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Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features

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Abstract

Purpose

In 2016, non-invasive encapsulated follicular variant of papillary thyroid carcinoma (NI-EFVPTC) was renamed as noninvasive thyroid follicular neoplasm with papillary-like nuclear features (NIFTP). However, as the study cohort did not mention tumors with oncocytic features, such lesions are still labeled by some as FVPTC. It is therefore crucial to evaluate the outcome and molecular profile of oncocytic NI-EFVPTC.

Methods

A multi-institutional clinico-pathologic review was conducted to select 61 patients having oncocytic NI-EFVPTC. A detailed molecular profile was carried out in 15 patients.

Results

Oncocytic NI-EFVPTCs predominantly affected women in their 50s. There was no distant metastasis, lymph node metastases, or structural recurrence in the entire cohort. Among patients with ≥5 years of FU, all 33 individuals did not recur with a median FU of 10.2 years. Oncocytic NI-EFVPTC commonly had RAS (33%) mutations, a high frequency of mitochondrial DNA mutations (67%) and multiple chromosomal gains/losses (53%). No fusion genes were detected.

Conclusions

Oncocytic NI-EFVPTC, when stringently selected for, lacks metastasis at presentation and follows an extremely indolent clinical course, even when treated conservatively with lobectomy alone without RAI therapy. These tumors share a similar mutational profile as NIFTP, FVPTC, and follicular neoplasm and are predominantly RAS-related. Like Hurthle cell neoplasms, they harbor a high frequency of mitochondrial DNA mutations, which contribute to the oncocytic cytomorphology. However, they lack the widespread chromosomal alterations observed in Hurthle cell carcinoma. Consideration should be given to include oncocytic NI-EFVPTCs as NIFTP in order to avoid overtreatment of these highly indolent tumors.

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Funding

Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was also supported in part by an Italian Government-Ministero della Salute Grant No. RF-2011-02350857 (to G.T.)

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Author notes

  1. These authors contributed equally: Bin Xu, Ed Reznik

  2. These authors jointly supervised this work: Ronald Ghossein, Ian Ganly

Authors and Affiliations

  1. Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Bin Xu

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer center, New York, NY, USA

    Ed Reznik & Venkatraman Seshan

  3. Department of Medicine, Memorial Sloan Kettering Cancer center, New York, NY, USA

    R. Michael Tuttle, Jeffrey Knauf & James A. Fagin

  4. Department of Pathology, Memorial Sloan Kettering Cancer center, New York, NY, USA

    Nora Katabi, Snjezana Dogan, Nathaniel Aleynick, Sumit Middha & Ronald Ghossein

  5. Department of Otolaryngology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Danny Enepekides

  6. Anatomic Pathology Unit, Ospedale Maggiore, Bologna, Italy

    Gian Piero Casadei

  7. Endocrinology Unit, Ospedale Maggiore, Bologna, Italy

    Erica Solaroli

  8. Department of Experimental, Diagnostic and Specialty Medicine-Anatomic Pathology, University of Bologna School of Medicine, Bologna, Italy

    Giovanni Tallini

  9. Department of Surgery, Memorial Sloan Kettering Cancer center, New York, NY, USA

    Ian Ganly

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Xu, B., Reznik, E., Tuttle, R.M. et al. Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features. Endocrine 64, 97–108 (2019). https://doi.org/10.1007/s12020-019-01848-6

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