Interobserver Variation in the Diagnosis of Gastric Epithelial Dysplasia and Carcinoma between Two Pathologists in Japan and Korea

Kushima, Ryoji,Kim, Kyoung-Mee The Korean Gastric Cancer Association 2011 Journal of gastric cancer Vol.11 No.3

Although the biological potential of gastric epithelial dysplasia (GED) as a precursor of gastric cancer has never been in doubt, the classification of these lesions has been controversial and fraught with marked variations in approach to diagnosis across the world. The complexity of cyto-architectural features has been considered to be of paramount importance for the diagnosis of carcinoma in Japan, while breach of the basement membrane and invasion into the lamina propria has been considered the sine qua non of malignancy and hence a pre-requisite for the diagnosis of cancer in the West. In Korea, although the incidence of gastric cancer is similar to Japan, the diagnostic approach to GED or cancer seems to lie midway between Western and Japanese criteria. In this review, we will discuss the difference in the diagnosis of GED and cancer between two pathologists working in the comprehensive cancer center located in Japan and Korea, one of the most prevalent areas in the world for gastric cancer.

Interobserver Variation in the Diagnosis of Gastric Epithelial Dysplasia and Carcinoma between Two Pathologists in Japan and Korea

Ryoji Kushima,김경미 대한위암학회 2011 Journal of gastric cancer Vol.11 No.3

Although the biological potential of gastric epithelial dysplasia (GED) as a precursor of gastric cancer has never been in doubt, the classification of these lesions has been controversial and fraught with marked variations in approach to diagnosis across the world. The complexity of cyto-architectural features has been considered to be of paramount importance for the diagnosis of carcinoma in Japan, while breach of the basement membrane and invasion into the lamina propria has been considered the sine qua non of malignancy and hence a pre-requisite for the diagnosis of cancer in the West. In Korea, although the incidence of gastric cancer is similar to Japan, the diagnostic approach to GED or cancer seems to lie midway between Western and Japanese criteria. In this review, we will discuss the difference in the diagnosis of GED and cancer between two pathologists working in the comprehensive cancer center located in Japan and Korea, one of the most prevalent areas in the world for gastric cancer.

Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases

박은수,김경미,김영은,박철근,Takashi Yao,Ryoji Kushima 대한병리학회 2012 Journal of Pathology and Translational Medicine Vol.46 No.3

Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.

CASE REPORTS : Repeatedly Recurrent Colon Cancer Involving the Appendiceal Orifice after Endoscopic Piecemeal Mucosal Resection: A Case Report

Masau Sekiguchi,Takahisa Matsuda,Shigeki Sekine,Taku Sakamoto,Takeshi Nakajima,Ryoji Kushima,Takayuki Akasu,Yutaka Saito 대한소화기학회 2013 대한소화기학회지 Vol.61 No.5

Magnified single-balloon enteroscopy in the diagnosis of intestinal follicular lymphoma: a case series

( Kenichiro Takahashi ),( Shigeki Bamba ),( Masahiro Kawahara ),( Atsushi Nishida ),( Osamu Inatomi ),( Masaya Sasaki ),( Tomoyuki Tsujikawa ),( Ryoji Kushima ),( Mitsushige Sugimoto ),( Katsuyuki Kit 대한장연구학회 2018 Intestinal Research Vol.16 No.4

The objective of this study was to evaluate the magnified endoscopic findings in the diagnosis of follicular lymphoma in the small intestine in comparison with those of intestinal follicular lymphoma and lymphangiectasia. Four patients with follicular lymphoma and 3 with lymphangiectasia in the small intestine were retrospectively analyzed. A prototype magnifying single-balloon enteroscope was used. The findings of the intestinal follicular lymphoma and lymphangiectasia were retrospectively analyzed to determine the magnified endoscopic findings of follicular lymphoma in the small intestine. Opaque white granules were observed in 3 of the 4 patients with follicular lymphoma. Magnified narrow-band imaging (NBI) of the opaque white granules showed stretched microvessels, which had a diminutive tree-like appearance. The remaining patient had no opaque white granules and only displayed whitish villi. Magnified NBI observation of the whitish villi revealed the absence of marginal villus epithelium, which was confirmed by histology. The magnified NBI enteroscopy revealed the diminutive tree-like appearance on the opaque white granules and the absence of marginal villus epithelium of the whitish villi in intestinal follicular lymphoma. These findings may be useful in diagnosing follicular lymphoma. (Intest Res 2018;16:628-634)

Dysregulated Wnt signalling and recurrent mutations of the tumour suppressor <i>RNF43</i> in early gastric carcinogenesis

Min, Byung‐,Hoon,Hwang, Jinha,Kim, Nayoung KD,Park, Gibeom,Kang, So Young,Ahn, Sangjeong,Ahn, Soomin,Ha, Sang Yun,Lee, Yun Kyung,Kushima, Ryoji,Van Vrancken, Michael,Kim, Min Jung,Park, Changho John Wiley Sons, Ltd 2016 The Journal of pathology Vol.240 No.3

<P><B>Abstract</B></P><P>Several recurrent mutations and epigenetic changes have been identified in advanced gastric cancer, but the genetic alterations associated with early gastric carcinogenesis and malignant transformation remain unclear. We investigated the genomic and transcriptomic landscape of adenomas with low‐grade dysplasia (LGD) and high‐grade dysplasia (HGD), and intestinal‐type early gastric cancer (EGC). The results were validated in an independent cohort that included EGCs directly adjacent to adenoma (EGC‐adenomas) that were in the process of malignant transformation, and <I>de novo</I> EGCs that do not seem to have been derived from adenoma. The expression patterns clearly divided into normal, LGD, and EGC, whereas those of HGD overlapped with LGD or EGC. These results suggest that HGD is the critical stage determining malignant transformation. We found that genes related to focal adhesion and extracellular matrix receptor interaction pathways were upregulated as LGD progressed to EGC, whereas canonical Wnt signalling and peroxisome proliferator‐activated receptor (PPAR) signalling pathway genes were downregulated in EGC. Genomic alterations such as somatic mutation, gene fusion and copy number variation increased gradually from LGD to EGC. <I>APC</I> mutations were present in 67% of LGDs, 58% of HGDs, and 18% of EGCs. <I>RNF43</I> mutations were present only in HGD and EGC, and <I>TP53</I> mutations were present only in EGC. In a validation cohort, <I>RNF43</I> mutations were present in 35.2% of EGC‐adenomas, but in only 8.6% of <I>de novo</I> EGCs. This is the first study to investigate the genomic and transcriptomic landscape of multistep gastric carcinogenesis. We investigated important alterations and their related pathways in each step as tumours progressed from LGD to HGD and eventually to EGC. We suggest that mutations and downregulation of <I>RNF43</I> may play a critical role in the transition from adenoma to carcinoma. Given these findings and Wnt dependency in tumours with <I>RNF43</I> mutation, intestinal‐type gastric cancer or adenoma with <I>RNF43</I> mutation might represent a promising indication for Wnt‐targeted agents. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Pyloric Gland Adenoma in Lynch Syndrome

Lee, Seung Eun,Kang, So Young,Cho, Junhun,Lee, Boram,Chang, Dong Kyung,Woo, Hyein,Kim, Jong Won,Park, Ha Young,Do, In Gu,Kim, Young Eun,Kushima, Ryoji,Lauwers, Gregory Y.,Park, Cheol Keun,Kim, Kyoung Raven Press 2014 The American journal of surgical pathology Vol.38 No.6

<P>The prevalence of gastric cancer associated with Lynch syndrome (LS) is highly variable, and the underlying histologic pathway or molecular mechanisms remain unclear. From 1995 to 2012, 15 patients had been treated for both gastric and colonic adenocarcinomas and diagnosed as LS. In all cases, pathologic review, immunohistochemical analysis for mismatch-repair proteins, and microsatellite instability (MSI) tests were performed. To confirm LS, germline mutation tests and multiplex ligation-dependent probe amplification were performed. All gastric and colonic carcinomas were MSI-high and lost expressions of MLH1/PMS2 in 11 (73%) cases and MSH2/MSH6 in 4 (27%) cases. Remarkably, in a patient with LS and germline mutation of <I>MLH1</I> gene, pyloric gland adenoma (PGA) transformed to adenocarcinoma during follow-up. In 2 additional cases, PGA was found adjacent to advanced gastric cancers. All PGAs in LS patients were MSI-high and lost expression of mismatch-repair proteins (MLH1/PMS2 in 2 cases and MSH2/MSH6 in 1 case), whereas none of the 14 sporadic PGAs was MSI-high or had lost expression of mismatch-repair proteins. On the basis of these observations, although very rare, we suggest the possibility that PGA may be a precursor lesion to gastric adenocarcinoma in LS and that the mismatch-repair deficient pathway of carcinogenesis is involved early in the gastric carcinogenesis pathway.</P>