<p>Thyroid tumors with questionable capsular invasion (CI) or angioinvasion (AI) pose diagnostic and management challenges. The World Health Organization (WHO) recognizes these borderline entities as follicular tumors of uncertain malignant potential (FT-UMP) or well-differentiated tumors of uncertain malignant potential (WDT-UMP). We have conducted a retrospective, single-center study of all thyroid tumors diagnosed as UMP (2005–2025). Of 534 tumors initially labeled “uncertain malignant potential,” application of exclusion criteria yielded 324 tumors from 318 patients with questionable CI and/or AI. Clinicopathological characteristics, molecular testing data, postoperative laboratory values, imaging, and outcomes were analyzed. UMP was diagnosed in 0.5% of thyroid surgeries; median age 53-years and 2:1 female predominance. Cohort classification included oncocytic FT-UMP (OFT-UMP) (40%), FT-UMP (34%) and WDT-UMP (26%). Median tumor size was 3.2&#xa0;cm. Molecular testing yielded <i>RAS</i> variants most frequently (79%), followed by <i>RAS</i>-like variants (4%), gene fusions (4%), <i>PTEN</i> loss (4%), and <i>TERT</i> promoter alterations (3%). With follow-up extending up to 15 years, no recurrences or metastases were recorded, supporting the UMP designation as tumors of low biological potential and favoring conservative management. Longer-term, multi-institutional studies will refine risk stratification and clinical management.</p>

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Thyroid Tumors of Uncertain Malignant Potential (UMP)- Clinicopathologic and Molecular Characterization of 324 Cases

  • Bayan A. Alzumaili,
  • William C. Faquin,
  • Adam S. Fisch,
  • Tejas S. Athni,
  • Gregory W. Randolph,
  • Marika D. Russell,
  • Peter M. Sadow

摘要

Thyroid tumors with questionable capsular invasion (CI) or angioinvasion (AI) pose diagnostic and management challenges. The World Health Organization (WHO) recognizes these borderline entities as follicular tumors of uncertain malignant potential (FT-UMP) or well-differentiated tumors of uncertain malignant potential (WDT-UMP). We have conducted a retrospective, single-center study of all thyroid tumors diagnosed as UMP (2005–2025). Of 534 tumors initially labeled “uncertain malignant potential,” application of exclusion criteria yielded 324 tumors from 318 patients with questionable CI and/or AI. Clinicopathological characteristics, molecular testing data, postoperative laboratory values, imaging, and outcomes were analyzed. UMP was diagnosed in 0.5% of thyroid surgeries; median age 53-years and 2:1 female predominance. Cohort classification included oncocytic FT-UMP (OFT-UMP) (40%), FT-UMP (34%) and WDT-UMP (26%). Median tumor size was 3.2 cm. Molecular testing yielded RAS variants most frequently (79%), followed by RAS-like variants (4%), gene fusions (4%), PTEN loss (4%), and TERT promoter alterations (3%). With follow-up extending up to 15 years, no recurrences or metastases were recorded, supporting the UMP designation as tumors of low biological potential and favoring conservative management. Longer-term, multi-institutional studies will refine risk stratification and clinical management.