Hürthle Cell Carcinoma Research Articles

Rare Case of Oncocytic Carcinoma of Thyroid: Successful Surgical Management of a Large 20 Cm Tumor

Oncocytic carcinoma of the thyroid (OTC), also known as Hürthle cell carcinoma (HCC), is an extremely rare diagnosis accounting for 3% to 5% of all thyroid cancers. Historically, Hürthle cell carcinoma was considered as a variant of follicular carcinoma because of its origin in the follicular epithelium. However, later reports suggested that they are more aggressive, and most cases were found to be refractory to Radioiodine ablation (RAI). The rarity of HCC and the historical overlap with follicular thyroid cancer has made it difficult to develop Hürthle cell carcinoma-specific management strategies. Management varies based on tumor size and extent, with total thyroidectomy being recommended for larger tumors. The role of radioactive iodine therapy remains controversial. In this report, we present a 71-year-old female who presented to our hospital with a massive (20 cm) thyroid tumor that was diagnosed as oncocytic carcinoma of the thyroid and was successfully managed with total thyroidectomy.

A rare case report of hurthle cell adenoma mimicking malignancy

Thyroid lesions are the most common endocrine diseases, occurring in usually all age groups, though accurate diagnosis still remains a challenge, as due to oncocytic potentials of Thyroid cells leads to like indeterminate or suspicious diagnosis. Long standing benign Thyroid lesion shows atypical presentation suspicious to malignancy. Now a days with the help of WHO classification and available advanced diagnostic measures helping to confirm the diagnosis, avoiding overdiagnosis and wrong treatment. Hence this study review the importance of Histopathological study with coordination with immunohistochemistry (IHC) study, where suspicious thyroid malignant lesion finally diagnosed as benign Hurthle cell/ Oncocytic adenoma in Nodular Goitre.: 72 year old female presented huge neck swelling since one year, was reviewed in our departments of Pathology and ENT. Fine needle aspiration cytology (FNAC) features are suspicious of Malignancy, further Histopathological features were studied with co ordance of IHC study. FNAC features, which were suspicious of Malignancy were further studied with Histopathological and IHC studies diagnosed as Hurthle cell/ Oncocytic adenoma in Nodular Goitre. Histopathology remains the cornerstone for the diagnosis of thyroid oncocytic lesions and also in distinguishing between adenoma and carcinoma.

7079 Analysis of the Association Between Recent Exposure to Pregnancy and the Histological Subtype of Thyroid Cancer

Abstract Disclosure: T.L. Danehy: None. A. Manavalan: None. C. Schechter: None. Y. Tomer: None. Objective: Thyroid cancer is the second most common cancer diagnosed in pregnancy (1). Both HCG and estrogen have been implicated in this increased risk (2). While the classic variant of papillary thyroid cancer is the most common subtype in non-pregnant women, the effect of exposure to pregnancy on histological subtype remains unclear and could have clinical implications. Methods: This is a retrospective cohort study conducted at Montefiore Medical Center. All women of childbearing age (18-45) with a diagnosis of thyroid cancer between the years of 2015 -2020 (n=152) were identified. 43 participants were excluded due to missing data. The remaining 114 participants were divided into 2 groups; Group 1 or the exposed (n=25) included those diagnosed with thyroid cancer during pregnancy or in the 2 years postpartum and had carried their pregnancy to term, and Group 2 or the unexposed (n =89) included those who were nulliparous or diagnosed with thyroid cancer prior to pregnancy or more than 2 years post-partum. Charts were reviewed to obtain data on the initial histopathology and were classified into Follicular Thyroid Cancer (FTC), Hurthle cell carcinoma (HCC), Medullary Thyroid Cancer (MTC), and Papillary Thyroid Cancer (PTC). Results: Women in the unexposed group were significantly younger than those exposed to pregnancy (28.7 vs 32.7 p=0.005). The distribution of histological types in the two groups was as follows:Group 1: FTC (13.0%), HCC (0%), MTC (0%), and PTC (87%). Group 2: FTC (5.7%), HCC (2.3%), MTC (3.4%), PTC (88.5%). Thus, the incidence of follicular thyroid cancer in the exposed group was > 2-fold that observed in unexposed group, but this difference did not meet statistical significance (p=0.594). Conclusions: Our study showed a non-statistically significant increased incidence of FTC in women who were diagnosed with thyroid cancer during pregnancy or 2 years postpartum compared to unexposed women. While this did not meet statistical significance, our study sample was small and may have been underpowered. Therefore, our findings merit further investigation given their potential clinical implications.

7925 Cowden Disease Occurring in Association with Common Variable Hypogammaglobulinemia: A Case Report

Abstract Disclosure: M.K. Shakir: None. I.C. Ebrahim: None. D.B. Maxwell: None. N.O. Vietor: None. T.D. Hoang: None. Carriers of a pathogenic germline mutations in the PTEN gene, a tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, including thyroid, breast, endometrial and colon cancer, termed as PTEN Hamartoma Tumor Syndrome (PHTS). Recent studies have shown that PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. We are reporting a 47-year-old female with Cowden disease (CD) and common variable hypogammaglobulinemia (CVH). Our patient was diagnosed with CVH at the age of 25 after several episodes of pneumonia as well as poor wound healing. Since then, she is being treated with monthly intravenous immunoglobulin therapy. At the age of 24 years, she had a fainting episode and a diagnosis of gangliocytoma of cerebellum was made and she underwent resection of the tumor. At this time, she was also diagnosed with CD. She has a personal history of multiple other tumors including phyllodes tumor of breast, s/p bilateral mastectomy at the age of 32, status post hysterectomy for endometrial hyperplasia at the age 35. Hurthle cell adenomas of thyroid s/p total thyroidectomy at the age of 38. Her family history was significant for sister and father with CD. Physical examination was remarkable for only acral keratosis without mucocutaneous neuromas, oral papillomas and trichilemmomas. Cowden syndrome is the best-described phenotype of PHTS; it is characterized by mucocutaneous lesions and an elevated risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as various benign manifestations such as macrocephaly and dysplastic gangliocytoma of the cerebellum. Our patient was diagnosed with CD when she presented with gangliocytoma of the cerebellum. Immunodeficiency has been reported previously in patients with CD, and these patients often present with recurrent cellulitis and abscesses, and reduced T cell numbers and in vitro T cell proliferative function. Thus, PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. Additionally, a decreased ability of dendritic cells to prime CD8+ T cells may occur, leading to impaired tumor eradication. Immune dysfunction in PHTS patients might be a potentially manageable contributing factor to the increased cancer risk in PHTS. In conclusion, patients presenting with CD should also be screened for disorders of immunological dysregulation. Presentation: 6/2/2024

Unraveling the Enigma: A Five-Year Comprehensive Analysis of Hurthle Cell Tumors in South India's Tertiary Care Center.

Hurthle cell tumors of the thyroid gland constitute a rare and enigmatic group of neoplasms, characterized by the presence of Hurthle cells exhibiting abundant eosinophilic cytoplasm and numerous mitochondria. Despite their low incidence, they pose diagnostic challenges and display diverse clinical outcomes. This study aims to provide a comprehensive analysis of the clinicopathological profile of Hurthle cell tumors within a tertiary care center in South India. Through a retrospective approach, we analyzed cases of Hurthle cell tumors diagnosed and treated at a tertiary care center over a five-year period. Clinical, radiological, and histopathological data were meticulously collected and scrutinized. The study focused on examining demographic details, presenting symptoms, imaging features, cytological findings, surgical management, and postoperative outcomes of the patients. A total of 32 cases of Hurthle cell tumors were identified during the study period. The majority of patients were female (84%), with a mean age of 49.6 years for Hurthle cell carcinoma. Thyroid enlargement and neck mass were the most common presenting complaints. Fine-needle aspiration cytology showed characteristic features suggestive of Hurthle cell tumors in 33% of cases. Total thyroidectomy remains the mainstay surgical approach. Histopathological evaluation confirmed 62.5% of cases as benign adenomas and 37.5% as malignant carcinomas. Among malignant cases, 67% showed capsular invasion and 33% demonstrated vascular invasion. Of the patients,33.3% received adjuvant radiotherapy. The overall survival rate was 100%. In our study, we found that thyroid nodules larger than 3 cm demonstrated a higher propensity for Hurthle cell carcinoma. Our findings support the multidisciplinary approach in managing Hurthle cell tumors, with a focus on tailored treatment plans for each patient based on individual characteristics. By recognizing the female predominance, assessing nodule size, and employing a combination of thyroidectomy and ablative therapy, clinicians can optimize patient care and contribute to better long-term prognosis and quality of life for those affected by Hurthle cell tumors. Continued research and collaborative efforts are necessary to advance our understanding and refine treatment strategies, paving the way for improved outcomes and enhanced patient management in the future.

Abstract 5082: Novel TSHR CAR T therapy for targeting oncocytic carcinoma

Abstract Oncocytic carcinoma (Hurthle cell carcinoma) has the highest incidence of metastasis among the differentiated thyroid cancers. Metastatic disease is reported at the initial diagnosis in 10-20% of patients and 34% overall. Thyroid-stimulating hormone receptor (TSHR) expression is limited to the thyroid gland. It is abundantly expressed on thyroid tumor cells, making TSHR a compelling target for advanced thyroid cancer diagnostics and therapeutics. We developed a potent anticancer strategy for treating oncocytic carcinoma using a novel thyroid hormone stimulating receptor (TSHR)- targeted (chimeric antigen receptor) CAR T cell therapy. TSHR CAR T was generated by transducing T cells derived from healthy donors. In vitro effector functions (cytotoxicity, proliferation, degranulation) were tested in TSHR+ tumor models, and subsequent in vivo studies using NSG mice were performed to assess anti-tumor activity efficacy. We observed strong anti-tumor activity against metastatic oncocytic carcinoma cell line XCT.UC1 using the TSHR CAR T therapy in vivo. Re-challenging treated mice with XCT.UC1 cells reactivated TSHR CART cells with enhanced proliferation and complete suppression of tumor growth of the newly injected tumor cells. Our work represents a promising strategy to improve treatment outcomes of patients with metastatic oncocytic carcinoma that may provide a durable response. Citation Format: Justyna J. Gleba, Aylin Alasonyalilar-Demirer, Matthew Pawlush, Claudia Manriquez-Roman, Elizabeth L. Siegler, Robert C. Smallridge, Abba Zubair, Han W. Tun, Saad S. Kenderian, John A. Copland. Novel TSHR CAR T therapy for targeting oncocytic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5082.

Two synchronous paraneoplastic endocrine syndromes in a 53-year-old male with broadly metastatic widely invasive Hürthle cell carcinoma.

Unlike medullary thyroid carcinomas, follicular cell-derived thyroid malignancies have rarely been associated with paraneoplastic endocrine syndromes. An ultrarare case of a middle-aged man with heavily treated broadly metastatic radioactive iodine-refractory widely invasive Hürthle cell carcinoma (HCC) of the thyroid with two synchronous paraneoplastic endocrine syndromes, T3 thyrotoxicosis and hypercalcemia of malignancy, is discussed here. The levothyroxine-induced T3 thyrotoxicosis was a gradual process that became more noticeable as the tumor burden, refractory to different modalities of therapy, expanded. The 1,25-dihydroxyvitamin-D-mediated hypercalcemia, on the other hand, developed in a manner of weeks, as it usually happens. It is important to emphasize that in patients with metastatic Hürthle cell and follicular carcinomas of the thyroid, on TSH suppressive therapy, the unexplained and progressive decline in FT4 and rise in FT3 levels, resulting in an elevated FT4/FT3 ratio, could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from the prohormone T4 into the active metabolite T3 via outer ring deiodination. Albeit extremely rare, some patients with thyroid cancer can present with more than one concomitant paraneoplastic syndrome. Although medullary thyroid carcinoma is the thyroid malignancy that is usually associated with paraneoplastic endocrine syndromes, follicular cell-derived thyroid cancers have been rarely described as being the culprit. In patients with metastatic Hürthle cell and follicular thyroid carcinomas, the unexplained and progressive decline in FT4 and rise in FT3 levels could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from T4 into T3 leading to T3 thyrotoxicosis.

Malignant tumor implants after endoscopic thyroidectomy for oncocytic thyroid adenoma: A rare case report

Oncocytic carcinoma of the thyroid, previously referred to as Hurthle cell carcinoma, is a rare and aggressive form of thyroid cancer. In this particular case, a 71-year-old female presented with a palpable neck mass and a history of endoscopic thyroidectomy performed five years prior. Histopathological analysis confirmed the diagnosis of oncocytic carcinoma. In this report, we describe a unique case involving the implantation of a malignant tumor in a postoperative oncocytic thyroid adenoma, which notably exhibited the "flip-flop" phenomenon, as identified through nuclear imaging modalities.

Genomic profiling of primary and metastatic thyroid cancers.

The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer

BackgroundOf the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium–iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. MethodsWe immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, β+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high–thyroid-stimulating hormone receptor and low–thyroid-stimulating hormone receptor–expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor–positive THJ529T tumors. ResultsImmunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor–positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor–expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. ConclusionOur observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor–positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

SAT572 Concomitant Metastatic Hurthle Cell Carcinoma And Rectal Cancer, Challenges In Diagnosis And Management

Abstract Disclosure: D. Khurram: None. R. Pansare: None. S.L. Mokshagundam: None. Hurthle cell carcinomas (HCC) are aggressive tumors and account for 5% of follicular cell thyroid malignancies. Tumor size, extra-thyroid extension and distant metastases indicate poor prognosis. 20-30% of HCCs have mets at initial diagnosis, frequent sites being lungs and bones. Metastatic HCCs are exceedingly difficult to manage. Detecting two primary cancers concomitantly is uncommon and poses additional challenges in diagnosis and management. We present an interesting case of HCC with mets to the manubrium, vertebrae, lungs and concomitant rectal adenocarcinoma. A 69-year-old male had MRI spine for back pain which showed multiple lytic osseous lesions within T3 and L1 vertebrae. Further imaging revealed a large lesion in the manubrium. Manubrial mass biopsy was positive for poorly differentiated carcinoma, immunohistochemical staining for CAM5.2, cytokeratin, CD 138, CD56 and TTF-1 (weak). He underwent 6 cycles of palliative chemotherapy with carboplatin and Taxol for carcinoma of unknown origin. PET scan following chemotherapy showed a large heterogenous thyroid mass with intense FDG uptake, along with a suspicious rectal mass. Left thyroid nodule FNA reported Bethesda IV follicular neoplasm, Hurthle cell type. Rectal mass biopsy reported moderately differentiated adenocarcinoma. Histology after total thyroidectomy showed unifocal oncocytic HCC, with lymphovascular invasion but no extrathyroidal extension. Molecular markers showed low TMB, stable microsatellite status, negative PDL-1, negative NTRK fusion and positive ATM E839. He received suppressive dose levothyroxine. Radio-iodine ablation was postponed owing to prioritization of radiation therapy for rectal cancer. Thyroglobulin level increased from 53 ng/ML to 216 ng/ML. He received 149 milli Curies of I131 after Thyrogen stimulation. There was mild radioiodine uptake in the thyroid bed, but the metastatic lesions were not radioiodine avid. Follow-up scans showed multiple bilateral pulmonary nodules with worsening osseous mets. Endoscopic biopsy was consistent with HCC, TTF-1 and PAX8 positive. He was started on Lenvatinib but developed diarrhea, hence switched to Pembrolizumab. Thyroglobulin level improved on Pembrolizumab but was complicated by adrenal insufficiency. For rectal cancer, he received radiation therapy and capecitabine. Our case is interesting for several reasons. Firstly, although bone mets are commonly seen in HCC, manubrial mets, especially as the presenting feature is rare. Secondly, concomitant rectal cancer delayed the treatment of the thyroid cancer. Thirdly, there is no major consensus regarding management of HCC, especially metastatic HCC. HCCs are often not radioactive iodine avid. Combination therapy with Lenvatinib and Pembrolizumab is currently under trial for aggressive thyroid malignancy. It will be interesting to follow the clinical outcomes in this individual. Presentation: Saturday, June 17, 2023

THU675 A Case Report For Hurthle Cell Neoplasm Suspicious For Carcinoma

Abstract Disclosure: J. Wu: None. P. Rimal: None. S. Ying: None. R. Jasaraj: None. F. Ali: None. A. Havrylyan: None. Hurthle cell carcinoma, also called Hurthle cell thyroid cancer, is an extremely rare type of thyroid tumor. It accounts for approximately 3-4% of all thyroid cancers, [3][19] usually diagnosed when patients present clinically with thyroid nodules or incidental findings on neck imaging. [1][2] In this case, we present a case for suspicious Hurthle cell carcinoma occurring in a 76-year-old male patient. He initially presented with progressive worsening dyspnea. An initial chest CT scan showed multiple pulmonary nodules; meanwhile, it also noted an incidental finding of thyroid nodules on the CT scan. Thyroid function tests, including thyroid-stimulating hormone (TSH) and thyroxine (T4), are mild hypothyroidism, indicating non-thyrotoxic thyroid nodules; ultrasound of the thyroid gland showed one right upper solid isoechoic nodule. Further fine-needle aspiration (FNA) biopsy revealed cells suspicious for hurtle cell neoplasm. The patient was subsequently referred to otolaryngology for thyroid lobectomy or thyroidectomy.Case reports: A 74-year-old male with a past medical history of Hypertension, type2 Diabetes mellitus, Deep vein thrombosis, Atrial fibrillation, Aortic stenosis, and hypothyroidism initially presented with chronic dyspnea caused by severe aortic stenosis, with scheduled aortic valve replacement in August 2022. A pre-procedure chest CT showed multiple 3 -5 mm pulmonary nodules throughout the lungs and an incidental finding of thyroid nodules. The patient was referred to the endocrinology department for his thyroid nodules. The patient was in a clinically euthyroid state, denied compressive symptoms, and denied dysphagia, hoarseness, and past exposure to radiation. The thyroid function test reveals elevated TSH and a high level of thyroid peroxidase antibodies; However, free T4, free T3, and Total T3 are all within normal limits. Subsequently, a thyroid ultrasound revealed one right upper solid isoechoic 2.5 x 1.7 x 2.1 cm nodule (TI-RADS 3). A fine-needle aspiration (FNA) biopsy on 01/23/2023 revealed findings suspicious for hurtle cell neoplasm. This patient was subsequently referred to an otolaryngologist (ENT) for thyroid lobectomy or thyroidectomy to confirm the diagnosis. ENT recommends at least a right thyroid lobectomy. Conclusion: Despite being rare, Hurthle cell carcinoma still affects several patients every year. It is usually diagnosed when patients present clinically with thyroid nodules or incidental findings on imaging of the neck, like in this case. It is characterized by the presence of Hurthle cells in histology. However, FNA cannot distinguish between a benign adenoma and malignant carcinoma. Distinguishing them requires a thyroid lobectomy or thyroidectomy. We hope that highlighting this case report will help clinicians across specialties recognize and diagnose this condition with the appropriate level of care. Presentation: Thursday, June 15, 2023

KLİNİK PRATİKTE ACR-TIRADS’IN UYGULANMASI

Objective&#x0D; To investigate the diagnostic accuracy of the Thyroid&#x0D; Imaging, Reporting and Data System of the American&#x0D; College of Radiology in thyroid nodules.&#x0D; Material and Method&#x0D; A total of 151 nodules were collected from 62 patients&#x0D; undergoing thyroid surgery in our center between&#x0D; August 2017 and September 2018. Ultrasonographic&#x0D; features of each nodule were recorded and classified&#x0D; according to the Thyroid, Imaging Reporting and Data&#x0D; System of the American College of Radiology by two&#x0D; radiologists and compared with a one-to-one basis on&#x0D; histopathology.&#x0D; Results&#x0D; The median size of 151 thyroid nodules measured on&#x0D; the ultrasound and in the pathology specimens were&#x0D; 19 (3-85) mm and 17 (0-97) mm, respectively. Papillary&#x0D; carcinoma was demonstrated in 28 patients (45%),&#x0D; papillary microcarcinoma in 14 patients (22.5%), and&#x0D; Hurthle cell carcinoma in 1 (1.6%) patient. Overall&#x0D; sensitivity, specificity, positive predictive value,&#x0D; and negative predictive value for this nodule risk&#x0D; stratification model were analyzed as 82.5%, 57%,&#x0D; 64.58%, and 77.67%, respectively.&#x0D; Conclusion&#x0D; Setting a definitive size threshold for fine needle&#x0D; aspiration might be misleading, instead signifying the&#x0D; malignant features on ultrasonography, and making a&#x0D; decision for surgery on an individual base should be&#x0D; recommended.

Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment

Somatostatin receptor type 2 (SSTR2) and thyroid-stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore the differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) vs oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin-embedded tissue blocks were used for tissue microarray construction. Tissue microarray blocks were cut into 5-μm sections and stained with anti-SSTR2 and anti-TSHR antibodies. Immunostains were analyzed by 3 independent pathologists. χ2 and logistic regression analysis were used to analyze clinical and pathologic variables. Sixty-seven specimens were analyzed with 15 OA and 52 OC. The mean age was 57 years, 61.2% were women, and 70% were White. SSTR2 positivity was noted in 2 OA (13%) and 15 OC (28%; 10 primary, 4 recurrent, and 1 metastatic) (P = .22). TSHR positivity was noted in 11 OA (73%) and 32 OC (62%; 31 primary and 1 metastatic) (P = .40). Those who presented with or developed clinical recurrence/metastasis were more likely to be SSTR2-positive (50% vs 21%; P = .04) and TSHR-negative (64.3% vs 28.9%; P = .02) than primary OC patients. Widely invasive OC was more likely to be SSTR2-positive compared to all other OC subtypes (minimally invasive and angioinvasive) (P = .003). For all patients with OC, TSHR positivity was inversely correlated with SSTR2 positivity (odds ratio, 0.12; CI, 0.03-0.43; P = .006). This relationship was not seen in the patients with OA (odds ratio, 0.30; CI, 0.01-9.14; P = .440). Our results show that recurrent/metastatic OC was more likely to be SSTR2-positive and TSHR-negative than primary OC. Patients with OC displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in patients with OA. This may be a key relationship that can be used to prognosticate and treat OCs.

Fine-Needle Aspiration Biopsy Findings of the Thyroid Gland in Renal Transplant Patients.

For patients with end-stage renal disease, thyroid diseases are common due to altered hormone excretion and transport, and for renal transplant recipients this is due to immunosuppressive drugs. We investigated the prevalence of thyroid disorders, including thyroid cancer, by fine-needle aspiration biopsy in kidney transplant candidates and recipients and estimated the outcomes. For 305 thyroid fine-needle aspiration biopsies performed from January 2000 to December 2020 in patients with end-stage renal disease, we recorded patient demographics, thyroid ultrasonography, and biopsy findings. Of biopsy results from 305 patients, 272 (89.2%) were benign, 24 (7.9%) showed atypia of undetermined significance/follicular lesion of undetermined significance, 2 (0.7%) had suspicion for malignancy, and 7 (2.3%)were malignant.Thyroid surgery was performed for 13 patients with benign results, 6 with atypia of undetermined significance/follicular lesion of undetermined significance, 2 with suspicion for malignancy, and 7 with malignancy. In 13 patients with benign cytology, the histopathology finding was also benign in lobectomy specimens. In 6 patients with atypia of undetermined significance/follicular lesion of undetermined significance, the final diagnosis was papillary thyroid carcinoma in 3 patients, adenomatous hyperplasia in 2 patients, and Hurthle cell adenoma in 1 patient. For all 9 patients for whom fineneedle aspiration biopsy was suspicious for malignancy or malignant, histopathologic examination showed papillary thyroid carcinoma in total thyroidectomy materials. Among 12 papillary thyroid carcinoma patients, 4 underwent renal transplant after thyroidectomy, and survival for these 4 patients was 116.25 ± 29.30 months after transplant without tumor recurrence or distant metastases. Thyroid diseases are more frequent in patients with end-stage renal disease or renal transplant versus the normal population and also affect morbidity and mortality at higher rates in these patients. Fine-needle aspiration biopsy is a useful diagnostic modality in evaluation and treatment of thyroid nodules in both kidney transplant candidates and recipients.

455 Fine-Needle Aspiration, Ultrasound and Thyroidectomies in Patients with Thyroid Nodules Presenting to a District General Hospital – a Retrospective Audit

Abstract Aim To determine whether fine-needle aspiration, ultrasound and thyroidectomies were being performed appropriately in patients with thyroid nodules, and to compare the percentage of malignant cases for each histological classification with the national standards. Method Patients undergoing thyroidectomy in Northwest Anglia Trust (East of England) between October 2021 – October 2022 was identified retrospectively using the OPSC-4 codes. Medical records of 132 patients were retrieved, and data points extracted. Results We identified 103 female and 29 patients. The female cohort had a younger age distribution (median 52y) compared to the male cohort (59y). 42 patients underwent total thyroidectomy, 89 underwent hemithyroidectomy and 1 underwent lobectomy. 21% of the specimen was reported to be malignant, of which 74% was papillary cell carcinoma, 15% follicular cell carcinoma and 11% Hurthle cell carcinoma. Our percentage of malignancy in the Thy1a/c category was higher (5%) compared to the national figures of malignancy risk reported by RCPath (4%), whilst the rest were lower than the national figures (Thy2 = 0%, Thy3a = 13%, Thy3f = 19%, Thy4 = 50%, Thy5 = 94%). 100% of Thy3, Thy4 and Thy5 patients underwent diagnostic hemithyroidectomy. 15 patients did not have documentation of the U classification prior to thyroidectomy. There was 84% compliance with repeat FNAC requirements prior to surgery and 97% compliance with MDT discussion. Conclusions Current BAETS guideline states that thyroid nodules with benign appearances (U1 and U2) do not need to be followed-up, however we found a 15% of malignancy in these patients. Costs, risks and benefits of regularly undertaking fine needle aspiration in these patients must be considered.

Hurthle cell carcinoma: a rare variant of thyroid malignancy - a case report.

The authors present a case of a 49-year-old female with a known case of chronic obstructive pulmonary disease and hypertension who presented to our hospital with anterior neck swelling for 4 months that has gradually increased over the time. Physical examination, laboratory test, various radiological imaging, and cytological study led to the diagnosis of Hurthle cell neoplasm. With prompt diagnosis, she was admitted and surgery was done that include right hemithyroidectomy. Though it is a rare type of thyroid malignancy, early diagnosis and proper treatment has shown a very good prognosis. Hurthle cell carcinoma initially presents with a single, painless palpable mass in the thyroid with pressure symptoms in advanced cases including dysphagia, dyspnea, and hoarseness. Pain, rapid growth, or significant compressive symptoms are suggestive of an invasive one. This case highlights on rarity of disease, presentation, and availability of treatment modality.

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis.

Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG.

Large (>4 cm) Intrathyroidal Encapsulated Well-Differentiated Follicular Cell-Derived Carcinoma Without Vascular Invasion May Have Negligible Risk of Recurrence Even When Treated with Lobectomy Alone.

Background: Thyroid carcinoma >4 cm in size is staged as T3a. The current American Thyroid Association guidelines recommend subtotal/total thyroidectomy and consideration for postoperative radioactive iodine (RAI) treatment for these tumors. In this retrospective cohort study, we aimed to explore the clinical course of large encapsulated thyroid carcinoma without other risk factors. Methods: Eighty-eight patients with large (>4 cm) encapsulated well-differentiated thyroid carcinoma resected between 1995 and 2021 were included in this retrospective cohort study. Exclusion criteria were tall cell variant, any extent of vascular invasion, extrathyroidal extension (microscopic or gross), high-grade histology, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), infiltrative tumors, positive resection margin, and cases with follow-up <1 year. The primary outcomes are risk of nodal metastasis at the initial resection, disease-free survival (DFS), and disease-specific survival (DSS). Results: The tumor histotype was follicular carcinoma (n = 18, 21%), oncocytic (Hurthle cell) carcinoma (n = 8, 9%), and papillary thyroid carcinoma (PTC; n = 62, 70%). Among PTC, 38 were encapsulated follicular variant, 20 classic type, and 4 solid variant. Four cases had extensive capsular invasion (CI), 61 (69%) had focal CI, whereas 23 did not have CI. Thirty-two cases (36%) were treated with lobectomy/hemithyroidectomy alone, and 55 patients (62%) did not receive RAI. Five patients had nodal metastasis at the time of primary resection, all of whom had classic-type PTC. The median follow-up period was 4.8 years (interquartile range: 3.2-9.7 years). No recurrence, being local, regional, or distant, was observed in the entire cohort, including those patients treated with lobectomy alone without RAI. The 10-year DFS and DSS were 100%, respectively. Conclusion: Large intrathyroidal encapsulated well-differentiated thyroid carcinoma without vascular invasion follow an extremely indolent clinical course with negligible risk of recurrence. Lobectomy alone without RAI may be the appropriate treatment strategy for this selected group of patients.

Abstract 228: Recurrent mitochondrial mutations in thyroid cancer

Abstract Despite the importance of mitochondrial function on the bioenergetics and metabolism of the cell, understanding the functional impact of somatic mitochondrial mutations has been difficult. Additionally, small cohorts, as used in previous studies, lack the power to estimate the prevalence of specific recurrent mutations. We evaluated 177540 advanced cancer patients, across 84 different tumor types, who were sequenced as part of routine clinical care on the FoundationOne®CDx platform. Off-target sequencing reads were mapped to the mitochondrial genome (rCRS) and variant calling was performed. We had a median read depth of 18 and filtering by allele frequency (&amp;lt;= 95% and &amp;gt;= 5%) led to the identification almost 400,000 predicted somatic mitochondrial variants. Over 80% of patients had at least one mitochondrial variant detected, with an average of 2.2 mitochondrial variants detected per patient. We next assessed each recurrent mitochondrial short variant to look for associations with specific cancers. The alteration with the strongest enrichment was G3224A, a mutation in the mitochondrial leucine tRNA gene (MT-TL1), which had a prevalence of 3.6% (51/1426) in thyroid cancer samples, as compared to 0.05% (85/176114) in all other disease types (OR=76.8, P&amp;lt;2.2e-16). The G3244A mutation has been previously identified as occurring in thyroid cancer, specifically Hurthle cell carcinomas, as well as in the mitochondrial disease MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Thyroid cancer samples in our dataset with G3244A were found to be associated with thyroid follicular carcinomas (7/124, 5.6%) and Hurthle cell carcinomas (7/57, 12.2%). Additional recurrent MT-TL1 mutations were identified in the thyroid cancer cohort at positions 3242 (9/1426) and 3248 (5/1426). We also identified a mutation in the NADH dehydrogenase subunit MT-ND1. G3380A has been previously shown to occur in thyroid and colorectal cancer and results in a R25Q mutation that is thought to affect ND1 function. G3380A was identified in 26/1426 (1.8%) of thyroid cancer patients. The majority of G3380A variants occurred in thyroid anaplastic carcinomas 23/26 (88.5%). Our dataset has allowed us to identify and determine the prevalence of rare mitochondrial short variant alterations in cancer. Further research is needed to investigate associations of these alterations with other clinical features. Citation Format: Julia F. Hopkins, Zoe Fleischmann, Dexter X. Jin, Jonathan Keith Killian, Meagan Montesion. Recurrent mitochondrial mutations in thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 228.