The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy.

CONTEXT: Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported. OBJECTIVE: To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy. METHODS: A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated. RESULTS: Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET. CONCLUSION: True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.

A Significance of Concomitant BRAFV600E and TERT Mutations in Polish Patients with Papillary Thyroid Microcarcinoma: A Retrospective Cohort Study Based on 430 Cases.

Background: The incidence of papillary thyroid cancer is increasing worldwide due to more frequent pathological detection of papillary thyroid microcarcinomas (PTMC), which are cancers measuring 1 cm or less in diameter. In rare cases, the course of PTMC can be aggressive, with an increased risk of recurrence/persistent disease. The aim of this study of Polish patients diagnosed with PTMC was to assess the impact of concomitant B-type Raf kinas-activating mutation in codon 600 of exon 15 (BRAFV600E) and telomerase reverse transcriptase (TERT) hotspot mutations on clinicopathological features, response to treatment, potential recurrence, and the final outcome. Methods: A retrospective analysis of the 430 PTMC cases diagnosed during 2001-2020 at a single center was performed. All PTMC cases were assessed histopathologically, and analyses of BRAFV600E and TERT promoter were performed based on DNA isolated from tumor blocks. Results: There were 29/430 (6.7% [confidence interval: 4.6-9.5]) patients in whom the TERTC228T and/or TERTC250T mutations coexisted with the BRAFV600E mutation. A statistical comparison between PTMC cases with concomitant BRAFV600E and TERT hotspot mutations and those without any of those mutations revealed no significant differences between the two groups with respect to risk stratification, response to primary treatment, clinical course, or final disease status. Conclusion: Regardless of the molecular background of PTMC, the overall response to therapy is excellent, and long-term disease-free survival rates can be achieved by most patients.

Are molecular tests necessary to diagnose NIFTP?

In 2016, encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In 2018 the criteria for NIFTP were widened by the inclusion of the complete lack of papillae. Secondary criteria, which include molecular examination, are helpful but not required for NIFTP diagnose. The aim of this study was to assess the molecular background of NIFTP and to answer the question if the aplication of revised criteria for NIFTP diagnosis is associated with the lack of oncogenic mutation. Repeat histopathological assessment of 1117 cases of papillary thyroid carcinoma (PTC) from 2000-2016 was conducted. Using initial (2016) and revised (2018) diagnostic criteria, NIFTP was diagnosed in 23 and 13 patients respectively. 50 tumor genes hotspots mutation analysis was conducted. BRAF V600E mutations were detected in patients who fulfilled only initial NIFTP criteria. Other high-risk mutations (TP53) were found in both groups of patients. The application of restrictive, revised diagnostic criteria for NIFTP negates the need for BRAF V600E examination, but these tumors still can harbor other high-risk oncogenic mutations nonetheless. Thus, molecular examination should be considered as a necessary step in NIFTP diagnostic process.

Is Male Sex A Prognostic Factor in Papillary Thyroid Cancer?

Identifying risk factors is crucial for predicting papillary thyroid cancer (PTC) with severe course, which causes a clinical problem. The purpose of this study was to assess whether male sex can be such a predictive factor and to verify whether including it as a predictive factor of high initial risk of recurrence/persistence would help to enhance the value of the American Thyroid Association initial risk stratification system (ATA). We retrospectively analyzed 1547 PTC patients (1358 females and 189 males), treated from 1986 to 2018. The relationship between sex and clinicopathological features, response to therapy, and disease status was assessed. Men with PTC showed some adverse clinicopathological features more often than women, including angioinvasion, lymph node metastases, and tumor size > 40 mm. There were sex-related disparities with respect to response to initial therapy and final follow-up. Male sex is associated with some unfavorable clinicopathological features of PTC, which may affect response to initial therapy or final disease status. In our study, modification of the ATA system by including male sex as a risk factor does not enhance its value. Thus, further studies are needed to assess whether males require treatment modalities or oncological follow-up protocols that are different from those of females.

Does the TT Variant of the rs966423 Polymorphism in DIRC3 Affect the Stage and Clinical Course of Papillary Thyroid Cancer?

Thyroid cancer (TC) is the most common cancer of the endocrine system. Most new diagnoses are of low-grade papillary thyroid cancer (PTC), suggesting that PTC may be over-diagnosed. However, the incidence of advanced-stage PTC has increased in recent years. It is therefore very important to identify prognostic factors for advanced PTC. Somatic mutation of the BRAF gene at V600E, or the coexistence of the BRAF V600E mutation and mutations in the TERT promoter are associated with more aggressive disease. It would also be valuable to identify genetic risk factors affecting PTC prognosis. We therefore evaluated the impact of the rs966423 polymorphism in the DIRC3 gene, including its relationship with unfavorable histopathological and clinical features and mortality, in differentiated thyroid cancer (DTC). The study included 1466 patients diagnosed with DTC from one center. There was no significant association between the DIRC3 genotype at rs966423 (CC, CT, or TT) and any histopathological or clinic factor examined, including initial response to therapy, response at follow-up, or overall mortality, in DTC patients.