Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Tissue Pathology & Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia.
Mod Pathol. 2021 Nov;34(11):1999-2008. doi: 10.1038/s41379-021-00870-2. Epub 2021 Jul 10.
Regression in melanoma is an immunological phenomenon that results in partial or complete replacement of the tumor with variably vascular fibrous tissue, often accompanied by pigment-laden macrophages and chronic inflammation. In some cases, tumor-infiltrating lymphocytes (TILs) may represent the earliest phase of this process. The prognostic significance of regression has long been a matter of debate, with inconsistent findings reported in the literature to date. This study sought to determine whether regression in primary cutaneous melanomas predicted sentinel lymph node (SLN) status and survival outcomes in a large cohort of patients managed at a single centre. Clinical and pathological parameters for 8,693 consecutive cases were retrieved. Associations between regression and SLN status, overall survival (OS), melanoma-specific survival (MSS) and recurrence-free survival (RFS) were investigated using logistic and Cox regression. Histological evidence of regression was present in 1958 cases (22.5%). Regression was significantly associated with lower Breslow thickness, lower mitotic rate, and absence of ulceration (p < 0.0001). Multivariable analysis showed that regression in combination with TILs independently predicted a negative SLN biopsy (OR 0.33; 95% C.I. 0.20-0.52; p < 0.0001). Patients whose tumors showed both regression and TILs had the highest 10-year OS (65%, 95% C.I. 59-71%), MSS (85%, 95% C.I. 81-89%), and RFS (60%, 95% C.I. 54-66%). On multivariable analyses, the concurrent presence of regression and TILs independently predicted the lowest risk of death from melanoma (HR 0.69; 95% C.I. 0.51-0.94; p = 0.0003) as well as the lowest rate of disease recurrence (HR 0.71; 95% C.I. 0.58-0.85; p < 0.0001). However, in contrast, in the subgroup analysis of Stage III patients, the presence of regression predicted the lowest OS and RFS, with MSS showing a similar trend. Overall, these findings indicate a prognostically favorable role of regression in primary cutaneous melanoma. However, in Stage III melanoma patients, regression may be a marker of more aggressive disease.
黑色素瘤的消退是一种免疫现象，导致肿瘤的部分或完全被富含血管的纤维组织取代，通常伴有色素沉着的巨噬细胞和慢性炎症。在某些情况下，肿瘤浸润淋巴细胞 (TIL) 可能代表该过程的最早阶段。消退的预后意义一直是争论的焦点，迄今为止，文献中报道的结果不一致。本研究旨在确定在单一中心管理的大量患者中，原发性皮肤黑色素瘤中的消退是否预测前哨淋巴结 (SLN) 状态和生存结局。检索了 8693 例连续病例的临床和病理参数。使用逻辑回归和 Cox 回归分析消退与 SLN 状态、总生存 (OS)、黑色素瘤特异性生存 (MSS) 和无复发生存 (RFS) 之间的关系。在 1958 例病例中存在组织学消退证据 (22.5%)。消退与较低的 Breslow 厚度、较低的有丝分裂率和无溃疡显著相关 (p<0.0001)。多变量分析表明，消退与 TIL 联合独立预测 SLN 活检阴性 (OR 0.33；95%CI 0.20-0.52；p<0.0001)。肿瘤同时具有消退和 TIL 的患者 10 年 OS（65%，95%CI 59-71%）、MSS（85%，95%CI 81-89%）和 RFS（60%，95%CI 54-66%）最高。在多变量分析中，消退和 TIL 的同时存在独立预测黑色素瘤死亡风险最低 (HR 0.69；95%CI 0.51-0.94；p=0.0003)，疾病复发率最低 (HR 0.71；95%CI 0.58-0.85；p<0.0001)。然而，相比之下，在 III 期患者的亚组分析中，消退的存在预测了最低的 OS 和 RFS，MSS 也呈现出类似的趋势。总体而言，这些发现表明原发性皮肤黑色素瘤中的消退具有预后有利的作用。然而，在 III 期黑色素瘤患者中，消退可能是疾病更具侵袭性的标志物。
