Polychromatic polarization microscopy identified malignant collagen fiber patterns in four percent of pancreatic tissue cores labeled as “adjacent normal,” suggesting potential diagnostic value in detecting subtle stromal changes near tumor margins.
In a study published in Modern Pathology, researchers evaluated the ability of polychromatic polarization microscopy (PPM) to differentiate collagen fiber morphology in benign pancreatic tissues and pancreatic ductal adenocarcinoma (PDAC) using standard hematoxylin and eosin–stained slides. Given the limitations of second harmonic generation microscopy in clinical workflows, the researchers sought a method suitable for routine pathology.
The study, led by Mahsa Chitsaz of the Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio, and colleagues analyzed 60 histologic specimens—20 each of normal pancreas, chronic pancreatitis, and PDAC—as well as 96 tissue microarray cores from a commercially available panel. Collagen fiber features such as alignment, thickness, periodicity, and orientation relative to epithelium were assessed via PPM using a microscope equipped with a Polychromatic PolScope module. Two additional pathologists were trained using 53 annotated photomicrographs before four total pathologists independently evaluated 48 TMA punches for malignant collagen signatures. After initial training, interobserver concordance was seventy-nine percent. Following review of discrepant cases, agreement increased to ninety percent. Notably, two cores (four percent) labeled as “adjacent normal” displayed collagen patterns consistent with PDAC stroma.
PPM revealed marked differences between tissue types. In normal pancreas, collagen fibers exhibited regular periodicity and loose, concentric orientation not apposed to ductal epithelium. Chronic pancreatitis displayed tightly bundled, directionally aligned fibers, while atrophic tissue retained organized, corrugated bundles. In contrast, PDAC tissues showed randomly oriented, straight or angular fibers with irregular striations and loss of periodicity. Malignant collagen often appeared directly apposed to tumor epithelium, including concentric or perpendicular arrangements and, in some cases, crossing malignant cell clusters.
The researchers concluded that PPM enables high-resolution visualization of stromal architecture in routinely processed histologic samples and effectively distinguishes malignant from benign collagen configurations. Given its compatibility with standard diagnostic microscopes and existing pathology workflows, PPM may serve as a practical alternative to second harmonic generation microscopy for identifying prognostically relevant stromal changes in PDAC.