Myofibroblastic sarcomas: a brief review of sarcomas showing a myofibroblastic line of differentiation and discussion of the differential diagnosis

Abstract

Although myofibroblasts have been intensively studied during the last three decades there is still a lack of consensus regarding their exact role and position in the spectrum of proliferative and neoplastic spindle cell lesions. This especially concerns the question of whether myofibroblastic neoplasms, or in other words a myofibroblastic line of differentiation in mesenchymal neoplasms, exist or not. Some authors question the existence of benign and particularly malignant myofibroblastic neoplasms, and suggest rather that myofibroblasts represent a functional stage in neoplastic processes arising from fibroblasts, smooth muscle cells or pericytes. It has been claimed that the ultrastructural evidence of so-called fibronexus (microtendons) and stress fibres plays a crucial role in the diagnosis of myofibroblastic neoplasms, and that myofibroblasts are defined essentially by electron microscopy. However, in diagnostic surgical pathology mesenchymal neoplasms are classified according to the cell type they most closely resemble, and it is not surprising that, in neoplastic processes, variable genetic and morphological changes occur. Therefore it seems impractical that a single specialised organelle such as the enigmatic fibronexus should be the limitation for the delineation of a line of differentiation. For practical purposes, myofibroblastic neoplasms are composed of spindle-shaped tumour cells set in a more or less collagenous matrix. Myofibroblastic tumour cells contain ill-defined eosinophilic cytoplasm and fusiform nuclei that are either elongated and wavy or plumper and vesicular. Neoplastic myofibroblasts stain positively for muscle actin, alpha-smooth muscle actin, and/or desmin and are characterised by a variable immunophenotype. Ultrastructurally, myofibroblasts share features of fibroblasts and smooth muscle cells but differ from both cell types. Given these diagnostic criteria it is most likely that, in addition to well-known reactive and benign myofibroblastic proliferations, a variety of clinicopathological forms of myofibroblastic sarcomas (myofibrosarcomas) occur. In this spectrum congenital and infantile fibrosarcoma, inflammatory myofibroblastic tumour, low-grade myofibroblastic sarcoma, and high-grade (‘MFH’-like) myofibroblastic sarcoma are briefly reviewed and their differential diagnosis is discussed.