Expert Histopathologic Evaluation and Molecular Analyses for Ambiguous Cutaneous Melanocytic Tumors
In brief
Expert review plus molecular testing diagnosed 97% of ambiguous skin tumors
At a Dutch referral center, expert pathology alone diagnosed 42% of 994 ambiguous primary skin melanocytic tumors; molecular testing helped bring the total with a diagnosis to 97%. Over a median follow-up of about five years, none of those diagnosed as nonmelanoma had melanoma-related events, while 5.7% of melanoma patients did. The findings support this stepwise approach, though referral-center results may not generalize.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 15 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Chiel F Ebbelaar, Anthonie W A Lensing, Gerben E Breimer, Marijke R van Dijk, Martin H Prins, Remco van Doorn, et al.
- PMID
- 42879715
- DOI
- 10.1200/JCO-26-00432
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 16 October 2026): Expert histopathologic and molecular analysis of ambiguous melanocytic tumors
Abstract
PURPOSE: A subset of cutaneous melanocytic tumors has ambiguous histopathologic features that preclude reliable classification as benign or malignant. We evaluated the diagnostic yield and long-term clinical validity of expert histopathologic evaluation and, when inconclusive, additional molecular analyses in patients with ambiguous primary cutaneous melanocytic tumors. METHODS: In this prospective cohort study, consecutive patients with primary cutaneous melanocytic tumors deemed ambiguous by referring pathologists were evaluated at a tertiary dermatopathology referral center in the Netherlands from September 2018 through December 2021. Tumors underwent expert histopathologic evaluation, with next-generation sequencing, single-nucleotide polymorphism array, and targeted RNA sequencing when inconclusive. Tumors were classified as nonmelanoma, melanoma, or borderline melanoma. Clinical validity was assessed by melanoma-related events during follow-up. RESULTS: Among 258,562 patients with excised melanocytic tumors nationwide, 2,685 (1.0%) had ambiguous tumors. We included 994 patients and reached a diagnosis in 966 (97.2%): 417 (42.0%) after expert histopathologic evaluation alone and 549 (55.2%) after additional molecular analyses. Among 608 patients (61.2%) with a nonmelanoma diagnosis, no melanoma-related events occurred during median follow-up of 5.4 years (incidence, 0.0%; 95% CI, 0.0 to 0.6). Among 358 patients (36.0%) with a melanoma diagnosis, 33 of 186 (17.7%) had a positive sentinel node biopsy, and 20 developed melanoma-related events during median follow-up of 5.0 years (cumulative incidence, 5.7%; 95% CI, 3.3 to 8.1). No events occurred in 28 patients (2.8%) with a borderline melanoma diagnosis. CONCLUSION: Expert histopathologic evaluation combined with molecular analyses provided a definitive diagnosis in nearly all patients with ambiguous primary cutaneous melanocytic tumors. Long-term follow-up supported the clinical validity of this stepwise diagnostic approach.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.