Type-II pneumocyte differentiation in pulmonary sclerosing hemangioma: ultrastructural differentiation and immunohistochemical distribution of lineage-specific transcription factors (TTF-1, HNF-3 alpha, and HNF-3 beta) and surfactant proteins.

Sclerosing hemangioma (PSH) is a rare pulmonary tumor, in which two types of tumor cells could be histologically discerned--surface and stromal tumor cells. Nine tumor-tissue specimens from six female Japanese patients were studied, focusing on the distribution of several transcription factors related to lung epithelial development and surfactant proteins and comparing the ultrastructural features of the tumor cells. The immunohistochemical analysis revealed that the surfactant proteins of surfactant apoprotein A, surfactant protein B, and prosurfactant protein C were distributed in many of the surface-lining cells and in a small number of stromal-tumor cells. In addition, the nuclei of the tumor cells stained positive for thyroid transcription factor 1 (TTF)-1, hepatocyte nuclear factor (HNF)-3 alpha, and HNF-3 beta. In situ hybridization staining for TTF-1 showed similar positive signals. Ultrastructurally, two types of tumor cells showed similar features, but stromal tumor cells lost the definitive apico-lateral differentiation compared with the surface tumor cells and showed restricted surface differentiation between the adjacent tumor cells, forming small lumina accompanied by microvilli and occasional multi-vesicle or multi-lamellar bodies. Conclusively, the real tumoral population being undifferentiated stromal cells, the lining cells are fully differentiated type-II pneumonocytes. PSH is a proliferation of rather fetal type-II pneumonocytes (pneumocytoma or pneumoblastoma?).