NDLI: The variable phenotype and low-risk nature of RAS-positive thyroid nodules

Content Provider	Springer Nature : BioMed Central
Author	Medici, Marco Kwong, Norra Angell, Trevor E. Marqusee, Ellen Kim, Matthew I. Frates, Mary C. Benson, Carol B. Cibas, Edmund S. Barletta, Justine A. Krane, Jeffrey F. Ruan, Daniel T. Cho, Nancy L. Gawande, Atul A. Moore, Francis D. Alexander, Erik K.
Abstract	Background Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. Methods We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. Results Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100 %). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47 %). All RAS-positive malignancies were low risk – all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. Conclusions While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.
Related Links	https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-015-0419-z.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	17417015
DOI	10.1186/s12916-015-0419-z
Journal	BMC Medicine
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2015-08-07
Access Restriction	Open
Subject Keyword	Medicine Public Health Biomedicine Papillary Thyroid Carcinoma Fine Needle Aspiration Thyroid Nodule Papillary Carcinoma Malignant Nodule Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	8.8/2023

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