CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Paul N. Staats, MD
Benjamin L. Witt, MD
January 2017—A recent landmark study performed under the auspices of the Endocrine Pathology Society has proposed a new diagnostic entity in the thyroid: noninvasive follicular thyroid neoplasm with papillary-like nuclear features, or NIFTP.1 While the study focused on histologic features and clinical outcomes, any significant change in surgical pathology classification will raise important questions for the practice of thyroid cytology as well, since nearly all thyroid nodules are initially evaluated by fine needle aspiration. While much remains to be settled about this new entity and its effect on cytology, we attempt to answer some of these questions.
What is NIFTP?
NIFTP is the proposed terminology for neoplasms previously classified as noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC), which account for 10 to 20 percent of all diagnoses of PTC.
Why create a new name?
Over the past several decades the rate of diagnosis of thyroid cancer has markedly increased, with essentially all of the increase attributable to PTC.2,3 This has been due mostly to increasing radiological detection of thyroid nodules. However, it is also due in part to pathologists increasingly recognizing that the nuclei within some follicular-patterned neoplasms have features that resemble those seen in classic PTC, resulting in higher rates of diagnoses of the follicular variant of PTC (FVPTC). Despite a marked increase in the diagnosis of PTC, the mortality associated with PTC has remained entirely unchanged, raising concerns that these diagnoses largely represent indolent lesions and that the diagnosis of PTC may result in unnecessary and harmful overtreatment. In particular, the available literature shows extremely indolent behavior for the encapsulated, noninvasive form of FVPTC. The Endocrine Pathology Society gathered 109 such cases with 10 to 25 years of clinical follow-up and identified no recurrences or evidence of lymph node involvement. Similarly, unpublished data from the University of Utah on a retrospective review of cases that would meet the criteria for NIFTP found that none of the 47 NIFTP patients had nodal disease either at the time of surgery or on clinical follow-up.
Moreover, they and others have found an absence of the BRAF V600E mutation common to classic PTC in NIFTP. Instead of BRAF V600E mutations, they found mutations commonly seen in follicular adenomas and carcinomas, most commonly RAS mutations, further supporting a distinction from PTC.
Based on the literature and the data the Endocrine Pathology Society collected, revised terminology was believed to be needed to remove the term carcinoma from the name of these lesions; hence the recommendation of NIFTP. They did not claim that the lesion was necessarily benign but that it was better classified as an indolent neoplasm than as carcinoma. Moreover, they proposed that hemithyroidectomy should be sufficient treatment for this lesion, with no role for completion thyroidectomy or radioactive iodine therapy.
What are the diagnostic criteria for NIFTP?
The formal criteria for diagnosis are as follows:
- Encapsulation or clear demarcation.
- Follicular growth pattern with
- Nuclear score 2–3 (as defined here).
- No vascular or capsular invasion.
- No high mitotic activity (
The nuclear score is based on: