Calponin and h-caldesmon in soft tissue tumors: Consistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicates traits of smooth muscle differentiation

Currently, the immunohistochemical evaluation of smooth muscle differentiation is usually based on desmin, which also reacts with skeletal muscle and is not present in all smooth muscle tumors, and a-smooth muscle actin, which reacts with myoepithelial cells. Neither marker typically reacts with gastrointestinal stromal tumors (GISTs), previously classified as smooth muscle tumors or presently often classified as smooth muscle/stromal tumors. Two cytoskeleton-associated actin-binding proteins, calponin (CALP) and h-caldesmon (HCD), are putative smooth muscle markers that also react with myoepithelia These markers are of particular interest in the immunohistochemical analysis of tumors; neither of them has been extensively documented in soft tissue tumors. In this study, we evaluated selected normal and reactive tissues and more than 250 mesenchymal tumors for CALF and HCD. Both markers were expressed in parenchymal and vascular smooth muscle cells in various organs and in myoepithelial cells. CALF also reacted with myofibroblasts of desmoplastic stroma. All of our 25 benign smooth muscle tumors from various locations were positive for CALP and HCD, as were most of the retroperitoneal and uterine leiomyosarcomas. HCD was more specific, because CALF also reacted with myofibroblastic lesions. The common reactivity of malignant fibrous histiocytomas with CALP and HCD suggests a combination of myofibroblastic and smooth muscle differentiation in these tumors. The GISTs (c-kit positive, usually actin negative) showed nearly consistent HCD reactivity, suggesting traits of smooth muscle differentiation. GISTs were usually CALP negative and showed a CALF expression pattern similar to that of a-smooth muscle actin. Although nonmuscle, non-myofibroblastic tumors were negative for CALF and HCD, synovial sarcomas showed streaks of CALP-positive cells of unknown significance. CALF and HCD should be explored as markers to identify myofibroblastic and smooth muscle cell differentiation in mesenchymal tumors.