Abstract
Follicular patterned nodules are sometimes complex to be classified due to ambiguous nuclear features and/or questionable capsular or vascular invasion. In this setting, there is a poor inter-observer concordance even among expert pathologists. Raman spectroscopy was recently used to separate benign and malignant thyroid nodules based on their molecular fingerprint; anyway, some histologically proved follicular adenomas were clustered as having a characteristic profile of malignant lesions. In this study, we analyzed five follicular thyroid adenomas with a malignant spectroscopic profile compared to five follicular adenomas with a benign Raman spectrum in order to assess possible molecular differences between the two groups. Morphological, immunohistochemical, and molecular analyses evidenced expression of malignancy-associated proteins in four out of five malignant clustered adenomas. The remaining malignant clustered adenoma showed a TSHR mutation previously associated with autonomously functioning follicular carcinomas. In conclusion, thyroid follicular adenomas are a group of morphologically benign neoplasms that may have altered the mutational or expression profile; cases of adenomas with altered immunophenotype are recognized as showing a profile associated with malignancy by Raman spectroscopy. This correlation warrants a more extensive evaluation and suggests a potential predictive value of spectroscopic assessment in recognizing characteristics associated with tumor progression in follicular thyroid neoplasms.
Highlights
Follicular patterned thyroid lesions are a diagnostic dilemma both at cytological and histological examinations
All experiments were performed in full accordance with the principle of Good Clinical Practice (GCP) and the ethical principles contained in the current version of the Declaration of Helsinki
We found five cases histologically diagnosed as adenomas that were reclassified as malignant in the Raman clustering, in particular, two were reported as PTC, one as FV-PTC, and two as follicular carcinomas (FC)
Summary
Follicular patterned thyroid lesions are a diagnostic dilemma both at cytological and histological examinations. Molecular analysis gives little support in differentiating benign from malignant follicular patterned lesions [5,6] In these cases, the reported genetic alterations usually involve mutations in RAS genes, whereas p.V600E missense mutation in BRAF, which is a typical hallmark of PTCs, has not been detected [7]. The authors identified a cluster of 14 genes, including LGALS3, BCL2L1, and TIMP1, that accurately differentiated these lesions [9] Other molecular alterations such as HGF/cmet signal expression and cellular distribution in thyroid tumors are currently under evaluation with a 20% expression in FA compared with 100% expression in PTC and 0% in FC [10]. There is no evidence about a possible malignant potential in lesions morphologically diagnosed as adenomas
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