The role of cytological subcategorization in indeterminate thyroid nodules: Optimizing management strategies by refining malignancy risk stratification.

PURPOSE: Indeterminate Thy3a (Bethesda III equivalent) thyroid nodules pose significant diagnostic and therapeutic dilemmas. This study evaluates a novel institutional approach that utilizes cytological subcategorization by nuclear atypia, to refine malignancy risk and guide management between active surveillance (AS) and surgery.

METHODS

A retrospective cohort of adult patients with Thy3a cytology following ultrasound-guided aspiration (2019-2023) was reviewed. Exclusion criteria were incomplete records or < 2 years follow-up for the AS subgroup. Patients with non-nuclear atypia were offered surveillance unless symptomatic, while those with nuclear atypia were recommended for surgery. Primary outcomes included both histopathology-based (hROM) and overall estimated risk of malignancy (oROM), oncological outcomes including disease-free (DFS) and disease-specific survival (DSS).

RESULTS

188 patients with 190 thy3a thyroid nodules met inclusion criteria (female = 66%, median age = 49 years). AS was followed in 56.4% (n = 71) of the non-nuclear atypia subgroup, while 89.1% (n = 57) of the nuclear atypia subgroup underwent surgery. From the AS Thy3a non-nuclear cohort, 95.8% (n = 68/71) remained stable for ≥ 24 months. hROM and oROM were significantly higher in the nuclear than non-nuclear atypia nodules (59.6% versus 23.6% and 55.6% versus 11.3%, both p<.001). On multivariable analysis, nuclear atypia was an independent predictor of malignancy. Overall, 95.7%, (n = 45/47) of malignant Thy3a nodules were low-risk differentiated thyroid cancers. Over a median 42-month follow-up, 5-year DFS and DSS were 95.3% and 97.9% respectively.

CONCLUSION

Cytological subcategorization of Thy3a thyroid nodules by nuclear atypia offers a valuable tool for risk stratification, enabling a tailored management approach, minimizing unnecessary surgeries, while ensuring prompt surgical intervention for high-risk cases.