PDF(Pubmed)
Abstract：
BACKGROUND: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP.
METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations.
RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations.
CONCLUSIONS: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.
METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations.
RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations.
CONCLUSIONS: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.
摘要：
背景：头颈部淋巴结原发不明的转移性癌（HNCUP）产生了独特的诊断考虑因素。在许多情况下,高危型人乳头瘤病毒(HR-HPV)的检测发现了隐匿性口咽鳞状细胞癌(SCC).在转移性HR-HPV非依赖性癌中，应考虑其他主要站点，包括可模仿HR-HPV相关SCC的皮肤恶性肿瘤。在这种情况下，紫外线（UV）特征突变，定义为在二嘧啶位点具有≥5%CC→TT取代的≥60%C→T取代，在暴露于阳光区域的肿瘤中发现，在转移性HNCUP的背景下，是一种有吸引力且未充分利用的工具。
方法：对机构记录进行回顾性审查，重点关注HR-HPV阴性HNCUP病例。对所有病例进行下一代测序分析以评估UV特征突变。
结果：我们确定了14例HR-HPV阴性的HNCUP转移到宫颈或腮腺淋巴结，其中，11（11/14，79%）有紫外线特征突变，其中4例(4/10,40%)p16阳性。所有UV特征突变阳性病例具有至少一个显著的TP53突变和大于20个独特的基因突变。
结论：转移性皮肤癌的治疗明显不同于其他HNCUP，尤其是转移性HR-HPV相关SCC；因此，在HNCUP的下一代测序报告中,应常规纳入高比例的C→T和CC→TT取代的观察结果.UV突变特征测试是一种强大的诊断工具，可用于日常临床实践。
方法：对机构记录进行回顾性审查，重点关注HR-HPV阴性HNCUP病例。对所有病例进行下一代测序分析以评估UV特征突变。
结果：我们确定了14例HR-HPV阴性的HNCUP转移到宫颈或腮腺淋巴结，其中，11（11/14，79%）有紫外线特征突变，其中4例(4/10,40%)p16阳性。所有UV特征突变阳性病例具有至少一个显著的TP53突变和大于20个独特的基因突变。
结论：转移性皮肤癌的治疗明显不同于其他HNCUP，尤其是转移性HR-HPV相关SCC；因此，在HNCUP的下一代测序报告中,应常规纳入高比例的C→T和CC→TT取代的观察结果.UV突变特征测试是一种强大的诊断工具，可用于日常临床实践。
