Re-appraisal of the Diagnostic Value of PAS-D Staining in TTF-1-NEGATIVE NSCLC Subclassification: A Large Real-World Cohort Study
In brief
PAS-D staining classifies about 30% of TTF-1-negative lung cancers as adenocarcinoma
In a review of 2,611 NSCLC samples, PAS-D identified adenocarcinoma in 30.3% of tumors lacking both TTF-1 and p40, and was far more sensitive than Napsin A (89.7% vs 25.9% in TTF-1-negative cases). Adding PAS-D to the standard panel raised overall sensitivity to 97.5%, suggesting a simple way to improve subclassification, especially when tissue is limited.
- Journal
- Pathology international (Q1)
- Published
- 1 July 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Dogu Vuralli Bakkaloglu, Hafize Ozdemir, Melek Buyuk, Dilek Yilmazbayhan, Yasemin Ozluk
- PMID
- 42502894
- DOI
- 10.1111/pin.70154
Why clinicians should know about it
- Picked for Histology (paper of the day, 27 July 2026).
Abstract
Subclassification of NSCLC is critical for therapeutic decision-making, particularly in small biopsies and cytology specimens where ancillary testing must be limited. Although the TTF-1/p40 panel is widely used to distinguish adenocarcinoma (ADC) from squamous cell carcinoma, a subset of NSCLCs remains unclassified, highlighting the need for adjunctive markers. Periodic acid-Schiff with diastase (PAS-D) is readily available but underutilized. We retrospectively reviewed 2611 NSCLC specimens from 2298 patients. Diagnosis was based on morphology alone in 38.6% of cases, while ancillary testing was required in 57.7%. Among 287 TTF-1neg/p40neg tumors, 30.3% were classified as ADC using PAS-D and/or Napsin A. PAS-D demonstrated higher sensitivity than Napsin A (71.8% vs. 69.3%), and markedly outperformed Napsin A in TTF-1-negative ADCs (89.7% vs. 25.9%, p < 0.001). This finding reflects biological differences between terminal respiratory unit-derived ADCs and non-terminal airway tumors, in which PAS-D positivity is more diagnostically informative. Combined testing improved sensitivity, with the TTF-1/PAS-D panel achieving 97.5%. This study highlights the underappreciated diagnostic value of PAS-D, particularly in TTF-1-negative tumors. PAS-D represents a simple, effective adjunct to routine diagnostic panels. Therefore, incorporating PAS-D into routine panels can enhance NSCLC subclassification, particularly in TTF-1neg/p40neg tumors and support accurate diagnosis and optimal clinical management.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.