Clinicopathological features and outcomes of intrathyroidal thymic carcinoma: a single institution study.

Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or adjacent to, the thyroid. We analyzed the backgrounds, clinicopathological features, and prognosis of 20 patients with ITTC, treated at our hospital. Thirteen of the 15 patients (86%) who underwent ultrasonography were diagnosed as malignant, based on imaging findings. 16 of the 17 patients (93%) who underwent cytology, were diagnosed or suspected to be malignant. Locally curative surgery (thyroidectomy and lymph node dissection) was performed for 19 patients. Large tumor size (>4 cm) was positively related to pathological node metastasis (p = 0.0389). Fourteen patients, including nine Ex-positive patients, underwent adjuvant external beam radiotherapy (EBRT) of the neck after surgery. Two patients showed recurrence of thyroid bed after and neither of them underwent adjuvant EBRT after surgery. Two patients who underwent EBRT showed recurrences of the lateral nodes (level V and level II), but they were easily dissected by re-operation. Ten- and 20-year local recurrence-free survival rates were 84.9% and 60.6%, respectively. To date, four patients showed distant recurrence, and 10- and 20-year distant recurrence-free survival rates were 75.0% and 75.0%, respectively. Our findings indicate that 1) the prognosis of ITTC is generally favorable, and 2) large tumor size is significantly related to lymph node metastasis. Two patients showing recurrence of the central region did not undergo EBRT; thus, further comparative studies are desirable to elucidate whether EBRT can prevent significant local recurrence.

Prognostic significance of patient age in papillary thyroid carcinoma with no high-risk features.

Older age is recognized as a predictor of poor prognosis in papillary thyroid carcinoma (PTC) patients. However, young age is associated with disease progression of PTC measuring 1 cm or smaller in patients on active surveillance. In this study, we investigated the relationship between patient age and prognosis of PTC belonging to very low-, low-, and intermediate-risk groups based on the guidelines published by the Japan Association of Endocrine Surgery in 2018. We enrolled 4,870 PTC patients with no high-risk features and assigned each to one of three categories: very low risk (N = 1,161), low risk (N = 1,746), and intermediate risk (N = 1,963). In very low-risk patients, the local recurrence-free survival (RFS) rate of young patients (<55 years) was significantly worse (p = 0.0437) than that of older patients (≥55 years). In low-risk patients, although age did not affect local recurrence, older patients were more likely to show distant recurrence on univariate (p = 0.0005) and multivariate analyses (p = 0.0017). In the intermediate-risk series, the local RFS rate of older patients tended to be poor (p = 0.0538), and older age was significantly associated with distant RFS (univariate, p = 0.0356; multivariate, p = 0.0439) and carcinoma death (univariate, p < 0.0001; multivariate, not done because of no other suitable factors). The prognostic significance of patient age depends on risk classification: younger age significantly predicts local recurrence in very low-risk PTC, while older age predicts worse prognosis in low- and intermediate-risk patients. These findings indicate that young age is related to rapid growth in early-phase PTC.

Prognostic factors for follicular thyroid carcinoma: the importance of vascular invasion.

The World Health Organization (WHO) classifies follicular thyroid carcinoma (FTC) into three categories: minimally invasive (mFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wFTC). This study investigated whether this classification is appropriate. We enrolled 523 patients who underwent initial surgery at Kuma Hospital between 1998 and 2015 and were diagnosed with FTC. Capsular invasion (CI) was classified as none, minimal (microscopic), or wide (macroscopic) invasion. Vascular invasion (VI) was divided according to the number of invasive foci into three degrees: VI(-), VI(1+), and VI(2+). For 507 M0 patients, age ≥55 years (p = 0.004), non-oxyphilic histology (p = 0.043), and male sex (p < 0.001) predicted poor distant recurrence-free survival (DR-FS) on univariate analysis; however, tumor size >4 cm and wide CI did not. The DR-FS rates significantly decreased from VI(-) to VI(2+) in a step-by-step fashion, including VI(-) vs. VI(1+) (p = 0.011) and VI(1+) vs. VI(2+) (p = 0.014). Multivariate analysis revealed that older age (p = 0.0004), non-oxyphilic histology (p = 0.041), male sex (p = 0.0052), VI(1+) (p = 0.017), and VI(2+) (p < 0.001) independently predicted distant recurrence. The DR-FS rates did not significantly differ among mFTC, wFTC/VI(-), and eaFTC/VI(1+). The DR-FS rate of eaFTC/VI(2+) was worse than that of eaFTC/VI(1+) (p = 0.042), but did not differ from that of wFTC/VI(1+/2+). Our findings suggest that subclassifying eaFTC according to the degree of VI and restricting wFTC to VI-positive cases would be better in the WHO classification. Revising the definition for wide CI is recommended.

Clinical outcomes of follicular tumor of uncertain malignant potential of the thyroid: real-world data.

Thyroid tumors arising from follicular cells can generally be divided into malignant and benign tumors. However, some cases are difficult to clearly diagnose whether they are benign or malignant. Therefore, in the most recent version of World Health Organization (WHO) classification, some borderline lesions such as follicular tumor of uncertain malignant potential (FT-UMP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were proposed. In this study, we investigated the clinical aspects, including the prognosis, of FT-UMP patients. We investigated the clinical features of 339 patients with FT-UMP. On ultrasound, 68% of the tumors were diagnosed as intermediate, and only 5% of those tumors were diagnosed as malignant. On cytology, 40% of the tumors were diagnosed as follicular neoplasm, and only 1% of these were suspected to be or diagnosed as malignancy. The diagnosis was based on questionable capsular invasion for 332 patients, questionable vascular invasion for 2 patients, and both for 5 patients. Eighty-six percent of the tumors showed low cell proliferation activity. To date, five patients (1%) have shown distant recurrence during postoperative follow-up and underwent various treatments such as radioactive iodine therapy, orthopedic surgery, and denosumab injection. None of these patients have died due to thyroid carcinoma. Our findings suggest that FT-UMP is generally an indolent disease, but some patients show distant recurrence. Physicians should carefully follow patients, although it remains unknown how long they should be observed after surgery.

Lipoadenoma of the parathyroid: characteristics of a rare cause of hyperparathyroidism.

Parathyroid Lipoadenoma (PLA) contains abundant mature adipose tissue and is a rare cause of hyperparathyroidism. This study aimed to investigate the clinical features of PLA in nine patients with primary hyperparathyroidism, including two men and seven women, with ages ranging from 45-84 years (median 60 years). PLA accounted for 0.5% of all parathyroid tumors during the study period. One patient presented with anorexia due to hypercalcemia; however, the other eight patients were asymptomatic. The median preoperative serum intact-parathyroid hormone (iPTH) and calcium levels were 143 pg/mL (range, 102-378) and 10.8 mg/dL (range, 10.3-11.3), respectively. PLA was difficult to identify using ultrasonography (US) as it appears as a moderately hyperechoic nodule and is difficult to distinguish from the surrounding adipose tissues. Only 33% of the lesions (three out of nine lesions) were accurately identified. However, they could be distinctly differentiated from the surrounding tissue using computed tomography (CT). All PLAs were also detected using the sesta-methoxyisobutylisonitrile single-photon emission-computed tomography (SPECT). All the patients were treated by a single gland extirpation. The median size and weight of the PLA were 14 mm (range, 10-22) and 567 mg (range, 200-1,533), respectively. In conclusion, the clinical manifestations of PLA are similar to those of ordinal parathyroid adenomas, except for their unique US and CT images. PLA should be considered as a potential etiologic factor in cases of hyperparathyroidism when the lesions are demonstrated as hyperechoic nodules or unidentified by US but detected by CT or SPECT imaging.

Observational management of papillary microcarcinoma appearing in the remnant thyroid after hemithyroidectomy.

Active surveillance for papillary thyroid microcarcinomas (PTMCs) initiated in Japan is becoming adopted worldwide as a management option. However, it remains unclear how to manage newly appearing PTMCs in the remnant thyroid after hemithyroidectomy. We investigated the outcomes of similar observational management (OM) for PTMCs appearing in the remnant thyroid after hemithyroidectomy for papillary thyroid carcinoma (PTC) and benign thyroid nodules. Eighty-three patients were newly diagnosed with PTMC in the remnant thyroid between January 1998 and March 2017. Of these, 42 patients underwent OM with >3 times ultrasound examinations. Their initial diagnoses were PTC (initially malignant group) in 37 patients and benign nodule (initially benign group) in 5 patients. We calculated the tumor volume doubling rate (TV-DR) during OM for each PTMC. The TV-DR (/year) was <-0.1, -0.1-0.1, 0.1-0.5, and >0.5 in 12, 19, 5, and 6 patients, respectively. The TV-DRs in both groups did not statistically differ, but six patients (16%) in the initially malignant group showed moderate growth (TV-DR >0.5/year). They underwent conversion surgery and none of them had further recurrence. The remaining 36 patients retained OM without disease progression. The TV-DR in the initially malignant group was not significantly associated with patients' backgrounds or their initial clinicopathological features. None of the patients in this study showed distant metastases/recurrences or died of thyroid carcinoma. Although a portion of PTMCs appearing after hemithyroidectomy for thyroid malignancy are moderately progressive, OM may be acceptable as a management option for PTMCs appearing in the remnant thyroid after hemithyroidectomy.

Histological alterations following fine-needle aspiration for parathyroid adenoma: Incidence and diagnostic problems.

This study aimed to clarify the histological alterations following fine-needle aspiration for parathyroid adenoma and discuss the occurrence of diagnostic problems. Among the 392 patients with parathyroid adenoma who underwent resection, fine-needle aspiration was performed for 21 (5.1%) parathyroid adenoma nodules. Histological findings that were significantly more frequent in cases that underwent fine-needle aspiration were considered histological alterations following fine-needle aspiration for parathyroid adenoma, including the following six findings: thick fibrous capsule (71.4%), multilayered fibrous capsules (14.3%), capsular pseudo-invasion (42.9%), fibrous bands (57.1%), hemosiderin deposition (14.3%), and tumor implantation (14.3%). Eighteen parathyroid adenoma nodules (85.7%) exhibited one or more of the six findings. Tumor cells and adipocytes entrapped within the thick fibrous capsule were occasionally observed. The fibrous bands were frequently connected to the thick fibrous capsule. The number of passes, duration between fine-needle aspiration and resection, tumor size, and purpose of fine-needle aspiration were not related to the incidence of histological findings. Because of the histological alterations following fine-needle aspiration for parathyroid adenoma that can be easily mistaken for signs of atypical adenoma or parathyroid carcinoma, we recommend that the six findings be excluded from pathological findings indicating atypical adenoma or parathyroid carcinoma in patients with preoperative fine-needle aspiration.

Long-term outcomes of cytologically benign thyroid tumors: a retrospective analysis of 3,102 patients at a single institution.

Some thyroid tumors that are cytologically diagnosed as benign may be pathologically diagnosed as malignant. Here, we investigated the long-term outcomes of patients with thyroid tumors with benign cytology, and the factors for malignancy. We retrospectively reviewed the cases of 3,102 patients with thyroid tumors >1 cm cytologically diagnosed as benign at our hospital during a 1-year period from January 2007. The median follow-up duration for all patients was 68.7 (range 0.0-168.7) months. Immediate surgery and delayed surgery were performed in 393 and 148 patients, respectively. Eventually, 541 (17.4%) of the 3,102 patients underwent a thyroidectomy, and 2,561 (82.6%) were observed without surgery. Among the surgically treated patients, the tumors of 525 (97.0%) and 16 (3.0%) were pathologically diagnosed as benign and malignant, respectively. There was no significant difference in age, gender, tumor size, serum thyroglobulin level at surgery, or the tumor volume-doubling rate (TV-DR) between the benign and malignant cases. Only the ultrasonographic findings based on our hospital's classification system were directly and significantly linked to pathological diagnosis (p < 0.01). Among the tumors of the 667 patients who were followed without surgery for >10 years, 89.9% remained unchanged and 7.2% were reduced in size. Ultrasonographic evaluation provides important information for therapeutic decision-making regarding surgery versus observation for cytologically benign tumors.

Diagnosis and management of hyalinizing trabecular tumor of the thyroid: a single-institution experience.

Hyalinizing trabecular tumor (HTT) of the thyroid is a mostly benign disease. Its cytological and pathological diagnosis is often difficult, because HTT cells and papillary thyroid carcinoma (PTC) cells share similar features (e.g., intranuclear cytoplasmic inclusions and nuclear grooves). At our institution, 38 patients were diagnosed as or highly suspected of having HTT without the possibility of PTC, based on cytology: 19 of these patients underwent immediate surgery (surgery group) and the remaining 19 underwent active surveillance without surgery (AS group). The surgery-group patients' tumor sizes were significantly larger (p < 0.0001) than those in the AS group. During AS (median 38 months), only one patient (5%) showed tumor enlargement by ≥3 mm; the AS was continued. Of the 34 patients pathologically diagnosed with HTT, 22 (65%) were cytologically diagnosed or highly suspected as having HTT without the possibility of PTC. Of the nine patients who were suspected to have HTT but PTC was possible and surgery was performed, two (22%) and seven (78%) were pathologically diagnosed as having PTC and HTT, respectively. Five patients were cytologically diagnosed with PTC, but pathologically diagnosed as having HTT. No patients showed HTT recurrence during postoperative follow-up (median 60 months). These findings suggest that (1) active surveillance can be a valid strategy for managing tumors that are cytologically diagnosed as HTT with no possibility of PTC; (2) surgery is recommended for tumors suspected of being HTT but may be PTC, and (3) the prognosis of HTT in both the AS and surgery groups was excellent.

Prognostic significance of vascular invasion and cell-proliferation activity in widely invasive follicular carcinoma of the thyroid.

Widely invasive follicular thyroid carcinoma (wi-FTC) is regarded as having an aggressive character and a dire prognosis, but it has not been known whether all wi-FTCs have a dire prognosis. Herein we retrospectively analyzed the cases of 133 patients with wi-FTCs to determine the prognostic significance of vascular invasion and cell-proliferation activity based on the Ki-67 labeling index (LI). Of the 119 patients without distant metastasis (M0), 11 (9.2%) showed recurrence during the postoperative follow-up. In a univariate analysis, the recurrence-free survival (RFS) rates of the M0 patients with vascular invasion and those with a Ki-67 LI ≥5% were significantly poorer (p = 0.0013 and p = 0.0268, respectively) than those of the patients without vascular invasion or with a Ki-67 LI <5%. Other clinicopathological factors such as patient age, gender, tumor size, and oxyphilic tumor were not significantly related to the patients' RFS. In a multivariate analysis, positive vascular invasion independently affected the RFS (p = 0.0133), but Ki-67 >5% did not (p = 0.1348). To date, only five patients have died of their thyroid carcinoma; four cases were M1. In conclusion, although M0 wi-FTC generally has a favorable prognosis, cases with positive vascular invasion or a high Ki-67 LI are likely to recur, and careful postoperative follow-up is necessary.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Subclassification of Tumor Extension and Nodal Metastasis in Papillary Thyroid Cancer to Improve Prognostic Accuracy of the Eighth Edition of the Tumor-Node-Metastasis Classification.

BACKGROUND: The eighth edition of the tumor-node-metastasis classification system (TNM-8th) reflects the prognosis of papillary thyroid cancer (PTC) better than the seventh edition. This study investigated methods to further improve the prognostic accuracy of the TNM-8th. METHODS: We enrolled 5683 patients who underwent surgery for PTC at the Kuma Hospital. We subdivided tumor extension (T4a) into T4a1 and T4a2 based on intraoperative gross findings and N1 according to size ( < 3 cm and ≥ 3 cm) based on preoperative imaging findings. RESULTS: The corresponding 20-year cancer-specific survival (CSS) rates of 4846, 403, 406, and 28 patients with TNM-8th stages I, II, III, and IVB, respectively, were 99.3%, 93.4%, 82.6%, and 11.3%. Owing to a CSS similar to that of stage II patients, N2 or T4a2 patients <55 years were upstaged to revised stage (re-stage) II. The CSS of stage III patients with T4a1 was significantly better (p < 0.0001) than that of those with T4a2, and the CSS of T4a1 patients was similar to that of stage II patients. Therefore, T4a1 patients ≥ 55 years were downstaged to re-stage II. Owing to a CSS similar to that of T4a2 stage III patients, N2 stage II patients were upstaged to re-stage III. The 20-year CSS was poorer in re-stage III (69.5%) than in stage III patients and similar in re-stage II patients (91.8%) and stage II patients. CONCLUSION: Subdivision of clinical tumor extension and node metastasis further improves the TNM-8th for PTC and identifies poor risk patients more accurately.

Prognostic Value of Extranodal Tumor Extension in Papillary Thyroid Carcinoma: Proposal for Upstaging of Cases with Extranodal Tumor Extension.

BACKGROUND: Recently, we have created a revised version of the eighth edition of the tumor-node-metastasis classification for papillary thyroid carcinomas (PTCs) by subdividing the T4a (T4a1 [moderate] and T4a2 [significant]) and N (N1 [N ≤ 3 cm] and N2 [N > 3 cm]) classifications. This re-staging better stratified patient outcomes. In this study, we investigated the prognostic significance of extranodal tumor extension (LNEx) in PTC. METHODS: Five thousand six hundred and eighty-three patients with PTC surgically treated in Kuma Hospital were enrolled. We evaluated LNEx based on intraoperative findings. RESULTS: One hundred and twenty-seven patients (2%) displayed LNEx. In contrast to what we observed for extrathyroid extension, the prognostic value of LNEx did not change based on the organ that had been invaded, and we therefore analyzed LNEx patients as a single group. In patients aged 55 or older, LNEx independently affected patients' prognoses, as did T4a2 and N2. The cancer-specific survival (CSS) of patients in Stage I but having LNEx demonstrated the similar prognosis to patients in Stage II. Further, in the subset analysis for Stage II patients aged 55 or older, LNEx had a significant prognostic value for CSS in both the univariate and multivariate analyses, as did N2. The CSS of Stage II patients aged 55 or older with LNEx did not differ from that of Stage III patients. CONCLUSIONS: It is appropriate that, similar to T4a2 or N2 patients, LNEx-positive patients younger than 55 years in Stage I and those aged 55 or older in Stage II are re-staged to II and III, respectively.

Older Age Significantly Affects Mortality of Patients with Papillary Thyroid Carcinoma Only When They Have High-Risk Features.

BACKGROUND: Old age is a known prognostic factor for mortality in patients with papillary thyroid carcinoma (PTC). This study aimed to investigate the relationship between cause-specific survival (CSS) following PTC and the extent of old age. METHODS: We enrolled 4692 patients aged ≥ 55 years with PTC who underwent surgery between 1989 and 2009 at Kuma Hospital (median follow-up period 140 months). The presence of at least one of the following was used to classify the patients as high risk: (1) tumor sizes > 4 cm, (2) node metastasis ≥ 3 cm, (3) significant extrathyroid extension corresponding to T4a, (4) extranodal tumor extension, and (5) distant metastasis. T1N0M0 PTC was classified as low risk, and all other patients were classified as intermediate risk. We divided all patients into three categories based on age: 55-64, 65-74, and ≥ 75 years. RESULTS: One low-risk patient (0.04%), 18 intermediate-risk patients (1.5%), and 105 high-risk patients (9.4%) died of PTC, and CSS of high-risk patients was poorer than that of others (p < 0.0001). The CSS of low and intermediate-risk patients did not differ with age. However, CSS of high-risk patients became significantly poorer with advancing age (p = 0.0017 for 55-64 years vs. 65-74 years, and p = 0.0109 for 65-74 years vs. ≥ 75 years). CONCLUSIONS: Advanced age has a significant prognostic impact on CSS only for high-risk patients with PTC.

Ultrasound findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features compared with those of follicular variant of papillary carcinoma and encapsulated papillary carcinoma: a single-institution study in Japan.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new entity adopted by the newest World Health Organization classification. It is differentiated from follicular variant papillary thyroid carcinoma (FVPTC) and regarded as non-malignant disease. Here, we compared the ultrasound findings of NIFTP (n = 40) with those of FVPTC (n = 94) and encapsulated PTC (encap-PTC) (n = 157). The NIFTP group showed benign findings on ultrasound significantly more frequently than the FVPTC group based on the Japan Society of Ultrasonics in Medicine criteria: a regular shape (p < 0.001), well edge definition (p = 0.007), smooth character (p < 0.001), isoechoic and homogeneous internal echoes (p < 0.001), lack of punctate microcalcification (p = 0.027), and a regular marginal hypoechoic zone (p < 0.001). Compared to encap-PTC, NIFTP has a significantly higher incidence of benign findings: isoechoic and homogeneous internal echoes (p < 0.001), lack of punctate microcalcification (p < 0.001), and a regular marginal hypoechoic zone (p = 0.004). Based on the ultrasound classification (USC) system at Kuma Hospital, no cases were classified as malignant (USC ≥3.5), but 55.4% of the FVPTCs and 53.5% of the encap-PTCs were diagnosed as malignancy. However, on cytology, the incidence of NIFTP classified as Bethesda-V or -VI (PTC) was very high at 86.9%. All patients underwent surgical treatment, but none of the NIFTP patients showed postoperative recurrence. Although avoiding surgery might be difficult because of the high incidence of malignant cytology, overtreatment (including extensive surgery) for NIFTP can be avoided by paying close attention to the lack of malignant findings on ultrasound.

Case report: exceptionally rapid growth character of hobnail variant of papillary thyroid carcinoma: a report of four cases.

The newest WHO classification adopts hobnail variant as an aggressive variant of papillary thyroid carcinoma (PTC). We here report four cases (ages 70-76 years, all females) with hobnail variant PTC treated at Kuma Hospital. Their lesions were cytologically diagnosed as PTC before surgery, but not as hobnail variant. All patients underwent a total thyroidectomy with central node dissection, and two patients also underwent therapeutic lateral node dissection. The clinical courses of three of the patients were very eventful. One patient showed recurrence to lymph nodes in the lateral compartment only 5 months after the initial surgery. In the initial surgery, one patient had a 36-mm lymph node metastasis in the lateral compartment, which was diagnosed as hobnail variant on pathology; 9 months post-surgery, metastases to the ipsilateral lateral lymph node, lung, and bone were newly detected. Her lung metastasis grew rapidly; its tumor volume-doubling time was 0.15 years and its tumor-doubling rate was 6.67/year. One patient underwent annual ultrasound examinations as postoperative follow-up after hemithyroidectomy for a benign nodule, but a 35-mm nodule diagnosed as PTC on cytology and lateral node metastases appeared within a short period, and she underwent a second surgery. Both the primary lesion and lymph nodes were diagnosed as hobnail variant by postoperative pathology. Three of the four patients showed exceptionally rapid growth of primary and/or metastatic/recurred lesions, indicating that patients with the hobnail variant should undergo very close and careful post-operative observation.

Subset analysis of the Japanese risk classification guidelines for papillary thyroid carcinoma.

Guidelines published by the Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) for patients with papillary thyroid carcinoma describe four risk classes (very low-, low-, intermediate- and high-risk) for deciding on therapeutic strategies. Here, we investigate cause-specific survival (CSS) of high- and intermediate-risk patients, taking their age into consideration. CSS of intermediate-risk patients ≥55 years was poorer than that of those <55 years (p < 0.0001) (20-year CSS rates, 96.9% vs. 98.7%). CSS of intermediate-risk patients <55 years was excellent but still poorer (p = 0.0152) than that of low- or very low-risk patients (20-year CSS rates, 100%). CSS of high-risk patients <55 years (20-year CSS rates, 96.0%) was similar (p = 0.7412) to that of intermediate-risk patients ≥55 years, while high-risk patients ≥55 years (20-year CSS rates, 80.6%) showed much poorer prognosis (p < 0.0001) than the others. In high-risk patients <55 years, distant metastasis (M1), extrathyroid extension (Ex), node metastasis ≥3 cm, and extranodal tumor extension, and in those ≥55 years, M1, Ex, and tumor size >4 cm were regarded as prognostic factors on multivariate analysis. We therefore conclude that 1) prognosis of high-risk patients ≥55 years should be carefully treated because of significantly poor prognosis, 2) prognostic factors of high-risk patients vary according to patient age, and 3) overtreatment of intermediate-risk patients and young high-risk patients should be avoided; however, appropriate treatment strategies need to be established, considering that their prognoses are excellent, but still poorer than low- or very low-risk patients.

Spontaneous Deceleration and Acceleration of Growth Rate in Medullary Thyroid Carcinomas Suggested by Changes in Calcitonin Doubling Times Over Long-Term Surveillance.

BACKGROUND: Based on our long-term observation of medullary thyroid carcinoma (MTC) patients, we hypothesized that some MTCs have spontaneous deceleration or regression of tumor growth over a long term and that a minority may acquire growth acceleration. We thus compared the calcitonin doubling time (Ct-DT) in the earlier and later half-periods of MTC patients' postoperative course. METHODS: We followed 26 MTC patients (14 hereditary and 12 sporadic MTCs) with postoperative hypercalcitoninemia with periodic measurements of serum calcitonin (Ct) for >10 years without major interventions. The median period of Ct measurements was 18.3 years (range 10.6-30.2 years). We divided the individual patients' study periods into the earlier and later halves and calculated the Ct-DTs for both periods. RESULTS: In the hereditary group, the Ct-DT in the later half-period (Later-Ct-DT) was significantly longer than that in the earlier half-period (Earlier-Ct-DT) (median 20.0 years vs. 7.1 years, p = 0.013). These values in the sporadic group were 20.0 years versus 11.1 years, respectively (p =0.774). Twelve patients (seven hereditary and five sporadic) had Later-Ct-DTs significantly longer than their Earlier-Ct-DTs (median 27.4 years vs. 4.9 years) and good prognoses. Two patients (one hereditary, one sporadic) had Later-Ct-DTs significantly shorter than their Earlier-Ct-DTs, and both developed structural recurrence and died of the disease. CONCLUSION: Many of the hereditary and some of the sporadic MTC patients had elongated Ct-DTs over a long period, suggesting spontaneous deceleration and regression of tumor growth. A minority of the MTC patients showed Ct-DT shortening, suggesting tumor growth acceleration.

Appropriateness of the revised Japanese guidelines' risk classification for the prognosis of papillary thyroid carcinoma: a retrospective analysis of 5,845 papillary thyroid carcinoma patients.

The revised Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) guidelines for patients with papillary thyroid carcinoma (PTC) describe four risk classes: very-low-risk, low-risk, intermediate-risk, and high-risk. Here we conducted a retrospective analysis to evaluate the appropriateness of these guidelines' risk classification of PTCs. Lymph node recurrence-free, distant recurrence-free and cause-specific survivals at 15-year of high-risk group were significantly poorer than those at 15-year of intermediate-group and these survivals of intermediate-group were poorer than of low- or very-low-risk patients. In the subset analyses based on patient age (≥55 years and <55 years), we obtained the same results in both subsets. Age significantly worsen the whole prognosis of high-risk patients and cause-specific survival of intermediate-risk patients, but not the prognosis of low- or very-low-risk patients. Therefore, the risk classification of the revised JAES/JSTS guidelines is appropriate, and therapeutic strategies should be decided based on the risk class together with the patients' age.

Thyroid function related symptoms during levothyroxine monotherapy in athyreotic patients.

Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT4) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT3 levels and patients with strongly suppressed serum TSH had elevated serum FT3 levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT4 after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT3 levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT4 following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.