Frozen section biopsy showed consistently high specificity but variable sensitivity across 15 studies, with accuracy influenced by tumor grade, the presence of lesions, and pathologist experience.
In a systematic review, which followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, investigators evaluated studies comparing intraoperative frozen section (FS) biopsy with final paraffin-embedded histopathology, the reference standard. Across 240 initially identified records identified using the PubMed, Scopus, Web of Science, and Embase databases, 15 studies met the inclusion criteria, encompassing sample sizes from 23 to 868 patients and predominantly retrospective designs.
FS biopsy showed specificity frequently reaching 100% across multiple studies and a high positive predictive value, with some studies reporting 100%, indicating that the method had a strong ability to confirm malignancy when present and supporting its role in intraoperative decision-making when gross lesions are identified.
Sensitivity varied widely, ranging from about 41% to 97%. Lower performance was reported in complex atypical hyperplasia and early-stage cancers, where studies noted diagnostic challenges and reduced reliability. Negative predictive value also varied substantially, with values as low as 12.5%, underscoring limitations in ruling out malignancy.
Overall diagnostic accuracy ranged from approximately 43.5% to 97%, with most studies reporting values above 80%. For instance, a retrospective analysis reported 97% accuracy with sensitivity of 97% and specificity of 100%, whereas another study showed accuracy of 43.5% with substantial discordance between FS and final pathology.
Agreement between FS biopsy and final histopathology was consistently high for detecting malignancy and evaluating myometrial invasion. One study found concordance near 97% for malignancy, while another reported agreement reflected by a kappa value of 0.75. In contrast, performance was weaker in complex atypical hyperplasia, where one study observed discordance in about 61% of cases.
Diagnostic performance was higher in high-grade tumors and in cases with visible lesions. By contrast, sampling from endometrium without apparent abnormalities provided limited usefulness, and the depth of myometrial invasion was frequently misjudged.
Methodologic variability limited quantitative synthesis. Differences in study design, FS protocols, histologic classification, and pathologist experience prevented quantitative pooling of results, prompting a narrative synthesis approach. Risk of bias was low in nine of 15 studies, with moderate or high risk primarily associated with unclear selection criteria, subgroup-focused cohorts, or small sample sizes.
The review described FS biopsy as useful during surgery but not sufficient on its own for diagnosis. Its strong specificity could make it effective in identifying malignancy, particularly when lesions are visible. In contrast, inconsistent sensitivity and low negative predictive value could reduce confidence in ruling out disease, particularly in premalignant and early-stage cases.
“FS biopsy should be viewed as a complementary-rather than definitive-diagnostic method, with final histopathology remaining the gold standard for endometrial pathology assessment,” wrote lead study author Mudather Abdelgabar Ali Mohammed, of Anatomical Sciences at St. George’s University in Grenada, and colleagues.
The researchers reported no conflicts of interest.
Source: Cureus