Diffuse Leiomyomatosis of the Esophagus: Disorder of Cell-Matrix Interaction?

Abstract

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.

Leiomyomatosis-Like Lymphangioleiomyomatosis of the Colon in a Female with Tuberous Sclerosis

“…"Leiomyomatosis" is a term used to describe the occurrence of multiple, confluent masses in the bowel wall caused by multifocal proliferation of smooth muscle cells forming focal tumor masses (8). In the gastrointestinal tract, diffuse leiomyomatosis is more often reported in the esophagus and upper gastrointestinal tract, being usually associated with X-linked Alport syndrome (9), but this is an uncommon event with fewer than 100 cases in the literature, most of which are single case reports (9,10,11,12,13).…”

Collagens: building blocks at the end of the development line

“…The most striking effect of mutations in the type IV collagen genes is the combined Alport syndrome and diffuse esophageal leiomyomatosis seen with deletions that extend from intron 2 of the COL4A6 gene into the COL4A5 gene [38]. It is not clear if there is a gene involved in the control of smooth muscle growth located in the large intron 2 or if the presence of both gene products is important for that function [39,40].…”

Deletion of the 5′exons ofCOL4A6is not needed for the development of diffuse leiomyomatosis in patients with Alport syndrome

“…As a result, degradation of the physical support for ECM components provided by the BM type IV collagen network, and the deregulation of the tissue-specific ECM-cell interactions that coordinate intracellular signalling essential for cell growth and proliferation, might favour the development of the leiomyomata 7 20 43 48. Further studies are needed to test these assumptions.…”