Context: Sclerosing hemangioma of the lung is well characterized histologically, but the line of differentiation expressed by the tumor cells has been unclear. Despite the implication by its name of a vascular neoplasm, sclerosing hemangioma is considered by most authorities to be an epithelial tumor, possibly related to the pulmonary epithelium.
Objectives: To determine the line of differentiation of the tumor cells with immunohistochemistry and to review the related literature.
Design: Nine cases of histologically typical pulmonary sclerosing hemangioma were studied with pan-epithelial (epithelial membrane antigen [EMA] and CAM 5.2), endothelial (CD31), neuroendocrine (chromogranin A), and pulmonary epithelial markers (thyroid transcription factor-1 and PE10). Staining intensity was separately evaluated in the pale cells of the solid areas and the cells lining the papillary structures.
Results: Both cell types were positive for thyroid transcription factor-1 and EMA in all cases (100%). Thyroid transcription factor-1 showed diffuse strong staining, and EMA staining varied from focal weak to diffuse strong. The pale cells showed focal staining for keratin (CAM 5.2) in 2 (28%) of 7 cases, and for PE10 in 5 (62%) of 8 cases. The papillary lining cells were at least focally positive with CAM 5.2 and PE10 in all cases (100%). Reactions for chromogranin and CD31 were negative in both cell types in every case. The number of PE10- or CAM 5.2-positive papillary lining cells was less than the number of EMA-positive papillary lining cells.
Conclusion: The uniform positivity for EMA is consistent with the notion that the tumor cells of sclerosing hemangioma are epithelial, and the strong thyroid transcription factor-1 positivity suggests differentiation toward pulmonary epithelium. The papillary lining cells expressing EMA as well as PE10 or CAM 5.2 likely represent entrapped metaplastic alveolar epithelium, whereas the papillary lining cells expressing only EMA more likely constitute true neoplastic cells similar to those in the solid areas.