Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
IMPORTANCE: In cutaneous melanoma, the accuracy of frozen section (FS) analysis of sentinel lymph node biopsies (SLNB) remains controversial. FS could be used to guide patient-surgeon decision-making on completion lymphadenectomy, which may be influenced by the opportunity to have completion lymphadenectomy performed simultaneously with SLNB instead of as a return to the operating room.
OBJECTIVE: To summarize the sensitivity, specificity, and accuracy of FS analysis of SLNB and margins in cutaneous melanoma.
DATA SOURCES: In compliance with PRISMA guidelines, a librarian-led systematic search was performed of Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from 1946 to 2023.
STUDY SELECTION: Two independent reviewers (TV, CM) performed screening and data abstraction. Inclusion criteria included English language studies reporting a comparison of the results of FS analysis and final pathology (FP) analysis of SLNB or tumor margins in the setting of cutaneous melanoma. Exclusion criteria included reviews, case reports and studies using samples from Mohs microsurgery or mucosal melanoma.
DATA EXTRACTION AND SYNTHESIS: Primary outcomes included true negatives, false negatives, true positives and false positives.
MAIN OUTCOMES AND MEASURES: Using RevMan and Meta-DiSc 2.0, a pooled meta-analysis using a univariate model was performed on 9 studies that used H&E for FS and immunohistochemistry (IHC) as the gold standard. An additional bivariate model was fitted on 6 studies that either consistently or conditionally used the same immunostains for their gold standard. The Quality Assessment of Diagnostic Accuracy Studies-2 template was utilized for risk of bias assessment.
RESULTS: 319 unique articles were identified in the search, of which 20 were included in the systematic review. 17 studies reported the accuracy of FS in SLNBs and 3 reported FS accuracy in primary tumor margins. A total of 2,661 patients across 9 studies were included in the meta-analysis. The univariate model had a pooled sensitivity of 54% (95%CI: 48-60%) and pooled specificity of 100% (95%CI: 0-100%). Specificity metrics were completely homogenous (I2 = 0), while sensitivity metrics demonstrated moderate heterogeneity (I2 = 0.321). The bivariate model showed that conditionally using S-100 and HMB-45 immunostains during FP increased the sensitivity of FS compared to those that always used those stains (0.43 v 0.60, β=1.41, CI: 0.979-2.032, p<0.05).
Demographic and tumor features are described in Table 1. There was a high risk of bias among included studies, including selection bias (excluding patients with head and neck or stage 4 melanoma) and sampling bias (utilizing fewer sections for FS than FP or using only different sections for FS and FP).
CONCLUSIONS AND RELEVANCE: In the setting of cutaneous melanoma, use of intraoperative FS of SLNB is highly specific. A positive FS result can reliably be used to guide completion lymphadenectomy, with little risk of increased patient morbidity from overly aggressive surgery. On the other hand, a variable sensitivity suggests that patients should be counseled on the risk of identifying a positive node on FP after a negative FS result.