LGR5 and benign neoplasm: However, it is noteworthy that, even though a short-term subcutaneous transplantation of AM 3D organoids into nude mice led to xenograft formation (Fig. 4), demonstrating the self-renewal and propagating capabilities of LGR5+ EpiSCs in vivo, we still cannot establish an appropriate animal model for long-term observation of the role of this unique subpopulation of epithelial stem-like cells in the initiation and progression of AM, a common challenge for most types of benign tumors due to their intrinsically benign and slow progression properties.