Risk of malignancy and management of indeterminate thyroid nodules with HRAS/NRAS mutations

Background and objectives

Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog (HRAS/NRAS) mutations being among the most prevalent molecular alterations. The study aimed to evaluate the malignancy risk of ITNs with these mutations.

Methods

We conducted a retrospective study involving ITNs (Bethesda category III and IV) that underwent ThyroSeq testing between February 2016 and January 2022. A smaller subset of ITNs also underwent Afirma testing. We specifically identified nodules with HRAS/NRAS mutations and collected radiological, clinical, histological, and follow-up data.

Results

Our analysis identified 45 ITNs with NRAS (29 cases) and HRAS (15 cases) mutations. Of the 29 nodules with NRAS mutations, 25 underwent surgical treatment (14 total thyroidectomies and 11 hemithyroidectomies), resulting in a surgical resection rate of approximately 86%. Among the resected nodules, six were malignant, yielding a calculated risk of malignancy (ROM) ranging from 20.6% to 25%. Three of these malignant nodules were managed with total thyroidectomy, while the other three underwent hemithyroidectomy. During a follow-up period of 43.8 months for total thyroidectomy and 32.9 months for hemithyroidectomy, no recurrence or metastasis was detected among the patients. Among the four nodules treated conservatively, three remained stable, with an average follow-up duration of 34.7 months, while one patient was lost to follow-up. Regarding HRAS mutations, 15 nodules were identified, with 12 of them undergoing surgical treatment (six total thyroidectomies and 6 hemithyroidectomies), resulting in an 80% surgical resection rate. Two of the resected nodules were malignant, with a calculated ROM of 13.3% to 16.7%. Both malignant nodules were managed with total thyroidectomy, and during a follow-up period of 37.9 months, no recurrence or metastasis occurred. Of the three nodules managed conservatively, all remained stable, with an average follow-up duration of 31.1 months.

Conclusions

The ROM for nodules with NRAS (20.6–25%) or HRAS (13.3–16.7%) mutations was found to be low. Therefore, before opting for total thyroidectomy, conservative management, including limited resection, should be considered as a viable alternative.

Full text

https://www.xiahepublishing.com/2771-165X/JCTP-2024-00011

The study was recently published in the Journal of Clinical and Translational Pathology.

Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.

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