Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy -
Minerva Endocrinol (Torino). 2021 Mar;46(1):35-44. doi: 10.23736/S2724-6507.20.03302-7. Epub 2020 Oct 12.
Multifocality is a common finding in papillary thyroid cancer but the molecular pathogenesis, prognosis and management of multifocal papillary thyroid cancer are debated. The clonal origin of multifocal papillary thyroid cancer represents a controversial aspect, as two opposite viewpoints have been proposed: independent origin or intraglandular spread. Different approaches have been used for inferring the clonality of multifocal papillary thyroid cancer, including X-chromosome inactivation, mutational analysis, determination of loss of heterozygosity and, more recently, next-generation sequencing. Next-generation sequencing, able to provide information on genetic heterogeneity and phylogenetic evolution in multifocal tumors, represents the most reliable approach. While most evidences indicated an independent origin of multifocal papillary thyroid cancer, a minority of studies suggested that multifocal papillary thyroid tumors might be monoclonally derived. This discrepancy may reflect technical limitations; nevertheless, studies based on next-generation sequencing indicated that both independent and clonal origins are possible. The co-existence of multiple tumors implies a high degree of genetic heterogeneity, which may influence the best and targeted therapeutic strategy. On the other hand, intrathyroidal dissemination may indicate metastatic potential of the dominant tumor, thereby prompting more aggressive treatments. In conclusion, data available in the literature indicated that multifocal papillary thyroid cancer may derived from both intraglandular spread and independent tumor foci. The understanding of the clonal origin of multifocal papillary thyroid tumors might represent an important issue in patient treatment.
多灶性是甲状腺乳头状癌的常见表现，但多灶性甲状腺乳头状癌的分子发病机制、预后和处理仍存在争议。多灶性甲状腺乳头状癌的克隆起源是一个有争议的问题，因为提出了两种相反的观点：独立起源或腺内播散。已经采用了不同的方法来推断多灶性甲状腺乳头状癌的克隆性，包括 X 染色体失活、突变分析、杂合性丢失的测定以及最近的下一代测序。下一代测序能够提供多灶性肿瘤中遗传异质性和系统发育进化的信息，是最可靠的方法。虽然大多数证据表明多灶性甲状腺乳头状癌是独立起源的，但少数研究表明多灶性甲状腺乳头状瘤可能是单克隆起源的。这种差异可能反映了技术上的局限性；然而，基于下一代测序的研究表明，多灶性甲状腺癌的起源既可以是独立的，也可以是克隆的。多个肿瘤的共存意味着存在高度的遗传异质性，这可能会影响最佳和靶向治疗策略。另一方面，甲状腺内播散可能表明优势肿瘤具有转移潜能，从而促使采取更积极的治疗方法。总之，文献中的数据表明，多灶性甲状腺乳头状癌可能源于腺内播散和独立肿瘤灶。了解多灶性甲状腺乳头状瘤的克隆起源可能是患者治疗的一个重要问题。
