Combined smooth muscle and melanocytic differentiation in lymphangioleiomyomatosis

Pulmonary lymphangioleiomyomatosis (LAM) is characterized by abnormal proliferation of immature-looking smooth muscle (SM)-like cells (LAM cells), leading to lung destruction and cyst formation. In addition to expressing some SM markers, scattered LAM cells express the melanocytic maker gp100, which is recognized by antibody HMB45, suggesting that at least a few LAM cells may have melanocytic differentiation. Here we immunostained 26 LAM samples for several melanocyte-related proteins. These studies showed that all LAM cells express tetraspanin CD63, a melanoma-associated protein that belongs to the transmembrane 4 superfamily. The majority of LAM cells also immunoreacted with PNL2, an antibody against a yet uncharacterized melanocytic antigen. Furthermore, we examined the co-expression of PNL2 and Ki-67, an indicator of cell proliferation, and found that PNL2-positive LAM cells showed a significantly lower proliferation rate compared with their negative counterparts. Our findings shed new light on the nature of the LAM cells by demonstrating their combined SM and melanocytic differentiation and the existence of subpopulations with different proliferative potential. Furthermore, these studies provided two new antibodies useful in the diagnosis of LAM.