Independent Comparison of the Afirma Genomic Sequencing Classifier and Gene Expression Classifier for Cytologically Indeterminate Thyroid Nodules.

Background: For thyroid nodules with indeterminate cytology, the Afirma Gene Expression Classifier (GEC) identified benign nodules to reduce diagnostic surgery, though many nodules classified as suspicious still proved histopathologically benign. The current Afirma Genomic Sequencing Classifier (GSC) demonstrates improved specificity, suggesting more nodules will have a benign result (benign call rate [BCR]), but independent data are needed to confirm this in clinical practice. Methods: Retrospective analysis was performed of all Bethesda III or IV cytology thyroid nodules ≥1 cm tested with GEC (between January 1, 2011, and July 19, 2017) or GSC (between July 20, 2017, and August 27, 2018) at the authors' institution. Afirma testing was not performed reflectively for all nodules with Bethesda III or IV cytology, but rather was applied based on physician-patient decision making. Demographic, sonographic, and cytologic data were collected. The BCR for GEC- versus GSC-tested nodules was compared and further stratified by Bethesda classifications. Results: The study evaluated 600 nodules in 563 patients tested with either GEC (n = 486) or GSC (n = 114). The BCR was 233/486 (47.9%) for the GEC compared to 75/114 (65.8%) for the GSC (p = 0.0006). Hürthle-cell cytology was present in 99/486 (20.4%) nodules in the GEC group compared to 31/114 (27.2%) nodules in the GSC group (p = 0.28). The GSC BCR was significantly higher than the GEC BCR for Bethesda III nodules characterized by Hürthle cells (p = 0.006), but the BCRs were similar for nodules with architectural or cytologic atypia. In Bethesda IV nodules suspicious for follicular neoplasm, BCR for the GEC and GSC were similar (p = 0.68), but for cytology suspicious for Hürthle-cell neoplasm, the GSC BCR was 68.2% (15/22) compared to the GEC BCR of 16.4% (10/61; p < 0.0001). Positive predictive value in resected nodules with a suspicious result was 16/32 (50%) for GSC nodules and 75/221 (33.9%) for GEC nodules (p = 0.1). Conclusions: The higher BCR for the GSC compared to the GEC for indeterminate thyroid nodules, predominantly among nodules with Hürthle-cell cytology, will likely lead to further reduction in surgical management.

Quantitative Analysis of the Benefits and Risk of Thyroid Nodule Evaluation in Patients ≥70 Years Old.

BACKGROUND: In older patients, thyroid nodules are frequently detected and referred for evaluation, though usually prove to be benign disease or low-risk cancer. Therefore, management should be guided not solely by malignancy risk, but also by the relative risks of any intervention. Unfortunately, few such data are available for patients ≥70 years old. METHODS: All consecutive patients ≥70 years old assessed by ultrasound (US) and fine-needle aspiration (FNA) between 1995 and 2015 were analyzed. Clinical, US, and histologic data, including patient comorbidities and outcomes, were obtained. Imaging and cytology results from initial evaluation were reviewed to detect significant-risk thyroid cancer (SRTC), which was defined as anaplastic, medullary, or poorly differentiated carcinoma, or the presence of distant metastases. Overall survival analyses were then performed to assist with risk-to-benefit assessment. RESULTS: A total of 1129 patients ≥70 years old with 2527 nodules ≥1 cm were evaluated. FNA was safe in all, and cytology proved benign in 67.3% of patients. However, FNA led to surgery in 208 patients, of whom 93 (44.7%) had benign histopathology. Among all patients who underwent FNA, only 17 (1.5%) SRTC were identified, all of which were preoperatively identifiable by imaging and/or cytology. These SRTC were responsible for all (n = 10; 0.9%) thyroid cancer deaths. Among all other patients (n = 1112), 160 deaths (14.4%) were confirmed during a median follow-up of four years. None of these were thyroid cancer related. Survival analysis for these 1112 patients demonstrated that a separate non-thyroidal malignancy or coronary artery disease at the time of nodule evaluation was associated with increased mortality compared to those without these diagnoses (hazard ratio = 2.32 [confidence interval 1.66-3.26]; p < 0.01), confirming these are important variables to identify prior to thyroid nodule evaluation. CONCLUSIONS: For patients ≥70 years old, US and FNA are safe and prove helpful in identifying SRTC and benign cytology. However, the surgical management of patients ≥70 years old presenting without high-risk findings should be tempered, especially when comorbid illness is identified.

Thyroid FNA biopsies comprised of abundant, mature squamous cells can be reported as benign: A cytologic study of 18 patients with clinical correlation.

BACKGROUND: A thyroid nodule comprised almost exclusively of mature, benign-appearing squamous cells is an uncommon finding in fine-needle aspiration (FNA) biopsies of thyroid nodules. Reporting such specimens was not originally addressed by The Bethesda System for Reporting Thyroid Cytopathology. The authors correlated the biologic behavior of the specimens with their benign cytologic appearance through clinical, radiographic, and surgical follow-up. METHODS: The pathology archives of 3 tertiary hospitals were searched for thyroid FNA specimens consisting of mature squamous cells without atypia. The authors reviewed all available slides and included only cases that were moderately to highly cellular; nucleated or anucleate squamous cells without atypia comprised the vast majority of the cellularity. Available clinical information and/or thyroid ultrasound examination(s) were reviewed by an endocrinologist or radiologist, respectively. RESULTS: A total of 18 patients (7 men and 11 women; age range, 19-76 years) with 20 nodules met the prespecified inclusion criteria. The average nodule size was 2.1 cm. Common sonographic characteristics included a well-defined appearance, the lack of internal vascularity, a thin outer wall, general hypoechogenicity with low-intermediate internal echoes, and posterior acoustic enhancement. Clinical and radiographic follow-up (mean, 3.8 years; range, <1 to 9 years) was available for 9 patients, and all nodules were stable. All 4 cases with histologic follow-up were benign squamous-lined cysts. CONCLUSIONS: The findings of the current study suggest that thyroid FNA specimens comprised almost exclusively of mature squamous cells can be reported as benign. Cancer Cytopathol 2018;126:336-41. © 2018 American Cancer Society.

Differential Growth Rates of Benign vs. Malignant Thyroid Nodules.

Context: Thyroid nodule growth was once considered concerning for malignancy, but data showing that benign nodules grow questioned the use of this paradigm. To date, however, no studies have adequately evaluated whether growth rates differ in malignant vs. benign nodules. Objective: To sonographically evaluate growth rates in benign and malignant thyroid nodules ≥1 cm. Design: Prospective, cohort study of patients with tissue diagnosis of benign or malignant disease, with repeated ultrasound evaluation six or more months apart. Main Outcomes: Growth rate in largest dimension of malignant compared with benign thyroid nodules. Regression models were used to evaluate predictors of growth. Results: Malignant nodules (126) met inclusion criteria (≥6-month nonoperative followup) and were compared with 1363 benign nodules. Malignant nodules were not found to be uniquely selected or prospectively observed solely for low-risk phenotype. Median ultrasound intervals were similar (21.8 months for benign nodules; 20.9 months for malignant nodules). Malignant nodules were more likely to grow >2 mm/y compared with benign nodules [relative risk (RR) = 2.5, 95% confidence interval (CI), 1.6 to 3.1; P < 0.001], which remained true after adjustment for clinical factors. The RR of a nodule being malignant increased with faster growth rates. Malignant nodules growing >2 mm/y had greater odds of being more aggressive cancers [intermediate risk: odds ratio (OR) = 2.99; 95% CI, 1.20 to 7.47; P = 0.03; higher risk: OR = 8.69; 95% CI, 1.78 to 42.34; P = 0.02]. Conclusions: Malignant nodules, especially higher-risk phenotypes, grow faster than benign nodules. As growth >2 mm/y predicts malignant compared with benign disease, this clinical parameter can contribute to the assessment of thyroid cancer risk.

Qualifiers of atypia in the cytologic diagnosis of thyroid nodules are associated with different Afirma gene expression classifier results and clinical outcomes.

BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) on fine-needle aspiration (FNA) have a low risk of malignancy that appears to vary based on specific features described in the AUS diagnosis. The Afirma gene expression classifier (GEC) is a molecular test designed to improve preoperative risk stratification of thyroid nodules, but its performance for different patterns of AUS has not been defined. The objective of this study was to assess GEC results and clinical outcomes in AUS nodules with architectural atypia (AUS-A), cytologic atypia (AUS-C) or both (AUS-C/A). METHODS: This was a retrospective review of all thyroid nodules with AUS cytopathology that underwent GEC testing at the authors' institution over a period of >4 years. RESULTS: In 227 nodules that had AUS cytology results and Afirma GEC testing, the rate of benign GEC results was higher in AUS-A nodules (70 of 107; 65%) than in AUS-C/A nodules (25 of 65; 38%; P = .0008), and AUS-C nodules exhibited an intermediate rate of benign results (27 of 55 nodules; 59%). The risk of cancer among patients who had GEC-suspicious nodules, 86% of whom underwent resection, was 19% (6 of 25) for AUS-A nodules compared with 57% (21 of 37) for AUS-C/A nodules (P = .003) and 45% (10 of 22) for AUS-C nodules (P = .07). In nodules that had an indeterminate repeat cytology result, no difference was observed in the rate of benign GEC results or in the malignancy rate compared with nodules that had a single cytology result. CONCLUSIONS: The performance characteristics of Afirma GEC testing vary, depending on qualifiers of cytologic atypia. Recognition of these differences may enable clinicians to provide improved counseling and treatment recommendations to patients. Cancer Cytopathol 2017;125:313-322. © 2017 American Cancer Society.

Imaging appearance of topical haemostatic agents: pictorial review.

Topical haemostatic agents have become an essential tool to assist with the control of bleeding during surgery as well as to facilitate wound closure. The imaging appearance of these agents can overlap that of abscess or tumour. Knowledge of the appearance of these various agents on ultrasound and CT is crucial to avoid misdiagnosing pathology, potentially resulting in unnecessary interventional procedures.

Clinical, Sonographic, and Pathological Characteristics of RAS-Positive Versus BRAF-Positive Thyroid Carcinoma.

CONTEXT: Mutations in the BRAF and RAS oncogenes are responsible for most well-differentiated thyroid cancer. Yet, our clinical understanding of how BRAF-positive and RAS-positive thyroid cancers differ is incomplete. OBJECTIVE: We correlated clinical, radiographic, and pathological findings from patients with thyroid cancer harboring a BRAF or RAS mutation. DESIGN: Prospective cohort study. SETTING: Academic, tertiary care hospital. PATIENTS: A total of 101 consecutive patients with well-differentiated thyroid cancer. MAIN OUTCOME MEASURE: We compared the clinical, sonographic, and pathological characteristics of patients with BRAF-positive cancer to those with RAS-positive cancer. RESULTS: Of 101 patients harboring these mutations, 71 were BRAF-positive, whereas 30 were RAS-positive. Upon sonographic evaluation, RAS-positive nodules were significantly larger (P = .04), although BRAF-positive nodules were more likely to harbor concerning sonographic characteristics (hypoechogenicity [P < .001]; irregular margins [P = .04]). Cytologically, 70% of BRAF-positive nodules were classified positive for PTC, whereas 87% of RAS-positive nodules were indeterminate (P < .001). Histologically, 96% of RAS-positive PTC malignancies were follicular variants of PTC, whereas 70% of BRAF-positive malignancies were classical variants of PTC. BRAF-positive malignancies were more likely to demonstrate extrathyroidal extension (P = .003), lymphovascular invasion (P = .02), and lymph node metastasis (P < .001). CONCLUSIONS: BRAF-positive malignant nodules most often demonstrate worrisome sonographic features and are frequently associated with positive or suspicious Bethesda cytology. In contrast, RAS-positive malignancy most often demonstrates indolent sonographic features and more commonly associates with lower risk, "indeterminate" cytology. Because BRAF and RAS mutations are the most common molecular perturbations associated with well-differentiated thyroid cancer, these findings may assist with improved preoperative risk assessment by suggesting the likely molecular profile of a thyroid cancer, even when postsurgical molecular analysis is unavailable.

Testicular microlithiasis: prevalence and association with primary testicular neoplasm.

PURPOSE: To assess the prevalence of testicular microlithiasis and its association with primary testicular neoplasm. METHODS: Evaluated were 6,002 patients undergoing scrotal ultrasound at our institution. Data recorded included age, ultrasound date, presence of microlithiasis, presence of testicular mass on ultrasound, and pathologic diagnosis for those who had subsequent orchiectomy. RESULTS: Four hundred fifty-six of 6,002 patients (7.6%) demonstrated testicular microlithiasis. The prevalence increased from 4.6% for those examined before 2001 to 9.02% for those examined since 2001 (p < 0.001). The prevalence of primary testicular neoplasm in patients without microlithiasis was 1.5% (84/5,546), whereas in those with microlithiasis it was 12% (53/456) (p < 0.001). The prevalence of pure seminoma was 39% (33/84) in the nonmicrolithiasis group with tumor versus 64% (34/53) in the microlithiasis group with tumor (p < 0.001). Germ cell tumors made up 98% of neoplasms in patients with microlithiasis, but only 85% in patients without microlithiasis (p = 0.009). CONCLUSIONS: Advances in ultrasound technology have led to an increased detection of testicular microlithiasis. We observed an eight-fold increased prevalence of primary testicular neoplasm in patients with microlithiasis than in those without as well as an increased prevalence of germ cell tumors, particularly pure seminoma. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:423-426, 2014.