Tumours of connective tissues in cattle, sheep and pigs.
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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 alpha-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 CALP and HCD. Both markers were expressed in parenchymal and vascular smooth muscle cells in various organs and in myoepithelial cells. CALP 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 CALP 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 CALP expression pattern similar to that of alpha-smooth muscle actin. Although nonmuscle, nonmyofibroblastic tumors were negative for CALP and HCD, synovial sarcomas showed streaks of CALP-positive cells of unknown significance. CALP and HCD should be explored as markers to identify myofibroblastic and smooth muscle cell differentiation in mesenchymal tumors.
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Soft tissue malignancies often show divergent differentiation, including myogenic lineage. Five rat tumors induced with 20-hydroxymethylcholanthrene (20-OH-MCA), were cultured in vitro, and three cell lines (YMC-1, YMC-2, YMC-3) were established from them. YMC-2 and -3 cells were spindle-shaped, and YMS-1 cells round and epithelioid. In confluency, YMC-3 cells formed myotubes. The nude mouse xenotransplants showed morphological features consistent with their myogenic phenotypes. Muscle-specific enzyme activities were highest in YMC-3 cells. These lines may be useful in the investigation of the myogenic differentiation of undifferentiated mesenchymal cells.
The caveolins belong to a newly described group of membrane-scaffolding proteins. Their presence in benign endothelial cells has been used to discriminate benign from malignant vascular neoplasms. The extent of caveolin expression in cutaneous mesenchymal neoplasms has not yet been evaluated, and thus the diagnostic utility of these antibodies is not yet known. In our study, we immunohistochemically examined a spectrum of tumors derived from smooth muscle and adipocytes for caveolin expression. We found that both benign and malignant smooth muscle tumors and tumors comprised of adipocytes expressed caveolins. The presence of this protein in a range of mesenchymal neoplasms is important to know about as this decreases the reported specificity of a positive finding. It is doubtful that caveolin down-regulation contributes to the pathogenesis of liposarcomas and leiomyosarcomas. This finding also may suggest a common origin between endothelial cells and other mesenchymal cells.
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Fifty-six gastrointestinal stromal tumors (GIST) were subclassified by ultrastructural examination and by immunophenotypic analysis using a panel of 13 antibodies. Eighty percent of the tumors originated in the stomach and small intestines. The neoplasms were classified as follows: 42.9% smooth muscle tumors (4 leiomyomas, 9 spindle cell and 8 epithelioid leiomyosarcomas, and 3 mixed spindle cell and epithelioid leiomyosarcomas); 37.5% gastrointestinal autonomic nerve tumors (GANT), 47.6% of which arose in the small intestines; 8.9% mixed leiomyosarcoma/neurogenic tumors; and 10.7% undifferentiated GIST, not otherwise specified. The muscle common actin antibody HHF-35, variably reactive with tumor cells composing 23 of 24 smooth muscle tumors, was found to be the most sensitive marker of leiomyocyte differentiation. One immunophenotypically questionable spindle cell leiomyosarcoma was diagnosed by electron microscopy. Since neuron specific enolase positive cells were found in 1/3 of the leiomyosarcoma cases, the ultrastructural demonstration of synapse-like structures and neurosecretory granules was required for diagnosing GANTs. The immunophenotype of the ultrastructurally undifferentiated GIST was vimentin and CD34+. Variable numbers of ultrastructurally undifferentiated cells also we found in all of the tumors except 2 leiomyomas. CD34 was also expressed in smooth muscle (54%) and GAN (62%) tumors. Despite their similar light microscopic appearance, GIST are phenotypically heterogeneous, requiring both ultrastructural and immunohistochemical studies for accurate characterization.
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The light microscopic and immunohistochemical features of 30 primary mesenchymal neoplasms of the urinary bladder are reported. Half of the cases represented smooth and striated muscle tumors (five leiomyomas, seven leiomyosarcomas including epithelioid and myxoid subtypes, one rhabdomyoma, one embryonal rhabdomyosarcoma and one alveolar rhabdomyosarcoma). One third of the tumors were of fibrohistiocytic origin (one fibrous histiocytoma and eight malignant fibrous histiocytomas including fascicular and storiform, inflammatory and pleomorphic subtypes). In addition, a malignant epithelioid schwannoma, a round cell liposarcoma, two hemangiomas and two mixed mesodermal tumors were observed. The morphology of the vesical mesenchymal tumors was identical to that of their counterparts known to occur in other sites, particularly in the soft tissue. Muscle-specific actin, alpha-1-antichymotrypsin, S-100-protein and neuron-specific enolase proved to be useful and reliable immunomarkers for differential diagnosis of poorly differentiated leio- and rhabdomyosarcomas, malignant fibrous histiocytomas and malignant schwannomas. Since some tumors coexpressed several classes of intermediate filaments, diagnostic immunocytochemistry should only be used considering a larger panel of antibodies and in close correlation with the histological and cytological features of the neoplasms.
This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs.