Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study

Background: Rigid diagnostic criteria for NIFTP have been recently proposed. The frequency of NIFTP using the new criteria is unknown, and whether abortive papillae are associated with BRAF^V600E mutation has not been studied. The aim of this study is to identify NIFTP by a retrospective review of Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), and to study its incidence as well as the association between immunohistochemical BRAF^V600E expression and abortive papillae in NIFTP.

Design: Thyroid tumors diagnosed as FVPTC or NIFTP over a period of 18 years (2000-2017) were identified using the laboratory information system. The final pathology reports were reviewed and potential NIFTP were retrieved. The archived slides for these cases were independently reviewed by 2 pathologists. BRAF^V600E (clone: VE1) immunostain was performed on representative tumor blocks. Clinical information including follow-up data was obtained from the electronic medical records.

Results: Among the 1918 cases with the diagnosis of papillary thyroid carcinoma (PTC), 589 (30.7%) of FVPTC and 136 cases of potential NIFTP were identified. After the review of the archived pathology slides, 29 lesions were morphologically reclassified as NIFTP. Four (13.7%) of these were positive for BRAF^V600E; no association was found between the presence of abortive papillae and BRAF^V600Eexpression (p=0.3). Exclusion of the 4 cases with BRAF^V600Eexpression resulted in 25 lesions of final NIFTP, representing 4.2% of the FVPTC and 1.3% of the PTC. The mean age of the NIFTP patients was 50 years, 87.5% were females. The mean size of the lesions was 1.4 cm (0.1-4.0 cm). Intranuclear pseudoinclusions were not identified, and abortive papillae were identified in 60% of NIFTP. The average follow-up was 70 (28-166) months. There were no adverse events (recurrence or metastasis) in the NIFTP group.

Conclusion: When strictly defined, NIFTP comprises 1.3% of cases perviously classified as PTC. In morphological NIFTP, no correlation is found between the presence of abortive papillae and the BRAF^V600E expression. Intranuclear pseudo-inclusions are not observed in NIFTP. Modification of current morphological criteria to include BRAF^V600E immunohistochemistry test may stratify NIFTP with benign outcome.