Department of Otolaryngology Head and Neck Surgery, Nottingham University Hospitals, Queens Centre Campus, Nottingham, UK.
Department of Pathology, Sahlgrenska Center for Cancer Research, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Virchows Arch. 2024 Jul;485(1):3-11. doi: 10.1007/s00428-024-03798-5. Epub 2024 Apr 17.
Primary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should only be made after the exclusion of mSCCP. Moreover, all of the histological diagnostic criteria proposed to be in favor of pSCCP (such as, for example, dysplasia of ductal epithelium) can be encountered in unequivocal mSCCP, thereby representing secondary growth along preexistent ducts. Squamous cell differentiation has also been reported in rare genetically defined primary parotid carcinomas, either as unequivocal histological squamous features (e.g., NUT carcinoma, mucoepidermoid carcinoma), by immunohistochemistry (e.g., in NUT carcinoma, adamantinoma-like Ewing sarcoma, basal-type salivary duct carcinoma, mucoepidermoid carcinoma), or a combination of both. Another major issue in this context is that the International Classification of Diseases (ICD) coding system does not distinguish between primary or metastatic disease, resulting in a large number of patients with mSCCP being misclassified as pSCCP. Immunohistochemistry and new molecular biomarkers have significantly improved the accuracy of the diagnosis of many salivary gland neoplasms, but until recently there were no biomarkers that can accurately distinguish between mSCCP and pSCCP. However, recent genomic profiling studies have unequivocally demonstrated that almost all SCCP analyzed to date have an ultraviolet light (UV)-induced mutational signature typical of mSCCP of skin origin. Thus, mutational signature analysis can be a very useful tool in determining the cutaneous origin of these tumors. Additional molecular studies may shed new light on this old diagnostic and clinical problem. This review presents a critical view of head and neck experts on this topic.
腮腺原发性鳞状细胞癌（pSCCP）长期以来一直被认为是一种独立的实体，被纳入世界卫生组织（WHO）的唾液腺肿瘤分类。然而，在头颈部病理学家中，pSCCP 极为罕见已被广泛接受。然而，有许多出版物描述了 pSCCP 系列，并且来自 SEER 和其他癌症登记数据库的数据错误地表明 pSCCP 的发病率正在增加。重要的是，pSCCP 和转移性（继发性）腮腺鳞状细胞癌（mSCCP）具有几乎相同的组织学特征，只有排除 mSCCP 后才能诊断为 pSCCP。此外，所有提出的有利于 pSCCP 的组织学诊断标准（例如，导管上皮的发育不良）都可以在明确的 mSCCP 中遇到，因此代表沿着先前存在的导管的继发性生长。在罕见的遗传定义的原发性腮腺癌中，也有报道鳞状细胞分化，表现为明确的组织学鳞状特征（例如，NUT 癌、黏液表皮样癌），通过免疫组织化学（例如，在 NUT 癌、尤文肉瘤样间叶性横纹肌肉瘤、基底样唾液导管癌、黏液表皮样癌），或两者的结合。在这种情况下，另一个主要问题是国际疾病分类（ICD）编码系统不能区分原发性或转移性疾病，导致大量 mSCCP 患者被错误地归类为 pSCCP。免疫组织化学和新的分子生物标志物显著提高了许多唾液腺肿瘤诊断的准确性，但直到最近，还没有可以准确区分 mSCCP 和 pSCCP 的生物标志物。然而，最近的基因组分析研究明确表明，迄今为止分析的几乎所有 SCCP 都具有源自皮肤的 mSCCP 的紫外线（UV）诱导的突变特征。因此，突变特征分析可以成为确定这些肿瘤的皮肤来源的非常有用的工具。其他分子研究可能会为这个旧的诊断和临床问题提供新的线索。这篇综述介绍了头颈专家对这一主题的批判性观点。
