Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
Expert Histopathologic Evaluation and Molecular Analyses for Ambiguous Cutaneous Melanocytic Tumors.
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Ebbelaar Chiel F, Lensing Anthonie W A, Breimer Gerben E, van Dijk Marijke R, Prins Martin H, van Doorn Remco, Schrader Anne M R, de Leng Wendy W J, Bloem Lourens T, Suijkerbuijk Karijn P M, Jansen Anne M L, Blokx Willeke A M, MOLecular Evaluation of Melanocytic Ambiguous Tumors (MOLEMAT) Investigators
Аннотация
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.
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.