A critical examination of the immunophenotype of pulmonary sclerosing hemangioma

The authors studied a series of 21 cases of pulmonary sclerosing hemangioma (SH) to address conflicting and unconfirmed reports of immunohistologic evidence of differentiation that have been made in the literature. They found the lesional cells of SH to be epithelial membrane antigen (EMA) positive (21 of 21 cases), to be keratin positive only infrequently and focally (six of 21), and to be nonreactive for carcinoembryonic antigen, S-100, smooth muscle actin, and CD34. Faint nuclear staining was seen for estrogen receptors, whereas progesterone receptors were expressed strongly in 17 cases. Neuroendocrine markers (chromogranin A, adrenocorticotrophic hormone, human growth hormone, and calcitonin) were negative uniformly on the lesional cells except for one case in which rare chromogranin-positive cells were present and another case in which rare human growth hormone-positive cells were seen. In contrast to the general EMA-positive, keratin-negative phenotype of the lesional cells, the cells lining the papillae or air spaces within the SH were typically positive for both markers. The following other lesions were identified in the cases studied: carcinoid tumorlets (n = 2), a neuroendocrine body (n = 1), and multiple meningothelial-like nodules (n = 1). All were clearly separable from the SH on morphologic grounds. The authors interpreted these to be chance occurrences of unrelated lesions. Recognition of the phenotype of SH as EMA positive, keratin weak to negative, and negative for S-100, smooth muscle actin, and neuroendocrine markers is notable in its differential diagnosis from other lesions. This phenotype does not suggest a precise lineage or type of differentiation for SH.