Diagnostic Lobectomy Research Articles

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.

Monitoring Outcomes of Indeterminate Thyroid Nodules and Predictive Capabilities of Molecular Testing.

This study aimed to compare the effectiveness of reflex molecular testing at identifying thyroid malignancy in indeterminate thyroid nodules (ITNs) since its implementation at our institution. Identified all ITNs at our institution from January 2010 to October 2020. Calculated the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ThyroSeq since the initiation of universal reflex testing of all first-time ITNs beginning in March 2016. Analyze effect on frequency of diagnostic surgeries. Study group: March 2016 to October 2020, 378 ITNs underwent ThyroSeq (318 Bethesda III and 60 Bethesda IV). Mean age 52 years, 35.9% male, 61.1% female. 145 surgically excised with overall resection rate of 38.4% (III: 32.7%; IV 68%). Final histology: 49 malignant with overall rate of malignancy (ROM) of ITNs at 33.8% (III: 31.7%; IV: 39%). ThyroSeq sensitivity for ITNs at 84% (III 78.8%, IV 93.8%). ThyroSeq NPV for ITNs at 86% (III 84%, IV 93.3%). ThyroSeq specificity for ITNs at 52% (III 50.7%, IV 56%). ThyroSeq PPV for ITNs at 47% (III 42.6%, IV 57.7%). Control group: From January 2010 to February 2016 there were 242 ITNs (152 Bethesda III, 90 Bethesda IV). Mean age 52.6 years, 25.8% male, 74.2% female. 157 cases were surgically excised, with an overall resection rate of 64.9% (III: 57.2%; IV: 77.8%). Final histology: 32 malignant, with overall ROM of ITNs at 20.4% (III: 27.6%; IV: 11.4%). The initiation of universal Thyroseq (sensitivity 84% and NPV 86%) of ITNs at our institution has significantly decreased our percentage of diagnostic lobectomies, with a decreased resection rate of 26.5%.

Malignancy Risk of Follicular Neoplasm (Bethesda IV) With Variable Cutoffs of Tumor Size: A Systemic Review and Meta-Analysis.

The decision on diagnostic lobectomy for follicular neoplasms (FN) is challenging. This meta-analysis investigates whether an appropriate size cutoff exists for recommending surgery for thyroid nodules diagnosed as FN by fine needle aspiration. The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched for studies reporting the malignancy rate of FN/suspicious for FN (FN/SFN) according to tumor size, using search terms "fine needle aspiration," "follicular neoplasm," "lobectomy," "surgery," and "thyroidectomy." Fourteen observational studies comprising 2016 FN/SFN nodules with postsurgical pathologic reports were included, and 2 studies included malignancy rates with various tumor sizes. The pooled malignancy risk of FN/SFN nodules according to size was: odds ratio (OR) 2.29 (95% CI, 1.68-3.11) with cutoff of 4 cm (9 studies), OR 2.39 (95% CI, 1.45-3.95) with cutoff of 3 cm (3 studies), and OR 1.81 (95% CI, 0.94-3.50) with cutoff of 2 cm (5 studies). However, tumors ≥2 cm also showed a higher risk (OR 2.43; 95% CI, 1.54-3.82) based on the leave-one-out meta-analysis after removal of 1 influence study. When each cutoff size was evaluated by summary receiver operating characteristic (sROC) curves, the cutoff of 4 cm showed the highest summary area under the curve (sAUC, 0.645) compared to other cutoffs (sAUC, 0.58 with 2 cm, and 0.62 with 3 cm), although there was no significant difference. Although the risk of malignancy increases with increasing tumor size, the risk remains significant at all tumor sizes and no cutoff limit can be recommended as a decision-making parameter for diagnostic surgery in Bethesda IV thyroid nodules.

Clinical utility of a microRNA classifier in cytologically indeterminate thyroid nodules with RAS mutations: A multi-institutional study

BackgroundMolecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules. MethodsWe performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT–ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy. ResultsWe identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR– (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR– groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively. ConclusionAlthough testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.

Malignancy risk in Bethesda class IV thyroid nodules in an iodine deficient region.

According to the latest guidelines, in patients with high-risk nodules with indeterminate cytology, diagnostic lobectomy should be the preferable surgical approach in the absence of factors that suggest a total thyroidectomy. This retrospective observational study has as its main aim the evaluation of the cases that underwent surgery, for Bethesda class IV nodules in our iodocarent geographical area. Particular attention was paid to carcinoma incidence, preoperative nodule size, histological characteristics of the neoplasm, surgical approach and eventual need of radiometabolic treatment. A total of 320 patients were included that underwent surgery for Bethesda IV nodules, between January 2010 and December 2020, at the General Surgical Clinic of the University Hospital of Parma, Italy. A total of 230 total thyroidectomies (71.9%) and 90 lobectomies (28.1%) were performed. Our data showed a strong impact of the 2015 ATA Guidelines on the surgical approach choice, with a progressive propensity towards a conservative approach and an increase of lobectomies from 7.2% to 41.5% after the new guidelines introduction. However, in our sample the percentage of lobectomies remains below 50%; this data is certainly influenced by the number of cases of multinodular pathology, often bilateral, in our geographical area. The nodules malignancy rate resulted 28.8%. Our data showed that increasing size correlated with an increasing malignancy rate (P<0.01), and follicular carcinomas were found to be larger than papillary carcinomas (P<0.001). A statistically significant correlation also emerged between nodule size increase and local/lymphovascular invasion (P<0.05). On the other hand, there was no statistically significant correlation between nodule size and multifocality, and between nodule size and presence of lymph node metastases. Out of the patients where it was possible to find this data, 66% underwent radioiodiometabolic treatment: 59% with papillary carcinoma, and 85% with follicular carcinoma. In patients with Bethesda IV thyroid nodules, diagnostic lobectomy should be the preferable surgical approach in absence of factors that suggest total thyroidectomy. In our opinion, total thyroidectomy remains the first choice in large nodules (≥4 cm) as these nodules have a high malignancy rate, greater local/lymphovascular invasion and a consequent frequent indication for post-operative radiometabolic treatment.

Lobectomy for Suspected Lung Cancer Without Prior Diagnosis

BackgroundWe describe use, patients, and outcome of diagnostic lobectomy for suspected lung cancer without pathologic confirmation. MethodsA retrospective review of consecutive lobectomy or bilobectomy for suspected or confirmed primary pulmonary malignancy was conducted using our participant’s sample of The Society of Thoracic Surgeons database. Surgeons performed lobectomy based on clinical diagnosis or confirmation on a biopsy specimen. Lung cancer confirmed by biopsy specimen was compared with cases clinically suspected. Univariate and multivariate analyses identified variables associated with lobectomy without biopsy specimen confirmation. ResultsAmong 2651 lobectomies performed between 2006 and 2019 in 2617 patients, lung cancer was confirmed by preoperative biopsy specimen in 51.6% (1368 of 2651) or was clinically suspected before the operation in 48.4% (1283 of 2651). The intraoperative biopsy specimen in 585 of 1283 cases (45.6%) proved lung cancer before lobectomy, whereas lobectomy proceeded in 698 cases (54.4%) without a diagnosis. Final pathology proved lung cancer in 90% (628 of 698) without a diagnosis before lobectomy and nonmalignant disease in 10% (70 of 698). Nonneoplastic pathology included granulomas (30 of 70 [43%]), pneumonia (12 of 70 [17%]), bronchiectasis (7 of 70 [10%]), and other lesions (21 of 70 [30%]). Operative mortality was 0.94% (25 of 2651) for the cohort and 1.0% (7 of 698) for diagnostic lobectomy only. Multivariate analysis identified patient age, type of lobectomy (right middle lobe), and the intermediate study tercile as associated with diagnostic lobectomy. ConclusionsLobectomy for suspected lung cancer without diagnosis is common, represents practice variation, and infrequently (10% diagnostic, 2.6% all lobectomies) removes nonmalignant disease. Tissue confirmation before lobectomy is preferred, particularly when operative risk is increased. Diagnostic lobectomy is acceptable in carefully selected patients and lesions.

Indeterminate thyroid cytology in an iodine-deficient population: Prevalence, operation rate, risk of malignancy anddiagnostic value of thyroid scintigraphy and 18F-FDG PET imaging parameters.

Patients with indeterminate thyroid cytology often have a diagnostic hemithyroidectomy. The role of molecular imaging, particularly fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), is controversial, and demographic variations in tumor prevalence and histology influence test performance and clinical utility. We retrospectively assessed the prevalence of indeterminate thyroid cytology and the malignancy rate in patients from an iodine deficient area, and evaluated the diagnostic value of preoperative thyroid scintigraphy and 18F-FDG PET/CT among operated patients. From 2006-2018, all patients with indeterminate thyroid cytology from the North Denmark region were included in the study (population 600,000).Clinical data, including operation rate, preoperative molecular imaging, and histopathological diagnosis, were retrieved. The results from preoperative thyroid scintigraphy and 18F-FDG PET/CT-scanning were compared to the final histopathological diagnosis. Four hundred and thirty-three patients were found with indeterminate thyroid cytology.The main registered reasons for conducting a fine needle aspiration biopsy (FNAB) were "cold nodule", goiter or a palpable nodule (n=312). In 40 patients (9%), FNAB was registered as conducted due to a PET incidentaloma. Four hundred and two patients (93%) underwent diagnostic lobectomy, and this population formed the study population for the following explorative study: One-hundred and two patients (25%) had a malignant diagnosis. In 226 (56%) and 51 (25%) patients, respectively, preoperative thyroid scintigraphy and 18F-FDG PET/computed tomography (CT) was performed. Among patients with a final malignant disease who had a thyroid scintigraphy (40 patients), a cold nodule was seen in 90% of cases; one (atypical) patient presented a warm nodule. Among patients with a final malignant disease 16 patients (16%) had a 18F-FDG PET (incl. 3 missing PET scans). Among the 51 patients with preoperative 18F-FDG PET/CT, no difference in the PET-derived parameters was found between benign (n=33) and malignant tumors (n=13). The prevalence of malignancy (25%) was comparable with that in other studies. In patients with a preoperative thyroid scintigraphy, 90% of malignant cases had a cold nodule on scintigraphy. In patients with a preoperative PET/CT-scanning presenting focal 18F-FDG-uptake, PET-derived parameters had no diagnostic value. However, the diagnostic value of 18F-FDG-avidity vs. non-avidity needs to be addressed prospectively.

Thyroid nodules: Global, economic, and personal burdens.

Thyroid nodules have garnered attention due to changes in population surveillance systems and rising concerns about the associated financial burden on healthcare systems, payers, and patients. In this review, we find that prevalence rates vary widely based on method of detection and may particularly pronounced in asymptomatic patients undergoing routine screening. Incidence rates may be particularly rising in lower-income and middle-income countries and may be declining in higher-income countries. Despite high incidence rates, survival rates continue to be as high as 97% for papillary thyroid cancer. Over the last few decades, thyroid nodule workup and management has grown more sophisticated with the advent of fine-needle aspiration biopsy, specialized biomarkers, and molecular testing. However, gaps remain in risk stratification that can lead to substantial costs of care. Certain molecular tests, such as the Afirma Gene Sequencing Classifier can lead to a cost per diagnosis of $17,873 while achieving only mild decreases in diagnostic lobectomies for patients (11.6% to 9.7% in one study). Out-of-pocket costs associated with thyroid nodule management continue to drive significant financial toxicity for patients, especially for individuals with thyroid cancer. Financial toxicity has been defined as a term that describes how direct and indirect medical costs of cancer care strain patients and households via decreased income, assets, and spending on basic necessities. Recent studies suggest that such toxicity can lead to adverse financial outcomes, such as foreclosure and bankruptcy. Additional cost-effectiveness analyses are needed to improve existing thyroid nodule management systems and new clinical tools are needed to avoid unnecessary workup and management.

PSAT293 Uncommon Presentation of Hashimoto Thyroiditis

Abstract Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in developed countries, which presents with diffuse goiter or atrophic gland. Staii et al. reported a 7.4 per cent prevalence of localized HT diagnosed by fine needle aspiration (FNA) cytology in euthyroid patients during thyroid cancer screening. Although, a transient solitary focal presentation of HT in euthyroid patients has not been described so far. Here we describe a case of localized HT presented with a thyroid mass peripartum, which progressed into diffuse thyroiditis after FNA biopsy. A 27-year-old woman who is 10-day post-partum presents to our endocrine clinic for thyroid mass evaluation noticed by her spouse a few weeks before delivery. The patient has no hypothyroid, hyperthyroid, or mass effect symptoms. On the physical exam: BP 100/64 mmHg, Temp 36.5 C, HR 76 bpm, RR 20 bpm, BMI 24.6 kg/m2. There is a palpated 5-cm non tender right thyroid nodule. Thyroid stimulating hormone (TSH) is 2.04 uiu/ml (N: 0.3-4.2). Thyroid ultrasound (US) shows a 47×25×31 mm right hyperechoic nodule with some septation of hypoechoic areas. It has thin continuous halo, smooth but lobulated margins and Grade 3 doppler. No microcalcification is seen. Left lobe and isthmus are homogenous with no nodules. There is a reactive lymphadenopathy on the right cervical region. An ultrasound guided-FNA cytology shows clusters of follicular cells forming micro- and macro-follicles with background of hemorrhage but no colloid is seen. Cytology is suspicious of a follicular neoplasm, Bethesda IV category. Diagnostic Lobectomy is discussed but the patient opts for repeat biopsy at a different facility. She presents with a similar cytology result after 3 months. She elects follow up as she remains asymptomatic. After 6 months follow up, she has spontaneous reduction of the nodule size and it is not palpated. Neck US shows diffusely heterogeneous gland with hypoechoic areas and significant reduction in size of the right hyperechoic nodule to 22×14×11 mm. Ultrasound findings are suggestive of thyroiditis and further labs are requested. Thyroid peroxidase antibodies &amp;gt;1000 iu/mL (N: &amp;lt;5.61), anti-thyroglobulin antibodies 161.71 iu/mL (N: &amp;lt;4.11), TSH 3.4 uiu/ml (N: 0.35-4.9), free T4 is 10.38 pmol/L (N: 9-19), thyroglobulin 76.76 ng/mL (N: 3.5-77). These findings suggest that HT may present as a localized form in euthyroid phase and should be considered in the differential diagnosis of thyroid nodule. Serologic evidence of HT and serial US follow-up should be recommended instead of other unnecessary procedures. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP493 Malignant Struma Ovarii with Papillary Thyroid Carcinoma and concomitant High Risk Thyroid Nodule

Abstract Introduction Struma ovarii is a rare teratoma consisting of &amp;gt;50% thyroid tissue. Malignant transformation very seldomly occurs; most pathology shows papillary thyroid carcinoma. The risk and prevalence of concurrent thyroid gland neoplasm is unclear. Thyroid cancer surveillance post-oophorectomy in these patients may be pertinent but has not yet been established. Case Report A nulliparous 54 year-old woman with one year of menopause without HRT had pelvic and back pain. Imaging detected bilateral ovarian teratomas. Pathology from laparoscopic bilateral salpingo-oophorectomy revealed a 10.7×9.9×10.9cm noninvasive struma ovarii with focal papillary thyroid carcinoma of the left ovary and a benign teratoma of the right ovary. Importantly, the patient had a known thyroid nodule. Two years prior, a FNA of the 1.4cm hypoechoic, hypervascular nodule in the left lower pole yielded benign (Bethesda 2) cytology. After struma ovarii resection, thyroid ultrasound showed highly suspicious TIRAD5. She denied symptoms of hyper- or hypothyroidism and had a normal TSH. She consequently underwent two FNA biopsies, both of which were non-diagnostic. The patient deferred further attempts. History of an initial benign biopsy and stability of the nodule size provide some reassurance. With the patient's reluctance for surgery, serial thyroglobulin (Tg) and ultrasounds will be followed. Post-operative Tg was normal with negative Tg antibody. If Tg becomes markedly elevated, a thyroidectomy will be indicated. Discussion Given the TIRAD5 nodule, this patient's risk of thyroid malignancy is 60-70%. This is compounded with her setting of malignant struma ovarii, which may imply genetic predisposition for thyroid carcinogenesis. Since cytology could not be obtained on the two recent biopsies, definitive pathology by diagnostic lobectomy or thyroidectomy may be considered. A total thyroidectomy would provide the advantage of following Tg for cancer surveillance of both thyroid and ovarian malignancies. There is scant evidence on the treatment of malignant struma ovarii. A few small case series and a pooled review of 57 cases of low-risk (confined to the ovary) malignant struma ovarii in which 50 patients did not undergo thyroidectomy/I-131 ablation showed only a 7.5% recurrence rate at 25 years (Marti et al Thyroid 2012 Apr; 22 (4): 400-406). Hence, this study recommends reserving prophylactic thyroidectomy for patients with extra-ovarian extension or metastases. Treatment of malignant struma ovarii may be extrapolated from those used in differentiated thyroid cancer; high-risk lesions would be those measuring &amp;gt;4cm, have local or distant invasion, or have a BRAF mutation (indicating an aggressive tumor). In conclusion, conservative measures of the thyroid gland with a suspicious nodule may be acceptable in patients with noninvasive malignant struma ovarii, provided strict adherence to cancer surveillance of Tg with both thyroid and pelvic sonography. Presentation: No date and time listed

How Effective is the Use of Molecular Testing in Preoperative Decision Making for Management of Indeterminate Thyroid Nodules?

We performed Thyroseq v2 molecular testing on indeterminate thyroid nodules and evaluated whether they underwent a management change from the standard of thyroid lobectomy. We conducted a retrospective analysis of all indeterminate thyroid nodules that underwent Thyroseq v2 molecular testing from 2014 to 2019 at a large academic center. Pathology was reviewed by thyroid cytopathologists. Thyroseq results were reported benign (malignancy probability less than 10%) or suspicious (malignancy probability greater than 30%). The primary endpoint was a management change from a diagnostic lobectomy. A total of 142 nodules were included: 113 (80%) Bethesda III and 29 (20%) Bethesda IV. Seventy-three nodules underwent surgical management and 69 did not. We noted a change in management in 64% (91/142) of nodules. Patients who underwent a change in management to no surgery had a significantly higher rate of benign Thyroseq result than those without a change (75.8% vs. 49.0%, p = 0.001). On logistic regression analysis, a benign Thyroseq result was a positive independent predictor of a change to no surgery (OR 3.87, 95% CI 1.69-8.89). Nodule size, multiple nodules, compressive symptoms, and history of hypothyroidism were not significant.Of the 91 patients who underwent a management change, 71% (65/91) did not undergo surgery. On follow-up (average 985 ± 615days), 12% (8/65) of those nodules were growing or developed suspicious features requiring surgery. Molecular testing helped avoid surgery in almost half our population with indeterminate thyroid nodules, and benign results may help avoid surgery in asymptomatic patients with indeterminate thyroid nodules.

Benign cytology does not rule out malignancy in thyroid nodules larger than 4cm.

For thyroid nodules ≥4cm, the accuracy of fine-needle aspiration biopsy (FNAB) is controversial and the approach is unclear. We aimed to compare FNAB and operation of thyroid nodules and to determine the accuracy of FNAB. All total thyroidectomies performed between January 2015 and December 2021 were evaluated. In the study, 301 patients were included. Euthyroid patients with preoperative thyroid ultrasound, FNAB results and operation results were recorded retrospectively. The nodule size was <4cm in 79.1% of the patients, and ≥4cm in 20.9%. In patients with nodule size ≥4cm, 50.8% of FNAB results were reported as benign, and 43.7% of these patients were found to be malignant at the end of the operation. In nodules <4cm, 36.8% of the patients whose FNAB results were found to be benign were malignant. False-negativity rate was found to be quite high in ≥4cm nodules. For thyroid nodules, diagnostic lobectomy may be necessary because the false-negative rate of FNAB was high, especially in nodules ≥4cm. In addition, intermediate results, such as AUS/FN, have a higher risk of malignancy in nodules of ≥4cm compared to nodules of <4cm.

Patient Compliance With Surveillance of Thyroid Nodules Classified as Atypia of Undetermined Significance.

To determine whether thyroid nodule surveillance compliance is influenced by patient demographics or plan type. Retrospective case series from 2010 to 2018. United States Military Health System. There were 481 patients with a thyroid nodule fine-needle aspiration classified as atypia of undetermined significance for whom treatment and follow-up information were available. Demographic information and surveillance plan type were extracted from the medical record and statistical analysis was performed to determine whether these characteristics influenced compliance rates. A total of 289 nodules were surveilled and 192 diagnostic lobectomies were performed. An initial surveillance plan was documented in 93% (268/289) and 86% (231/268) complied. The most common plans were repeat biopsy in 78% (210/268) or ultrasound in 20% (53/268). A second plan was documented in 88% (204/231) of those who complied with the first. The most common second plans were ultrasound in 87% (178/204) or repeat biopsy in 8% (17/204). Compliance with the second plan was 64% (130/204), significantly lower than with the first (OR 3.6, 95% CI: [2.3, 5.6], P < .0001). Only 45% (130/289) were surveilled twice. Age and gender did not significantly affect compliance rates. Compliance with primary care ultrasound surveillance was 40% (21/52), significantly lower than with a specialist (77% [137/179]; OR 4.8, 95% CI: [2.5, 9.3, P < .0001). Compliance with surveillance of thyroid nodules classified as atypia of undetermined significance was poor in this military cohort. Ultrasound surveillance by a specialist may be more reliable than with primary care.

Apparent Diffusion Coefficient Map-Based Radiomics Features for Differential Diagnosis of Pleomorphic Adenomas and Warthin Tumors From Malignant Tumors.

PurposeThe magnetic resonance imaging (MRI) findings may overlap due to the complex content of parotid gland tumors and the differentiation level of malignant tumor (MT); consequently, patients may undergo diagnostic lobectomy. This study assessed whether radiomics features could noninvasively stratify parotid gland tumors accurately based on apparent diffusion coefficient (ADC) maps.MethodsThis study examined diffusion-weighted imaging (DWI) obtained with echo planar imaging sequences. Eighty-eight benign tumors (BTs) [54 pleomorphic adenomas (PAs) and 34 Warthin tumors (WTs)] and 42 MTs of the parotid gland were enrolled. Each case was randomly divided into training and testing cohorts at a ratio of 7:3 and then was compared with each other, respectively. ADC maps were digitally transferred to ITK SNAP (www.itksnap.org). The region of interest (ROI) was manually drawn around the whole tumor margin on each slice of ADC maps. After feature extraction, the Synthetic Minority Oversampling TEchnique (SMOTE) was used to remove the unbalance of the training dataset. Then, we applied the normalization process to the feature matrix. To reduce the similarity of each feature pair, we calculated the Pearson correlation coefficient (PCC) value of each feature pair and eliminated one of them if the PCC value was larger than 0.95. Then, recursive feature elimination (RFE) was used to process feature selection. After that, we used linear discriminant analysis (LDA) as the classifier. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the ADC.ResultsThe LDA model based on 13, 8, 3, and 1 features can get the highest area under the ROC curve (AUC) in differentiating BT from MT, PA from WT, PA from MT, and WT from MT on the validation dataset, respectively. Accordingly, the AUC and the accuracy of the model on the testing set achieve 0.7637 and 73.17%, 0.925 and 92.31%, 0.8077 and 75.86%, and 0.5923 and 65.22%, respectively.ConclusionThe ADC-based radiomics features may be used to assist clinicians for differential diagnosis of PA and WT from MTs.

Rate and Clinical Predictors of Malignancy in Thyroid Nodules with Indeterminate Cytology

Background: Fine needle aspiration cytology (FNAC) cannot differentiate between benign and malignant conditions in cytologically indeterminate thyroid lesions. Therefore, a minimum of diagnostic lobectomy is required for definitive diagnosis. The objective of this study is to identify the rate of malignancy and clinical features that may possibly predict malignancy in patients with these lesions, in Ethiopian hospitals. Methods: This was a retrospective review of the medical records of patients who underwent surgery for cytologically indeterminate thyroid lesions in three referral hospitals between September 2015 and September 2020. Results: Of 85 patients with indeterminate cytology findings, 56 (63.5%) were follicular, and 29 (34.1%) were reported to be hurthle cell neoplasms. Follicular lesions of undetermined significance (FLUS) and suspicious for follicular neoplasm were each reported in single cases (1.7%). Malignant disease was diagnosed in 19 (22.4%) of patients. A follicular variant of papillary cancer was detected in 7 (11.5%) patients. Hard nodule consistency was reported in 9 of 11 malignant lesions and 5 of 66 benign lesions. In multivariate binary logistic regression, hard nodule consistency was found to be associated with malignancy (P = 0.012, AOR = 7.28 (1.5, 34.54) 95% CI ). The ill-defined surface of a nodule was found to be associated with malignancy though the association was not statistically significant (P = 0.088, AOR = 0.162 (0.020, 1.313) 95% CI. Ultrasound evaluation of thyroid nodule was performed only in 41 (47.7%) of patients. Conclusion: The rate of malignancy in thyroid nodules with indeterminate cytology was 22.4%. The risk of malignancy was higher in patients with hard thyroid nodule consistency and ill-defined surface. Despite the established benefits of ultrasound for the evaluation of thyroid nodules, the current practice of its use in our setup is suboptimal. Keywords: Follicular; hurthle cell; indeterminate cytology; predictors of malignancy

Unique Molecular Signatures Are Associated with Aggressive Histology in Pediatric Differentiated Thyroid Cancer.

Background: Molecular testing (MT) enhances the diagnostic accuracy of thyroid fine-needle aspiration biopsy, reducing the need for diagnostic lobectomy in adult patients with indeterminate nodules (Bethesda class III/IV). However, little is known about genetic alterations in pediatric thyroid carcinoma (TC). Our aim was to analyze MT results of pediatric differentiated TC (DTC) cases to determine associations with histological and clinical features. Methods: A retrospective review identified all patients (aged <19 years) diagnosed with DTC from 2001 to 2017 at the University of Pittsburgh Medical Center. Histology was rereviewed to confirm diagnosis and identify tissue for MT using next-generation sequencing (ThyroSeq, version 3, TSv3). Correlation with histological and clinical features was analyzed using regression analysis. Results: Of 71 patients with MT results, 62 (87%) patients had papillary TC. All patients were alive at a median follow-up of 6 years (range 18 days to 18 years). Genetic alterations were identified in 65 (92%) patients. These alterations were grouped as BRAF-like point mutations or fusions (39, 55%), RAS-like mutations or fusions (21, 30%), or copy number alterations (5, 7%). On multiple regression analysis accounting for patient sex and tumor size in patients with papillary TC, increased tumor stage (β: 0.234, p < 0.001), multifocal disease (odds ratio [OR]: 3.60, p = 0.042), and lymph node metastases (OR: 6.13, p = 0.044) were associated with BRAF-like gene fusions. When considering individual mutations, ETV6/NTRK3 fusions were associated with increased tumor stage (β: 2.07, p = 0.023) and BRAF-like point mutations were associated with increased likelihood of surgery for recurrence over time (hazard ratio: 19.5, p = 0.004). Conclusions: Among our cohort of pediatric TC patients who underwent comprehensive MT, >90% had an identifiable genetic alteration. Aggressive features were primarily associated with BRAF-like gene fusions. Preoperative MT results may be useful in guiding the extent of the initial operation in pediatric patients (aged <19 years) with TC.

Radiofrequency ablation for symptomatic, non-functioning, thyroid nodules: a single-center learning curve.

ObjectiveRadiofrequency ablation (RFA) is increasingly considered the prime option for treating symptomatic, benign, non-functioning thyroid nodules (NFTN). However, little is known about the degree of operator experience required to achieve optimal results. This study describes the RFA learning curve of a single-center team.MethodsA retrospective cohort study of the first 103 patients receiving RFA treatment for a single, symptomatic, and benign NFTN, with a follow-up of at least 1 year. The primary outcome measure was technique efficacy, defined as the percentage of patients with a 6-month nodal volume reduction ratio (VRR) >50% after single-session RFA. Optimal treatment efficacy was defined as a 6-month VRR >50% achieved in at least 75% of patients. Secondary outcomes were complications of RFA and indications of secondary interventions.ResultsMedian nodal volume at baseline was 12.0 mL (range 2.0–58.0 mL). A 6-month VRR >50% was achieved in 45% of the first 20 patients, 75% of the next 20, and 79% of the following 63 patients. Complications included minor bleeding (N = 4), transient hyperthyroidism (N = 4), and transient loss of voice (N = 1). Poor volume reduction or nodular regrowth led to diagnostic lobectomy in 11 patients and a second RFA in 5. Lobectomy revealed a follicular carcinoma (T2N0M0) in 2 patients. In 1 patient, nodule regrowth was caused by an intranodular solitary B-cell lymphoma.ConclusionAbout 40 procedures are required to achieve a 6-month VRR >50% in the majority of patients. Appropriate follow-up with re-evaluation is recommended for all patients with a VRR <50% and in those with regrowth to exclude underlying malignancy.

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.

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.

Radiomics analysis improves 18FDG PET/CT-based risk stratification of cytologically indeterminate thyroid nodules

PurposeAs ~25% of cytologically indeterminate thyroid nodules harbour malignancy, diagnostic lobectomy is still performed in many cases. 18FDG PET/CT rules out malignancy in visually negative nodules; however, none of the currently available interpretation criteria differentiates malignant from benign 18FDG-avid nodules. We evaluated the ability of PET metrics and radiomics features (RFs) to predict final diagnosis of 18FDG-avid cytologically indeterminate thyroid nodules.MethodsSeventy-eight patients were retrospectively included. After volumetric segmentation of each thyroid lesion, 4 PET metrics and 107 RFs were extracted. A logistic regression was performed including thyroid stimulating hormone, PET metrics, and RFs to assess their predictive performance. A linear combination of the resulting parameters generated a radiomics score (RS) that was matched with cytology classes (Bethesda III and IV) and compared with final diagnosis.ResultsTwo RFs (shape_Sphericity and glcm_Autocorrelation) differentiated malignant from benign lesions. A predictive model integrating RS and cytology classes effectively stratified the risk of malignancy. The prevalence of thyroid cancer increased from 5 to 37% and 79% in accordance with the number (score 0, 1 or 2, respectively) of positive biomarkers.ConclusionsOur multiparametric model may be useful for reducing the number of diagnostic lobectomies with advantages in terms of costs and quality of life for patients.