Tumours and tumour-like lesions of myofibroblasts may present diagnostic difficulty because of their rarity and because of uncertainties in identifying the myofibroblast. The objectives of this review are to provide a definition of the myofibroblast and an account of its biology for facilitating an understanding of the cell and of myofibroblastic lesions; and to describe, in the context of common diagnostic problems, the features of benign and malignant myofibroblastic lesions. The main characteristics of the myofibroblast include a spindled or stellate morphology; immunostaining for α-smooth muscle actin and the extra domain A variant of cellular fibronectin; and an ultrastructure of rough endoplasmic reticulum, peripheral contractile filaments and the cell-to-matrix junction known as the fibronexus. On this basis, lesions traditionally regarded as myofibroblastic are shown to vary in their level of differentiation, and some appear to be smooth muscle rather than myofibroblastic. Immunohistochemistry and electron microscopy, used together, are emphasised as being important for maximum diagnostic confidence in some myofibroblastic lesions.
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