Bin Xu1, R Michael Tuttle2, Mona M Sabra2, Ian Ganly3, Ronald Ghossein1. 1. 1 Department of Pathology, Memorial Sloan-Kettering Cancer Center , New York, New York. 2. 2 Department of Medicine, Memorial Sloan-Kettering Cancer Center , New York, New York. 3. 3 Department of Surgery, Memorial Sloan-Kettering Cancer Center , New York, New York.
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.
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.
Authors: Bin Xu; Tihana Ibrahimpasic; Laura Wang; Mona M Sabra; Jocelyn C Migliacci; R Michael Tuttle; Ian Ganly; Ronald Ghossein Journal: Thyroid Date: 2016-09-07 Impact factor: 6.568
Authors: J A van Heerden; I D Hay; J R Goellner; D Salomao; J R Ebersold; E J Bergstralh; C S Grant Journal: Surgery Date: 1992-12 Impact factor: 3.982
Authors: Jasna M Mihailovic; Ljubomir J Stefanovic; Milica D Malesevic; Marko D Erak; Dusanka D Tesanovic Journal: Nucl Med Commun Date: 2009-07 Impact factor: 1.690
Authors: Brian Hung-Hin Lang; Kai Pun Wong; Chung Yeung Cheung; Koon Yat Wan; Chung-Yau Lo Journal: Ann Surg Oncol Date: 2012-10-28 Impact factor: 5.344
Authors: Bin Xu; Theresa Scognamiglio; Perry R Cohen; Manju L Prasad; Adnan Hasanovic; Robert Michael Tuttle; Nora Katabi; Ronald A Ghossein Journal: Hum Pathol Date: 2017-05-25 Impact factor: 3.466
Authors: Danielli Matsuura; Avery Yuan; Laura Wang; Rohit Ranganath; Dauren Adilbay; Victoria Harries; Snehal Patel; Michael Tuttle; Bin Xu; Ronald Ghossein; Ian Ganly Journal: Thyroid Date: 2022-03 Impact factor: 6.506