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Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF V600E Harboring Pediatric Papillary Thyroid Carcinomas

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Abstract

This study is aimed to investigate the BRAF V600E and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16 years (range, 6–18). No TERT promoter mutations were identified in this series. The BRAF V600E mutation was present in 15 (30 %) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF V600E mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF V600E mutation. Nine of 15 BRAF V600E harboring tumors had central lymph node metastases. There was no significant correlation with BRAF V600E mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF V600E mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF V600E mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF V600E harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs.

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Acknowledgments

The authors would like to thank Dr. Yasemin Ozluk (Istanbul University, Istanbul Faculty of Medicine, Department of Pathology) for her invaluable assistance in the statistical analyses.

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Authors and Affiliations

  1. Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Semen Onder, Sule Ozturk Sari, Gulcin Yegen & Yersu Kapran

  2. Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Ismail Cem Sormaz & Yasemin Giles Senyurek

  3. Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey

    Ismail Yilmaz

  4. Department of Pediatric Endocrinology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Sukran Poyrazoglu

  5. Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Yasemin Sanlı

  6. Department of Pathology, University Health Network, Toronto, ON, Canada

    Ozgur Mete

  7. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Ozgur Mete

  8. Endocrine Oncology Site Group, Princess Margaret Cancer Center, Toronto, ON, Canada

    Ozgur Mete

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  1. Semen Onder
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Onder, S., Ozturk Sari, S., Yegen, G. et al. Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF V600E Harboring Pediatric Papillary Thyroid Carcinomas. Endocr Pathol 27, 153–161 (2016). https://doi.org/10.1007/s12022-016-9420-0

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  • DOI: https://doi.org/10.1007/s12022-016-9420-0

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