Molecular Profiling for Bethesda III to VI Nodules: Results of a Multicenter International Retrospective Study.

OBJECTIVE: Molecular testing is a well-established tool that assists in the management of thyroid nodules. We describe our experience using molecular testing of thyroid nodules with Bethesda III to VI cytology. METHODS: This is a retrospective multicenter, multinational study of thyroid nodules that underwent preoperative molecular profiling with ThyGenX/ThyGeNEXT or ThyroSeq V3 between 2015 and 2022. The clinical characteristics and mutational profiles of tumors were compared. Collected data included demographics, cytology results, surgical pathology, and molecular alterations. Molecular alterations were categorized into 3 main phenotypes: BRAF-like, RAS-like, and non-BRAF-non-RAS (NBNR). RESULTS: Overall, 784 patients who had surgery were included, of which 603 (76.2%) were females. The most common histologic type was papillary thyroid cancer (PTC) with 727 (91.9%) cases. In total, 205 (28.2%) cases showed an aggressive subtype of PTC (eg, tall cell and hobnail). BRAF-like alterations were most likely to be found in Bethesda V and VI nodules and show extrathyroidal extension (ETE), nodal disease, and/or aggressive subtypes of PTC (P < .001 for all). RAS-like alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive histology (P < .001 for all). NBNR alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive subtypes of PTC. However, they were rarely but significantly associated with poorly differentiated thyroid cancer (P < .005). CONCLUSION: Molecular testing of thyroid nodules can help determine the likelihood of malignancy and classify nodules into several tumor phenotypes, predicting their behaviors and potentially allowing for a more tailored treatment. NBNR alterations should be managed with caution.

Neurovascular conflict and sudden unilateral sensorineural hearing loss: coincidence or coexistence?

OBJECTIVE: To study the association between neurovascular conflict (NVC) of the 8th cranial nerve (CN8) and unilateral sudden sensorineural hearing loss SSNHL (SSNHL). METHODS: A systematic literature search of "MEDLINE" via "PubMed," "Embase," and "Google-Scholar" was conducted. Meta-analysis of pooled data was performed for NVC prevalence of SSNHL affected ears versus controls. RESULTS: The literature search identified 941 publications, of which, 9 included in qualitative synthesis (1030 ears) and 5 in quantitative synthesis (484 ears). NVC was as prevalent as 0.8-69% for affected ears and as 19-57% for controlled ears. No association between MRI protocol and NVC prevalence was proved. An odds ratio of 1.05 (95% confidence interval = 0.79-1.39) was calculated for association of NVC in unilateral SSNHL ears versus controls. CONCLUSION: The prevalence of NVC of CN8 in unilateral SSNHL affected ears is not significantly bigger than controls. Hence, NVC of CN8 is probably NOT associated with unilateral SSNHL.

Investigation of genetic sex-specific molecular profile in well-differentiated thyroid cancer: Is there a difference between females and males?

BACKGROUND: Although more common in females, thyroid cancer is deemed to be more aggressive in males. The reasons for sex disparities in thyroid cancer are not well understood. We hypothesised that differences in molecular mutations between females and males contribute to this phenomenon. METHODS: Retrospective multicentre multinational study of thyroid nodules that underwent preoperative molecular profiling between 2015 and 2022. The clinical characteristics and mutational profiles of tumours in female and male patients were compared. Collected data included demographics, cytology results, surgical pathology, and molecular alterations. RESULTS: A total of 738 patients were included of which 571 (77.4%) were females. The extrathyroidal extension was more common in malignancies in males (chi-squared, p = 0.028). The rate of point mutations and gene fusions were similar in both sex groups (p > 0.05 for all mutations). Patients with nodules with BRAFV600E mutations were significantly younger than BRAF wild-type nodule patients (t-test, p = 0.0001). Conversely, patients with TERT promoter mutations were significantly older than patients with wild-type TERT (t-test, p < 0.0001). For patients harbouring both BRAFV600E and TERT mutations, the difference in age at presentation was significantly different in females (t-test, p = 0.009) but not in males (t-test, p = 0.433). Among females, patients with BRAFV600E and TERT mutations were significantly older than their wild-type or single-mutation counterpart (t-test, p = 0.003). CONCLUSION: The absolute rate of molecular mutations was similar in females and males. We found that extrathyroidal extension was more common in males. Moreover, BRAFV600E and TERT mutations occur at a younger age in males than in females. These two findings are factors that may explain the tendency of more aggressive disease in males.