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Background: Lymph node yield (LNY) was implemented in the stratification of papillary thyroid cancer (PTC) patients. The effect of LNY may be related to the extent of surgery. This study aims to identify influencing factors for LNY in central compartment neck dissection (CND). Methods: Data of 13 712 consecutive PTC patients were analyzed retrospectively. Risk factors for LNY in CND and distribution characteristics of LNY were evaluated. Its relationship with prognosis was studied in another cohort of 136 cases. Results: LNY in therapeutic CND was significantly higher than prophylactic CND (Unilateral: 5.55 ± 3.79 vs 3.41 ± 2.77; Bilateral: 8.90 ± 5.10 vs 6.47 ± 4.17, P <.001). Other independent factors included extranodal extension (ETE), tumor size, and concurrent Hashimoto's thyroiditis. The inconsistency distribution of LNY in bilateral CND was associated with preoperative and intraoperative assessment. Patients with significant difference between major and minor LNY suffered from poorer prognosis (10y‐RFS: 58.3% vs 92.0%; HR = 6.719, 95%, P <.0001). Conclusions: CND surgical procedure, ETE, and Hashimoto's thyroiditis were independent factors of LNY. Inconsistent distribution of LNY was associated with prognosis of bilateral PTC patients. The impact of preoperative and intraoperative assessment on the actual extent of CND can be used to explain the relationship between LNY and PTC prognosis. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022. Among the cohort, 2337 (82%) cases possess genetic alterations, including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%), and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF-positive papillary thyroid cancer (PTC) patients tend to have older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Purpose: The majority of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are thought to dedifferentiated from differentiated thyroid cancer (DTC). PDTC is regarded as an intermediate form, through which DTC dedifferentiates into ATC. Although accumulation of gene mutations has been observed in PDTC and ATC, evidence of a direct link between DTC, PDTC, and ATC is still lacking. This work aims to illustrate if PDTC is the intermediate state between DTC and ATC., Patients and Methods: Whole-exome sequencing was performed in a single patient presenting with primary papillary thyroid cancer (PTC) with simultaneous PTC, PDTC, and ATC in metastatic lymph nodes., Results: 167 nonsynonymous mutations were identified, and 24 of them were exclusive to metastatic loci. Comparison of mutational spectra revealed following results: 1) PDTC and ATC were associated with PTC-LN2 but not PTC-LN1; 2) the majority (5/6) of non-ubiquitous mutations in ATC were also present in PDTC; and 3) despite one mutation observed simultaneously in PTC-LN2, PDTC and ATC, no other associations were found between the ATC and PTC samples (primary or metastatic). Additionally, we identified five mutations (four mutations present in both PDTC and ATC, and one exclusive to ATC), including TP53 p.N107&#95;S108delinsX, possibly related with DTC dedifferentiation., Conclusions: We observed an apparent potential, stepwise dedifferentiation process linking DTC, PDTC, and ATC, with PDTC serving as an intermediate state between DTC and ATC in one certain patient. One key mutation, combined with several low-frequency mutations, appears to underlie this dedifferentiation pathway., Competing Interests: None., (IJCEP Copyright © 2019.)

Yes-associated protein 1 (YAP1) stimulates cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis in several cancers. Here, we investigated the involvement of YAP1 in papillary thyroid carcinoma (PTC) by assessing YAP1 mRNA and protein levels in PTC tissues and matched normal thyroid epithelial tissues from 50 patients. YAP1 mRNA and protein levels were higher in PTC tumor tissues than in control tissues, and correlated positively with the levels of proliferation-related genes (KI67 and c-MYC). We also used lentiviral vectors to overexpress or silence YAP1 expression in the K1 PTC cell line so that we could investigate the effects of YAP1 on cancer cell proliferation. YAP1 overexpression enhanced PTC cell proliferation by activating ERK1/2 and AKT, and these effects were impaired by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor GSK690693. Finally, YAP1 overexpression dramatically induced growth of tumors from PTC cells in a xenograft mouse model. These results suggest that YAP1 enhances cell proliferation in PTC, and thus may be a promising target in the treatment of PTC.