Malignancy Rate in Thyroid Nodules with Atypia or Follicular Lesion of Undetermined Significance

Original Research Malignancy Rate in Thyroid Nodules with Atypia or Follicular Lesion of Undetermined Significance Hamdan Ahmed Pasha1  http://orcid.org/0000-0001-6349-7024 Rahim Dhanani1  Ainulakbar Mughal1  Kaleem S. Ahmed1  Anwar Suhail1  1Department of Surgery, Section of Otolaryngology/Head and Neck Surgery, Aga Khan University, Karachi, Pakistan Abstract Introduction Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is one of the six diagnostic categories of the Bethesda System for Reporting Thyroid Cytopathology. The prevalence of malignancy among Bethesda category III cytology is variable, ranging from 5% to 37% in the literature. Objective To determine the rate of malignancy in thyroid nodules reported as Bethesda category III. Methods A total of 495 patients underwent surgical intervention for thyroid nodules from January 2015 to December 2017. The present study included 81 cases reported as Bethesda category III, and their medical records were reviewed. Results Out of 495 fine-needle aspiration cytology samples, 81 (16.4%) samples were labeled as AUS/FLUS. Among these 81 patients, the mean age was 43.0 years (±13.9), with only 11 (14%) patients older than 55 years of age.Most of our patients were female (n=69; 85.2%), and the rest were male. The rate of malignancy based on the final histology was of 33.3% (n=27). The majority were 17 cases (21%) of papillary carcinoma, followed by follicular carcinoma (n=6) (7.4%). Conclusion The risk of malignancy can be higher than it is commonly believed, and guidelines should be based on the data from the institutions themselves for a better assessment of the outcomes. Keywords: atypia of undetermined significance; thyroid nodule; bethesda; fine-needle aspiration Introduction The global incidence of thyroid cancer is rapidly increasing largely due to incidental thyroid nodules being found on ultrasonography. Nodules have been reported in 50% of patients aged 50 years, with a low overall malignancy risk of 5% to 7%.1 2 The most commonly employed preoperative diagnostic tool is fine-needle aspiration cytology (FNAC) for cancer risk stratification.1 2 3 It is not only a reliable screening test, but also a reliable and cost-effective method for the differential diagnosis of a thyroid nodule, and it reduces the rate of unnecessary thyroidectomies.1 The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in 2007, and it consists of 6 tiered categories (Table 1) to enhance and standardize the practice of thyroid cytopathology, and subsequently facilitate the better management of thyroid nodules. This has enabled a standardized system for the reporting and management of thyroid gland FNAC results.4 Each category has an implied cancer risk and subsequent recommended management guidelines. Table 1 Distribution of the cytological interpretation of thyroid fine-needle aspiration  Bethesda Category N % Nondiagnostic/Unsatisfactory (I) 44 8.9 Benign (II) 275 55.6 AUS/FLUS (III) 81 16.4 FN/SFN (IV) 32 6.5 Suspicious for malignancy (V) 46 9.3 Malignant (VI) 15 3.0 Total 495 100 Abbreviations: AUS, atypia of undetermined significance; FLUS, follicular lesion of undetermined significance; FN, follicular neoplasm; SFN, suspicious for follicular neoplasm. Among its six categories, category III, or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) was introduced for cytological features that are neither definitively benign nor definitively neoplastic, and, as such, was meant to encompass a small number of lesions that were difficult to classify. This category, however, remains under heated debate due to variations in outcomes observed across multiple studies. It now includes cases with non-specific patterns affected by compromising factors such as air-drying artifacts, low cellularity or obscuring elements.5 6 Currently, the reported risk of malignancy of AUS/FLUS is between 5% and 15%, but recent studies have considered a reevaluation of this probability range.7 Some have reported the potential feasibility of using thyroid ultrasound to improve predictions of malignancy of nodules assigned as undetermined cytology in the initial FNAC.8 9 10 11 A few studies reported very high malignancy rates of up 48%, suggesting diagnostic lobectomy for all cases of AUS/FLUS nodules.12 Others have gone on to suggest further dividing AUS/FLUS into a two-tiered subclassification consisting of low cellularity with predominant microfollicular architecture and absence of colloid, and nuclear atypia (non-benign characteristics) attributable to the strict probability of cancer probability evaluation.13 14 15 Moreover, genetic studies have played their role in predicting cancer risks in such nodules, making some authors suggest their routine use.16 Our study focuses on the diagnostic distribution of Bethesda-III nodules in our institution, and we analyzed the outcomes of AUS/FLUS cases comparing them with reports in the literature. The aim of the study was to determine the rate of malignancy in thyroid nodules reported as Bethesda category III. Materials and Methods The present study was reviewed and approved by the ethical review committee of a tertiary healthcare center. Due to the observational design of the study, consent from patients was not needed. The data was obtained from the retrospective review of patient medical records from January 2015 to December 2017. The data collected included: patient age and gender, FNAC result, surgical intervention performed, and final histopathology diagnosis. A total of 495 patients underwent surgical intervention for thyroid nodule, and 81 patients who had AUS/FLUS on the FNAC were recruited for inclusion in the study. Patients whose FNAC results were other than AUS/FLUS, those who had history of any prior surgical intervention for the thyroid, and those who did not underwent surgical intervention were excluded. The data analysis was performed using the Statistical Package for the Social Sciences (SPSS, IBM Corp., Armonk, NY, US) software, version 23. The FNAC result was compared with the final histopathology report in patients who had AUS/FLUS on the initial cytology, and the frequency of benign nodules and malignancies was observed to calculate the risk. Results Over the period of two years, preoperative FNAC was performed in 495 patients who underwent thyroid surgery. Out of these 495 FNAC samples, 81 (16.4%) were labeled as having AUS/FLUS (Table 1). Amongst these 81 patients, the mean age was 43.0 years (± 13.9), with only 11 (14%) patients older than 55 years of age. Most patients were female (n= 69; 85.2%), and the rest were male. A total of 39 (48.1%) patients underwent total thyroidectomy, whereas the remaining 42 (51.9%) underwe (...truncated)