Thyroid Carcinoma Coexisting with Hashimoto’s Thyreoiditis: Clinicopathological and Molecular Characteristics Clue up Pathogenesis

Abstract

Thyroid cancer (TC) coexisting with Hashimoto’s thyroiditis (HT) presents with several characteristic features including multifocality and lower clinical stages compared to de novo carcinomas but its exact biology is still not understood. We reexamined clinico-pathological and molecular correlations between Hashimoto’s thyroditis and papillary thyroid cancer. A total of 262 patients with TC was evaluated who underwent thyroidectomy at the Surgical Department of the University of Debrecen. Clinical data, histology and molecular data were evaluated. Our cohort included 43 patients (16.4%) with (5 male, 38 female) and 219 (83.6%) patients without coexisting HT (48 male, 171 female). Hashimoto’s thyroiditis related thyroid cancer presented predominantly (93.0% of the cases) with the papillary histological type. Multifocality was observed more frequently with coexisting HT (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%)( p = 0.034). In contrast, lymphatic metastasis (pN1) with a significantly reduced frequency in patients with HT (4/11; 36.4%) then without HT (34/41 pN1; 82.9%)( p = 0.002). BRAF V600E mutation could be demonstrated at significantly lower rates in cases of PTC + HT (32.1 vs 60.7%, p < 0.005). High incidence, multifocality and papillary morphology strongly support a causal relation between TC and preexisting Hashimoto’s thyroiditis, the latter to be considered as a preneoplastic condition promoting thyroid carcinogenesis.

Comparison of PTEN expression in hashimoto thyroiditis, follicular adenoma, papillary and follicular carcinomas

“…PI3K inhibitor, PTEN is expressed in normal thyroid follicular epithelial cells. Hashimoto is also expressed in thyrocyte affected thyroiditis, but is suppressed in PTC transformed epithelial cells (4). The loss or reduction of PTEN expression is observed in thyroid neoplasms.…”

“…The development of multifocal carcinoma in multiple areas of the thyroid parenchyma simultaneously supports the aetiology of PTC. The only evidence-based etiologic factor in the pathogenesis of thyroid cancer is ionizing radiation (4). The association of autoimmune lymphocytic thyroiditis with PTC was demonstrated in cross-sectional studies.…”

“…PTEN expression reduction in benign and malignant lesions of thyroid has been reported. There is no study comparing benign lesion/adenomas of thyroid with well-differentiated malignant follicular epithelial tumors (4). In this study, we aimed to compare the relationship between carcinogenesis and PTEN expression in papillary and follicular carcinomas and benign lesions of thyroid (Hashimoto thyroiditis, follicular adenomas).…”

High Genetic Diversity and No Evidence of Clonal Relation in Synchronous Thyroid Carcinomas Associated with Hashimoto’s Thyroiditis: A Next-Generation Sequencing Analysis

“…On the other hand, there is only limited information regarding the origin and genetic background of thyroid cancer (TC) associated with HT. Interestingly, BRAF V600 mutations were under-represented in association with HT-related PTC; however, other characteristic changes or frequent gene variant patterns could not be identified [9]. Findings on multiple neoplastic nodules and their clonal relation in the context of HT have also not been reported in the literature so far.…”

“…Parenchymal hypofunction, on the other hand, triggers a constant proliferative stimulus by thyroid-stimulating hormone (TSH), enabling increased survival and adaptive selection, which are both important factors in the process of carcinogenesis. According to the current view, not only has the association between HT and especially papillary-type thyroid carcinoma (PTC) been established, but the frequent multifocality of PTC can also be explained by HT-related injury and consequent stimulatory mechanisms [6,9].…”