Reproducibility of histological cell type in high-grade endometrial carcinoma

Abstract

Subclassification of endometrial carcinoma according to histological type shows variable interobserver agreement. The aim of this study was to assess specifically the interobserver agreement of histological type in high-grade endometrial carcinomas, recorded by gynecological pathologists from five academic centers across Canada. In a secondary aim, the agreement of consensus diagnosis with immunohistochemical marker combinations was assessed including six routine (TP53, CDKN2A (p16), ER, PGR, Ki67, and VIM) and six experimental immunohistochemical markers (PTEN, ARID1A, CTNNB1, IGF2BP3, HNF1B, and TFF3). The paired interobserver agreement ranged from j 0.50 to 0.63 (median 0.58) and the intraobserver agreement from j 0.49 to 0.67 (median 0.61). Consensus about histological type based on morphological assessment was reached in 72% of high-grade endometrial carcinomas. A seven-marker immunohistochemical panel differentiated FIGO grade 3 endometrioid from serous carcinoma with a 100% concordance rate compared with the consensus diagnosis. More practically, a three-marker panel including TP53, ER, and CDKN2A (p16) can aid in the differential diagnosis of FIGO grade 3 endometrioid from endometrial serous carcinoma. Our study demonstrates that the inter-and intraobserver reproducibility of histological type based on morphology alone are mostly moderate. Ancillary techniques such as immunohistochemical marker panels are likely needed to improve diagnostic reproducibility of histological types within high-grade endometrial carcinomas.

Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma

“…They are frequently expressed in low-grade to intermediate-grade EC (> 70% tumors) but are usually negative in CCC. 18,[47][48][49][50] However, they may be less useful in the setting of a high-grade EC, as up to two thirds of these tumors can exhibit a loss of expression of 1 or both receptors. 49 Hoang and colleagues examined the immunoexpression patterns of HNF1b and ER in endometrial CCC, EC, and serous carcinomas and observed moderate to strong, diffuse nuclear HNF1b staining and no ER expression in 14/15 CCCs and 1/15 serous carcinomas.…”

“…Studies have shown that the diagnosis of endometrial or ovarian carcinomas with a clear cell component is associated with low to moderate interobserver reproducibility. [16][17][18] The presence of focal or, less commonly, extensive areas of clear cells in endometrioid neoplasms may be 19 Squamous differentiation is not infrequently encountered in EC, and squamous cells can exhibit cytoplasmic clearing due to an accumulation of glycogen. However, EC with glycogenated squamous cells will almost invariably exhibit more typical foci of squamous metaplasia.…”

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

“…Significant inter-observer variability exists, even amongst expert gynecopathologists, when subtyping and grading endometrial. [1][2][3][4] In most cases, tumor cell type and grade are diagnosed based on hematoxylin and eosin slides according to the WHO histopathological criteria. 5 The use of immunomarkers for distinguishing subtype has increased during the past years.…”

Comparative Use of Napsin A and Glypican 3 to Distinguish Endometrial Clear Cell from Serous and Endometrioid Carcinomas

“…In some cases, distinguishing CCC from other carcinomas with ''clear cell features'' and benign clear cell mimics proves challenging, and multiple authors have reported low interobserver and intraobserver reproducibility of histologic cell type in highgrade ECs with and without the presence of clear cells. 16,17 To date, immunohistochemistry (IHC) has had modest use in improving diagnostic reproducibility of high-grade ECs. However, recent literature suggests that glypican 3, hepatocyte nuclear factor IA, and napsin A show promise in distinguishing CCC from other high-grade ECs.…”