Background: Prospective trials of active surveillance for asymptomatic papillary microcarcinoma (T1aN0M0) since the 1990s have shown progression rates of only 5-10%. Late rescue surgery after progression had no deleterious effects on mortality and morbidity. The 2015 American Thyroid Association guidelines approved active surveillance for very low-risk papillary thyroid carcinoma (PTC) as an alternative method to immediate surgery. However, there is no study that evaluates long-term active surveillance for T1b tumors. Methods: A prospective trial of active surveillance with 360 very low-risk PTC (T1aN0M0) patients has been conducted since 1995. Of the 392 T1bN0M0 patients, 61 selected active surveillance over surgery and eventually participated in this trial, while the remaining 331 patients underwent surgery. To find an appropriate management strategy for patients with T1bN0M0 PTC, the outcomes of active surveillance for T1bN0M0 to T1aN0M0 PTC were investigated and compared, and the outcomes of surgery for T1bN0M0 PTC were studied. Results: After a mean of 7.4 years of active surveillance, 29 (8%) T1aN0M0 tumors and four (7%) T1bN0M0 tumors had increased in size ( p = 0.69). Development of lymph node metastasis was seen in three (0.8%) patients and two (3%) patients, respectively ( p = 0.10). No significant difference in progression rate was seen between groups. Among T1bN0M0 tumors, weak calcification and rich vascularity were risk factors for tumorsize increase, and younger age was a predictor for the development of lymph node metastasis. Mean initial tumor size was significantly greater in T1bN0M0 patients who underwent immediate surgery (14.5 -2.8 mm) than it was in patients who chose observation (11.7 -1.1 mm; p < 0.0001). No postoperative recurrence was seen in patients with tumor <15 mm in diameter. Conclusions: Active surveillance is an option for selected patients with T1bN0M0 PTC.

PMCs in older patients showed significantly stronger calcification patterns and poorer vascularity. Both consolidation of calcification and loss of vascularity occurred in a time-dependent manner during observation and were significant indicators for non-progressive disease.

Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma. We conducted direct sequencing for BRAF, TERT promoter and PIK3CA, and immunohistochemistry for p53, TTF-1 and subunits of the SWI/SNF complex (ARID1A, ARID1B, ATRX, SMARCA2, SMARCA4, SMARCB1, and PBRM1). BRAF and TERT promoter mutated at the rate of 90% and 95%, respectively, and these mutational statuses were almost identical between the papillary carcinoma and anaplastic carcinoma components. PIK3CA mutation was positive in 33% of our samples with a heterogeneous mutation pattern of the papillary carcinoma and anaplastic carcinoma components. Aberrant expression of p53 and loss of TTF-1 were present in 63 and 59%, respectively, and these two alterations were confined to the anaplastic carcinoma components. There was a loss of the SWI/SNF complex in a subset of the tumors with a heterogeneous pattern of the papillary carcinoma and anaplastic carcinoma components: SMARCA4 in 4% and PBRM1 in 4%. In a multivariate comparison between the antecedent papillary carcinoma components and control papillary carcinomas without anaplastic transformation, TERT promoter mutation was independently associated with anaplastic transformation. Collectively, papillary carcinoma-derived anaplastic carcinomas are characterized by BRAF and TERT promoter mutations, and these mutations occur prior to anaplastic transformation. Alterations of PIK3CA and the SWI/SNF complex are relatively rare and temporally heterogeneous. Of note, a papillary carcinoma harboring TERT promoter mutation is at higher risk for anaplastic transformation.

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Background: The tumor–node–metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. Methods: The revised system was evaluated using a large database of ATC patients. Results: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). Conclusion: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B.

We report four cases of acute transient thyroid swelling following fine-needle aspiration biopsy, a rare complication of still unknown origin. The ultrasonographic pattern was fairly similar to that in previous reports: swelling of the thyroid with a patchy and heterogeneous appearance and diffusely scattered hypoechoic "cracks" that showed no blood flow signals with color Doppler ultrasound. There were also some features that differed from those in previous reports. Though thyroid swelling is typically diffuse and bilateral, it was unilateral or asymmetrical in some of our cases. While thyroid swelling is said to resolve spontaneously within 1-20 h, abnormal ultrasonographic findings persisted for more than 48 h in one case. Unlike previous reports, we have experienced cases with ultrasonographic findings of concomitant minor subcapsular hematomas. In one case, CT demonstrated not only thyroid swelling but also abnormal attenuation in perithyroid tissue extending to the retro-hypopharyngeal space and to the paraesophageal mediastinum. Although vasodilatation and diffuse vascular leakage are speculated to be the underlying mechanisms, our ultrasonograms at the time of the complication failed to demonstrate enlarged intrathyroidal vessels or hypervascularity with color Doppler ultrasound. More awareness and a description of the cases may help to clarify the pathogenesis of this self-limited complication.

Background Prospective trials of active surveillance (AS) have shown low rates of progression in low‐risk papillary thyroid microcarcinoma (PTMC; T1aN0M0). However, the significance of multifocality as a prognostic factor remains controversial. Methods Data from 571 patients (mean age, 53.1 years; 495 females) who underwent AS were reviewed. PTMC was unifocal in 457 patients (80.0%) and multifocal in 114 patients (20.0%), with 2–5 lesions each (261 tumors in total). Tumor progression was defined as tumor size enlargement ≥ 3 mm and/or development of clinically evident lymph node metastasis (LNM). Results After a mean duration of AS of 7.6 years, 53 patients (9.3%) showed tumor enlargement and 8 patients (1.4%) developed LNM. The 10‐year progression rate was 13.1%. Age, sex, and calcification pattern did not differ significantly between uni‐ and multifocal diseases. However, anti‐thyroglobulin antibody and/or anti‐thyroid peroxidase antibody was more frequently positive with multifocal PTMCs (46.7%) than with unifocal disease (34.4%, p = 0.024). Patients with uni‐ and multifocal disease showed no significant differences in 10‐year rate of tumor enlargement (11.4% vs. 14.8%), LNM development (1.1% vs. 2.4%), or progression (12.4% vs 15.9%). Multivariate analysis of predictors for progression showed multifocality was not a significant risk factor (odds ratio, 1.45; 95% confidence interval, 0.79–2.54; p = 0.22). Eventually, 9 patients (7.9%) with multifocal PTMCs underwent surgery and 7 needed total thyroidectomy, although 7 still showed T1N0M0 low‐risk cancer. Conclusions Even patients with multiple PTMCs (T1amN0M0) are good candidates for AS. Many patients can avoid total thyroidectomy and subsequent surgical complications.

There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1–4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, p < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, p < 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1–4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.