Diffuse leiomyomatosis of the esophagus: disorder of cell-matrix interaction?

Diffuse leiomyomatosis (DL) is rare condition characterized by proliferation of smooth muscle in the upper gastrointestinal tract. Most cases are associated with X-linked Alport syndrome and have partial deletions in the genes encoding both the alpha5 and alpha6 chains of collagen type IV. We studied aspects of cell-matrix interaction of myocytes in an esophagogastrectomy specimen from a 12-year-old patient with DL. Myocytes had central areas of cytoplasmic rarefaction, which were actin positive and desmin poor, with the reverse pattern of staining at the cell periphery. Electron microscopy (EM) showed that the areas of rarefaction consisted of disorganized aggregates of filaments. The basement membranes ranged from thickened to thinned or absent. Immunohistochemical staining for the alpha1-alpha4 chains of collagen type IV, the alpha1, alpha2, beta2, and gamma1 chains of laminin, nidogen, type VI collagen, and fibronectin was normal. There was loss of the alpha5 and alpha6 chains of collagen type IV and the beta1 chain of laminin. Normal staining for alpha1, alpha2, alpha3, alpha4, alpha6, alpha8, and beta1 integrins was noted. Staining for alpha5 integrin varied from normal to reduced or negative in different cells. In DL, a primary abnormality of basement membrane may be associated with disorganization of the contractile apparatus and alterations of certain integrins. This may reflect a disturbance of cell-matrix interactions that play a role in cell differentiation and internal organization.