Papillary thyroid microcarcinomas that metastasize to lymph nodes.

PURPOSE: We aimed to determine clinicopathological features that can predict lymph node metastasis (LNM) in papillary thyroid microcarcinomas (PTMC). METHODS: Medical records of 872 patients with papillary thyroid cancer >1 cm (PTC > 1 cm) and 1184 patients with papillary thyroid microcancer (PTMC) (≤1 cm) were reviewed retrospectively. Demographical, clinical and histopathological features of (PTC > 1 cm) and PTMC were compared. Association between clinicopathological features and LNM in PTMC was investigated. RESULTS: The median age of patients with PTMC was significantly higher than patients with PTC > 1 cm (49 vs 46 years old, p < 0.001). Multifocality, capsular invasion, vascular invasion, extrathyroidal extension (ETE) and LNM were more frequent in patients with PTC > 1 cm compared to patients with PMTC (p < 0.001 for each). In PTMC group, those with LNM had significantly higher proportion of multifocality, capsular invasion, vascular invasion and ETE compared to those without LNM (p = 0.007, <0.001, p = 0.011 and p < 0.001, respectively). Multifocality and ETE were significant factors for LNM with logistic regression analysis. Multifocality increased the risk of LNM by 1.737 times (95% CI: 1.079-2.979) and ETE increased the risk by 3.528 times (95%: 1.914-6.503). Primary tumor diameter ≥ 5.75 mm was predictive for LNM with a sensitivity of 0.782 and a specificity of 0.517 in PTMC. CONCLUSIONS: LNM should be investigated more carefully in patients with PTMC in the presence of tumor diameter ≥ 5.75 mm, multifocality or ETE.

Mapping of parathyroid neoplasms based on grey scale ultrasound images and histopathological whole slide images.

PURPOSE: In this study, echogenicity and histopathological projections of parathyroid neoplasia in grey mode ultrasonography were compared with whole side imaging (WSI). The utility of the data obtained for clinical assessment was evaluated. METHODS: In 57 patients operated for hyperparathyroidism, the parathyroid gland was sampled in the sagittal plane. The lesion slides were scanned. The WSI was rendered digital. The histopathological slide images scanned with USG images were matched. With the Image J program, the areas of cell types and morphological changes were measured. RESULTS: In parathyroid neoplasms, hypoechoic areas were found to be matched with 21% [55.3%] chief cell, 2 [5.0%] oncocytic cell and 8%[20.0%] cystic morphology. Of the 57 patients, 26 [45.61%] had a cystic area. It was seen that hyperechogenic areas match more connective tissue areas than chef cell [p < 0.05]. There was less clear cell in hyperechogenic areas than iso-hyperechogenic areas [p < 0.05]. The ratio of fat tissue echogenicity was lower in hypoechoic areas than hyperechoic [p < 0.05]. There was a positive correlation between PTH and the entire tissue area [r = 0.377, p = 0.004]. A positive directional moderate linear relationship was found between blood calcium level and parathyroid adenoma [rho = 0.530, p = 0.009] and percentage [rho = 0.416, p = 0.048]. When atypical adenomas and adenoma cases were compared, no significant difference was found between the cystic and chief cell areas [p > 0.05]. CONCLUSION: The hypoechogenicity seen in USG was observed to be compatible with chief cell, hyperechogenic areas in USG were compatible with connective tissue and fat tissue. As the cystic area increased, blood calcium levels were higher in adenomas. We think that the results of this study will be guiding to evaluate the reflections of the detailed morphometric studies.

SHOULD MULTIFOCAL PAPILLARY THYROID CARCINOMAS CLASSIFIED AS T1A WITH A TUMOR DIAMETER SUM OF 1 TO 2 CENTIMETERS BE RECLASSIFIED AS T1B?

OBJECTIVE: Considering the diameter of the largest tumor while determining T stage in multifocal papillary thyroid microcarcinomas (PTMCs) might cause underestimation of tumoral stage. We aimed to investigate the effect of total tumor diameter (TTD) on tumor node metastasis (TNM) classification in multifocal T1a PTMCs. METHODS: T1 tumors were grouped as T1a or T1b according to 7th TNM edition. For patients with multifocal T1a, TTD (the sum of the maximal diameter of each focus) was calculated, and these patients were further subgrouped as TTD ≤1 cm or TTD 1 to 2 cm. RESULTS: There were 724 patients with T1 tumors. Multifocality was observed in 150 (28.5%) of 527 patients with T1a and 84 (42.6%) of 197 patients with T1b tumors (P<.001). Lymph node metastasis (LNM), thyroid capsule invasion, and lymphovascular invasion were significantly higher in T1b compared to T1a (P<.001, P<.001, and P = .015, respectively). There were 8 (1.5%) patients with persistence but not any with recurrence in the T1a group. Persistence and recurrence were observed in 3 (1.5%) and 5 (2.5%) patients in the T1b group, respectively. Among 150 T1a patients with multifocal tumors, TTD was ≤1 cm in 89 (59.3%) and 1 to 2 cm in 61 (40.7%) patients. Number of tumor foci, LNM, and thyroid capsule invasion were significantly higher in multifocal T1a patients with TTD 1 to 2 cm compared to with TTD ≤1 cm (P<.001, P = .032, P = .014, respectively). CONCLUSION: TTD might be used as a parameter to determine patients at higher risk for persistence, and T1a multifocal PTMCs with TTD 1 to 2 cm can be reclassified as T1b. ABBREVIATIONS: ETE = extrathyroidal extension LNM = lymph node metastasis PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radioactive iodine TNM = tumor, node, metastasis TTD = total tumor diameter.

Can ratio of the biggest tumor diameter to total tumor diameter be a new parameter in the differential diagnosis of agressive and favorable multifocal papillary thyroid microcarcinoma?

OBJECTIVES: In this study, we aimed to evaluate the usefulness of a new parameter -ratio of the biggest tumor diameter to total tumor diameter- for the differentiation of agressive and favorable papillary thyroid microcarcinomas (PTMC). MATERIALS AND METHODS: The diameter of the biggest tumor focus was taken as the primary tumor diameter. Total tumor diameter was calculated as the sum of the maximal diameter of each lesion. Ratio of primary tumor diameter to total tumor diameter was defined as tumor diameter ratio (TDR). Positive and negative predictive value, sensitivity and specificity of TDR to predict capsular invasion, extrathyroidal extension (ETE) and lymph node metastasis (LNM) were determined. RESULTS: Mean TDR was significantly lower in multifocal PTMC patients with capsular invasion, ETE, lymphovascular invasion and LNM compared to patients without these features. The sensitivities of TDR for the detection of LNM, ETE and capsular invasion were 100%, 100% and 94.2%, respectively. Specificity of TDR was 86.2% for LNM, 88% for ETE and 94.7% for capsular invasion. Best cut off values of TDR that can predict capsular invasion, ETE and LNM in multifocal PTMC were 0.62, 0.57 and 0.56, respectively. Multifocal papillary thyroid carcinoma patients with capsular invasion, ETE and LNM had significantly lower mean TDR when compared to ones without these features. CONCLUSION: Decreased TDR was associated with capsular invasion, ETE and LNM in patients with multifocal PTMC and PTC. This new parameter might be particularly helpful for the detection of aggressive behavior in multifocal PTMCs.

Concomitant thyroid lesions in patients with primary hyperparathyroidism.

BACKGROUND: Concomitant thyroid pathologies in patients with primary hyperparathyroidism (PHPT) present a challenge in the clinical and surgical decision-making for these patients. In this study, we aimed to evaluate concomitant thyroid pathologies in patients who underwent operations for PHPT to determine the sensitivity (Sn) of neck ultrasonography (US) and Tc99m sestamibi scintigraphy in detecting parathyroid adenoma. We also aimed to determine the clinical impact of preoperative neck US in patients with PHPT. METHODS: One hundred thirty-eight patients with PHPT were included in this retrospective study. All patients underwent preoperative Tc99m sestamibi scintigraphy and/or thyroid US. Nodules of ≥1 cm or <1 cm with suspicious US features underwent fine needle aspiration biopsy (FNAB). RESULTS: Preoperative thyroid US revealed that 93.5% of patients with PHPT had thyroid abnormalities and 66.7% of patients had at least one thyroid nodule. Postoperative histopathology results showed that 79.2% of patients had benign thyroid disease and 20.8% of patients had malignant thyroid disease. In the detection of parathyroid adenoma, US had 89.1% Sn and Tc99m sestamibi scintigraphy had 82.6% Sn. CONCLUSION: We recommend the routine use of US in combination with Tc99m sestamibi scintigraphy, especially in endemic goiter regions, to detect any concomitant thyroid disease and thus determine the best surgical strategy for patients with PHPT.

Importance of ectopic thyroid tissue detected in the midline of the neck: single center experience

Objective Ectopic thyroid tissue (ETT) is a rare abnormality of the thyroid gland and the true prevalence and importance is not known. The aim of this study was to evaluate ultrasonography (US) guided fine needle aspiration biposy (FNAB) results, sonographic features, and frequency of ETT detected in the midline of the neck. Subjects and methods Five thousand five hundred and twenty outpatients who were referred to our thyroid clinic between September 2010 and April 2012 and underwent thyroid US, were retrospectively analyzed. Patients with ETT, detected in the midline of the neck in US were included in the study. Thyroid functions, sonographic features, and US guided FNAB results were evaluated. Results There were 81 (81.8%) female and 18 (18.2%) male patients with a mean age of 50.9 ± 11.7. The ETT in the midline was present in 1.79% (99/5,520) of the patients. In the majority of the patients, benign sonographic features (isoechoic, regular margin, type 1 vascularization) were detected. There were 92 (92.9%) patients with a previous history of thyroidectomy and all were histopathologically benign. In 7 (7.1%) patients, there was no history of thyroid operation. FNAB results of ETT were benign. Conclusion This study evaluated the importance of ETT detected incidentally in the midline of the neck. Especially in patients with a history of thyroidectomy, the thyroid masses in the midline of the neck can be found as incidental with imaging methods. Our results suggests that the incidence of malignancy in this group is much lower than orthotopic thyroid nodules and they are often benign.

Association of multifocality, tumor number, and total tumor diameter with clinicopathological features in papillary thyroid cancer.

Tumor multifocality is not an unusual finding in papillary thyroid carcinoma (PTC), but its clinical significance is controversial. In this study, we aimed to evaluate impact of multifocality, tumor number, and total tumor diameter on clinicopathological features of PTC. Medical records of 912 patients who underwent thyroidectomy and diagnosed with PTC were reviewed retrospectively. Patients were grouped into four according to number of tumoral foci: N1 (1 focus), N2 (2 foci), N3 (3 foci), and N4 (≥4 foci). The diameter of the largest tumor was considered the primary tumor diameter (PTD), and total tumor diameter (TTD) was calculated as the sum of the maximal diameter of each lesion in multicentric tumors. Patients were further classified into subgroups according to PTD and TTD. Multifocal PTC was found in 308 (33.8 %) patients. Capsular invasion, extrathyroidal extension, and lymph node metastasis were significantly higher in patients with multifocal tumors compared to patients with unifocal PTC. As the number of tumor increased, extrathyroidal extension and lymph node metastasis also increased (p = 0.034 and p = 0.004, respectively). The risk of lymph node metastasis was 2.287 (OR = 2.287, p = 0.036) times higher in N3 and 3.449 (OR = 3.449, p = 0.001) times higher in N4 compared to N1. Capsular invasion, extrathyroidal extension, and lymph node metastasis were significantly higher in multifocal patients with PTD ≤10 mm and TTD >10 mm than unifocal patients with tumor diameter ≤10 mm (p < 0.001, p < 0.001 and p = 0.001, respectively). There was no significant difference in terms of these parameters in multifocal patients with PTD ≤10 mm and TTD >10 mm and unifocal patients with tumor diameter >10 mm. In this study, increased tumor number was associated with higher rates of capsular invasion, extrathyroidal extension, and lymph node metastasis. In a patient with multifocal papillary microcarcinoma, TTD >10 mm confers a similar risk of aggressive histopathological behavior with unifocal PTC greater than 10 mm.

A new approach for standardization and increased accuracy of lymph node washout thyroglobulin in patients with differentiated thyroid carcinoma.

BACKGROUND: High values of fine needle aspiration washout thyroglobulin (FNAB-Tg) are diagnostic for metastatic lesions of thyroid cancer. However, there is not a consensus on cutoff for high FNAB-Tg level. In this study, we aimed to determine a more accurate and standardized parameter for FNAB-Tg. METHODS: Ultrasonographically suspicious lymph nodes of patients with histopathologically confirmed differentiated thyroid cancer or malignant/suspicion for malignancy cytology were included. Tg washout was obtained by aspiration and nonaspiration fine needle biopsy (nonaspiration-FNB). Simultaneous Tg was measured from serum. Aspiration and washout procedures were also performed from whole blood and serum using syringes and needles identical to ones used for lymph node biopsy. RESULTS: Data of 19 lesions in 17 patients who underwent lymph node dissection were analyzed. Nonaspiration FNB-Tg, FNAB-Tg/whole blood washout-Tg, nonaspiration FNB-Tg/whole blood washout-Tg, nonaspiration FNB-Tg/serum washout-Tg, nonaspiration FNB-Tg/serum Tg ratios were significantly higher in malignant lymph nodes compared to benign ones. Areas under the ROC curve for nonaspiration FNB-Tg, FNAB-Tg/whole blood washout-Tg, FNAB-Tg/serum washout-Tg, nonaspiration FNB-Tg/whole blood washout-Tg, nonaspiration FNB-Tg/serum washout-Tg, and nonaspiration FNB-Tg/serum Tg were statistically significant for the discrimination of benign and malignant lymph nodes. Best cutoff value for nonaspiration FNB-Tg was 4.21. Among ratios, best cutoff values were 5.40 for nonaspiration FNB-Tg/whole blood washout-Tg and 3.28 for nonaspiration FNB-Tg/serum washout-Tg. CONCLUSION: For detection of malignant lymph nodes, determining ratios of nonaspiration FNB-Tg to whole blood and/or serum washout-Tg might be a promising method to increase accuracy and provide standardization of lymph node washout procedure.

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis.

OBJECTIVE: To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein-induced acute pancreatitis. MATERIAL AND METHODS: In 30 Wistar albino rats (male; 240-260 g), acute pancreatitis was induced by an intraperitoneal injection of cerulein (50 µg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained. RESULTS: Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose-dependent manner (35% in Group 2, 75% in Group 3; p=0.048). CONCLUSION: Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied the specific inhibition of inflammatory response pathways.

Importance of ectopic thyroid tissue detected in the midline of the neck: single center experience.

OBJECTIVE: Ectopic thyroid tissue (ETT) is a rare abnormality of the thyroid gland and the true prevalence and importance is not known. The aim of this study was to evaluate ultrasonography (US) guided fine needle aspiration biposy (FNAB) results, sonographic features, and frequency of ETT detected in the midline of the neck. SUBJECTS AND METHODS: Five thousand five hundred and twenty outpatients who were referred to our thyroid clinic between September 2010 and April 2012 and underwent thyroid US, were retrospectively analyzed. Patients with ETT, detected in the midline of the neck in US were included in the study. Thyroid functions, sonographic features, and US guided FNAB results were evaluated. RESULTS: There were 81 (81.8%) female and 18 (18.2%) male patients with a mean age of 50.9 ± 11.7. The ETT in the midline was present in 1.79% (99/5,520) of the patients. In the majority of the patients, benign sonographic features (isoechoic, regular margin, type 1 vascularization) were detected. There were 92 (92.9%) patients with a previous history of thyroidectomy and all were histopathologically benign. In 7 (7.1%) patients, there was no history of thyroid operation. FNAB results of ETT were benign. CONCLUSION: This study evaluated the importance of ETT detected incidentally in the midline of the neck. Especially in patients with a history of thyroidectomy, the thyroid masses in the midline of the neck can be found as incidental with imaging methods. Our results suggests that the incidence of malignancy in this group is much lower than orthotopic thyroid nodules and they are often benign.

Cytomorphologic features and ultrasonographic characteristics of thyroid nodules with Hurthle cells.

This study was designed to evaluate the ultrasonographic and histopathologic features of nodules composed predominantly of Hurthle cells detected during cytological examination. Fifty-seven patients with thyroid nodules composed predominantly of Hurthle cells on fine needle aspiration cytology were retrospectively analyzed. Patients were evaluated by thyroid ultrasonography (US), and biopsy samples taken by US-guided fine needle aspiration cytology were assessed histopathologically. There were 57 patients and 57 nodules with Hurthle cells in cytological examination; 49 (86%) were classified as Bethesda 1, and 8 (14%) were classified as Bethesda 3. Histopathologically, 45 (78.9%) nodules were benign and 12 (21.1%) were malignant. Nuclear groove, transgressing blood vessel, and absence of colloid were observed with a higher frequency in malignant nodules compared to benign nodules (P < .05). There were no specific morphological features (nodule echogenity, presence of microcalsification, presence of cystic areas, absence of halo, margin irregularity, and increased blood flow) predicting malignancy in the US evaluation of nodules including Hurthle cells. Nuclear groove, transgressing blood vessel, and absence of colloid on cytomorphological evaluation are indicative of malignancy in nodules containing Hurthle cells.

Malignancy rate of thyroid nodules defined as follicular lesion of undetermined significance and atypia of undetermined significance in thyroid cytopathology and its relation with ultrasonographic features.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as the most accurate, safe, and cost-effective method for evaluation of thyroid nodules. The most challenging category in FNAB is atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS). The Bethesda system (BS) recommends repeat FNAB in that category due to its low risk of malignancy. In our study, we aimed to investigate the malignancy rate of thyroid nodules of AUS and FLUS and whether there were different malignancy rates among the different patterns in this category, and to evaluate the presence of biochemical, clinical, and echographic features possibly predictive of malignancy related to AUS and FLUS. Data of 268 patients operated for AUS and FLUS cytology were screened retrospectively. Ultrasonographic features and thyroid function tests, thyroid antibodies, scintigraphy, and histopathological results were evaluated. Of the 268 patients' results, 276 nodules are evaluated. Malignancy rates were 24.3 % in the AUS group, 19.8 % in the FLUS group, and 22.8 % in both groups. In the evaluation of all nodules, the predictive features of malignancy are hypoechogenicity and peripheral vascularization of the nodule. We determined that the malignancy rates in these nodules are higher than that in the literature rate. This high ratio may be due to the fact that we studied only patients who underwent surgery. The ultrasonographic features alone may be insufficient to predict the malignancy; therefore, all the clinical and ultrasonographic features must be considered in the evaluation of the thyroid nodules. In addition, we think that the recommended management of repeat FNAB in these groups must be reconsidered with the clinical and ultrasonographic features.