Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Clinical Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
Mod Pathol. 2020 Mar;33(3):496-513. doi: 10.1038/s41379-019-0340-7. Epub 2019 Aug 5.
Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.
原发性肛门直肠黏膜黑色素瘤的病理分期通常根据美国癌症联合委员会（AJCC）的皮肤黑色素瘤指南进行，因为不存在专门针对肛门直肠黑色素瘤的分期系统。然而，目前尚不清楚从皮肤黑色素瘤中得出的预后因素是否也能分层肛门直肠黑色素瘤的风险。我们回顾性地确定了 160 例患者的临床病理参数与疾病特异性生存之间的相关性。根据就诊时的临床分期（局部疾病、区域或远处转移）将患者分组。Cox 比例风险回归模型确定了与疾病特异性生存相关的因素。我们还总结了在一组肿瘤中分析的热点突变癌相关基因面板中鉴定的体细胞突变。大多数患者为白人（82%）和女性（61%）。中位年龄为 62 岁。中位随访时间为 1.63 年，中位疾病特异性生存率为 1.75 年，121 例（76%）患者死于肛门直肠黑色素瘤。与疾病局限于肛门直肠的患者（42%）相比，区域（34%）或远处转移（24%）的患者疾病特异性生存率显著缩短。在分析 71 例肛门直肠黑色素瘤肿瘤的热点基因改变中，涉及 KIT 基因的体细胞突变（24%）最常见，其次是 NRAS（19%）。原发肿瘤厚度增加、血管淋巴管侵犯和无消退也与较短的疾病特异性生存相关。在出现局限性疾病（肿瘤厚度）或区域转移（肿瘤厚度、无消退和血管淋巴管侵犯）的患者中，原发肿瘤参数与较短的疾病特异性生存相关，但在出现远处转移的患者中则不然。根据第 8 版 AJCC 皮肤黑色素瘤分期系统修改后的方案对患者进行分组，可对肛门直肠黑色素瘤的生存情况进行分层。我们的研究结果支持肛门直肠黑色素瘤中主要肿瘤参数与疾病特异性生存之间的特定分期关联。此外，AJCC 皮肤黑色素瘤分期系统及其轻微修改预测了肛门直肠黑色素瘤患者的生存情况。
