Papillary Carcinoma Research Articles

6847 Poorly Differentiated Thyroid Cancer: A Rare Entity

Abstract Disclosure: S. Fatima: None. S. Ward: None. A. Champion: None. Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. Regarding the degree of differentiation, PDTC ranks between differentiated thyroid cancer and anaplastic thyroid cancer. We hereby present a rare case of PDTC. Case: 29-year-old female with a history of metastatic papillary thyroid cancer (PTC) presented to the emergency department with shortness of breath. She initially noticed a left thyroid mass in 2021. CT neck in 1/2022 showed a 7 cm left thyroid mass with substernal extension, small right thyroid mass with tracheal compression, left bulky cystic nodal masses extending anterior and posterior to carotid and internal jugular vein. PET scan in 3/2022 showed left 7.6 cm thyroid mass SUV 12.1 with tracheal compression, left level II-IV adenopathy with level IV nodal masses 5.1 cm SUV 4.5. Ultrasound-guided FNA in 4/2022 showed PTC in left 8.7cm thyroid nodule; right 2.8 cm nodule showed Atypia of Undetermined Significance; Left 5.5 cm neck level III lymph node (LN) showed PTC metastasis; right 5.1 cm neck level III LN showed PTC metastasis (+ thyroglobulin and TTF-1). CT chest in 11/2022 showed additional involvement of manubrium. Repeat core needle biopsy of left thyroid mass showed left invasive thyroid carcinoma. She was started on neoadjuvant Lenvatinib in 1/2023. Follow-up CT neck in 5/2023 showed a reduction in the size of the left thyroid mass to 5.5cm x 5.8cm x 6.5cm. At this time, she had symptoms of dysphagia, orthopnea, weight loss of about 60 lbs and neck pain. In 11/2023 at time of current presentation she underwent total thyroidectomy, bilateral modified radical neck dissection and manubriectomy. Surgical pathology showed PDTC in left thyroid mass, PTC in right thyroid mass with metastatic PDTC in left proximal sternocleidomastoid, manubrium and LN involvement in neck and mediastinum. OmniSeq Insight testing showed APC and BRCA1 gene mutations, negative BRAF V600E, RET fusion, RET mutation, NTRK1/2/3 fusion and PD L1 immunohistochemistry score is <1%. The patient is planned to receive [1]3[1]I ablation therapy. Conclusion: PDTC accounts for 3–5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50–85%, 34–50%, and 0%, respectively. RAS gene alterations are found in 25–35%, BRAF mutation in 15–27%, TERT promoter mutation in 40% and mutant TP53 in 16–28% of PDTCs. TERT promoter gene and TP53 mutation usually indicate an aggressive phenotype and a dismal prognosis. Surgery, [1]3[1]I therapy, and external beam radiotherapy constitute the mainstay of traditional treatment for patients with advanced disease; however, treatment is challenging. Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to [1]3[1]I therapy. Immunotherapy may be an option in PD-L1-positive tumors. Presentation: 6/1/2024

8465 Diagnostic Conundrum: The Mystery of Metastatic Papillary Thyroid Cancer with Persistently Elusive Thyroglobulin

Abstract Disclosure: P. Vemparala: None. M. Bollineni: None. Introduction- Among endocrine malignancies, differentiated thyroid cancers account for the majority with most of them boasting a favorable prognosis. Thyroglobulin, a pivotal biochemical marker, aids in detecting recurrence or persistent disease when combined with neck ultrasound, I-131 scintigraphy, and FDG PET scans. Anti-thyroglobulin antibodies, found in a quarter of cases, can falsely lower serum thyroglobulin levels in immunometric assays. Our intriguing case features a patient with metastatic papillary thyroid cancer, yet thyroglobulin levels persistently eluded detection. CASE PRESENTATION- A 33-year-old female presented initially to an outside facility with neck swelling, leading to a diagnosis of a 4 x 3 cm papillary thyroid cancer (PTC) in the right lobe and a 0.5 x 0.5 cm focus of PTC in the left lobe, accompanied by capsular extension, malignant cells in the left lobe margin, and lymphovascular invasion. After total thyroidectomy and lymph node exploration, radioactive iodine scan detected disease in right-sided lymph nodes, treated subsequently with radioactive iodine ablation. Two years later, she presented to our clinic with neck swelling, voice changes, and fatigue. Thyroglobulin level was measured which returned at <0.1 ng/ml, however thyroglobulin antibodies were elevated at 292 IU/ml, albeit decreased from a value of 431.5 IU/ml at initial diagnosis. Elevated thyroglobulin antibodies complicated interpretation, prompting liquid chromatography-mass spectrometry (LC-MS) for accurate measurement of thyroglobulin, which returned at <0.5 ng/ml. Ultrasound indicated metastatic disease in right cervical lymph nodes, confirmed by fine needle aspiration. In-office ultrasound-guided FNA of additional nodes validated metastasis. Modified radical neck dissection revealed metastatic PTC in 7 out of 34 lymph nodes. Surprisingly, thyroglobulin levels remained <0.5 ng/ml, pre- and post-operatively. Referred for radioactive iodine ablation, her complex journey underscored the challenges in monitoring thyroid cancer recurrence or persistent disease with thyroglobulin levels even by methods such as mass spectrometry. Conclusion- Key learnings from this case highlight the importance of cognizance in utilizing thyroglobulin levels to guide adjuvant therapy decisions and for postoperative monitoring in high risk patients, as low levels do not rule out recurrence or persistence. Anti-thyroglobulin antibodies pose challenges, necessitating techniques like LC-MS. Finally, recognizing “nonsecretor” thyroid cancers, an aggressive subgroup with poorer prognosis, is vital as they often present with low or undetectable thyroglobulin levels. Presentation: 6/2/2024

6404 Iodide Metabolism Anomalies in Patients with Thyroid Cancer; A Case Series

Abstract Disclosure: G.I. Uwaifo: None. Thyroid cancer is often treatable and often involves iodine ablation therapy. Iodine based imaging and/or therapy can be complicated in patients with abnormal iodide metabolism. We present two patients with thyroid cancer and disparate abnormal iodide metabolism. Case 1 is a 35 yr old Caucasian lady with papillary thyroid cancer (PTC) stage 1 with no metastases. After total thyroidectomy and prior to I-131 remnant ablation she had a contrast Chest CT for shortness of breath. A month after serum iodine was elevated (545 Ug/L; 40—92). 24 hr urine iodine levels was also elevated; (2,300Ug/day; 150-500). She denied dietary intake of iodine rich foods. Ablation was postponed and she commenced a strict “zero” iodine diet. Despite this and despite having no further contrast imaging serum and urinary iodine remain elevated for nearly 3 yrs. Further history indicated episodes of sensitivity to several medications and Cytochrome P450 genetic profiling revealed two polymorphisms of CYP P450 2C19 and 2D6 associated with slow drug metabolizer phenotype. 34 months after her Chest CT with serum iodine of 127Ug/L and 24 hr Urine iodine of 652 she had radio iodine-ablation (RIA) with 130Mci of I-131. She had post treatment dysgeusia and parotitis. She remains on a low iodine diet and is presumably cured. Case 2 is a 66 yr old Caucasian man referred for second opinion regarding therapeutic options for known metastatic PTC with metastases to thoracic spine and lungs. He was diagnosed with follicular variant PTC 7 yrs ago. He had total thyroidectomy and repeated RIAs with a total accumulated dose of ∼ 850Mci and last RIA 3 yrs ago. His latest two whole body I-131 scans were -ve despite elevated thyroglobulins and metastatic disease. He was unable to tolerate sorefanib. He is on thyroid hormone repletion and quarterly denosumab. Contrast PET-CT scan a week prior showed extensive metastatic disease and thyroglobulins in the 300—650 ng/ml range. Work up for repeat whole body I-131 scan revealed curiously that serum iodine was 46 Ug/L (40-92) despite his recent contrast study and this was confirmed on two repeats. 24 hr urine iodine was reduced; 87 ug/day (150-500) and he had a typical diet with no excess intake of goitrogens. Based on history of often needing significantly higher doses of medications like opioids, anesthetics and sedatives cytochrome P450 genetic profile obtained showed two polymorphisms (of CYP P450 2C-19 and CVPs 3A4 +3A5) associated with fast metabolizer phenotype. Given his unusually rapid iodine clearance the utility of any further iodine based imaging and/or therapy was deemed dubious. His current management continues without change. We present two patients with extremes of iodine metabolic processing that had clinical management significance. Careful evaluation of ambient iodine status of patients is an important part of the preparation of thyroid cancer patients for iodine based imaging and/or therapy. Presentation: 6/1/2024

7962 Transformation of Poorly Differentiated Papillary Thyroid Carcinoma to Anaplastic Thyroid Carcinoma, an Atypical Course!

Abstract Disclosure: T. Altaweel: None. S. Makadsi: None. M. Hussein: None. J. Samantray: None. Introduction: Anaplastic thyroid cancers are undifferentiated, rare and aggressive. The transformation of papillary thyroid cancer to anaplastic thyroid cancer is documented in literature, however, rare. In this report, we present a case of Anaplastic thyroid carcinoma likely arising from a co-existing poorly differentiated Papillary carcinoma. Case Presentation: A 74-year-old male with past medical history of tobacco smoking who presented with the onset of voice hoarseness for 6 months. He has also noticed a left neck mass that is in the mid supraclavicular region. A Neck CT neck was performed at the time of presentation and was significant for a 4.6x3.4x5.9 cm left thyroid mass with displacement of the trachea. FNA biopsy showed papillary carcinoma with focal features of Tall Cell Variant. Poorly differentiated components with fragments of stroma and muscle were seen and suggested invasion. These findings raised the possibility of anaplastic thyroid carcinoma in the setting of papillary carcinoma and poorly differentiated carcinoma. BRAF V600E pathogenic variant mutation along with TERT mutation were found. Patient underwent direct laryngoscopy, bronchoscopy with biopsies, and tracheostomy with surgical pathology confirming papillary thyroid cancer with muscles invasion. Combination dabrafenib and trametinib were started. No surgical resection of thyroid tissue was planned. A follow up CT showed a significant decrease in the low-density soft tissue involving the medial thyroid gland bilaterally, consistent with interim positive response to therapy. Three months later, CT neck showed near complete resolution of low-density soft tissue involving the medial thyroid and parathyroid glands and subglottic trachea consistent with further interim positive response to therapy. Six months post initiation of therapy, CT Neck showed focal low density in the mid and inferior right thyroid gland which may represent residual and/or recurrent thyroid carcinoma. That density was further demonstrated on a repeat CT neck as a 1.8 cm hypodense nodule in the inferior right thyroid gland and concerning for recurrent thyroid tumor with possible infiltration of the trachea. Conclusion: ATC prognosis is affected by many factors such as metastasis, age, treatment strategies, socioeconomic status and the presence of BRAF V600E and TERT mutations. Diagnosis can be challenging. Our patient presented months after his symptoms started and this is an atypical course of Anaplastic Thyroid Carcinoma as it usually progresses aggressively and rapidly. Given the pathology reports and the more slow presentation of this patient’s carcinoma, it can be suggested that this is a case of papillary carcinoma with a later transformation to ATC. In these cases, surgical resection Presentation: 6/2/2024

8728 Radiofrequency Thermal Ablation in Thyroid Microcarcinomas: Experience of the Brazilian Group with 143 Cases

Abstract Disclosure: L.G. Amato: None. P.H. Carani: None. L.D. Volpi: None. A. Rahal: None. E.M. Volpi: None. Introduction: Thyroid nodules are quite prevalent worldwide, with papillary thyroid carcinoma (PTC) being the most common histological subtype of thyroid malignant neoplasm, accounting for approximately 85% of thyroid cancers. When this carcinoma is less than 10 mm in its longest axis, it is defined as papillary thyroid microcarcinomas (mPTCs) which has had an increasing proportion of thyroid cancers and with a disease-specific survival of patients having this diagnosis more than 99% after 10 years of follow-up. Most guidelines concerning thyroid cancer care recommend a lobectomy as the first-line treatment strategy for low-risk unifocal mPTC but often results in aggressive overtreatment. Thyroid surgery comes with significant costs and morbidity rates caused by iatrogenic hypothyroidism and recurrent laryngeal nerve damage, resulting in poor quality of life, justifying the growing search for minimally invasive and effective methods in the treatment of mPTC and in this context Radiofrequency thermal ablation (RFA), a minimally invasive treatment that preserves thyroid function have been proposed for patients with low-risk mPTC. Clinical case: From April 2018 to January 2024, 143 patients with mPTC, were submitted to RFA and patient's follow-up were dated 1, 3, 6, 12 and 18 months after the procedure. During the follow-up we observed 3 (2%), complications, 1 case of permanent paralysis unilateral vocal cord, 1 Horner Syndromes and 1 case of transient paralysis, with total reversal. In all cases there was a reduction in the volume of the node after 6 months of the procedure. Conclusion: The reported incidence rate of postoperative hypothyroidism in patients underwent hemithyroidectomy is 10.9-48.8%, therefore, risks of complications with radioablation in our series were lower than those previously described during hemithyroidectomy. Radiofrequency thermal ablation (RFA) is a minimally invasive treatment that preserves thyroid function with a lower incidence of complications compared to thyroidectomy or lobectomy, and and should be considered the selection procedure for low-risk thyroid microcarcinomas. Presentation: 6/3/2024

8426 Recurrence of Papillary Thyroid Carcinoma Despite Undetectable Levels of Thyroglobulin Measured by Both Immunoassay and LCMS

Abstract Disclosure: M.G. Hamilton: None. G. Patel: None. S. Teja Sathi: None. K. Win: None. P. Lekprasert: None. Serum thyroglobulin (Tg) levels are affected by the presence of anti-thyroglobulin antibodies (anti-Tg Abs) during surveillance of differentiated thyroid cancer (DTC). About 20% of patients have positive anti-Tg Abs post-thyroidectomy and laboratory investigations for DTC surveillance may lead to false negative results. Liquid chromatography-tandem mass spectrometry (LCMS) is superior to immunoassay in measuring Tg levels in patients with the presence of anti-Tg Abs. Mass spectrometry is the only currently available method that could eliminate the interference of anti-Tg Abs in the quantification of Tg but is not readily available. We present the case of a patient who had a recurrence of DTC despite persistently undetectable Tg levels using both immunoassay and LCMS methods. The patient is a 49-year-old female with a history of papillary thyroid cancer who underwent total thyroidectomy followed by adjuvant radio-ablation. She presented to our endocrinology office for routine follow up for her DTC. She reported subjective unknown weight loss over four months. Her physical exam was unremarkable with no palpable neck swelling or mass. Vital signs were within normal limits. She continued to have undetectable levels of Tg as measured by immunoassay, stable levels of anti-Tg Abs ranging from 19 IU/mL to 33 IU/mL, and negative findings on her thyroid ultrasound for the first four years post-op. When she presented to the office five years post-thyroidectomy her anti-Tg Ab level had increased to 114 IU/mL and subsequently to 137 IU/mL a few months later despite undetectable Tg levels on both immunoassay and LCMS. A thyroid ultrasound was completed due to rising anti-Tg Abs levels which showed a suspicious one cm mass at the right thyroid bed and suspicious bilateral cervical lymph nodes. Repeated FNA biopsy of the bilateral cervical lymph nodes confirmed follicular epithelium with nuclear inclusions and grooves, compatible with recurrent papillary thyroid carcinoma. This patient had a recurrence of her DTC despite undetectable Tg levels on both immunoassay and LCMS. Tg is an important aspect of surveillance post-treatment for all patients with DTC because its presence is a surrogate for the presence of thyroid tissue and therefore the recurrence of thyroid malignancy. Clinicians must have a high index of suspicion when monitoring a patient with a history of DTC and the presence of anti-Tg Abs because it interferes with the accurate measurement of Tg levels. A study conducted by Azmat et al. demonstrated that measuring Tg levels via LCMS has been found to eliminate the confounding effect of anti-Tg Abs with a sensitivity and specificity of 44.4% and 94.1% respectively. However, our case illustrates that even LCMS is not always reliable in such situations, and increasing levels of anti-Tg Abs should be an individual risk factor for suspecting recurrence of DTC. Presentation: 6/3/2024

8675 Dosing of Radioactive Iodine for Papillary Thyroid Cancer in Advanced Chronic Kidney Disease

Abstract Disclosure: C. Cheatham: None. D. Beckman: None. INTRO Radioactive Iodine (RAI) ablation is an important treatment for patients diagnosed with papillary thyroid carcinoma. Most studies completed on RAI in renal dysfunction were focused on End Stage Renal Disease (ESRD) patients on dialysis to establish protocols on timing of dialysis to allow desired clinical response to RAI without increased risks and minimizing exposure of dialysis staff to radiation dose. The ideal RAI dosing and monitoring of patients with advanced chronic kidney disease (CKD) stage 4 or 5 not requiring dialysis has not been systematically reviewed. CASE 26 year-old female with CKD stage 4/5 secondary to chronic hydronephrosis from vesicoureteral reflux with baseline eGFR 15-20 mL/min/1.73 m2 was diagnosed with papillary thyroid cancer. She underwent total thyroidectomy with central and left lateral neck dissection, resulting in pathologic stage I, pT2 N1b M0 disease, high risk for recurrence according to the 2015 American Thyroid Association guidelines due to 17 positive lymph nodes from left level II-IV and VI, multiple with extranodal extension, as well as 1 vessel angioinvasion. She was referred for adjuvant RAI ablation after withdrawal from thyroid hormone. Decision was made to proceed with a 50% dose reduction and close monitoring of radioactivity clearance as an inpatient given decrease of eGFR to 10-12 mL/min/1.73 m2. She was cleared for discharge 4 days after RAI dose of 74.8mCi when activity level dropped to <2mR/hr. Post-ablation whole body scan showed activity in the thyroid bed and parasternal notch without evidence of metastatic disease. Post-treatment non-stimulated thyroglobulin 6 weeks later was 0.4 ng/mL down from 269.7 ng/mL. DISCUSSION Given RAI is predominately renally cleared, decreased renal function affects clearance rates and associated exposure to radiation. Risks with decreased RAI clearance include bone marrow toxicity and prolonged isolation requirements. In a 2017 retrospective review, patients with eGFR <30 mL/min/1.73 m2 had delayed clearance leading to a mean proportional reduction of exposure rate at 48 hours of -67.2% compared to -94.3% in healthy controls. While protocols exist for patients on hemodialysis, no such protocols have been established for patients with advanced CKD not requiring dialysis. For this patient, after multidisciplinary discussion with nuclear medicine, health physics, and nephrology in setting of further eGFR reduction during hormone withdrawal, decision was made to reduce the intended dose by 50% with inpatient monitoring and backup to dialyze if no significant decrease in radiation activity level was seen or if she were to progress to anuric or oliguric renal failure. This case highlights the need for established protocols and long-term studies to evaluate risk and treatment response in relation to dosing of RAI in this population, but a 50% dose reduction appears to be effective without adverse event. Presentation: 6/2/2024

12214 Metastatic Functional Thyroid Carcinoma As An Unusual Cause Of Hyperthyroidism

Abstract Disclosure: S. Jimenez Salazar: None. N. Aristizabal Henao: None. C. Aguilar Londoño: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Differentiated thyroid carcinoma (DTC) represents the most prevalent endocrine neoplasm. Less than 10% present distant metastases, with the lung (50%), and skeleton (25%) being the most frequently affected sites. The location of bone metastases predominates in the spine and pelvis; usually as osteolytic lesions, being more frequent in follicular thyroid cancer (FTC) (7-28%) than in patients with papillary thyroid cancer (PTC) (1.4-7%). In rare cases this metastasis can be functional and trigger a thyrotoxicosis syndrome with or without recombinant human TSH injections prior to therapy with 131-I. Clinical case: 59-year-old woman with a history of bone metastatic follicular thyroid cancer (FTC) presented with 1 month of palpitations, 4 kg weight loss, non-dysenteric diarrhea and progressive dyspnea. Her FTC had been diagnosed 8 years prior her consultation. In that time iodine refractoriness was considered due to the progression of bone lesions, and Sorafenib 800 mg per day was initiated, which was not tolerated due to severe dermatological manifestations, and the patient decided not to continue with TKI therapy. Since then, she has been treated with zoledronic acid and local radiotherapy as part of palliative care. On physical examination, she was tachycardic (150 bpm), and hypertensive (BP 160/100 mmHg). A suppressed TSH (<0.01 uUI/mL, n: 0.4-4 uUI/mL) with elevation of thyroid hormones (free T4 3.99 ng/dL, n: 0.8-2 ng/dL and total T3 480 ng/dL, n: 45-140 ng/dL) was documented, associated with a patient who had required a dose adjustment of levothyroxine from 700 mcg to 350 mcg weekly 2 months prior to admission. Additionally, she had a significantly elevated thyroglobulin (>5000 ng/mL, n: 0.1-64.1 ng/mL) with undetectable antithyroglobulin antibodies (1.09 UI/mL, n: 0-4.11 UI/mL). Considering the history of total thyroidectomy and the high tumor burden, secondary thyrotoxicosis due to functioning bone metastases of DTC was considered. Levothyroxine was discontinued, and propranolol was initiated for the control of adrenergic symptoms, along with methimazole, cholestyramine, and systemic steroids to control thyroid hormone production. 3 days after therapy adjustment dyspnea, palpitations, and thyroid function tests improved significantly (free T4 1.43 ng/dL, n: 0.8-2 ng/dL and total T3 178 ng/dL, n: 45-140 ng/dL). A new administration of therapy with 131-I 200 mCi was indicated. Antithyroid therapy and beta-blockers were continued with sustained biochemical control. Conclusion: Functional bone metastases of FTC can lead to high morbidity and mortality. Treatment consists of surgical cytoreduction of any large accessible metastatic lesion, therapy with 131-I, and high-dose antithyroid drugs to control hyperthyroidism. It is important to avoid the use of recombinant human TSH due to the risk of secondary thyrotoxicosis following its administration. Presentation: 6/2/2024

7357 Microscopic Papillary Thyroid Cancer Presenting with Cranial Nerve Palsies due to Metastatic Cervical Lymphadenopathy: A Case Report

Abstract Disclosure: N.N. Mukhtar: None. C. Zuo: None. B.R. Haugen: None. Introduction: Tumors metastasizing to head and neck are considered a rare cause of cranial nerve palsy (CNP). In this report, we describe an unusual presentation of metastatic microscopic follicular variant papillary thyroid cancer (FVPTC) presenting with CNP. Case Summary: A 68-year-old previously healthy female presented to her primary care physician with a 6-week history of difficulty speaking and chewing food. She did not notice any dysphagia, change in voice or shortness of breath. Cranial nerve examination was evident for palatal asymmetry, left-sided uvular and right-sided tongue deviations suggesting right glossopharyngeal and hypoglossal nerve palsies. Neck examination revealed a normal thyroid gland without palpable nodules however, the patient had multiple enlarged painless right cervical lymph nodes (CLN). MRI of the brain was normal. CT of the neck and chest showed enlarged, calcified right level II and III CLN (largest 4x3.5 cm) compressing the right internal jugular vein. In addition, bilateral pulmonary nodules (largest 1.7x1.5 cm) suspicious for metastasis were seen. CT-guided biopsy of left upper lobe lung nodule was consistent with metastatic thyroid cancer (positive PAX-8 and TTF-1 immunostaining). Neck ultrasound did not show any thyroid nodules, but did confirm 4 enlarged right CLN (largest 2.9 cm). The patient was referred to our multidisciplinary clinic for further evaluation. Based on the duration of her symptoms (6 weeks), her CNP was most-likely irreversible and agreement to proceed with total thyroidectomy, central and right lateral neck dissection aiming for complete resection in preparation for future treatment with radioactive iodine. Preoperative thyroglobulin level was 30.7 ng/ml (1.6-50), thyroglobulin antibody 24 U/mL (<40) and TSH 0.6 mIU/L (0.4-4.6). Intra-operatively; the patient had extensive, bulky lymphadenopathy extending to surrounding neck muscles and completely encasing right jugular vein. Histopathological examination of the resected tissue showed a unifocal right thyroid lobe microscopic (6x4x3 mm) infiltrative follicular variant papillary thyroid cancer (FVPTC). No extrathyroidal extension, necrosis, angioinvasion or lymphatic invasion were identified. Mitotic index was 3/ 2mm2. 13 out of 36 lymph nodes were positive for metastatic thyroid cancer (3/3 level II, 2/17 level III, 8/16 level IV), largest was 4.6 cm with extra-nodal extension. The patient was discharged on suppressive dose levothyroxine. Molecular studies: Next generation sequencing of the lung biopsy was negative for BRAFV[6]00E mutation and further molecular analyses are ongoing. Conclusion: This case describes two unique presentations of thyroid cancer; a microscopic FVPTC associated with large lateral cervical lymph node metastasis and, CNP as the initial presentation of thyroid cancer which to our knowledge, has not been reported previously. Presentation: 6/2/2024

8390 It's not Cancer: Establishing the Diagnosis of Hyaline Trabecular Tumor

Abstract Disclosure: R.A. Zielinski: None. M. Khalifa: None. M. Dillon: None. M. Kaur: None. Background: Hyaline trabecular tumor (HTT) is a rare benign follicular thyroid neoplasm characterized by extensive intra-trabecular hyaline stromal material. Resemblances to other follicular neoplasms create difficulty in distinguishing HTT from its more nefarious counterparts such as medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC).Clinical Case:Our patient is a 56-year-old female with Hashimoto’s thyroiditis diagnosed in her twenties who has been on different strengths of levothyroxine based on her fluctuating TSH. A thyroid ultrasound done to evaluate left-sided neck fullness on physical exam showed a solid, hypoechoic 2.3 cm x 1.4 x 0.9 cm left middle thyroid nodule without calcifications (TI-RADS 4) and benign-appearing lymph nodes, the largest of which was 1.5 cm at level 1B. Cytology from a thyroid FNA biopsy was suspicious for PTC, Bethesda category IV. A thyrosure genetic panel was negative for genetic mutations. FNA biopsy of the 1.5 cm lymph node was negative for malignancy. The patient was referred for thyroid lobectomy but instead elected to undergo total thyroidectomy with level VI lymph node dissection. Pathology revealed a 2.2 cm HTT in the left lobe, scattered psammoma bodies in adjacent soft tissue, and a 0.2 cm multifocal papillary microcarcinoma in the right lobe. The microcarcinoma had negative margins, no lymphatic or vascular invasion, and 7/7 benign level VI lymph nodes; staging it as pT1aN0. Immunohistochemistry staining was positive for TTF-1 and thyroglobulin and negative for calcitonin, chromogranin, and synaptophysin. Post-thyroidectomy she was started on Tirosint 175 mcg daily with good response. No I-131 treatment was pursued due to the microcarcinoma being categorized as low risk.Discussion and Conclusion: HTT is a benign neoplasm and management is usually conservative with surgical excision. The diagnosis of HTT by cytology alone is challenging due to the presence of nuclear clearing, grooves and intranuclear pseudo-inclusions that may be mistaken for PTC or MTC. Cell membrane immunoreactivity of MIB1 monoclonal to Ki67 and the molecular identification of the novel PAX8-GLIS1 or PAX8-GLIS3 fusions may aid in making the correct diagnosis.

7466 The Effects Of Various Forms Of Diabetes On Features Of Tumor Aggressiveness In Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m2, mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

7642 A Mixed Model of Clinical Characteristics and Ultrasound ACR-TIRADS Predicts Malignancy in Thyroid Micro Lesions

Abstract Disclosure: N. Angelopoulos: None. I. Iakovou: None. D. Goulis: None. R. Paparodis: None. S. Livadas: None. A. Boniakos: None. J.C. Jaume: None. Background: The frequency of papillary thyroid carcinoma (PTC) has increased, mainly due to the detection of small tumors incidentally found during unrelated imaging. While most of these small cancers have a non-aggressive course, some can be more biologically hostile, with potential for metastasis. Current guidelines discourage routine biopsy for nodules ≤10 mm, but the challenge is identifying higher-risk microcarcinomas. This study aims to identify ultrasound and clinical characteristics indicating malignancy in small thyroid lesions. Patients and methods: 151 patients with accidentally discovered solid nodules in thyroid ultrasound were enrolled in the study. All patients were stratified according to both ACR and EU-TIRADS systems. Two qualified endocrinologists performed ACR-TIRADS scoring and accordingly, all patients were stratified to the five ACR categories TR1-5 Strain elastography was also performed in all nodules and the elastography ratio (E2/E1) was calculated (E2 elastography of the nodule, E1 elastography of healthy thyroid gland). FNA was performed in nodules classified as EU-TIRADS 5 Results: 41 patients were classified as EU-TIRADS 5. The rest of the patients were classified as 69 EU-TIRADS 4, 40 EU-TIRADS 3, and one EU-TIRADS 2. According to FNA results, 11 patients had Bethesda II cytology (Group A), 2 Bethesda III, one Bethesda IV, 10 Bethesda V, and 17 Bethesda VI (V and VI comprised Group B). FNAs indicative of malignancy (Group B) were more frequent in patients with autoimmune thyroiditis (Chi-squared 5,833, df(1), p=0.015). In Group B, both ACR-scoring points and ACR-TIRADS categories were significantly higher than those detected in patients in Group A. Logistic regression analysis revealed a significant prognostic role of ACR-scoring points in discriminating suspicious FNA results for thyroid cancer. ROC analysis (AUC:0.993 with Youden Index:0.926, associated criterion >6, Sensitivity 92.59 % and Specificity 100 %). To analyze the predictive power of the clinical parameters in the presence of thyroid malignancy, age, BMI, gender, autoimmune disease, therapy, nodule diameter, and elastography ratio were examined in a “clinical model”. The overall prognostic value of the model was significant (p=0.0029, AUC:0.744) with a sensitivity of 77.78% and specificity of 72.73%, (Youden Index: 0.505, associated criterion >0.6). Finally, a “mixed model”, combining the clinical characteristics and the ACR scoring points, was generated for methodological reasons. The model was overall significant (p<0.001) with AUC:1 (95% Confidence interval: 0.907 to 1), Youden Index:1, sensitivity, and specificity 100%. Conclusion: ACR- TIRADS points > 6 may be a strong indicator of thyroid malignancy and the “mixed model” is an excellent predictor of thyroid malignancy, but its usefulness in everyday clinical practice may be cumbersome. Presentation: 6/1/2024

7466 The Effects of Various Forms of Diabetes on Features of Tumor Aggressiveness in Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m[2], mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

5179 Uncommon Benign Mimics Of Suspicious Adrenal Nodules

Abstract Disclosure: L. Zhu: None. L. Loh: None. V. Gan: None. P. Kek: None. Introduction: Adrenal incidentaloma is often detected in imaging studies. In addition to biochemical testing, imaging plays a key role in guiding the management of such lesions. We describe two uncommon cases of benign lesions masquerading as suspicious adrenal nodules. Case 1. A 54-year-old man with hypertension, diabetes, dyslipidaemia, ischaemic heart disease and atrial fibrillation (on warfarin) underwent CT scan to exclude malignancy when he presented with thigh DVT, and was found to have a right 3.2cm adrenal nodule. Adrenal hormone profile was unremarkable. CT contrast characterization showed attenuation of 30, 35, and 32 HU on pre-contrast, venous and 10-minute delayed phase respectively. Given the minimal enhancement in high density areas, possible haemorrhage was considered and he was put on imaging surveillance. CT scans over the following 5 years showed stability of the lesion, resolution of high-density areas, and pre-contrast attenuation of -35HU, suggestive of myelolipoma. Further follow-up over the next 2 years then revealed tumour enlargement to 8.5cm, progressive predominance of dense areas (58 HU), and development of compressive symptoms. In view of mass effect, growing heterogeneity and possibility of a collision tumour, right adrenalectomy was performed. Histopathology revealed myelolipoma with extensive haemorrhage and no evidence of malignancy. Case 2. A 65-year-old woman had hypertension, ischaemic heart disease, dialysis-dependent end-stage renal disease secondary to glomerulonephritis, and oncological history of left renal cell carcinoma (RCC) and low-grade papillary urothelial carcinoma, both surgically resected 10 years ago. A new 1.6cm right adrenal nodule was seen on her surveillance CT scan for RCC. It was not present in a CT scan 7 years ago. The nodule displayed suspicious features such as nodular avid rim enhancement, persistent enhancement on delayed phase of contrast washout and central cystic change. Biochemical screening revealed plasma free metanephrine of 0.33 nmol/L (NR: <0.33) and plasma free normetanephrine of 0.99 nmol/L (NR: <0.71). Other adrenal hormone profiles were unremarkable. Cystic phaeochromocytoma was suspected and she underwent right adrenalectomy and nephrectomy following alpha blockade. Histopathology revealed a well-circumscribed nodule in the supra-renal adipose tissue, with vascular proliferation and features of anastomosing haemangioma. The right kidney was reported to have acquired cystic disease associated RCC. She was well post-operatively and remained on follow-up with the urologist for her RCC. Discussion: Haemorrhagic adrenal myelolipoma and supra-renal anatomosing haemangioma are benign lesions that may have CT characteristics similar to those of sinister lesions. Pre-operative diagnosis can be challenging. Surgical excision may be required to confirm diagnosis and exclude malignancy. Presentation: 6/3/2024

8062 Uncommon Presentation of Multiple Myeloma as a Rapidly Growing Thyroid Goiter Initially Thought to be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

7355 A Case of High-Risk Thyroid Tumor Markers Found in Subcutaneous Thyroid Implants in a Patient with Benign Thyroid Pathology

Abstract Disclosure: J. Fedorko: None. S. Fatima: None. A.P. Amblee: None. C.A. Poku: None. Background: While fine needle aspiration (FNA) remains the primary diagnostic tool for thyroid malignancies, the utilization of molecular markers has become increasingly common in the workup of thyroid nodules. They play a useful role in distinguishing between malignant and benign pathology when cytology is indeterminate and in formulating treatment plans. The vast majority of research for these genetic markers is conducted in cases with thyroid malignancy. However, there have been numerous cases where these genetic markers were identified in benign thyroid tissue. Case: A 73-year-old male with left hemithyroidectomy (benign left nodule) presented 6 years later with new superficial neck nodules along the midline, left thyroid bed and R thyroid lobe. FNA of the right thyroid nodule was benign. Three months later the patient underwent an excision of the midline neck nodules which revealed thyroid tissue arranged in nests of fibrotic tissue without definite features of papillary thyroid carcinoma. Molecular analysis (Thyroseq) was positive for HRAS, E1F1AX and TERT mutations thus metastatic follicular carcinoma was suspected. The patient underwent complete thyroidectomy. Pathology revealed normal thyroid tissue and a diagnosis of thyroid neck implants was made. Given the benign pathology, the plan was for close follow-up with neck imaging every 6 months. Discussion: Thyroid tissue implants can rarely be caused by previous surgical interventions, especially partial thyroidectomy. There is literature documenting similar clinical cases in which subcutaneous thyroid implants are found in patients after undergoing total or subtotal thyroidectomy. In one case series, there were cases in which thyroid implants were discovered 26 years post-surgery, with most of the cases reporting benign pathology. Given our patient’s presentation and clinical history, the possibility remains that his subcutaneous tissue findings were caused by his prior partial thyroidectomy. A recent article reviewed 60 publications and >8000 patients for the prevalence of high-risk tumor markers (RAS mutation, RET/PTC, and PAX8/PPAR-gamma chromosomal rearrangements) in benign thyroid tissue. They concluded that prevalence findings were highly variable, warning providers to exercise caution when using these genetic markers to guide diagnosis and treatment decisions. Conclusion: While certain high-risk genetic tumor markers are increasingly used to help identify thyroid malignancies, it is important to keep in mind that these genetic markers are not exclusively found in cancerous tissue, and should not be used as the sole diagnostic tool for diagnosis and treatment. While it is imperative that metastatic disease is ruled out, it is essential to consider other pathologies when evaluating recurrent thyroid and neck masses in patients with a history of benign thyroid lesions. Presentation: 6/3/2024

8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n< 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases. Presentation: 6/3/2024

7685 Outcomes of Low-Risk Differentiated Thyroid Carcinomain a Predominantly Hispanic Pediatric Population

Abstract Disclosure: E.A. Delgado: None. A. Martinez: None. N. Solano: None. D. Baboun: None. F. Alkhoury: None. A. Carrillo-Iregui: None. C.L. Bustamante Escobar: None. Background: The American Thyroid Association (ATA) guidelines for the management of low-risk differentiated thyroid carcinoma (DTC) in children, recommend total thyroidectomy and central neck dissection without iodine ablation. Surveillance for recurrence in these patients includes serial TSH-suppressed thyroglobulin levels and thyroid ultrasounds. Iodine ablation is reserved for patients classified as ATA intermediate and high-risk given their risk of persistent cervical disease and distant metastasis, respectively. There is ongoing concern whether withholding Iodine-131 will result in higher rates of disease recurrence among ATA low-risk pediatric patients. To our knowledge this is the first study addressing a predominantly Hispanic pediatric population. Objective: Evaluate the recurrence rate of differentiated thyroid cancer (DTC) in ATA low risk patients since implementing the 2015 ATA pediatric guidelines in a predominantly Hispanic pediatric population. Methods: After obtaining Institutional Review Board approval, we performed a retrospective chart review of patients 19 years and younger, between 2012 and 2023, for DTC. We analyzed demographics, histopathological diagnoses, risk stratification, and post-diagnosis follow up. Results: From a cohort of 63 pediatric patients diagnosed with DTC, a significant majority (n=55, 87%) comprised Hispanic individuals, while non-Hispanic cases represented the minority (n= 8, 13%). The mean age at diagnosis was 14.7 ± 2.6 years. Papillary thyroid carcinoma emerged as the prevailing type in 58 (92%), while 5 (8%) were follicular carcinoma. Among the patients, 12 (20%) were categorized as low risk level and underwent surgery alone. Over a median follow-up period of 2.6 years (IQR 2.97, range 0.94-5.18), 2 out of the 12 (18%) in this low-risk group experienced disease recurrence, with an average time to recurrence of 1.6 ± 0.9 years. Notably, one of the patients had a history of autoimmune thyroiditis. Subsequently, these 2 patients underwent further evaluation and treatment with iodine ablation. Conclusion: In a free-standing hospital with a predominantly Hispanic population, we found a recurrence rate of 18% in patients with ATA low-risk DTC not treated with radioactive iodine. Our rates align closely with those observed in earlier studies, which featured a non-Hispanic population and reported a 24% recurrence rate during the surveillance period. This underscores the crucial role of surveillance in low-risk patients with DTC in a Hispanic pediatric population. Presentation: 6/1/2024

6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology

Abstract Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors. Presentation: 6/3/2024