30-Second Takeaway
- Cyst-fluid NGS in mixed-type IPMN sharply improves specificity for advanced neoplasia over imaging-based criteria alone.
- MTAP and S100P immunostains materially enhance diagnostic confidence for PDAC on scant FNAB material.
- Routine H&E features—tumor budding and cell nest size—offer inexpensive pre-treatment risk stratification in cervical cancer.
Week ending December 27, 2025
Practice-Shaping Updates in Surgical, Molecular, and Digital Pathology
Cyst-fluid NGS HRM panel strongly predicts advanced neoplasia in mixed-type IPMN
In 674 IPMN patients, mixed-type lesions showed substantially higher rates of high-risk mutations (TP53, SMAD4, CTNNB1, MTOR) than branch-duct IPMN. Mixed-type IPMN were independently associated with high-risk mutations on multivariable analysis (odds ratio 3.42; 95% CI, 1.72–6.82). Preoperative cyst-fluid NGS detection of any high-risk mutation predicted advanced neoplasia in mixed-type IPMN with 90% sensitivity and 100% specificity. Imaging-based worrisome features or high-risk stigmata were highly sensitive but had very poor specificity for advanced neoplasia.
MTAP and S100P IHC panel improves PDAC diagnosis in EUS-FNAB samples
This study evaluated MTAP and S100P immunohistochemistry in 27 EUS-FNAB pancreatic masses, correlating MTAP loss with CDKN2A alterations. About 25% of FNAB-diagnosed PDACs showed complete loss of MTAP expression, giving 100% positive predictive value but modest sensitivity (31.5%). S100P was positive in 71% of PDAC cases, while the single benign case was S100P negative, supporting its utility as a malignancy marker. Combining MTAP and S100P increased sensitivity to 75% while maintaining 100% specificity for PDAC diagnosis on FNAB material.
Tumor budding and cell nest size on H&E biopsies predict cervical cancer survival
In 182 FIGO 2018 stage I–IIA cervical cancers, pretreatment biopsy tumor budding and cell nest size independently predicted overall survival. Multivariable analysis showed tumor budding (HR 2.06) and small cell nest size (HR 2.16) as adverse prognostic factors. Tumor budding alone (AUC 0.7065) slightly outperformed cell nest size (AUC 0.6975) for survival discrimination. Combining tumor budding and cell nest size yielded the best performance (AUC 0.7192) in time-dependent ROC analyses.
References
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Additional Reads
Optional additional studies from this edition.