Central Compartment Lymph Node Dissection Research Articles

Can Calcitonin Levels Guide Prophylactic Neck Dissection in Sporadic Medullary Thyroid Carcinoma?

Medullary thyroid carcinoma (MTC) comprises less than 5% of thyroid cancers but is responsible for over 10% of deaths related to thyroid cancer. Regional lymph node metastasis is common and associated with mortality, thus total thyroidectomy with central compartment lymph node dissection is the standard surgical treatment for MTC. In this best practice submission, we aim to review the existing literature and determine whether calcitonin levels can serve as a reliable method for risk-stratifying MTC without overt lymph node involvement.

Outcome of Total Thyroidectomy Versus Total Thyroidectomy + Prophylactic Central Compartment Lymph Node Dissection in Intrathyroidal Papillary Thyroid Carcinoma: A Propensity Score-Matched Analysis

Outcome of Total Thyroidectomy Versus Total Thyroidectomy + Prophylactic Central Compartment Lymph Node Dissection in Intrathyroidal Papillary Thyroid Carcinoma: A Propensity Score-Matched Analysis

Carbon nanoparticles beneficial for prophylactic central compartment lymph node dissection in cN0 papillary thyroid carcinoma

ObjectiveThis study explored prophylactic central compartment lymph node dissection (pCCLND) for patients with cN0 papillary thyroid carcinoma (PTC) and the effect of carbon nanoparticles (CNP) on surgical outcomes. MethodsThis retrospective study reviewed PTC cases treated at our tertiary medical institution between January 2019 and December 2022. Only patients with indications for total thyroidectomy and cN0 disease were included. CNP has been associated with a higher number of harvested lymph nodes and a lower rate of accidental parathyroid gland (PTG) removal. Patients who used CNP in this study were classified as group 1, while those who denied its use were classified as group 2. ResultsIn total, 116 cases were included, with 80 patients in group 1 and 36 in group 2. Most patients were in stage T1, with 68 (85.0 %) patients in group 1 and 31 (86.1 %) in group 2. Postoperative hoarseness occurred in 3 (3.8 %) patients in group 1 and 1 (2.8 %) in group 2, which recovered within two months. In group 2, 250 nodes were harvested, 72 (28.8 %) of which were metastatic; in group 1, 889 nodes were harvested, 316 (35.5 %) of which were metastatic; the difference regarding the rates of metastatic lymph nodes between the 2 groups was statistically significant (P = 0.047). Differences in postoperative blood calcium and parathyroid hormone levels between the two groups were statistically significant (P = 0.035 and P = 0.034, respectively). There were symptoms of hypocalcemia in 6 (16.7 %) patients in group 2 but in only 2 (2.5 %) in group 1, all of which recovered within three months; the difference was statistically significant (p = 0.017). ConclusionpCCLND is worth undertaking for cN0 PTC. CNP is beneficial for achieving more thorough dissection and reducing temporary hypoparathyroidism.

Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.

Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized. Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis. In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months). PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.

Central Compartment Involvement in T3 & T4 Papillary Thyroid Carcinoma

Background: Lymphatic metastasis in papillary thyroid cancer (PTC) is common; however, the extent of central compartment lymph nodes dissection (CCD) is controversial and requires the knowledge of pattern for central compartment (level VI) lymph nodes metastasis (CCM).
 Objective: To determine the frequency of central compartment (level VI) lymph node metastasis in T3 & T4 papillary thyroid carcinoma.
 Methods: This study was conducted in the Department of Otolaryngology-Head &Neck Surgery, BSMMU, Dhaka, from January 2019 to June 2020. A total of 31 cases of T3 & T4 PTC were selected after obtaining clearance and approval from the IRB of BSMMU; the subjects were included based on the inclusion and exclusion criteria. After taking informed written consent detailed history and examination was done. Ultrasound neck and fine-needle aspiration cytology was taken from all thyroid swelling. All patients had underwent total thyroidectomy with central compartment dissection. The data were analyzed by computer-based statistical software SPSS version 26. Results were expressed as frequency and percentage. Z proportion test was done as applicable.
 Results: In this study, mean (±SD) tumor size was 3.66 (±1.34) cm. 20 (64.52%) had T3 and 11 (35.48%) T4 PTC. 11 (35.48%) had N0, 20 (64.52%) N1a and 8 (25.81%) N1b. 20 (64.52%) had overall central compartment lymph nodes metastasis. Among T3 papillary thyroid carcinoma, 12 (60%) had overall central compartment lymph nodes metastasis, and inT4 papillary thyroid carcinoma, 8 (72.7%) had overall central compartment lymph nodes metastasis. This difference was not statistically significant.
 Conclusion: The frequency of central compartment (level VI) lymph node metastasis (CCM) is high (64.52%) in T3 & T4 papillary thyroid carcinoma. So central compartment (level VI) should be dissected in advanced (T3 & T4) papillary thyroid carcinoma.
 Bangladesh J Otorhinolaryngol 2022; 28(2): 149-156

Modification and application of "zero-line" incision design in total endoscopic gasless unilateral axillary approach thyroidectomy: A preliminary report.

Gasless unilateral trans-axillary approach (GUA) thyroidectomy has witnessed rapid development in technologies and applications. However, the existence of surgical retractors and limited space would increase the difficulty of guaranteeing the visual field and disturb safe surgical manipulation. We aimed to develop a novel zero-line method for incision design to access optimal surgical manipulation and outcomes. A total of 217 patients with thyroid cancer who underwent GUA were enrolled in the study. Patients were randomly classified into two groups (classical incision and zero-line incision), and their operative data were collected and reviewed. 216 enrolled patients underwent and completed GUA; among them, 111 patients were classified into the classical group, and 105 patients were classified into the zero-line group, respectively. Demographic data, including age, gender, and the primary tumor side, were similar between the two groups. The duration of surgery in the classical group was longer (2.66 ± 0.68 h) than in the zero-line group (1.40 ± 0.47 h) (p < 0.001). The counts of central compartment lymph node dissection were higher in the zero-line group (5.03 ± 3.02 nodes) than that in the classical group (3.05 ± 2.68 nodes) (p < 0.001). The score of postoperative neck pain was lower in the zero-line group (1.0 ± 0.36) than that in the classical group (3.3 ± 0.54) (p < 0.05). The difference in cosmetic achievement was not statistically significant (p > 0.05). The "zero-line" method for GUA surgery incision design was simple but effective for GUA surgery manipulation and worth promoting.

Robotic versus endoscopic transoral thyroidectomy in papillary thyroid cancer: A comparative analysis of surgical outcomes in 240 consecutive patients.

This study compared the surgical outcomes of transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transoral robotic thyroidectomy (TORT) in papillary thyroid cancer (PTC). The TOETVA and TORT groups comprised 119 and 121 patients between November 2016 and May 2022. Clinico-surgical outcomes and operation times were retrospectively reviewed. The TORT group showed a higher number of retrieved central compartment lymph nodes, shorter hospital stays, and lower pain score after 48 h than the TOETVA group. No significant difference was observed in the other postoperative complications, including permanent vocal cord palsy. Total operation, working space creation, and endoscopic or robotic surgery times of the TORT group were longer than those of the TOETVA group. TORT and TOETVA are feasible and safe. TORT may have some advantages, such as central compartment node dissection, shorter hospital stays, and pain score after 48 h in PTC, despite a longer operative time.

Defying expectations: follicular carcinoma thyroid with lung metastasis and elevated CA 125: images

Background: Follicular thyroid carcinoma (FTC) is a type of thyroid cancer that arises from the follicular cells of the thyroid gland. It accounts for about 10%-15% of all thyroid cancers. CA 125 is a protein that is often used as a tumor marker for ovarian cancer, but it can also be elevated in other types of cancers, including thyroid cancer. The significance of raised CA 125 levels in FTC is not clear, but it indicates a more advanced or aggressive form of the disease [1,2]. Case Presentation: A 62-year-old male presented with a painless neck mass (Figure 1) for 8 years. Ultrasonography revealed a solid nodule in the left lobe of the thyroid gland. Fine-needle aspiration cytology of the nodule showed features of follicular neoplasm. Contrast-enhanced computed tomography (CECT) abdomen and blood routine ruled out other causes of raised CA 125. Chest X ray and CECT neck (Figure 2) and thorax showed lung (Figure 3) and thoracic vertebra metastasis (Figure 5). Total thyroidectomy with bilateral central compartment lymph node dissection was performed. Histopathology confirmed FTC (Figure 4) with capsular invasion, and lymphovascular and perineural invasion and lymph node-positive. The tumor was classified as T3bN1a according to the tumor, nodes, and metastasis staging system. I131 scan post-surgery showed uptake in lung metastasis sites which confirmed the diagnosis. Conclusion: The role of serum tumor markers, such as CA 125, in predicting the prognosis of FTC is not well established. However, elevated CA 125 levels have been reported in some cases of thyroid carcinoma with metastasis, and may reflect the presence of peritoneal or pleural involvement [3,4]. This case highlights the aggressive nature of FTC with metastasis and the limited treatment options available for patients with advanced disease. CA 125 as a prognostic marker in FTC warrants further investigation [5].

Predictive factors for nodal recurrence in differentiated thyroid cancers

IntroductionDifferentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. MethodologyThis study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. ResultsOut of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (<6 month) had TERT/BRAF V600 E mutations. ConclusionIn our study, we have noted extrathyroidal extension and multifocality as significant risk factors for nodal recurrence. BRAF and TERT mutations are associated with aggressive clinical course and early recurrences. There is limited role of prophylactic central compartment node dissection.

The Role of Frozen Section Examination in Thyroid Surgery.

In endocrine pathology, frozen section (FS) examination is most commonly used for the intraoperative evaluation of thyroid and parathyroid tumors, as well as cervical lymph nodes. In the past, frozen section was considered a fundamental tool in thyroid surgery. However, with advancements in preoperative ultrasound and fine-needle aspiration biopsy (FNAB), there have been increasing queries about its routine use due to the improved preoperative diagnosis. Nowadays, while the use of FS during thyroidectomy has decreased, it is still used as an additional method for different purposes intraoperatively. FS may not always provide definitive results. If FS will alter the surgical plan or extent, it should be applied. Routine FS is not recommended for evaluating thyroid nodules. But in addition to FNAB, if FS results may change the operation plan or extent, they can be utilized. FS should not be applied for thyroid lesions smaller than 1 cm, and the entire lesion should not be frozen for FS. For the assessment of thyroid nodules, the use of FS is recommended based on the Bethesda categories of FNAB. In Bethesda I category nodules, FS may contribute to distinguishing between malignant and benign lesions and guide surgical treatment. In Bethesda II nodules, where the malignancy rate is low, the performance of FNAB and FS can be compared, but it's not recommended due to the lack of a significant contribution to the surgical strategy. The sensitivity of FS in Bethesda III and IV nodules is low; its contribution to the diagnosis is limited, and it does not provide an apparent benefit to treatment; therefore, it is not recommended. In Bethesda V nodules, FS can effectively confirm the malignancy diagnosis, contribute to the surgical strategy, and reduce the possibility of completion thyroidectomy, and accordingly, it is recommended for use. Nonetheless, in Bethesda V nodules with a benign FS report, the malignancy rate remains high, so it should not be used to rule out malignancy. In Bethesda VI nodules, the performance of FS is lower or comparable to FNAB and does not significantly contribute to the treatment strategy; hence, it is not recommended. Particularly in patients with papillary thyroid cancer, intraoperative FS can be effective in detecting extrathyroidal extension and can assist the surgeon in determining the extent of thyroid surgery and central neck dissection. FS has high sensitivity and specificity in evaluating the lymphatic status of the central region intraoperatively and can be used to determine the extent of central compartment node dissection. During thyroidectomy, FS examination can be used in recognizing parathyroid tissue and distinguishing it from fatty tissue, thymus, thyroid, lymph nodes, especially in differentiating metastatic lymph nodes.

PSAT211 Low Grade Parathyroid Carcinoma: A Challenging Diagnosis in the Evaluation of Primary Hyperparathyroidism

Abstract Background Parathyroid carcinoma often presents with severe symptomatic hypercalcemia, bone and kidney involvement, and PTH &amp;gt; 4x the upper limit of normal. Diagnosis is challenging and requires classic pathologic findings. Case Presentation A 34-year-old woman presented with hypercalcemia. She was found to have primary hyperparathyroidism with elevated total calcium (11.8 mg/dL), elevated PTH (352.8 pg/mL), and elevated 24-hour urine calcium (758 mg/24hr). A 99mTc sestamibi scan showed focal uptake in the right inferior thyroid pole. Intraoperatively, there was a lobulated, fibrotic right parathyroid mass sized 3.5×2.5×2.0 cm. Pathology showed low-grade parathyroid carcinoma with lymphovascular invasion, extension into soft tissue, and focal positivity in resection margin. Post-operative PTH was 19.5 pg/mL. One month later, PTH was elevated to 82.0 pg/mL with calcium of 9.1 mg/dL. PET scan did not show metastases. The patient then underwent a right thyroid lobectomy with central compartment lymph node dissection. Pathology showed residual parathyroid carcinoma within the perithyroidal scar tissue but was negative for lymph node involvement. Postoperatively, her PTH was 52.5 pg/mL. Genetic studies showed no mutations in CDC73, MEN1, RET, RB1, and TP53 genes. She underwent external beam radiation treatment. Following radiation, her total calcium and PTH level remained in the normal range with no recurrence on thyroid ultrasound. Clinical Lessons On ultrasound, parathyroid carcinomas are large, have increased heterogeneity and lobulations, as well as suspicious lymph nodes. Intraoperative suspicion is based on large size, capsular or local tissue invasion, and lymph node metastases. Histologic assessment can be challenging as findings of parenchymal mitoses, trabeculated parenchyma, and thick fibrous bands are also seen with parathyroid adenomas. Local tissue invasion (angiolymphatic, perineural or adjacent structures) or metastases such as lymph nodes seen on pathology are diagnostic of parathyroid carcinoma. PET can be used post-operatively to identify recurrence or metastases. Genetic studies especially for mutations in CDC73 can be helpful in diagnosis as it is the most common cause of syndromic and sporadic parathyroid carcinoma.Resection of the tumor and adjacent tissues is the mainstay of treatment. A regional lymph node dissection should be done if there are suspicious lymph nodes. Neither thyroidectomy, chemotherapy nor radiation has been shown to improve overall survival. Radiation has shown to have some benefit for local recurrence and disease-free survival. Lifelong monitoring of calcium and PTH levels is required, and if elevated, should prompt imaging with thyroid ultrasound and PET scan. Prognosis is generally poor but does improve if there is complete surgical resection on initial diagnosis. Almost all patients experience recurrence within 2-23 years after resection Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Value of dissection of lymph nodes posterior to the right recurrent laryngeal nerve in patients with cN0 papillary thyroid carcinoma.

BackgroundTumor metastasis to lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) is a main cause of disease recurrence in patients with papillary thyroid carcinoma (PTC), which may increase the risk of recurrence and secondary surgery, and the disruption of normal anatomical relationships during secondary surgery increases the risk of laryngeal nerve injury and hypoparathyroidism. However, controversy remains as to whether the dissection of LN-prRLN is required in cN0 PTC patients. The purpose of this study is to explore the factors associated with LN-prRLN metastasis in patients with cN0 PTC and the need for LN-prRLN node dissection in patients with cN0 PTC who undergo right central compartment dissection.MethodsThe clinical data of 290 patients with cN0 PTC who received radical thyroid cancer surgery from December 2019 to March 2022 at our center were retrospectively analyzed. All the patients underwent thyroid lobectomy and right central lymph node dissection (CLND), along with other treatments. SPSS 26.0 statistical software was used for the analysis. The measurement data were compared using the rank-sum test, and the count data were compared using the chi-square test.ResultsLN-prRLN metastasis was detected in 65 (22.4%) of the 290 cN0 PTC patients. The metastasis sites included level VIa (51.72%), the left central compartment (22.76%), and the prelaryngeal compartment (8.97%). The univariate analysis revealed that tumor multifocality, a tumor diameter >1 cm, capsular invasion, LN metastasis in the left central compartment, and level VIa positivity were influencing factors of LN-prRLN metastasis in PTC patients. The logistic regression analysis showed that a tumor diameter >1 cm (OR =2.897, 95% CI: 1.630–5.147, P<0.001), LN metastasis in the left central compartment (OR =3.724, 95% CI: 2.039–6.801, P<0.001), and level VIa (OR =3.405, 95% CI: 1.846–6.281, P<0.001) positivity were independent risk factors of LN-prRLN metastasis in PTC patients.ConclusionsThe high-risk factors of LN-prRLN metastasis in cN0 PTC patients include a large tumor (a diameter >1 cm), lymph node metastasis in the left central compartment, and lymph node metastasis in level VIa. For patients with cN0 PTC undergoing right CLND, with high-risk factors of LN-prRLN metastasis, LN-prRLN dissection is recommended.KeywordsPapillary thyroid carcinoma (PTC); lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN); central compartment lymph node dissection; risk factor

Real-World Evidence on the Sensitivity of Preoperative Ultrasound in Evaluating Central Lymph Node Metastasis of Papillary Thyroid Carcinoma.

IntroductionGuidelines for prophylactic dissection in clinical central negative node (cN0) of papillary thyroid carcinoma vary among different countries due to the uncertainty on the benefit of dissection. The Chinese guidelines recommend prophylactic central compartment lymph node dissection (pCLND) under professional technology. Preoperative ultrasound (US) evaluation of central lymph node determines the surgical strategy used. Sensitivity differs significantly when US is conducted by different physicians even in diverse hospitals. In this study, the aim was to explore why the Chinese guidelines were different from the America Thyroid Association (ATA) guidelines through the real-world evidence on the preoperative diagnosis of cN0.MethodsPreoperative US and surgical pathology data for 1,015 patients with PTC attending 13 Grade-A tertiary hospitals in 2017 were collected. A retrospective analysis using US assessment of CLNM was the conducted to explore the benefits of this approach in China. US physicians in our hospital were trained on scanning the thyroid gland and its regional lymph nodes in normalization. Data of 1,776 patients were collected under the same condition from 2012 to 2017, whose ultrasonography was performed by diverse physicians and doctors. Further, data of 339 patients evaluated by the same sonographer and operated by the same surgical team was collected between 2015 and 2017. In this set of data, US combined CT versus US alone was compared. Patients were grouped into metastasis group and non-metastasis group based on postoperative pathological diagnosis of CLNM. Diagnostic efficacy of US was evaluated.ResultsA total of 925 patients who underwent preoperative ultrasonography in central lymph node, including 825 cases who underwent thyroidectomy and central lymph node dissection were included in this study. The sensitivity of ultrasonography in detecting CLNM was 23.18%, with occult metastasis rate of 40.8%. Data for 1,776 patients comprising paired ultrasonic report and pathological report were collected in our hospital, whose physicians underwent standardized training. The sensitivity was 37.58%. Furthermore, specialized evaluation showed high sensitivity in US/CT (84.58%) than US (58.21%) alone.ConclusionAlthough the sensitivity of US could be enhanced by standardized training and combination with CT, the prevalence of low sensitivity of US in real-world multicenter data and the high occult metastasis rate indicated that the Chinese guidelines were based on the current conditions.

Fortuitously detected Paget’s bone disease in a patient with TENIS syndrome on FDG PET/CT

A 74-year-old lady presented with a complaint of progressive neck swelling for two years. FNAC from the swelling was suggestive of papillary carcinoma thyroid (PCT). She underwent total thyroidectomy with central compartment lymph node dissection. Histopathology revealed multifocal PCT with central compartment lymph node metastases. Her baseline stimulated sTg was 5.3 ng/ml after levothyroxine withdrawal. WBS showed uptake in the operative bed (not shown). She was treated with 100 mCi of I-131 and was kept on a suppressive dose of thyroxin hormone. Her sTg gradually increased (77.5 ng/ml) in follow-up after three years. WBS was negative for metastatic disease. She underwent FDG PET/CT, that revealed cervical and upper mediastinal lymph nodes. Apart from that, multiple pagetic lesions were also noted. The patient had a history of mild localized pain and tenderness over these. Her Serum Alkaline phosphatase level was elevated (269 U/L). The patient refused resurgery for cervical lymph nodes. She is on Zolendronic acid infusion and remains asymptomatic. She is in regular follow-up, and her suppressedsTg remains stable even after two years.

Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignant tumor originating from parafollicular C-cells producing calcitonin. Most of cases (75%) are sporadic while the remaining (25%) are hereditary. In these latter cases medullary thyroid carcinoma can be associated (multiple endocrine neoplasia type IIA and IIB) or not (familial medullary thyroid carcinoma), with other endocrine diseases such as pheochromocytoma and/or hyperparathyroidism. RET gene point mutation is the main molecular alteration involved in MTC tumorigenesis, both in sporadic and in hereditary cases. Total thyroidectomy with prophylactic/therapeutic central compartment lymph nodes dissection is the initial treatment of choice. Further treatments are needed according to tumor burden and rate of progression. Surgical treatments and local therapies are advocated in the case of single or few local or distant metastasis and slow rate of progression. Conversely, systemic treatments should be initiated in cases with large metastatic and rapidly progressive disease. In this review, we discuss the details of systemic treatments in advanced and metastatic sporadic MTC, focusing on multikinase inhibitors, both those already used in clinical practice and under investigation, and on emerging treatments such as highly selective RET inhibitors and radionuclide therapy.

Factors associated with postoperative hypocalcemia following thyroidectomy in childhood.

Postoperative hypocalcemia is a frequent complication after thyroidectomy. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. We analyzed factors associated with the development of postoperative hypoparathyroidism and in detail PtHP following thyroid surgery in a pediatric population. A retrospective multicenter study analyzing 326 patients was carried out. We recorded gender, age, tumor size, thyroiditis, extrathyroidal extension, lymph node dissection (central/lateral compartment, unilateral/bilateral), parathyroid autotransplantation, and histology. Additionally, calcium levels were acquired postoperatively. We analyzed pediatric patients ≤18 years who underwent thyroidectomy clustered into age groups (≤15 or>15). Patients' mean follow-up was 5.8 years (1-11 years). Postoperative hypoparathyroidism occurred in 36 (11.0%): 20 cases (6.13%) developed PtHP. Postoperative hypoparathyroidism was more frequent in younger patients (P=0.014), in larger tumors (P<0.001), in case of extrathyroidal extension (P=0.037), and in central compartment (P=0.020) and bilateral lymph node dissection (P=0.030). PtHP was more frequent in older patients (P=0.014), in case of thyroiditis (P<0.001), and extrathyroidal extension (P<0.001). Concerning the first postoperative calcium level measurement, in the postoperative hypoparathyroidism group, we registered a 8.17mg/dL value with 14% pre/postoperative decrease (ΔCa ), whereas in PtHP patient group calcium level was 7.91mg/dL with 16.7% ΔCa . The risk of postoperative hypoparathyroidism is related to younger age, tumor size, central compartment and bilateral lymph node dissection, extrathyroidal extension, and decrease in postoperative calcium levels. The risk of PtHP is related to older age, thyroiditis, extrathyroidal extension, and decrease in postoperative calcium levels.

Extension of Prophylactic Surgery in Medullary Thyroid Carcinoma. Differences Between Sporadic and Hereditary Tumours According to Calcitonin Levels and Lymph Node Involvement

IntroductionCurrently, there is no consensus on the indication of prophylactic surgery of the nodal compartments in the treatment of medullary thyroid carcinoma (MTC). The aim of our study was to perform a correlation study between preoperative calcitonin (basalCT) values and lymph node involvement to establish a criterion on which to base prophylactic surgery in these patients.Material and MethodsWe conducted an observational, retrospective and multicentre study with 29 hospitals. Patients over 18 years of age with a diagnosis of MTC with a pre-surgical calcitonin registry were included. The minimum surgery in all patients had to have been total thyroidectomy (TT) with central compartment lymph node dissection (CCLND). Receiver operating characteristic (ROC) curve analysis was used to establish basalCT cut-off values as predictors of postoperative lymph node involvement.ResultsA total of 244 patients were included. Baseline calcitonin (basalCT) was a good predictor of nodal involvement (AUC 0.718 and 95%CI 0.66–0.978). Heritability was identified as a preoperative factor correlated with baseline tumour CT values (p = 0.000). With a probability of lymph node involvement below 10%, new cut-off points were established. A prophylactic bilateral lateral lymph node dissection in sporadic tumours should be performed at a basalCT > 600 pg/mL; in the case of RET-mutated tumours this value would be 200 pg/mL.ConclusionThe baseline CT value is a good predictor of postoperative lymph node involvement in MTC, however, cut-off points should depent on the hereditary nature of the tumour.

Multifocal Diffuse Sclerosing Papillary Thyroid Carcinoma: A Rare Variant with Diagnostic Challenges

Diffuse sclerosing papillary thyroid carcinoma (DS PTC) is a relatively rare variant of papillary thyroid carcinoma. It is characterized by distinct histological features like scattered microscopic tumor islands, diffuse sclerosis, lymphocytic infiltration, numerous psammoma bodies, radiological features like snowstorm appearance and biologically aggressive behavior in the form of invasion and metastasis. A preoperative diagnosis is often challenging in the absence of nodules and scanty fine needle aspiration cytology sample. We describe a case of multifocal diffuse sclerosing variant of papillary thyroid carcinoma in a 29 year old young male who presented with a swelling in the right side of neck of 2 month duration in the absence of a visible thyroid swelling. Neck swelling was non tender, well defined, firm, not moving with deglutition. Laboratory studies showed normal thyroid function, neck ultrasound revealed heteroechoic right lobe with multiple punctate echogenic foci and enlarged right sided cervical nodes with echogenic foci, fine needle aspiration cytology of which was consistent with metastasis from papillary adenocarcinoma. Based on the above investigations, a total thyroidectomy with central compartment lymph node dissection and modified radical neck dissection of right side was performed. Histological analysis revealed Multifocal Diffuse Sclerosing variant of papillary Thyroid Carcinoma. Clinical and histological challenges usually occur when DS PTC present as diffuse thyroid enlargement, dispersed microscopic tumor islands, extensive fibrosis, abundant lymphocytic infiltration mimicking thyroiditis and when the fine needle aspiration cytology sample is non representative.

Effect of Prophylactic Central Lymph Node Dissection on Locoregional Recurrence in Patients with Papillary Thyroid Microcarcinoma.

There is a consensus that central compartment lymph node dissection or modified radical lateral neck dissection should be performed in papillary thyroid microcarcinoma (PTMC) patients with lymph node metastases. Prophylactic central lymph node dissection (PCLND) in patients with clinically node-negative (cN0) PTMC to reduce locoregional recurrence (LRR) rate and improve prognosis remains controversial. The present study aimed to analyze the effect of PCLND on LRR and postoperative complications of PTMC in cN0 patients. We reviewed a cohort of patients with cN0 PTMC who underwent surgery between January 1997 and October 2019. The patients were divided into the PCLND and no lymph node dissection (NLND) groups. Kaplan–Meier curves were constructed to estimate 15-year locoregional recurrence-free survival rate of the two groups, and the difference was compared by the log-rank test. Three Cox regression models were performed to evaluate the correlation between PCLND and LRR. All patients underwent thyroidectomy, and 25 patients developed LRR; of whom, 23 underwent PCLND at initial surgery and 2 went without lymph node dissection. Cox regression analysis showed that PCLND had no effect on LRR. Postoperative hematoma and permanent recurrent laryngeal nerve injury did not occur in the NLND group, and their incidences were 0.5% and 0.3% in the PCLND group, respectively. PCLND had no significant correlation with LRR in patients with cN0 PTMC, and the absolute benefit for PTMC was small.

Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center.

IntroductionMedullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center.MethodFrom 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels.ResultNineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient’s postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%.ConclusionSince incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.