Papillary Thyroid Cancer Cases Research Articles

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

SAT530 Use of Tamoxifen and Cabergoline to Suppress Breast Tissue Uptake of Radioactive Iodine Among Differentiated Thyroid Cancer Patients

Abstract Disclosure: A.H. Mohamed: None. M. Basina: None. Background: Radioactive iodine (RAI) has been used in thyroid cancer treatment. Physiologic breast tissue uptake and accumulation of RAI are not desirable due to increased carcinogenesis risk. Case1:31 years old non lactating female diagnosed with stage IVB papillary thyroid cancer and underwent total thyroidectomy and bilateral neck dissection. She had high initial risk with stage of T3N1bM1 and underwent 118 mCi of I-131 treatment with pulmonary foci. One year later, she had biochemical and structural incomplete response and underwent I-123 RAI uptake scan demonstrating residual disease in the right neck and diffuse breast uptake, thus, I-131 treatment was deferred. The patient was started on cabergoline 0.5 mg daily for 2 months. Repeated I-123 uptake scan during day 2 of Cabergoline remained with diffuse breast uptake. Four months later, another repeated RAI uptake scan after 4 months showed minimal breast uptake and RAI I-131 treatment was given. She had normal mammogram screening. Case2: 41 years old non lactating female diagnosed with stage II papillary thyroid cancer and underwent total thyroidectomy with right neck dissection. She had moderate initial risk with stage of T3 N1aM0 and underwent 159 mCI of I-131 treatment. Two years later, she had structural incomplete response and repeated I-123 uptake scan showed thyroid bed foci of avid uptake and diffuse bilateral breast uptake, thus, I-131 therapy was deferred. The patient was started on cabergoline 0.25 mg daily for 4 weeks and Tamoxifen 10 mg twice daily for 10 days prior to repeated I-123 RAI scan that redemonstrated thyroid bed foci without breast tissue uptake. She had normal mammogram screening. DiscussionPotential malignancy risk secondary to non-thyroidal RAI accumulation in tissues was reported. The mechanism of breast RAI uptake involves Na/iodide symporter channel regulated by prolactin and estrogen. Blocking the effect of these hormones prior to I-131 administration are believed to prevent breast uptake. We describe two papillary thyroid cancer cases with breast RAI uptake that was suppressed partially with Cabergoline (prolactin lowering agent) and fully with combination of Cabergoline and Tamoxifen (estrogen receptor blocker). Further studies are needed to evaluate the efficacy of Tamoxifen and cabergoline in suppressing physiologic breast RAI uptake. Presentation Date: Saturday, June 17, 2023

SAT540 A Case of Simultaneous Medullary Thyroid Cancer (MTC) And Papillary Thyroid Cancer (PTC) In a Patient With Germline RET Mutation

Abstract Disclosure: N. Vaghasia: None. G. Jaiswal: None. Introduction: There are only handful of cases reported of concurrent MTC and PTC in a patient with germline RET proto-oncogene mutation. Case: A 41 year old female with no PMH presented to Endocrine clinic for evaluation of recently diagnosed RET mutation. Patient’s nephew passed away at 5 weeks of age from abnormal organogenesis of heart and brain. Genetic testing showed germline RET mutation. Subsequently her brother and his two children was tested positive for RET mutation. Patient underwent genetic testing which was positive for RET mutation. Patient was found to be heterozygous for p.V804M (c.2410G>A) mutation reported as moderate risk mutation in the RET gene. The result was consistent with an increased risk for RET-related cancers. No family history of MTC, pheochromocytoma or primary hyperparathyroidism was identified. Patient was asymptomatic on presentation and no previous symptoms concerning for any RET mutation related disease. Her physical examination was normal. Patient underwent testing for pheochromocytoma and hyperparathyroidism which was unremarkable. Patient’s calcitonin level was also normal. Patient had US thyroid done to evaluate for nodule and was found to have 1.62 x 0.97 x 1.50 cm mixed solid cystic, hypoechoic, irregular margins and punctate echogenic foci right sided nodule. No abnormal cervical lymph nodes. Patient underwent FNA of the suspicious nodule which was reported as benign based on Bethesda classification. Patient’s calcitonin level was undetectable <0.2 pg/ml (0.0-5.0). Patient underwent total thyroidectomy and on surgical pathology had three papillary microcarcinomas, classic type, 0.4 cm (right lobe), 0.3 cm (left lobe) and 0.1 cm (right lobe). Patient had medullary microcarcinoma 0.2 cm on left lobe. Background thyroid with C-cell hyperplasia. No lymphovascular invasion, no extrathyroidal extension and margins cleared. Discussion: Association of simultaneous MTC-PTC have been reported in few case reports in patient with germline RET mutation. There has been no risk factors or specific patient phenotype identified in previous cases to suggest any association between the two. One important feature in our case is the presence of highly suspicious thyroid nodule which on FNA was benign. This raise an important question on whether the co-existence of MTC and PTC in germline RET mutation decreases sensitivity of FNA. Also it is yet unknown if specific mutation like in our case p.V804M (c.2410G>A) is associated with higher incidence of multi-tumor pathology or not. Finally, our patient had normal calcitonin level despite having MTC which is unusual. Conclusion: Coexistence of MTC and PTC in germline RET mutation is an uncommon association and more information is required to understand common features, risk factors, phenotype and cancer aggressiveness in these patients. At this point it cannot be concluded that the association is a mere coincidence. Presentation Date: Saturday, June 17, 2023

SAT535 ANKRD26-RET Fusion Positive Metastatic Papillary Thyroid Carcinoma - Advanced Presentation of a Rare Mutation

Abstract Disclosure: H. Hashmi: None. A. Ankireddypalli: None. L. Burmeister: None. A. Nelson: None. K. Amin: None. Background: While rearranged during transfection (RET) protooncogene mutations have been commonly associated with thyroid malignancy, ankyrin repeat domain containing protein 26 (ANKRD26) has been primarily linked to hematologic malignancy. Exon 29 of ANKRD26 (Chromosome [Chr] 10p12.1) has been shown to fuse with exon 12 of RET (Chr 10q11.21), resulting in a genetic fusion mutation ANKRD26:RET. This is a rare genetic mutation in papillary thyroid cancer with only one previously reported case. We report the first case in the US of this novel genetic mutation with a unique clinical presentation. Clinical Presentation: A 48-year-old, male patient presented with lower back pain radiating to the lower extremities of one year duration. MRI lumbar spine revealed an irregular mass lesion in the L1 vertebral body with extraosseous soft tissue extension, L1 compression fracture and extension into the T12 body. CT CAP revealed a 4.8 x 3.6 cm, heterogenous right thyroid lobe with tracheal compression and sub centimeter pulmonary nodules in the left lower and right middle lobes. Biopsy of the L1 paravertebral mass was diagnostic for metastatic thyroid carcinoma of a follicular pattern. Molecular testing with a next generation sequencing fusion profile assay was positive for ANKRD26:RET gene rearrangement. Thyroid ultrasound was notable for a solid, hypoechoic, 3.2 x 3.1 x 2.9 cm right lobe nodule with echogenic foci and level 4 lymph nodes with loss of reniform shape and fatty hilum. FNA of the nodule and right level 4 lymph node was suspicious for follicular neoplasm. The patient was admitted for acute cord compression necessitating extensive laminectomy, vertebral reconstruction and resection of the L1 paraspinal tumor. Pathology was positive for metastatic, follicular variant, papillary thyroid carcinoma. Total thyroidectomy, central and right modified radical neck dissection was performed. Pathology demonstrated a 4.2 cm papillary carcinoma, follicular type with tall cell variant; confined to the thyroid. Extensive angioinvasion (≥ 4 vessels) and lymphatic invasion was present. 10/32 positive lymph nodes. TNM grading was T3aN1bM1. Summary: The only other case of ANKRD26-RET fusion positive papillary thyroid cancer in the literature was reported by Staubitz et al in Germany in 2019. They reported a case of a 78-year-old male with follicular variant papillary thyroid carcinoma (pT3,pN0,M0). To our knowledge, our case is the second worldwide and the first to be reported in the United States of this rare fusion protein positive thyroid cancer. Such an aggressive presentation with distant osseous metastases has to our knowledge not been previously described. Conclusion: The clinical and therapeutic implications of this rare genetic mutation are not currently well elucidated. We present this case with the intent to expand the existing literature and increase recognition of this rare genetic mutation. Presentation Date: Saturday, June 17, 2023

THU673 Unusual Metastasis Of Differentiated Thyroid Carcinoma

Abstract Disclosure: M. Aiad: None. O.A. Aluko: None. B. Bhatt: None. Background: Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid malignancy. Distant metastasis of PTC are rare and usually occur in the bones, lungs, and lymph nodes of the neck. Retinal and skin metastases are extremely rare. We present a case of PTC with metastasis to the distal extremity with sites including retina, skin and breasts. Clinical Case: A 40-year-old Caucasian female with a past medical history of papillary thyroid cancer at age 16 status post total thyroidectomy followed by two radioactive iodine treatments, who is incidentally found to have recurrent metastatic disease to lungs, retina, subcutaneous soft tissue and bones. After having an accident, trauma CT revealed pulmonary nodules and around the time patient started to notice subcutaneous lumps on the chest and gradually worsening blurry vision indicating further imaging as well as ophthalmological evaluation. The biopsy of the right lower lung nodules showed metastatic differentiated follicular variant papillary thyroid cancer, positive for RET mutation. TSH was appropriately suppressed at 0.128uIU/mL on levothyroxine 100 mcg daily, with elevated thyroglobulin level 47ng/mL and antibody 1.7IU/mL. The molecular testing was positive for RET gene mutation; thus she started targeted therapy with selpercatinib 120 mg twice daily. Shortly after starting therapy, she presented to the ER with complaints of headaches and refractory nausea. Imaging done showed evidence of intracranial metastases, bilateral intraocular lesions in the posterior globe as well as intraventricular hemorrhage. She received IV steroids, selpercatinib was held due to the possibility of exacerbating intraventricular hemorrhage. Following multidisciplinary discussion between neuro-oncology and radiation oncology, she started stereotactic radiotherapy (SRT) to choroidal plexus lesions with a plan to restart systemic therapy once SRT is completed. Conclusion: The epidemiological aspects of thyroid metastases in rare sites are likely unknown and could significantly impact patient management. Most cases of uncommon metastasis have been reported after several years of diagnosis such as in our patient who developed multiple metastasis to rare sites including skin, retina, breast and choroid plexus. Presentation: Thursday, June 15, 2023

Molecular features of thyroid cancer in children

Background. Malignant neoplasms of the thyroid gland are the most common endocrine malignant neoplasms in the children’s age group. Unlike adults, who most often have BRAF and RAS mutations, children have chromosomal displacements. The relevance is explained by the lack of comprehensive studies on thyroid cancer in children in the Russian-language literature.The aim of the study is — to summarize and systematize the literature data on the molecular features of thyroid cancer in children.Materials and methods. The authors conducted a search for publications in the PubMed electronic database using the following algorithm: Molecular AND Thyroid cancer AND pediatrics. We found 451 publications, and after reviewing the annotations, 111 studies describing the molecular features of thyroid cancer in the pediatric population were included in the review. Publications were excluded due to duplication and inconsistency with the subject of this study.Results. Instead of point mutations of BRAF and RAS, characteristic of adults, regardless of radiation status, chromosomal displacements are more common in children. Re-arrangement of RET/PTC genes is the most common, followed by BRAF fusions. Mutations of the TERT promoter, which are markers of the aggressive course of the disease in adults, are rare in children. DICER1 mutations appear to play a key role in pediatric cases of follicular and papillary thyroid cancer. Medullary thyroid cancer (MTC) in children requires the exclusion of multiple endocrine neoplasia syndrome (MEN type 2). Tumors originating from follicular cells other than MTC can rarely be familial. Literature data on the role of microRNA as a biomarker in thyroid carcinomas in children is currently limited.

Overall survival trends of papillary thyroid cancer: A Surveillance, Epidemiology, and End Results (SEER) population-based data (2002-2016).

e18108 Background: In the United States, the 5-year survival rate for patients with thyroid cancer is 98%. However, survival rates are mainly influenced by the type of thyroid cancer and the stage of the disease. The tremendous research in the area and the need to assess outcomes of recently implemented treatments necessitate the evaluation of the epidemiology and overall survival rates of the most common type of this malignancy, papillary thyroid cancer (PTC). Although the cause-specific survival (CSS) of Papillary Thyroid Cancer (PTC) patients has been extensively investigated, the overall survival (OS) of these patients is unclear. In this study, we aim to conduct an evaluation of survival trends after PTC diagnosis by stage of disease for the years 2002 through 2016 in the United States. Methods: We used the SEER 9 database to study PTC cases during 2002-2016. The patient survival data for the three disease stages (local, regional, and distal) were compared for the two time periods of interest, (2002-2008) and (2009-2016). The data for each cohort were split into six groups, (those whose deaths were in each of the five one-year intervals and those surviving the five-year follow-up period). These categorical counts were compared by the chi-square test of contingency table data. Statistical significance was taken as a p-value less than 0.05. Results: We reviewed 73,333 PTC cases in the United States from 2002 through 2016. There was an overall survival improvement with the exception of the distal stage, which did not demonstrate any statistical difference in the 2-time frames of interest. For local sites, there was a highly significant difference between the survival distributions of patients in the two time periods of interest (p = 0.0095; chi-square test statistic = 15.20 with 5 degrees of freedom). For regional sites, there was a highly significant difference between the survival distributions of patients in the two time periods of interest (p = 0.0077; chi-square test statistic = 15.72 with 5 degrees of freedom). For the distant stage, there was no significant difference between the survival distributions of patients in the two time periods of interest (p = 0.28; chi-square test statistic = 6.25 with 5 degrees of freedom). Conclusions: PTC’s survival rates have shown an improvement over the years 2002 through 2016, mostly noted in the local and regional stages. Although most patients with PTC have a favorable prognosis when conventional treatments are implemented, local recurrence and distant metastasis of advanced PTCs still hamper the survival and clinical management in certain patients.

Study to Evaluate the Pattern of Nodal Distribution in Papillary Thyroid Cancer.

Among the thyroid cancers, papillary thyroid cancer (PTC) is the most common with lymphatic metastasis. It has the propensity to spread to the level II-VI lymph nodes in a predictable manner. We evaluated the pattern of nodal distribution at different levels of neck in papillary thyroid cancer in this Observational Prospective study. Total 41 patients of PTC (Papillary thyroid cancer) were included in the study. 36 out of them were diagnosed as PTC by FNAC and underwent total thyroidectomy and central neck dissection, while 5 patients were histologically confirmed cases of PTC on previous hemithyroidectomy and underwent completion thyroidectomy and central neck dissection .Patients with T3/T4 stage or N1 underwent lateral neck dissection also. Clinicopathological factors such as age, sex, tumor stage, nodal metastasis and extracapsular invasion, were evaluated. Lymph node metastasis was noted in 21 patients (51.2%) and all these patients had central (level VI) lymph node involvement. Among 21 patients, pathological ipsilateral lateral neck metastasis was noted in 6 patients (28.57%) at level II, 10 patients (47.62%) at level III and 8 patients (38.10%) at level IV. Only 5 patients (23.81%) had metastasis at level V. Extracapsular invasion was observed in 10 (24.4%) patients. We concluded that patients with PTC show higher rates of metastasis at central neck (level VI) and are not easily detected on clinical examination or by USG due to low sensitivity but are sensitive and specific for lateral neck nodes in late stages . Thus, ipsilateral selective neck dissection should be considered with total thyroidectomy and central neck dissection in presence of clinically or radiologically evident lateral lymph nodes (preoperatively) and in T3, T4 stage (late stages) tumors.

Characterization of mortality and high-risk characteristics of thyroid cancer in Filipinos using the California Cancer Registry.

Filipinos are the third largest Asian American subgroup and have the highest incidence of thyroid cancer among all races. To better understand this racial/ethnic disparity in thyroid cancer affecting Filipinos we analyzed the California Cancer Registry (CCR) data in Filipino thyroid cancer cases from 1988 to 2018. 97,948 thyroid cancer cases in California from 1988 to 2018 (until 2015 for Asian subgroups) were evaluated. We examined the case distribution by sex, age at diagnosis, race/ethnicity including Asian ethnic subgroups, histology, TNM stage, tumor size, lymph node involvement, lymphovascular invasion, and multifocality. We also looked at treatment data including surgery and radiation including radioactive iodine therapy. We calculated age-adjusted mortality rates (AAMR) for each major racial group and each Asian ethnic subgroup. Binary logistic regression was used to determine the likelihood of high-risk characteristics and treatment when comparing Filipinos to other racial/ethnic groups. Kaplan-Meier Estimate was performed to evaluate thyroid cancer survival across all race/ethnicities. Multivariate Cox proportion hazards regression was performed to evaluate mortality risk from all causes of death by race. There were 5,243 (5.35%) Filipino thyroid cancer cases in California from 1988 to 2018. Filipinos had the highest AAMR (1.22 deaths per 100,000) in 2015. Filipinos had a higher likelihood of Stage IV thyroid cancer compared with Non-Hispanic Whites, Non-Hispanic Blacks, Hispanics and nearly all Asian subgroups. Filipinos had a worse 5-year and 10-year overall survival (OS) than the combination of all other Asian/Pacific Islanders. Filipinos compared to Non-Hispanic Whites had significant mortality risk in overall and papillary thyroid cancer cases (Overall HR: 1.10, 95% CI 1.07-1.13, p < 0.0001, Papillary HR: 1.11, 95% CI 1.07-1.14, p < 0.0001) when adjusted for race/ethnicity, age, gender, socioeconomic status, and stage. When stratified by Charlson comorbidity score, Filipinos compared to Non-Hispanic Whites still had significant mortality risk (Charlson 0 HR: 1.07, 95% CI 1.02-1.11, p = 0.0017, Charlson 1+ HR: 1.07 95% CI 1.002-1.14, p = 0.0434). Filipino thyroid cancer patients have higher incidences of high-risk pathological features and greater AAMR and mortality risk. These findings warrant further investigation into better understanding the connection between the greater incidence of high-risk characteristics and increased mortality in Filipinos.

The allelic regulation of tumor suppressor ADARB2 in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) is one of the histological subtypes of thyroid cancer which is the most common endocrine malignancy in the world. The disrupted balance of the adenosine-to-inosine (A-to-I) RNA editing due to dysregulation of the editing genes exists in thyroid cancer. However, it is still largely unknown how functional single nucleotide polymorphisms (SNPs) in the A-to-I RNA editing genes contribute to PTC genetic susceptibility. In this study, we systematically annotated and investigated the role of 28 potential functional SNPs of ADAR, ADARB1, ADARB2 and AIMP2 in PTC. We identified ADARB2 rs904957 and rs1007147 genetic variants which are associated with significantly elevated PTC risk in two case-control sets consisting of 2020 PTC cases and 2021 controls. Further investigations disclosed that ADARB2 could inhibit cell viability and invasion capabilities of PTC cells as a novel tumor suppressor. The ADARB2 rs904957 T-to-C polymorphism in gene 3'-untranslated region enhances miR-1180-3p binding affinity and represses ADARB2 expression through an allele-specific manner. In line with this, carriers with the rs904957 C allele correlated with decreased tumor suppressor ADARB2 expression in tissue specimens showed notably increased risk to develop PTC compared to the T allele carriers. Our findings highlight that the A-to-I RNA editing gene ADARB2 SNPs confer PTC risk. Importantly, these insights would improve our understanding for the general roles of RNA editing and editing genes during cancer development.

What has changed in the last 20 years in the postoperative specimen findings of the papillary thyroid cancer cases? A retrospective analysis.

In this study, it was aimed to investigate the changes in surgical approaches and histopathological evaluation of the tumor according to years of patients who were operated on with the diagnosis of thyroid papillary cancer (PTC) in our center in the last 20 years. The records of the cases who underwent thyroidectomy in our department were divided into four groups of five years each and analyzed retrospectively. Demographic characteristics, surgical procedures, presence of chronic lymphocytic thyroiditis, histopathological features of tumour and hospital stay of the cases in the groups were evaluated. Based on tumor size, PTCs were classified into five subgroups. PTCs of 10 (mm) or less were accepted as papillary thyroid microcarcinoma (PTMC). There was a significant increase in PTC and multifocal tumors in the groups over the years (p <0.001). There was a significant increase between the groups in the presence of chronic lymphocytic thyroiditis (p <0.001). In contrast, the total number of metastatic lymph nodes (p= 0.486) and the largest metastatic lymph node size were similar between the groups (p> 0.999). In our study, it was observed that there was a significant increase over the years in both the total/near-total thyroidectomy cases and the number of cases with a postoperative hospital stay of one day (p <0.001). In the present study, it was found that papillary cancer sizes decreased gradually and the frequency of papillary microcarcinoma increased gradually in last 20 years. Also, a significant increase was detected in the rates of total/near-total thyroidectomy and lateral neck dissection over the years.

PSAT285 A Rare Case of Co-Existing Papillary Thyroid Cancer with Lung Metastasis and Lung Adenocarcinoma

Abstract Introduction Multiple primary tumors are defined as the presence of two primary tumors of different histologies in the same individual, which can be diagnosed at the same time or at different times. We present a rare case of papillary thyroid cancer (PTC) with pulmonary metastasis and lung adenocarcinoma diagnosed simultaneously and highlight the importance of identifying multiple primary cancers to guide management and improve patient outcomes. Clinical Case A 57-year-old female with no prior history of malignancy was found to have a 12 mm left upper lobe lung nodule on CT chest as a part of evaluation of worsening cough. A fluorodeoxyglucose PET scan showed increased uptake in the left upper lobe nodule as well as a hypermetabolic thyroid nodule in the right thyroid lobe. She underwent a thoracoscopy, wedge resection, and left lung lobectomy with lymph node dissection, and pathology revealed adenocarcinoma of the lung as well as incidentally found PTC. Subsequently, thyroid ultrasound was obtained which showed a right upper mid-pole thyroid nodule measuring 1.7 cm. She underwent a total thyroidectomy, and pathology showed PTC, tall cell variant in the right lobe, with largest tumor dimension 1.5 cm with no extrathyroidal extension, no lymphatic, and no vascular invasion. A nuclear uptake scan post thyroidectomy showed focal uptake in the thyroid corresponding to residual thyroid tissue, without evidence of metastatic disease. She subsequently received 152.6 mCi of radioactive iodine (RAI). A post-therapy scan obtained one week later showed no new uptake. After RAI, her thyroglobulin antibody remained negative and thyroglobulin became undetectable. She remains on levothyroxine therapy with her TSH at target of 0.1-0.4 U/L. However, she unfortunately had recurrent disease of her lung adenocarcinoma and is continuing to undergo treatment with chemotherapy Conclusion PTC is the most common type of differentiated thyroid cancer and generally has a better prognosis than other types of thyroid cancer given its indolent course. Histologic subtype, presence of extra thyroidal extension, lymph node involvement, and distant metastasis play a role in prognosis, and PTC metastasizes to the lungs in about 5% of cases. Clinicians should be aware of the possibility of multiple primary tumors, and the use of diagnostic modalities like FDG-PET and tissue biopsy can help differentiate a second primary tumor from metastatic disease. Radioactive iodine therapy (RAI) for management of differentiated thyroid carcinoma has been linked to predisposition to other primary malignancies such as leukemia and lymphoma, however our patient was found to have both malignancies simultaneously prior to receiving RAI. This suggests the possibility of genetic susceptibility or alterations in the immune constituency. Further studies are needed to analyze the genetic and environmental factors that lead to development of two primary tumors in certain individuals. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT282 A Case of Papillary Thyroid Cancer in a Thyroglossal Duct Cyst

Abstract Background Thyroglossal duct cysts (TGDC) are common congenital neck anomalies. They persist through adulthood in 7% of the general population. Associated malignancy is rare, occurring in &amp;lt;1% of cases. Over 90% of such malignancies are papillary thyroid carcinoma (PTC). Twenty to 60% of patients with TGDC malignancies are found to have concomitant cancer in the thyroid. The rarity of TGDC malignancy make its management particularly challenging, given limited long term outcome data. We describe a case of a 4cm TGDC PTC. Case A 49-year-old female with a history of autoimmune thyroid disease presented for evaluation of a goiter. She reported 6 months of painful midline neck swelling. No family history of thyroid cancer and she had no history of radiation to her head or neck. She denied swallowing, dyspnea, or hoarseness. Physical exam was notable for a mildly tender, firm 2.5 cm submental midline neck mass overlying the hyoid. TSH was normal and thyroid peroxidase antibody was &amp;gt;1000 (n: &amp;lt;5 IU/mL). Neck ultrasound showed a 3.7×2.5×1.6 cm mixed solid/cystic midline neck mass and a mildly enlarged, heterogeneous, and vascular thyroid without discrete intrathyroidal nodules. A neck CT with contrast indicated that the midline mass was heterogeneously enhancing with tiny internal cystic spaces. The differential diagnosis included an infected thyroglossal duct cyst versus malignant transformation. Fine needle aspiration of the mass was suggestive of PTC. The patient underwent the Sistrunk procedure, with excision of the thyroglossal duct cyst, the middle of the hyoid bone, and the tissue surrounding the thyroglossal tract. Final pathology was consistent with a 4 cm PTC, classical type, without lymphatic, vascular or perineural invasion. Surgical margins were negative for malignancy. Two months postoperatively, TSH remained normal, and the thyroglobulin (TG) level was 78 with negative TG antibodies. She declined a thyroidectomy. Conclusion To date, there is no consensus guideline regarding optimal management for malignancy involving TGDC. Studies suggest that surgical decision making be based on patient risk stratification. High risk factors include age older than 45 years, tumor &amp;gt;4 cm in size, extension of tumor to adjacent soft tissue, and/or the presence of nodal or distant metastases. In high-risk patients, treatment with Sistrunk procedure combined with thyroidectomy, neck dissection and radioactive iodine therapy have shown excellent results. In younger than 45 years with tumor size &amp;lt;1.5 cm, without extension beyond cyst wall and normal thyroid ultrasound Sistrunk procedure alone might be sufficient. Despite low risk factors patients should still be advised to have thyroidectomy as there could be a 20% risk of coexisting thyroid cancer. Additional longitudinal studies are needed to confirm that this approach leads to optimal long-term outcomes for patients with TGDC-associated malignancy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT286 A Rare Case of Papillary Thyroid Cancer of the Thyroglossal Duct Cyst with Benign Thyroid

Abstract Introduction While the thyroglossal duct cyst (TGDC) is the most commonly seen midline neck mass, thyroglossal duct cyst carcinoma is rare (1-2%) with only a few hundred cases published in the literature. The disease can be challenging to diagnose and treat because most TGDC carcinoma are diagnosed post-operatively and data is limited regarding the extent of surgical resection, adjuvant therapy and long-term outcomes. We report a case of papillary thyroid carcinoma arising from TGDC without any evidence of disease in the thyroid gland. Case Report A 31-year-old male presented with complaints of progressively worsening dysphagia and weight loss for 4 months. An initial CT neck with contrast revealed a soft tissue mass along the anterior aspect of the thyroid cartilage measuring 3.4×2.0×2.2 cm that extended anteriorly from the base of the tongue, favoring a thyroglossal duct cyst. The thyroid gland appeared normal on this imaging. He was given a 2-week course of antibiotics and pantoprazole with no improvement in his symptoms. He underwent a thyroid ultrasound, which showed a large hypoechoic mass, partially cystic, anterior to thyroid. FNA of the TGDC was suspicious for papillary thyroid cancer. Follow-up CT scan redemonstrated known TGDC with increased size of adjacent lymph nodes, concerning for metastasis. Given FNA results, regional lymph node involvement, and the patient's symptoms, he underwent successful Sistrunk procedure for TGDC removal. He declined to wait for intraoperative frozen pathology and opted to discuss pathology and next steps after surgery. Pathology of the TGDC confirmed papillary thyroid cancer (conventional type) with uninvolved margins and metastasis to one of four lymph nodes with the largest lymph node being 7 mm. At the tumor board conference, it was recommended he further undergo a total thyroidectomy with possible post-operative radioactive iodine (RAI) treatment. He underwent a total thyroidectomy, and pathology showed benign thyroid gland with a few colloid cysts. Post-operatively, he was started on levothyroxine. He did not have any improvement in dysphagia following both surgeries. After extensive discussion of the risks and benefits of RAI, the patient chose to defer RAI treatment until further evaluation of his dysphagia was completed. Ultimately, the decision was made to monitor with serial ultrasounds and thyroglobulin levels. Conclusion Optimal treatment of TGDC carcinoma is debatable. A Sistrunk procedure involving resection of cyst plus mid-portion of hyoid bone is universally recommended for adequate excision of the cyst. However, no clear consensus guidelines exist for further management with total thyroidectomy and/or post-operative RAI. Total thyroidectomy permits excision of unsuspected thyroid carcinomas and enables a better follow-up. However, decisions can vary based on extent of disease, tumor characteristics, demographics, and patient preferences. Management decisions should be made on an individualized basis, using a multidisciplinary and shared decision-making approach. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSUN378 A Turducken Phenomenon: A Case of Papillary Thyroid Carcinoma Arising Within Struma Ovarii Associated With a Large Mucinous Cystadenoma

Abstract Introduction Struma Ovarii (SO) is one of the types of mature teratoma accounting for up to 3% of all ovarian tumors, with predominant thyroid tissue (&amp;gt;50%). Most cases are reported in middle-aged women. We are presenting a case of asymptomatic papillary thyroid cancer (PTC) presented in SO that was incidentally found and treated successfully Case presentation A 72-year-old Hispanic female with a history of hysterectomy, tobacco smoking was found to have a suspicious lung nodule on screening with CT scan of Chest. A subsequent PET/CT Scan revealed incidental findings of left adnexal lesion of 12×12 cm with no FDG uptake and had a minimal uptake in lung nodule favoring a hamartoma. At the gynecology clinic, patient denied having vaginal bleeding, bowel dysfunction, abdominal pain or weight loss. She did report urinary incontinence. Pelvic exam demonstrated a mobile left adnexal mass without tenderness. MRI of Pelvis revealed a 15 cm multi-cystic, left ovarian mass compressing the urinary bladder without any lymphadenopathy. Tumor markers of CEA and CA-125 were normal. The patient underwent bilateral salpingo-oophorectomy with extensive adhesolysis. Entire ovarian mass was removed intact. Surgical Pathology revealed a 1.2 cm Unifocal PTC arising in 3 cm SO associated with mucinous cystadenoma without lympho-vascular invasion and extra-ovarian extension. No malignant cells were identified in peritoneal washing. This was staged according to AJCC 8th edition as pT1aNxMna. Immunostaining of TTF-1 and TG were positive, which additionally supported above diagnosis. Mutational testing of BRAF, K-RAS and N-RAS were negative. Post-operatively, at the Endocrine clinic, her TSH and Free T4 were normal. No nodules were detected on the thyroid ultrasound. She was deemed low risk for recurrence and no further treatment was advised except serial monitoring of Thyroglobulin levels and goal TSH &amp;lt; 2.5 mIU/L. Discussion In general, SO can be diagnosed only on a histopathological specimen and no specific radiological or biomarkers are available. Most patients are euthyroid and remain asymptomatic like our patient. Thyrotoxicosis occurs in only 5–15% of patients. SO is mostly benign. Its malignant transformation occurs in only 5% of all cases. The most widespread malignant forms of SO are papillary and follicular carcinomas. There are no well-established guidelines for optimal management of malignant SO. After undergoing oophorectomy, the decision to perform a prophylactic thyroidectomy and administration of 131I-Radioiodine is typically reserved for presence of metastatic disease or high risk of recurrence (&amp;gt;4 cm tumor size, gross extra-ovarian extension, BRAF positivity or histology other than papillary type). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

A case of warthin-like papillary thyroid cancer. surgical decision based on eu-tirads criteria

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The incidence and features of Delphian lymph node involvement in patients with papillary thyroid carcinoma

IntroductionIn papillary thyroid cancer patients, the extent of dissection is still a matter of debate. Evaluating Delphian lymph nodes (DLNs) during the surgery has been speculated as a valuable tool to determine the extent of dissection. Herein, we aimed to evaluate the incidence and features of DLNs involvement in patients with papillary thyroid carcinoma.MethodWe conducted this cross-sectional study among surgical cases of papillary thyroid cancer. Patients were divided based on their DLNs involvement status. Their age, gender, location of the mass, lymphatic involvement, tumor size, tumor characteristics, pathology report, and operation note features were compared between the two groups. Definitive pathology slides of the patients were evaluated regarding DLN features.ResultsOf the 61 patients (mean age: 38.2 ± 12.0), 45 (73.8%) were females. In 13 (21.3%) patients, DLNs involvement was reported. A statistically significant relationship was noted between DLNs involvement and other lymph nodes' involvement on the same side of the mass (P < 0.001), the opposite side (P = 0.041), and also central lymph nodes (P < 0.001). Vascular invasion was also significantly higher among patients with DLNs involvement (P = 0.012).ConclusionSince DLNs involvement is significantly associated with extensive nodal involvement, intraoperative evaluation of DLNs is recommended to establish the extent to which dissection should be performed.

DeepThy‐Net: A Multimodal Deep Learning Method for Predicting Cervical Lymph Node Metastasis in Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) accounts for more than 80% of thyroid cancers, and ultrasound (US) imaging is the preferred method for the diagnosis of PTC. However, accurate prediction of different patterns of cervical lymph node metastasis (CLNM) in PTC continues to be a challenge. Herein, US images and clinical factors of PTC patients from three hospitals for more than 11 years are collected, and a multimodal deep learning model called DeepThy‐Net is then developed to predict different CLNM patterns. The proposed model not only uses the convolutional features extracted by deep learning but also integrates traditional clinical factors that are highly related to lymph node metastasis. Finally, the model is tested in two independent test sets, and the experimental results show that the area under curve (AUC) is between 0.870 and 0.905, indicating clinical applicability. The proposed method provides an important reference for the treatment and management of PTC. Moreover, for PTC cases involving an active surveillance strategy, the proposed method can serve as an important CLNM early warning tool.

Unraveling the Effects of Carotenoids Accumulation in Human Papillary Thyroid Carcinoma.

Among the thyroid cancers, papillary thyroid cancer (PTC) accounts for 90% of the cases. In addition to the necessity to identify new targets for PTC treatment, early diagnosis and management are highly demanded. Previous data indicated that the multivariate statistical analysis of the Raman spectra allows the discrimination of healthy tissues from PTC ones; this is characterized by bands typical of carotenoids. Here, we dissected the molecular effects of carotenoid accumulation in PTC patients by analyzing whether they were required to provide increased retinoic acid (RA) synthesis and signaling and/or to sustain antioxidant functions. HPLC analysis revealed the lack of a significant difference in the overall content of carotenoids. For this reason, we wondered whether the carotenoid accumulation in PTC patients could be related to vitamin A derivative retinoic acid (RA) biosynthesis and, consequently, the RA-related pathway activation. The transcriptomic analysis performed using a dedicated PCR array revealed a significant downregulation of RA-related pathways in PTCs, suggesting that the carotenoid accumulation in PTC could be related to a lower metabolic conversion into RA compared to that of healthy tissues. In addition, the gene expression profile of 474 PTC cases previously published in the framework of the Cancer Genome Atlas (TGCA) project was examined by hierarchical clustering and heatmap analyses. This metanalysis study indicated that the RA-related pathways resulted in being significantly downregulated in PTCs and being associated with the follicular variant of PTC (FV-PTC). To assess whether the possible fate of the carotenoids accumulated in PTCs is associated with the oxidative stress response, the expression of enzymes involved in ROS scavenging was checked. An increased oxidative stress status and a reduced antioxidant defense response were observed in PTCs compared to matched healthy thyroids; this was possibly associated with the prooxidant effects of high levels of carotenoids. Finally, the DepMap datasets were used to profile the levels of 225 metabolites in 12 thyroid cancer cell lines. The results obtained suggested that the high carotenoid content in PTCs correlates with tryptophan metabolism. This pilot provided novel possible markers and possible therapeutic targets for PTC diagnosis and therapy. For the future, a larger study including a higher number of PTC patients will be necessary to further validate the molecular data reported here.

Temporal Trends in Papillary and Follicular Thyroid Cancer Incidence from 1995 to 2019 in Adults in Denmark According to Education and Income.

Background: Thyroid cancer incidence has increased over the past decades. Differences in incidence trends have been observed depending on socioeconomic status. Here, we describe trends in the incidence of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) in Denmark by level of education and income. Methods: All PTC and FTC cases registered in the Danish Cancer Registry from 1995 to 2019 were identified. Individual-level information on education and income was obtained from nationwide registries. We calculated age-standardized incidence rates according to sex, tumor size, education and income, and estimated incidence trends by average annual percentage change (AAPC) and corresponding confidence intervals [CIs] for the periods 1995 to 2004 and 2005 to 2019 by using Poisson regression models. Results: We identified 3454 cases of PTC and 972 cases of FTC. From 2005 to 2019 among women, the incidence of PTC increased across all levels of education (AAPCshort education = 12.5% [CI 9.8 to 15.3]; AAPCmedium education = 8.1% [CI 6.4 to 9.9]; AAPClong education = 7.3% [CI 5.4 to 9.2]). The same pattern was seen for income. The incidence of FTC increased in all levels of education (AAPCshort education = 10.5% [CI 5.8 to 15.4]; AAPCmedium education = 4.0% [CI 0.9 to 7.3]; AAPClong education = 4.3% [CI 0.6 to 8.1]), with the same pattern for income. Similar trends were observed among men, in both small (≤2 cm) and large (>2 cm) PTCs and from 1995 to 2004 in both sexes. Conclusions: Enhanced detection of thyroid cancer among all levels of education and income cannot be ruled out, and in addition, our results may suggest a true increase in the incidence of differentiated thyroid cancer.