Ultrastructural Similarities and Differences of Synovial Sarcoma, Epithelioid Sarcoma, and Clear Cell Sarcoma of the Tendons and Aponeuroses

The ultrastructural features of synovial sarcoma, epithelioid sarcoma, and clear cell sarcoma of the tendons and aponeuroses were compared to identify differential markers and similarities. A continuous spectrum of modulation of morphologic features of synovial and epithelioid sarcomas was observed. Biphasic synovial sarcoma with pseudoglandular and stromal components represents one extreme of this spectrum. The gradual disappearance of the pseudoglands and the formation of nests of epithelial-like cells, which are characteristic of epithelioid sarcoma, were observed. The cells of clear cell sarcoma, as well as those of synovial and epithelioid sarcomas, form epithelial-like islands; however, the presence of premelanosomes in the former is a feature of neural crest derivatives.     

Ultrastructural similarities and differences of synovial sarcoma, epithelioid sarcoma, and clear cell sarcoma of the tendons and aponeuroses

The ultrastructural features of synovial sarcoma, epithelioid sarcoma, and clear cell sarcoma of the tendons and aponeuroses were compared to identify differential markers and similarities. A continuous spectrum of modulation of morphologic features of synovial and epithelioid sarcomas was observed. Biphasic synovial sarcoma with pseudoglandular and stromal components represents one extreme of this spectrum. The gradual disappearance of the pseudoglands and the formation of nests of epithelial-like cells, which are characteristic of epithelioid sarcoma, were observed. The cells of clear cell sarcoma, as well as those of synovial and epithelioid sarcomas, form epithelial-like islands; however, the presence of premelanosomes in the former is a feature of neural crest derivatives.     

Synovial Sarcoma: A Review and Update, with Emphasis on the Ultrastructural Characterization of the Nonglandular Component

Classic triphasic synovial sarcoma is usually not a problem in identification, whereas the monophasic spindle cell form continues to be a challenge in the differential diagnosis of spindle cell neoplasms. Most synovial sarcomas do not arise from a joint or tendon sheath, and by electron microscopy and immunohistochemistry they differ in several ways from nonneoplastic synovium. The cell of origin of synovial sarcoma is unknown, but certain features are rather consistently observed in the biphasic tumors and are useful in identifying monophasic samples. These features are apparent by immunohistochemistry and electron microscopy, both of which indicate early epithelial differentiation in the nonglandular component of the neoplasm. With immunohistochemistry, some of these cells stain for keratin. By electron microscopy, a gradient of differentiation from unclassifiable spindle cells to fully differentiated epithelial lining cells is demonstrable. A review and illustration of the ultrastructural characteristics in this spectrum of intermediate cells constitute the main emphasis of the article. The cells tend to be oval and polygonal; to be arranged in clusters surrounded by basal lamina or flocculent matrix; to have junctions, including tight junctions, and to form villuslike filopodia, true microvilli, canaliculi, and microlumina. This range of ultrastructural features is usually diagnostic of the nonglandular phase of synovial sarcoma.     

Synovial Sarcoma: A Review and Update,with Emphasis on the Ultrastructural Characterization of the Nonglandular Component

Classic triphasic synovial sarcoma is usually not a problem in identification, whereas the monophasic spindle cell form continues to be a challenge in the differential diagnosis of spindle cell neoplasms. Most synovial sarcomas do not arise from a joint or tendon sheath, and by electron microscopy and immunohistochemistry they differ in several ways from nonneoplastic synovium. The cell of origin of synovial sarcoma is unknown, but certain features are rather consistently observed in the biphasic tumors and are useful in identifying monophasic samples. These features are apparent by immunohistochemistry and electron microscopy, both of which indicate early epithelial differentiation in the nonglandular component of the neoplasm. With immunohistochemistry, some of these cells stain for keratin. By electron microscopy, a gradient of differentiation from unclassifiable spindle cells to fully differentiated epithelial lining cells is demonstrable. A review and illustration of the ultrastructural characteristics in this spectrum of intermediate cells constitute the main emphasis of the article. The cells tend to be oval and polygonal; to be arranged in clusters surrounded by basal lamina or flocculent matrix; to have junctions, including tight junctions, and to form villuslike filopodia, true microvilli, canaliculi, and microlumina. This range of ultrastructural features is usually diagnostic of the nonglandular phase of synovial sarcoma.     

Monophasic synovial sarcoma, epithelioid sarcoma and chordoid sarcoma: ultrastructural evidence for a common histogenesis, despite light microscopic diversity

Ultrastructural examination of six rare sarcomas-four monophasic spindle cell tumours, one epithelioid sarcoma, one chordoid sarcoma-has revealed marked similarities at the electron microscopic level despite widely divergent light microscopic appearances. These features consisted of: 1 the presence of two cell types, viz. a clear cell and a cell resembling the fibroblast; 2 pseudoglandular spaces with projecting microvilli or filopodia, and with related tight junctions; 3 an amorphous intercellular ground substance with focal condensation into recognizable basement membrane. The findings suggest a common maturation of these diverse tumours to synovial-like tissue, and support the proposal of Hajdu Shiu & Fortner (1977) that these be considered variants of synovial sarcoma. Published ultrastructural studies of synovial, epithelioid and chordoid sarcoma are reviewed in the light of these findings. The ultrastructural differentiation of synovial sarcoma from extra-skeletal myxoid chondrosarcoma, chordoma and the spectrum of malignant spindle cell tumours is discussed.     

Monophasic synovial sarcoma–a histological entity?

Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.     

Ultrastructure of Human Tendon Sheath and Synovium: Implications for Tumor Histogenesis

Normal human tendon sheath and synovium were studied by scanning and transmission electron microscopy. The lining cells of the two tissues appear to be identical ultrastructurally. The most superficial cells (B-cells) possess long cytoplasmic extensions that clothe the membrane surface. Intermingled with deeper B-cells are the so-called A-cells, which have similar cytoplasmic features but lack long processes and instead have many filopodia. The frequent occurrence of intermediate forms indicates that the two cells form part of a morphologic spectrum. Comparison with cells of tumors that have been ascribed to synovium or tendon sheath (synovial sarcoma, epithelioid sarcoma, clear cell sarcoma) do not reveal any close similarities that might support a histogenetic relationship.     

Expression of c-Met receptor and hepatocyte growth factor/scatter factor in synovial sarcoma and epithelioid sarcoma

 Overexpression of c-Met receptor/hepatocyte growth factor (scatter factor) system (c-Met/HGF/SF) as a physiologically paracrine cellular signaling system is thought to be involved in the progression of malignant tumours. In 26 synovial sarcomas and epithelioid sarcomas, c-Met and HGF/SF expression was analysed immunohistochemically. There were 10 biphasic synovial sarcomas, 7 of which showed moderate to strong c-Met expression in epithelial areas compared with the fibrous component, with corresponding expression of HGF/SF. Six of 9 monophasic fibrous synovial sarcomas showed only very faint c-Met and corresponding HGF/SF expression. In 7 epithelioid sarcomas strong expression of c-Met and HGF/SF was observed within epithelioid tumour cells. Non-radioactive in situ hybridization demonstrated the synthesis of c-Met receptor in tumor cells by detecting c-met-mRNA. This analysis shows that in synovial sarcomas and epithelioid sarcomas, tumour entities with epithelial and mesenchymal structures, c-Met and HGF/SF overexpression can be detected, indicating a role of this signaling system in these subtypes of sarcoma, and especially in the more epithelioid tumour phenotype. An autocrine interaction between overexpressed c-Met receptor and HGF/SF may be hypothesized. Received: 21 July 1997 / Accepted: 19 November 1997     

Epithelioid Monophasic Synovial Sarcoma

A 47-year-old man presented with a soft tissue mass of the distal right thigh near the knee. The tumor was highly vascular with epithelioid tumor cells growing in a peritheliomatous pattern, suggesting a soft tissue glomus tumor. Yet many tumor cells contained hemosiderin pigment and formed papillary structures suggestive of pigmented villonodular synovitis. Tumor cells were cytologically bland, and there was minimal mitotic activity. The tumor cells were strongly immunoreactive for cytokeratin, however, and contained true desmosomes, gland lumina, microvilli, tonofilaments, and well-developed basal lamina. These findings plus the absence perinuclear aggregates of intermediate filaments rule out malignant rhabdoid tumor and epithelioid sarcoma. Also, magnetic resonance imaging revealed no other lesions to suggest metastatic carcinoma. Thus this tumor appears to be a predominantly epithelioid form of monophasic synovial sarcoma. Recognition of this variant of synovial sarcoma is important for prognostication and therapeutic decision making because some studies indicate that this variant of synovial sarcoma follows a relatively benign clinical course.     

Synovial Sarcoma with Squamous Metaplasia

We report on a biphasic synovial sarcoma showing slight squamous cell differentiation of their epithelioid component under the light microscope. The electron microscopical examination revealed numerous tono-filaments arranged in dense bundles, which could be characterized as tonofibrils with keratohyalin granules in the same cells. The presence of such structures indicates the possibility of squamous metaplasia in biphasic synovial sarcoma.     

Synovial Sarcoma with Squamous Metaplasia

We report on a biphasic synovial sarcoma showing slight squamous cell differentiation of their epithelioid component under the light microscope. The electron microscopical examination revealed numerous tono-filaments arranged in dense bundles, which could be characterized as tonofibrils with keratohyalin granules in the same cells. The presence of such structures indicates the possibility of squamous metaplasia in biphasic synovial sarcoma.     

Imprint cytological features of soft tissue sarcomas]

The imprint cytologic features in typical sarcomas, such as malignant fibrous histiocytoma (MFH), fibrosarcoma, malignant peripheral nerve sheath tumor (MPST), liposarcoma, synovial sarcoma, clear cell sarcoma and epithelioid sarcoma, were presented in comparison with each histologic feature. Cytological diagnosis of soft tissue sarcomas is usually difficult because of their rarity, various kinds, wide range of features in the tumor and similar features to those of other tumors. Based on the cellular morphology, sarcoma cells were divided into five cell types as follows: small cell type, spindle cell type, epithelioid cell type, epithelioid-spindle type, and pleomorphic type. The results obtained from "retrospective" immunostainings for decolorized Papanicolau's stained sections with a panel of markers, together with differentiation of the cell type, were useful for the cytological diagnosis of the tumors examined. Since the value of aspiration cytology is much higher than that of imprint cytology in the cytopathologic diagnosis, methods, such as immunostaining and differentiation of the cell type, are recommended in aspiration cytology to make a definitive cytological diagnosis in sarcoma cases.     

Identification of poorly differentiated synovial sarcoma: a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma

AIMS: Poorly differentiated areas in synovial sarcomas (SS) are known to be associated with a poorer prognosis. The aim of our study was to describe the morphological spectrum of poorly differentiated synovial sarcomas (PDSS) and refine the criteria for their recognition. METHODS AND RESULTS: The clinicopathological features of 28 PDSS were compared with those of 26 classic SS. Common cell types in PDSS included epithelioid, spindle and Ewing sarcoma-like small round cells. Unusual features included presence of desmoplastic small cell tumour-like areas and extraskeletal myxoid chondrosarcoma-like areas. The presence of necrosis (P = 0.002), a mitotic rate over 10/10 high-power fields (P < 0.001), a haemangiopericytomatous vascular pattern (P < 0.001) and vascular invasion (P = 0.003) were significantly associated with PDSS, while mast cells (P < 0.001), calcification (P < 0.001) and hyaline bands (P < 0.001) were significantly associated with classic SS. Poorly differentiated areas showed increased proliferative activity with Ki67. PDSS showed a tendency to be larger (P = 0.008) and to be located in proximal more than distal sites (P = 0.025). Three entirely poorly differentiated tumours were diagnosed by demonstration of the t(X;18)(p11;q11) translocation. PDSS showed additional cytogenetic abnormalities. CONCLUSIONS: Poorly differentiated synovial sarcomas show a spectrum of histological features, which may simulate other malignant neoplasms. The diagnosis of entirely poorly differentiated synovial sarcomas requires cytogenetic analysis.     

Synovial sarcoma enzyme histochemistry of a typical case

Summary A typical case of biphasic synovial sarcoma was studied using enzyme histochemistry. A marked difference between the staining characteristics of the spindle cells and the epithelial-like cells was demonstrated by reactions for various hydrolytic enzymes. The epithelial-like cells exhibited a strong reactivity for alkaline phosphatase, acid phosphatase, adenosine triphosphatase and nonspecific esterase, whereas spindle-cells were completely unreactive when tested for these enzymes.This is, to our knowledge, the first report demonstrating differences in the enzymatic pattern of the two cell populations which compose synovial sarcoma.     

HLA-DR (Ia-like) reactivity in tumors of bone and soft tissue: an immunohistochemical comparison of monoclonal antibodies LN3 and LK8D3 in routinely processed specimens.

Recent studies of Class II histocompatibility antigen expression in bone and soft tissue sarcomas have suggested that malignant fibrous histiocytoma (MFH) may express HLA-DR, whereas histologically similar pleomorphic, epithelioid, and spindle cell malignant neoplasms generally do not. To test whether these observations are reproducible in the differential diagnosis of soft tissue sarcomas, anti-HLA-DR antibodies LK8D3 and LN3 were applied to formalin-fixed, paraffin-embedded sections of MFH, neurofibrosarcoma (NFS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), angiosarcoma (AS), Kaposi's sarcoma (KS), chondrosarcoma (ChS), "dedifferentiated" chondrosarcoma (DChS), osteosarcoma (OS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS; malignant melanoma of soft parts). The only consistent difference in Class II antigen expression was seen in the group of neoplasms composed of large polygonal cells. Among the latter lesions, four of six clear cell sarcomas were labeled by LK8D3 or LN3, but none of 12 epithelioid sarcomas were reactive. Otherwise, a diversity of tumors in other morphologic categories expressed Class II antigens, with no clear diagnostic patterns. These results may be of use in the diagnostic separation of large cell epithelioid tumors of soft tissue, but neither LN3 nor LK8D3 appears to be helpful in the identification of other sarcomas.     

Synovial sarcoma--a misnomer.

For an evaluation of the putative histogenetic relationship of synovia and synovial sarcomas, normal synovia, villonodular synovitis, and synovial sarcomas were compared for their patterns of expression of intermediate filaments of keratin and vimentin type and epithelial membrane antigen and for lectin binding sites. The lining cells in both normal synovia and villonodular synovitis reacted with anti-vimentin antibodies, but not with antibodies to different types of keratins or epithelial membrane antigen. The cleft-lining cells in synovial sarcoma, on the other hand, showed only keratin positivity, and epithelial membrane antigen could also be detected in these cells. Nonneoplastic synovial lining cells bound peanut agglutinin (PNA), Ricinus communis agglutinin (RCA), soybean agglutinin (SBA), concanavalin A (Con A), and wheat germ agglutinin (WGA) conjugates, but not Ulex europaeus I lectin (UEA I). In contrast, the epithelial-like cleft lining cells in synovial sarcomas showed an apical cytoplasmic binding of PNA, UEA I, RCA, and SBA, and binding of WGA to the whole cytoplasm but did not bind Con A. The distinct differences between synovial lining cells and synovial sarcoma cells speak against synovial cell features in synovial sarcoma. These results indicate that synovial sarcoma is a carcinosarcomalike tumor with true epithelial differentiation, and the term "synovial sarcoma" apparently is a misnomer that should be abandoned.     

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues

CONTEXT: Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. OBJECTIVE: To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. DESIGN: Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. RESULTS: Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). CONCLUSIONS: Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).     

Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation

The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.