Assessment of Melanocyte Density in Anorectal Mucosa for the Evaluation of Surgical Margins in Primary Anorectal Melanoma

Abstract

Objectives: Accurate histopathologic evaluation of surgical resection margins for anorectal melanoma (AM) is diagnostically challenging but essential to clinical management. We studied intraepithelial melanocyte density and growth pattern in anorectal mucosa and BRAF V600E mutation status in AM compared to controls.

Methods: Histomorphology and melanocytic immunostains, microphthalmia transcription factor (MITF) and human melanoma black 45 (HMB45), were evaluated. Utility of VE1 immunostaining for determination of BRAF V600E mutation status was studied.

Results: Immunostains aid in the distinction between "trailing" melanoma in situ (MIS) and benign melanocyte hyperplasia (BMH), by facilitating assessment of melanocyte density, and evaluation of nuclear atypia and growth pattern. While respective melanocyte densities overlapped, "trailing" MIS could be distinguished by melanocyte nuclear atypia and near confluent growth, compared to the banal cytology and scattered growth of BMH.

Conclusions: In the histopathologic assessment of AM resections, MITF and HMB45 immunostains aid in distinguishing between "trailing" MIS and BMH, by highlighting melanocyte density, nuclear atypia, and growth pattern, with the latter two being reliable features. VE1 showed nonspecific immunopositivity in anorectal glandular epithelium, a potential diagnostic pitfall when assessing BRAF mutation status.

Keywords: Anorectal; BRAF V600E; Gastrointestinal; Human melanoma black 45 (HMB45); Melanoma; Microphthalmia transcription factor (MITF).