, Volume 64, Issue 1, pp 97–108 | Cite as

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

  • Bin Xu
  • Ed Reznik
  • R. Michael Tuttle
  • Jeffrey Knauf
  • James A. Fagin
  • Nora Katabi
  • Snjezana Dogan
  • Nathaniel Aleynick
  • Venkatraman Seshan
  • Sumit Middha
  • Danny Enepekides
  • Gian Piero Casadei
  • Erica Solaroli
  • Giovanni Tallini
  • Ronald GhosseinEmail author
  • Ian GanlyEmail author
Original Article



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.


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.


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.


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.


Encapsulated follicular variant Papillary thyroid carcinoma Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) RAS Oncocytic 



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.)

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Supplementary material

12020_2019_1848_MOESM1_ESM.pptx (2.1 mb)
Supplementary Materials


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Bin Xu
    • 1
  • Ed Reznik
    • 2
  • R. Michael Tuttle
    • 3
  • Jeffrey Knauf
    • 3
  • James A. Fagin
    • 3
  • Nora Katabi
    • 4
  • Snjezana Dogan
    • 4
  • Nathaniel Aleynick
    • 4
  • Venkatraman Seshan
    • 2
  • Sumit Middha
    • 4
  • Danny Enepekides
    • 5
  • Gian Piero Casadei
    • 6
  • Erica Solaroli
    • 7
  • Giovanni Tallini
    • 8
  • Ronald Ghossein
    • 4
    Email author
  • Ian Ganly
    • 9
    Email author
  1. 1.Department of Laboratory Medicine and Molecular DiagnosticsSunnybrook Health Sciences CentreTorontoCanada
  2. 2.Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer centerNew YorkUSA
  3. 3.Department of MedicineMemorial Sloan Kettering Cancer centerNew YorkUSA
  4. 4.Department of PathologyMemorial Sloan Kettering Cancer centerNew YorkUSA
  5. 5.Department of OtolaryngologySunnybrook Health Sciences CentreTorontoCanada
  6. 6.Anatomic Pathology UnitOspedale MaggioreBolognaItaly
  7. 7.Endocrinology UnitOspedale MaggioreBolognaItaly
  8. 8.Department of Experimental, Diagnostic and Specialty Medicine-Anatomic PathologyUniversity of Bologna School of MedicineBolognaItaly
  9. 9.Department of SurgeryMemorial Sloan Kettering Cancer centerNew YorkUSA

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