The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. Part 1--normal and reactive cells.

The myofibroblast is essential for the integrity of the mammalian body by virtue of its role in wound-healing, but it can also threaten it by its ability to promote tumour progression. It is an almost universal cellular component in mammalian lesions, but not a typical component of normal untraumatised tissues. Partly because of its absence from normal tissue, it has not been part of conventional histology teaching. This has contributed to difficulties in appreciating the nature of the myofibroblast and defining it by scientists interested in the mechanism of disease and pathologists wanting to diagnose myofibroblastic rumours. This paper documents the features of the myofibroblast with an emphasis on ultrastructure. A base-line of understanding is first provided by a description of normal cells found in untraumatised tissues, from which the myofibroblast has on occasion been postulated as arising, or with which, to varying degrees, the myofibroblast has been confused--fibroblasts, smooth-muscle cells, endothelium, pericytes, myoepithelium and lymphoid reticulum cells. The biology, light microscopy features and ultrastructure of the myofibroblast are then documented for comparison. Features emphasised for defining the myofibroblast include: a spindled cell morphology, an abundant matrix, immunostaining for alpha-smooth-muscle actin (in the absence of desmin and h-caldesmon) and the ED-A splice variant of cellular fibronectin, rough endoplasmic reticulum, peripherally located smooth-muscle type myofilaments, a Golgi apparatus producing collagen-secretion granules, gap junctions and fibronexus junctions. The fibronexus is emphasised as a distinctive organelle for identifying the myofibroblast and lamina is emphasised as absent. The mechanism by which myofibroblasts arise in granulation tissue and promote tumour progression is discussed briefly, and an appendix provides summaries of the involvement of myofibroblasts in non-neoplastic diseases.