Fig. 3: PICTURE highlighted cellular changes indicative of glioblastoma and primary central nervous system lymphoma (PCNSL) in formalin-fixed paraffin-embedded (FFPE) and frozen section tissues.
From: Uncertainty-aware ensemble of foundation models differentiates glioblastoma from its mimics
Red and blue regions denote areas highly indicative of PCNSL and glioblastoma, respectively. In the uncertainty heatmaps, brighter regions correspond to areas where the model exhibits greater confidence in its prediction. The slides are reviewed by six pathologists independently (T.M.P., A.W., S.C.L., N.S., J.A.G., M.P.N.). a PICTURE predictions of four representative glioblastoma FFPE samples. The PICTURE model highlighted regions with compact tumor and spindle cells as strong indicators of glioblastoma. Regions with polymorphous nuclei, blood, and surgical material obtained low confidence scores. In addition, perivascular inflammation and thrombosis are highlighted by PICTURE. b PICTURE predictions of four representative PCNSL FFPE samples. Cell-dense regions showing typical lymphoid morphology and scattered “tangible body macrophages” in a “starry sky” pattern are highlighted with high confidence for differentiating PCNSL from primitive glioblastoma mimics. Regions with pronounced squeezing artifacts, such as hemorrhage, are marked as areas with low diagnostic confidence. c PICTURE predictions for two representative glioblastoma frozen section samples. PICTURE associated regions with dense glioma cells, edemas, and necrosis with high prediction confidence. Low-confidence regions have lower cellularity but exhibit microvascular proliferation. d PICTURE predictions for two representative PCNSL frozen section samples. PICTURE marked compact tumors with clear intercellular separation as low confidence, and regions with clustered compact tumors received high confidence in the diagnostic prediction. PICTURE’s uncertainty mechanism can correct inaccurate preliminary direct model predictions in difficult cases, highlighting malignant cells. Characteristic features include angiocentric malignant cells and perivascular cuffs. Scale bars: 1 mm.
