Repeat Fine-needle Aspiration Research Articles

Case Report : Undifferentiated Synovial Sarcoma Presenting as a Large Thoracic Mass: A Rare and Challenging Diagnosis

Background: Undifferentiated synovial sarcoma (USS) is a rare and aggressive subtype of soft tissue sarcoma. Its presentation as a large thoracic mass poses significant diagnostic and therapeutic challenges.  Case Presentation: A 34-year-old male presented with a three-month history of progressive chest pain and hemoptysis. Imaging studies revealed a large, cystic thoracic mass with pleural effusion. Initial serological testing suggested hydatid cyst, but subsequent testing revealed negative Echinococcus (Hydatid) IgG antibodies.  Diagnostic and Therapeutic Interventions: Repeat fine-needle aspiration cytology (FNAC) was deferred due to revised ultrasound findings indicating a solid fibrocystic vascular lesion. Bronchial artery embolization (BAE) was performed to control life- threatening hemorrhage. Thoracotomy and en-bloc mass excision were subsequently undertaken.  Histopathological Diagnosis: Histopathological examination of the resected specimen revealed undifferentiated synovial sarcoma and spindle cell sarcoma.  Clinical Implications: This case highlights the importance of correlating imaging and serological findings, managing vascular complications, and the efficacy of BAE in controlling hemorrhage. The significance of thoracotomy and mass excision in achieving diagnostic clarity and therapeutic success is underscored.  Conclusion: Undifferentiated synovial sarcoma presenting as a large thoracic mass poses significant diagnostic and therapeutic challenges. A multidisciplinary approach, incorporating imaging, serological testing, and surgical intervention, is crucial for achieving optimal patient outcomes.

6477 Surprise Finding For A Thyroid Nodule: Metastatic Renal Cell Carcinoma

Abstract Disclosure: A. Xu: None. E. Hsu: None. Introduction: A patient with an incidental and asymptomatic thyroid nodule underwent fine needle aspiration biopsy (FNA) after the nodule increased in size. Without a definite pathology after three FNA attempts, thyroidectomy was performed, where pathology found metastatic renal cell carcinoma (RCC). Clinical Case: A 64 year old woman had a past medical history of obesity, type 2 diabetes, RCC (stage I: pT1bN0M0) treated with right radical nephrectomy five years prior and thought to be in remission, remote smoking history smoking, and coronary artery disease with coronary artery bypass graft (CABG) two months prior, on anticoagulation. The patient reported a distant history of right thyroid lobectomy over a decade prior for unclear reasons, but she was adamant that the pathology was benign. Two years prior to presentation, CT chest done for RCC surveillance had detected a left thyroid nodule. Ultrasound at the time revealed a 3.6 x 1.9 x 2.3 cm solid, isoechoic nodule in the upper left lobe, which was not taller than wide, and had smooth margins and no echogenic foci. A repeat ultrasound at the time of presentation showed interval growth of the nodule, now measuring 4.3 x 2.1 x 2.9 cm. FNA was unsatisfactory, yielding predominantly blood. Patient felt well and had no compressive neck symptoms. We opted to wait two months and repeat FNA, which resulted as atypia of undetermined significance - Bethesda category III (AUS). We recommended completion thyroidectomy, but patient preferred to avoid surgery. We decided to wait two months and repeat FNA with molecular testing. This third FNA resulted AUS again; however, due to non-medical reasons, molecular testing was not performed. Another ultrasound showed slight growth of the nodule, 5.1 x 2.9 x 2.0 cm, which appeared hypoechoic now, but was still not taller than wide, with smooth margins and no echogenic foci. Completion thyroidectomy was performed, with pathology showing metastatic clear cell renal cell carcinoma. Immunostains were positive for carbonic anhydrase and renal cell carcinoma marker and negative for TTF-1. Whole-body PET-CT showed no hypermetabolic foci, and a repeat PET-CT one year later still showed no evidence of metastatic disease. Other than a hospitalization for COVID-19, patient is doing well and asymptomatic now over a year after her thyroidectomy. Oncology will continue routine surveillance imaging for her metastatic renal cell carcinoma thought to be in remission. Clinical Lessons: This case of metastatic renal cell carcinoma to the thyroid adds to the small body of literature showing the thyroid as a possible site of RCC metastasis. The long time interval between initial RCC presentation and metastasis to the thyroid makes this diagnosis more difficult; however, clinicians should be aware of the possibility, making thyroidectomy a stronger option in cases where FNA cytology is indeterminate. Presentation: 6/2/2024

6477 Surprise Finding for a Thyroid Nodule: Metastatic Renal Cell Carcinoma

Abstract Disclosure: A. Xu: None. E. Hsu: None. Introduction: A patient with an incidental and asymptomatic thyroid nodule underwent fine needle aspiration biopsy (FNA) after the nodule increased in size. Without a definite pathology after three FNA attempts, thyroidectomy was performed, where pathology found metastatic renal cell carcinoma (RCC). Clinical Case: A 64 year old woman had a past medical history of obesity, type 2 diabetes, RCC (stage I: pT1bN0M0) treated with right radical nephrectomy five years prior and thought to be in remission, remote smoking history smoking, and coronary artery disease with coronary artery bypass graft (CABG) two months prior, on anticoagulation. The patient reported a distant history of right thyroid lobectomy over a decade prior for unclear reasons, but she was adamant that the pathology was benign. Two years prior to presentation, CT chest done for RCC surveillance had detected a left thyroid nodule. Ultrasound at the time revealed a 3.6 x 1.9 x 2.3 cm solid, isoechoic nodule in the upper left lobe, which was not taller than wide, and had smooth margins and no echogenic foci. A repeat ultrasound at the time of presentation showed interval growth of the nodule, now measuring 4.3 x 2.1 x 2.9 cm. FNA was unsatisfactory, yielding predominantly blood. Patient felt well and had no compressive neck symptoms. We opted to wait two months and repeat FNA, which resulted as atypia of undetermined significance - Bethesda category III (AUS). We recommended completion thyroidectomy, but patient preferred to avoid surgery. We decided to wait two months and repeat FNA with molecular testing. This third FNA resulted AUS again; however, due to non-medical reasons, molecular testing was not performed. Another ultrasound showed slight growth of the nodule, 5.1 x 2.9 x 2.0 cm, which appeared hypoechoic now, but was still not taller than wide, with smooth margins and no echogenic foci. Completion thyroidectomy was performed, with pathology showing metastatic clear cell renal cell carcinoma. Immunostains were positive for carbonic anhydrase and renal cell carcinoma marker and negative for TTF-1. Whole-body PET-CT showed no hypermetabolic foci, and a repeat PET-CT one year later still showed no evidence of metastatic disease. Other than a hospitalization for COVID-19, patient is doing well and asymptomatic now over a year after her thyroidectomy. Oncology will continue routine surveillance imaging for her metastatic renal cell carcinoma thought to be in remission. Clinical Lessons: This case of metastatic renal cell carcinoma to the thyroid adds to the small body of literature showing the thyroid as a possible site of RCC metastasis. The long time interval between initial RCC presentation and metastasis to the thyroid makes this diagnosis more difficult; however, clinicians should be aware of the possibility, making thyroidectomy a stronger option in cases where FNA cytology is indeterminate. Presentation: 6/2/2024

6641 Observation in Lieu of Surgical Management in Hurthle Cell Neoplasm: Role of Thyroseq V3 Molecular Testing

Abstract Disclosure: R. Kaur: None. L. Kaur: None. T. Chaudhary: None. M. Shrivastava: None. N. Patel: None. The diagnostic utility of fine needle aspiration biopsy with cytology is often confounded in thyroid nodules with predominance of hurthle cells, often interpreted as an oncocytic/hurthle cell lesion with intermediate risk of malignancy, bethesda category (BC) III or IV. With the advent of molecular testing like thyroseq V3, it is helpful in ruling out substantial risk of cancer and considering observation in lieu of surgical management in such difficult cases. We present a case of a 75 year old woman with past medical history significant for type 2 diabetes mellitus and hypothyroidism who was found to have a left lobe complex nodule within a non-toxic multinodular goiter In 2022. Ultrasound of the neck showed a 1.6 x 1.8 x 2 cm intermediate nodule, followed by a fine needle aspiration biopsy which was non-diagnostic and reported as benign, showing only cystic contents and insignificant follicular cells, Bethesda class II. Follow up for the nodule was recommended in one year. Repeat Imaging one year later revealed left nodule without significant changes and repeat fine needle aspiration cytology was advised. The biopsy result was reported as an oncocytic/ Hurthle cell neoplasm, Bethesda class IV. The specimen was also submitted for thyroseq molecular testing and results were awaited. The patient was euthyroid with negative anti thyroid antibodies. There was no family history of thyroid cancer or radiation exposure. The patient denied any active symptoms like shortness of breath, neck pain or pressure, recent voice changes, dysphasia, loss of appetite or weight .On examination the patient was found to have a left thyroid nodule with no signs of tracheal deviation. CT scan of the neck demonstrated a left thyroid nodule with no compression. The patient was followed by both endocrinology and oncology and surgical options were discussed depending upon the biopsy results while awaiting molecular testing report. Molecular testing with thyrosec V3 revealed an absence of gene mutations and reported a low probability of cancer. Depending upon the results observation was considered in lieu of surgical management. Hence It was decided to keep the patient under observation considering the molecular test results in conjunction with all relevant imaging, clinical findings, symptoms, patients family history as well as patients preference. This case report demonstrates the crucial role of molecular Diagnostics specifically thyroseq V3 in the often difficult clinical management of hurthle cell thyroid nodules for ruling out surgical management. Thyroseq V3 shows reliable performance in Hurthle cell cancers with sensitivity of 93% and specificity of 69%. In times of patient guided decision making and ability to narrow down the need of surgery based on pre-operative fine needle aspiration cytology, molecular profiling of thyroid nodules has become increasingly utilized. Presentation: 6/1/2024

12345 Staying Ahead of Cowden’s Syndrome in Differentiated Thyroid Cancer

Abstract Disclosure: M.S. Gordon: None. M.B. Gordon: None. Cowden’s syndrome or multiple hamartoma syndrome, is an uncommon autosomal dominant genodermatosis and is a member of the spectrum of disorders involving mutations in the phosphatase and tensin homolog gene (PTEN). It is associated with differentiated thyroid cancer (DTC), ¾ papillary, including follicular variant (FVPTC), 1/4 follicular (FTC), and other malignancies, including breast (most common), colorectal, renal cell, endometrial and skin cancers. We report a case of Cowden’s syndrome in which the patient presented with FVPTC but had no other apparent indication of a genetic abnormality until she was found to have a melanoma and was noted to have macrocephaly. The patient presented at age 26 with a thyroid nodule of 2.7 cm in maximal dimension. FNA was benign. By age 31 the lesion had grown to 3.3 cm and a repeat FNA showed a follicular neoplasm. She underwent left lobectomy and isthmusectomy revealing a 3.0 cm FVPTC with focal Hurthle cell features. There was capsular irregularity, and subsequently she underwent completion thyroidectomy showing a right sided 8mm FVPTC. She then received 30 mCi I 131. There were no apparent pathologic mucocutaneous lesions, intellectual deficits, and no family history of Cowden’s syndrome. At age 39 she was found to have a Stage IA malignant melanoma of the periumbilical skin which was resected. With two malignancies diagnosed at a relatively young age, she was evaluated for genetic syndromes and it was simultaneously noted that she had macrocephaly with head circumference of 66 cm. (>99 percentile). An analysis of 69 genes by Ambry genetics revealed a pathogenic variant in the PTEN gene (c.388 C>T (p.R130*). PTEN R130* results in a premature truncation of the PTEN protein at amino acid 130 of 403 within the phosphatase tensin-type domain resulting in loss of function. Macrocephaly (2% population frequency) is seen in 80% of patients with PTEN mutations. Twenty percent of patients with thyroid carcinoma and macrocephaly have a PTEN mutation and lifetime risk of melanoma in DTC is 25%. BRAF and RAS mutations may cooperate with PTEN loss and explain the increased co-occurrence of malignancies with BRAF and RAS mutations such as melanoma, FTC, and PTC in Cowden’s syndrome. In conclusion, we suggest that head circumference should be measured in all patients with DTC to screen for PTEN abnormalities. Patients with DTC also should have a thorough skin examination. Presentation: 6/2/2024

8161 A Rare Case of Malignant Melanoma Metastatic to the Thyroid Gland

Abstract Disclosure: J. Ferri-Guerra: None. O. Abdulhussein: None. E. Kasper-Guerra: None. G. Madrigal Loria: None. L. El Hage: None. 69 yo female presented with neck swelling in 2014. TSH was normal. Thyroid ultrasound showed multiple nodules with a right 2.9 x 2.3 x 2.1 cm that was cold on subsequent thyroid uptake scan. FNA of the right nodule in 08/2014 showed malignant cells with spindle cell pattern thought to be medullary thyroid cancer. She was scheduled for total thyroidectomy but presented with small bowl obstruction prior to her surgery and was diagnosed with metastatic melanoma (BRAF +). Initial PET scan showed a 4.1 x 2.8 x 2.8 cm hypermetabolic right thyroid lobe lesion in addition to other multiple hypermetabolic lesions consistent with known melanoma. The thyroid FNA specimen correlated with the small bowel excision specimen and showed similar features diagnosing metastatic melanoma to the thyroid gland.She was started on ipilimumab with subsequent scan in 04/2015 showing increase in right thyroid mass size to 5.4 x 4.2 x 9 cm with mixed results of other metastatic locations. She was switched to pembrolizumab and later dobrafenib/trametinib in 05/2015. Imaging thereafter showing significant improvement including a decrease in the right thyroid nodule size to 1.6 cm x 2.5 cm x 2.4 cm with no hypermetabolic activity on further PET scans. Repeat thyroid ultrasound in 2021 showed multiple nodules with a 2.2 x 1.5 x 1 cm nodule in the right. Repeat FNA of the right nodule was benign. Last imaging in 2023 showed stable nodules. Conclusion: metastasis to thyroid gland from malignant melanoma is a rare finding and should be considered in rapidly growing thyroid nodules. These lesions can be treated with targeted therapy that can spare affected individuals surgery. Presentation: 6/1/2024

Thyroid Nodules with Atypia of Unknown Significance (TBSRTC III): Evaluating the Role of Repeat FNA, Molecular Testing, and Surgery Across Five Hospitals

Thyroid Nodules with Atypia of Unknown Significance (TBSRTC III): Evaluating the Role of Repeat FNA, Molecular Testing, and Surgery Across Five Hospitals

Thermal ablation for Bethesda III and IV thyroid nodules: current diagnosis and management.

The diagnosis and management of Bethesda III and IV thyroid nodules remain clinical dilemmas. Current guidelines from academic societies suggest active surveillance or diagnostic lobectomy. However, the extent of surgery is often inappropriate, and a considerable percentage of patients experience under- or over-treatment. Thermal ablation has gained popularity as a safe and effective alternative treatment option for benign thyroid nodules. This review explores the feasibility of thermal ablation for Bethesda III or IV thyroid nodules, aiming to preserve the thyroid organ and avoid unnecessary surgery. It emphasizes individualized management, the need to consider factors including malignancy risk, clinical characteristics, and sonographic features, and the importance of supplemental tests such as repeat fine needle aspiration cytology, core needle biopsy, molecular testing, and radioisotope imaging.

Fate of nondiagnostic thyroid fine needle aspirations.

Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA. Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections. In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×). Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs.

The Milan system atypia of undetermined significance: 5-year performance data.

The objective of this study was to evaluate the diagnostic performance of the category atypia of undetermined significance (AUS) at the authors' institution based on the Milan System for Reporting Salivary Gland Cytopathology. All AUS cases diagnosed at Fimlab Laboratories between January 1, 2018, and December 31, 2022, were included. Histologic verifications were checked until May 31, 2023. The upper-bound and lower-bound risk of malignancy and risk of neoplasm were calculated. The timelines between the pathology laboratory workflow and patient management were also calculated. From 1157 fine-needle aspirations (FNAs), 162 (14.0%) AUS cases were diagnosed in 146 patients, with an average±standard deviation age of 66.1±14.9 years. There was variation in the AUS percentages, with higher values during the coronavirus disease 2019 pandemic years (15% and 17.5% in 2020 and 2021, respectively). Seventy-five cases (46.3%) had histologic follow-up: 16 were malignant neoplasms, and 36 were benign neoplasms. The upper and the lower bounds of the-risk of malignancy and risk of neoplasm were 21.3% and 69.3% and 9.9% and 32.1%, respectively. The average time from the first FNA with an AUS diagnosis to surgical resection ranged from 6 to 682 days, and the time to the first repeat FNA ranged from 10 to 691 days. The results indicated higher percentages of AUS cases compared with the reference value, which may be attributed to the impact of the coronavirus disease 2019 pandemic. The risk of malignancy calculated in this study was closer to the reference value from the first edition of the Milan System for Reporting Salivary Gland Cytopathology compared with the second edition.

Timing of the repeat thyroid fine-needle aspiration biopsy: does early repeat biopsy change the rate of nondiagnostic or atypia of undetermined significance cytology result?

To determine whether early repeat fine needle aspiration biopsy (FNA) has an effect on adequate or atypia of undetermined significance (AUS) cytology rates in thyroid nodules with inadequate or AUS result in the first FNA. Nodules of patients who underwent repeat biopsy due to insufficient or AUS cytology between 2019-2022 were included. Data of the patients and ultrasonographic, cytological and histopathological results of the nodules were recorded. Additionally, the time between the two biopsies was noted. The first was called "initial" and the second was called "rebiopsy". Five different paired groups were formed according to the time between two consecutive biopsies; before and after 1 month, 45 days, 2 months, 3 months, and 6 months. The groups were compared in terms of adequate and AUS cytological results. We evaluated 1129 patients with 2187 nodules undergoing FNAB. After excluding nodules with one FNA result and/or missing data, 966 nodules of 628 patients who underwent FNA at least twice were included. Initial cytology was nondiagnostic (ND) in 665 (30.4%) and AUS in 301 (13.8%) nodules. The mean age of the patients was 52.0 ± 11.9 years, and the female sex ratio was 78.8% (n = 495). There were no differences in adequate or AUS rebiopsy results according to the different time interval groups (p > 0.05 for all). AUS result was statistically insignificantly more frequent in nodules with initially AUS nodules when rebiopsy was performed before 1 month in comparison to after 1 month (53.8%, 27.1%; p = 0.054). Accuracy of rebiopsy was also similar in the time intervals groups (p > 0.05 for all). In patients with inadequate or AUS initial biopsy, the rate of adequate or AUS cytology results at rebiopsy did not vary with the timing of repeat biopsy indicating that there may be no need to wait 1 month for a repeat biopsy. In patients with suspicious nodules, biopsy might be repeated before 1 month.

Validation of the Bethesda System for Reporting Thyroid Cytopathology in a Danish tertiary centre.

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is used to categorise thyroid fine-needle aspiration (FNA). The aim of this study was to validate the BSRTC in a consecutive cohort and to evaluate the derived management in terms of performing repeat FNA or thyroid surgery. Results of thyroid FNAs assessed at the Department of Pathology, Aarhus University Hospital, in the period 2016-2019 were retrieved from The Danish Pathology Registry. FNA category according to the BSRTC along with the histological diagnosis (if available) were linked to the individual patient. In total, 3,669 biopsies were included from 2,873 thyroid nodules in 2,547 patients. Repeat FNA was performed in 23.6% of nodules. The majority of primary FNAs were Benign (BSRTC II; 52.4%). Non-diagnostic (ND) (BSRTC I) was found in 26.3% and BSRTC III-VI were found in 3.6-7.5%. Compared with the first with the last FNA, the frequency of Benign (BSRTC II) increased (61.3%), whereas the frequency of ND (BSRTC I) decreased (14.8%). Surgery was performed in 38.2% (n = 1,097) of nodules. The malignancy rate of 11.5% correlated positively with the BSRTC category, being 2.8% in Benign (BSRTC II) and 95.7% in Malignant (BSRTC VI). The malignancy rates in the BSRTC categories were in accordance with reports from other countries. Since the BSRTC ensures a standardised and concise communication of cytopathology assessments, application of the BSRTC for thyroid nodule management in a Danish setting is recommended. None. Not relevant.

An audit of “Repeat” fine needle aspiration cytology procedures in a cytopathology laboratory—An important quality indicator

Abstract Background: The cytopathology department mainly conducts audits to evaluate the diagnostic efficiency of procedures across different organs. However, the common occurrence of repeat aspirations, typical in many cytology laboratories, has largely been overlooked. This study sought to examine the frequency of repeat Fine Needle Aspiration Cytology (FNAC) procedures within a cytopathology laboratory and to explore the root causes for such repetition. Materials and Methods: A retrospective descriptive analysis was conducted at the cytopathology laboratory affiliated with a tertiary care facility. This study included all FNAC cases reported over six months. Data were extracted from cytology records, and multiple factors leading to repeat aspirations were examined. The rate of repeat FNAC procedures was calculated by dividing the number of “repeat” FNAC procedures in a specific month by the total number of FNACs performed. A quality manager set a benchmark of 15% for the repeat FNAC rate. Results: About 39 out of 303 FNACs (12.8%) were repeated for 6 months. Soft tissue lesions, predominantly lipomas, accounted for most (35.9%) of these repeated aspirations. The principal reason for the need for repeat aspirations was insufficient material obtained during the initial aspiration. Conclusion: In many laboratories, the frequency of repeat FNAC procedures and their root causes often need to be checked. Evaluating the quantity of repeat aspirations in a laboratory indicates its performance and is a vital quality measure, especially when accreditation is required. This research proved beneficial by providing valuable insights into the prevalence of repeat aspirations within a cytology laboratory.

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.

Cost-Effectiveness Analysis of Molecular Testing for Indeterminate Thyroid Nodules in Nova Scotia.

The objective of the following retrospective review was to perform a cost-effectiveness analysis of the use of molecular testing of indeterminate thyroid nodules compared to current management practices in Nova Scotia, Canada. All cases of cytologically indeterminate thyroid nodules from January 1st, 2014 to December 31st, 2018 were reviewed. All interventions related to an indeterminate thyroid nodule were recorded. Patients were excluded if less than 18 years old if no further information regarding medical management was electronically available beyond the diagnosis of an indeterminate thyroid nodule, history of radiation, or previous thyroid surgery prior to diagnosis of an indeterminate thyroid nodule in the remaining lobe. Microcosting was performed to determine the cost of all relevant interventions including repeat fine needle aspiration biopsy, ultrasound, thyroid surgery(s), and molecular testing. Institution-specific transition state probabilities were calculated and used to build a cost-effectiveness analysis model. Model output was an incremental cost-effectiveness ratio, defined as the ratio of cost difference to effectiveness difference between routine molecular testing and the current management strategy, yielding cost per surgery avoided. The mean effectiveness of the current management of indeterminate thyroid nodules in Nova Scotia based on the American Thyroid Association guidelines is 64% at a mean cost of $6431, while the simulated mean effectiveness of routine molecular testing is 89% at a mean cost of $8414. Differences in management strategies generated an incremental cost-effectiveness ratio of $7876 per surgery avoided. Routine molecular testing is the more effective strategy for the appropriate management of indeterminate thyroid nodules; however, it comes at a higher mean cost compared to the current management strategy. As the cost of molecular testing continues to decrease, and the cost of OR resources continues to rise, molecular testing is likely to become the optimal strategy in Nova Scotia.

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