Interobserver reproducibility in assessing eosinophilic cells in ovarian serous borderline tumors to predict BRAF mutational status Journal Article


Authors: Chui, M. H.; Murali, R.; Soslow, R. A.; Matrai, C.; Xing, D. Y.; Vang, R.
Article Title: Interobserver reproducibility in assessing eosinophilic cells in ovarian serous borderline tumors to predict BRAF mutational status
Abstract: Ovarian serous borderline tumors (SBTs) harboring the BRAF(V600E) mutation are associated with decreased risk of progression to low-grade serous carcinoma, and often prominently feature tumor cells with abundant eosinophilic cytoplasm. Since eosinophilic cells (ECs) may be a marker of the underlying genetic driver, we proposed morphologic criteria and evaluated the interobserver reproducibility for assessing this histologic feature. Following the completion of an online training module, representative tumor slides from 40 SBTs (BRAF(V600E)-mutated, n=18, BRAF-wildtype, n=22) were independently reviewed by 5 pathologists. For each case, reviewers provided a semiquantitative assessment of the extent of ECs (0: absent, 1: <10%, 2: 10%-50%, or 3: >50%, of tumor area). Interobserver reproducibility for estimating the extent of ECs was moderate (& kappa;=0.41). Applying a cut-off score of & GE;2, the median sensitivity and specificity for predicting BRAF(V600E) mutation were 67% and 95%, respectively. With a cut-off score of & GE;1, median sensitivity and specificity were 100% and 82%, respectively. Morphologic mimics of ECs, including tumor cells with tufting or hobnail change and detached cell clusters in micropapillary SBTs, were possible contributing factors for discordant interobserver interpretations. BRAF(V600E) immunohistochemistry showed diffuse staining in BRAF-mutated tumors, including those with few ECs. In conclusion, the finding of extensive ECs in SBT is highly specific for BRAF(V600E) mutation. However, in some BRAF-mutated SBTs, ECs may be focal and/or difficult to distinguish from other tumor cells with overlapping cytologic features. The morphologic finding of definitive ECs, even when scarce, should therefore prompt consideration for BRAF(V600E) mutation testing.
Keywords: reproducibility; braf; features; low-grade; interobserver; lymph-node involvement; microinvasion; low-grade serous carcinoma; serous borderline tumor; eosinophilic cells
Journal Title: International Journal of Gynecological Pathology
Volume: 42
Issue: 5
ISSN: 0277-1691
Publisher: Lippincott Williams & Wilkins  
Date Published: 2023-09-01
Start Page: 472
End Page: 481
Language: English
ACCESSION: WOS:001048516000006
DOI: 10.1097/pgp.0000000000000933
PROVIDER: wos
PUBMED: 36867514
PMCID: PMC10363243
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is M. Herman Chui -- Source: Wos
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MSK Authors
  1. Robert Soslow
    793 Soslow
  2. Rajmohan Murali
    219 Murali
  3. Michael Herman Chui
    60 Chui