Papillary Thyroid Cancer—Aggressive Variants and Impact on Management: A Narrative Review

Abstract

Introduction: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. Methods: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. Results: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor This article was written by members and invitees of the International Head and Neck Scientific Group (https:// www.IHNSG.com).

Genetic Profiles of Aggressive Variants of Papillary Thyroid Carcinomas

“…The BRAF V600E mutation is the most common genetic alteration in PTC, and it is associated with poor clinical outcomes such as regional recurrence and distant metastasis [ 26 , 27 , 28 ]. The results of the current study are consistent with those of previous studies, which reported that BRAF mutation was detected in 80–100% of TCV-PTC and 33% in CCV-PTC [ 2 , 9 ]. As most (69.4%) of the tissue sample from current study was TCV-PTC, the frequency of BRAF mutation was 89%, which was close to that of TCV-PTC.…”

“…Despite notable progress in the elucidation of genetic profiles of thyroid cancers, studies investigating the mutational profile of aggressive variant PTC are limited and unclear. The BRAF V600E mutation, which has emerged as a marker of aggressive behavior in thyroid cancer, was observed in 80–100% of TCV, 33% of CCV, and 25.3–57.1% of HV [ 9 , 10 , 11 , 12 , 13 ]. The RAS mutation, which may play an important role in follicular thyroid carcinogenesis, is more frequent and may be more relevant as a prognostic indicator in follicular pattern lesions (FV-PTC, follicular thyroid carcinoma (FTC), and PDTC) than in classical PTC [ 14 , 15 ].…”

Molecular Pathology of Non-familial Follicular Epithelial–Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification

“…The main difference regarding the diffuse involvement of thyroid gland by a PTC concerns the association of diffuse sclerosing variant of PTC with BRAF-like features [72] and the association of diffuse/multinodular FVPTC with RAS-like features. The prognosis of these two variants is associated with usual clinico-pathological factors (Age, Gender, Staging, Lympho-vascular invasiveness) and, as far as we know, there is no evidence for molecular features in risk stratification.…”

“…In most instances, the demonstration of rearrangements such as the BRAF fusions may be diagnostically important but the prognostic impact is not clear [76,77]. The same applies to the detection of a number of other rearrangements including RET/PTC1, RET/PTC3, ETV6/ NTRK3 PAX8/PPARγ, ROS1, and ALK [72,76,[78][79][80].…”

Thyroid Lobectomy for Low to Intermediate Risk Differentiated Thyroid Cancer

“…Microscopic extrathyroidal extension is thus considered to be a risk factor for locoregional recurrence but is no longer considered a risk factor for disease-specific mortality; the TNM T3 classification now only includes macroscopic extrathyroidal extension. Aggressive histology, even for small tumors, is considered to be a factor for an intermediate risk of recurrence and includes tall cell, hobnail, columnar cell, and diffuse sclerosing papillary carcinomas [16]. For follicular carcinoma, low-risk tumors include the encapsulated variant, minimally invasive follicular carcinoma, and encapsulated minimally invasive follicular carcinoma with a small number of foci of vascular invasion and without extracapsular vascular invasion [1].…”