Cancer Res Treat.  2019 Oct;51(4):1568-1577. 10.4143/crt.2019.019.

Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study

Affiliations
  • 1Department of Pathology, Inha University School of Medicine, Incheon, Korea.
  • 2Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. jhpath.sohn@samsung.com
  • 3Department of Pathology, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea.
  • 4Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Pathology, Kosin University College of Medicine, Busan, Korea.
  • 6Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 7Department of Pathology, National Cancer Center, Goyang, Koreaa.
  • 8Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea.
  • 9Department of Pathology, Korea University College of Medicine, Seoul, Korea.
  • 10Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 11Department of Pathology, Inje University Busan Paik Hospital, Busan, Korea.
  • 12Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
  • 13Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun, Korea.
  • 14Department of Pathology, Pusan National University College of Medicine, Busan, Korea.
  • 15Department of Pathology, Samsung Medical Cancer, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 16Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Korea.
  • 17Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea.
  • 18Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Asan Digestive Disease Research Institute, Seoul, Korea.
  • 19Department of Statistics, Inha University, Incheon, Korea.
  • 20National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.

Abstract

PURPOSE
The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance.
MATERIALS AND METHODS
We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions.
RESULTS
The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important.
CONCLUSION
The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Keyword

Intraepithelial neoplasia; Stomach neoplasms; Endoscopic mucosal resection; Discrepancy; Reproducibility

MeSH Terms

Consensus
Diagnosis*
Retrospective Studies
Stomach Neoplasms

Figure

  • Fig. 1. Examples of underdiagnosed cases. (A-C) Carcinoma originally diagnosed as high-grade dysplasia. (A) Although the glandular polarity is maintained, irregular branching and fusion of glands are observed (×40). (B) Irregular branching of glands, papillary growth into the lumen, and focal surface maturation is present. A few angular glands are found (arrows, ×200). (C) In high power view, invasion of tumor cells into the lamina propria is present (arrow). Blurring of the outside of basement membrane is also present (arrow head). The nucleus shows vesicular chromatin and prominent nucleoli (×400). (D-F) Carcinoma originally diagnosed as low-grade dysplasia. (D) Low power view shows maintained glandular polarity but small glandular proliferation in basal portion (arrowhead) of the lesion (×40). (E) Crowding, stratification and atypia of surface epithelia are present (×400). (F) Invasions and blurring of basement membrane are identified in high power view (arrows, ×400). (G-I) Carcinoma showing obvious cytologic atypia originally diagnosed as high-grade dysplasia. (G) Hyperchromasia is easily noted in low power view (×40). (H) Not only marked cytologic atypia but also structural abnormality such as glandular branching and fusion is present. Definite invasion is not found (×200). (I) Marked cytologic atypia is present showing single-layer arrangement, prominent nucleoli and vesicular chromatin. In careful examination, minute invasions are identified (arrows, ×400).

  • Fig. 2. Examples of over-diagnosed cases. (A, B) Low-grade dysplasia originally diagnosed as high-grade dysplasia. (A) At low power, the glands are evenly distributed and not crowded. The size and shape of glands are relatively uniform without branching or papillary projection. However, polarity loss of glandular axis is present (×40). (B) Intraepithelial neutrophilic infiltration may cause marked nuclear stratification in low-grade dysplasia (×400). (C, D) Another example of low-grade dysplasia originally diagnosed as high-grade dysplasia. (C) The superficial portion of glands are irregularly proliferated due to regenerative change, mimicking high-grade dysplasia. However, the glands in deeper portion are evenly distributed and not crowded (×40). (D) The glandular epithelia show intraglandular proliferation, tufting and papillary features but surface maturation is evident (arrows). Atypical cytologic features such as nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli are occasionally found (×400). (E, F) High-grade dysplasia originally diagnosed as carcinoma. (E) Low power view demonstrates uneven distribution of glands with loss of polarity in the left side (×40). (F) Intraglandular proliferation, tufting and papillary features with cellular atypia is present. Atypical nuclear features mimicking carcinoma such as polarity loss and vesicular chromatin are focally present (×400). (G, H) Regenerative change originally diagnosed as carcinoma. (G) Glandular branching and irregularity are mimicking carcinomas (×40). (H) Stratification or hyperchromasia of the surface epithelium is not evident in regenerative change (×400).


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