Representation of melanoma depth staging with limited central section sampling: a retrospective simulation study

BACKGROUND AND OBJECTIVES: For thick melanomas, retaining the primary lesion during neoadjuvant therapy may enhance immune response through increased antigen load. This study assessed whether a central section from serially processed melanoma specimen, representing a transectional incisional biopsy, accurately reflects Breslow thickness and ulceration compared to full serial sectioning. PATIENTS AND METHODS: From a single center, histological slides of 78 invasive melanomas from 76 patients were retrospectively collected. Specimen were digitized, tumor-thickness and ulceration were measured across all tissue sections. The most central section was compared to the overall specimen. RESULTS: Across 78 paired comparisons, the median difference between central and maximum depth measurement was below 0.2 mm (0 mm, IQR 0.02, p < 0.001), with 64 (82.1%) cases ≤ 0.2 mm. Ulceration was present in 9 cases (11.5%), always detectable in the central section. T-stage remained unchanged in 73/78 cases (93.6%), the remaining 5 cases showed higher stages with full workup within T-stages ≤ 2. CONCLUSIONS: In this retrospective cohort, a central section provided Breslow thickness and T-stage equivalent to full serial sectioning in most cases, underestimation occurred only in thin melanomas. These findings provide a pre-clinical foundation for trials testing whether retaining the primary melanoma during neoadjuvant therapy may enhance treatment efficacy.