J Pathol Transl Med.  2021 Jan;55(1):43-52. 10.4132/jptm.2020.10.04.

Interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma

• Jung HJ
• Lee SY
• Hong JH
• Chun YK

• KMID: 2511512
• DOI: http://doi.org/10.4132/jptm.2020.10.04

Abstract

Background
The accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features.
Methods
Three pathologists reviewed 21 surgically resected cases of advancedstage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis.
Results
The primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement).
Conclusions
We investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

Keyword

Endometrial neoplasms; Uterine neoplasm; Observer variation

Figure

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  Fig. 1 Representative microscopic features of cases 1–4. (A) In case 1 (mesonephric-like adenocarcinoma), the tumor showed ductal/glandular and papillary patterns. (B) Nuclear features of tumor cells were similar to those of papillary thyroid carcinoma, showing nuclear overlapping and openness of vesicular chromatin. Immunohistochemical (IHC) staining showed positivity in GATA3 (inset). (C) In case 2 (carcinosarcoma), the tumor predominantly showed complex papillary components and small foci of hypercellular stromal lesions. (D) On higher magnification, this lesion consisted of atypical pleomorphic spindle cells with frequent mitosis. (E) In case 3 (clear cell carcinoma), the tumor mainly showed a solid pattern. The tumor cells had hyperchromatic nuclei with vesicular chromatin and eosinophilic or clear cytoplasm. (F) A portion of the tumor showed a glandular pattern with high-grade nuclear atypia. On IHC stains, the tumor cells exhibited granular positivity for napsin A (inset). (G) In case 4 (large cell neuroendocrine carcinoma), the tumor showed well-defined nests with peripheral palisading. (H) Geographic tumor necrosis and diffuse immunoreactivity to CD56 was seen (inset).

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  Fig. 2 Representative microscopic features of cases 5–8. (A) In case 5 (large cell neuroendocrine carcinoma), a portion of the tumor was composed of well-defined nests with peripheral palisading and geographic necrosis. (B) The tumor also partly showed complex glandular and papillary pattern. The Immunohistochemical (IHC) staining of tumor cells showed diffuse positivity for synaptophysin (inset). (C) In case 6 (dedifferentiated carcinoma), the tumor showed complex glandular architecture consisting of columnar cells. (D) The undifferentiated carcinoma component was composed of solid sheets of monotonous dyscohesive cells. (E) In case 7 (serous carcinoma), the tumor showed a focal complex glandular and papillary pattern. (F) It was mostly comprised of solid architecture with high-grade nuclei and diffuse positivity to WT1 (inset). (G) In case 8 (serous carcinoma), some areas of the tumor showed papillary and micropapillary architecture composed of columnar cells with prominent nucleoli and nuclear pleomorphism. (H) Most of the tumor showed a solid pattern with focal glandular differentiation with tumor cells showing mild nuclear atypia. On immunostaining, the tumor cells exhibited aberrant p53 expression (inset).

Reference

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