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Purpose <p>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.</p> Methods <p>A retrospective cohort of adult patients with Thy3a cytology following ultrasound-guided aspiration (2019–2023) was reviewed. Exclusion criteria were incomplete records or &lt; 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).</p> Results <p>188 patients with 190 thy3a thyroid nodules met inclusion criteria (female = 66%, median age = 49 years). AS was followed in 56.4% (<i>n</i> = 71) of the non-nuclear atypia subgroup, while 89.1% (<i>n</i> = 57) of the nuclear atypia subgroup underwent surgery. From the AS Thy3a non-nuclear cohort, 95.8% (<i>n</i> = 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 <i>p</i>&lt;.001). On multivariable analysis, nuclear atypia was an independent predictor of malignancy. Overall, 95.7%, (<i>n</i> = 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Stavroula Mouratidou,
  • Mark Yanni,
  • Aleix Rovira,
  • Asit Arora,
  • Jean-Pierre Jeannon,
  • Martina T. Munonyara,
  • Anu Malhorta,
  • Paul V. Carroll,
  • Ashish Chandra,
  • Ricard Simo

摘要

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.