{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:13:12Z","timestamp":1783343592587,"version":"3.54.6"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:sec id=\"ab-doi230053-4\"><jats:title>Importance<\/jats:title><jats:p>Ulceration represents a key feature in cutaneous melanoma, contributing to staging according to the current American Joint Committee on Cancer (AJCC) system. However, cases with incipient ulceration do not quite fulfill the AJCC definition of ulceration and are consequently classified as nonulcerated, presenting interpretive difficulty for pathologists. The prognostic implication of incipient ulceration is uncertain.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi230053-5\"><jats:title>Objective<\/jats:title><jats:p>To evaluate the prognostic significance of incipient ulceration in cutaneous melanoma.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi230053-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This case-control study consisted of resected primary cutaneous melanomas diagnosed between 2005 and 2015, identified from the Melanoma Institute Australia research database and with slides available for review at Royal Prince Alfred Hospital. Slides were reviewed by pathologists experienced in the diagnosis of melanocytic lesions to identify cases (incipient ulceration) and controls (ulcerated or nonulcerated). Incipient ulceration cases were matched at a 1:2 ratio with nonulcerated and ulcerated controls, respectively. Study analysis was conducted from March to June 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi230053-7\"><jats:title>Main Outcomes<\/jats:title><jats:p>Clinicopathological factors and clinical outcomes: overall survival (OS), melanoma-specific survival (MSS), and recurrence-free survival (RFS) were compared between cases and controls.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi230053-8\"><jats:title>Results<\/jats:title><jats:p>Of 2284 patients with melanoma identified, 340 patients (median [IQR] age, 69 [24-94] years; 136 [68%] men; median follow-up, 7.2 years) met the criteria. The matched cohort consisted of 40 cases of incipiently ulcerated melanoma matched 1:2 with 80 nonulcerated controls, and 80 ulcerated controls. The median (IQR) Breslow thickness differed significantly between cases and controls; 2.8 (1.7-4.1) mm for incipient cases compared with 1.0 (0.6-2.1) mm and 5.3 (3.5-8.0) mm for nonulcerated and ulcerated melanomas, respectively. Median (IQR) tumor mitotic rate was 5.0 (3.0-9.0) per mm<jats:sup>2<\/jats:sup> in incipiently ulcerated cases compared with 1 (0-3.0) per mm<jats:sup>2<\/jats:sup> in nonulcerated controls and 9 (5.0-14.0) per mm<jats:sup>2<\/jats:sup> in ulcerated controls. Based on the matched cohorts, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49; 95% CI, 0.27-0.88; <jats:italic>P<\/jats:italic>\u2009=\u2009.02) and RFS (HR, 0.37; 95% CI, 0.22-0.64; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) than patients with incipient ulceration. The RFS was significantly worse in ulcerated tumors compared with incipiently ulcerated cases (HR, 1.67; 95% CI, 1.07-2.60; <jats:italic>P<\/jats:italic>\u2009=\u2009.03). After adjusting for pathological factors, no statistically significant differences in clinical outcomes were observed between cases and either control group.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi230053-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The findings of this case-control study indicate that incipient ulceration in a primary melanoma represents an adverse prognostic feature that should be noted by pathologists in their reports and considered in future guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2023.4193","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T16:17:14Z","timestamp":1698855434000},"page":"1359","source":"Crossref","is-referenced-by-count":13,"title":["Prognostic Significance of Incipient Ulceration in Primary Cutaneous Melanoma"],"prefix":"10.1001","volume":"159","author":[{"given":"Elizabeth C.","family":"Paver","sequence":"first","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and New South Wales Health Pathology, Sydney, New South Wales, Australia"},{"name":"Department of Anatomical Pathology, The Canberra Hospital, Canberra, Australian Capital Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasnia","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel","family":"Burke","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn P. M.","family":"Saw","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Stretch","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Spillane","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerwin F.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael A.","family":"Vergara","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serigne N.","family":"Lo","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Scolyer","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and New South Wales Health Pathology, Sydney, New South Wales, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 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