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Background: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. Methods: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. Result: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. Conclusions: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

The efficacy of thyroxine suppressive therapy in reducing nodular growth and its effect to bone mineral density (BMD) in postmenopausal women is still debated. This study aimed to evaluate the therapeutic effect of thyroxine and its influence on BMD. Postmenopausal women with nodular or multinodular goiter during 2013-2015 at Chang Gung Memorial Hospital were enrolled and retrospectively traced back to the first date of visit or treatment. Ninety-four eligible patients were enrolled, of whom 45 were thyroxine-treated (LT-4 group) and 49 were treatment-naïve (control group). Data, including volume of nodules, were analyzed retrospectively. BMD was measured in each LT-4 group patient since the year of enrollment. Nodular volumes were reduced in both LT-4 (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, p = 0.033) and control group (3.48 ± 4.36 to 3.09 ± 2.88 mL, p = 0.239) at initial 2-year follow-up. Nodular volume in LT-4 group increased insignificantly (from 4.89 ± 4.46 to 4.91 ± 5.40 mL, p = 0.711) at the end of 7-year follow-up. The best cut-off predictive nodular volume that may have responded to thyroxine is 2.6 mL (AUC, 0.740; sensitivity, 0.750; specificity, 0.733) during first 2 year. Lumbar spine, total hip and femoral neck BMD were not significantly changed during 2 year's thyroxine suppression therapy. In conclusion, thyroxine suppressive therapy in postmenopausal women had significant reduction in nodule volume at initial 2 years of treatment, especially in volume larger than 2.6 mL. Prolonged thyroxine treatment did not benefit nodular size reduction and may affect BMD minimally in postmenopausal women.

Objectives It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. Methods The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. Results The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I–III) had a median US risk score of 6 (range, 0–11), which was higher than that of nodules with high categorization (IV–VI; median, 3; range, 0–11). Conclusions The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

Objective: The objective of this study was to determine the therapeutic outcome of papillary thyroid cancer (PTC) patients in different risk groups in one institute. Methods: A total of 1,759 PTC patients were categorized into low- (n = 1,123), intermediate- (n = 75), and high-risk (n = 561) groups according to tumor-node-metastasis (TNM) stage. Results: Of the patients, 15.1% presented with lymph node metastases, and 4.6% presented with distant metastases at the time of thyroid operation. After 8.0 ± 0.1 years of follow-up, 73 (4.2%) patients died of thyroid cancer. Tumor size, local invasion, and lymph node metastases adversely influenced recurrence and survival. Of the patients in the 3 groups, 9 (0.8%), 8 (10.7%), and 56 (10.0%) died of thyroid cancer, respectively. In addition, 88 (7.8%), 14 (18.7%), and 144 (25.8%) patients showed recurrence during the follow-up period. Patients with highly aggressive histological patterns showed increased recurrence and cancer mortality compared with the low-risk group; otherwise, values were not higher than those of the high-risk group. Conclusions: The cancer-related mortality was nearly 10% in the intermediate- and high-risk groups, and the patients in these groups required aggressive surgical and postoperative adjuvant therapies.

Purpose. To correlate sonographic (US) characteristics and results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with surgical pathological findings. Method. Forty AT patients with 40 nodular lesions were analyzed retrospectively. Five sonographic characteristics were recorded for each nodule: diameter, echogenicity, microcalcification, halo sign, and margin. Preoperative sonograms and FNAB results were compared with postoperative histopathological findings. Result. Twenty-four of the 40 nodules were malignant, including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic thyroiditis, and 1 each follicular adenoma and Hurthle cell adenoma. The only US parameter that was significant in malignant vs. benign nodules was the presence of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly identified. The positive predictive value was 78.6%, and the negative predictive value was 93.7%. Conclusion. No single US parameter can predict thyroid malignancy in patients with AT. A combination of US and FNAB provides the most sensitive and specific approach available preoperatively. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009

There is limited clinical information comparing presentations and results of treatment of papillary and follicular thyroid carcinoma patients with distant metastases. We retrospectively analyzed data of 1,257 thyroid cancer patients who received their treatment and follow-up at Chang Gung Memorial Hospital. We found 992 patients with papillary carcinoma and 205 patients with follicular thyroid carcinoma. Of these, 68 patients with papillary thyroid carcinoma (6.9%) had distant metastases at the time of diagnosis or during the follow-up period. Of the follicular thyroid carcinoma patients, 69 (33.7%) had distant metastases. Of the 68 patients with papillary carcinoma, only 33 were categorized as stage IV at the time of diagnosis. Nine of the patients were categorized as clinical stage I carcinoma, 10 as stage II, and 16 as stage III. Sixteen patients (23.5%) died during the study period, all but 2 of thyroid cancer. Twelve of the 68 patients were disease-free after treatment. Of the 69 patients with follicular thyroid carcinoma, 58 were categorized as stage IV at the time of diagnosis. Six of the patients were categorized as clinical stage I carcinoma, 2 as stage II, and 3 as stage III at the time of diagnosis; all of these patients deteriorated to stage IV during the follow-up period. Of the 42 patients with follicular thyroid carcinoma involving bone, 24 presented with bone metastases during the initial diagnosis. After treatment, 25 of 69 patients with follicular carcinoma died of follicular carcinoma. Only 3 patients were disease-free after the treatment. In patients with follicular carcinoma, only tumor size was an important prognostic factor. In this study, 8 patients categorized as clinical stages I to III at the time of operation had thyroglobulin (Tg) levels less than 5 ng/mL and developed distant metastases during the follow-up period. In conclusion, at diagnosis a large group of Asian patients with metastatic well-differentiated thyroid cancer was more likely to have follicular than papillary histology, and that, as expected, metastases from follicular cancer were present earlier and more frequently, were more likely to involve bone, were more likely to be associated with mortality, and were linked to tumor size but not gender. Also unlike some other reports, treatment producing a low Tg did not always produce a good outcome. More aggressive surgical procedures may be able to improve outcomes.

OBJECTIVE To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.

The study was to investigate the relationship between diabetes mellitus ( DM), specific cancers, age, and gender.This was a retrospective study that examined the frequency of different forms of cancer among male and female patients with or without DM admitted to a single hospital in Taiwan between January 2009 and June 2010.Of 101,002 study patients admitted to the hospital, 15,901 (15.74%) were diagnosed with DM and 16,748 (16.58%) with a malignancy. The frequency of DM differed between males and females (17.5% vs 14.2%; P0.001), and males had a higher cancer incidence than females (20.2% vs 13.5%; P0.001). Patients with DM had a greater frequency of cancer diagnosis than non-DM patients (18.1% vs 16.3%, respectively), with pancreatic, liver, uterine, urinary tract, lung, and secondary cancers being more frequent in DM compared with non-DM patients. In contrast, the proportion of patients with thyroid, esophagus, breast, NPC, and other cancers was lower in DM versus non-DM patients.This study found that DM was associated with the incidence of specific cancers and that males had a higher frequency of cancer than females. The association of DM and cancer depended upon cancer type, gender, and age.

Tumor-node-metastasis (TNM) staging is the most commonly used model for evaluating therapeutic strategies for papillary thyroid cancer (PTC). Additionally, different histopathological patterns and variants of PTC have been reported to influence the prognosis of these patients. We reviewed the clinical presentation, cancer recurrence, and cancer-specific mortality of the most frequent histological patterns, including the follicular variant (FVPTC), insular pattern, tall cell pattern, diffuse sclerosing type, PTC with Hashimoto's thyroiditis, and multicentric PTC. The tall cell variant of PTC is a more aggressive variant than classical PTC and has a poor prognosis. The high expression of Muc 1 and type IV collagenase in these tumors may facilitate stromal degradation and increase the invasive potential. In contrast, approximately 18% of PTC patients have been identified as having FVPTC. FVPTC patients have a better survival rate than those with follicular thyroid cancer, and fewer instances of lymph node or soft tissue invasion than control patients with classical PTC. The diffuse sclerosing variant of PTC predominantly observed in young patients is a rare aggressive tumor that requires intensive treatment. Despite characteristic clinical and histological features that facilitate easy diagnosis, pre-operative fine needle aspiration cytological diagnosis of this variant is often challenging. Different histological variants of PTC with other histological patterns are important for predicting cancer recurrence. In addition to TNM staging, high-risk histological patterns of PTC require more aggressive follow-up examinations and postoperative adjuvant therapies.

Thyroid nodule is common disorder in endocrine clinics. In Taiwan, thyroid ultrasonography with fine-needle aspiration cytology (FNAC) is the first-line examination procedure. Data in large series on the incidence of thyroid malignancy presenting with thyroid nodules are lacking in this area. To determine the incidence of malignancy in thyroid nodules and compare the results with other populations, this investigation retrospectively reviewed 21,748 subjects who were examined in one medical center from January 1986 to December 1999. All patients underwent thyroid ultrasonography studies using a real-time ultrasonographic machine and a 10-MHz transducer. Fine-needle aspirations were made in the suspected thyroid nodule and stained using the Romanowsky- based method developed by Liu. By the end of 2002, some 3629 patients (16.7%) had thyroid nodules after surgical treatment. This group comprised 3011 women with a mean age of 41.5 +/- 13.9 years, and 618 men with a mean age of 45.7 +/- 14.9 years. Of patients undergoing surgical treatment, 2761 (76.1%) patients were diagnosed with benign nodules, 858 (23.6%) with malignant nodules, and 10 (0.3%) with atypical adenoma (7 follicular and 3 Hurthle cells). The percentages of thyroid malignancy in each age group revealed two peaks in both genders, namely in patients aged 20 to 29 years and in elderly patients (aged over 65 years). The peak age for thyroid malignancy in both genders was 41 to 60 years (male) and 21 to 40 years (female). The highest ratio of malignancy occurred in the elderly group (37.2%) receiving surgical treatment. In young patients (below 19 years) the percentage of malignancy was no greater than for the whole age group (20.2% versus 25.6%). Anaplastic and metastatic cancers affecting the thyroid were the main subjects in the age group. The present results demonstrated a younger distribution for well-differentiated thyroid cancer, particularly papillary thyroid carcinoma, compared to previous studies. This outcome may have resulted from the routine application of ultrasonography with FNAC in assessing the thyroid nodules, possibly helping to achieve more timely detection. The incidence of thyroid malignancy in young patients was no higher than in adults. Early detection of thyroid malignancy may be the main reason for this phenomenon. Male subjects with thyroid nodules displayed a higher incidence of this malignancy than females. Aging subjects with thyroid nodules suffered a higher rate of malignancy and were poorly differentiated. In conclusion, this retrospective large-series study demonstrated that 3.9% (858/21,748 cases) of patients with thyroid nodules showed histopathologically proven malignancy. Thyroid cancer detected by ultrasonography with FNAC occurred an average of 10 years younger than in prior studies.

We assessed the accuracy of ultrasonography and fine-needle aspiration cytology (FNAC) in diagnosing cystic thyroid cancer and compared the results with solid thyroid cancer patients. We also compared the results of treatment between these patient groups. We retrospectively reviewed 1013 thyroid cancer patients who received treatment at Chang Gung Memorial Hospital. For this study, 910 cases of papillary or follicular thyroid carcinomas were considered eligible. Of these, 682 patients received preoperative high-resolution ultrasonographic and FNAC examinations. The nodules of 583 (85.5%) patients were diagnosed as solid masses, 80 (11.7%) as mixed masses, and 19 (2.8%) as cystic masses. Of the 19 patients with cystic thyroid carcinoma, only 4 papillary thyroid carcinomas were diagnosed by ultrasonography with FNAC as malignant before operation. Six patients presented as occult thyroid carcinomas with the tumor size less than 1 cm. Despite the low rate of accurate diagnosis for the cystic malignancy, clinical staging and the survival rates were not statistically different when they were compared with the other groups. In conclusion, low diagnostic rates were observed in well-differentiated thyroid cancer with prospective ultrasound-guided FNA when lesions were cystic or in mixed lesions. If the solid portion of the cystic masses is aspirated under ultrasound-guided FNA and cytology is performed after the centrifugation of the aspirated fluid, diagnostic accuracy may be improved.

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hurthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P

To investigate the value of serum alkaline phosphatase in evaluating hyperplasia of parathyroid glands in hemodialysis patients, 28 hemodialysis patients who had parathyroid sonography examinations for secondary hyperparathyroidism were studied retrospectively. There were significant elevations of serum alkaline phosphatase, parathyroid hormone (PTH), serum total calcium, and dialysis duration in patients with sonography-detectable parathyroid (N = 17) as compared with those of sonography-undetectable (N = 11) parathyroid. Hemodialysis patients who have both higher serum alkaline phosphatase (> 94 IU/L) and considerably elevated serum PTH (9 x or higher) are likely to have sonography-detectable parathyroids (positive predictive value of 93%). Patients with mildly or moderately elevated serum PTH but normal serum alkaline phosphatase are less likely to have sonography-detectable parathyroids (negative predictive value is 100%). These findings suggest that the elevation of serum alkaline phosphatase could be a valuable parameter in addition to the high serum PTH level in predicting hyperplasia of parathyroid glands in chronic hemodialysis patients.

SUMMARY To investigate the natural killer (NK) cell mediated immunity in Graves' disease (GD) and the effect of antithyroid drugs upon NK cell activity, 51Cr release assay for NK cytotoxicity against K562 cells was examined in patients with GD before and during antithyroid medication and after drug withdrawal. Fifty-eight patients were divided into three groups: the untreated thyrotoxic patients (n= 33), the euthyroid patients under antithyroid treatment (n= 19) and the euthyroid patients after drug withdrawal (n= 6). The results of the three groups were compared to 23,15 and 5 sex- and age-matched controls, respectively. The data revealed a significant NK dysfunction in the untreated hyperthyroid patients, although the number of the NK cells was not decreased. NK function was normal when patients were no longer taking antithyroid medication and in euthyroid state. However, euthyroid patients under antithyroid medication had markedly depressed NK activity, suggesting an immunosuppressive effect of the antithyroid drugs. This study demonstrated that both the hyperthyroid state and the antithyroid drugs exerted immunosuppressive effects upon the NK cells. Since such an immunosuppressive effect on NK cells might be associated with a decreased immune surveillance against tumour growth, this study implies that a long-term follow up of GD patients treated with antithyrdid drugs may be indicated to guard against a possible increased incidence of malignancy.