Thyroid Gland Oncocytic Carcinoma

We describe a patient with radioactive iodine-refractory, metastatic oncocytic thyroid carcinoma with an NBN gene (c.2166_2167delGCinsAT) pathogenic variant, who developed progressive disease despite receiving systemic therapy with lenvatinib and pembrolizumab. A mutual exclusivity analysis demonstrated a tendency for pathogenic variants in one MRN complex genes to co-occur with pathogenic variants in the other two MRN complex genes. In conclusion, the MRN complex pathogenic variants could be potentially oncogenic in TCs and may be linked to aggressive forms of TC.

According to the review, adaptation and treatment of HCC based on existing standards for other thyroid cancers seem to be insufficient, and the risks outweigh the benefits. The key recommendations resulting from the 5th edition of the WHO Classification of Endocrine Neoplasms are only the beginning of refuting many myths and biases.

P2, N=29, Completed, Massachusetts Eye and Ear Infirmary | Active, not recruiting --> Completed

P=N/A, N=340, Active, not recruiting, University of Wuerzburg | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> May 2031

P2/3, N=504, Active, not recruiting, University College, London | Trial primary completion date: Dec 2024 --> Mar 2031

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.