Reconfirmation of the accuracy of the taller-than-wide sign in multicenter collaborative research in Japan.

The taller-than-wide sign indicates that the anteroposterior dimension-to-transverse dimension ratio (AP/T ratio) is higher than 1. The aim of the present study was to reconfirm the accuracy of the taller-than-wide sign for diagnosing malignant thyroid nodules by ultrasonography in multicenter collaborative research, and investigate differences according to tumor sizes, histological types, and the influence of the tilt and orientation of the probe. At 6 registered institutes, 2,032 thyroid nodules were successively operated on and diagnosed pathologically. The accuracy of the taller-than-wide sign for diagnosing malignant tumors by ultrasonography was retrospectively analyzed across all nodules as well as in analyses separately stratified by tumor size and histology. The influence of the tilt and orientation of the probe was also assessed. The taller-than-wide sign showed high specificity for diagnosing malignancy in all nodules tested. It also showed high specificity regardless of the tumor size. When tumors were analyzed by histological types, the AP/T ratio of papillary carcinoma was significantly higher than that of benign nodules, whereas no significant difference was observed between follicular carcinoma and benign nodules. The specificity of longitudinal sections was significantly higher, while the AUC of longitudinal sections was significantly larger than those of transverse sections. The AP/T ratio obtained when the probe was tilted was not significantly different from that when it was straight. The present results support the usefulness of the taller-than-wide sign for diagnosing malignant tumors regardless of size, but not follicular carcinoma. The influence of the tilt and orientation of the probe was negligible.

Thyroid Cancer Active Surveillance Program Retention and Adherence in Japan.

Importance: Small papillary thyroid cancers are the most common type of thyroid cancer, with the incidence increasing across the world. Active surveillance of appropriate cancers has the potential to reduce harm from overtreatment but is a significant de-escalation from prior practice. Mechanisms that inform the rates of retention and adherence have not been described and need to be understood if broader uptake is to be considered. Objective: To evaluate patient retention, adherence, and experience in the largest and most long-standing thyroid cancer active surveillance program, to our knowledge. Design, Setting, and Participants: A cohort study using convergent design mixed-methods analysis of attendance data, semistructured interviews, and field observation was conducted at Kuma Hospital, Kobe, Japan. Participants included 1179 patients who were enrolled in surveillance between February 1, 2005, and August 31, 2013, and followed up through December 31, 2017. Data analysis was performed from January 25, 2018, through September 30, 2020. Main Outcomes and Measures: Patients were considered adherent if they underwent ultrasonography within at least 13 months of the previous ultrasonographic examination. Patients were considered retained if they continued surveillance with an ultrasonographic examination at least every 2 years, without having had surgery for patient preference or clinical reasons. Results: Of the 1179 patients included in the study, 1037 (88%) were women. The mean (SD) age was 56 (13.5) years (median, 57 years). Patients were followed up for up to 12.76 years (median, 5.97 years) and underwent a median of 9 ultrasonographic examinations (range, 2-50); 76 patients (6.4%) had surgery for clinical reasons. In analysis of retention, 53 of 1179 patients (4.5%) changed to surgery after a mean (SD) of 2.14 (1.53) years (median, 1.47; range, 0.14-7.17 years); at the study end point, 101 of 1179 patients (8.6%) had not been seen at Kuma Hospital in at least the past 2 years. Kaplan-Meier analysis to 10 years of follow-up time without structural progression estimated that 21.5% (95% CI, 17.0%-28.2%) of patients would not have had an ultrasonographic examination within at least the past 2 years. Mean adherence over a surveillance period of 10 follow-up ultrasonographic examinations (8878 person-examinations) was 91% (range, 85%-95%). Receipt of detailed test results, education regarding active surveillance, and supportive/collaborative style interactions with their physician were identified by patients as key factors for continuing surveillance. Conclusions and Relevance: For patients with low-risk papillary thyroid cancer participating in active surveillance, retention in the program and adherence to follow-up ultrasonographic examination do not appear to be barriers to broader implementation of surveillance. The program's success may benefit from an approach analogous to traveler (patient) and their guide (clinician): the clinician advising on options, advocating for the optimal path over time, and supportively reaffirming the care plan or recommending alternatives as conditions change.

Compact integrated optical sensors and electromagnetic actuators for vibration isolation systems in the gravitational-wave detector KAGRA.

This paper reports on the design and characteristics of a compact module integrating an optical displacement sensor and an electromagnetic actuator for use with vibration-isolation systems installed in KAGRA, the 3-km baseline gravitational-wave detector in Japan. In the technical concept, the module belongs to a family tree of similar modules used in other interferometric gravitational-wave detector projects. After the initial test run of KAGRA in 2016, the sensor part, which is a type of slot sensor, was modified by increasing the spacing of the slot from 5 mm to 15 mm to avoid the risk of mechanical interference with the sensor flag. We confirm that the sensor performance is comparable to that of the previous design despite the modification. We also confirm that the sensor noise is consistent with the theoretical noise budget. The noise level is 0.5 nm/Hz1/2 at 1 Hz and 0.1 nm/Hz1/2 at 10 Hz, and the linear range of the sensor is 0.7 mm or more. We measured the response of the actuator to be 1 N/A and also measured the resistances and inductances of coils of the actuators to confirm consistency with theory. Coupling coefficients among the different degrees of freedom were also measured and shown to be negligible, varying little between designs. A potential concern about thermal noise contribution due to eddy current loss is discussed. As of 2020, 42 of the modules are in operation at the site.

Thyroid Lymphoepithelial Cysts Mimicking Calcified or Solid Nodules on Ultrasonography.

PURPOSE: Thyroid lymphoepithelial cysts (TLECs) are rare, and detailed ultrasonography (US) findings have not been reported. This study aimed to examine in detail the US findings for 32 TLECs and to clarify the diagnostic problems associated with them. MATERIALS AND METHODS: We examined 32 TLECs resected from 21 patients at the Kuma hospital between January 2008 and April 2018. All patients underwent US before resection. From the patients' medical records, we retrospectively assessed US reports and photographs of TLECs. RESULTS: The following four types of TLECs were classified: cystic, mixed solid and cystic, pseudo-solid, and pseudo-calcified types. The incidences were 50.0%, 12.5%, 12.5%, and 25.0%, respectively. Among the four types, pseudo-calcified TLECs were the smallest in size (mean: 7.1 mm). Of 24 nodules that had been interpreted in US reports, 11, 9, 1, 2, and 1 were benign, very low, low, intermediate, and high, respectively. Calcification and intramural solid growth were not identified by histological examination. CONCLUSION: We should be aware that approximately half of TLECs do not exhibit US appearances typical of simple cysts, and TLECs may mimic calcified or solid nodules on US, although the reason remains unknown.

Patient Experience of Thyroid Cancer Active Surveillance in Japan.

Importance: The burden of concern for patients with thyroid cancer who undergo surgical intervention with or without radioactive iodine is known to be substantial. For patients under active surveillance, this aspect of the patient experience has not been described to date and could be a potential barrier to broader acceptance of surveillance as a cancer management strategy. Objective: To describe the experiences of patients in the longest-standing and largest thyroid cancer active surveillance program. Design, Setting, and Participants: This study used a mixed method of survey, semistructured interviews, and field observation and was conducted at Kuma Hospital in Kobe, Japan. The survey was administered from September 4, 2017, through October 18, 2017, and the field observation was conducted from August 28, 2017, to October 20, 2017. Survey participants were a consecutive sample of 249 patients under active surveillance who were attending the hospital for a surveillance visit, and the semistructured interviewees were a subset of 21 patients. The English-language survey instrument was translated by native Japanese speakers, back-translated into English, and then further refined by a panel of Japanese speakers with expertise in health research. Main Outcomes and Measures: Survey and interview responses and field observations. Results: In total, 249 surveys were distributed to patients with thyroid cancer on active surveillance. Two hundred forty-three patients (97.6%) completed the survey. Among the respondents, 195 (80.2%) were female and 20 (8.2%) were male (28 [11.5%] responses were missing). Among the subset of 21 patients who participated in the semistructured interview, 3 were male (14.3%), and the mean (range) age was 64 (32-85) years. Thirty-seven percent rated the frequency of cancer worry as occurring sometimes or more. Thirty-two percent said their worry affected their mood somewhat or a lot. Fourteen percent reported that their worry affected their ability to carry out daily activities somewhat or a lot. Cancer spread, later need for surgical intervention, and difficulty with interpreting bodily experiences in the general location of the cancer were among the main sources of worry. Most respondents (60.0%) said their worry was less than it was when they first found out about their cancer. By 3 years after diagnosis, the proportion of participants who reported they were not at all worried increased from 14% (95% CI, 12%-16%) to 25% (95% CI, 23%-26%). Eighty percent (95% CI, 79%-81%) of respondents agreed or strongly agreed that their decision to do active surveillance matched their personal values, and 83% (95% CI, 82%-84%) agreed or strongly agreed that choosing active surveillance was the best decision for them personally. Most patients (77%) had not heard of active surveillance before they were offered the option. Conclusions and Relevance: Cancer concern was common among patients with thyroid cancer under active surveillance, which is comparable to the worry among actively treated patients. Levels of cancer worry reported by patients under active surveillance decreased over time, and patients expressed satisfaction with their disease management decision. These findings suggest that the possibility of cancer worry should not be viewed as prohibitive to successful active surveillance in thyroid cancer.

Natural history of papillary thyroid microcarcinoma: Kinetic analyses on tumor volume during active surveillance and before presentation.

BACKGROUND: We report on the growth of papillary microcarcinoma during active surveillance and before clinical presentation. METHODS: We conducted a retrospective study of 169 patients with papillary microcarcinoma who were enrolled in active surveillance at our hospital between 2000 and 2004. Patients were followed for a median of 10.1 years using serial ultrasonography (median, 12 examinations), used to calculate the tumor doubling time. To contextualize tumor growth rates during active surveillance, we calculated the hypothetical tumor doubling time before clinical presentation. To resolve the limitations in tumor doubling time, tumor doubling rates were inversely transformed into doubling rates. RESULTS: The doubling rates (per year) during active surveillance (median: 0.0) were >0.5, 0.1 to 0.5, -0.1 to 0.1, and <-0.1 in 5, 38, 97, and 29 cases, respectively. The proportions of tumors with rather rapid growth, slow growth, stable, and a decrease in size were 3%, 22%, 57%, and 17%, respectively. CONCLUSION: Tumor growth of papillary microcarcinomas varies from rather rapid growth to a decrease in size during active surveillance.

Calcitonin measurement in fine-needle aspirate washout fluid by electrochemiluminescence immunoassay for thyroid tumors.

PURPOSE: For the differential diagnosis of medullary thyroid carcinoma (MTC) on thyroid nodules, ultrasound-guided fine-needle aspiration cytology is a useful and safe procedure, but its diagnostic accuracy is not high enough. As an ancillary method to accurately diagnose MTC, the calcitonin in fine-needle aspirate washout fluid (FNA-Ct) is used. However, no data are available about cut-off values of FNA-Ct using the currently available electrochemiluminescence immunoassay (ECLIA). METHODS: We investigated 180 thyroid nodules in 141 patients. After smearing, the syringe and needle used for the FNA were rinsed with normal saline (0.5 mL). The calcitonin in the washout was measured by ECLIA. RESULTS: The FNA-Ct in the non-MTC nodules of MTC patients, non-MTC nodules of non-MTC patients, and MTC nodules were 10.6-2100 pg/mL (median 24.6 pg/mL), < 0.5-21.0 pg/mL (median < 0.5 pg/mL), and 94.9-4,070,000 pg/mL (median 177,000 pg/mL), respectively. A receiver operating characteristic analysis of the MTC nodules and the non-MTC nodules of the non-MTC patients indicated that the cut-off value was 21.0 pg/mL, leading to 100% sensitivity and 100% specificity. CONCLUSIONS: This is the first study to determine the cut-off value of FNA-Ct with an ECLIA, and we propose that the optimal cut-off value is 21.0 pg/mL.

Phantom Nodules Detected by Ultrasound Examination of the Neck: The Possibility of Ectopic Cervical Thymic Tissue in Adults.

PURPOSE: The aim of this study was to investigate the ultrasound characteristics and clinical significance of slightly hyperechoic lesions, referred to as phantom nodules, in the perithyroidal area in patients. MATERIALS AND METHODS: A total of 128 patients who underwent thyroidectomy with central neck lymph node dissection at Kuma Hospital in Hyogo, Japan were included in the study. We detected 16 phantom nodules during preoperative ultrasound examinations, defined as slightly hyperechoic masses located in the perithyroidal areas, in 13 of these 128 patients (10.2%; mean age: 55.6 years, range: 36-75 years). RESULTS: All phantom nodules were located in the caudal region of the thyroid gland, and the mean maximum dimension was 7.2 mm. 12 of the 16 nodules were round or oval, while the remaining 4 were fusiform and molded by the surrounding tissue. All nodules were well-defined, solid, homogeneous, hyperechoic masses. No speckled echo pattern, internal linear echo, or vascular flow signal was observed. All 4 nodules subjected to histological examination were composed of ectopic thymic tissue. In 2 of these 4, the parenchyma was severely involuted and almost entirely replaced by adipose tissue. CONCLUSION: To the best of our knowledge, this is the first report wherein some of the detected hyperechoic perithyroidal masses were composed of ectopic thymic tissue, and some were primarily composed of adipose tissue that completely replaced involuted ectopic thymic tissue. The results of the study suggest that these so-called phantom nodules are clinically insignificant and do not require fine needle aspiration cytology or further investigation.

Re-Evaluation of 162 Malignant Thyroid Nodules that were Interpreted as Benign Based on Ultrasound Findings.

PURPOSE: The goal of this study was to estimate the risk of malignant thyroid nodules being interpreted as benign based on ultrasound findings and to clarify the pathological features of these malignant nodules. MATERIALS AND METHODS: We retrospectively re-evaluated ultrasound and pathological findings for 162 malignant thyroid nodules that were initially interpreted as benign based on ultrasound findings at Kuma Hospital between April 2012 and June 2015. RESULTS: The incidences of malignancy among "benign" thyroid nodules were 0.5% overall and 6.2% among resected nodules. In addition, 82.7% of thyroid nodules that were originally judged to have low or very low suspicion patterns were subsequently re-categorized as having high or intermediate suspicion patterns. The incidences of irregular margins (63.6%) and low echogenicity (36.4%) were higher than those of punctate microcalcification (17.9%) and the taller-than-wide shape (20.4%). Among microcarcinomas, the incidences were 65.7% for irregular margins and 51.4% for low echogenicity. Rim calcification with small extrusive soft tissue components and extrathyroidal extensions were not observed. After re-evaluation, 40.0% of papillary thyroid carcinomas remained benign based on their variants, such as the encapsulated, follicular, macrofollicular, and oxyphilic cell variants. CONCLUSION: We conclude that more careful observation, especially for lesions with irregular margins and low echogenicity, can help improve the diagnostic accuracy of thyroid ultrasonography. Furthermore, greater care may decrease the incidence of malignancy among thyroid nodules with low or very low suspicion patterns. Some variants of papillary thyroid carcinoma can have benign ultrasound findings.

Sonographic Evaluation of Nodules Newly Detected in the Neck After Thyroidectomy: Suture Granuloma Versus Recurrent Carcinoma.

PURPOSE: This study aimed to clarify the sonographic features of suture granuloma and recurrent carcinoma newly detected after thyroidectomy. MATERIALS AND METHODS: We retrospectively analyzed ultrasound reports with images of 25 cases of suture granuloma and 18 cases of recurrent carcinoma that newly appeared in the resected area after thyroidectomy in our institution. RESULTS: Both suture granulomas and recurrent carcinomas more frequently exhibited multiple lesions rather than solitary lesions. Suture granulomas tended to appear in the more superficial areas than the carotid artery, while recurrent carcinomas were more common between the trachea and carotid artery. A total of 10 of the 11 suture granulomas that we followed up decreased in size. Recurrent carcinomas showed irregular shape (55.6%), taller-than-wide shape (38.9%), low internal echogenicity (83.3%), and no punctate microcalcifications. By contrast, suture granulomas were fusiform in shape (56.0%) and showed linear internal echo parallel to the tissue plane on the longitudinal scan (64.0%). The vascular flow sign was mild to none in the majority of both lesions. CONCLUSION: Fusiform shape and linear internal echoes indicate suture granuloma, while irregular shape, taller-than-wide shape, and low echogenicity indicate recurrent carcinoma. Given that the clinical management of suture granuloma differs from that of recurrent carcinoma, it is important to distinguish between these two lesions.

Calcifications in Thyroid Tumors on Ultrasonography: Calcification Types and Relationship with Histopathological Type.

PURPOSE: The purpose of the study is to clarify the prevalence of calcifications within thyroid tumors on ultrasonography as well as the relationship between the calcification and histopathological types. MATERIALS AND METHODS: Calcifications were classified into 6 (or 8) types according to their shape, size, and region. The prevalence of calcifications and types were investigated in new outpatients and patients who underwent thyroid surgery. RESULTS: Among 2,902 nodules in 2,678 new outpatients, 747 nodules (26%) had calcifications. The types showed a wide distribution. Among 941 patients with papillary carcinoma (PC), 725 patients (77%) had calcifications, and the types showed a wide distribution. 18 patients with the diffuse sclerosing variant of PC only showed punctate microcalcifications in the parenchyma (100%), 32 patients with the cyst-forming type of PC mostly fragmentary and massive types (100%), and 161 metastatic lymph nodes from PC mostly punctate microcalcifications and fragmentary types (48%). Among 337 patients with follicular carcinoma, 79 patients (23%) had calcifications, and the types were mostly fragmentary, massive, and egg-shell types. Among 41 patients with undifferentiated carcinoma, 33 patients (80%) presented with calcifications, which were mostly the massive and egg-shell types. Among 137 patients with medullary carcinoma, 99 patients (72%) had calcification, and the types showed a wide distribution. None of 173 patients with primary thyroid lymphoma had calcifications (0%). CONCLUSION: Calcifications on ultrasonography can be one of the characteristic findings and a full understanding of the prevalence of calcifications and types will markedly contribute to the ultrasonic diagnosis of thyroid tumors.

Can Ultrasound Alone Predict Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis? A Retrospective Analysis of 13 Cases, Focusing on the Stromal Area.

PURPOSE: Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) is extremely rare. So far, only 4 cases describing the ultrasound findings of this variant have been reported. Here, we describe the ultrasound findings of 13 cases of PTC-DTF, focusing especially on the DTF area. MATERIALS AND METHODS: We retrospectively analyzed the clinical reports, ultrasound reports, and ultrasound photographs obtained from medical records at Kuma Hospital. RESULTS: The patients included 8 women and 5 men with a mean age of 47.9 years. The widest dimension of the nodules ranged from 16 to 79 mm (mean: 37.5 mm). The original ultrasound reports classified the nodules as either intermediate suspicion or high suspicion. A diagnosis of PTC was suspected in 12 nodules, and anaplastic carcinoma was suspected in 1 nodule. PTC-DTF presented with an irregularly shaped nodule (100%), taller-than-wide sign (84.6%), heterogeneous echogenicity (100%), no microcalcification (76.9%), and no or mild flow signal on Doppler (75.0%). The DTF area was identified in the ultrasound photographs of 8 nodules. DTF areas were generally heterogeneous (62.5%) and more hypoechoic (71.4%) than PTC areas. Microcalcification was not observed in the DTF areas. All of the DTF areas revealed no or mild flow signal. On ultrasound elastography, the DTF areas were not stiff, and they were more elastic than the PTC areas. CONCLUSION: It is difficult to predict PTC-DTF using ultrasound alone, and B-mode ultrasonography is more reliable than ultrasound elastography in the ultrasound diagnosis of malignant thyroid nodules.

Static Prognostic Factors and Appropriate Surgical Designs for Patients with Medullary Thyroid Carcinoma: The Second Report from a Single-Institution Study in Japan.

BACKGROUND: Medullary thyroid carcinoma (MTC) originates from calcitonin-producing cells of the thyroid. In 2009, we published our first report on the biological characteristics and prognosis of 118 MTC patients. Herein, we enrolled a larger number of patients with longer follow-up periods to further study the biological characteristics and appropriate therapies for MTC. METHODS: In general, hemithyroidectomy and total thyroidectomy were performed for sporadic MTC confined to the thyroid lobe and for hereditary MTC with central node dissection, respectively. Moreover, prophylactic modified radical neck dissection was performed on the side of macroscopic tumors. RESULTS: In total, 233 patients (99 hereditary and 134 sporadic) were enrolled. The median follow-up time was 128 months (range 7-445 months). Biochemical cure was obtained in 36 (62%) of the 58 patients who underwent prophylactic MND and were pathologically positive for lateral node metastasis. None of the patients had recurrence in the preserved thyroid. Distant recurrence was detected in 19 patients, and 12 died of MTC. Preoperative calcitonin and carcinoembryonic antigen levels, tumor size (T) > 4 cm, the male sex, clinical and pathological node metastases (N1), distant metastasis (M1), extrathyroid extension (Ex), and a lack of biochemical cure had prognostic impacts on distant recurrence and/or carcinoma-related mortality on univariate analysis. On multivariate analysis, Ex was independently correlated with distant recurrence, and Ex, T > 4 cm, and M1 independently affected carcinoma-related mortality. CONCLUSION: MTC patients had excellent prognosis in our institutions, indicating that our surgical strategies were appropriate.

Trends in the Implementation of Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital: Gradual Increase and Heterogeneity in the Acceptance of This New Management Option.

BACKGROUND: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PMC) was adopted as a management modality in both the Japanese guidelines in 2011 and the American Thyroid Association guidelines in 2015. AS was initiated at Kuma Hospital in 1993 but was not immediately accepted by all physicians. This study investigated the history of acceptance of AS at Kuma Hospital over time. The results should assist in the implementation of AS at other hospitals in Japan and other countries. METHODS: This study included 4023 patients who were cytologically diagnosed with low-risk PMC at Kuma Hospital during the 24-year period between October 1993 and June 2016. The trend in the frequency of AS use over time was analyzed, dividing the 24-year study period into five parts based on the change in frequency of AS use: 1993-1997, 1998-2002, 2003-2006, 2007-2013, and 2014-2016. RESULTS: The frequency of AS use in the present cohort was 65%. The frequency gradually increased from 30% in 1993-1997 to 88% in 2014-2016, with a slight decrease from 51% in 1998-2002 to 42% in 2003-2006. Until 2007, patients were mostly seen by surgeons, and the frequency of AS use varied remarkably among individual surgeons. Since 2007, the number of patients whose therapeutic strategies are determined by endocrinologists has increased, and the frequency of AS use for low-risk PMC by endocrinologists has been higher than that by surgeons. CONCLUSIONS: At Kuma Hospital, acceptance of AS for low-risk PMC gradually increased over the 24-year study period, but AS was not equally accepted by all physicians. Such variations in the acceptance of AS among individual physicians are also expected to exist in other hospitals. However, due to increasing evidence of the safety and superiority of AS over immediate surgery for this indolent disease, it is expected that AS will gain faster acceptance in other hospitals in Japan and around the world.

Prognostic value of the 8th tumor-node-metastasis classification for follicular carcinoma and poorly differentiated carcinoma of the thyroid in Japan.

Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

Prognostic value of the 8th edition of the tumor-node-metastasis classification for patients with papillary thyroid carcinoma: a single-institution study at a high-volume center in Japan.

The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6-357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia distinct from the salivary type.

We report three cases of thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE), which is an extremely rare variant of mucoepidermoid carcinoma (MEC). The aims of this report were to describe the clinicopathological findings, including results from immunohistochemical and fluorescence in situ hybridization analysis of thyroid SMECE, as well as to discuss the distinction between thyroid SMECE and its salivary counterpart. The cases included a 63-year-old female, a 44-year-old male, and a 66-year-old female, with all patients presenting with Hashimoto's thyroiditis. Nodal metastasis was not found in any of the three cases. Neither regional recurrences nor distant metastases were found in any patient during the follow-up, which was 20 years, 3 years, and 18 months, respectively. Histologically, tumors were composed of epidermoid carcinoma cells, intermediate type carcinoma cells, and goblet cell-type mucus-secreting carcinoma cells, with all tumors displaying a sclerotic stroma with eosinophilic and lymphocytic infiltration. The formation of eosinophilic abscess in the tumor nests that might be a novel characteristic finding of SMECE was observed. Immunohistochemically, the carcinoma cells were positive for cytokeratin 34ßE12, TTF-1, and PAX8, but negative for thyroglobulin. In two cases, increased IgG4-positive plasma cells were observed. Mastermind-like transcriptional coactivator 2 (MAML2), according to fluorescence in situ hybridization, was intact in all cases. In conclusion, thyroid SMECE has favorable outcomes and seems to be genetically different from salivary MEC. This is the first report to describe the presence of increased IgG4-positive plasma cells in the stroma of SMECE.

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

INTRODUCTION: In Japan, prophylactic central node dissection (p-CND) for papillary thyroid carcinoma (PTC) has been routinely performed in many institutions, including ours (Kuma Hospital, Japan). We evaluated the recurrence to a central lymph node in patients with cN0M0 PTC who underwent routine p-CND. MATERIALS AND METHODS: We enrolled 4301 patients with cN0M0 PTC who underwent an initial surgery between 1987 and 2005 (median age 51 years). The postoperative follow-up periods ranged from 4 to 362 months (median 164 months). Only 15 patients underwent radioactive iodine (RAI) ablation (≥30 mCi) after total or near total thyroidectomy. RESULTS: Of the 4301 patients with N0M0 PTC who underwent p-CND, 2548 (59%) were diagnosed as pN1a on postoperative pathological examination. To date, only 52 cases (1.2%) showed recurrence to a central lymph node. The 10-year and 20-year central node recurrence-free survival rates were excellent at 99.1 and 98.2%, respectively. On multivariate analysis, age ≥55 years, significant extrathyroid extension, tumor size >2 cm, and ≥5 pathologically confirmed central node metastases (but not the presence of central node metastasis) independently affected central node recurrence. CONCLUSIONS: Under the situation of routine p-CND, the central node recurrence-free survival of cN0M0 PTC is excellent. However, future studies, including double-arm studies from Japan, should examine whether the omission of p-CND cN0M0 PTC is appropriate without RAI ablation in consideration of various factors, including the pros and cons of p-CND.

Overall Survival of Papillary Thyroid Carcinoma Patients: A Single-Institution Long-Term Follow-Up of 5897 Patients.

INTRODUCTION: Papillary thyroid carcinoma (PTC) generally shows an excellent prognosis except in cases with aggressive backgrounds or clinicopathological features. Although the cause-specific survival (CSS) of PTC patients has been extensively investigated, the overall survival (OS) of these patients is unclear. We herein investigated both the OS and CSS of a large PTC patient series. MATERIALS AND METHODS: We enrolled 5897 PTC patients who underwent initial surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years). Their median postoperative follow-up period was 177 months. Univariate and multivariate analyses for OS and CSS assessed the effects of gender, older age (≥55 years), distant metastasis at diagnosis (M1), significant extrathyroid extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N ≥ 3 cm), and extranodal tumor extension. RESULTS: To date, 387 patients (7%) in this series have died from various causes, including 117 (2%) due to PTC. The 10-, 15-, and 20-year OS rates are 97, 95, and 90%, respectively. Older age and M1 were important prognostic factors for OS and CSS. Older age was a more significant factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a prominent prognostic factor for both OS and CSS. In the young patients, M1 had less prognostic impact than in the older patients, and the prognostic values of M1 and N ≥ 3 cm for OS and CSS were identical and similar, respectively. CONCLUSIONS: The most important prognostic value for OS was patient age, indicating that PTC is generally indolent. However, the control of distant metastasis in older patients remains a future challenge in order to further improve their OS and CSS. PTC of ≥3 cm in young patients should be carefully followed, even in the absence of metastases, and these patients should undergo aggressive therapies for recurrent lesions and metastases.

Estimation of the lifetime probability of disease progression of papillary microcarcinoma of the thyroid during active surveillance.

BACKGROUND: We reported that a minority of patients with low-risk papillary microcarcinoma of the thyroid showed disease progression during active surveillance and that older patients had significantly lower disease progression rates than younger patients. Here, we estimated lifetime (≤85 years old) probabilities of disease progression during active surveillance according to the age at presentation based on age decade-specific disease progression rates. METHODS: From 1993-2013, 1,211 low-risk papillary microcarcinoma patients aged 20-79 years underwent active surveillance at Kuma Hospital. We calculated the disease progression rate at the 10-year point of active surveillance for each age-decade group (20s to 70s) with the Kaplan-Meier method. The lifetime disease progression probability for each age group was calculated as (1 - cumulative probability of progression-free survival calculated with age decade-specific disease progression rates) until the patients reached their 80s (i.e., 85 years on average). RESULTS: The age decade-specific disease progression rates at 10 years of active surveillance were 36.9% (20s), 13.5% (30s), 14.5% (40s), 5.6% (50s), 6.6% (60s), and 3.5% (70s); the respective lifetime disease progression probabilities were 60.3%, 37.1%, 27.3%, 14.9%, 9.9% and 3.5% according to the age at presentation. CONCLUSION: The estimated lifetime disease progression probabilities of papillary microcarcinoma during active surveillance vary greatly according to the age at presentation.