mm, pSM2(3000
μ m),
ly0, v0, pHM0, pVM0]. (C) The adenocarcinoma was covered by non-
neoplastic mucosa. Note the intact muscularis mucosae (arrowheads). (D) An area of minute depression observed during the endoscopic examination showed granulomatous inflammation extending to the mucosal layer. The surface was covered by non-neoplastic epithelium (arrows). There was no continuity between the adenocarcinoma (asterisk) and the adenoma (arrowheads).
This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
