Primary thyroid carcinoma with low-risk histology and distant metastases: Clinicopathologic and molecular characteristics Journal Article
| Authors: | Xu, B.; Tuttle, R. M.; Sabra, M. M.; Ganly, I.; Ghossein, R. |
| Article Title: | Primary thyroid carcinoma with low-risk histology and distant metastases: Clinicopathologic and molecular characteristics |
| Abstract: | Background: Distant metastases (DM) are a rare occurrence in well-differentiated thyroid carcinoma. The aim of this study was to analyze the clinical, pathologic, and molecular features of primary thyroid carcinoma with low-risk histology that develop DM. Methods: A detailed clinicopathologic review and targeted next-generation sequencing were performed on a cohort of well-differentiated thyroid carcinoma lacking gross extrathyroidal extension, extensive vascular invasion, or significant lymph node metastases but exhibiting DM. Results: Primary well-differentiated thyroid carcinoma with low-risk histologic features and DM was a rare occurrence, accounting for only 3% of metastatic non-anaplastic thyroid carcinoma. All 15 cases meeting the inclusion criteria harbored DM at presentation. The majority (11/15) of these tumors were follicular variant of papillary thyroid carcinoma (PTC), especially the encapsulated form (n = 8). The remaining patients harbored encapsulated Hürthle cell carcinoma (n = 2), encapsulated follicular carcinoma (n = 1), and an encapsulated papillary carcinoma classical variant (n = 1). Of the 12 encapsulated carcinomas, 10 had capsular invasion only and no vascular invasion. Ninety-two percent of the tumors exhibited extensive intra-tumoral fibrosis. Among the eight tumors that were subjected to next-generation sequencing analysis, a RAS mutation was the main driver (5/8), and TERT promoter mutation was highly prevalent (6/8). In four cases, TERT promoter mutations were associated with RAS or BRAF mutations. BRAF-mutated classical variant of papillary carcinoma also presented with DM but was less common (1/8). In 11/15 cases, the clinician was able to diagnose distant disease based on the clinical presentation. In 3/4 incidental cases that were genotyped, TERT promoter mutations were found. Conclusions: When DM occur in primary thyroid carcinoma with low-risk histology, they are almost always found at presentation. The majority are encapsulated follicular variant of PTC with capsular invasion only. TERT promoter mutations occur at a higher rate than that seen in PTC in general and may help explain the aggressive behavior of these histologically deceptive primary carcinomas. © Copyright 2017, Mary Ann Liebert, Inc. |
| Keywords: | distant metastasis; ras; hürthle cell carcinoma; follicular variant; papillary thyroid carcinoma; tert |
| Journal Title: | Thyroid |
| Volume: | 27 |
| Issue: | 5 |
| ISSN: | 1050-7256 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2017-05-01 |
| Start Page: | 632 |
| End Page: | 640 |
| Language: | English |
| DOI: | 10.1089/thy.2016.0582 |
| PROVIDER: | scopus |
| PMCID: | PMC5421603 |
| PUBMED: | 28049366 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |
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