Repeat Fine-needle Aspiration Research Articles

Thyroid diseases in children and adolescents requiring surgical treatment-indications, techniques, results, and complications based on 10 years of the single center's own experience.

Although thyroid abnormalities are observed less frequently in children than in adults, the increased incidence of thyroid cancer makes it mandatory for all pediatric surgeons to be knowledgeable about the disorders of this gland. Thyroid abnormalities can be associated with hyperthyroidism or hypothyroidism and euthyroidism and/or symmetric or asymmetric enlargement of the gland. The present study was undertaken to retrospectively analyze the indications, surgical techniques used, results obtained, and complications found in the surgical treatment of thyroid diseases in children and adolescents in a surgical center for the macro-region of western Poland. The data of 148 patients undergoing total or partial thyroidectomy between 2013 and 2022 were analyzed from the medical records of the Department of Pediatric Surgery, Traumatology, and Urology of the Medical University of Poznan, Poland. A total of 95 children underwent subtotal thyroidectomy and 64 underwent total thyroidectomy, of which the procedure was widened to include prophylactic removal of neck lymph nodes in 45 patients. There were 113 girls (76%) in the analyzed group, and the average age of the patients at the time of surgical treatment was 15 years. The average time from the diagnosis of thyroid disease to surgery was 4 months, ranging from 2 weeks to 3 years. Of the 64 patients undergoing total thyroid resection, 35 (54.69%) were diagnosed with thyroid cancer. Collaboration within a multidisciplinary team ensures optimal surgical outcomes in children and adolescents with thyroid disease. With extreme caution, thyroid removal is a safe procedure with few complications, but the experience of the surgeon performing thyroid surgery in children remains crucial. Despite the absence of such a diagnosis in the first fine-needle aspiration biopsy, the high percentage of thyroid carcinomas in the analyzed group may be because the initial biopsy was performed in a less experienced center, also in terms of histopathological laboratory. Hence, we point out the necessity of performing a repeat fine-needle aspiration biopsy (according to the Bethesda classification) in a more experienced center before the final decision of thyroidectomy.

The Diagnostic Utility of Repeat Fine-needle Aspirations of Benign Thyroid Nodules.

Objective This study aims to analyze the diagnostic utility of multiple repeat FNA on thyroid nodules with initially benign diagnosis. Methods In a 5-year period, 1658 thyroid nodules with initially benign FNAs were retrospectively reviewed and followed for subsequent resection and repeat biopsy. Results Out of 2150 thyroid nodules, 1658 (77.1%) were diagnosed as benign on FNAs. The average age was 57.4 years (range 11-93 years), and most were females (83.8%). Repeat FNA was performed on 183 benign nodules, of which 141 (8.5%) were sampled a second time and 42 (2.5%) had 2 or more repeat samplings. For the benign nodules without repeat FNAs, 124 had benign resection. Of cases with one-time repeat FNA, most (n=101) remained benign on repeat FNAs, 13 of which were benign on resection. Eleven had atypical repeat FNAs, 5 were resected, 4 of which were benign and one was atypical follicular neoplasm with HRAS and TERT promoter mutations. Of cases with multiple repeat FNA, most (n=35) were still benign on repeat FNAs, one had benign resection. Two had atypical repeat biopsies, one was PTC on resection with CCD6::RET fusion. The positive predictive value significantly decreased from 41.1% on single FNA to 8.3% on one-time repeat (p<0.001) and 16.7% on multiple repeat (p=0.002). The total cost for workup of previously benign nodules was $285,454. Conclusions Repeat FNA biopsies did not provide an additional diagnostic value in the evaluation of benign thyroid nodules, and often led to unwarranted follow-up procedures and significantly increased health care cost.

A comparative analysis of core needle biopsy and repeat fine needle aspiration in patients with inconclusive initial cytology of thyroid nodules.

To assess and compare the effectiveness of ultrasound-guided core needle biopsy (CNB) in comparison to repeat fine-needle aspiration(rFNA) for thyroid nodules that yield inconclusive results following the initial fine-needle aspiration (FNA). A cohort of 471 patients who received an inconclusive cytological diagnosis following the initial FNA were included in this study. These patients subsequently underwent either CNB (n=242) or rFNA (n=229). The inconclusive FNA results encompassed categories I, III, and IV of The Bethesda System for Reporting Thyroid Cytopathology(TBSRTC), as well as the ultrasound images indicating malignancy despite FNA results falling under TBSRTC category II. This study assessed the sampling satisfaction rate, diagnostic efficacy, and complications associated with CNB compared to rFNA. Additionally, the impact of repeat puncture time and nodule size on diagnostic efficacy was analyzed. Following repeat punctures, the satisfaction rate of the CNB sampling was found to be significantly higher than that of rFNA (83.9% vs 66.8%). The diagnostic rate in the CNB group was significantly greater compared to that of the rFNA group (70.7% vs 35.8%). In patients with nodule maximum diameters ranging from 5 mm to 20 mm, the diagnostic accuracy was significantly higher in the CNB group compared to that in the rFNA group. In patients with intervals less than 90 days, between 90 days and one year, the diagnostic rate in the CNB group was found to be higher compared to that in the rFNA group. In CNB, not immediately adjacent to the capsule was a risk factor for nodular puncture bleeding (37.0% vs 22.7%.). CNB demonstrated higher rates of satisfaction and diagnosis compared to the rFNA. The diagnostic effectiveness of CNB was not influenced by the time interval or the size of the thyroid nodule. Therefore, in cases where the initial FNA diagnosis of thyroid nodules is inconclusive, CNB should be considered as a viable option for re-puncture.

Malignancy in Thyroid Nodules with Bethesda III Category on Repeat Fine Needle Aspiration Biopsy.

This study aimed to evaluate the risk of malignancy for nodules repeatedly classified as Bethesda category III on fine needle aspiration biopsy (FNAB). A chart review on a series of 59 patients seen with thyroid nodules who underwent both initial and repeat FNAB at the Diabetes, Thyroid and Endocrine Center of St. Luke's Medical Center, Quezon City was conducted. The Thyroid Registry was utilized to collect each patient's demographic and clinical characteristics, ultrasonographic features of thyroid nodules along with the cytopathologic and histopathologic results. The subclassification of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) were retrieved from the cytopathology reports using the institution's electronic Healthcare-Results Management System. A total of 59 adult patients with thyroid nodules were included. Nodules which were initially AUS/FLUS turned out to be malignant on repeat FNAB in 38 patients with a prevalence of 64.41% (95% CI: 50.87-76.45%). There was no significant difference with regards to clinical, ultrasonographic and cytopathologic features of malignancy between benign and malignant nodules. Findings of this study support surgical intervention as a reasonable option after a repeat Bethesda III classification on FNAB. However, the small sample size warrants confirmation in future studies with a representative sample of patients.

Evaluation of Recurrent Lymphadenitis after Six Months Anti-Tuberculous Therapy

Background: Recurrence or persistence of tuberculous lymphadenitis even after treatment occurs due to paradoxical immune response, non-tubercular mycobacterial (NTM) infection, drug resistance tuberculosis or because of misdiagnosis. In these situations sometimes the patients are asked to continue category-1 more than six months on the basis repeat fine needle aspiration cytology (FNAC) findings. This study evaluated the cause of persistence or appearance of new lymph node after anti-TB category-1. Methods: This observational study was done from January, 2013 to March, 2014 after getting ethical clearance from Bangabandhu Sheikh Mujib Medical University (BSMMU). Patients who had persistent or new lymphadenitis after completing anti-TB category-1 for six months were selected. After analysis of treatment records, patients were selected for either FNAC or biopsy with local surgical clearance. Cyto/histopathological analysis, AFB stain (LED fluorescent), AFB culture (MGIT and L-J media) and GeneXpert test was done. Follow-up of the patients were done after two weeks and six months of FNA/surgery. Results: Thirty-two patients (M/F=11/21) with mean age 25(±12) years were investigated. Altogether 26 cases (81.25%) Journal of Bangladesh College of Physicians and Surgeons Vol. 41, No. 4, October 2023 were confirmed as tuberculous lymphadenitis and six (18.75%) were non-tuberculous (03 lymphomas, 01 sarcoidosis, 01 reactive lymphadenitis and 01 pyogenic abscess). Among the TB patients, granuloma was present in 23 cases (88.46%) (FNA-07, biopsy-16). Twenty-three (88.46%) cases were GeneXpert positive, comprising 21 rifampicin sensitive and 02 rifampicin resistant. One rifampicin resistant case was confirmed by culture and the remaining 25 were culture negative. One case was AFB stain positive and no NTM was found in AFB culture. After surgery, rapid healing was observed within two weeks among tuberculous lymphadenitis patients. Conclusions: Persistent granuloma after anti-TB category-1 does not indicate active tuberculosis if it is culture negative. It may occur due to immunological reaction against dead bacilli in deep seated sinus. Local surgical clearance results rapid recovery and other diagnosis should be excluded without further continuation of anti-TB category-1. J Bangladesh Coll Phys Surg 2023; 41(4): 262-268

SAT522 Validating Molecular Testing As An Adjunct To Fine Needle Aspiration In Pediatric Thyroid Malignancy

Abstract Disclosure: A. Aekka: None. N. Arva: None. M. Raval: None. J. Rastatter: None. S.D. Finkelstein: Employee; Self; Interpace Biosciences. J. Levine: Employee; Self; Interpace Biosciences. J. Josefson: None. The standard diagnostic approach for thyroid malignancy includes evaluation of cytopathology derived from thyroid fine needle aspiration (FNA). Nearly 40% of pediatric cases have indeterminate FNA results, and there is no clear consensus regarding the management of these cases. Molecular analysis is beneficial in increasing diagnostic yield and informing treatment stratification in adults, although its use remains limited in pediatrics. This study sought to assess the validity of next-generation sequencing mutational analysis and microRNA (miRNA)-based risk classification of FNA cytopathology derived from a single-center cohort of pediatric patients. The study hypothesized that molecular analyses improve diagnostic performance of FNA for children with thyroid cancer. Interpace Diagnostics’ validated multiplatform tool comprised of ThyGeNEXT (mutational panel capturing 10 oncogene sequence variants and 38 fusions) and ThyraMIR (miRNA risk classifier including 11 miRNA markers) was utilized for this study. Multiplatform testing was performed on 27 archived FNA thyroid samples collected from patients ages 7-20 years (mean age 14.1 years, 78% female). Molecular results were compared with final surgical pathology or repeat FNA results to determine validity. Surgical pathology confirmed papillary thyroid carcinoma in 14 patients and benign pathology in 6 patients. Repeat FNA confirmed benign pathology in 2 patients. Surgical pathology or repeat FNA was unavailable for 5 cases, all of which had benign initial cytopathology. The most common mutational finding was BRAF_V600E (6/14) followed by RET-PTC fusions (3/14). MiRNA findings were as follows: 16 high-risk expression profiles, 3 low-risk expression profiles, and 8 negative profiles. The validation analysis included 22 samples that had corresponding surgical or repeat FNA results. All cases of malignancy demonstrated high-risk miRNA profiles and all benign cases demonstrated negative or low-risk miRNA profiles. Multiplatform molecular testing demonstrated 100% sensitivity, 87.5% specificity, 93.3% positive predictive value, and 100% negative predictive value in detecting malignant versus benign pathology in our population. Molecular analyses appear to be a valid adjunct to FNA in pediatric thyroid cancer evaluation. Incorporation of molecular diagnostics advances precision medicine in pediatric thyroid care and may better inform presurgical treatment stratification, mitigate risks associated with unnecessary procedures, and ultimately improve outcomes for children and adolescents with thyroid nodules. Presentation Date: Saturday, June 17, 2023

SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None. Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique. Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results. A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date. Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology. Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935 Presentation: Saturday, June 17, 2023

THU677 Performance Of American Thyroid Association And American College Of Radiology Scoring Systems In The Evaluation Of Pediatric Thyroid Nodules

Abstract Disclosure: L. Garabet Diramerian: None. M. Douek: None. G. Tse: None. P. Iskander: None. S. Li: None. M.W. Yeh: None. M.J. Livhits: None. A.M. Leung: None. H.K. Chiu: None. J.X. Wu: None. Background: The underlying malignancy rate of thyroid nodules is higher in pediatric patients compared to adults. Ultrasound scoring systems developed for adult thyroid nodules may not be applicable to pediatric populations. Objective: To evaluate the performance characteristics of adult American Thyroid Association (ATA) and American College of Radiology Thyroid Imaging and Reporting Data System (TIRADS) scoring systems in risk-stratifying pediatric thyroid nodules. Methods: This was a retrospective chart review of pediatric patients aged ≤18 years with thyroid nodules at UCLA Health from 2002-2022. Patients with no available ultrasound images or cytopathology results (fine needle aspiration [FNA] or surgical pathology) were excluded. Each thyroid nodule was scored according to the ATA and TIRADS systems through independent, blinded review by two study radiologists; discordances were arbitrated by a third. For patients who did not undergo thyroid surgery, we considered thyroid nodules benign if their size was stable on repeat ultrasound or if a repeat FNA was benign. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each system. Sensitivity analyses were performed to determine the optimal size cut-off to recommend FNA biopsy while maintaining a sensitivity equivalent to that of adults. Results: There were 77 patients (median age, 15 years [range 2-18]); 71.4% female) with 115 thyroid nodules. The underlying malignancy rate was 27.8%. Using adult-size cut-offs for FNA biopsy, the ATA scoring system would have failed to recommend biopsy for 11 of 32 malignant nodules, and had the following performance: sensitivity 66%, specificity 55%, NPV 81%, and PPV 36%. The TIRADS scoring system would have failed to recommend biopsy for 15 of 32 malignant nodules and had the following performance: sensitivity 53%, specificity 87%, NPV 83%, and PPV 61%. In sensitivity analyses, the optimal size cut-offs for FNA using the ATA scoring system were: 2 cm for very low risk, 1 cm for low risk, and 0.5 cm for intermediate and high risk categories (sensitivity 94%; specificity 33%). The optimal size cut-offs for FNA using TIRADS were: 3 cm for TIRADS-2, 0.8 cm for TIRADS-3 and TIRADS-4, and 0.5 cm for TIRADS-5 (sensitivity 91%; specificity 59%). Conclusion: The adult ATA and TIRADS ultrasound scoring systems have low sensitivity for thyroid cancer in pediatric thyroid nodules. Lowering the size cutoffs for recommending thyroid FNA biopsy increases sensitivity to &amp;gt;90% for both ATA and ACR TIRADS scoring systems. Presentation: Thursday, June 15, 2023

SAT532 A Rare Case of Thyroid Carcinoma Noted in a Patient with Thyroid Nodule Showing Prior Benign Biopsy and Prior Negative Molecular Testing

Abstract Disclosure: M.M. Hillhouse: None. P. Madhavan: None. F.M. Woron: None. Background: Molecular studies have a high sensitivity for ruling out malignancy (1). This patient was diagnosed with the follicular variant of papillary thyroid carcinoma despite negative molecular testing and benign cytology in multiple prior biopsies. Clinical Case: 31 y.o. female with a past medical history of Hashimoto's disease on levothyroxine presented for follow up of thyroid nodules. She does not have a family history of thyroid cancer or personal history of neck radiation. The patient was noted to have a right thyroid nodule around 14 years of age and this was monitored during her childhood. The nodule measured 2.3 x 0.6 cm on ultrasound in 2015. The nodule measured 2.0 x 1.6 x 1.5 cm in 2017. FNA in 2017 revealed benign cytology (Bethesda II). On ultrasound in 03/2019, the nodule measured 2.2 x 1.5 x 1.8 cm. The nodule demonstrated a greater than 20% increase in all dimensions on ultrasound images in 12/2020 to 2.9 x 2.0 x 2.6 cm. A repeat ultrasound in 04/2021 demonstrated no significant change in size. Repeat FNA performed in 07/2021 demonstrated clusters of follicular cells in flat and microfollicular groups and was interpreted as atypia of undetermined significance (Bethesda III). AFIRMA testing was benign (∼4% of malignancy. The nodule increased in size to 3.5 x 2.6 x 3.1 cm on ultrasound in 07/2022. It appeared solid and hyperechoic and was classified as TI-RADS 3. A new 0.8 cm nodule on the left lobe was also identified. Repeat FNA of the right nodule in 09/2022 demonstrated macrophages, colloid and groups of follicular cells and was classified as non-diagnostic (Bethesda I). She reported difficulty breathing in the supine position and she underwent a right hemithyroidectomy and isthmusectomy in 11/2022. Pathology results were remarkable for invasive encapsulated follicular variant of papillary thyroid carcinoma with focal angioinvasion and tumor capsular invasion. The margins were negative for tumor. The parenchyma was consistent with lymphocytic thyroiditis. Ultrasound after interval right hemithyroidectomy in 12/2022 in an outside facility demonstrated an unchanged subcentimeter left thyroid nodule and multiple bilateral anterior cervical/level 6 lymph nodes suspicious for metastatic disease given the absence of hilum. Patient is currently undergoing repeat imaging and work up for the lymphadenopathy. Conclusion: This case study highlights the importance of maintaining high clinical suspicion for thyroid malignancy in cases of increasing thyroid nodule size and compressive symptoms despite negative cytological and molecular testing.

SAT545 Erythropoietic Thyroid Nodule in the Setting of Myelofibrosis

Abstract Disclosure: L.M. Vasquez: None. J.M. Bruder: None. M. Koops: None. J. Trejo: None. Background: Extramedullary hematopoiesis is frequently seen in non-osseous locations but not endocrine organs, this is a case of hematopoesis in a thyroid nodule. Clinical Case: A 79-year-old man with myelofibrosis diagnosed at age 66, CAD post CABG, atrial fibrillation on anticoagulation and HFrEF was referred to the endocrinology clinic due to enlarging left lobe thyroid nodule. He was diagnosed with a goiter at age 72 but denied compressive symptoms. He had no history of radiation to his neck or family history of thyroid cancer. On physical exam, the left thyroid lobe was visibly enlarged with slight right tracheal deviation without lymphadenopathy. TSH level was normal. Thyroid ultrasound demonstrated a 6.4 x 4.0 x 4.8 cm, complex cystic-solid, taller than wide nodule in the left lobe and a sub-centimeter cystic nodule in the right lobe. FNA showed hematopoietic elements, including maturing cells in three lineages of hematopoiesis. On repeat ultrasound 5 years later. The left nodule increased in size to 7.3 x 5.4 x 4.4 cm and highly suspicious (TR4 and TR3) by Ti-RADS criteria. Repeat FNA of the nodule showed many red blood cells with few hematopoietic cells, flow cytometry did not show any abnormal populations. No thyroid follicular cells were reported. Myelofibrosis was diagnosed by bone marrow biopsy many years prior. He had maintained a stable CBC without palpable spleen or hepatomegaly. Given this history without thyroid dysfunction or reported symptoms, surgery was not pursued. External beam radiation was a treatment option should the nodule cause symptoms. He continued to have mild anemia not requiring blood transfusions. He passed away 2 years later in hospice care after hospitalization for severe heart failure decompensation. Conclusion: Extramedullary hematopoiesis involving the thyroid is rare but has been reported(1). This type of extramedullary hematopoiesis. can be treated with surgery or low-dose radiation because of the radiosensitivity of hematopoietic tissue (2). This was a potential treatment modality if compressive symptoms arose, but they did not. This case illustrates a situation in which surgical intervention on highly suspicious nodules would not have been the optimal treatment choice. Reference: 1. Jan I., Weng M., Wang C., et al. Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature. Journal of the Formosan Medical Association. (2018) 117, 1108-1114. 2. Taher A, Vichinsky E, Musallam K et al., authors; Weatherall D, editor. Guidelines for the Management of Non-Transfusion Dependent Thalassaemia (NTDT) [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Chapter 11, EXTRAMEDULLARY HEMATOPOIESIS. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190455/ 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

Prospective Validation of ThyroSPEC Molecular Testing of Indeterminate Thyroid Nodule Cytology Following Diagnostic Pathway Optimization.

Background: Molecular testing for cytologically indeterminate thyroid nodules (ITNs) is often reported with incomplete data on clinical assessment and ultrasound malignancy risk (USMR) stratification. This study aimed to clinically validate the diagnostic accuracy of a novel molecular test, assess the incremental preoperative malignancy risk of other clinical factors, and measure the impacts of introducing molecular testing at the population level. Methods: Comprehensive clinical data were collected prospectively for the first 615 consecutive patients with ITNs in a centralized health care system following implementation of a reflexive molecular test. Clinical data include patient history, method of nodule discovery, clinical assessment, USMR, cytology, molecular testing, and surgery or follow-up along with surgeon notes on surgical decision-making. Accuracy of molecular testing and the impact of the introduction of molecular testing were calculated. A multivariable regression model was developed to identify which clinical factors have the most diagnostic significance for ITNs. Results: A locally developed, low-cost molecular test achieved a negative predictive value (NPV) of 76-91% [confidence interval, CI 66-95%] and a positive predictive value (PPV) of 46-65% [CI 37-75%] in ITNs using only residual material from standard liquid cytology fine-needle aspiration (FNA). Sensitivity was highest (80%; [CI 63-92%]) in the American Thyroid Association (ATA) intermediate-suspicion ultrasound category, and lowest (46%; [CI 19-75%]) in the ATA high-suspicion ultrasound category. Following implementation of molecular testing, diagnostic yield increased by 14% (p = 0.2442) and repeat FNAs decreased by 24% (p = 0.05). Mutation was the primary reason for surgery in 76% of resected, mutation-positive patients. High-risk mutations were associated with a 58% (p = 0.0001) shorter wait for surgery. Twenty-six percent of patients with a negative molecular test result underwent surgery. Multivariable regression highlighted molecular testing and USMR as significantly associated with malignancy. Conclusions: Molecular testing improves preoperative risk stratification but requires further stratification for intermediate-risk mutations. Incorporation of clinical factors (especially USMR) with molecular testing may increase the sensitivity for detection of malignancy. Introduction of molecular testing offers some clinical benefits even in a low resection rate setting, and directly influences surgical decision-making. This study illustrates the importance of the local diagnostic pathway in ensuring appropriate integrated use of molecular testing for best outcomes.

Repeat Fine Needle Aspiration for Thyroid Nodules Classified as Follicular Neoplasm: Evaluation of Cytologic, Molecular, and Histologic Outcomes

Repeat Fine Needle Aspiration for Thyroid Nodules Classified as Follicular Neoplasm: Evaluation of Cytologic, Molecular, and Histologic Outcomes

Effective Use of microRNA, BRAF and Sonographic Risk Assessment in Bethesda III Thyroid Nodules Requires a Different Approach to Nodules with Features of Nuclear Atypia and Other Types of Atypia.

The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine-needle aspiration.

There is limited data comparing the performance of Afirma Genomic Sequencing Classifier (GSC) in thyroid nodules carrying an initial versus a repeat diagnosis of atypia of undetermined significance (AUS). This study reported an institutional experience in this regard. This retrospective study included consecutive thyroid nodules that had an initial or a repeat AUS diagnosis and had a subsequent GSC diagnostic result (benign or suspicious) from 2017 to 2021. All nodules were followed by surgical intervention or by clinical and/or ultrasound monitoring. GSC's benign call rate (BCR), rate of histology-proven malignancy associated with a suspicious GSC result, and diagnostic parameters of GSC were calculated and compared between the two cohorts (initial versus repeat AUS). Statistical significance was defined with a p-value of <.05 for all analysis. A total of 202 cases fulfilled inclusion criteria, including 67 and 135 thyroid nodules with an initial and a repeat AUS diagnosis, respectively. BCR was 67% and 66% in initial and repeat AUS cohorts, respectively. Rate of histology-proven malignancy associated with a suspicious GSC result were 22% and 24% in initial and repeat AUS cohorts, respectively. Compared with the repeat AUS cohort, the initial AUS cohort showed slightly lower sensitivity (83% vs. 100%), specificity (70% vs. 73%), PPV (23% vs. 24%), NPV (98% vs. 100%), and diagnostic accuracy (72% vs. 75%). Nevertheless, these differences did not reach statistical significance. GSC demonstrated comparable performance in thyroid nodules with a repeat AUS diagnosis versus nodules with an initial AUS diagnosis.

Improvement in neck ultrasound report quality following the implementation of European Thyroid Association guidelines for postoperative cervical ultrasound for thyroid cancer follow-up, a prospective population study.

The aim of this study was to prospectively evaluate the quality of postoperative neck ultrasound (POU) for thyroid cancer patients after implementing European Thyroid Association (ETA) guideline-based POU assessment. Our analysis involved 672 differentiated thyroid cancer patients. POU report quality was compared between the implementation radiology group (IRG), which implemented ETA guideline-based assessment in 2018, and all non-implementation radiology groups (NIRG). Differences in POU quality were evaluated before and after the implementation of guideline-based assessment. Additionally, we evaluated the ability of serum thyroglobulin (Tg) level <0.2 ng/mL or between 0.21 and 0.99 ng/mL and normal POU lesion status at 1-year follow-up to predict the absence of persistent disease or relapse at 3-year follow-up. IRG had significantly higher mean utility scores for POU reports of abnormal thyroid bed nodules compared to NIRG (P < 0.001). IRG's POU reports for suspicious nodules and lymph nodes were considered sufficient in 94% and 85% of cases, respectively, compared to 45% and 68% for NIRG. For patients with normal US lesion status and Tg <0.2 ng/mL or Tg 0.21-0.99 ng/mL at 1-year follow-up, the negative predictive values were 96% for both. Implementation of 2013 ETA POU-reporting guidelines allowed for the provision of high-quality POU reports, which may lead to increased accuracy in assessing the response to treatment and in estimating the risk of recurrence of thyroid cancer and likely reduce unnecessary repeat POU or FNA.

Does timing of repeat fine needle aspiration biopsy in thyroid nodules alter the adequate or AUS/FLUS cytology result?

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

Abstract #1408170: Familial Hypocalciuric Hypercalcemia, Primary Hyperparathyroidism, or Both?

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia, and it is characterized by hypercalcemia and normal or inappropriately high levels of parathyroid hormone (PTH). Familial Hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant benign disease caused by inactivating genetic mutations in the calcium sensing receptor. Genetic analyses are expensive and not widely available, making the differential diagnosis challenging. A 77-year-old male with a past medical history of hypertension and chronic kidney disease was referred to the endocrinology clinic for evaluation of hypercalcemia. Routine tests showed total corrected calcium level of 10.5 mg/dL, hypophosphatemia 2.6 mg/dL and low 24h urinary calcium of 79 mg/24h with calcium creatinine clearance ratio (CCCR) of 0.008. 25 hydroxyvitamin D, 1,25 Dihydroxyvitamin D and magnesium were normal. PTH level was 33 pg/dL (normal 15-65 pg/dL). Patient had no hypercalcemic symptoms, history of nephrolithiasis, or bone fractures. No family history of hypercalcemia. Cancer screening and PTH related peptide were normal. He was not taking hydrochlorothiazide or lithium. Renal ultrasound showed no nephrolithiasis and DXA revealed no osteoporosis. Thyroid ultrasound showed a right 1.2cm thyroid nodule without visualization of parathyroid glands. Fine-needle aspiration biopsy (FNA) of the nodule with PTH washout was benign with PTH<10. The patient was diagnosed with FHH and was monitored semiannually. Four years after the initial evaluation, total corrected calcium level was elevated at 14 mg/dL with PTH of 378 despite 25 hydroxyvitamin D level >40, repeated urinary calcium 90 mg/24h, and CCCR 0.01. His renal function was unchanged. Parathyroid scintigraphy revealed increased uptake in the right upper thyroid lobe, and thyroid ultrasound revealed increased right thyroid nodule volume. Repeat FNA was benign, this time with a PTH washout >200. The patient opted against surgical consultation for parathyroidectomy. He was treated with cinacalcet 30 mg twice daily. The co-existence of FHH and PHPT is rare. The few reported cases include patients who maintained hypercalcemia after surgical treatment of PHPT. The best cost-effective test available is a CCCR < 0.02. Our patient had CCCR measured at different times with values < 0.01 and a PTH level that over time increased by 900%. The overlap of biochemical values in patients with FHH and PHPT contributes to the challenges in the differential diagnosis and highlights the importance of close follow up with a high degree of clinical suspicion.

Abstract #1384628: An Incidental Thyroid Lesion on FDG-PET Scan in a Patient with Long History of Hypothyroidism and Radiation Exposure

An 81-year-old woman with history of lung cancer and hypothyroidism with an incidental thyroid lesion on (FDG)-positron emission tomography (PET) scan is subsequently diagnosed with primary thyroid lymphoma (PTL) using flow cytometry. An 81-year-old woman with a history of lung cancer and hypothyroidism presented to the endocrinology office for evaluation of a thyroid lesion. Primary hypothyroidism was diagnosed 30 years prior to presentation and was controlled with levothyroxine 88 mcg daily. Lung cancer was diagnosed 8 years prior, and treated with radiation therapy. Patient had an FDG-PET scan obtained for the evaluation of lung nodules, and a hypermetabolic focus was noted in the left thyroid region with a max SUV of 18. On thyroid ultrasound, the left thyroid lobe appeared heterogenous with solid nodular areas. The physical exam revealed a smooth but firm thyroid gland, without cervical lymphadenopathy. Laboratory workup showed thyroid stimulating hormone and free thyroxine in the normal range. Microsomal antibody was 4.2 IU/mL (< 5.6 IU/mL), and thyroglobulin antibody was 356.4 IU/mL (< 14.4 IU/mL). Fine needle aspiration (FNA) biopsy showed a polymorphous lymphoid sample. Given the high SUV on PET-scan and longstanding history of Hashimoto’s thyroiditis, repeat FNA biopsy with flow cytometry was subsequently performed and showed a lymphoid population consistent with a non-Hodgkin lymphoma (NHL). The patient was referred to oncology and diagnosed with indolent NHL. Further staging revealed interval growth in lung nodules, with biopsy showing recurrence of adenocarcinoma, but no other metastatic disease. The patient underwent radiation therapy for both her lung adenocarcinoma and primary thyroid lymphoma (PTL). Primary thyroid lymphoma accounts for less than 5% of thyroid cancers. It presents with a female predominance in the 7th decade of life, with Hashimoto’s thyroiditis as the main risk factor. Patients may present with an enlarging neck mass, with or without compressive symptoms, and cervical lymphadenopathy. Diagnosis of PTL can be made through FNA biopsy, core biopsy, or open surgical biopsy. It is important to note that because these lesions have few pathognomonic features, diagnosis with FNA biopsy alone can be difficult, and sensitivity is increased to 97% with the use of flow cytometry, as was demonstrated in our case. Treatment is with radiation therapy or combined chemoradiotherapy. Surgery has a role limited to the management of airway compromise, as surgical resection has not proven to improve overall survival. This case highlights the utility of including flow cytometry with FNA sample when diagnosing PTL.

Abstract #1394898: Ethanol Sclerosis of Recurrent Intrathyroidal Parathyroid Cyst

The incidence of parathyroid cyst varies between 0.08 % and 3.4 %. To date about 300 cases have been reported in the worlds’ literature. Parathyroid cysts may be functional or not, with functionating cysts tending to occur in men and at more advanced ages. Non-functionating parathyroid cysts are typically pure cysts that are usually asymptomatic unless they are large enough to cause compressive type symptoms. The treatment for a functionating parathyroid cyst is primarily surgical. We present the case of a 58-year-old Caucasian female who presented with a recurrent parathyroid cyst first being noted in 1993. Initial FNA drainage was reported to have yielded acellular, clear fluid (amount unknown) and fluid PTH was not assessed. A cycle of cyst re-accumulation and repeat FNA drainage occurred. Subsequent FNA drainage in 2008 yielded 20cc of clear fluid and 16.5 cc in 2013. The incidence of parathyroid cyst varies between 0.08 % and 3.4 %. To date about 300 cases have been reported in the world’s literature (1, 2). Parathyroid cysts may be functional or not, with functionating cysts tending to occur in men and at more advanced ages Non-functionating parathyroid cysts are typically pure cysts that are usually asymptomatic unless they are large enough to cause compressive type symptoms (1). The treatment for a functionating parathyroid cyst is primarily surgical. We present the case of a 58-year-old Caucasian female who presented with a recurrent parathyroid cyst first being noted in 1993. Initial FNA drainage was reported to have yielded acellular, clear fluid. A cycle of cyst reaccumulation and repeat FNA drainage occurred. In 2008, cyst fluid PTH was assessed to be 372 pg/ml. Serum calcium levels were consistently normal between 9.2 – 9.4 mg/dl and serum PTH 23.8 – 34 pg/ml from Oct 2012 through Dec 2017. In June 2017, patient returned with a sensation of left neck pressure. Ultrasound revealed a simple cyst encompassing most of the left thyroid lobe measuring 5.1 x 2.1 x 1.7 cm. To prevent recurrence, ethanol sclerosis of the cyst was performed. Follow up evaluation in 2020 revealed patient to feel well, having normal calcium and thyroid blood tests with US documenting resolution of the left intrathyroidal cyst. While treatment of the functionating parathyroid cysts typically remains surgical, there are additional options for non-functionating parathyroid cysts management to include non-surgical options such as sclerosis with ethanol or possibly tetracycline.