Walthard Cell Nests/Transitional Cell Metaplasia in Distal Fallopian Tubes and Pelvic Peritoneum Derived From Reserve Cells

Transitional cell metaplasia (TCM) resembling benign urothelium is commonly seen around the distal fallopian tube and/or neighboring mesothelial surface; however, its histogenesis remains largely unknown. We observed the emergence of a cytokeratin (CK) 17-positive reserve cell layer in early TCM foci beneath the tubal epithelium, leading us to hypothesize that TCM could be derived from reserve cells. To elucidate the histogenetic process of TCM, we analyzed the histomorphologic features and immunoprofiles for CK17, CK5/6, p63, GATA-3, estrogen receptor (ER), and androgen receptor (AR) in TCM foci arising in the tubal epithelium (31 foci) and pelvic mesothelium (35 foci). Overall, the histologic features and immunoprofiles of TCM in the tubal epithelium and pelvic mesothelium were similar, but distinct differences appeared during TCM development. A single-layered CK17-expressing reserve cells became apparent beneath the tubal epithelium, and the CK17 expression disappeared as these cells multiplied. In contrast, a short segment of normal mesothelium next to the tubo-peritoneal junction expressed CK17 even before the emergence of a single-layered reserve cells beneath the mesothelium, suggesting a potential reserve/stem cell function within the mesothelium itself. Then, the single-layered cells in both areas multiplied and differentiated to display urothelial characteristics, including nuclear grooves and clear cytoplasm. Strong CK5/6, p63, and GATA-3 expression appeared in the single-layered reserve cell stage and was maintained thereafter to the fully differentiated TCM. AR was expressed in both normal tubal epithelium and pelvic mesothelium, and the intensity of AR and ER were reciprocal during the entire histogenetic process of TCM in most reserve cell-derived populations (98.5%), AR expression being significantly stronger than ER. The histogenesis of TCM was initiated from the emergence of reserve cells beneath the tubal epithelium and pelvic mesothelium, which then multiplied and differentiated into urothelium. AR might have an important role during the histogenesis of TCM.