Thyroid nodules are common and mostly harmless. Doctors use The Bethesda System for Reporting Thyroid Cytopathology to classify thyroid nodules. This system categorizes findings from a fine-needle aspiration (FNA) biopsy.
What Bethesda Category 3 Means
Bethesda Category 3, known as “Atypia of Undetermined Significance” (AUS) or “Follicular Lesion of Undetermined Significance” (FLUS), indicates atypical thyroid nodule cells that cannot be definitively classified as benign or malignant. It represents an indeterminate diagnosis.
Interpreting Category 3 results is challenging due to subtle cellular changes and inherent variability in cell appearance. This diagnostic ambiguity often requires further evaluation.
While the Bethesda System aims to standardize reporting, Category 3 remains controversial due to inconsistent results and varying malignancy risks. “Atypia of undetermined significance” signifies an intermediate histological grade between benign and malignant classifications.
Understanding the Malignancy Risk
A primary concern with a Bethesda Category 3 diagnosis is the likelihood of cancer. The reported malignancy risk for these nodules has varied in scientific literature, initially estimated between 5% and 15%.
However, more recent studies suggest higher rates, with some reports indicating malignancy rates as high as 38% to 55%. Other analyses have found rates ranging from 26.6% to 37.8%. The overall malignancy rate can also vary depending on specific cytological features.
Several factors influence the actual malignancy risk for a Bethesda Category 3 nodule. A patient’s clinical history, such as family history of thyroid cancer or prior radiation exposure, can increase suspicion. Ultrasound features also play a role; nodules with suspicious characteristics like irregular margins, microcalcifications, or a taller-than-wide shape are associated with a higher risk. Specific cytological findings, such as nuclear atypia, can also elevate the malignancy risk.
Navigating Treatment Approaches
Managing Bethesda Category 3 thyroid nodules involves several tailored approaches. These options aim to confirm the nodule’s benign nature or identify malignancy to guide intervention.
Observation
One management strategy involves careful observation of the nodule. This typically entails repeat ultrasound examinations to monitor for changes in nodule size or suspicious features. Clinical follow-up also assesses the patient’s general health and any new symptoms related to the thyroid. This conservative approach is often chosen when the initial malignancy risk is considered lower, or when other factors suggest a less aggressive course.
Repeat Fine Needle Aspiration (FNA)
A common next step for indeterminate Bethesda Category 3 nodules is a repeat FNA. This involves performing another biopsy of the nodule, usually after a period of several months, to obtain additional cells for analysis. The rationale is that a second biopsy may yield a more definitive diagnosis, either benign, suspicious, or malignant, thereby clarifying the initial indeterminate result. While a repeat FNA can be beneficial, approximately 38.5% of repeat FNAs may still result in an AUS/FLUS diagnosis, highlighting the persistent challenges in some cases. However, some studies indicate that a significant portion, around 42.7%, of repeat FNAs can result in a benign diagnosis.
Molecular Testing
Molecular testing has emerged as a valuable tool for further stratifying the risk of malignancy in Bethesda Category 3 nodules. These tests analyze the genetic material from the nodule cells for specific gene mutations or gene expression patterns that are associated with thyroid cancer. Examples include gene expression classifiers or mutation panels.
A negative molecular test result, indicating the absence of certain genetic markers, often has a high negative predictive value, meaning a very low likelihood of malignancy. This information can help patients and their doctors avoid unnecessary diagnostic surgeries, allowing for continued observation. Conversely, a positive molecular test may indicate a higher risk, guiding a decision toward surgical intervention.
Surgical Options
Surgical removal of the thyroid nodule or a portion of the thyroid gland may be recommended, particularly when the suspicion of malignancy remains high despite other diagnostic efforts. A common surgical option is a lobectomy, where only the lobe of the thyroid containing the nodule is removed. This procedure is often considered when the nodule’s characteristics or molecular test results suggest a moderate risk of cancer, or if the nodule is large and causing symptoms.
A total thyroidectomy, which involves removing the entire thyroid gland, might be recommended in cases where there is a higher suspicion of malignancy, confirmed malignancy, or if the patient has multiple suspicious nodules. The decision for surgery, and the extent of the surgery, is carefully considered based on the estimated risk of malignancy, the size and features of the nodule, the patient’s overall health, and their personal preferences. A multidisciplinary team discussion, involving endocrinologists, surgeons, and pathologists, often guides the final management plan to ensure the most appropriate and individualized approach.