Repeat Fine-needle Aspiration Research Articles

1629 The Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules

Abstract Introduction Fine needle aspiration (FNA) is the gold standard for the diagnostic assessment of thyroid nodules, with cytology stratified using the Thy classification (Thy 1-5). The management of cases where cytology is indeterminate (Thy-3) is challenging and subject to controversy. The current British Thyroid Association guidelines subclassify Thy-3 lesions into Thy-3a (atypia) and Thy-3f (follicular). Repeat FNA is generally recommended for Thy-3a specimens, whilst Thy-3f lesions should proceed to diagnostic hemithyroidectomy. The aim of this study was to determine the risk of malignancy in Thy-3a and Thy-3f lesions. Method This was a retrospective study of all patients who underwent FNA of a thyroid nodule from 01/01/2018 – 31/12/19. Those with Thy-3 cytology were identified and results correlated with final surgical histology. Results In total, there were 179 patients with Thy-3 cytology: 37 Thy-3a and 142 Thy-3f. The rate of malignancy was 21.6% (n = 8) for Thy-3a lesions and 20.4% (n = 29) for Thy-3f. When excluding microcarcinoma, the rates fell to 20.4% (n = 7) and 12.7% (n = 18) respectively. There was no statistically significant difference in malignant conversion between the two groups (p = 0.20). Conclusions This study does not demonstrate any statistically significant difference in the risk of malignancy between the Thy-3a and Thy-3f groups, suggesting that this subclassification does not add any additional utility to clinical decision making. Consideration should be given to the use of local malignant conversion rates to guide further management and pre-operative patient counselling in the Thy3 group.

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real-world setting.

American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine-needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification. Retrospective chart review. Adults with CIN that underwent MMP from 2017 to 2020. Pearsons' χ2 , Fisher's exact test, nonparametric testing and multiple regression analysis were performed. A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well-defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%-94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%. US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high-risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.

Outcomes of repeat fineneedle aspiration biopsy for AUS/FLUS thyroid nodules.

To determine the proportion of aspirates reclassified into each Bethesda category and to assess the rates of malignancy in each of them on repeat fine-needle aspiration biopsy (RFNA) following an AUS/FLUS diagnosis. Systematic review and meta-analysis. On February 2019, Pubmed/MEDLINE, EMBASE, WoS, and the Cochrane Library were searched for articles published from January 1, 2007. All studies published in English describing RFNA outcomes in AUS/FLUS nodules were included. PRISMA and MOOSE guidelines were followed. Five investigators independently assessed the eligibility of the studies. Two investigators extracted summary data and assessed the risk of bias. Data were pooled using a random-effects model. The rate of malignancy was calculated on resected nodules only (upper limit of true value); and considering all unresected nodules were benign (lower limit of true value). The protocol was registered in PROSPERO (CRD42019123114). Of 2937 retrieved studies, 27 were eligible. The meta-analysis was conducted on summary data of 3932 AUS/FLUS thyroid nodules with RFNA. RFNA cytology would reclassify into categories I through VI of Bethesda: 4% (3%, 5%), 48% (43%, 54%), 26% (20%, 32%), 4% (3%, 6%), 5% (3%, 6%), and 2% (1%, 2%) of AUS/FLUS nodules. Malignancy rates of resected nodules were 24% (9%, 38%), 4% (1%, 7%), 40% (28%, 52%), 37% (27%, 47%), 79% (69%, 90%), and 99% (95%, 100%) for categories I through VI of Bethesda. There was high heterogeneity in these data. RFNA reclassified two-thirds of the AUS/FLUS specimens into a more definitive cytological category, with a benign call rate of nearly 50% and a negative predictive value greater than 96%.

Clinical Effects of Microwave Ablation in the Treatment of Low-Risk Papillary Thyroid Microcarcinomas and Related Histopathological Changes.

ObjectiveThis study aimed to evaluate the feasibility and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) in the treatment of low-risk papillary thyroid microcarcinoma (PTMC), and to observe the histopathological changes after MWA.MethodsMWA was performed under ultrasound guidance for 73 unifocal PTMC patients without clinically cervical or distant metastasis. The target ablation zone exceeded the tumor edge (judged by contrast-enhanced US) to avoid marginal residue and recurrence. Ultrasound evaluation was performed at 1 day, 1, 3, 6, 12 and 24 months after treatment, and thyroid function evaluation at the first 6 months. Repeated fine needle aspiration cytology or core needle biopsy pathology was performed at 3 or 6 months after MWA to evaluate residual tumors. Any adverse event associated with MWA was evaluated.ResultsThe follow-up after MWA lasted 6 (6, 12) months. Tumor volume decreased significantly from 0.06 mm3 (0.04, 0.11 mm3) to 0.03 mm3 (0.00, 0.06 mm3) at 12 months after MWA (P< 0.001), with a median volume reduction ratio of 80.28% (-7.43, 100%) and 16 cases (21.92%) presenting complete remission. The largest diameter, volume and ablation energy were found to be different in patients with and without complete remission 12 months after MWA. On histopathological examinations, no atypical or malignant follicular cells were identified after thermal ablation. The most common pathological characteristics were fibroblastic proliferation (34/39, 87.18%) and chronic inflammation (32/39, 82.05%), followed by infarction (21/39, 53.85%). Five patients were transferred to thyroidectomy and 4 of them were confirmed with local recurrence and/or lymph node metastasis. Serum thyrotropin decreased transiently after MWA (P< 0.01) but normalized thereafter. No serious and permanent complications were reported.ConclusionsMWA is a safe and effective treatment for low-risk PTMC. Fibroblastic proliferation and chronic inflammation are the most common pathological changes after MWA of PTMC.

Можливості передопераційних та інтраопераційних методів діагностики вузлової патології щитоподібної залози

При вузловій патології щитоподібної залози (ЩЗ) важливо своєчасно встановити характер патологічного процесу, оскільки від цього залежить алгоритм лікування пацієнта. Основним та ефективним методом передопераційної діагностики залишається тонкоголкова аспіраційна пункційна біопсія (ТАПБ). Однак на цьому етапі не завжди вдається отримати інформативні результати, а також запобігти зайвих операцій або чітко виявити/виключити злоякісний процес. Зменшити частку неінформативних результатів у деяких випадках допомагає стрижнева біопсія голкою, яку пропонують виконувати як альтернативу повторної ТАПБ. Ще один підхід, який достатньо широко використовують для поліпшення перед­операційної діагностики вузлової патології ЩЗ, полягає у додатковому дослідженні з використанням специфічних молекулярних маркерів і тестів. Для ідентифікації доброякісних утворень найчастіше застосовують класифікатор експресії генів, а для виявлення злоякісного процесу — тест на наявність мутацій і генетичних перебудов. Оскільки навіть такий комплексний підхід не завжди дозволяє розмежувати доброякісні та злоякісні пухлини, актуальними залишаються інтраопераційні експрес-гістологічні дослідження (ЕГД). При цьому паралельне виконання ЕГД та інтраопераційної цитології підвищує ефективність інтраопераційної діагностики. Отже, спектр наданих методів широкий, тому в даному огляді були розглянуті особливості кожного підходу, зокрема, ефективність, можливості та обмеження, а також було показано, в яких ситуаціях доцільно проводити ті чи інші дослідження або їх комплекс.

1745P Prediction of BSRTC class of repeated FNA based on molecular testing result upon the first FNA

According to the 2017 bethesda system for reporting thyroid cytopathology (BSRTC), a repeat FNA is recommended for cytologically ND/UNS nodules and some cytologically AUS/FLUS nodules as well. This study would explore correlation between molecular testing upon the first FNA and BSRTC class of repeated FNA (Re-FNA).

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.

Malignancy outcomes and the impact of repeat fine needle aspiration of thyroid nodules with Bethesda category III cytology: A multicenter experience.

The clinical management of Bethesda III category thyroid nodules has some undefined points and differs among centers and conflicting malignancy rates are present in the literature. The aim of this study was to investigate the Bethesda category III thyroid nodule outcomes in our centers, to determine malignancy rates and also to evaluate clinical and sonographic features which may help to predict malignancy. This retrospective study included 333 patients with thyroid nodules who had Bethesda category III on fine needle aspiration (FNA) in three tertiary medical centers of Turkey. Among 333 patients, 302 had appropriate follow up. Eighteen patients received thyroidectomy after the first FNA, with a malignancy rate of 38.89% (7/18) and 284 patients received a second FNA. After the second FNA, thyroidectomy was performed in 80 patients and 41 patients needed the third FNA. Thirteen thyroidectomies were performed after the third FNA. Totally 111 patients received thyroidectomy with a malignancy rate of 48.65% (54/111) among patients with surgery and the lower bound was detected as 17.88% (54/302). Of these patients the malignancy rates of patients receiving thyroidectomy with two and three FNAs were 47.50% (38/80) and 69.23% (9/13), respectively. Hypoechogenicity, microcalcification, and irregular margin were found as good predictors for malignancy. We demonstrated that the malignancy rate was 48.65% in patients receiving thyroidectomy. We showed a higher malignancy rate than the traditionally rate of 5%-15%. This study showed that repeat FNAs decrease the rate of unnecessary surgery performed for benign lesions by increasing the rate of malignancy detection.

Diagnostic value of puncture feeling combined with BRAF V600E mutation in repeat US-FNA biopsy of Bethesda III thyroid nodules.

The diagnosis and treatment of Bethesda III thyroid nodules has always been controversial. Our aim is to study the value of puncture feeling combined with BRAF V600E mutation detection in the diagnosis of Bethesda III thyroid nodules in repeat fine needle aspiration (FNA). From January 1, 2017 to December 31, 2021, a total of 1,114 thyroid nodules were included, of which Bethesda III thyroid nodules accounted for 12.1%. We analyzed the correlation between puncture feeling and postoperative pathology. Then, the diagnostic value of puncture feeling in Bethesda III thyroid nodules and the mutation rate of BRAF V600E in repeated FNA and its correlation with puncture feeling were analyzed. The results showed that there was a significant correlation between puncture feeling and postoperative pathology in the 1114 thyroid nodules (P<0.001). Additionally, 93.4% (299/320) of the thyroid nodules with soft puncture feeling were benign, 89.0% (460/517) of the thyroid nodules with hard puncture feeling were malignant, and 93.1% (258/277) of the thyroid nodules with a puncture feeling of hard with grittiness were malignant. There was high consistency of puncture feelings among different operators (P<0.001). The distribution of puncture feeling between benign and malignant thyroid nodules was significantly different (P<0.001) in Bethesda III thyroid nodules. In the puncture feeling ROC curve of Bethesda III thyroid nodules based on pathology, the AUC was 0.895 (95% CI: 0.817-0.973, P<0.001). In repeat FNA, BRAF V600E was significantly correlated with puncture feeling (P<0.001). BRAF V600E mutation was found in 22 (68.8%) malignant nodules. Puncture feelings of hard and hard with grittiness were malignant risk factors. Repeated FNA and BRAF V600 mutation detection should be performed for Bethesda III thyroid nodules with a hard or hard with grittiness puncture feeling.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives: Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. Materials and Methods: A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. Results: The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). Conclusion: To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Outcome of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid fine-needle aspirations: A six-year institutional experience.

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). The goal of our study is to assess the outcome of cases classified as AUS/FLUS at our institution. AUS/FLUS cases were identified by computer searching of the thyroid fine-needle aspiration (FNA) cases performed between 2010 and 2016. Outcomes were categorized as: follow-up surgery, repeat FNA or no follow-up available. Demographics, ultrasound findings and FNA diagnostic criteria were reviewed for AUS/FLUS cases with follow-up surgical pathology diagnosis. Our AUS/FLUS thyroid FNA rate was 6% (117 out of 1984 FNAs). Only 15% of the AUS/FLUS cases had repeat FNA, while 41% underwent surgery. The risk of malignancy (ROM) for cases with follow-up surgery was 17%. When considering all AUS/FLUS cases, the ROM was 7%. Statistically, benign neoplasms were more likely to be single lesions on ultrasound comparing to malignant neoplasms, and to exhibit architectural atypia as opposed to non-neoplastic lesions on FNA. The malignancy rates among patients that directly went to surgical resection (17%) and patients having repeat FNA after the first AUS/FLUS diagnosis followed by surgery (29%) was not significantly different. However, repeat FNA was able to reclassify the majority of cases into more definitive categories. The outcome of the thyroid FNAs diagnosed as AUS/FLUS in our institution meets the benchmark statistics for AUS/FLUS rate and ROM. This study constitutes a valuable quality assurance measure and serves as a baseline for subsequent quality improvement.

The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management

Abstract Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct &amp;gt;500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response. This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now. MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.

Will Real Time Visualization of Needle in Target Thyroid Nodules Minimize False Negative FNA Results?

Abstract Introduction: Prevalence of thyroid nodules in the adult population based on detection by ultrasonography is about 20-76% of which only 5% account for thyroid cancer. All patients with a suspected thyroid nodule either on physical examination or noted incidentally on other imaging should be evaluated with thyroid ultrasound. Any thyroid nodule &amp;gt;= 1 cm on ultrasound should be investigated with FNAC. Ultrasound guided FNAC techniques are used to reduce false negative results. We present a patient with suspicious finding on initial thyroid ultrasound and subsequent negative FNAC presenting a few years later with papillary thyroid cancer. Case Presentation: A 32 y.o. female with history of thyroid nodule and thyroiditis presented to the endocrine clinic for follow-up of her thyroid nodule. 5 years ago, she was diagnosed with thyroid nodule, which was found on an ultrasound scan for workup of her dysphagia. The thyroid ultrasound then showed diffusely heterogeneous thyroid gland with an ill-defined area of decreased echogenicity in the right lobe and left superior lobe and possible nodule in the lower pole left thyroid. Blood work showed TSH of 1.71 (n 0.34-3.00 uIU/ml) and thyroid peroxidase antibody levels was 27.8 (n &amp;lt; 9.0 IU/ml). A CT scan of neck with contrast was done and no concerning mass was seen. The patient had a follow-up ultrasound after 8 months which showed small bilateral thyroid lesions, somewhat ill-defined. The patient had an FNA biopsy of the right thyroid nodule: the results were consistent with a benign follicular nodule. A follow-up thyroid ultrasound was done in a year, and the findings were unchanged. The patient came back 3 years later for follow-up with complaints of a new palpable nodule in the neck. Ultrasound showed unchanged right thyroid nodule and some new cervical adenopathy. The ultrasound showed a 2.2 cm heterogeneous lymph node with punctate echogenic foci along the right lateral margin of the right internal jugular vein at the level of the thyroid gland, Subsequently FNA biopsy of the right cervical node and right thyroid node were done. The cells from lymph nodes were positive for malignancy and cells from the right thyroid nodule were atypical. Overall the appearance was consistent with papillary thyroid carcinoma. Subsequently the patient underwent total thyroidectomy and right modified lymph node dissection and the pathology results came back as multifocal papillary thyroid cancer right side 1.2 cm and left side 0.4 cm, with metastasis to 2 lymph nodes. Conclusion: The reported false negative rate of ultrasound-guided FNAC is variable. Success of US-FNA depends on experience of operator and cyto-pathologist and the intrinsic nature of the nodule. Malignancy rates of only 1-2% are reported with repeat FNA in prior benign nodules. Good FNA techniques and real-time visualization of needle in target nodules can further decrease false negatives.

Thyroid Abscess After FNA Biopsy: A Case Report

Introduction: FNA biopsy of thyroid nodules is a common bedside procedure that rarely causes serious complications. Thyroid abscess is a rare complication of FNA that requires prompt diagnosis and treatment. We present a case of a thyroid abscess occurring 4 weeks after FNA in a 46 year old female, treated successfully with surgery. Clinical Case: A 46 year old woman with history of acne presented with dysphagia, right sided neck pain and swelling 4 weeks after FNA of a 4.8cm right thyroid nodule with benign cytology. On physical examination, the right thyroid lobe appeared larger and was tender to palpation. The patient was afebrile. Laboratory evaluation was significant for acutely low TSH 0.06 uIU/mL [0.50 - 6.00 uIU/mL], thrombocytosis 547 K/uL [140 - 400 K/uL] and marked elevated sedimentation rate 98 mm/hr [0 - 20mm/hr]. Interestingly, she had a normal leukocyte count of 9.8 K/uL [4.00 - 10.80 K/uL]. US imaging showed acute increase in size of the right thyroid nodule to 7.6cm. CT neck confirmed a large, partially cystic right thyroid mass and further showed mass effect on surrounding structures and mild stranding in the subcutaneous fat. The patient elected for surgical treatment rather than repeat FNA with drainage of fluid components. Right thyroid lobectomy was planned but converted to surgical abscess drainage with subtotal thyroidectomy due to intense inflammatory changes in the neck. A large amount of purulent material was drained and sent for cultures, which grew multiple Staphylococcus species and Propionibacterium acnes. Surgical pathology showed granulation and connective tissue including skeletal muscle tissue with marked active chronic inflammation, micro abscess formation, few multinucleated giant cells, and fibrosis. Following surgery, TSH normalized, and the patient reported immediate improvement in symptoms of neck fullness, pain, and dysphagia. She was discharged home on post operative day one with a two week course of oral Augmentin 875mg twice daily. 6 weeks post operatively the patient remains symptom free in her usual state of health. Conclusion: Thyroid abscess following FNA is a rare occurrence with few reported cases in the literature. Because of its rarity, diagnosis and treatment may be delayed, resulting in a life-threatening emergency. Both repeat needle aspirations and surgical management, combined with culture directed antibiotics, are acceptable methods for treatment. Immunocompromise, not present in our patient, is the main risk factor reported for thyroid abscess. Propionibacterium and Staphylococcus commonly cause acne, which may have increased our patient’s risk of infection. Our case highlights the importance of maintaining a high level of clinical suspicion for abscess in patients who develop neck pain and swelling following FNA, even in the absence of significant risk factors, in order to facilitate prompt diagnosis and treatment.

Molecular Testing Can Impact Clinical Decision Making and Therapeutic Approach in Thyroid Cancer

Abstract We present the case of a patient with a thyroid nodule of indeterminate cytology on fine-needle aspiration (FNA) biopsy whose molecular profile significantly impacted clinical decision making and treatment. A 77-year-old woman with a history of hyperthyroidism presented to our clinic for a second opinion regarding management of a recently discovered right thyroid nodule. Thyroid ultrasound (US) 6 months prior showed a 2.6 cm, heterogeneous nodule with peripheral vascular flow; not characterized based on ATA or TIRADS criteria. Family history was significant for papillary thyroid cancer in daughter at age 35 years. The patient had no history of head or neck irradiation. She had no compressive symptoms or manifestations of hyper or hypothyroidism. FNA biopsy of the nodule was done twice in 4 months, and cytology was consistent with follicular lesion of undetermined significance (FLUS, Bethesda III) in both occasions. Repeat FNA biopsy at our institution showed follicular neoplasm (FN, Bethesda IV), and molecular testing using ThyroSeq v3 was positive for HRAS and TERT mutations, which conferred a &amp;gt;95% risk of cancer. Patient was referred to Endocrine Surgery and total thyroidectomy was recommended based on nodule’s molecular profile and associated hyperthyroidism. No suspicious lymph nodes were noted on preoperative US. No gross local invasion observed intraoperatively. Surgical pathology showed intrathyroidal FN without invasion. However, given disparity between pathology findings and molecular markers, specimen was sent for outside blinded pathology review which concluded to be a follicular thyroid carcinoma with capsular invasion but no angiolymphatic invasion or extrathyroidal extension. Based on these findings, along with the known HRAS and TERT mutations, it was advised to proceed with radioiodine (RAI) remnant ablation. Patient was prepared with thyrotropin alfa and received 29 millicuries of RAI. Post-treatment scan showed focal neck uptake consistent with ablated thyroid tissue and no distant metastases. Patient had an excellent response to therapy, without evidence of biochemical or structural recurrence 2 years later. Molecular testing of cytologically indeterminate thyroid nodules (Bethesda III, IV) has become an important tool to better refine risk of malignancy. Furthermore, the presence of certain mutations or mutation combinations, such as RAS and TERT co-occurrence, suggests a more aggressive behavior associated with worse outcomes. As a result, a more aggressive approach might be recommended. Our case illustrates how molecular testing can significantly influence therapeutic decisions such as extent of surgery, interpretation of surgical pathology and/or use of RAI. Further research is needed to determine if its routine use may lead to improved cancer-related outcomes or if it is cost-effective in the risk stratification of differentiated thyroid cancer.

Clinicopathologic Characteristics of Thyroid Nodules Positive for PTEN Mutations on Preoperative Molecular Testing

Somatic and germline mutations of PTEN tumor suppressor gene are associated with follicular-pattern thyroid tumors and PTEN Hamartoma Tumor Syndrome (PHTS). The incidence of cancer in thyroid nodules positive for PTEN mutations on fine-needle aspiration (FNA) is not well defined. The aim of this study was to characterize diagnostic and phenotypic features of thyroid nodules with preoperatively detected PTEN mutations and their impact on management. Thyroid nodules with PTEN mutations on ThyroSeq v3 GC testing of FNA and core needle biopsy specimens from November 2017 to July 2020 were identified from the ThyroSeq Molecular Database. Demographic and clinicopathologic data were obtained through retrospective chart review. We identified 49 PTEN mutation-positive nodules from 48 patients. Patients were 57 years old on average (range 14-88) and 80% female. Cytology was predominantly indeterminate (73% atypia of undermined significance, 18% follicular neoplasm). There were 18 (29%) frameshift, 6 (10%) splice site, and 39 (62%) single nucleotide variant PTEN mutations. Fourteen (29%) nodules had two PTEN mutations, 5 (10%) had copy number alterations, and single cases had concurrent BRAF K601N, EZH1, and NRAS mutations. Surveillance was pursued for 27 (56%) and surgery for 21 (44%) patients (16 lobectomies, 5 total thyroidectomies). There were 14 follicular adenomas (FA), 4 oncocytic FA’s, 1 oncocytic hyperplastic nodule, and 1 encapsulated follicular variant papillary thyroid carcinoma (EFVPTC). The EFVPTC had two low-frequency PTEN mutations, PTEN locus loss, an NRAS mutation, and was a low-risk tumor with capsular but no angiolymphatic invasion. Four (8.3%) patients had confirmed or suspected PHTS, all with multiple nodules. Two had surgery finding no malignancies (2 FA). One PHTS patient had a prior thyroidectomy for a MET mutation-positive nodule that was follicular carcinoma. On US, the mean nodule size of patients who had surgery was larger than the surveillance group (3.2 cm vs. 2.3 cm, p=0.02) but there was no difference in TI-RADS level (p=0.54). There was no difference in mean nodule size (3.5 cm vs. 2.6 cm, p=0.35) or TI-RADS level (p=0.81) between PHTS and non-PHTS patients. Among surveillance patients, follow-up US was done at 1 year in 13/19 (68%) and 2 years in 3/6 (50%) of eligible cases. Only 1/19 (5%) underwent repeat FNA for increased nodule size. No thyroid malignancy was found with a mean of 1.75 years of follow-up (range 1.00-2.78). The EFVPTC patient had no recurrence after 1.05 years of follow-up. In summary, thyroid nodules with isolated somatic PTEN mutations are primarily benign and can be safely followed with serial imaging. Nodules with multiple PTEN mutations were only associated with malignancy when accompanied by an additional NRAS mutation. About 8% of patients with PTEN mutations may be PHTS patients who may be at greater risk for malignancy.

Mystery Case of Parathyroid Carcinoma Masquerading as a Thyroid Nodule

Introduction: Parathyroid carcinoma is a rare malignancy with a prevalence of 0.005%. Patients typically present with symptoms of hypercalcemia and elevated parathyroid hormone (PTH) levels. Non-functional parathyroid carcinoma presenting with neck pain and normal calcium is a unique and challenging entity. We describe a challenging case of normocalcemic parathyroid carcinoma presenting as neck pain. Case Description: A 59-year old woman with a history of asthma, type 2 diabetes, and tobacco use presented with neck pain and swelling worsening over months. On physical exam, she was noted to have right-sided thyroid mass. CT scan of the neck showed an enlarged thyroid gland with a 1.6 cm nodule with evidence of the trachea’s compression. Subsequent thyroid US revealed a 2.1 cm dominant solid, hypoechoic nodule in the right thyroid lobe. Initial testing revealed normal calcium levels; however, PTH level was not available. FNA of the nodule was non-diagnostic with subsequent repeat FNA interpreted as benign mass. Due to suspicious imaging features and significant neck discomfort, she underwent right hemithyroidectomy. During the surgery, the nodule was noted to be invasive with evidence of extrathyroidal extension. Postoperatively calcium was 8.9 mg/dl (8.6–10.4 mg/dl), ionized calcium 4.7 mg/dl (4.8–5.6mg/dl), PTH 48 pg/mL (14–64 pg/ml), and vitamin D25OH 48 ng/dL (30-100ng/dl). TSH was mildly elevated at 4.59 uIU/ml (0.27–4.2 uIU/ml) with free T4 of 1.09 ng/dl (0.93–1.70ng/dl). The preliminary pathology report described follicular thyroid carcinoma; however, immunostains failed to confirm primary thyroid cancer. The lesion was negative for TTF-1, PAX8, TG, CEA, calcitonin, chromogranin, and synaptophysin. The tumor was strongly positive for GATA3, PTH and positive in nuclear staining for parafibroma. The specimen was evaluated by two pathologists who favored the diagnosis of parathyroid carcinoma. A separate incidental microscopic 4mm papillary thyroid carcinoma (PTC) was found and tested positive for BRAF mutation. Genetic testing for CDC73 was negative. PET scan showed increased uptake in the right thyroid bed. Given microscopic PTC and mildly elevated TSH, she was started on levothyroxine. The patient recovered successfully after the surgery with the resolution of symptoms. She was evaluated by an oncologist, and adjuvant radiation therapy was recommended. Conclusion: Non-functional parathyroid carcinoma is a unique entity, and its diagnosis may be delayed given an atypical presentation and normal endocrine function. Differentiation between nonfunctioning parathyroid carcinoma, parathyroid adenoma, and thyroid disease based on location and proximity to the thyroid may be challenging. Although concomitant thyroid disease is not uncommon, synchronous thyroid cancer is very rare.

Comparison of Four Ultrasonography-Based Risk Stratification Systems in Thyroid Nodules with Nondiagnostic/Unsatisfactory Cytology: A Real-World Study.

Simple SummaryAlthough ultrasound-based risk stratification systems (RSSs) including Thyroid Imaging, Reporting and Data Systems (TIRADSs) may play an important role in triaging nodules with nondiagnostic/unsatisfactory cytology, no previous studies have compared ultrasound-based RSSs for these nodules. In this retrospective, longitudinal, real-world study in Korea including 1143 thyroid aspirations with nondiagnostic/unsatisfactory results from 1125 patients, further diagnostic evaluations, including repeat fine-needle aspiration, were conducted more commonly as the categories of ultrasound-based RSSs increased. The American Thyroid Association (ATA) guidelines, Korean (K)-TIRADS, and American College of Radiology (ACR) TIRADS were more competent in predicting malignancy from nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although it was also helpful, demonstrated less effective diagnostic performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, where iodine intake is more than adequate. These findings have implications for developing and verifying universal guidelines for the ultrasound-based stratification of thyroid nodules and applying these guidelines to nondiagnostic/unsatisfactory nodules.We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87–3.00% in EU-TIRADS 3–4. In the other systems, the minimum malignancy rate was 14.29–16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of >5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022; all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.

Repeat Fine Needle Aspiration Cytology Refines the Selection of Thyroid Nodules for Afirma Gene Expression Classifier Testing.

Background: Molecular testing (MT) refines risk stratification for thyroid nodules that are indeterminate for cancer by fine needle aspiration (FNA) cytology. Criteria for selecting nodules for MT vary and remain largely untested, raising questions about the best strategy for maximizing the usefulness of MT while minimizing the harms of overtesting. We used a unique data set to examine the effects of repeat FNA cytology-based criteria for MT on management decisions and nodule outcomes. Methods: This was a study of adults (age 25-90 years; 281 women and 72 men) with cytologically indeterminate (Bethesda III/IV) thyroid nodules who underwent repeat FNA biopsy and Afirma Gene Expression Classifier (GEC) testing (N = 363 nodules from 353 patients) between June 2013 and October 2017 at a single institution, with follow-up data collected until December 2019. Subgroup analysis was performed based on classification of repeat FNA cytology. Outcomes of GEC testing, clinical/sonographic surveillance of unresected nodules, and histopathologic diagnoses of thyroidectomies were compared between three testing approaches: (i) Reflex (MT sent on the basis of the initial Bethesda III/IV FNA), (ii) SemiRestrictive (MT sent if repeat FNA is Bethesda I-IV), and (iii) Restrictive (MT sent only if repeat FNA is Bethesda III/IV) testing approaches. Results: Restricting MT to nodules that remain Bethesda III/IV on repeat FNA would have missed 4 low-risk cancers and 3 noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) (collectively 2% of the test population) but would have avoided diagnostic surgery for 42 benign nodules (12% of the test population). The Restrictive testing strategy was more specific (delta 0.126 confidence interval [CI 0.093 to 0.159] and 0.129 [CI 0.097 to 0.161], respectively) but less sensitive (delta -0.339 [CI -0.424 to -0.253] and -0.340 [CI -0.425 to -0.255], respectively) than the Reflex and SemiRestrictive approaches for detecting NIFTP or cancer. Conclusions: Repeat FNA cytology can guide the selection of cytologically indeterminate thyroid nodules that warrant MT. The Restrictive model of performing Afirma GEC only on nodules with two separate biopsies showing Bethesda III/IV cytology would reduce the rate of diagnostic surgery for histologically benign nodules while missing only rare low-risk tumors. Given the low but nontrivial risks of thyroidectomy, the higher specificity of the Restrictive testing approach disproportionately outweighs the potential harms.

Histopathologic and clinical outcomes of Milan System categories “non-diagnostic” and “non-neoplastic” of salivary gland fine needle aspirations

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) specifies six categories with estimated risks of malignancy (ROM) and suggested management. The estimated ROM is 25% for Non-Diagnostic (ND) category, and 10% for Non-Neoplastic (NN). This study aimed to investigate histopathologic and clinical outcomes of MSRSGC categories ND and NN at the authors' institution. Cytopathology fine needle aspiration reports from 2008-2020 were searched for the word "salivary", "parotid", and "submandibular". Cases fitting Non-Diagnostic (ND) and Non-Neoplastic (NN) categories were identified. Follow-up cyto-/histopathologic and clinical data were extracted. There were 43 ND and 46 NN cases. The average age was 58.3 years. Neoplastic lesions were found in 13 of 43 (30%) ND and 3 of 46 (6.5%) NN. The rate of malignancy in ND category was 14.0% (6/43) and 0% (0/46) in NN category. Four cases in ND (9.3%) and 6 (13.0%) in NN had no neoplasm and instead had an underlying reactive condition (e.g., chronic sialadenitis) or inflammatory lesion (e.g., lymphoepithelial cyst) on histologic follow-up. There was no follow-up pathology in 46.5% NDs (20/43) and 82.6% NNs (38/46); however, no lesions were apparent clinically with a mean follow-up of 3 years and 1.5 years, respectively. MSRSGC categories ND and NN are helpful for reporting salivary gland FNA results. With proper clinical and radiologic correlation, ROM of NN is low; however, ROM of ND remains significant. Repeat FNA after correlation for ND cases seems prudent as neoplasms and malignancies may have gone undetected.