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Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has emerged as the most controversial category because of its heterogeneity and inconsistent reporting. There is a definite paucity in data available from the Indian subcontinent about the outcome of nodules carrying Bethesda category III or Bethesda category IV diagnoses. Aims and Objectives: The primary objective of our study was to determine the malignancy rate in Bethesda categories III and IV nodules. The secondary objectives were to determine predictive value of BRAFV600E mutation analysis on indeterminate thyroid nodules, predictive value of Thyroid image reporting and data system (TI-RADS) in malignancy prediction and to study the common histological variants in indeterminate nodules. Materials and Methods: This prospective study included 176 consecutive nodules of Bethesda categories III and IV, diagnosed over a period of 2 years from August 2015 to August 2017. A part of the fine needle aspirate was used to perform the BRAFV600E mutation analysis. The malignancy risk associated with these Fine needle aspiration Cytology categories were discussed with the patients. Those with Bethesda category IV diagnosis was advised surgery, whereas those with Bethesda category III were given the options of close follow-up with repeat FNA in 3 months or immediate surgery. Results: In our prospective study, there were 176 consecutive samples of categories III (140/79.5%) and IV (36/20.5%). Seventy-five (53.6%) category III nodules and 29 (80.6%) category IV nodules underwent immediate surgical excision. Fifty-five consecutive indeterminate cytology nodules were subjected for BRAFV600E. One of the samples was found to be positive for BRAF T1799A (V600E) mutation. The second sample harboured a missense mutation at position 1819 (TCC--GCC), wherein the codon 607 (TCC) coding for serine was substituted by alanine (GCC) which is a variant of unknown significance. In our study, the malignancy rate of Bethesda categories III and IV, which were triaged for immediate surgery were 54.6% and 72.4%, respectively. Conclusion: Malignancy rate in Category III at our center was much higher than that described by ATA and by other studies published from centers around the world, including the only two studies from India. In view of the strikingly high malignancy rate in these indeterminate nodules, strong consideration to surgery should be given to patients with FNA results suggesting these two categories. BRAFV600E mutation analysis in FNA specimen has limited utility in improving the preoperative diagnostic rate for malignancy. [ABSTRACT FROM AUTHOR]

Background: Thyroid Imaging Reporting and Data System (TIRADS) scoring is used to assess the nature of nodules in the thyroid gland, especially with regards to the possibility to predict chances of malignancy of those nodules. The commonest used system worldwide is the one by the American College of Radiology (ACR-TIRADS). Majority of thyroid cancers are hard; hence the stiffness evaluation can become part of nodule characterization. Strain or stress elastography is the elastography technique in which the ultrasound probe is placed in front of the thyroid nodule with interposition gel. The beating of the carotid artery generates a sufficient deformation to create a qualitative map image in the region of interest. Addition of strain elastography to the TIRADS scoring can improve the sensitivity & specificity of the modalities in predicting the malignant potential of thyroid nodules. Methods: In this cross-sectional study, among the USG Thyroid cases done in Endocrinology Dept. of a tertiary care hospital in South India, the cases which showed Solitary Thyroid Nodule (STN) among them during 6-month study period were selected. All of them had undergone Strain Elastography (SE) also. The data with regards to the USG nature of those STNs including ACR-TIRADS scoring, & the SE nature of them including Rago scoring, were taken &analysed. Both TIRADS score &Rago score were analysed together. From among those STNs, only those nodules with either TIRADs score 5 or Rago score >2 was included in the detailed analysis because those would be the nodules with more chance of being malignant. All such nodules also underwent USG guided Fine Needle Aspiration Cytology (FNAC) & the report of FNAC was analysed to find whether they belonged to Bethesda Category less than III (benign) or belonged to Bethesda Category III or more (suspicious for malignancy). Results: Out of the total 91 STNs studied, 36 (40%), 40 (44%) & 15 (16%) were of Rago 3/4, Rago 2 &Rago 1 scoring respectively on SE. 10 out of the 91 STNs were of ACR-TIRADS 5 scoring. 2 out of the 7 Rago 3/4 with TIRADS 5 STNs had FNAC showing Bethesda Cat. III or more nature. 2 out of the 29 Rago 3/4 with TIRADS <5 STNs had FNAC showing Bethesda Cat. III or more nature. 1 out of the 3 Rago 1 or 2 with TIRADS 5 STNs had FNAC showing Bethesda Cat. III or more nature. 36 Rago 3/4 STNs on FNAC yielded Bethesda Cat III or more (4/36 = 11.1%). 55 STNs had Rago < 3 score & based on TIRADS criteria only, 18 of them underwent FNAC & Bethesda Cat. III or more was seen in 2 (2/18 = 11.1%). FNACs on the 10 TIRADS 5 nodules showed Bethesda Cat III or more nature was seen in 4 (4/10 = 25%). These results show that even though not needing FNAC study based on TIRADS criteria, those Rago 3, 4 nodules on FNAC have showed to have suspicious result in FNAC. This means that more stiff nodules as represented by Rago 3, 4 scores in SE could be suspicious for malignancy even when they were not suspected to be of so based on ACR TIRADS USG criteria alone. Conclusion: Sometimes when based on TIRADS criteria alone, some STNs with suspicious for malignant nature may be missed; but when Strain Elastography is also added to the same, the chance of detecting stiffer nodules increases, that could have malignant nature. Strain Elastography modality in USG machine needs to be used more along with conventional TIRADS scoring of thyroid nodules. [ABSTRACT FROM AUTHOR]