Follicular Lesion Of Undetermined Significance Research Articles

An economically efficient strategy for diagnosing atypia of undetermined significance or follicular lesion of undetermined significance thyroid nodules with ultrasound-based risk stratification systems and BRAFV600E testing.

The management of thyroid nodules classified as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) has been a subject of ongoing debate. Therefore, the aim of this study was to investigate a cost-effective approach for managing these nodules by combining BRAFV600E mutation analysis with the guidelines provided by the American Thyroid Association (ATA) or the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). This study included 762 AUS/FLUS nodules in 551 patients with a postoperative pathology. A preoperative BRAFV600E gene test and an evaluation using the ATA guidelines and ACR-TIRADS were performed. Two combined diagnostic approaches were employed: In method 1, all nodules underwent BRAFV600E gene testing, and nodules testing positive for BRAFV600E or for risk stratification systems (RSSs) were diagnosed as malignant, while those with negative results in both tests were considered benign. In method 2 (modified combination method), nodules were reclassified into low-risk (category 2 and 3 in the ATA guidelines and ACR-TIRADS), medium-risk (category 4), and high-risk (category 5) groups based on the malignancy rate of the RSSs. BRAFV600E gene testing was applied only with the medium-risk group. Nodules with positive BRAFV600E mutation were upgraded to the high-risk group, while negative cases remained in the medium-risk group. Both malignancy rates and positive BRAFV600E mutation rates increased with the increase in RSS category (P<0.001). The combination of ACR with BRAFV600E gene testing significantly improved the area under the curve (AUC) compared to the use of ACR or BRAFV600E alone (the AUCs for ACR combined with BRAFV600E, modified ACR combined with BRAFV600E, ACR alone, and BRAFV600E alone were 0.875, 0.878, 0.832, and 0.839, respectively; P<0.05 for both combinations vs. ACR or BRAFV600E alone). Similarly, ATA combined with BRAFV600E showed significant improvements in AUC compared to ATA alone (the AUCs for ATA combined with BRAFV600E, modified ATA combined with BRAFV600E, and ATA alone were 0.851, 0.846, 0.809, respectively; P<0.001 for both combination methods vs. ATA alone), but there was no significant difference observed compared to using BRAFV600E alone (P=0.450 and P=0.680 for both combination methods vs. BRAFV600E). Notably, the AUC of ACR combined with BRAFV600E was greater than that of ATA combined with BRAFV600E (P=0.047 and P=0.007 for both combination methods, respectively). There were no significant differences in diagnostic performance between the two combination approaches (P=0.428 for ACR combined with BRAFV600E and P=0.314 for ATA combined with BRAFV600E). Performing BRAFV600E gene testing only on the medium-risk groups (modified combination method) significantly reduced the rate of BRAFV600E gene testing (P<0.001) without increasing the false-negative rate (P=0.818 and P=0.394 for ACR and ATA, respectively). Incorporating the BRAFV600E gene test exclusively for nodules in the medium-risk group significantly improved diagnostic efficacy, reduced the utilization of gene tests, and maintained a consistent false-negative rate.

SAT508 Siblings With Heterozygous DICER1 c.322C&amp;gt;T, pGln108* Variant: A Novel Genetic Variant for DICER1 Syndrome

Abstract Disclosure: N.L. Yamashita: None. J. Austin: Consulting Fee; Self; Ascendis, Vertice. Research Investigator; Self; IBSA Pharmaceuticals. Background: Several genetic variants are implicated in DICER1 syndrome - a neoplasm predisposition syndrome with a spectrum of presentations with both benign and malignant tumors. DICER1 c.322C&amp;gt;T, pGln108* variant is a new mutation that was found in this case of two siblings presenting with thyroid cancers. Clinical case: Sibling A is a 10-year-old female who presented to the emergency department (ED) with a rapidly progressing right neck mass. She underwent fine needle aspiration (FNA) that returned as Follicular Lesion of Undetermined Significance (FLUS), Bethesda III. Subsequently, she had a right lobectomy, and pathology results revealed multiple follicular adenomatous nodules with focal papillary hyperplasia. Approximately one year later, she re-presented with a new left sided neck swelling with ultrasound revealing three new nodules. She underwent left lobectomy and pathology showed follicular variant papillary thyroid carcinoma (FVPTC). She was started on levothyroxine replacement daily. Her surveillance regimen included I-123 thyroid uptake scans which showed uptake in the neck. Her TSH-stimulated thyroglobulin was as high as 4.3 ng/mL with negative thyroglobulin antibody titer. She did not receive radioactive iodine ablation (RAI). Since then, routine thyroglobulin levels have remained low and neck ultrasounds have been reassuring. She is currently 19 years old. Approximately three years after Sibling A’s second lobectomy, her sister, Sibling B, presented as an 11-year-old female to the ED with neck swelling. Thyroid ultrasound showed multiple solid and cystic nodules on both right and left thyroid lobes. FNA returned with Bethesda Category IV (suspicious for follicular neoplasm) on the left lower nodule and Bethesda II (benign follicular nodule) on other nodules. She underwent total thyroidectomy and was found to have follicular thyroid carcinoma (FTC). TSH-stimulated thyroglobulin was as high as 8.9 ng/mL. Her surveillance thyroid scan showed uptake in the right thyroidectomy bed and 1.6 cm nodule was found on ultrasound. FNA of this lesion was benign with stable repeat thyroid scans with downtrending TSH-stimulated thyroglobulin. This patient is currently 15 years old. Soon after the Sibling B was diagnosed with FTC, the decision was made to pursue genetic analysis. Both siblings underwent mutation analysis which were both positive for heterozygous DICER1 c.322C&amp;gt;T, pGln108* variant.Conclusion: This case introduces a novel variant to DICER1 syndrome: DICER1 c.322C&amp;gt;T, pGln108* variant. Without a family history of multinodular goiter (MNG), thyroid cancers, or other associated tumors to this syndrome, these siblings had unusual presentations of a germline DICER1 syndrome variant. This case highlights the expressive variability in DICER1 syndrome and this variant may be of consideration when children present without other predisposing tumors. Presentation Date: Saturday, June 17, 2023

SAT476 A Case of Thyroid Hemiagenesis

Abstract Disclosure: P. Kachhadia: None. S. Khan: None. S. Aldasouqi: None. A. Abu Limon: None. Introduction: Thyroid hemiagenesis is congenitally rare, in which one side of the thyroid does not develop. Hemiagenesis is more common with an absent left thyroid lobe, at a 4:1 ratio. Though prevalence is sited at 0.05%, actual incidence of hemiagenesis amongst the population is unknown as most patients are euthyroid and asymptomatic. We present a case of a patient who was referred to our clinic for unilateral thyroid enlargement on physical exam. Thyroid Ultrasound (US) was done which showed an absent left thyroid lobe along with enlarged right thyroid lobe and hypervascularity. There was also an incidental thyroid nodule noted on US. Case Presentation: Patient is a 38 year old female who presented to the clinic 4 years prior for enlarged thyroid nodule noted on ultrasound. With symptoms of dysphagia and a visibly enlarged gland, an US with labs was prompted by her primary physician. US showed absent left thyroid lobe and right lobe enlargement with hypervascularity and incidental subcentimeter nodule. Clinically and biochemically, the patient was euthyroid. Singular right lobe was verified on clinic real time ultrasound and on NM uptake scan. The 24 hour uptake was at 30.5%, with the upper limit of normal being 30%. With increased uptake and hypervascularity, thyroid stimulating immunoglobulin and thyrotropin receptor antibodies were checked and were not detected. It was thought that the right thyroid gland enlargement and hypervascularity were compensatory due to the left hemiagenesis. The thyroid nodule was monitored, and within 3 years of original imaging, it enlarged to 0.98 x 0.59 x 0.39 cm, with TI-RADS 5 assessment per ACR criteria. Patient chose to undergo thyroid biopsy which showed Bethesda III, Follicular Lesion of Undetermined Significance (FLUS). Microscopy showed follicular cells arranged in microfollicles and crowded groups with round, enlarged, irregular nuclei and overlapping nucleoli. Intranuclear chromatin clearing and intranuclear grooves are present. Background is hemorrhagic with minimal colloid. Molecular Thyroseq testing was at 5-10% chance of malignancy or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Genetic markers were only positive for copy number alterations. Discussion: Thyroid Hemiagenesis, though rare, has been associated with other thyroid pathologies such as hypothyroidism, hyperthyroidism and thyroid malignancies. Genetic studies have not found a common background within cases reported. As these patients are more likely to incur additional thyroid pathologies, questions still remain as to the clinical management and outcome of such patients. Due to concerning cytological features for PTC, the patient was offered right thyroidectomy and will be looking to make a decision in the near future. Presentation Date: Saturday, June 17, 2023

SAT198 Parathyroid Adenoma Masquerading As A Thyroid Nodule

Abstract Disclosure: A. Arida: None. M. Papaleontiou: None. N. Esfandiari: None. Background: The diagnosis of parathyroid adenomas using a neck ultrasound (US) can be challenging when not performed by an experienced radiologist. Additional methods of diagnosis have been implemented to distinguish the differential diagnosis of a nodule in the neck. Clinical Case: A 48-year-old woman with a history of type 2 diabetes, hypercalcemia, and kidney stones presented for evaluation of a lump in the neck of 5 years duration. Prior thyroid US showed a solid hypoechoic nodule superior to the left thyroid lobe measuring 2.2 x 1.2 x 1.1 cm with hypervascularity. Her first FNA biopsy of this nodule reported benign cytology 5 years ago. A parathyroid scintigraphy scan was negative. Repeat FNA biopsy of this nodule showed follicular lesion of undetermined significance (Bethesda category III). Surgical consultation was recommended but she decided to seek a second opinion. A repeat neck US identified a solid vascular 1.6 cm nodule along the anterior margin of the superior left thyroid lobe. Some vascularity was extending from the thyroid tissue into the nodule. It was noted that this may represent an extrathyroidal nodule or arise from the thyroid gland with a score of TIRADS 4. Laboratory tests confirmed primary hyperparathyroidism with an iPTH of 126 pg/mL (normal range, 10-65 pg/mL) and serum calcium of 10.9 mg/dL (normal range, 8.6-10.3 mg/dL). After normalizing vitamin D levels, these values remained elevated. A repeat FNA biopsy of this nodule showed evidence of intrathyroidal parathyroid tissue. Immunostains were performed on the cell block material from the FNA biopsy. Scattered groups of cells were positive for PTH while being negative for TTF-1. Further needle washout for iPTH measurement revealed an iPTH &amp;gt;2000 pg/mL confirming the diagnosis of a parathyroid adenoma. Parathyroid surgery was recommended as per guidelines. Discussion: Once primary hyperparathyroidism is confirmed, the localization of parathyroid adenoma is pursued by a neck US and/or parathyroid scintigraphy. Parathyroid glands are located in the superior poles and in the inferior poles of the thyroid gland but ectopic locations like retropharyngeal, intrathyroidal, and mediastinal are possible. Typical US appearance is oval, solid, well-circumscribed, homogenous, and hypoechoic compared to the thyroid tissue. The color Doppler shows that the blood supply enters at the center and distributes peripherally presenting a “vascular arch” pattern that helps differentiate them from other lesions such as tumors or lymph nodes where the distribution is more centralized. Further needle washout for PTH level can confirm the diagnosis of parathyroid adenoma. Once a parathyroid adenoma is confirmed, minimally invasive parathyroid surgery can be recommended if surgery is indicated. Conclusion: A needle washout for measuring PTH in an FNA biopsy sample should be recommended when it is unclear whether a nodule is a thyroid nodule or a parathyroid adenoma. Presentation: Saturday, June 17, 2023

Radiofrequency ablation for thyroid Bethesda III nodules: preliminary results.

The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III). A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, 'moving-shot' technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed. The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture. RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.

Revisiting the cytomorphological features of poorly differentiated thyroid carcinoma: a comparative analysis with indeterminate thyroid fine-needle aspiration samples.

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon high-grade carcinoma of follicular cell origin that is usually overlooked on preoperative fine-needle aspiration (FNA) due to its rarity and cytomorphological overlap with follicular-patterned neoplasms. Definitive diagnosis of PDTC usually requires histologic examination of the resected thyroid tumor. Herein, we describe the cytological and architectural findings of histologically confirmed PDTC cases. A search for all thyroid FNAs with a corresponding surgical diagnosis of PDTC was performed. Surgical diagnoses were reviewed and confirmed using the Turin criteria. In addition, the control group consisted of indeterminate thyroid nodules (FLUS [follicular lesion of undetermined significance] and FN [follicular neoplasm]) that were either benign or well-differentiated thyroid tumors on resection. The PDTC and control groups were both subjected to cytological assessment using specific cytological and architectural parameters, which included cellularity, growth pattern, mitoses, necrosis, chromatin change, discohesion, and anisonucleosis. A total of 36 thyroid FNAs were included in the study. This consisted of 12 histologically confirmed PDTC FNAs and 24 indeterminate thyroid FNAs (FLUS and FN, 12 each). The most frequent findings among PDTC groups were hypercellularity (75%), trabecular/insular growth pattern (58%), branching capillaries (67%), and cellular discohesion (92%). Necrosis (25%), ≥3 mitoses (50%), and anisonucleaosis (42%) were less frequently observed. A peculiar finding was the presence of adenoid cystic carcinoma-like globules in 50% of PDTC cases. Certain findings such as colloid, necrosis, mitoses, and cellular discohesion were helpful in differentiating the two groups. Thyroid fine-needle aspiration remains an essential diagnostic/triage tool for most thyroid nodules/tumors. PDTC can be diagnosed or at least suspected preoperatively based on the demonstration of certain architectural and cytological alterations. Although mitoses and necroses are not always readily identified, an elevated Ki-67 labeling expression could provide additional clues to the diagnosis in some cases.

Should encountering atypia of undetermined significance / follicular lesion of undetermined significance after thyroid biopsy lead to the operation?

Objectives: Nodular goiter is the most common disease of the thyroid gland. Thyroid nodules are malignant in 3-5% cases. To determine the incidence of malignancy in patients defined as atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) as a result of fine needle aspiration biopsy (FNAB) and evaluate the clinical, biochemical and sonographic features as possible predictors of malignancy. Methods: Patients who had undergone at least one FNAB and diagnosed as AUS/FLUS from January 2011 to December 2015 were included in the study. Age, gender, benign disease, thyroid stimulating hormone (TSH) level, size, localization, number, time of FNAB, ultrasonography (USG) characteristics, follow-up data on repeated FNAB results and, if surgical excision was performed, final pathological results were analyzed. Results: A total of 5181 thyroid nodules were biopsied in 4089 patients, and the biopsy specimen taken from 611 nodules was diagnosed histopathologically as AUS/FLUS (11.79%). After FNAB, 167 of 611 patients diagnosed with AUS/FLUS were operated. While 65.9% (n = 110) of 167 patients who underwent surgery were made a benign diagnosis; malign diagnosis was made to 34.1% (n = 57). Conclusions: The rate of malignancy in surgically confirmed nodules was 34.1% in this study, which is higher than the Bethesda classification. Due to the high malignancy rate which determined in cytologically diagnosed AUS/FLUS, we think that the repeat decision of the FNAB should be reconsidered and the surgical plan after the first FNAB should be considered more seriously.

Thyroid Nodules in Children and Adolescents: A Single Institution's Experience.

The risk of malignancy in pediatric thyroid nodules is higher compared to the risk in adults. Our aim was to investigate the clinical, radiological, and histopathological characteristics of pediatric thyroid nodules. The data of 132 children and adolescents who had thyroid nodules were collected retrospectively from medical records. The mean age of the patients was 12.07 ± 4.08 years and 67% were female. Fine-needle aspiration biopsy was performed in 86 patients (65%) and the results were as follows: benign in 53.4% (n = 46), atypia or follicular lesion of undetermined significance in 3.5% (n = 3), suspicious for follicular neoplasia in 2.3% (n = 2), and malignancy in 32.5% (n = 28). The overall malignancy rate was 22.7% (n = 30). Malignancy was detected after surgery in 2 thyroid nodules belonging to the atypia or follicular lesion of undetermined significance category. Malignancy was detected in 7 patients who had autoimmune thyroiditis and in 1 patient who had congenital dyshormonogenesis. The malignancy rate of the nodules in the patients, who had autoimmune thyroiditis, was found to be 13.4%. Mixed echogenicity, microcalcifications, nodules larger than 10 mm, abnormal lymph nodes, and irregular borders were more common in the malignant group. The nodule size, abnormal lymph nodes, and irregular borders were found to be significant in terms of predicting malignancy. We found malignancy in 22.7% of the thyroid nodules, and the malignancy rate of nodules in the patients, who had autoimmune thyroiditis, was 13.4%. The nodule size, abnormal lymph nodes, and irregular nodule borders emerged as the most significant risk factors for malignancy.

Evaluation and management of pediatric thyroid nodules and thyroid cancer at a single institution after adoption of the American Thyroid Association 2015 guidelines.

The study purpose is to correlate clinical findings with rates of differentiated thyroid cancer (DTC) ina cohort of children presenting with thyroid nodules atasingle institution since the adoption of the 2015 American Thyroid Association (ATA) Guidelines Task Force on Pediatric Thyroid Cancer. Clinical, radiographic, and cytopathologic findings were retrospectively analyzed in a pediatric cohort (≤19 years) identified with ICD-10 codes for thyroid nodules and thyroid cancer from January 2017 until May 2021. We analyzed 183 patients with thyroid nodules. The mean patient age was 14 years (interquartile range 11-16) with a female (79.2 %) and white Caucasian (78.1 %) predominance. The overall DTC in our pediatric patient cohort was 12.6 % (23 out of 183). Most of the malignant nodules measured from 1-4 cm (65.2 %) with TI-RADS score of≥4 (69.6 %). Among the fine-needle aspiration results (n=49), the highest frequency of DTC was within the malignant category (16.33 %), followed by suspicious for malignancy (6.12 %), then atypia or follicular lesion of undetermined significance (8.16 %), and lastly follicular lesion or neoplasm and benign with 4.08 % and 2.04 % respectively. Of the forty-four thyroid nodules that underwent surgical intervention, pathology was remarkable for 19 papillary thyroid carcinoma (43.18 %) and 4 follicular thyroid carcinoma (9.09 %). Based on the analysis of our pediatric cohort in the southeast region at a single institution, adoption of the 2015 ATA guidelines could lead to an increased accuracy in detecting DTC while reducing the number of patients requiring interventions, such as FNA biopsy and/or surgeries. Further, based on our small cohort, it would be reasonable for thyroid nodules 1 cm or less to be monitored clinically with physical exam and ultrasonography, with further therapeutic or diagnostic intervention considered based on concerning features or parental shared decision making.

Önemi Belirsiz Foliküler Lezyonda Malignitenin Prediktif Faktörleri

Follicular lesion of undetermined significance (FLUS) is defined in the same Group III with the atypia of undetermined significance according to Bethesda Classification but these subgroups have different malignancy rates and tumor characteristics according to the studies. In this study, the aim was to evaluate the preoperative clinicopathologic features of the patients with cytological Bethesda Category III/FLUS thyroid nodules. The 44 patients were divided into two groups based on fine needle aspiration cytology (FNAC) results as benign (pB) and malignant (pM) and compared the preoperative clinical, ultrasonographic findings and FNAC results of two groups. According to the univariate analyses the presence of hiopechogenicity and presence of microcalcification are found to be significantly higher in malignancy (p&amp;lt;0.05 for all). Also, the presence of microcalcifications (p=0.048), and hypoechogenicity (p=0.014) were found to be independent risk factors for malignancy according to logistic regression analysis. In patients with FLUS, it should be remembered that the incidence of malignancy increases and treatment should be considered in the forefront of surgery instead of recurrent FNAC in the presence of hypoechogenicity and microcalcification in ultrasonography, and in patients with nuclear membrane irregularity according to FNAC.

The influence of papillary features on the risk of malignancy in thyroid nodules diagnosed as atypia of undetermined significance or follicular lesion of undetermined significance

BackgroundThe objective of this study was to the assess the risk of malignancy in thyroid lesions that were diagnosed as AUS/FLUS when using a novel cytology subclassification system that is based on the presence or absence of papillary features. MethodsAUS/FLUS case cytology was re-reviewed and subclassified into minor or major concern groups based upon the absence or presence of papillary features, respectively. The risk of malignancy (ROM) was calculated and compared between the two groups. Inter-pathologist agreement in case subclassification was also measured. ResultsThe minor concern group had a 12.6% associated ROM, while the major concern group had a significantly higher ROM (58.4%), (P < 0.001). Based on 108 cases, the inter-pathologist agreement in case subclassification was 79%, and the κ value was 0.47. ConclusionsThe identification of papillary features significantly increases the ROM in thyroid lesions with an AUS/FLUS diagnosis.

Core Needle Biopsy in the Diagnosis of Thyroid Nodules.

Core needle biopsy (CNB) is a relatively new technique for the diagnosis of thyroid nodules, and there are currently no large clinical series available. CNB results from 3000 cases are presented in this article. A spring-loaded 20-gauge needle was used for CNB under local anesthesia and ultrasonography guidance for 3000 patients with nodular goiter (584 males, 2416 females, mean age: 48.5). One physician performed all biopsy procedures without conducting on-site pathological examinations. There were non-diagnostic 22 (.7%), benign 2620 (87.4%), atypia of undetermined significance and/or, follicular lesion of undetermined significance 90 (3%), follicular neoplasms and/or suspicious for follicular neoplasm 53 (1.7%), suspicious for malignancy 160 (5.4%), and malignant 55 (1.8%) cases. The CNB procedure was repeated in 19 non-diagnostic cases, and 17 of these patients were benign and two had malignancy. Thyroidectomy was performed on patients who had malign CNB results. All final pathology reports, except for one, were malignant for the patients who had malignant CNB results. The specificity and the sensitivity of CNB were found to be 99.9% and 100%, respectively. There were no serious complications. In thyroid nodules, core needle biopsy is a highly sensitive, specific, and reliable method that could be performed by a single physician. It does not require on-site pathological analysis and has a low incidence of complications and non-diagnostic rates.

The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules

ObjectivesAtypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is a heterogeneous category of fine needle aspiration cytology (FNAC); the management of this condition remains controversial. The clinical significance of such patients relies on the exclusion of malignancy. In this study, we aimed to determine the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) (2017) for predicting malignancy in this specific category of patients. MethodsIn this study, we analysed a cohort of patients from our previous retrospective study. This four-year retrospective cohort study included all cases undergoing surgery with a cytological diagnosis of AUS/FLUS. We enrolled 110 cases with documented final histopathological diagnoses and ultrasound examinations. ResultsThe study included 83 females (75.5%) and 27 males (24.5%). The overall risk of malignancy (ROM) for AUS/FLUS thyroid nodules was 47.3%. The ROMs of TI-RADS 3 (TR3), TI-RADS 4 (TR4), and TI-RADS 5 (TR5) were 43.5%, 49.4% and 40%, respectively. There was no significant association between TI-RADS and final pathological analysis. ConclusionsRepeated FNAC with initial AUS/FLUS nodules is crucial. Our findings showed that ACR TI-RADS did not contribute to the cancer risk stratification of AUS/FLUS nodules. A large prospective multi-institutional study is now required to determine the validity of ACR TI-RADS and whether other adjunct clinical, cytological, molecular, or biochemical tools could facilitate the management of patients with these heterogeneous nodules.

ODP481 Frequency and outcomes of reporting Bethesda class III thyroid cytopathology- An integrated health network's experience

Abstract Introduction Indeterminate thyroid nodule cytologic diagnosis causes anxiety and confusion to the patient and typically results in additional intervention including thyroid surgery. This increases risk of harm and cost of healthcare. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends that cytologists attempt to limit reporting 'indeterminate' [Bethesda III (B-III)] category when interpreting thyroid fine needle aspiration (FNA) specimens, and that all effort be made to limit this diagnosis to less or equal to 7% of all thyroid FNA cases. B-III encompasses follicular lesion of undetermined significance (FLUS) and atypia of undetermined significance (AUS). Because we noted a high reporting of B-III cases at our institution, we aim to review the cytologic interpretation of thyroid FNAs, specifically, the rate of indeterminate cytologic diagnoses. Our second aim is to assess the outcomes of nodules labeled as B-III category. Methods We reviewed the electronic medical records of adults who underwent FNA of thyroid nodules at Allegheny Health Network between January 1, 2016 and December 31, 2019. Results 700 patient records were reviewed, out of which 167 records were excluded (non-thyroid FNA or no relevant records). Meaningful records were available for 725 thyroid nodules biopsied during the study period (533 patient records). Mean age in our sample was 54.7±13.9 years and female-to-male ratio was 4: 1. Percent reporting of diagnostic categories based on Bethesda system were as follows: non-diagnostic/unsatisfactory (B-I) 8%; benign (B-II) 52%; FLUS/AUS (B-III) 28%; FN/SFN (B-IV) 6.2%; suspicious for malignancy (B-V)2.3%; and malignant (B-VI) 3.2%. Out of 28% reported as B-III, 73% were FLUS and 27% were AUS. Results of molecular diagnostic testing (ThyGeNEXT-ThyraMIR; Interpace Diagnostics®) were available for 95/203 of B-III category cases, of which 76% were labeled as very likely benign (probability of malignancy ≤5%) and 15% had low to moderate (10-40%) probability of malignancy. Only 9/95 (9%) had a ≥ 45% probability of malignancy. Four cases out of the 9 above cases were confirmed malignant and 1 was 'indeterminate' on surgical pathology. One in four of all B-III category nodules (n=52) underwent partial or total thyroidectomy, of which 32 were reported as benign, 18 malignant, one NIFTP, and one indeterminate by final surgical pathology. Conclusion We observed higher than recommended (28%) rate of B-III thyroid cytology at our institution. Most of these nodules underwent further interventions (molecular testing and/or thyroidectomy) where the majority were determined to be benign. All efforts should be made to decrease this rate with the ultimate goal of improving patient care, decrease unnecessary intervention, and reduce healthcare cost. Presentation: No date and time listed

PSAT213 Intrathyroidal Parathyroid Adenoma Diagnosed on Thyroseq v2

Abstract Background The incidence of intrathyroidal parathyroid adenoma varies from &amp;lt;1% to 6% and can be a diagnostic dilemma. Intrathyroidal parathyroid adenomas can have suspicious sonographic features that prompt fine needle aspiration (FNA) to evaluate for thyroid cancer. Differentiation between thyroid and parathyroid tissue on cytology can be difficult, and these lesions may be diagnosed as indeterminate thyroid nodules. Molecular testing is a useful adjunct that allows for identification of parathyroid adenomas in this setting. Clinical Case A 59-year-old female with osteopenia and a recent history of traumatic vertebral fracture presented for workup of asymptomatic hypercalcemia. Labs showed intact parathyroid hormone (iPTH) 168 pg/mL (reference 11-51 pg/mL), serum total calcium 12.2 mg/dL (reference range 8.6-10.4 mg/dL), albumin 4.7 g/dL (reference 4.1-5.3 g/dL), phosphorus 2.1 mg/dL (reference 2.3-4.4 mg/dL), creatinine 0.7 (reference 0.6-1.3 mg/dL), and 25-OH vitamin of 28 ng/mL (reference 20-50 ng/mL). Cervical ultrasound showed a 2.1 cm hypoechoic left thyroid nodule. Subsequent 99mTc-Sesatmibi scan showed increased tracer retention in the left posterior thyroid lobe. FNA of the left thyroid nodule was performed with cytology showing follicular lesion of undetermined significance (FLUS). Molecular testing with Thyroseq v2 showed parathyroid tissue consistent with intrathyroidal parathyroid adenoma. The patient underwent successful left thyroid lobectomy with removal of an intrathyroidal parathyroid gland, with subsequent decrease of iPTH to 44 pg/mL (reference 11-51 pg/mL) and total serum calcium to 9.5 mg/dL (reference 8.6-10.4 mg/dL). Surgical pathology confirmed parathyroid adenoma. Discussion Due to the ubiquity of thyroid FNAs to rule out malignancy, there has been a rise in the number of incidental parathyroid gland aspirations. Thyroid lesions with diagnosis of FLUS or oncocytic features are prone to misdiagnosis due to similarities in morphologic overlap and anatomic proximity. Molecular testing such as Thyroseq v2 routinely tests for PTH and can identify parathyroid tissue in lesions initially diagnosed as indeterminate thyroid nodules. Newer molecular test versions including ThyroSeq v3 similarly have high analytical accuracy in detecting thyroid cancer and parathyroid lesions. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT290 Papillary Thyroid Cancer Discovered After Benign Afirma Gene Testing, A Case Report

Abstract Introduction Grave's disease is an autoimmune form of hyperthyroidism characterized by antibody stimulation of the thyrotropin receptor. Although there are conflicting study results, patients suffering from Grave's disease appear to have an increased incidence of thyroid cancer. Fine needle aspiration helps detect potential carcinoma, however, it is indeterminate in 15-30% of cases. In cases where fine needle aspiration of a thyroid nodule returns Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS), next-generation sequencing, including Afirma gene testing (created by Veracyte inc) provides guidance for therapy. However, like any screening test, the chance for false negatives still exists. We describe the case of a 41-year-old man suffering from Grave's disease with a solitary thyroid nodule which was found to be papillary thyroid carcinoma despite benign Afirma gene testing. Case description A 41-year-old male with no past medical history presented to his primary care provider with no active complaints but was found to have a blood pressure of 142/92 mmHg. He notably had a diffusely enlarged thyroid gland on examination. The patient was sent for thyroid function testing which demonstrated TSH: &amp;lt; 0. 01 uIU/ml and a free T4: 1.1 ng/dL. The patient was sent for a thyroid ultrasound which demonstrated a right-sided nodule measuring: 3.5 cm×2.4 cm×3.2 cm (TI-RADS 4). Radioactive idodine uptake scan revealed this was a cold nodule and the patient underwent fine-needle aspiration biopsy and Afirma gene testing. The patient's biopsy demonstrated AUS while Afirma gene testing was benign. After discussing treatment options for Grave's disease with his endocrinologist, the patient underwent total thyroidectomy. Post-surgical biopsy of the patient's thyroid demonstrated follicular variant papillary thyroid carcinoma with capsular invasion. The patient is currently being followed closely by endocrinology with regular TFT and thyroglobulin testing. Discussion Grave's disease is postulated to increase patients’ risk of developing papillary thyroid cancer. Many of the proposed hypotheses explaining this higher risk center around thyroid-stimulating antibodies promoting tumor invasion and angiogenesis. When these patients demonstrate suspicious thyroid nodules on imaging, they undergo fine-needle aspiration, however, these biopsies are indeterminate in 15-30% of cases. Afirma gene testing has been proposed as a sensitive test to rule out carcinoma in these indeterminate cases. We describe a case where, despite benign Afirma gene testing, the patient was found to have papillary thyroid cancer after thyroidectomy. We propose that Grave's disease patients with suspicious nodules with indeterminate biopsy and benign Afirma testing still be considered for total thyroidectomy given their increased risk of thyroid cancer. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT295 Low Grade B-CELL Lymphoma and Follicular Cancer in a Patient with Hashimoto's Thyroiditis Presenting as Two Different Thyroid Nodules

Abstract We present an 88 year old female with a history of hypothyroidism due to Hashimoto's thyroiditis who noted a lump in the left side of her neck. Thyroid ultrasound revealed multiple nodules throughout the thyroid gland. The right lobe contained a 4.3 cm solid, dominant nodule and the left lobe contained a 4.2 cm lobulated hyperechoic nodule. Ultrasound-guided fine-needle aspiration biopsy of the 4.3 cm right thyroid nodule revealed follicular lesion of undetermined significance with predominantly Hurthle cells. Thyroseq was positive for aTERT and EIF1AX mutations. Ultrasound-guided fine-needle aspiration biopsy of the 4.2 cm left thyroid nodule revealed malignant cells consistent with a low-grade B-cell lymphoma. She underwent a total thyroidectomy. The final pathology report revealed both a 5.5 cm follicular carcinoma in the right lobe and a low-grade B-cell lymphoma most compatible with extra nodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) involving predominantly the left lobe of the thyroid. She is beginning radiation treatment for the lymphoma. Three months after radiation treatment is completed, she will undergo radioactive iodine treatment for the follicular carcinoma. Thyroid cancer is the most common endocrine malignancy. However, the thyroid is an uncommon site of cancer overall, accounting for only 1.5% to 4.7% of new cancer cases in the general population of the United States. Malignant lymphoma presenting as a primary neoplasm in the thyroid is even more uncommon and represents only 1 to 5% of all thyroid malignancies. Hashimoto's thyroiditis is a known risk factor for MALT lymphoma. However, there is no known association between Hashimoto's thyroiditis and follicular carcinoma. There are several reports of patients with presence of both papillary thyroid cancer and MALT lymphoma. One case was reported of simultaneous MALT lymphoma and medullary thyroid cancer. This is the first case of a patient with both follicular thyroid cancer and MALT lymphoma in the thyroid gland. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP465 BRAF V600 and NRAS Q61 mutations in thyroid fine-needle aspiration (FNA) with indeterminate cytology in Argentina

Abstract   It is known that thyroid cancer initiation and progression occurs because of gradual accumulation of genetic and epigenetic alterations at cell level. Many mutations associated with this disease have been reported to be present in genes encoding proteins in the mitogen-activated protein kinase (MAPK) signaling pathway, specifically BRAF and RAS genes, as well as in the PI3K/Akt signaling pathway, among others. In particular, molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Previously we found BRAF and NRAS mutations are observed in a significant number of papillary and follicular thyroid carcinomas in our population, respectively. In this study, we tested the diagnostic performance of BRAF and NRAS mutation in thyroid carcinoma in fine-needle aspiration (FNA) specimens with indeterminate cytology. In total, residual material from 73 FNA samples was used (n= 16, Bethesda III; n=48, Bethesda IV and n=9 Bethesda V). BRAF codon 600 mutation and NRAS codon 61 mutations were investigated using qPCR and melting curve analysis was carried out. Diagnosis of malignancy was confirmed by histology on paired surgical specimen in 54 cases. Results In the cytologically indeterminate categories, 9.6% of specimens were BRAF V600 mutated: 1 of 16 were subcategorized as atypia of undetermined significance or follicular lesion of undetermined significance (6.3%); 2 of 48 as follicular neoplasm or suspicious for follicular neoplasm (4.1%); and 4 of 9 as suspicious for malignancy (44.4%). NRAS Q61 mutation was found in 4 patients (2 with Bethesda IV and 2 with cytology V). The BRAF V600 mutations were associated with carcinoma in 100% of cases (n = 7), whereas only 75% (n = 3) of the nodules with NRAS were associated with carcinoma. BRAF V600 and NRAS Q61 mutations had high specificity in predicting malignant carcinoma (96.8%); the sensitivity was 43.5% with a positive predictive value of 90.9% and a negative predictive value of 69.8%. In specific categories of indeterminate cytology, the pre-test risk of malignancy was 38%, 33% and 88% while the post molecular test risk of malignancy was 100%, 75% and 100% respectively. Conclusions BRAF V600 and NRAS Q61 molecular test in residual FNA samples improve diagnostic accuracy of the cytology analysis in our population and may help to better select patients for avoid inadequate or unnecessary surgeries. Presentation: No date and time listed

Ultrasonography screening in children and adolescents who have one parent with familial non-medullary thyroid carcinoma.

To evaluate ultrasonography (US) screening for thyroid cancer in children and adolescents who have one parent with familial non-medullary thyroid carcinoma (FNMTC) unrelated to known genetic syndromes. In this prospective study, we selected 72 children and adolescents (age ≤18 years) without a palpable thyroid nodule or history of radiation exposure, but who have one parent diagnosed with FNMTC (i.e. at least one other affected first-degree relative). The children and adolescents were evaluated by US during initial assessment and after 5 years. Initial US revealed pure cysts in five participants and nodules in seven, which were ≥5 mm in five. These patients were submitted to fine needle aspiration, which revealed benign cytology in four and a follicular lesion of undetermined significance in one. Fine needle aspiration was repeated in the last case and in one case with benign cytology but suspicious US. The second cytology was benign in both cases. After 5 years, another two participants with initially normal US had nodules <5 mm in the absence of suspicious findings. The frequency of lesions detected by US was not associated with participant sex or age, number of relatives with thyroid cancer (2 or 3), maternal or paternal origin of tumour, or age of the relatives at diagnosis. The present results suggest that US screening is not necessary in children or adolescents when one parent has a diagnosis of FNMTC (≥2 affected relatives).

Assessment of Preoperative TSH Serum Level and Thyroid Cancer Occurrence in Patients with AUS/FLUS Thyroid Nodule Diagnosis.

Thyroid-stimulating hormone (TSH) is a growth factor associated with the initiation and progression of well-differentiated thyroid cancer (WDTC). Atypia of undetermined significance and follicular lesion of undetermined significance (AUS/FLUS) are the most uncertain cytological diagnoses of thyroid nodules. The aim of the study was to determine the association of histopathological diagnosis with preoperative serum TSH levels in patients with AUS/FLUS thyroid nodule diagnosis. Among 5028 individuals with thyroid nodules, 342 (6.8%) with AUS/FLUS diagnoses were analyzed. The frequency of all histopathology diagnoses was assessed for associations with preoperative serum TSH levels. The median TSH concentration was significantly higher in patients with AUS/FLUS diagnosis and histopathology of WDTC than in patients with the same cytology result and histopathology of a benign tumor (p < 0.0001). The diagnostic potential of serum TSH level was determined to evaluate risk of malignancy in patients with thyroid nodules classified into the Bethesda III category. ROC analysis showed the TSH concentration at a cutoff point of 2.5 mIU/L to be an acceptable prognostic factor for WDTC. For this optimal cutoff point, the AUC was 0.877, the sensitivity was 0.830, and the specificity was 0.902. Preoperative serum TSH levels in patients with AUS/FLUS thyroid tumor diagnosis should be taken into consideration in the decision-making process and clinical management.