Molecular Genetics of Thyroid Cancer Part 4

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • As mentioned previously follicular tumors:
    • Develop through a multistep process where they can be identified via cytopathology at different stages in their development
  • These does not occur in BRAF-like tumors:
    • Where they develop from the early stages as microcarcinomas
  • The problem is that in clinical practice we want the tumors to be classified in a binary distribution (benign or malignant):
    • Which is very difficult because of the multistep process of their development
  • Noninvasive follicular thyroid neoplasm with papillary nuclear features (NIFTP):
    • Has partially resolved this problem (NIFTP would be a seen in the later stages of this multistep process)
  • The diagnostic features of NIFTP include:
    • Follicular architecture
    • Nuclear features of PTC
    • Formation of a capsule with lack of invasion
  • This entity was previously known as
    encapsulated follicular variant of papillary carcinoma
  • The histologic criteria of NIFTP are depicted in
    Table.

Revised Diagnostic Criteria for NIFTP
  • NIFTP should be viewed as a borderline malignant tumor (equivalent to carcinoma in situ):
    • If no invasion is identified on the final pathology:
      • The risk of recurrence is very low:
        • Less than 1%
  • This lesion still requires surgical resection by a minimalistic approach usually is sufficient (thyroid lobectomy)
  • The molecular characteristics of NIFTP include:
    • RAS and RAS-like mutations:
      • BRAF V600E and TERT mutations:
        • Should not be identified in this lesion
  • NIFTP is considered a precursor lesion for:
    • Invasive encapsulated follicular variant of PTC (EFVPTC)
  • The introduction of NIFTP did not resolve the uncertainty in the pathological diagnosis of PTC:
    • A study from four different institutions (Memorial Sloan Kettering Cancer Center
      – MSKCC, Moffit Cancer Center – MCC, Cedar Sinai Medical Center in Los Angeles – CSMC, Mount Sinai Health System in New York – MSHS) with RAS-positive thyroid nodules by Marcardis et al:
      • Identified a wide variation in the prevalence of NIFTP in resected indeterminate thyroid nodules across several institutions:
        • Ranging from 5% to 46%
      • At MSKCC:
        • The most common overall and non-malignant diagnosis in RAS-mutated
          nodules was:
          • NIFTP
      • This was significantly greater than the NIFTP rate at the other three institutions:
        • Where the most common overall and benign diagnosis was follicular adenoma / nodular hyperplasia
      • Significant variations in the rates NIFTP (5% to 13%) and follicular adenoma / nodular
        hyperplasia (63% to 85%) in the other three institutions (MCC, CSMC, MSHS) also occurred
      • This reflects the same issue that some thyroid nodules may be identified at stages in their development where the nuclear features
        of PTC are clearly absent        , some at stages where the nuclear features are clearly present, while others can be
        identified at different stages in the development of the nuclear features of PTC (in some of these stages the nuclear features of PTC are not fully expressed):
        • Depending on where the pathologist draws the line in this continuum more or less thyroid nodules, will be called cancers or NIFTP, leading to the difficulty in making a
          diagnosis (Figure)

The image depicts one tumor that has areas of well differentiated thyroid cancer, poorly differentiated
thyroid cancer and anaplastic thyroid cancer. The well differentiated tumors preserver all markers differentiation
(thyroglobulin, TTF-1, and cytokeratin) compared to the ATC which losses these markers.
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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