# Dermal Mitoses Correlate with Surgical Burden in Lentigo Maligna Melanoma: PRAME for Margin Assessment

## TL;DR

This study shows that dermal mitoses in melanoma correlate with more surgeries and questions the need for re-excision based on PRAME positivity alone.

## Contribution

The study introduces a correlation between dermal mitoses and surgical burden and challenges assumptions about PRAME positivity in margin assessment.

## Key findings

- Dermal mitoses correlate with increased surgical procedures for tumor clearance.
- PRAME-positive cells were found in margins previously labeled tumor-free without local recurrence.
- The findings suggest a need for a clinically relevant threshold for PRAME positivity in surgical decisions.

## Abstract

Achieving tumor-free margins in Lentigo maligna and Lentigo maligna melanoma is a significant surgical challenge. In our analysis of over 171 cases, we identified a direct correlation between the presence of dermal mitoses and an increased number of surgical procedures required for clearance. Beyond this, our primary goal was to clarify the clinical significance of PRAME-positive melanocytes at the resection edge. We retrospectively stained archival margins previously classified as negative and found PRAME-positive isolated and grouped cells in some cases. Critically, no local recurrences were observed in these patients (albeit with small numbers and limited follow-up). This finding questions the assumption that any PRAME positivity at a margin necessitates re-excision, highlighting an urgent need to establish a clinically relevant threshold to guide surgical decisions and prevent potential overtreatment.

Background/Introduction: Margin assessment in Lentigo maligna (LM) and Lentigo maligna melanoma (LMM) is challenging. Many of these lesions require extensive surgical procedures for R0 resections with unclear histological and clinical features predicting lateral spread. Recently, PRAME was described as a useful antibody to determine margins in these entities. However, several questions, like acceptable PRAME+ cell number and density in resection margins and optimal safety margins, especially in head and neck areas, remain. Methods: We analyzed cases of LMIS and LMM since the introduction of PRAME and before the introduction of PRAME, with more than 171 cases in total. We re-stained security margins with PRAME. Results: We identified a correlation between reported dermal mitoses in LMM and the number of surgical procedures. In many LMM cases before the widespread use of PRAME from our archives, we detected a high density of PRAME+ cells in melanoma security margins previously labeled tumor-free. No local recurrence could be identified in these cases, with the caveat of limited follow-up and small case numbers. Conclusions: Our findings raise important questions regarding margin assessment with PRAME and the reporting of residual cells in margins.