Malignancy rates for Bethesda category III and IV thyroid nodules that require surgery are approximately 25% and 27.6%, respectively, according to the results of a retrospective study published in BMC Endocrine Disorders.

Although fine-needle aspiration cytology (FNAC) is widely used to determine the risk for malignancy in thyroid nodules, cytologically indeterminate thyroid nodules remain a diagnostic challenge in approximately 10% to 30% of patients undergoing thyroidectomy. The Bethesda System for Reporting Thyroid Cytopathology is used to classify FNAC findings based on risk for malignancy. While categories II, V, and VI of this system are well established, data regarding the risks for malignancy, recurrence, and clinical management of nodules in categories III and IV are controversial and require additional clarification.

Bethesda category III nodules are further categorized as atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS). AUS nodules consist of follicular cells that are mostly benign in appearance. FLUS nodules are characterized by extensive Hurthle cells with moderate cellularity, scant colloid with no apparent increase in lymphoid cells, and follicular epithelial cell clusters showing a microfollicular pattern in the focal area. It is difficult to determine if these lesions are benign, suspicious, or malignant, and these nodules often require re-evaluation.

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Bethesda category IV nodules are described as follicular neoplasm or suspicious for follicular neoplasm (FN/SFN). This is the category with the greatest uncertainty, as follicular carcinomas resemble benign follicular neoplasms at the cellular level, making it difficult to distinguish between benign and carcinogenic nodules without additional indication.

To determine accurate malignancy rates for nodules classified as Bethesda III or IV, data from 155 patients who underwent thyroidectomies were analyzed. Patients who underwent FNAC as the primary diagnostic modality, who were diagnosed with Bethesda III or IV thyroid nodules, and who subsequently underwent total or partial thyroidectomy were included. Patients missing follow-up data were excluded.

Of the 155 patients included, 108 (69.7%) were diagnosed with Bethesda category III thyroid nodules and 47 (30.3%) were diagnosed with Bethesda category IV nodules. Of the nodules diagnosed as Bethesda category III, 59 were subcategorized as AUS and 49 as FLUS. The majority of patients were women (85.2%) and the mean age of patients was 52.5±1.0 years.

Of the 108 patients diagnosed with Bethesda III nodules, 69.4% underwent immediate surgery and 16% of these patients had nodules that were malignant. Patients with nodules that were diagnosed as AUS/FLUS after 2 successive FNAC tests had a malignancy rate of 45.5%. The rate of malignancy for all patients with nodules categorized as Bethesda III who were triaged to surgery was 25%.

Of the 47 patients diagnosed with Bethesda IV nodules, 74.5% underwent immediate surgery and 28.6% of these patients had nodules that were malignant. Patients with nodules that were diagnosed as FN/SFN after 2 successive FNAC tests had a malignancy rate of 25.0%. The rate of malignancy for all patients with nodules categorized as Bethesda IV who were triaged to surgery was 27.6%.

There was no statistical difference between AUS, FLUS, and FN/SFN nodules in terms of malignancy rates (P =.67). The most frequent categorization of malignant lesions was papillary thyroid carcinoma (81.5% of AUS/FLUS and 69.2% of FN/SFN nodules), and there was no significant difference between malignant nodules in terms of tumor type (P =.65) or size (P =.78).

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This study provided a more precise correlation of malignancy rates with thyroid nodules classified as Bethesda categories III (25.0%) and IV (27.6%), which were consistent with estimates provided in previous literature. The study authors noted that because there is heterogeneity in categorization at different institutions, it is important to determine the rates of malignancy at each institution.

Surprisingly, the rate of malignancy for nodules categorized as Bethesda III increased from 16% for patients who underwent immediate surgery to 45.5% for those who underwent 2 sequential FNAC tests, supporting repeated FNAC for this category of lesions. No significant difference was seen in this regard for Bethesda IV nodules.

Future studies investigating the use of gene expression assays and molecular assays on FNAC material in predicting the malignancy of undetermined thyroid nodules diagnosed as Bethesda classes III and IV could help to eliminate subjectivity. Future research should also examine whether there is a correlation between patient demographics and malignancy rates.

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Bayrak BY, Eruyar AT. Malignancy rates for Bethesda III and IV thyroid nodules: a retrospective study of the correlation between fine-needle aspiration cytology and histopathology. BMC Endocr Disord. 2020;20:48.