Benign Fine-needle Aspiration Research Articles

Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules.

Thyroid fine-needle aspiration (FNA) is a principal diagnostic procedure for thyroid nodules. A specific cytomorphological structure, known as the thyroid spherule, is often seen in FNA specimens. The clinical significance of these spherules in terms of diagnosis and prevalence remains largely unexplored. We performed a retrospective study on 310 thyroid FNA specimens and categorized them according to the Bethesda System for Reporting Thyroid Cytopathology. The presence, size and number of thyroid spherules in each specimen were examined and these data were subsequently correlated with the clinicopathological features. Thyroid spherules were almost exclusively detected in benign cases, comprising 7.6% of all benign diagnoses. The average diameter of spherules in benign cases was 84.9 μm. Benign cases and cases with atypia of undetermined significance cases primarily exhibited low cellularity, while follicular neoplasms and malignant cases typically showed moderate to high cellularity. In the subgroup of FNA cases with moderate to high cellularity, spherules were identified in 12 (20%) of 59 benign FNA cases. Within this group, the sensitivity and specificity of thyroid spherules for detecting benign FNA cases were 20% and 100%, respectively. Our results suggest that the presence of thyroid spherules in FNA specimens can serve as a highly specific marker for benign thyroid conditions. The prevalence of spherule detection is strongly influenced by the cellularity. In cases with moderate to high cellularity, the identification of spherules can assist the cytopathologists in diagnosing thyroid FNA cases as benign.

The Utility of ACR TI-RADS in Predicting False-Negative Fine Needle Aspiration for Thyroid Cancer.

Thyroid nodule fine needle aspiration (FNA) biopsies are associated with a low false-negative rate. There is limited data regarding the predictive value of American College of Radiology Thyroid Imaging Reporting and Data System for false-negative FNA. This single-center retrospective study evaluated 119 patients who underwent thyroidectomy. The association of TR category, along with other clinical variables, with false-negative FNA was evaluated. The overall false-negative rate of FNA was 10.8% (n = 9). False-negative FNAs were associated with younger age (mean 42years vs 50.6years, P = .04), larger nodule size (mean 4.4cm vs 3.2cm, P = .03), and a lower TR category (median 3 v 4, P = .01). Lower TR category, younger age, and larger nodule size were associated with false-negative FNA of thyroid nodules. These findings should be taken into context when counseling patients with thyroid nodules who have a benign FNA.

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

Prediction of cytology–histology discrepancy when Bethesda cytology reports benign results for thyroid nodules in women: with special emphasis on pregnancy

ABSTRACT Objectives: Benign category of Bethesda classification is generally well known to carry a false-negative rate of 0–3%. The current study was designed to investigate the rate of false-negative cytology in patients who underwent thyroidectomy for presumably benign thyroid diseases. Predictive risk factors for false results and malignancy were evaluated along with cytology–histology discrepant cases. Materials and methods: Females who underwent thyroidectomy between May 2014 and December 2022 were included. Demographics, ultrasound (US) features, fine-needle aspiration (FNA) diagnosis, surgical indications and outcomes, final histology reports, risk factors, and malignancy rate were recorded. Cytology–histology discrepant cases were further evaluated for interpretation errors and risk factors. Statistical analyses were performed using Fisher’s exact and Mann–Whitney U tests. Results: Of 581 women with a benign thyroid disease who underwent thyroidectomy, 91 was diagnosed as incidental carcinoma (15.6%) and most was T1a (4.9 ± 2.7 mm, 95.6%). Final histology reports revealed mostly papillary carcinoma (93.4%). Predictors of malignancy such as age, family history, previous radiation exposure, and iodine-deficient diet did not help in risk stratification (p > 0.05, for each). However, FNA taken during pregnancy was determined as a risk factor (n = 7, 7.6%, p < 0.05) since it may cause a delay in diagnosis. Cytology–histology discrepant cases were seen to be mostly due to sampling errors (45%, p < 0.05), followed by misinterpretations (37.3%, p < 0.05). There was no reason for discrepancy in 17.5%, and this was linked to inherent nature of thyroid nodule with overlapping cytologic features. Best identifiable risk factor for misinterpretation was pregnancy as well (n = 5, 14.7%, p < 0.05). Conclusions: Risk of malignancy in a presumably benign thyroid disease should not be ignored. Radiology–cytology correlation by an experienced dedicated team may help in decreasing sampling errors. Physiologic changes caused by pregnancy may shade malignant transformation in thyrocytes, and it would be appropriate to be cautious about benign FNA taken during this period.

Thyroid Nodule Margin Assessment Using ACR TI-RADS: Adding Points for Macrolobulation Impairs Performance.

We evaluated the performance of ACR TI-RADS when points for lobulated margins are applied only when the margins meet a quantified measure of margin microlobulation and not applied when nodules only demonstrate macrolobulation. We retrospectively reviewed ultrasound and pathology records (May 01, 2018 to July 31, 2020) to find all thyroid nodules at one institution characterized as having lobulated margins using the ACR TI-RADS lexicon and subsequently undergoing fine needle aspiration(FNA). Nodule margins were evaluated to note the presence or absence of microlobulation, quantitatively defined as a protrusion with a base <2.5 mm in length. The impact to detection of malignant nodules and avoidance of benign FNA when margin points for lobulation were added only when microlobulated was analyzed. 58 of 516 thyroid nodules undergoing US-guided FNA were classified as lobulated, comprising the study population. 21 (36.2%) had microlobulated margins, with 12 of the 21 (57.1%) being malignant. Comparatively, of the 37 nodules showing only macrolobulated margins without microlobulation, only 2 (5.4%) were malignant (P < .0001). For 53 nodules ≥10 mm, 15 (28.3%) benign nodules would not have met size criteria for FNA had points for margins not been applied when only showing macrolobulation, whereas all 10 malignant nodules would still have been sampled. Adding two points to the ACR TI-RADS score for lobulated thyroid nodules should only apply when microlobulations are present.

Comparison of diagnostic value of SWE, FNA and BRAF gene detection in ACR TI-RADS 4 and 5 thyroid nodules.

To compare the diagnostic value of shear wave elastography (SWE), fine needle aspiration (FNA) and BRAF gene detection (BRAFV600E gene mutation detection) in ACR TI-RADS 4 and 5 thyroid nodules. SWE images, FNA cytological results and BRAF detection results of ACR TI-RADS 4 and 5 thyroid nodules confirmed by pathology were analyzed retrospectively. The receiver operating characteristic (ROC) curve was drawn to determine the best cutoff value of SWE Emax. In the combined diagnosis of SWE, FNA and BRAF, firstly, the nodules with BRAF gene mutation were included in the positive ones, secondly, the nodules with benign and malignant FNA were included in the FNA + SWE or FNA + SWE + BRAF negative and positive ones respectively, finally, for FNA uncertain nodules: those whose SWE Emax were less than or equal to the cutoff value were included in FNA + SWE or FNA + SWE + BRAF negative ones, and those whose SWE Emax were greater than the cutoff value were included in positive ones. The diagnostic efficacy of SWE, FNA, SWE + FNA, FNA + BRAF and their combination in ACR TI-RADS 4 and 5 thyroid nodules were compared. The ROC curve showed that the best cutoff value of SWE Emax was 40.9 kpa, and the area under ROC curve (AUC) was 0.842 (0.800∼0.885). The sensitivity, specificity and accuracy of SWE were 76.3% (270/354), 75.5% (80/106) and 76.1% (350/460), respectively. The sensitivity, specificity and accuracy of FNA were 58.2% (206/354), 88.7% (94/106) and 65.2(300/460), respectively. The sensitivity, specificity and accuracy of FNA + BRAF were 95.5% (338/354), 88.7% (94/106) and 93.9% (432/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA were 85.9% (304/354), 98.1% (104/106) and 88.7% (408/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA + BRAF were 98.3% (348/354), 98.1% (104/106) and 98.3% (452/460), respectively. For the diagnostic accuracy, SWE + FNA + BRAF > FNA + BRAF > FNA + SWE > SWE > FNA, the difference was statistically significant (all P > 0.05). For ACR TI-RADS 4 and 5 thyroid nodules, SWE and FNA have high diagnostic efficiency. For the diagnostic accuracy, FNA + BRAF is better than FNA + SWE. FNA combination with BRAF gene detection further improves the diagnostic sensitivity and accuracy of FNA. The combined application of the three is the best.

Navigating the Debate on Managing Large (≥4 cm) Thyroid Nodules.

Purpose Discordant practice guidelines for managing large thyroid nodules may result in unnecessary surgeries and costs. Recent data suggest similar false-negative rates in fine needle aspiration (FNA) biopsies between small (<4 cm) and large (≥4 cm) nodules, indicating that monitoring rather than surgery may be appropriate for large biopsy-negative nodules. We investigated the management of thyroid nodules ≥4 cm to determine the proportion of surgeries not necessary for diagnostic purposes and examined for potential predictors. Methods This was a retrospective cohort study of patients who received a FNA of nodule(s) ≥4 cm between 11/1/2014 and 10/31/2019 at the University of Vermont Medical Center. A surgery was considered unnecessary if the FNA result was benign in the absence of any of the following: compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter, or substernal extension. Data were analyzed with Wilcoxon rank sum tests, chi square, or Fisher's exact tests. Results 177 patients had a ≥4 cm nodule during the timeframe and half (54.2%) had surgery. Patients who underwent surgery were significantly younger (51.5 years vs. 62 years; P < 0.001), more likely to report obstructive symptoms (34.4% vs. 12.1%; P < 0.001) and had a larger nodule size (5.0 cm vs. 4.7 cm; P=0.26). Forty-one patients with benign (Bethesda II) FNA results had surgery, all with negative surgical pathology. Thirteen percentage (23/177) of surgeries were potentially not necessary for diagnostic purposes. Conclusion Approximately half of our patients with ≥4 cm nodules had surgery, with 13% having surgery not necessary for diagnostic purposes revealing opportunities for improving care and costs.

Transcervical submandibular gland surgery; management, outcome, and complications of 120 cases

Objectives Surgical intervention is the treatment procedure of many diseases of the submandibular gland such as sialolithiasis, chronic sialoadenitis, and tumors. This study aims to analyze the management, outcomes, and complications of transcervical submandibular gland excision cases of a tertiary clinic and to discuss the results in light of the current literature knowledge. Materials and Methods 120 cases who applied to a tertiary otorhinolaryngology clinic between 2014-2019 and who underwent submandibular gland excision were analyzed retrospectively. Results Postoperative histopathological results revealed that 108 cases were benign and 12 of cases were malignant. The most frequent benign pathology was chronic sialoadenitis in 82 cases. The most common non-malignant tumor was pleomorphic adenoma in 16 cases. Although the result obtained with fine-needle-biopsy was benign in 2 patients, the histopathological result after surgery was malignant (adenocarcinoma in 1 patient, mucoepidermoid carcinoma in 1 patient). As complications of surgery; marginal mandibular nerve injury in 11 cases (permanent in 2 cases) and hematoma in 7 cases were noted. Conclusion A benign fine-needle aspiration biopsy result does not necessarily exclude malignancy in submandibular gland masses. As a result, we found that the percentage distribution of our submandibular gland histopathological results is consistent with the literature. Although marginal mandibular nerve injury is one of the most common complications of submandibular gland excision, transcervical submandibular gland excision is still a reliable surgery.

Suspicious thyroid nodules 4 cm require a diagnostic lobectomy regardless of their benign fine needle aspiration results

Background/objectiveThe diagnostic accuracy of fine needle aspiration biopsy (FNAB) seems limited in large thyroid nodules with Bethesda Cat. 2 result. We aimed to determine the incidence of carcinoma with benign cytology and the reason for the high false-positive rate in thyroid nodules ≥4 cm. MethodsThe records of 103 patients with thyroid nodules ≥4 cm with preoperative cytological diagnosis of Bethesda Cat. 2 who underwent thyroidectomy were consecutively reviewed. Characteristics between patients with malignant vs. benign pathology were compared. ResultsForty patients (38.8%) had malignancy. Malignancy was subclassified into follicular variant of papillary thyroid carcinoma (43%), minimally invasive follicular thyroid carcinoma (20.0%), and minimally invasive Hurthle cell thyroid carcinoma (10.9%). Patients with malignant cytology had significantly more suspicious ultrasound findings than those with benign cytology (p = 0.001). ConclusionsPreoperative FNAB showed high false-negative rates in patients with thyroid nodules ≥4 cm with benign cytology. These nodules have a high malignancy rate with suspicious ultrasound findings.

Evaluation of Children and Adolescents with Thyroid Nodules: A Single Center Experience

Objective:We aimed to evaluate the clinical, radiological and pathological findings of children and adolescents with thyroid nodules.Methods:Data of 121 children and adolescent with thyroid nodules and had fine needle aspiration (FNA) were examined retrospectively. Concomitant thyroid disease, ultrasonography (US) features of the nodule, FNA and histopathological results were recorded. FNA results were assessed according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).Results:Median (range) age of the cases was 14 (3-18) years and 81% were female. FNA results of patients were: insufficient in 1 (0.8%); benign in 68 (56.2%); indeterminate in 44 (36.4%); and malignant in 8 (6.6%) patients. Among 39 patients who underwent surgery, 10 (25.6%) had differentiated thyroid cancer (DTC) and the overall malignancy rate was 10.0% (10/100). Follow-up FNA results showed progress based on TBSRTC in 18.7% of benign results and 4/75 patients had DTC on surgical excision. Two of 22 patients with atypia of undetermined significance (AUS) who continued follow-up was diagnosed with DTC. Male gender, presence of Hashimoto thyroiditis and US findings of uninodularity, hypoechogenicity, increased blood flow, irregular margins, solid structure, microcalcification and presence of abnormal cervical lymph nodes were associated with malignancy.Conclusion:In this study 10% of thyroid nodules were malignant in children and adolescents. Patients with AUS have a 9% potential for malignancy. Patients with initially benign FNA result may have changes on repeat FNA when assessed with TBSTRC indicating a 5.3% false negative rate.

A tru-cut biopsy proven rare thyroid neoplasia in a giant nodule with a benign fine needle aspiration cytology

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

A tru-cut biopsy proven rare thyroid neoplasia in a giant nodule with a benign fine needle aspiration cytology

A tru-cut biopsy proven rare thyroid neoplasia in a giant nodule with a benign fine needle aspiration cytology

A tru-cut biopsy proven rare thyroid neoplasia in a giant nodule with a benign fine needle aspiration cytology

A tru-cut biopsy proven rare thyroid neoplasia in a giant nodule with a benign fine needle aspiration cytology

Navigating the Debate on Large (4+cm) Thyroid Nodules: Local Insight on a Persisting Problem

Abstract Background: Thyroid nodules are a common clinical finding, however discordant practice guidelines for managing large nodules may result in unnecessary surgeries and excess costs. Recent data suggest similar false negative rates in fine needle aspiration (FNA) biopsies between small (&amp;lt;4cm) and large (4+ cm) nodules, indicating that monitoring rather than surgery may be appropriate for large nodules. Evaluating current management strategies may reveal insights regarding excess surgeries, costs and opportunities for improvement. Objectives: The goal of this project was to describe the patients at our institution with large thyroid nodules and determine the proportion of potentially unnecessary surgeries and the associated predictors. Methods: This was a retrospective cohort study that included patients who received a FNA of nodule (s) ≥4cm between 11/1/2014 and 10/31/2019 at our tertiary care institution. Patient demographics, sonographic nodule size, fine needle aspiration cytology, molecular testing results, final surgical pathology, history of neck irradiation, family history of thyroid cancer, presence of compressive symptoms or presence of a toxic nodule or toxic multinodular goiter, were compared between patients who had surgery and those who did not. A surgery was considered inappropriate if the FNA result was benign in the absence of any of the following: a suspicious result on molecular testing, compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter or substernal extension. Continuous variables were evaluated using Wilcoxon rank-sum test while categorical variables were tested using chi-square or Fisher’s exact test. Results: A total of 177 patients had a 4+ cm nodule during the timeframe. Half of patients (54.2%)with 4+ cm nodules had surgery. Patients who underwent surgery were significantly younger (51.5 years vs 62 years; P&amp;lt;0.001), more likely to report obstructive symptoms (34.4% vs 12.1%; P=0.001) and have a larger nodule size (5.0 cm vs 4.7 cm; P=0.26) than patients who did not have surgery. Forty-one patients with benign (Bethesda II) FNA results went on to have surgery. All 41 patients were found to be negative at surgery, yielding a false negative rate of 0.0% in our cohort. Twenty-three surgeries (24.0%) were considered inappropriate and overall 13% (23/177) of patients with 4+cm nodules had unnecessary surgery. The median charge for these surgeries was $13,183. Conclusion: Approximately half of our patients with 4+ cm nodules had surgery, especially patients who are younger, report obstructive symptoms, and have larger nodule sizes. Overall 13% of our patients with 4+cm nodules had unnecessary surgery revealing opportunities for improving care and costs.

A Case of T3 Thyrotoxicosis With Concomitant Follicular Thyroid Carcinoma

Introduction: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. In these cases, the follicular thyroid carcinoma subtype is an even more rare finding. It is highly unlikely to find follicular carcinoma in a hyperactive thyroid nodule. Clinical Case: We report a case of an 85-year-old female with a past medical history of atrial fibrillation presenting to the clinic after she has noticed enlargement of her neck two weeks prior. The patient was seen by her primary care physician who ordered a CT neck that revealed a goiter and the patient was subsequently referred to our clinic. On further questioning, the patient denied palpitations, sweats, difficulty swallowing, heat or cold intolerance, weight changes, bowel changes, or any other complaints. The patient denied any prior history of thyroid disease or exposure to goitrogens. Her past medical history was not significant for any auto-immune related diseases. She denied any family history of thyroid disease or malignancy. On physical examination, the patient had a normal eye exam and mild goiter with a small palpated right thyroid nodule. Initial thyroid ultrasound revealed a heterogenous right lobe measuring 7.1 cm x 7.3 cm x 5.9 cm with one superior nodule measuring 1.3 cm x 0.7 cm x 0.8 cm and a heterogenous left lobe measuring 2.0 cm x 1.5 cm x 1.1 cm. Laboratory blood work up revealed total T4 of 10.5 μg/dL(normal: 5.0 to 12.0μg/dL), elevated total T3 at 322 ng/dl (normal: 80-220 ng/dL), suppressed TSH <0.01 uIU/mL (normal: 0.40-4.00 uIU/mL), markedly elevated thyroglobulin 2828 ng/mL(normal: 1-84 ng/mL), as well as elevated anti-TPO Ab 63.5 IU/mL (10.0-35.0 IU/mL). The patient underwent a thyroid uptake scan that revealed increased uptake in the right lobe. Three months after presentation, the patient underwent fine-needle aspiration (FNA) which was benign (Bethesda classification II). A decision was made to start the patient on Methimazole and the subsequent thyroid profile showed an improvement in her T3 and TSH, but thyroglobulin continued to uptrend despite treatment. The patient then underwent another thyroid ultrasound one year later that revealed increased right lobe size to 10.3 cm x 6.3 cm x 6.4 cm with enlargement of the superior nodule to 8.5 cm x 4.6 cm x 6.4 cm. The left lobe was also enlarged from the prior scan measuring 3.9 cm x 1.2 cm x 1.0 cm. The patient underwent a second FNA from that nodule which also revealed benign hyperplastic nodule (Bethesda classification II). Despite the benign FNA finding, a decision was made to perform genetic testing given the rapid progressive enlargement of the nodule. The genetic testing revealed TERT promoter gene mutation with a high risk for malignancy. The patient then underwent total thyroidectomy and the pathological analysis showed a 9 cm follicular thyroid carcinoma of the right nodule. The patient then underwent successful I-131 radioactive Iodine ablation. Subsequent thyroid ultrasounds were negative and TSH continued to downtrend while the patient continued to take thyroid hormone replacement. This patient’s presentation is unique in many aspects. The patient presented with a hyperactive hot nodule while follicular carcinoma of the thyroid gland is typically associated with clinical euthyroidism and a scan showing a cold nodule(1). In a study of 425 hyperthyroid patients, thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients, and histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in only 2 cases (2). Our patient also had two negative FNAs despite the presence of follicular carcinoma. Hence, we are shedding the light on the importance of genetic testing in the setting of negative FNA for rapidly enlarging thyroid nodules. Conclusion: We urge physician’s awareness that on rare occasions, follicular thyroid carcinoma can be present in a hyperactive thyroid with a hot nodule. In the presence of negative FNA, hyperfunctioning rapidly growing thyroid nodules should be carefully evaluated by further genetic testing for the presence of concurrent malignancy.

Clinical, sonographical, and pathological findings of pediatric thyroid nodules.

Thyroid nodules are less frequent in children than in adults. A higher rate of malignancy is highlighted in this group. We aimed to analyze the clinical, laboratory, and ultrasound (US) findings of children and adolescents with benign and malignant thyroid nodules. This was a retrospective review of children and adolescents evaluated at a tertiary pediatric institution between 2007 and 2019. Patients with autonomously functioning nodules, autoimmune thyroid diseases, and a history of oncohematological disorders were excluded. A total of 102 patients with 131 nodules were identified. The study population included 57 females (55.9%); the average age was 10.6 ±4 years. Thirty-five nodules (26.7%) ranging 4.5-36 mm had a fine-needle aspiration (FNA) done: 45.7% (n = 16) were benign, 11.4% (n = 4) were classified as atypia, and 8.5% (n = 3) were consistent with papillary carcinoma. Fourteen patients (13.7%) underwent surgery. Five (4.9%) were finally diagnosed with papillary thyroid cancer. Of the 6 patients with benign FNAs, all except one, which was initially reported as atypia by an earlier FNA but was later diagnosed with papillary carcinoma, had a colloid nodular goiter. Of the 3 patients with atypia FNAs, one was found to be papillary carcinoma. One hundred twenty-five benign nodules (21 based on cytology and/or histology, 104 on clinical and imaging follow-up) were diagnosed. Nodule size, microcalcifications, solid parenchyma, and pathologic lymph node alterations were associated with malignancy, but nodule growth was not.Conclusion: Diagnostic approach and management of children with thyroid nodules should be based on a stepwise evaluation including clinical, laboratory, and US findings. Of the 102 patients identified, 4.9% had thyroid carcinoma below the range described in previous literature. What is Known: • Thyroid nodules are less frequent in children than in adults but more frequently malignant. Research on factors associated with malignancy have mostly been conducted in adults; further studies in pediatric thyroid nodules are warranted. What is New: • Microcalcifications, pathologic lymph node alterations, solid parenchyma, and larger nodule size are associated with malignant nodules, but nodule growth is not always suggestive of thyroid malignancy. The incidence of thyroid malignancy in this population was below the reported worldwide incidence in children with thyroid nodules.

Abstract PS3-09: The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST)

Abstract Introduction: Immunotherapy use is increasing as an adjunct to current NST for breast cancer treatment with the goals of increasing pCR and down staging tumors. In this study, we assessed the effectiveness of MRI in the evaluation of tumor response after neoadjuvant immunotherapy in combination with NST. Methods: We retrospectively reviewed the clinicopathological data of 105 women undergoing Immunotherapy in conjunction with NST at a single institution. All patients had been enrolled in IRB approved protocols and had undergone definitive surgery. Patients were excluded for: failure to complete at least two thirds of treatment, no pre or post treatment MRI, or surgery in an outside institution. We analyzed 73 patients from 5 distinct treatment protocols including: (1) 24 Triple negative breast cancer (TNBC) patients (pts) treated with Intratumoral Talimogene laherparepvec (TVEC) in combination with weekly paclitaxel followed by dose dense Adriamycin and Cytoxan (ddAC); (2) 19 HER2/Neu positive (HER2+) pts treated with subcutaneous interferon gamma (IFN-γ) in combination with weekly paclitaxel with trastuzumab and pertuzumab (HP); (3), 7 HER2+ pts treated with 3 weeks of HER2 pulsed dendritic cell vaccines (DC1) followed by Taxotere, Carboplatin, and HP; (4), 14 pts on the ISPY2 trial: 8 TNBC and 4 Hormone receptor positive, HER2/Neu negative (HR+) pts randomized to treatment with pembrolizumab with weekly paclitaxel followed by ddAC (2 also received additional SD101), and 2 TNBC pts treated with Durvalumab, Olaparib and Paclitaxel, followed by ddAC and (5) 9 HR+ pts on neoadjuvant Durvalumab and an Aromatase Inhibitor for 6 cycles. Results: A total of 73 patients were included in the study. Median age was 51 years (range 27-76); 46.6% of patients had TNBC, 35.6% had HER2+ and the remaining 17.8% were HR+ HER2-. The median clinical tumor size was 3.4cm (range 1.3-10.6) pre therapy and 1cm (range 0-10.1) post therapy. The pCR was 38.2%, 57.7%, and 0% respectively for TNBC, HER2+, HR+ tumors. Complete radiological response (rCR) of both the axilla and breast was 41.2%, 61.5% and 7.7%, for TNBC, HER2+ and HR+ tumors. The sensitivity of MRI to detect in breast pCR was 65.6% with a specificity of 81%, NPV and PPV of 75% and 73.3% respectively. MRI identified 37 pts with suspicious axillary nodes on pretreatment MRI; of these 30 had fine needle aspiration (FNA) confirmed metastatic disease. Post treatment, 70.3% (26/37) had normalized axillary nodes. Of those with normalized nodes, 26.9% (7/26) had residual cancer on final pathology. Of the patients with confirmed FNA lymph node metastasis, axillary pCR of 63.3% was achieved. The sensitivity and specificity of MRI to detect pCR within the axilla was 87% and 50% and NPV and PPV 70% and 74.1%, respectively. 3 patients had axillary disease on final pathology but no suspicious imaging and a benign FNA. Conclusion: The addition of immunotherapy to current NST strategies can improve pCR and decrease residual cancer burden. The PPV and NPV of MRI to predict pCR in patients undergoing immunotherapy in combination with NST remains within the ranges described in patients undergoing NST alone. MRI remains a useful tool to guide surgical management but is not accurate enough to replace pathological evaluation. Citation Format: Noeline Rajarajan, Daniel Segarra, Robert J Weinfurtner, Adrian A Lopez, M Catherine Lee, John Kiluk, Hatem Soliman, Hung Khong, Han S Hyo, Marilin Rosa, Brian J Czerniecki, Nazanin Khakpour. The use of magnetic resonance imaging (MRI) in predicting pathological complete response(pCR) in the breast and axilla after the addition of immunotherapy to neoadjuvant systemic therapy (NST) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-09.

Ex vivo thyroid fine needle aspirations as an alternative for MALDI-MSI proteomic investigation: intra-patient comparison

Fine needle aspiration (FNA) is the reference standard for the diagnosis of thyroid nodules. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been successfully used to discriminate the proteomic profiles of benign and malignant thyroid FNAs within the scope of providing support to pathologists for the classification of morphologically borderline cases. However, real FNAs provide a limited amount of material due to sample collection restrictions. Ex vivo FNAs could represent a valuable alternative, increasing sample size and the power of statistical conclusions. In this study, we compared the real and ex vivo MALDI-MSI proteomic profiles, extracted from thyrocyte containing regions of interest, of 13 patients in order to verify their similarity. Statistical analysis demonstrated the mass spectra similarity of the proteomic profiles by performing intra-patient comparison, using statistical similarity systems. In conclusion, these results show that post-surgical FNAs represent a possible alternative source of material for MALDI-MSI proteomic investigations in instances where pre-surgical samples are unavailable or the number of cells is scarce.

The Prevalence of Thyroid Papillary Microcarcinoma in Patients With Benign Thyroid Fine Needle Aspiration.

IntroductionThyroid nodules are a very common clinical finding in the general population. We use fine needle aspiration (FNA) as the gold standard workup test for a thyroid nodule, as it is capable of differentiating malignant nodules from benign in the majority of cases. Usually, FNA is done for nodules that are more than 1 cm; small malignant lesions that are less than 1 cm in size can be missed. That’s why the risk of having undiagnosed microcarcinomas in an otherwise benign FNA needs to be explored.AimTo estimate the prevalence of thyroid papillary microcarcinoma in patients with benign FNA and evaluate and correlate the FNA cytological results with the final histopathological diagnoses.MethodsThis was a retrospective study of 1543 post-thyroidectomy patients who underwent FNA cytology, were classified according to the Bethesda scoring system, and were admitted to two tertiary care hospitals in Riyadh, Saudi Arabia, from 2010 to 2019.ResultsSix-hundred-seven (607) out of 1543 FNA cytology results were reported as benign, 215 as malignant, and 73 as suspicious of malignancy. On final histopathology diagnosis, 81/607 (13.34%) of benign cases and 35/215 (16.28%) of malignant cases did not meet the initial cytology and were confirmed as papillary microcarcinoma. In patients with microcarcinoma after initial benign FNA (89.2%) found to have benign multinodular changes, compared to only (31%) of initial malignant FNA patients.Conclusion When non-surgical intervention is chosen in patients with benign FNA, the possibility of coexisting microcarcinoma with its variable prognosis should be taken into account and explained to the patient.

Quality of Life Following Molecular Marker Testing for Indeterminate Thyroid Nodules

Thyroid cancer has a disproportionately negative effect on the quality of life (QOL) compared to malignancies with a worse prognosis. The QOL of patients with indeterminate thyroid nodules has not been previously evaluated. We aimed to assess the impact of molecular test results on the QOL of patients with indeterminate thyroid nodules. A short version of the Thyroid-Related Patient-Reported Outcome (ThyPro-39) was used to assess the QOL of patients who underwent thyroid fine needle aspiration (FNA) biopsy throughout UCLA Health from May, 2016, to June, 2017. All patients with indeterminate biopsy results underwent molecular testing with either Afirma Gene Expression Classifier or ThyroSeq v2 at the time of the initial biopsy. The QOL associated with symptoms of goiter, anxiety, depression, and impaired daily life were analyzed. Of 825 consented patients, 366 completed the assessment (44.4% response rate). FNA results included 76% benign, 7% malignant, and 17% indeterminate. There were no differences in QOL between patients with a benign FNA and patients with an indeterminate result with benign molecular testing. In patients with an indeterminate FNA, symptoms of goiter (20.5 versus 10.4; P = .033) and depression (33.3 versus 21.0; P = .026) were worse for patients with suspicious versus benign molecular test results; however, no significant differences were observed in anxiety or impaired daily life. A benign molecular test result may provide reassurance for patients with indeterminate thyroid nodules that the risk of malignancy is low. Long-term follow-up is necessary to determine if benign molecular test results maintain improved QOL.