Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group.
Soft-tissue tumors have proved to be a fruitful area for the identification of reproducible cytogenetic aberrations, especially among pediatric round-cell sarcomas and lipomatous tumors. Thus far, however, data regarding sarcomas of monomorphic spindle cell type have been limited and somewhat disappointing, with the notable exception of synovial sarcoma. As part of an ongoing international collaborative study, 130 karyotyped spindle-cell sarcomas were reviewed and classified histologically, without knowledge of the clinical and karyotypic data, with the aim of identifying objective correlations between morphology, karyotype, and clinical parameters. Clonal chromosomal abnormalities were identified in 82 cases studied (63%), but only in the group of synovial sarcomas was there clear correlation between the cytogenetic findings, in the form of a consistent t(X;18)(p11;q11), and morphology. Among leiomyosarcomas (41 cases) and malignant peripheral nerve sheath tumors (MPNSTs; 27 cases) as well as in individual examples of rarer entities, there was a general tendency for karyotypic complexity associated with frequent loss or rearrangement of chromosome arms 1p, 10p, 11q, 12q, 17p, and 22q. Rearrangements of 17q (the region of the NF1 gene) were seen in 9/27 (33%) of MPNSTs. Among nine cases of solitary fibrous tumor (in which previous cytogenetic data are very limited) no consistent aberrations were identified. We conclude that, with the exception of synovial sarcoma, most spindle-cell sarcomas share with pleomorphic sarcomas the tendency for karyotypic complexity. There was no indication (in most of these lesions) that detectable cytogenetic aberrations could either facilitate their diagnosis or help to determine prognosis. There is a clear need to further study and understand the significance of multiple chromosomal abnormalities in this group of mesenchymal neoplasms with the particular goal of determining their role in the process of tumor development. (+info
Solitary fibrous tumor of the meninges in the posterior cranial fossa: magnetic resonance imaging and histological correlation--case report.
A 58-year-old female presented with a rare case of intracranial solitary fibrous tumor (SFT) manifesting as progressive ataxic gait and hearing loss on the left persisting for 6 months with recent symptoms of increased intracranial pressure. Computed tomography demonstrated a large isodense irregular-shaped mass in the left posterior cranial fossa. T2-weighted magnetic resonance imaging showed two components appearing as very low intensity and high intensity. Extreme-lateral suboccipital craniotomy was performed. Gross total resection was achieved except for some dural attachment in the jugular foramen. All symptoms and signs subsided after surgery. Histological, immunohistochemical, and electron microscopic examinations led to a diagnosis of SFT. The strongly hypointense areas on the T2-weighted images were hypocellular region characterized by disorganized spindle cells and thick bands of collagen. The hyperintense areas on the T2-weighted images were hypercellular region mimicking hemangiopericytoma. Strong immunoreactivity for CD34 was also helpful in the diagnosis. Electron microscopy revealed absence of pinocytic vesicles and dense laminae which are characteristic of hemangiopericytoma. The magnetic resonance imaging appearance of SFT seems to be pathognomonic. (+info
Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas.
Caveolae are plasma membrane microdomains that have been implicated in the regulation of several intracellular signaling pathways. Previous studies suggest that caveolin-1, the main structural protein of caveolae, could function as a tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated mesenchymal cells including adipocytes, endothelial cells, and smooth muscle cells. To study whether caveolin-1 is a possible tumor suppressor in human mesenchymal tumors, we have analyzed the expression using immunohistochemistry in normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors. Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues. The expression of caveolin-1 was slightly reduced in four of six well-differentiated liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of 20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight synovial sarcomas. The immunohistochemical findings were confirmed by Western blot analysis in a number of tumors. High levels of both the 24-kd [alpha]- and the 21-kd [beta]-isoform of caveolin-1 were detected in the nontumorigenic human fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells, caveolin-1 is strongly down-regulated. We show that the [alpha]-isoform of caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen-activated protein kinase-signaling pathway with the specific inhibitor PD 98059, whereas the specific inhibitor of DNA methylation 5-aza-2'-deoxycytidine only marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we conclude that caveolin-1 is likely to act as a tumor suppressor gene in human sarcomas. (+info
Genetic and molecular abnormalities in tumors of the bone and soft tissues.
BACKGROUND: Malignant transformation requires the accumulation of multiple genetic alterations such as chromosomal abnormalities, oncogene activation, loss of tumor suppressor genes, or abnormalities in genes that control DNA repair and genomic instability. Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult histologic classification and strong genetic predisposition. This article provides a comprehensive review of the cytogenetic abnormalities observed in bone and soft-tissue tumors, emphasizing known downstream molecular changes that may play a role in oncogenesis. METHODS: The database of the National Library of Medicine was searched for literature relating to genetic and molecular mechanisms in sarcomas in general and in each of the main tumor entities. RESULTS: Recent techniques in chromosome analysis and molecular cytogenetics have improved our ability to characterize genetic changes in mesenchymal tumors. Some changes are so characteristic as to be virtually pathognomonic of particular histologic types, while others are complex, difficult to characterize, and of unknown relevance to pathogenesis. The implications to the cell of some of these abnormalities are now being recognized. CONCLUSIONS: The study of sarcomas will benefit from the information derived from genetic studies and translational research. The human genome project and new methodologies, such as computer-based DNA microarray, may help in the histogenetic classification of sarcomas and in the identification of molecular targets for therapy. (+info
Solitary fibrous tumor of the parapharyngeal space: MR imaging findings.
We report the MR imaging findings of a solitary fibrous tumor involving the parapharyngeal space. The tumor was a well-circumscribed solid mass with a lobulated contour. It had the same signal intensity as the muscle on T1-weighted MR images, heterogeneously high signal intensity on T2-weighted images, and homogeneous strong enhancement after the administration of contrast material. It mimicked a tumor originating from the deep lobe of the parotid gland. (+info
Clinical pathological analysis and immunohistochemical study of ten solitary fibrous tumors.
OBJECTIVE: To study the clinical and pathological characteristics of solitary fibrous tumor (SFT). METHODS: Clinical pathological analysis and immunohistochemical studies were performed on ten patients with SFT. RESULTS: The SFTs located variously and showed different histological features. All cases showed positive staining for CD(34), VM (vimentin) and Bcl-2, but negative staining for Desmin, S-100, CK (cytokeratin) and EMA (epithelial membrane antigen). CONCLUSIONS: SFT is described as a "patternless" growth pattern. According to clinical pathological features and immunohistochemistry, it is different from other soft tissue tumors. Long-term clinical follow-up is necessary for this kind of tumor. (+info
A case of solitary fibrous tumor of the parotid gland: review of the literatures.
We report a rare case of solitary fibrous tumor of the parotid gland. A 47-year-old woman presented with a 3-year-history of left-sided subauricular swelling. Computed tomographic scans and magnetic resonance images revealed a well-defined and dumbbell-shaped mass, measuring about 30 mm in its greatest dimension, in the left parotid gland. Because the tumor occupied both superficial and deep lobes of the gland, she underwent total parotidectomy with preservation of the facial nerve. The microscopic finding showed short-spindle and ovoid cells arranged in a haphazard pattern with interspersed thin collagen fibrils. Immunohistochemically, the tumor cells were strongly positive for CD34, bcl-2 and vimentin, whereas stains for S-100, cytokeratin, smooth muscle actin, collagen type IV and CD117 (KIT) were negative. On the basis of these findings, the tumor was diagnosed as solitary fibrous tumor. Her post-operative course was uneventful, and she is currently free from disease 14 months after surgery. Diagnosis, clinical behavior and treatment of solitary fibrous tumor are reviewed from perusal of the literature. (+info
Orbital malignant fibrous histiocytoma with extension to the base of the skull--case report.
An 18-year-old woman presented with a malignant fibrous histiocytoma (MFH) originating in the orbit and invading the frontal and temporal base of the skull manifesting as exophthalmos and double vision that had persisted for 2 months. Magnetic resonance imaging revealed a tumor in the left orbit that extended as far as the frontal and temporal base of the skull. The tumor was treated by radical resection with conservation of the eyeball and its contents, followed by orbit wall reconstruction. The histological diagnosis was MFH. Local radiotherapy was administered postoperatively. The preoperative symptoms improved, and there has been no evidence of local recurrence or metastasis in the year since the surgery. In this case, radical resection of the tumor was essential. Furthermore, the adjuvant therapy was apparently successful, probably because this histological type of tumor is highly sensitive to radiotherapy. (+info