A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies - TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium

Pulmonary sclerosing hemangioma (SH) is a lung neoplasm of uncertain histog enesis that is composed of two major cell types: surface and round cells. T he authors studied 100 cases of pulmonary SH that presented as a peripheral (95%), solitary (96%) mass of less than 3 cm in diameter (74%) in asymptom atic patients who were mostly women (83%) with a mean age of 46.2 years. Im munohistochemistry of multiple epithelial, mesothelial, pneumocyte, neuroen docrine, and mesenchymal markers was performed on 47 cases to investigate t he histogenesis of this neoplasm. Both surface and round cells stained with epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF- 1) in more than 90% of cases; however, the round cells were uniformly negat ive for pancytokeratin and positive for cytokeratin-7 and CAM5.2 in only 31 % and 17% of cases, respectively. Surfactant proteins A and B as well as Cl ara cell antigen were positive in varying numbers of surface cells but they were negative in the round cells. Neuroendocrine cells either as isolated scattered cells or as a tumorlet within the center of SH were detected (chr omogranin, Leu-7, synaptophysin positive) in three cases. The expression of TTF-1 in the absence of surfactant proteins A and B and Clara cell antigen s in the round cells of SH suggests that they are derived from primitive re spiratory epithelium. The alveolar pneumocytes and neuroendocrine cells map either represent phenotypic differentiation of a primitive respiratory epi thelial component or they may correspond to non-neoplastic entrapped or hyp erplastic elements. The concomitant positivity of both cell types in SH for TTF-1 and EMA, and the negativity of round cells for pancytokeratin and ne uroendocrine markers, provide useful clues not only for histogenesis but al so for the diagnosis of this lung neoplasm.