Thyroid Gland Oncocytic Carcinoma

With levothyroxine and growth hormone treatment, pituitary hyperplasia regressed, and height increased by 15 cm in 1 year...Oncocytic thyroid carcinoma is rare in children, and its coexistence with hypothyroidism is unusual. This case emphasizes the importance of thyroid function testing in children with growth failure and sellar lesions, and vigilance in evaluating pediatric thyroid nodules given their elevated risk of malignancy.

RNA sequencing analyses further indicated coordinated suppression of multiple metabolic and signaling pathways. These findings suggest that an FLCN-mutated oncocytic tumor in the thyroid represents a biologically distinct subset driven primarily by compensatory mitochondrial biogenesis rather than by classical oncogenic signaling activation or primary mitochondrial genome instability.

P4, N=50, Completed, Eisai Pharmaceuticals India Pvt. Ltd | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Apr 2025 --> Sep 2025 | Active, not recruiting --> Completed

P2, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

P2, N=30, Active, not recruiting, Massachusetts Eye and Ear Infirmary | Trial completion date: Nov 2026 --> May 2026 | Trial primary completion date: Oct 2025 --> May 2025

P=N/A, N=40, Not yet recruiting, University Medical Center Groningen | Trial completion date: Aug 2026 --> Dec 2028 | Trial primary completion date: May 2026 --> Mar 2028

However, notably, certain mutations were exclusive to specific groups, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), anaplastic lymphoma kinase/echinoderm microtubule-associated protein-like 4 (ALK/EML4), and paired box 8 - peroxisome proliferator activator receptor gamma (PAX8-PPARG) in OPTCs or EIF1AX in OCs. Importantly, only 3.6% (1/28) of malignant OPTC/ONs were tested negative on molecular analysis, suggesting that ONs with negative molecular test results are more likely to be benign than malignant.

The genomic landscape of OCA is marked by frequent TERT promoter mutations and distinct mutational patterns associated with patient gender and tumor metastatic status. These findings highlight potential molecular subtypes, reveal pathways potentially driving metastasis (eg, involving MEN1/TSC2), and identify novel sex-specific alterations (MST1R, PRKDC), offering avenues for improved development of targeted therapeutic strategies for OCA.

These findings unveil a new germline-driven mechanism of complex I loss and metabolic reprogramming in cancer, and provide further evidence of the strong selective pressure for complex I impairment in OCT. Germline mutations in complex I induce aerobic glycolysis in oncocytic carcinoma of the thyroid through somatic loss of heterozygosity.

P2, N=54, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jul 2027 | Trial primary completion date: Jul 2024 --> Jul 2026

In conclusions, MSO shares histomolecular overlap with primary thyroid carcinoma, validating WHO 2022 thyroid tumor classification for risk stratification in struma ovarii. Conservative surgical management achieves excellent outcomes in low-grade cases.

Marked PD-L1 upregulation in widely invasive OTC suggests immune checkpoint inhibition as a potential therapeutic strategy. Larger, independent studies will be critical to validate these findings.