The classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to prevent the overtreatment of indolent tumors that were formerly diagnosed as non-invasive encapsulated follicular variant papillary thyroid carcinomas (NIEFV-PTCs). Although NIFTP was initially estimated to account for 10%–20% of papillary thyroid carcinomas in Western populations, its incidence is substantially lower in Asian cohorts. However, a multi-institutional Japanese study revealed that 31.0% of tumors previously diagnosed as follicular adenomas (FAs) were reclassified as NIFTPs. NIFTP diagnosis requires a nuclear score (NS) of 2–3, and according to the recent World Health Organization criteria, molecular analysis is recommended, but not mandatory, to exclude high-risk subtypes, namely cases with the BRAFV600E mutation, particularly for NS3 tumors. Methods: We performed genetic analysis on 92 archival thyroid tumor samples, including 69 previously diagnosed as FA, of which 34 remained as FA upon re-evaluation (group A) and 35 were reclassified as NIFTP with NS2 (group B). Additional 23 tumors previously diagnosed as NIEFV-PTC were reclassified as NIFTP with NS3 (group C). Results: RAS mutations were detected in 8.8%, 34.3%, and 21.7% of the tumor samples in groups A, B, and C, respectively, whereas BRAF mutations were present in 43.5% of the tumor samples in group C only. Conclusions: These findings suggest the presence of two distinct tumor subsets within NIFTP-NS3, underscoring the need for routine molecular diagnostics in NIFTP-NS3 to facilitate appropriate clinical management.

Papillary thyroid carcinoma (PTC) is the most representative carcinoma among thyroid malignancies. The treatment strategy, especially surgery, in Japan traditionally differs from that in other countries, including Korea. Total thyroidectomy has been less frequently adopted, but lymph node dissection has been more actively performed in Japan than in other countries. Based on our data, total thyroidectomy is not necessary for low-risk patients, while it is, of course, mandatory for patients with high-risk features. Prophylactic central node dissection may not prolong patients' survival, but we routinely perform it because reoperation for recurrence to this compartment is troublesome. In the past, Japanese endocrine surgeons actively performed prophylactic lateral node dissection, but indications are narrowing. However, it may be better to perform prophylactic modified radical neck dissection for patients exhibiting certain characteristics to reduce the rate of lymph node recurrence. I hope that surgical strategies in Japan and other countries will fuse with each other in order to identify the best treatments for PTC patients throughout the world.
Asian Continental Ancestry Group ; Carcinoma ; Factor IX ; Humans ; Japan ; Korea ; Lymph Node Excision ; Lymph Nodes ; Neck Dissection ; Prognosis ; Recurrence ; Reoperation ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy