{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:45:19Z","timestamp":1792097119956,"version":"4.4.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00432","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:00:26Z","timestamp":1792094426000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Expert Histopathologic Evaluation and Molecular Analyses for Ambiguous Cutaneous Melanocytic Tumors"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-8967","authenticated-orcid":false,"given":"Chiel F.","family":"Ebbelaar","sequence":"first","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands"},{"name":"Department of Dermatology, Leiden University Medical Center, Leiden, the 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Assessment, University of Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-6673","authenticated-orcid":false,"given":"Remco","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Department of Dermatology, Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-0558","authenticated-orcid":false,"given":"Anne M.R.","family":"Schrader","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy W.J.","family":"de Leng","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht, Utrecht, the 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