Diagnostic pitfalls and therapeutic outcomes of the macrofollicular variant of papillary thyroid carcinoma.

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.

The effect of suppressive thyroxine therapy in nodular goiter in postmenopausal women and 2 year's bone mineral density change.

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.

Differentiation of the Follicular Variant of Papillary Thyroid Carcinoma From Classic Papillary Thyroid Carcinoma: An Ultrasound Analysis and Complement to Fine-Needle Aspiration Cytology.

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.

Therapeutic Outcomes of Patients with Multifocal Papillary Thyroid Microcarcinomas and Larger Tumors.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Incidences of cancers in diabetic and non-diabetic hospitalized adult patients in Taiwan.

BACKGROUND: The study was to investigate the relationship between diabetes mellitus ( DM), specific cancers, age, and gender. METHODS: 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. RESULTS: 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%; P<0.001), and males had a higher cancer incidence than females (20.2% vs 13.5%; P<0.001). 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. CONCLUSIONS: 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.

Well-differentiated thyroid carcinoma with concomitant Hashimoto's thyroiditis present with less aggressive clinical stage and low recurrence.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common differentiated thyroid cancers. Previous studies report that Hashimoto's thyroiditis (HT) concomitant with PTC is unusual and improves prognosis compared to classical PTC. Few previous studies address FTC concomitant with HT. In this study, we retrospectively analyzed data from one institution and compared clinical presentations and results of treatment of PTC and FTC with and without HT. In addition, studies comparing presentation and long term follow-up prognosis in classical PTC and FTC were conducted. A total of 1,788 PTC patients and 209 FTC patients underwent thyroidectomy with or without lymph node dissection and follow-up at Chang Gung Medical Center in Linkou, Taiwan. All thyroid carcinomas were pathologically classified according to World Health Organization criteria. Histological patterns of PTC were categorized as classical PTC, or PTC with HT. Follicular thyroid carcinoma patients were categorized as FTC or FTC with HT. The dataset contained a total of 1,703 PTC cases categorized as classical PTC, 85 cases of PTC with HT, 201 cases of FTC and eight cases of FTC with HT. Analysis of Classification of Malignant Tumors (TNM) stage revealed a higher percentage of classical PTC in stage IV than HT group (12.03% vs. 4.70%). Mean tumor size of classical PTC was larger than HT group. Although 42.3% of FTC cases presented with distant metastases, no cases of FTC with HT presented with distant metastasis. Cancer-specific mortality was higher in classical PTC group than in PTC with HT. There was 53.2% of FTC without HT assigned recurrent status, and six of them died of thyroid cancer. No cancer mortality or recurrence in HT with FTC. PTC and FTC with HT presented with better clinical stage and better prognosis after same therapeutic modality. In conclusions, both PTC and FTC with HT have less aggressive clinical presentation and better prognosis.

Therapeutic outcomes of papillary thyroid cancer patients in different risk groups.

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.

Papillary thyroid carcinoma with different histological patterns.

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.

Sonography and fine-needle aspiration biopsy in the diagnosis of benign versus malignant nodules in patients with autoimmune thyroiditis.

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 Hürthle 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.

Thyroid cancer in the thyroid nodules evaluated by ultrasonography and fine-needle aspiration cytology.

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 Hürthle 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.