Malignancy Rate of Bethesda Class III Thyroid Nodules Based on the Presence of Chronic Lymphocytic Thyroiditis in Surgical Patients

BackgroundHashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis (CLT), may interfere with the accurate cytological diagnosis of thyroid nodules. Recently, HT has been considered a premalignant condition for thyroid cancer development. The diagnosis of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) thyroid nodules is challenging and evidence for the malignancy risk of AUS/FLUS thyroid nodules coexisting with CLT is scarce. Therefore, we assessed the malignancy risk of AUS/FLUS thyroid nodules according to the presence of background CLT.MethodsThis study included 357 surgically resected thyroid nodules with AUS/FLUS cytology. Cases with concomitant malignant nodules were excluded. CLT was defined based on the pathologic report after thyroid surgery.ResultsAmong 357 tumors, 130 tumors (36%) were confirmed to have coexisting CLT, and 170 tumors (48%) were determined to be malignant after thyroidectomy. Malignancy rates were similar in both groups (48% in each) regardless of background CLT (62/130 with CLT vs. 108/227 without CLT). In the group with CLT, thyroiditis was more frequent in the final pathology (12% with CLT vs. 1% without CLT, P = 0.003). In multivariate analysis, positive BRAFV600E mutation, highly suspicious sonographic features (K-TIRADS 5), and smaller thyroid nodules were significant factors for thyroid malignancies.ConclusionThe malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Atypia and Follicular Lesions of Undetermined Significance in Subsequent Biopsy Result: What Clinicians Need to Know

Atypia and follicular lesions of undetermined significance (AUS/FLUS) is the most controversial category of The Bethesda System. The risk of malignancy (ROM) in this group is estimated as 5–15%, however, the occurrence of two or more subsequent biopsy results with AUS/FLUS diagnosis makes these clinical situations more complex. We evaluated the ROM and prognostic value of aggressive ultrasound (US) features in 342 patients with thyroid nodules (TNs) with subsequent biopsy results of AUS/FLUS. We assessed US features and compared them with the final histopathological diagnosis. Overall, 121 (35.4%) individuals after first AUS/FLUS diagnosis underwent surgery and 221 (64.6%) patients had repeated biopsies. The ROM after first, second, and third biopsies with subsequent AUS/FLUS diagnosis were 7.4%, 18.5%, and 38.4% respectively. We demonstrated significantly higher rates of occurrence of aggressive US features in patients with malignancy (p < 0.0001). The age <55 years old was also a significant risk factor for TC (p = 0.044). Significant associations were found between aggressive US features and malignancy in patients after first diagnosis of AUS/FLUS (p < 0.05). The juxtaposition of US features with the number of biopsy repetitions of TN with consecutive AUS/FLUS diagnoses may simplify the decision-making process in surgical management. Two or three consecutive biopsy results with AUS/FLUS diagnosis increases the ROM.

Triple diagnostic test in the evaluation of thyroid nodules

Background: Thyroid nodules are a common endocrine disease whose prevalence in India is approximately 12.2%. Although most patients with suspected nodules have benign conditions, the overestimation of malignancy leads to the performance of unnecessary procedures. No clinical, radiological and cytological parameters has singularly shown significant impact on clinical practice and post-operative histopathological examination remains the gold standard in the diagnosis of malignancy.Methods: 55 patients with thyroid nodules were evaluated and the Clinical assessment findings were recorded by McGill thyroid nodule score, ultrasonography findings using TIRADS and FNAC findings by the Bethesda system. The triple test was then used to classify them and these results were compared with the HPE of the post-operative specimen.Results: The sensitivity and specificity of TIRADS, FNAC were higher as compared to clinical score; clinical score had lowest sensitivity of 72.73%. The sensitivity, specificity, PPV, NPV and accuracy of triple test was 100%. Triple test had higher sensitivity, specificity and accuracy in differentiating thyroid nodules as compared to any of the three parameters used individually.Conclusions: Triple test has higher accuracy, sensitivity and specificity in determining the nature of thyroid nodule than each of the parameters used individually and it is especially useful in follicular lesions. On the basis of the results of this study, we conclude that the triple test can reliably be used to differentiate benign and malignant nodules preoperatively.

Sonographic Features Differentiating Follicular Thyroid Cancer from Follicular Adenoma–a Meta-Analysis

Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62–39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22–11.50), irregular margins: 5.11 (2.90–8.99), marked hypoechogenicity: 4.59 (3.23–6.54), and irregular shape: 3.6 (1.19–10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.

Atypia of undetermined significance/follicular lesions of undetermined significance: What radiologists need to know

Atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) refers to an intermediate histologic category of thyroid nodules in The Bethesda System for Reporting Thyroid Cytopathology. Although the risk of malignancy in this category was originally cited as 5–15%, recent literature has suggested higher rates of related malignancy ranging from 38% to 55%. Malignant nodules warrant surgery with total thyroidectomy or thyroid lobectomy, whereas benign nodules can be observed or followed with serial ultrasounds (US) based on their imaging characteristics. The management of nodules with a cytopathologic diagnosis of AUS/FLUS can be difficult because theses nodules lie between the extremes of benign and malignant. The management options for such nodules include observation, repeat fine-needle aspiration, and surgery. The use of molecular genetics, the identification of suspicious US characteristics, and the recognition of additional clinical factors are all important in the development of an appropriate, tailored management approach. Institutional factors also play a crucial role.

FAM172A promotes follicular thyroid carcinogenesis and may be a marker of FTC

Our aims were to uncover the role of FAM172A (Family with sequence similarity 172 member A) in the pathogenesis of follicular thyroid carcinoma (FTC) and to evaluate its value in the differential diagnosis between malignant and benign thyroid follicular lesions. FAM172A expression was evaluated by q-PCR, immunoblotting and immunohistochemistry (IHC). The ability of proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8 assay (CCK8), clone-formation and Transwell assays. Nude mouse tumorigenicity assays were used to investigate the role of FAM172A in the pathogenesis of FTC in vivo. The value of FAM172A in the differential diagnosis for FTC was assessed using 120 formalin-fixed paraffin-embedded (FFPE) tissues after the operation and 81 fine-needle aspiration biopsy (FNAB) samples before the operation. FAM172A was highly expressed in FTC tissues and FTC cell lines. Downregulation of FAM172A inhibited the proliferation, invasion and migration of FTC cells through Erk1/2 and JNK pathways. Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172A inhibited tumor growth and progression in vivo. The FAM172A IHC scores of 3.5 had 92% sensitivity and 63% specificity to separate FTC from benign/borderline thyroid follicular lesions, and 92% sensitivity and 80% specificity to discriminate FTC from benign thyroid follicular lesions in postoperative FFPE samples. The corresponding values were 75 and 78%, and 75 and 89% in preoperative FNA samples, respectively. FAM172A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK pathways. FAM172A may be a potential marker for the preoperative diagnosis of FTC based on the IHC results of thyroid FNAB samples.