Noninvasive Follicular Thyroid Neoplasms
with Papillary-like Nuclear Features and
Indeterminate Cytology Are Afirma GEC Suspicious Which Facilitates Surgical Treatment


Interview with Peter M. Sadow, M.D., Ph.D., Massachusetts General Hospital and Harvard Medical School

Dr. Peter Sadow is an Associate Professor of Pathology at Harvard Medical School and Director of Head and Neck Pathology at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary. He was coauthor of a seminal 2016 JAMA Oncology article that revised the term “noninvasive encapsulated follicular variant of papillary thyroid carcinoma” (EFVPTC) in thyroid nodule evaluation to “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) – to reflect the biological low risk in these tumors, removing their status as a cancer, to help reduce patient overtreatment. Here he speaks with us about his poster reporting on the Afirma GEC’s performance with thyroid nodule samples designated as NIFTP.

Q: Do patients with thyroid lesions designated as NIFTP still need surgery?

Dr. Sadow: Absolutely. In fact, the diagnosis of NIFTP cannot be made preoperatively, although it may be among the differential diagnosis by FNA biopsy. Based on the most recent ATA guidelines, these tumors still need to come out because that is the only way to tell that they are indeed NIFTP and not cancer.

Q: Why did you do this current study?

Dr. Sadow: Now that we have the NIFTP category, we wanted to see how the Afirma GEC performs on these samples when initial cytopathology was indeterminate – in other words, does it still enable proper treatment of these patients. The ENHANCE biorepository enabled us to do this because it contains the surgical excision cases along with paired cytology from thyroid fine needle aspiration samples, genomic testing and histopathology classification. We identified 25 nodules that were diagnosed as NIFTP by an expert panel and then determined what their Afirma GEC and other results had been.

Q: And what did you find?

Dr. Sadow: We found that the Afirma GEC designated the vast majority of NIFTP nodules – 24 of 25, or 96 percent – as GEC “suspicious.” As physicians typically direct patients with “suspicious” Afirma GEC results to surgery, our findings support this appropriate treatment pathway, as differentiating NIFTP from cancer requires post-surgical examination by the pathologist.

Q: How do these findings compare to molecular testing that detects specific mutations?

A: Previous research has shown that a mutation panel test identified 78 percent of NIFTP samples are positive for a cancer-associated mutation. This finding signifies two possibilities. Most importantly, this could lead to overtreatment among these cases. Conversely, more than 20 percent of cases lacking a mutation may be left in situ with inherent risks for malignancy.

Q: Were there any other interesting findings?

Dr. Sadow: Yes, we found that none of the NIFTP samples were determined to have high-risk radiologic features by ultrasound and most – 24 of 25 – of them were classified by cytopathology as either Bethesda III or IV, with only one falling into the Bethesda V category. The latter finding reinforces that the NIFTP nodules are less likely to be classified as definitely PTC by cytology.

Q: What is the key takeaway for patient care?

Dr. Sadow: NIFTP is a biologically indolent lesion, yet its diagnosis and distinction from malignant tumors still requires surgical excision, and use of the Afirma GEC reinforces this approach.

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