Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and New South Wales Health Pathology, Sydney, New South Wales, Australia.
JAMA Dermatol. 2023 Dec 1;159(12):1359-1367. doi: 10.1001/jamadermatol.2023.4193.
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.
To evaluate the prognostic significance of incipient ulceration in cutaneous melanoma.
DESIGN, SETTING, AND PARTICIPANTS: 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.
Clinicopathological factors and clinical outcomes: overall survival (OS), melanoma-specific survival (MSS), and recurrence-free survival (RFS) were compared between cases and controls.
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 mm2 in incipiently ulcerated cases compared with 1 (0-3.0) per mm2 in nonulcerated controls and 9 (5.0-14.0) per mm2 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; P = .02) and RFS (HR, 0.37; 95% CI, 0.22-0.64; P < .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; P = .03). After adjusting for pathological factors, no statistically significant differences in clinical outcomes were observed between cases and either control group.
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.
溃疡是皮肤黑色素瘤的一个关键特征，有助于根据当前的美国癌症联合委员会（AJCC）系统进行分期。然而，有初期溃疡的病例并不完全符合 AJCC 对溃疡的定义，因此被归类为非溃疡性，这给病理学家的诊断带来了一定的困难。初期溃疡的预后意义尚不确定。
评估皮肤黑色素瘤中初期溃疡的预后意义。
设计、地点和参与者：本病例对照研究包括 2005 年至 2015 年间诊断的切除的原发性皮肤黑色素瘤，这些病例来自澳大利亚黑色素瘤研究所的研究数据库，并且在皇家阿尔弗雷德王子医院可提供切片进行复查。由在黑素细胞病变诊断方面经验丰富的病理学家对切片进行复查，以确定病例（初期溃疡）和对照（溃疡或非溃疡）。初期溃疡病例分别与非溃疡和溃疡对照病例以 1:2 的比例进行匹配。研究分析于 2023 年 3 月至 6 月进行。
临床病理因素和临床结局：比较病例和对照组之间的总生存（OS）、黑色素瘤特异性生存（MSS）和无复发生存（RFS）。
在确定的 2284 名黑色素瘤患者中，340 名患者（中位[IQR]年龄，69[24-94]岁；136[68%]为男性；中位随访时间，7.2 年）符合入选标准。匹配的队列包括 40 例初期溃疡黑色素瘤病例，分别与 80 例非溃疡对照病例和 80 例溃疡对照病例进行 1:2 匹配。病例和对照组之间的 Breslow 厚度中位数（IQR）差异有统计学意义；初期病例为 2.8（1.7-4.1）mm，而非溃疡和溃疡黑色素瘤分别为 1.0（0.6-2.1）mm 和 5.3（3.5-8.0）mm。初期溃疡病例的肿瘤有丝分裂率中位数（IQR）为 5.0（3.0-9.0）/mm2，而非溃疡对照病例为 1（0-3.0）/mm2，溃疡对照病例为 9（5.0-14.0）/mm2。基于匹配队列，非溃疡肿瘤患者的 OS（风险比[HR]，0.49；95%CI，0.27-0.88；P=0.02）和 RFS（HR，0.37；95%CI，0.22-0.64；P<0.001）明显优于初期溃疡患者。与初期溃疡病例相比，溃疡肿瘤的 RFS 明显更差（HR，1.67；95%CI，1.07-2.60；P=0.03）。在调整病理因素后，病例与对照组之间在临床结局方面没有观察到统计学意义上的差异。
这项病例对照研究的结果表明，原发性黑色素瘤中的初期溃疡是一个不利的预后特征，病理学家在报告中应注意这一点，并在未来的指南中考虑这一点。
