“Nodule in Nodule” on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor

Abstract A high prevalence of activating mutation of the B type Raf kinase (BRAF) gene was recently reported in papillary thyroid cancer (PTC). However, the frequency of this mutation in several other types of thyroid neoplasms was not thoroughly investigated. In the present study, in addition to PTC, we evaluated various thyroid tumor types for the most common BRAF T1796A mutation by direct genomic DNA sequencing. We found a high and similar frequency (45%) of the BRAF T1796A mutation in two geographically distinct PTC patient populations: one composed of sporadic cases from North America, and the other from Kiev, Ukraine, that included individuals who were exposed to the Chernobyl nuclear accident. In contrast, we found BRAF mutation in only 20% of anaplastic thyroid cancers and no mutation in medullary thyroid cancers and benign thyroid hyperplasia. We also confirmed previous reports that the BRAF T1796A mutation did not occur in benign thyroid adenomas and follicular thyroid cancers. Specific analysis of the Ukraine patients with confirmed history of radiation exposure failed to show a higher incidence of BRAF mutation. Our results suggest that frequent occurrence of BRAF mutation is inherently associated with PTC, irrespective of geographic origin, and is apparently not a radiation-susceptible mutation. The lack or low prevalence of BRAF mutation in other thyroid neoplasms is consistent with the notion that other previously defined genetic alterations on the same signaling pathway are sufficient to cause tumorigenesis in most thyroid neoplasms.

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The Potential Diagnostic Utility of TROP-2 & C-Kit in Thyroid Neoplasms

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i1731035 ◽

2021 ◽

pp. 110-123

Author(s):

Amal Abd El-Halim El-Dakrany ◽

Yomna Abd El-Monem Zamzam ◽

Rania Elsayed Wasfy ◽

Assia Mahfouz Abd El-Raouf

Keyword(s):

Diagnostic Tool ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Thyroid Neoplasms ◽

Common Finding ◽

Diagnostic Utility ◽

Large Set ◽

Benign Thyroid ◽

Nuclear Features ◽

Thyroid Lesions

Background: Thyroid nodules are common finding, only 5% of nodules are malignant and the vast majority is non-neoplastic lesions or benign neoplasms. Thyroid cancer incidence is increasing faster than any other cancer types, thus representing one of the most common and clinically worrying malignant tumors of the endocrine system. Trophoblast antigen 2 (TROP2) is a transmembrane receptor glycoprotein encoded by the tumor-associated calcium signal transducer 2(Tacstd2) gene, which is located on chromosome 1p32. Although the biological function of TROP2 is unclear, accumulating evidence has demonstrated that its expression is elevated in various malignant tissues, whereas in human normal tissues relatively low or no TROP2 expression is observed. C-Kit is a type III receptor tyrosine kinase. C-Kit expression and signaling have been well characterized in several tumors, including gastrointestinal stromal tumors (GISTs). However, few studies have investigated c-Kit in the thyroid gland or in thyroid malignancies. The aim of this study was to investigate the diagnostic utility of TROP-2 on a large set of neoplastic thyroid lesions & to investigate the utility of TROP-2 & c-Kit markers to distinguish between benign and malignant thyroid neoplasms on Paraffin blocks. Methods: Immunohistochemistry for TROP2 and c-Kit was carried out on 85 different thyroid lesions (40 benign, 7 borderline and 38 malignant). Results: Malignant thyroid lesions were found to have negative expression of c-Kit in contrast to 80% of benign thyroid neoplasms. TROP2 was strong positive in 87.5% of papillary thyroid carcinomas (PTC), but there was no TROP2 expression in benign thyroid neoplasms, non-invasive follicular thyroid neoplasm with papillary like nuclear features, follicular carcinoma, anaplastic and poorly differentiated thyroid carcinoma. Conclusions: TROP2 is a good diagnostic tool for PTCs to differentiate between PTCs & other lesions with papillary like nuclear features as NIFTP, c-Kit is a good diagnostic tool for follicular adenoma & to differentiate between follicular adenoma & follicular carcinoma.

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