Jo Uiree, Sung Chang Ohk, Kim Kyu-Rae
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine.
Department of Pathology, Seegene Medical Foundation, Seoul, Korea.
Int J Gynecol Pathol. 2025 Sep 1;44(5):430-435. doi: 10.1097/PGP.0000000000001085. Epub 2024 Dec 3.
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.
类似于良性尿路上皮的移行细胞化生（TCM）常见于输卵管远端和/或邻近的间皮表面周围；然而，其组织发生学在很大程度上仍不清楚。我们观察到在输卵管上皮下方的早期TCM病灶中出现了细胞角蛋白（CK）17阳性储备细胞层，这使我们推测TCM可能起源于储备细胞。为了阐明TCM的组织发生过程，我们分析了在输卵管上皮（31个病灶）和盆腔间皮（35个病灶）中出现的TCM病灶的组织形态学特征以及CK17、CK5/6、p63、GATA-3、雌激素受体（ER）和雄激素受体（AR）的免疫表型。总体而言，输卵管上皮和盆腔间皮中TCM的组织学特征和免疫表型相似，但在TCM发展过程中出现了明显差异。单层表达CK17的储备细胞在输卵管上皮下方变得明显，随着这些细胞增殖，CK17表达消失。相比之下，在间皮下方出现单层储备细胞之前，输卵管 - 腹膜交界处旁边的一小段正常间皮就表达CK17，这表明间皮本身具有潜在的储备/干细胞功能。然后，两个区域的单层细胞增殖并分化，表现出尿路上皮特征，包括核沟和透明细胞质。在单层储备细胞阶段出现强烈的CK5/6、p63和GATA-3表达，并在此后维持到完全分化的TCM。AR在正常输卵管上皮和盆腔间皮中均有表达，在大多数储备细胞衍生群体中，在TCM的整个组织发生过程中AR和ER的强度呈反比（98.5%），AR表达明显强于ER。TCM的组织发生始于输卵管上皮和盆腔间皮下方储备细胞的出现，这些储备细胞随后增殖并分化为尿路上皮。AR可能在TCM的组织发生过程中起重要作用。
