This multi-institutional study investigated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) frequency and its diagnostic significance in Japan. We reviewed 4008 thyroid nodules resected in six institutions before NIFTP was proposed. Overall, 26 cases diagnosed as non-invasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) and 145 cases of follicular thyroid adenoma (FTA) were included. Of these nodules, 80.8% and 31.0%, respectively, were NIFTPs. In five institutions, NIFTPs were more commonly found in FTA than in PTC nodules. When NIFTP was included with PTC, the overall prevalence was 2.3%, with rates in five institutions below 5.0% (0.8%-4.4%). One NIFTP case with nuclear score 3 revealed nodal metastasis 2.5 years post-resection, and the carcinoma cells were immunohistochemically positive for BRAF. FTAs or NIFTPs with nuclear score 2 did not metastasize. NIFTP was more common among FTA than among PTC nodules, possibly due to underdiagnosis of PTC on nuclear findings. Considering the clinical findings, molecular pathogenesis, and therapeutic strategy in Japan, NIFTP with nuclear score 2 is not different from FTA, and use of this entity terminology is not meaningful. In contrast, NIFTP with nuclear score 3 has potential for metastasis and BRAFV600E mutation. Therefore, in NIFTP cases, nuclear scores 2 and 3 should be separately reported.

Background The most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines. Methodology This was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019. Results A total of 404 patients with thyroid carcinoma were sorted, of which 40 (10.1%) were FTC cases. Overall, 50% of the patients were in the age group of 41-60 years, and the female-to-male ratio was 1.5:1. The majority of patients (60%) presented with neck swelling, followed by bone and lung metastasis in 20% and compressive symptoms in another 20%. On fine needle aspiration cytology (FNAC), 50% had Bethesda category III-IV nodules while 10% had Bethesda category II. Overall, 50% had a total thyroidectomy while 50% had a lobectomy followed by a completion thyroidectomy. On histopathology, 23 (57.5%) patients had minimally invasive FTC while 17 (42.5%) had widely invasive FTC. A total of 17 (42.5%) patients had received RAI 30-100 mCi while 10 (25%) received more than 100 mCi. Conclusions FTC can present with both local or metastatic symptoms. The atypical presentation of metastatic FTC should be considered, diagnosed, and managed early to limit mortality and morbidity. Ultrasound is the best diagnostic investigation of choice followed by FNAC. Surgery is the mainstay of treatment and should be followed by RAI in select cases. Thus, understanding the trend of FTC and proper planning and utilization of the resources will help developing countries in effectively treating the FTC.

This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort.
We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS).
During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group.
Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Clear-cell carcinoma of the thyroid has been regarded as a variant of follicular (FTC) or papillary (PTC) thyroid carcinoma. Twenty-one primary thyroid carcinomas with clear-cell features, diagnosed in 20 patients (12 female) were identified between 1992 and 2012 (0.5% of in-house thyroid carcinomas).
Hematoxylin and eosin slides were reviewed. SNaPshot multigene mutational analysis and a translocation panel were successfully performed on 15 of these cases.
Twelve (57%) were FTC, five were conventional PTC, two were follicular variant of PTC, and two were poorly differentiated thyroid carcinomas. Five cases had RAS mutation (four FTC and one PTC); two had PAX8-PPARgamma translocations (both FTC, one with concurrent p53 mutation); one had an EML4-ALK translocation (PTC); and one had a TFG-MET translocation (follicular variant of PTC). Five carcinomas were metastatic to regional lymph nodes (three FTC and two PTC), and two were metastatic to bone (both FTC). Disease confined to the thyroid (67%) and rates of regional lymph node metastasis (24%) and distant metastasis (10%) were near the national averages (68%, 25%, and 5%, respectively). One patient with a poorly differentiated thyroid carcinoma died one year after diagnosis, and a patient with metastatic FTC died two years after diagnosis. Overall mortality was 10%.
Clear-cell change in thyroid carcinoma is rare, is more common in FTC than it is in PTC, is found focally or multifocally within a given lesion, and is frequently associated with RAS mutations (33%). Clear-cell change in thyroid neoplasia should raise the possibility of follicular carcinoma, and should not be treated differently from other carcinomas of similar grade and stage.

OBJECTIVE: This study aimed to evaluate the locoregional recurrence rate of follicular thyroid carcinoma (FTC) and to assess the appropriate frequency of postoperative ultrasonography (US) surveillance for detecting tumor recurrence.
METHODS: The review boards of the seven participating institutions approved this study. From 2000 to 2011, 186 patients underwent at postoperative US at least once; US was performed by experienced radiologists at each institution. Based on the US and histopathological results, locoregional tumor recurrence was assessed.
RESULTS: The T stages of the 186 patients were T1a (8.1%), T1b (21.5%), T2 (39.8%), T3 (30.6%), T4a (0%), and T4b (0%). The N stages were unknown (24.2%), N0 (71.5%), N1a (3.2%), and N1b (1.1%), and the M stages unknown (29.6%), M0 (66.1%), and M1 (4.3%). Tumors recurred in only 6 (3.2%) patients during the follow-up period over 5 years. Among them, no patients showed the initial suspicion of recurrences on routine follow-up US. The session number and interval of postoperative US differed significantly between patients with recurrence and those without recurrence. The mean interval of postoperative follow-up US at the first detection time of tumor recurrence was 37.5 ± 18.5 months (range 9-62 months). Significantly more FTCs were at an advanced N and M stage in the recurrence group than in the non-recurrence group (p < 0.05).
CONCLUSIONS: Routine postoperative US surveillance may be unnecessary for detecting tumor recurrence after thyroid surgery in FTC patients.