Central Node Dissection Research Articles

Development of a predictive nomogram for intermediate-risk differentiated thyroid cancer patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation.

The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

First experience of applying domestic video fluorescent equipment for visualization and blood flow evaluation of the parathyroid glands

In recent years, predictive methods for assessing the preservation of the parathyroid glands have been actively implemented. The article describes the first experience of evaluating the blood supply of the parathyroid glands by quantitative determination of the indocyanine green (ICG) accumulation index in real time in 6 patients before and after a thyroidectomy with central neck lymph node dissection for papillary thyroid cancer. Intraoperative fluorescent angiography was performed by using domestic equipment with a fluorescent module, as well as by using a domestic medication of ICG. Intraoperative values of the ICG accumulation index were compared with the levels of ionized calcium and parathyroid hormone perioperatively. No clinical manifestations of hypocalcemia were detected in the postoperative period. The obtained results showed the informativeness of the numerical assessment of the intensity of ICG fluorescence. The evaluation of the distribution (accumulation) of ICG has prospects for practical application in thyroid surgery in the formation of tactics for preserving the parathyroid glands and predicting postoperative hypoparathyreosis.

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.

Does the size of unifocal papillary thyroid carcinomas affect the status of the cervical lymph nodes?

Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy in humans. Cervical lymph node (LN) involvement is one of the major prognostic factors in disease recurrence and morbidity. Despite central lymph node dissection (CLND) is recommended in the case of involved LNs, prophylactic neck dissection is still controversial due to the potential complications associated with this procedure. The aim of the current review is to assess the correlation between the sizes of unifocal PTC with cervical LN involvement, which could help to choose the best treatment plan for patients with PTC. Materials and Methods: We performed a retrospective review for all patients who had unifocal PTC in our department from 2013 to 2019 with a minimum of 3 years of follow-up. SPSS software was used to calculate this correlation. Results: Fifty-nine patients (38 females and 21 males) were included in our study with an average age of 45.4 ± 17 years of age. Out of 17 patients (28.8%) with microcarcinomas, six of them (10.2%) had cervical LN involvement, whereas of the 42 patients (71.2%) with macrocarcinomas, 17 of them (28.8%) had cervical LN metastasis. The correlation between the tumor size and the number of metastatic LNs in our study was weakly positive (r = 0.332, P &lt; 0.05). Conclusion: The decision regarding CLND should be selected on an individual base as even small micro PTC could metastasize to the local LNs.

Optimal range of lymph node dissection in patients with unilateral papillary thyroid carcinoma with lateral cervical lymph node metastasis.

Whether patients with unilateral papillary thyroid carcinoma (PTC) with lateral cervical lymph node metastasis (LLNM) require prophylactic central regional lymph node dissection (CLND) remains unclear. Herein, we investigated the independent risk factors associated with contralateral central lymph node metastasis (cCLNM) in unilateral PTC with LLNM and analyzed the optimal extent of lymph node dissection by comparing the 5-year recurrence-free survival rates. We retrospectively analyzed 695 patients with unilateral papillary thyroid carcinoma and lateral cervical lymph node metastasis. Factors including sex, age, multifocal, location of primary tumor, tumor diameter, capsule invasion, thyroid nodular goiter, Hashimoto thyroiditis, ipsilateral central lymph node metastasis(iCLNM), and lateral cervical lymph node metastasis were analyzed using univariate and multivariate logistic regression analyses to explore the independent risk factors of cCLNM. Propensity scores were matched to compare the 5-year recurrence-free survival rates in patients divided by different lymph node metastases and dissections. Of all patients who underwent bilateral (b)CLND, 52% (149/286) had cCLNM. Receiver operating characteristic (ROC) curve analysis was performed on 286 patients who underwent bCLND, for which a tumor diameter of 20.5 mm and number of LLNM of 3.5 were used as the thresholds for predicting cCLNM. The 5-year recurrence-free survival (RFS) rates in the cCLN-negative and cCLN-positive groups were 98.6% and 91.2%, with statistically significant differences (P=0.034). The 5-year RFS rates showed no significant difference between the ipsilateral (i)CLND and bCLND groups (P=0.235). Multifactorial regression analysis showed that tumor diameter >2 cm, presence of iCLNM, and number of LLNM >3 were independent risk factors of cCLNM.But male sex, young age (<45 years), multifocality, location of primary tumor, capsule invasion, thyroid nodular goiter, and Hashimoto thyroiditis were not associated with cCLNM. Not all unilateral PTC with LLNM require prophylactic cCLND; however, prophylactic cCLND is necessary in cases which display high-risk factors for cCLNM, including primary diameter >2 cm, iCLNM, and number of LLNM >3.

Ultrasound and demographic predictors of papillary thyroid cancer local metastasis at the preoperative stage: a predictive model

Background. Due to the low sensitivity and specificity of neck ultrasound in the evaluation of the central lymph nodes, it is necessary to find alternative ways to predict central lymph node metastases in patients with papillary thyroid cancer (PTC). The purpose of the study is to develop a prognostic model for assessing the risk of local metastasis of papillary thyroid cancer based on preoperative ultrasound and demographic predictors. Materials and methods. A retrospective monocenter cohort study was conducted. The data of 401 patients who underwent surgery for PTC were processed. The main group included 179 patients in whom central lymph node metastases were detected during histopathological examination. The comparison group consisted of 222 patients without metastases according to the results of histopathological examination. When conducting the analysis, the following signs were considered as risk factors: subcapsular location of the tumor; size; blurred boundaries; the presence of calcification areas (microcalcifications); age of a patient. Inclusion criteria: PTC that was cytologically confirmed at the preoperative stage; surgeries (thyroidectomy/hemithyroidectomy and central neck lymph node dissection). Exclusion criteria: history of neck surgery; multifocal lesions of the thyroid gland. Results. The following logistic equation was obtained using the StatPlus program: y = –1.839 – 0.037 × X1 + 0.097 × X2 + 1.123 × X3 + 1.198 × X4 + + 0.692 × X5, where X1, X2, X3, X4, X5 are age (years), size (mm), subcapsular location (presence), blurred boundaries (presence), calcifications (presence), respectively. The obtained prognostic model provided the following operational characteristics when specifying the threshold value for P, which is equal to 0.44 (the decisive rule X &gt; T): sensitivity — 75.4 %, specificity — 79.3 %, diagnostic efficiency — 75.1 %. To assess the quality of the model, the receiver operator characteristic (ROC) analysis was performed. The following data were obtained: area under the ROC curve = 0.797 (95% confidence interval: 0.753–0.841), which corresponds to the good quality of the model, and Youden index J = 0.5155. Checking the quality of the model on a control group of 100 people gave the following results: sensitivity — 72.2 %, specificity — 76.1 %, diagnostic efficiency — 75.8 %. Conclusions. The application of a prognostic model based on ultrasound data and the patient’s age makes it possible to predict the presence of local metastases of the PTC at the preoperative stage with a diagnostic efficiency of 75.8 %. No prognostic model gives 100% prediction accuracy. When choosing the treatment, additional influencing factors (history of radiation exposure, burdened family history, etc.) for a specific patient should be considered.

Risk factors for central lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study.

Thyroid cancer is the most prevalent endocrine malignancy, with its global incidence increasing annually in recent years. Papillary carcinoma is the most common subtype, frequently accompanied by cervical lymph node metastasis early on. Central lymph node metastasis (CLNM) is particularly the common metastasis form in this subtype, and the presence of lymph node metastasis correlates strongly with tumor recurrence. However, effective preoperative assessment methods for CLNM in patients with papillary thyroid carcinoma (PTC) remain lacking. Data from 400 patients diagnosed with PTC between January 1, 2018, and January 1, 2022, at the Shandong Provincial Hospital were retrospectively analyzed. This data included clinicopathological information of the patients, such as thyroid function, BRAF V600E mutation, whether complicated with Hashimoto's thyroiditis, and the presence of capsular invasion. Univariate and multivariate logistic regression analyses were performed to assess the risk factors associated with cervical CLNM in patients with PTC. Subsequently, a clinical prediction model was constructed, and prognostic risk factors were identified based on univariate and multivariate Cox regression analyses. Univariate and multivariate analyses identified that age >45 years (P=0.014), body mass index ≥25 (P=0.008), tumor size ≥1 cm (P=0.001), capsular invasion (P=0.001), and the presence of BRAF V600E mutation (P<0.001) were significantly associated with an increased risk of CLNM. Integrating these factors into the nomogram revealed an area-under-the-curve of 0.791 (95% confidence interval 0.735-0.846) and 0.765 (95% confidence interval: 0.677-0.852) for the training and validation sets, respectively, indicating strong discriminative abilities. Subgroup analysis further confirmed that patients with papillary thyroid microcarcinoma and BRAF V600E mutations who underwent therapeutic central compartment neck dissection had significantly better 3-year disease-free survival than those who had prophylactic central compartment neck dissection (P<0.001). The study revealed that age >45 years, body mass index ≥25, tumor size ≥1 cm, BRAF V600E mutation, and capsular invasion are the related risk factors for CLNM in patients with PTC. For patients with clinically nodal-negative (cN0) papillary thyroid microcarcinoma, accurately identifying the BRAF V600E mutation is essential for guiding the central lymph node dissection approach and subsequent treatments.

Central node dissection from the perspective of lateral neck node metastasis in papillary thyroid carcinoma

ObjectivesControversy exists on how to handle central lymph nodes in papillary thyroid carcinoma, particularly regarding indications for prophylactic central neck dissection (CND). Central node metastases are more difficult to diagnose preoperatively than lateral node metastases. MethodsWe enrolled 493 patients with papillary thyroid carcinoma treated at our department in the past 22 years. Metastatic lymph nodes were diagnosed preoperatively mainly by ultrasonography. In principle, CND was performed for all cases; ipsilateral CND was performed for hemithyroidectomy, and bilateral CND was performed for total thyroidectomy. Lateral neck dissection (levels II to V; LND) was performed for metastases to lateral neck lymph nodes (clinical node (cN) 1b). ResultsThe cN stage was cN0 in 365 patients, cN1a in 10, and cN1b in 118. Of the 357 patients with stage cN0 who underwent CND, 42.9 % had pathologically positive nodes (pN+) in level VI, and of the 118 with stage cN1b who underwent CND, 78.0 % had pN+ in level VI. Cases with advanced T stage were significantly more common with pN+ in level VI. Level VI metastases were significantly associated with pN+ in level IV. As the total number of pN+ at each level of the lateral neck increased, the rate of patients with pN+ in level VI increased, and in patients with 3 or more pN+, about 85 % had level VI metastases. ConclusionBecause about half of the patients with cN0 patients had pN+ in level VI, and the rate of pN+ in level VI in each clinical T stage was 46 to 65 %, prophylactic CND should be performed, considering the various clinical benefits. Central nodes will have metastases in about 80 % of cases with lateral node metastases, requiring more accurate dissection. In lateral node metastases, there is a significant association between metastases in levels IV and VI.

Combining Clinicopathologic and Ultrasonic Features for Predicting Skip Metastasis of Lateral Lymph Nodes in Papillary Thyroid Carcinoma.

Skip metastasis, regarded as lateral lymph node metastasis (LLNM) without involving the central lymph node metastasis (CLNM), in papillary thyroid carcinoma (PTC) patients is commonly unpredictable. The purpose of the present research was to investigate the independent risk factors of skip metastasis in patients with PTC. In the present research, 228 consecutive PTC patients who experienced total thyroidectomy coupled with central and lateral lymph node dissection from May 2020 to September 2022 at the Affiliated hospital of Jiangsu University were included in our research. Univariate and multivariate analysis were then applied to investigate the risk factors of skip metastasis in patients with PTC. Furthermore, a predictive model of skip metastasis was then constructed based on risk factors. The skip metastasis rate was 11.8% (27/228) in the current research. After the univariate and multivariate analysis, tumor size ≤ 10 mm, unilaterality, microcalcification, and upper tumor location were determined to be predictive factors of skip metastasis. The risk score of skip metastasis was calculated: risk score = 1.229 × (if tumor nodule ≤ 10mm) + 1.518 × (if unilaterality nodule) + 1.074 × (if microcalcification in nodule) + 2.332 × (if nodule in upper location). Tumor size ≤ 10 mm, unilaterality, microcalcification, and upper tumor location can increase the occurrence of skip metastasis in patients with PTC, which is expected to provide useful information to guide the suitable intraoperative window.

Interpretable machine learning model based on the systemic inflammation response index and ultrasound features can predict central lymph node metastasis in cN0T1-T2 papillary thyroid carcinoma.

It is arguable whether individuals with T1-T2 papillary thyroid cancer (PTC) who have a clinically negative (cN0) diagnosis should undergo prophylactic central lymph node dissection (pCLND) on a routine basis. Many inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammatory index (SII), have been reported in PTC. However, the associations between the systemic inflammation response index (SIRI) and the risk of central lymph node metastasis (CLNM) remain unclear. Retrospective research involving 1,394 individuals with cN0T1-T2 PTC was carried out, and the included patients were randomly allocated into training (70%) and testing (30%) subgroups. The preoperative inflammatory indices and ultrasound (US) features were used to train the models. To assess the forecasting factors as well as drawing nomograms, the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were utilized. Then eight interpretable models based on machine learning (ML) algorithms were constructed, including decision tree (DT), K-nearest neighbor (KNN), support vector machine (SVM), artificial neural network (ANN), random forest (RF), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and categorical boosting (CatBoost). The performance of the models was evaluated by incorporating the area under the precision-recall curve (auPR) and the area under the receiver operating characteristic curve (auROC), as well as other conventional metrics. The interpretability of the optimum model was illustrated via the shapley additive explanations (SHAP) approach. Younger age, larger tumor size, capsular invasion, location (lower and isthmus), unclear margin, microcalcifications, color Doppler flow imaging (CDFI) blood flow, and higher SIRI (≥0.77) were independent positive predictors of CLNM, whereas female sex and Hashimoto thyroiditis were independent negative predictors, and nomograms were subsequently constructed. Taking into account both the auROC and auPR, the RF algorithm showed the best performance, and superiority to XGBoost, CatBoost and ANN. In addition, the role of key variables was visualized in the SHAP plot. An interpretable ML model based on the SIRI and US features can be used to predict CLNM in individuals with cN0T1-T2 PTC.

Risk factors associated with preferential lateral lymph node metastasis in papillary thyroid carcinoma.

Lateral lymph node metastasis (LLNM) is common in patients with papillary thyroid cancer (PTC), usually occurring after central lymph node metastasis (CLNM). However, some patients experience LLNM without first developing CLNM. This study aimed to identify the risk factors for developing LLNM without CLNM. We retrospectively reviewed 421 patients diagnosed with PTC who underwent lobectomy or total thyroidectomy with central and ipsilateral lateral lymph node dissection. We collected clinicopathological data and used univariate and multivariate logistic regression analyses to determine the risk factors associated with LLNM without CLNM. The LLNM without CLNM frequency was 18.3% (77/421). Univariate analyses demonstrated that age over 55 years, primary tumor in the upper portion of the thyroid, the number of central lymph node (CLN) and LLNM, primary tumor size, and the summed size of multi-foci tumors smaller than 1 cm were significantly associated with LLNM without CLNM (p < 0.05). Multivariate analysis revealed that LLNM without CLNM was more likely to occur in patients aged ≥55 years (odds ratio [OR], 2.309; 95% confidence interval [CI], 1.133-4.704; p = 0.021), and primary tumor in the upper portion of the thyroid (OR, 0.524; 95% CI, 0.295-0.934; p = 0.028). The lymph node metastasis pattern in patients with PTC is not constant. Therefore, surgeons should evaluate the lateral lymph nodes, especially in patients older than 55 years or when the primary tumor is in the upper portion of the thyroid.

Intraoperative pathologic evaluation of central compartment lymph nodes in patients undergoing lobectomy for unilateral papillary thyroid carcinoma

Background/ObjectiveAlthough papillary thyroid carcinoma (PTC) has an excellent prognosis, it can cause central lymph node metastasis (CLNM) which can increase local recurrence. Intraoperative pathologic evaluation (IOPE) can provide evidence regarding CLNM and help surgeons determine the appropriate surgical approach. The aim of this study was to evaluate the efficacy of IOPE and to determine risk factors associated with CLNM in unilateral PTC without preoperative clinical evidence of CLNM. MethodsMedical charts of 227 patients who had unilateral PTC without clinical lymph node metastasis preoperatively were reviewed retrospectively. They were scheduled for thyroid lobectomy and prophylactic central lymphadenectomy (CND) from January 1, 2017 to December 31, 2017. ResultsTotal follow-up period was 47.6 ± 10.6 months. CLNM was identified in 57 (25.1%) patients during IOPE and in 72 (31.7%) patients during final pathological analysis. The sensitivity and specificity of IOPE were 76.4% and 98.7%, respectively. IOPE through central lymph node dissection was safely performed with low complications (vocal cord palsy, 5.7%; hypoparathyroidism, 22.8%). Age < 55 years, echogenic foci on preoperative ultrasonography, and extrathyroidal extension at final pathological report were significantly associated with an increased risk of CLNM (p = 0.006, p < 0.001, and p < 0.001, respectively). In terms of oncological outcomes, there was no significant difference between the true negative and false negative results in IOPE. ConclusionIOPE can safely provide accurate information for determining disease status and surgical extent. Further long-term studies are needed to evaluate clinical benefits of IOPE.

Sentinel lymph node mapping: current applications and future perspectives in thyroid carcinoma.

Sentinel lymph node (SLN) mapping is a standard, minimally-invasive diagnostic method in the surgical treatment of many solid tumors, as for example melanoma and breast cancer, for detecting the presence of regional nodal metastases. A negative SLN accurately indicates the absence of metastases in the other regional lymph nodes (LN), thus avoiding unnecessary lymph nodal dissection. Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma (TC) with cervical LN metastases at diagnosis in 20-90%, and nodal involvement correlates with local persistence/recurrence. The SLN in PTC is an intraoperative method for staging preoperative N0 patients and for detecting metastatic LNs "in and outside" the cervical LN central compartment; it represents an alternative method to prophylactic central neck node dissection. In this review we summarize different methods and results of the use of SLN in TC. The SLN identification techniques currently used include the selective vital-dye (VD) method, 99mTc-nanocolloid planar lymphoscintigraphy with intraoperative use of a hand-held gamma probe (LS), the combination LS + VD, and the combination LS and preoperative SPECT-CT (LS + SPECT/CT). The application of the SLN procedure in TC has been described in many studies, however, the techniques are heterogeneous, and the role of SLN in TC, with indications, results, advantages and limits, is still debated.

Investigating the optimal parathyroid autotransplantation strategy in transareolar endoscopic thyroidectomy: A retrospective cohort study

There is ongoing debate about whether intraoperative parathyroid autotransplantation effectively prevents permanent hypoparathyroidism after thyroidectomy. This study aims to examine its impact on postoperative parathyroid function and determine the best autotransplantation strategy. A retrospective analysis was conducted on 194 patients who underwent total thyroidectomy with central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC). Patients were divided into four groups based on the number of parathyroid autotransplants during surgery: Group 1 (none, n=43), Group 2 (1 transplant, n=60), Group 3 (2 transplants, n=67), and Group 4 (3 transplants, n=24). Various clinical parameters were collected and compared among the groups. Parathyroid autotransplantation was identified as a risk factor for temporary hypoparathyroidism (OR: 1.74; 95% CI: 1.27-2.39, P=0.001) and a protective factor for permanent hypoparathyroidism (OR: 0.27; 95% CI: 0.14-0.55, P<0.001). At 12 months postoperative, systemic parathyroid hormone (PTH) levels increased progressively from Groups 1 to 4, with significant differences observed only between Group 1 and Group 2 (P<0.02). Difference values in systemic PTH levels between Month 1 and Day 1 postoperative increased progressively from Groups 1 to 4, with statistically significant differences observed between adjacent groups (P<0.02). The number of dissected positive lymph nodes increased progressively across the four groups, showing statistical differences (P<0.02). Parathyroid autotransplantation can prevent permanent hypoparathyroidism. Additionally, we recommend preserving parathyroids in situ whenever possible. If autotransplantation is required, it should involve no more than two glands.

SAT576 Change Is Not Always For The Best! A Transformation of Papillary Into Metastatic Anaplastic Thyroid Carcinoma

Abstract Disclosure: J. Syeda: None. R. Zafar: None. K. Rajamani: None. INTRODUCTION: Anaplastic thyroid carcinoma (ATC) can occur de-novo or from preexisting well-differentiated thyroid carcinoma (1). The presence or absence of certain driver mutations can help predict the likelihood of this transformation process. We present a case of an elderly female with an initial diagnosis of well-differentiated papillary thyroid cancer (PTC) with a transformation into metastatic anaplastic thyroid carcinoma (ATC). CASE PRESENTATION: An 81-year-old female patient was initially seen 8 years ago with a 35-year history of goiter. At the initial presentation, she felt well and did not have any symptoms. Physical examination revealed an enlarged thyroid gland with left lobe nodularity. A thyroid ultrasound showed a multinodular thyroid gland including a 2x1.7x1.2 cm solid nodule with macro calcifications in the right lobe, 2.8x2.6x2.5 cm solid nodule, and 1.6x1.3x1.6 cm heterogeneous solid nodule with calcifications and irregular margins in the left lobe. She had a fine needle aspiration of these three nodules. The right nodule was non-diagnostic and both left nodules were positive for PTC. She underwent a total thyroidectomy and central lymph node dissection. Radioactive iodine treatment with 163mCi was administered after surgery. One and a half years after surgery, her thyroglobulin levels started trending upward. This led to a further workup including a PET/CT scan, which showed a hyper metabolic 6 mm left supraclavicular lymph node. Needle biopsy of this lymph node disclosed metastatic PTC. The pathologic diagnosis following surgical resection was positive for metastatic poorly differentiated thyroid carcinoma. A subsequent PET/CT scan and a thyroid ultrasound showed an abnormal uptake of the left neck lymph node and additional metastatic nodes in the left neck respectively. A core needle biopsy of these lesions was positive for ATC. Foundation One CDx testing was positive for BRAF V600E, TP53, and TERT promoter mutations. Cellblock from the initial thyroidectomy was reevaluated by pathology and confirmed no evidence of ATC. Foundation One CDx testing of the thyroidectomy specimen was positive for BRAF V600E and TERT promoter mutations. Surveillance imaging shows mediastinal adenopathy, left pleural thickening, and bone and liver metastases. DISCUSSION: Anaplastic transformation is not uncommon (1). This case supports the evidence that TERT promoter mutations may not trigger anaplastic transformation but may predispose to the aggressive PTC phenotype prone to conversion to ATC when one of the ATC-related “second hit” genetic events occurs (2). This case suggests that the “second hit” event is a TP53 mutation. The detection of a TP53 mutation in PTC with an aggressive phenotype may help predict anaplastic transformation. REFERENCES: 1-Endocrine Pathology. 2021 Mar; 32(3):347-356. 2- Semin Cancer Biol. 2020 Apr; 61: 23-29. Presentation: Saturday, June 17, 2023

SAT562 Metastatic Oncocytic (Formerly Hürthle Cell) Thyroid Carcinoma in a Patient With Birt-Hogg-Dubé Syndrome

Abstract Disclosure: S. Vaid: None. R. Klein: None. P. Veeraraghavan: None. D.M. Blakaj: None. A. Agrawal: None. J. Sipos: None. S.I. Sherman: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Birt-Hogg-Dubé syndrome (BHD) is a rare, autosomal dominant disorder due to a germline loss-of-function mutation in the folliculin (FLCN) gene. Clinical manifestations include pulmonary cysts, renal cell carcinoma, and skin tumors, while tumors of other sites such as thyroid are uncommon. Here, we report an extremely rare case of oncocytic thyroid carcinoma (OTC) in a patient with BHD. Clinical case: A 55-year-old male with BHD noted a lump in his neck which was identified as a 3 cm right thyroid nodule on sonogram. Medical history only included BHD, which was diagnosed based on the presence of pulmonary cysts and two family members with BHD. No family members had thyroid tumors, and the patient denied any history of radiation exposure. Fine needle aspiration biopsy was indeterminate (Bethesda III). A total thyroidectomy and central lymph node (LN) dissection was performed as LN metastases were identified on intraoperative frozen section. Histopathology revealed 3 foci of OTC, largest being 3.8 cm, with extrathyroidal extension into fibroadipose tissue, 3/31 LN metastases with the largest deposit of 0.5 cm without extranodal extension. A 156.6 mCi dose of I-131 radioiodine (RAI) was administered. No uptake was noted on the post-therapy scan. Four months later, new right lateral cervical lymphadenopathy was noted on computed tomogram (CT). A right lateral selective neck dissection was performed, which identified 3/28 metastatic LNs without extranodal extension. Next generation gene sequencing testing of the metastatic tumor revealed the pathogenic FLCN (H429fs*27) variant, along with TP53 (R248Q), and DAXX (L666fs*29) pathogenic variants. Over the next 20 months, serum thyroglobulin increased from 1.8 ng/ml to 121 ng/mL (normal: 1.6 - 59.9 ng/mL). Several sub-centimeter lung nodules and new right cervical lymphadenopathy were noted on CT, and these lesions demonstrated increased uptake on fluorodeoxyglucose positron emission tomography (PET/CT) and on Ga-68 DOTATATE PET/CT scans. Due to close proximity to the right internal jugular vein, the cervical lymphadenopathy was deemed to be inoperable. Stereotactic radiation was administered to the neck, which resulted in substantial shrinkage of the neck metastases. The patient continues to be on active surveillance, with tyrosine kinase inhibitors or peptide receptor radionuclide therapy being potential future systemic therapy options in case of disease progression. Conclusion: Thyroid tumors have been occasionally reported in BHD. While most of them are papillary or follicular tumors, only one case of OTC in BHD has been previously reported in the literature [1]. This report underscores the importance of screening for thyroid neoplasms in patients with BHD. Reference: 1. Panagiotidis et al. World J Nucl Med. 2018;17(2):123-125 Presentation Date: Saturday, June 17, 2023

SAT565 Is Firefighting An Occupational Risk For Papillary Thyroid Cancer? A Case Report

Abstract Disclosure: S.A. Diamond-Rossi: None. P. Lee: None. C. Thomas: None. R. Stanislawski: None. J. Kim: None. Background: Papillary thyroid cancer (PTC) is the most prevalent histologic type of thyroid cancer. The toxic exposures associated with firefighting from both protective gear and combustion products have brought to question whether this population is at an increased risk of developing certain malignancies, including thyroid cancer. The objective of this case report is to raise awareness of the possible association between firefighting and thyroid cancer. Case Presentation: A 46-year-old asymptomatic male career firefighter presented to our clinic following a mobile screening thyroid ultrasound which revealed bilateral suspicious nodules. FNAs of a 1.0 cm right nodule and 1.2 cm left nodule were consistent with papillary thyroid cancer. Lymph node mapping revealed bilateral suspicious lymph nodes in levels 3 and 4 with FNAs confirming metastatic PTC. He underwent total thyroidectomy with bilateral central and lateral lymph node dissections confirming multifocal disease, which included numerous submillimeter foci of PTC. 21 of 68 lymph nodes had metastatic disease. He is now scheduled for adjuvant radioactive iodine therapy. Discussion: Compared to the general population, firefighters have a higher incidence of thyroid cancer. In 2022, the International Agency for Research on Cancer (IARC) announced that occupational exposure as a firefighter would be considered a Group 1 carcinogen, designating this exposure as having sufficient evidence for carcinogenicity in humans. In recognition of this risk, our local fire department, the Fairfax County Fire &amp; Rescue, has implemented a cancer screening protocol offered to firefighters which includes a mobile thyroid ultrasound. Our patient had extensive disease with bilateral lymph node involvement requiring radioactive iodine after surgical resection. Without a screening ultrasound, it can be presumed that our patient would have presented later and perhaps with even more advanced disease. Firefighters are exposed to carcinogens and possible endocrine disrupting chemicals as part of their work, either via their protective equipment or products of the fire itself. More research is needed to determine if the higher incidence of thyroid cancer can be attributed to this occupational exposure versus surveillance bias due to increased screening of this population in recent years. Presentation: Saturday, June 17, 2023

SAT536 A Case of Papillary Thyroid Cancer in Multiple Cervical Lymph Nodes, But Not Found in Thyroid Tissue on Pathology

Abstract Disclosure: M.A. Green: None. G.Y. Kim: None. Introduction:As technology advances, imaging becomes increasingly frequent and within the thyroid gland nodules can often be detected. After detection comes evaluation and lymph nodes within the neck are an integral part of this step. For that reason, fine needle aspiration (FNA) of cervical lymph nodes is known to lend a hand toward diagnosis. Here we present a patient who was diagnosed with Papillary Thyroid Cancer (PTC) from FNA pathology of a lymph node, but PTC was not noted within pathology of the thyroid tissue after total thyroidectomy. Case Presentation: This patient is a 34 year-old female with a history of ovarian cancer who presented to the clinic for a thyroid nodule and Hashimoto’s disease. A bed side ultrasound noted a right upper pole 1.6 x 0.6 x 0.6 cm thyroid nodule and a solid 1.8 x 1.5 x 0.8 cm nodule superior to the isthmus likely representing a delphian lymph node. As well, significant cervical lymphadenopathy was seen. A biopsy of the right upper pole nodule was nondiagnostic on FNA, but the delphian lymph node superior to the isthmus was positive for PTC. The patient then underwent total thyroidectomy and right and central neck lymph node dissections. Interestingly, PTC was noted in 3 of 27 lymph nodes in the central compartment, 5 of 18 lymph nodes excised with the thyroid tissue with extranodal extension, and 5 of 24 lymph nodes in the right neck compartment, but not noted in the thyroid tissue itself. The largest metastatic dimension of PTC within the cervical lymph nodes was noted to be 3 cm. The pathology noted a 1.0 cm tumor in the right lobe “approaching skeletal muscle” and psammoma bodies within the left lobe. After the patient’s surgery her stimulated thyroglobulin reported as 0.21 NG/mL and thyroglobulin antibody 2 IU/mL. She was then able to receive 30 mCi of I 131 sodium iodide. TSH maintained at goal on levothyroxine 200 mcg daily. Discussion: Diagnosis of PTC within multiple cervical lymph nodes, but not noted on thyroid pathology is very uncommon. It is highly unlikely in our patient that a cancer within the thyroid does not exist and there are theories to postulate this unique finding. These include missed pathology on the dissection, tumor regression prior to removal, or possibly ectopic tissue as the source of PTC. Although in our patient, given the significant amount of positive cervical lymph nodes, it is hard to believe that ectopic tissue away from the neck was the source or that tumor regression occurred. The pathological findings of psammoma bodies suggest the presence of PTC that spread to the lymphatic system. As well, the nature of thyroid removal leads to some destruction of tissue prior to evaluation. This case highlights the importance of thorough lymph node evaluation as a complete part of preoperative PTC assessment. Presentation Date: Saturday, June 17, 2023

SAT557 Unexpected Whole Body Scan Finding

Abstract Disclosure: A. Arce Gastelum: None. C.Y. Liu: None. K. McCowen: None. A 41-year-old man presented with a neck mass. Following total thyroidectomy with central and bilateral lateral neck node dissection, he received a diagnosis of stage I T2N1bMx multifocal papillary thyroid cancer with extensive extrathyroidal extension, angioinvasion and 14/65 positive lymph nodes. Surgery was complicated by temporary post operative hypoparathyroidism. Lab testing one week post thyroidectomy, before radioiodine ablation showed a serum TSH 23 uIU/mL, thyroglobulin: 34.1 ng/mL, with thyroglobulin antibody: &amp;lt;0.9 [IU]/mL.Post RAIA Whole Body Scan revealed increased uptake in the right orbit, concerning for metastatic disease. Confirmatory MRI of the brain showed a right superior intraorbital cystic lesion. Although orbital metastases are infrequent, a metastatic lesion was suspected due to the aggressiveness of his thyroid cancer. The patient was referred to ophthalmology several months after surgery and underwent right orbitotomy with excision and biopsy of the mass. The pathology was consistent with a multilocular cystic tumor lined by bland cuboidal epithelium, containing proteinaceous concretions and entirely negative for metastasis. Extensive thyroid cancer is treated with surgery followed by radioactive iodine (I-131) in case of tissue remnants or extra nodal metastases. Although unusual, false-positive scans exhibiting the presence of 131I uptake in the absence of residual thyroid tissue can occur.Fibrotic lung conditions, pleural effusions and bronchiectatic lesions have been reported to concentrate iodine in the absence of thyroid cancer metastasis. One prior report of a conjunctival inclusion cyst also resulted in radioiodine uptake in the orbit. Unless identified as a false positive, radioiodine uptake may result in a diagnostic fallacy. The correlation of clinical signs and serum thyroglobulin trends with imaging techniques should be emphasized to prevent unnecessary additional therapy. Presentation Date: Saturday, June 17, 2023

SAT555 Utility of 18F-DOPA PET/CT in the Diagnosis of Medullary Thyroid Cancer in a Patient with Multiple Endocrine Neoplasia Type 2B

Abstract Disclosure: D.G. Varghese: None. S. Akshintala: None. A. Jha: None. S. Gubbi: None. A. Reno: None. J. Klubo-Gwiezdzinska: None. K. Pacak: None. J. Glod: None. J. Del Rivero: None. Background: MEN2B is a cancer predisposition syndrome caused by an activating mutation in the RET proto-oncogene. It is characterized by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and extra endocrine features. U/S, CT, MRI and 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihyroxyphenylalanine (18F-FDOPA), 68Ga-DOTA-(0)-Tyr(3)-octreotate (68Ga-DOTATATE) PET/CT scans have been used for the diagnosis and follow up of MTC. However, there is increasing evidence of 18F-FDOPA PET as more specific imaging modality in the diagnosis of MTC since L-type amino acid transporters have shown to be present in MTC cells.Clinical Case: 26-year-old female presented with HTN at the age of 17. The patient developed episodes of nausea/vomiting, intermittent headaches with systolic BP in the 190’s. Further work-up revealed bilateral adrenal nodules with elevated plasma metanephrines. The patient underwent left adrenalectomy and a year later, right adrenal nodule resection confirming PHEO. On follow up, calcitonin was elevated, and the patient underwent a total thyroidectomy with bilateral central lymph node dissection. At age 19 she was diagnosed with MEN2B (RET mutation, p.Met918Thr). With rising calcitonin, she was referred to our institution for further evaluation. Her serum calcitonin was 31986(&amp;lt;7.6 pg/ml), CEA 631 (0.8-3.4 ng/ml), fractionated plasma normetanephrine 565 (18-112 pg/ml), and metanephrine 304 (12-61 pg/mL). MRI of the abdomen showed enlarging adrenal masses. 18F-FDG PET/CT scan showed a focus of uptake (SUVmax of 8.5) in posterior right thyroid bed, uptake in the liver (SUVmax of 7.5) and uptake in the right adrenal gland and left adrenal bed; 68Ga-DOTATATE PET/CT scan showed a faint uptake in the right thyroid lobe (SUVmax of 2.7) and an 18F-FDOPA PET/CT scan showed intense uptake in both lobe of the thyroid, multiple lesions in the liver and suspicious focus in the right adrenal bed. The patient underwent bilateral adrenalectomy for recurrent PHEO and her plasma metanephrines normalized. Conclusion: This case adds to the mounting evidence in the usage of 18F-FDOPA PET/CT scan as a useful imaging modality for MTC especially in the setting of MEN2B syndrome. A head-to-head comparison in 18 patients, both per patient and per lesion sensitivity by 18F-FDOPA PET/CT (72%, 85%) was found to be statistically superior compared to 68Ga-DOTATATE PET/CT (33%, 20%), and 18F-FDG PET/CT (17%, 28%). A meta-analysis conducted in MTC consisting of 306 patients from 14 studies, 18F-FDOPA compared to 18F-FDG and 68Ga-DOTATATE showed the highest surface under the cumulative ranking curve (SUCRA) value in both patient and lesion-based analyses irrespective of serum calcitonin/CEA values or calcitonin doubling time. The potential for use of 18F-FDOPA as a diagnostic agent and the potential to provide insight into possible therapeutic targets are unknown and should be further studied. Presentation Date: Saturday, June 17, 2023