Figure 4.

Histopathologic characterization of cholangiocellular lesions developing in Notch1 intracellular domain (Nicd)/Yes-associated protein (Yap) (YapS127A) mice, as revealed by hematoxylin and eosin (HE) staining. A: Most of the lesions developed as small microcysts lined by a flat benign epithelium, often increasing in size but retaining their benign appearance. B and C: The stromal component of these lesions was rich in inflammatory cells, which disappeared along with tumor progression. D–F: Although most of these lesions increased in size without altering the cytologic features, some evolved into an intracystic micropapillary proliferation of atypical cells (boxed area in D) and became eventually invasive (F), with the septa between the cysts being infiltrated by invasive intrahepatic cholangiocarcinoma (iCCA). G: Often the invasive iCCA destroyed the cystic architecture of the more benign lesions. H and I: Concomitantly with these lesions, a second type of lesions developed into iCCA without an intermediate step of cystic lesions. These tumor lesions consisted of malignant cells with atypical nuclei. Scale bars: 50 μm (C and E); 100 μm (A, B, F, H, and I); 500 μm (G); 1000 μm (D). Original magnification: ×20 (D); ×40 (G); ×200 (A, B, F, H, and I); ×400 (C and E).