The presence of telomerase reverse transcriptase (TERT) promoter mutations have been associated with a poor prognosis in patients with papillary thyroid carcinomas (PTC). The frequency of TERT promoter mutations varies widely depending on the population and the nature of the study. Data were prospectively collected in 724 consecutive patients who underwent thyroidectomy for PTC from 2018 to 2019. Molecular testing for BRAF V600E and TERT promoter mutations was performed in all cases. TERT promoter alterations in two hotspots (C228T and C250T) and C216T were found in 16 (2.2%) and 4 (0.6%) of all PTCs, respectively. The hotspot mutations were significantly associated with older age at diagnosis, larger tumor size, extrathyroidal extension, higher pathologic T category, lateral lymph node metastasis, and higher American Thyroid Association recurrence risk. The patients with C216T variant were younger and had a lower American Thyroid Association recurrence risk than those with hotspot mutations. Concurrent BRAF V600E was found in 19 of 20 cases with TERT promoter mutations. Of 518 microcarcinomas measuring ≤1.0 cm in size, hotspot mutations and C216T variants were detected in five (1.0%) and three (0.6%) cases, respectively. Our study indicates a low frequency of TERT promoter mutations in Korean patients with PTC and supports previous findings that TERT promoter mutations are more common in older patients with unfavorable clinicopathologic features and BRAF V600E. TERT promoter mutations in patients with microcarcinoma are uncommon and may have a limited role in risk stratification. The C216T variant seems to have no clinicopathologic effect on PTC.

PD-L1 harmonization studies revealed a strong correlation between the 22C3 and SP263 assays in non-small-cell lung cancer (NSCLC). However, the assays’ characteristics have yet to be validated in a variety of clinical and analytical settings. The results of 431 NSCLC samples tested concurrently in routine clinical practice with the PD-L1 22C3 and SP263 assays were reviewed, and both assays were performed on 314 archives of surgically resected NSCLCs to assess PD-L1 expression in relation to variables such as FFPE block age and FFPE section storage condition. In routine clinical samples, 22C3 showed the highest concordance rate with 94.5% of SP263 tumor proportion score (TPS) ≥50% and 92.3% of SP263 TPS ≥1%, while SP263 showed a concordance rate with 79.6% of 22C3 TPS ≥50% and 89.9% of 22C3 TPS ≥1%. In the archival analysis, the high TPS of 22C3 and SP263 (versus TPS 1%) were significantly associated with a more recent block (<3 years versus ≥3 years) ($\mathit{p}$ = 0.007 and $\mathit{p}$ = 0.009, respectively). Only the TPS of 22C3 was reduced when FFPE sections were stored at room temperature compared to SP263. However, when stored at 4 °C, the storage duration had no effect on expression in either assay. For 22C3 TPS 1–49 percent and ≥50 percent (OR = 1.73, $\mathit{p}$ = 0.006 and OR = 1.98, $\mathit{p}$ = 0.002, respectively). There was a considerably larger chance of preserved 22C3 expression in recent room-temperature paraffin section storage, although SP263 demonstrated preserved expression in prolonged room-temperature section storage. Despite the good association between PD-L1 22C3 and SP263 in routine clinical samples, FFPE blocks older than 3 years and sections held at room temperature for more than 1 week may result in an underestimation of PD-L1 status, particularly for the 22C3 test. However, the SP263 assay was more sensitive under these conditions.

Kim DK, et al. Korean J Radiol. 2026 Nov;27(11):1058-1074. https://doi.org/10.3348/kjr.2026.0593

Background/Objectives: Preoperative risk stratification of indeterminate thyroid nodules, particularly category IV nodules diagnosed as follicular neoplasm, remains challenging. Molecular testing may support clinical decision-making, but its cost and limited availability restrict routine use. This study evaluated whether the digitally quantified Ki-67 labeling index, alone and combined with the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), could predict malignancy in thyroid core needle biopsy (CNB) specimens. Methods: We retrospectively analyzed 130 thyroid nodules sampled by ultrasound-guided CNB. The Ki-67 labeling index was digitally quantified in immunohistochemically stained CNB sections, and ultrasound features were classified according to K-TIRADS. Receiver operating characteristic curve analysis was performed in the overall cohort. Logistic regression analyses were restricted to 57 category IV nodules. Results: In the overall cohort, the Ki-67 labeling index showed excellent diagnostic performance for predicting malignancy, with an area under the curve of 0.924. The optimal cutoff was 1.73%, with 88.7% sensitivity and 83.1% specificity. In category IV nodules, K-TIRADS category and Ki-67 labeling index were independently associated with malignancy. The odds ratios were 6.02 (95% CI, 1.53–23.74) for each one-category increase in K-TIRADS and 4.44 (95% CI, 1.69–11.70) for each percentage-point increase in Ki-67. In the Ki-67-only model, a Ki-67 index of 5% corresponded to a predicted malignancy probability of 98.1%. Conclusions: Digital Ki-67 quantification, integrated with K-TIRADS, may serve as a practical adjunct for malignancy risk stratification in thyroid CNB specimens, particularly for category IV nodules. Further external validation is warranted.