THE ROLE OF CALCITONIN IN THE PREOPERATIVE STAGE AS THE PREDICTOR OF MEDULLARY THYROID CANCER METASTASES

the aim of the stydy was to analyze the detectability of medullary thyroid metastases in patients at treatment and diagnostic stages, to investigate the applicability of serum calcitonin level as predictor of possible presence of medullary thyroid metastases. The study included data from 148 patients who underwent surgical treatment for the initial diagnosis of medullary thyroid cancer. The age of patients ranged from 12 to 83 years, the mean age was 48,2±1,9 years; the distribution by gender was as follows: men – 34 (23%), women – 114 (77%). Patients were divided into two groups depending on the pathomorphological report: 1 group (100 (67,6%) – patients without metastases), 2 group (48 (32,4%) – patients with locoregional metastases). Among 148 studied patients with medullary thyroid cancer, as a result of the histopathological conclusion, in 48 (32,4%) metastases were detected in regional lymph nodes, among which 10 (6,7%) patients had metastases only in the central collector and 38 (25, 7%) –both in the central and lateral collectors. At the preoperative stage, the level of undiagnosed metastases by ultrasound was 64,58% (31 patients). Subsequently, at the intraoperative stage, during the rapid histological biopsy, the number of undiagnosed metastases decreased to 37,5% (18 patients), and in the postoperative period, according to the results of histopathological examination, the remaining patients were diagnosed with the medullary thyroid cancer metastases. Ultrasound helped to detect metastases in 17 patients, which was 35,42% of all detected metastases. At the stage of intraoperative study, the detection of metastases increased and amounted to 30 (62,5%), and in the postoperative period as a result of histopathological examination metastases were confirmed in 48 patients (100%). Quantitative indicators of both detected and undiagnosed metastases at all stages of treatment and diagnostic search are statistically significant (p<0,01). The detection of metastases in the central lymphatic collector (N1a) at the preoperative stage was 2,08%, this index has doubled (to 4,16%) after intraoperative rapid histological conclusion, and after histopathological conclusion the index has increased more than 10 times (20,84 %). This tendency to grow of metastaseses detection was followed also on lateral collectors: N1b and psilateral were observed at 15 (31,2%) patients at the preoperative stage, their number increased to 23 (47,9%) intraoperatively and to 31 (64,6%) postoperatively; N1b contralateral was observed in 1 (2,1%), 5 (10,4%) and 7 (14,6%), respectively. Such a low percentage of metastases detection at the preoperative stage by ultrasound prompted to CT level study as the predictor of possible metastases. We investigated the preoperative basal blood CT value as a marker of the medullary thyroid cancer metastases presence probability. Due to the small number of the group (n=10) with N1a, the association of CT (cut-off level 137 pg/ml) with the possible presence of metastases was not significant (AUC = 0.594), while in the group with N1b there was a more significant difference. Thus, CT cut-off levels of 358 pg/ml for N1b ipsilateral, and 498 pg/ml for N1b contralateral detection of possible metastases in collectors, with AUC: 0.877 and 0.832, respectively, which justifies the importance of the lateral neck dissection in addition to the mandatory central dissection in order to remov possible medullary thyroid cancer metastases. Thus, ultrasound is insufficiently reliable method of metastases verifying in medullary thyroid cancer (DE = 35.4% at d mts <0.6 cm). In the absence of ultrasound data (or fine needle aspiration (FNA) biopsy results) on the presence of metastases to raise awareness of the disease prevalence, to clarify the prognosis of its development it’s important to use the additional criterion – the calcitonin level. Basal calcitonin level is the reliable predictor of the medullary thyroid cancer metastases. Its cut-off level of 137 pg/ml indicates the possible presence of metastases in the central group (N1a) (AUC=0,594). The CT cut-off level – 358 pg/ml (AUC=0,793) suggests the presence of the medullary thyroid cancer metastases (N1a+N1b). CT cut-off levels – 358 pg/ml for N1b ipsilateral, and 498 pg / ml for N1b contralateral (AUC: 0,877 and 0,832), respectively. The calculated values of the countersensitivity test to detect metastases for different levels of basal CT in the preoperative stage in the clinical setting will help the practitioner in deciding on treatment tactics to determine the extent of surgery in patients diagnosed (or suspected) with the medullary thyroid cancer metastases.

Breast metastasis from medullary thyroid carcinoma: a report of a case

Background Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis. Case presentation A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month. Conclusion Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

Mildly Elevated Basal Calcitonin Level in Patients With Thyroid Goiter: Using the Calcitonin Measurement in Fine-Needle Aspirate Washout Fluid of the Healthy Lobe to Define Medullary Thyroid Cancer and Reactive C-Cell Hyperplasia

Background: Mildly elevated basal calcitonin level (bCT), that suggests a bCT increase up to 100 pg/ml, may testify either medullary thyroid carcinoma (MTC) or reactive thyroid C-cell hyperplasia (CCH). The latter is observed under many conditions such as hypercalcemia, hypergastrinemia, thyroiditis, neuroendocrine tumors (NET), renal end-stage kidney disease, obesity, and smoking. The research is aimed at analyzing the clinical significance of the calcitonin measurement in the fine needle aspiration washout fluid sample (FNA-CT) for screening certain patients with nodular thyroidopathy and elevated bCT. Patients and Methods: 70 patients with mildly elevated bCT (for women 6-100 pg/ml, for men 19-100 pg/ml) underwent ultrasound-guided FNA-CT measurement of the thyroid nodules and healthy lobe tissue. After obtaining a FNA-CT specimen, the needle was washed with 0.5 ml of saline solution. The calcitonin (CT) was measured by ECLIA (LIAISON XL). Results: There were 51 females and 19 males, with a mean age of 46.8 ± 14.4 years (range 16-81). The mean value of bCT was 23.3 ± 19 pg/ml (range: 7-86.5). According to ultrasound, 66 patients (95%) presented with thyroid nodules, in 4 cases previously identified nodes were not confirmed. The mean lesion size was 10.8 ± 4.9 mm (range: 4-26). Thyroid nodules were evaluated by FNA biopsy which revealed according to the Bethesda system category I in 6 cases, II - 44, III - 2, IV - 4, V - 6, and VI - 1. Analyzing FNA-CT results we identified 13 cases (18%) with MTC with low CT level of healthy lobe tissue (1-89.6 pg/ml) and high CT level of the lesion (&gt;2000 pg/ml), which was confirmed by final histological examination. Low CT level from both healthy lobe and the nodule (&lt;20 pg/ml) was observed in 10 cases, we carried out the measurement of stimulated CT to exclude the extrathyroidal CT production, which was confirmed in 1 case. All 4 patients with no nodules possessed significantly higher T-rates (1650-2000 pg/ml). The remaining 43 cases (61%) had an increased CT-level of healthy tissue (&gt;2000 pg/ml) with a lower level from the lesion. Among these patients, the probable predisposing CCH factors were obesity - 8 cases, thyroiditis - 12, NET - 3, hypercalcemia - 3, renal kidney disease - 1, and smoking - 3. These 54 patients were kept under dynamic control. The observation period for patients - 1 year. 4 patients underwent surgical treatment, subsequently, histological examination revealed papillary thyroid cancer, follicular adenoma, colloid goiter against CCH, and CT-producing NET. Conclusion: The measurement of FNA-CT of the healthy lobe tissue may be useful to differentiate MTC and CCH, but requires new data in a major cohort of patients. The disadvantage of this study is the impossibility of CCH histological verification in the follow-up group.

Diagnosis of Medullary Thyroid Cancer During COVID-19 Pandemic, the Benefit of Using a Standardized Protocol

Introduction: The reported prevalence of malignancy in thyroid nodules ranges from 4% to approximately 10%, with a small percentage (~2-8%) being medullary thyroid cancer (MTC). During the COVID-19 pandemic, elective thyroid FNA was temporarily halted at our institution. In response to this, our institution has devised a new protocol to aid in the detection of MTC, which includes serum calcitonin measurement as a surrogate marker for potential MTC. A severely elevated calcitonin (&gt;100 pg/mL) is considered for surgery even without FNA diagnosis. We present a case of MTC that was detected due to the adopting of this protocol during COVID-19 pandemic at the Phoenix VAMC. Case Presentation: 71 year old male with an incidentally noted 3.0 cm solid, hypoechoic nodule with internal calcification, TI-RADS category 5. TSH level was normal at 3.309 mIU/mL. The patient denied any personal or family history of thyroid cancer, MEN syndrome, radiation exposure, or compressive symptoms. Following established protocol published by our institution in clinical thyroidology we performed a serum calcitonin that came back elevated at 1515 pg/mL (normal &lt; 10 pg/mL). Given the marked elevation in serum calcitonin levels and highly suspicious radiographic appearance of the thyroid nodule, we strongly suspected medullary thyroid cancer and elected to send him directly for total thyroidectomy without performing FNA. The patient underwent total thyroidectomy with central neck dissection. Pathology showed a 3.2 cm medullary thyroid carcinoma without extrathyroidal extension or perineural invasion. Lymphovascular invasion was present. 6/10 central comparement lymph nodes were positive for metastatic disease. Postoperative calcitonin level was 2 pg/mL. Discussion: Our patient had markedly elevated serum calcitonin levels in addition to a high-risk ultrasonographic features, which was highly suspicious for MTC. Per our COVID-19 protocol, we measured the serum calcitonin level to screen for MTC and then referred him directly to surgery without FNA given the high suspicion for MTC. By using this protocol, we were able to diagnose and treat MTC expeditiously. The measurement of serum calcitonin is still controversial in the U.S, with the ATA remaining equivocal on this method. We believe that our case can serve as a practical example that validates our institution’s use of calcitonin screening of thyroid nodules in diagnosing MTC during the COVID-19 pandemic.

Correlation between preoperative ultrasonic features of medullary thyroid carcinoma and postoperative recurrence

Background To investigate the factors that affect postoperative recurrence in medullary thyroid carcinoma (MTC) patients, including preoperative ultrasonic characteristics and other factors. Method A retrospective analysis of 7 MTC patients who underwent the first thyroid surgery from 2009 to 2018 and who had complete follow-up data was conducted. According to the follow-up results, these patients were divided into the recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin levels, and general informations of the two groups were recorded, respectively. Univariate and multivariate analyses were performed. Results Single factor Kaplan-Meier (K-M) analysis showed that: ① Preoperative ultrasonic characteristics including tumor size > 40.0 mm, capsular invasion, and metastatic cervical lymph nodes, as well as preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin (within one week) level > 45.0 pg/ml were positively correlated with the risk of postoperative recurrence of MTC (P < 0.05); ② There was no evidence to show that sex and age had a statistically significant effect on postoperative recurrence of MTC (P > 0.05). Multivariate Cox regression analysis showed that metastatic lymph nodes shown by ultrasound (HR = 5.368, 95%CI 1.063–27.104, P = 0.042) was an independent risk factor for postoperative recurrence of MTC. Conclusions MTC patients with metastatic lymph nodes shown by ultrasound are prone to postoperative recurrence of MTC. In addition, MTC patients with a tumor > 40.0 mm, capsular invasion, preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin level > 45.0 pg/ml are more likely to have postoperative recurrence.

Correlation between Preoperative Ultrasonic Features of Medullary Thyroid Carcinoma and Postoperative Recurrence

Background: To investigate the factors that affect postoperative recurrence in medullary thyroid carcinoma (MTC) patients, including preoperative ultrasonic characteristics and other factors. Method: A retrospective analysis of seventy four MTC patients who underwent the first thyroid surgery from 2009 to 2018 and who had complete follow-up data was conducted. According to the follow-up results, these patients were divided into the recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin levels, and general informations of the two groups were recorded, respectively. Univariate and multivariate analyses were performed. Results: Single factor Kaplan-Meier (K-M) analysis showed that: ① Preoperative ultrasonic characteristics including tumor size > 40.0 mm, capsular invasion, and metastatic cervical lymph nodes, as well as preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin (within one week) level > 45.0 pg/ml were positively correlated with the risk of postoperative recurrence of MTC (P <0.05); ② There was no evidence to show that gender and age had a statistically significant effect on postoperative recurrence of MTC (P> 0.05). Multivariate Cox regression analysis showed that metastatic lymph nodes shown by ultrasound (HR=5.368, 95%CI 1.063-27.104, P=0.042) was an independent risk factor for postoperative recurrence of MTC. Conclusions: MTC patients with metastatic lymph nodes shown by ultrasound are prone to postoperative recurrence of MTC. In addition, MTC patients with a tumor > 40.0 mm, capsular invasion, preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin level > 45.0 pg/ml are more likely to have postoperative recurrence.

Correlation between Preoperative Ultrasonic Features of Medullary Thyroid Carcinoma and Postoperative Recurrence

Background: To investigate the factors that affect postoperative recurrence in medullary thyroid carcinoma (MTC) patients, including preoperative ultrasonic characteristics and other factors.Method: A retrospective analysis of 74 MTC patients who underwent first thyroid surgery from 2009 to 2018 and who had complete follow-up data was conducted. According to the follow-up results, these patients were divided into the recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin level, and general information on the two groups were recorded, respectively. Univariate and multivariate analyses were performed.Results: Single factor Kaplan-Meier (KM) analysis showed that: ① Preoperative ultrasonic characteristics including tumor size > 40.0 mm, capsular invasion, and metastatic cervical lymph nodes, as well as preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin (within one week) level > 45.0 pg/ml were positively correlated with the risk of postoperative recurrence of MTC (P <0.05); ② There was no evidence to show that gender and age had a statistically significant effect on postoperative recurrence of MTC (P> 0.05). Multivariate Cox regression analysis showed that metastatic lymph nodes shown by ultrasound (HR=5.368, 95%CI 1.063-27.104, P=0.042) were an independent risk factor for postoperative recurrence of MTC.Conclusions: MTC patients with metastatic lymph nodes as shown by ultrasound are prone to postoperative recurrence of MTC. In addition, MTC patients with a tumor > 40.0 mm, capsular invasion, preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin level > 45.0 pg/ml are more likely to have postoperative recurrence.

Preoperative Serum Calcitonin and Its Correlation with Extent of Lymph Node Metastasis in Medullary Thyroid Carcinoma

The optimal initial surgical extent for medullary thyroid carcinoma (MTC) remains controversial. Previous studies on serum calcitonin are limited to reporting the calcitonin threshold according to anatomical disease burden. Here, we evaluated whether preoperative calcitonin levels can be used to predict optimal surgical extent. We retrospectively reviewed the 170 patients with MTC at a tertiary Korean hospital from 1994 to 2019. We extracted data on preoperative calcitonin level, primary tumor size and the number and location of lymph node metastases (LNMs). To evaluate disease extent, we divided the patients into five groups: no LNM, central LNM, ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis. We calculated the positive and negative likelihood ratios (LRs) for multiple categories of preoperative calcitonin levels. Preoperative calcitonin level positively correlated with primary tumor size (rho = 0.744, p < 0.001) and LNM number (rho = 0.537, p < 0.001). Preoperative calcitonin thresholds of 20, 200, and 500 pg/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. The negative LRs were 0.1 at a preoperative calcitonin cut-off of 100 pg/mL in the central LNM, 0.18 at a cut-off of 300 pg/mL in the ipsilateral lateral LNM, and 0 at a cut-off of 300 pg/mL in the contralateral lateral LNM. The preoperative calcitonin level correlates with disease extent and has diagnostic value for predicting LNM extent. Our results suggest that the preoperative calcitonin level can be used to determine optimal initial surgical extent.

Correlation Study Between Preoperative Ultrasonic Features of Medullary Thyroid Carcinoma and Postoperative Recurrence

Background: To investigate factors that affects postoperative recurrence in medullary thyroid carcinoma (MTC) patients in terms of preoperative ultrasonic characteristics and so on. Method: A retrospective analysis of 74 MTC patients who underwent the first thyroid surgery from 2009 to 2018 at hospital and had complete follow-up information. According to the follow-up results, these patients were divided into recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin level, and general information of the two groups were recorded separately. Univariate and multivariate analysis was performed. Results: Single factor KM analysis showed that: ①Preoperative ultrasonic characteristic of tumor size> 40.0 mm, capsular invasion, and abnormal cervical lymph node ,as well as preoperative calcitonin level > 565.8pg / ml, postoperative calcitonin (within one week) level > 45.0pg / ml are the factors that affect postoperative recurrence of MTC (P <0.05); ②There is no evidence shows that gender and age have statistical significance with postoperative recurrence of MTC patients (P> 0.05). Multi-factor COX regression analysis showed that abnormal cervical lymph node （HR=5.368,95%CI1.063-27.104，P=0.042）is an independent risk factor affecting postoperative recurrence of MTC patients. Conclusions: MTC patients with abnormal cervical lymph nodes prone to postoperative recurrence. In addition, MTC patients with tumor> 40.0mm, capsular invasion, preoperative calcitonin level > 565.8pg / ml, postoperative calcitonin level > 45.0pg / ml are more likely to have postoperative recurrence.