bromochloroacetic-acid and Sarcoma--Synovial

Synovial sarcoma is a tumor of unknown origin and is extremely rare in the central nervous system. We present a case involving an unusual cerebellar synovial sarcoma in a male infant. Neuroimaging revealed a large, solid, gadolinium-enhancing mass located in the parenchyma of the right cerebellar hemisphere and associated with multiple cyst formation. Histologically, the tumor was composed of uniform spindle cells with indistinct borders and numerous mitotic figures. The tumor cells were observed to form dense cellular sheets, but in some areas the tumor showed a hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. Immunohistochemistry showed that vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and focal reactivity for cytokeratin (AE1/AE3) and S-100 protein was also observed. The tumor cells were, however, negative for CK19, EMA, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization demonstrated the translocation t(X;18)(p11;q11). A diagnosis of primary cerebellar monophasic synovial sarcoma was made. To our knowledge, this is the first report of a synovial sarcoma in brain parenchyma. The present case indicates that it is essential to select the appropriate immunohistochemical panel and-especially-perform molecular analysis to accurately diagnose intracranial spindle cell tumors.

Topics: 12E7 Antigen; Antigens, CD; Biomarkers, Tumor; Cell Adhesion Molecules; Cerebellar Neoplasms; Cytogenetic Analysis; Diagnosis, Differential; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Keratins; Magnetic Resonance Imaging; Male; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; Sarcoma, Synovial; Translocation, Genetic; Vimentin

Topics: Adult; Biopsy; Cell Nucleus; Cytoplasm; Diagnosis, Differential; Humans; Keratin-7; Keratins; Male; Mucin-1; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-bcl-2; Sarcoma, Synovial; Tongue Neoplasms; Translocation, Genetic; Vimentin

This report describes the clinical, histological and immunohistochemical features of two patients with primary pulmonary synovial sarcoma in the context of the literature. Chest pain, cough, haemoptysis and an enlarging pleural-based mass are the main clinical manifestations. Diagnosis depends on identifying epithelioid or spindle cells microscopically and on immunohistochemistry showing positivity for cytokeratin and vimentin and epithelial membrane antigen stains. Surgical excision is the main treatment approach.

Topics: Adult; Chest Pain; Cough; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Sarcoma, Synovial; Vimentin

This is a case report of a rare patient with primary pulmonary synovial sarcoma. The patient was a 58-year-old woman who presented with a well-defined giant mass in the right lower field on a chest radiograph. A malignant pulmonary tumor was suspected and consequently a right middle and lower lobectomy was performed. Grossly, the tumor measured 10 x 8 x 7 cm, was whitish-yellow in color and friable with hemorrhage. Histologically, the tumor showed a dense proliferation of spindle cells. In some areas, a herringbone-like pattern with coagulation necrosis of large size was noted. Immunohistochemically, the tumor cells were focally positive for cytokeratin and epithelial membrane antigen (EMA). As these features suggested a monophasic synovial sarcoma, we looked for the presence of SYT-SSX fusion gene transcripts using RNA samples from the paraffin-embedded tissue. A reverse transcription-polymerase chain reaction (RT-PCR) amplified a single 118 bp fragment characteristic of the SYT-SSX1 fusion gene transcripts. As no tumor was found at other sites, it was diagnosed as primary pulmonary synovial sarcoma. Molecular testing proved to be very helpful or necessary when monophasic spindle cell synovial sarcoma was recognized in uncommon/unexpected sites. In our review of primary pulmonary synovial sarcomas confirmed by molecular detection of SYT-SSX fusion gene transcripts, the SYT-SSX2 fusion protein expression correlates with poorer prognosis. This is in contrast to the association between the SYT-SSX1 fusion protein expression and poorer prognosis in soft tissue synovial sarcomas.

Topics: Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Oncogene Proteins, Fusion; Paraffin Embedding; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Synovial; Transcription, Genetic; Vimentin

The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than 50 years ago continues to represent a source of uncertainty and disagreement among pathologists. In particular, questions exist regarding the synonymity of a hemangiopericytomatous growth pattern--defined by a monomorphic population of compact polygonal or bluntly fusiform cells and a branching stromal vascular pattern with a "staghorn" configuration--and the presence of a reproducible biological entity. It has been shown repeatedly that these same histologic features may be observed at least focally in a diversity of neoplasms, including "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas, infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite their potential sharing of the microscopic attributes in question, such neoplasms have individualistic clinical features and can also be distinguished from one another by specialized pathologic analyses. HPC is "defined" in that context by reactivity for vimentin, with or without CD34 and CD57, but it lacks other immunodeterminants of epithelial, neural, and myogenous differentiation. Paradoxically, this phenotype is indeed associated with the presence of myogenous-type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions that may resemble "true" HPC--but which possess dissimilar subcellular and clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas." Such observations suggest that the hemangiopericytoma is both a pathologic entity and a morphological pattern, and they emphasize the utility of adjuvant pathologic studies in this diagnostic context.

Topics: Actins; Bone Neoplasms; CD57 Antigens; Diagnosis, Differential; Hemangiopericytoma; Humans; Keratins; Meningioma; Myofibromatosis; Nasopharyngeal Neoplasms; Reticulin; Sarcoma, Synovial; Soft Tissue Neoplasms; Stromal Cells

Synovial sarcoma is rarely seen in the head and neck region. A case of synovial sarcoma of the pharynx in a child is presented.

Topics: Child; Humans; Immunoenzyme Techniques; Keratins; Male; Pharyngeal Neoplasms; Sarcoma, Synovial

It has been established that nonrandom chromosome rearrangements are characteristic of specific types of neoplasia. We present six new cases of sarcoma that had in common the same chromosome abnormality, i.e., a balanced translocation between chromosomes X and 18, t(X;18)(p11.2;q11.2), and evaluate the 15 cases with this translocation in the literature. The histological diagnosis was synovial sarcoma in 19 cases and malignant fibrous histiocytoma and fibrosarcoma in the remaining two tumors, respectively. The translocation was found in tumors of both the biphasic and monophasic types, as well as in poorly differentiated synovial sarcoma. The two nonsynovial sarcomas with the t(X;18) were described as spindle cell tumors but failed to show the presence of cytokeratins by immunohistochemical stains. Even with the numerous variabilities on which this test depends, the cytogenetic analysis holds great promise as a tool for the diagnosis of synovial sarcoma.

Topics: Adult; Chromosomes, Human, Pair 18; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Sarcoma, Synovial; Soft Tissue Neoplasms; Translocation, Genetic; X Chromosome

Synovial sarcoma (SS) is extremely rare in the jaws, and only 8 cases have been reported worldwide. The specific aims of this study were to report 15 cases of primary intraosseous SS (PISS) and analyze the histologic features and outcome-related prognostic factors.. Data from patients diagnosed with PISS from 2004 to 2013 were collected in this retrospective study. Patient characteristics (primary location, histologic subtype, tumor size, and surgical margin) were defined as predictor variables. Local recurrence and tumor-related death were outcome variables. The association of tumor-related outcomes with patient characteristics was analyzed using Kaplan-Meier and Cox regression statistics. Other clinical and pathologic characteristics were summarized as a third category of variables for further analysis.. This study examined 15 cases (women, n = 10; men, n = 5) with a mean age at diagnosis of 35 years. There was no imbalance in the distribution of primary SS locations (maxilla, n = 7; mandible, n = 8). Six patients (40%) developed local recurrence and 4 patients (26.7%) had a tumor-related death. The 5-year local recurrence-free survival (LRFS) and overall survival rates were 57% and 69.1%, respectively. The strong statistical association of surgical margin with 5-year LRFS rate was shown by univariate (P = .01) and multivariate (hazard ratio = 7.598; P = .028) analyses.. PISS is extremely rare in the jaw. Immunohistochemical analysis played an important role in the diagnosis of PISS. The surgical margin showed a strong association with local recurrence. Thus, ideal surgical margins should be achieved during surgery to obtain better local control.

Topics: 12E7 Antigen; Adolescent; Adult; Antigens, CD; Cause of Death; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Mandibular Neoplasms; Maxillary Neoplasms; Middle Aged; Mucin-1; Neck Dissection; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Plastic Surgery Procedures; Prognosis; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Sarcoma, Synovial; Survival Rate; Vimentin; Young Adult

The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs in unusual locations, atypical age groups, and/or have unusual morphology. We report a case of primary mediastinal SS in a 65-year-old male with a long smoking history who presented with increasing shortness of breath and was found to have a 14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine needle aspiration of the mass were moderately cellular consisting of loosely cohesive clusters, some of which demonstrated nuclear molding, and dispersed single cells. The relatively uniform tumor cells had a high nuclear-to-cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of the single cells had spindled morphology with unipolar wispy tails and naked nuclei. Based on the clinical presentation and the cytomorphologic features, our initial differential diagnoses included atypical carcinoid, small cell carcinoma, basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical studies on the cell block sections revealed that the tumor cells were focally positive for cytokeratin and diffusely positive for CD56, while negative for CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain for TLE-1 demonstrated diffusely strong nuclear positivity and molecular studies showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the diagnosis of SS. In this report, we describe the cytomorphologic features of SS, its diagnostic pitfalls, and potential mimics in the mediastinum.

Topics: Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; CD56 Antigen; Co-Repressor Proteins; Humans; Keratins; Ki-67 Antigen; Male; Mediastinal Neoplasms; Neoplasm Proteins; Pulmonary Disease, Chronic Obstructive; Repressor Proteins; Sarcoma, Synovial; Smoking; Translocation, Genetic

Small round blue-cell tumors (SRBCTs) of soft tissue, which mainly include rhabdomyosarcoma (RMS), synovial sarcoma (SS), and Ewing's sarcoma/peripheral primitive neuroectodermal tumors (EWS/ pPNETs), are malignancies with overlapping morphological and immunohistochemical characteristics. Immunohistochemistry is one of the most prevalent and convenient methods for pathological diagnosis; however, differentiation between SRBCT subtypes in the absence of valid diagnostic markers is still very challenging. The purpose of the present study was to investigate diagnostic immunohistochemistry for subtyping soft tissue SRBCTs.. Seventeen RMS, 25 SS, and 14 EWS/pPNETs were investigated. Reverse transcription RT-PCR and immunohistochemistry was performed to determine a diagnosis. Also, the expression of CD99, FLI1, PAX5, myogenin, and Keratin/EMA was assessed between subtypes. The sensitivity and specificity test was performed to evaluate their diagnostic significance.. The sensitivity and specificity of the target markers were evaluated as follows. FLI1 and CD99 expression displayed strong associations in EWS/pPNETs, with OR (95% CI) and p values of 3.82 (1.23 - 11.94), p = 0.021 and 123.50 (12.63 - infinity), p < 0.001, respectively. Keratin/EMA expression did not support the diagnosis of EWS/pPNETs [OR (95% CI) = 0.06 (0.01 - 0.53), p = 0.011]. Myogenin expression displayed strong association with RMS, with high sensitivity and specificity of 94.1% and 100%, respectively. Membrane expression of CD99 did not support the diagnosis of RMS [OR (95% CI) = 0.09 (0.01 - 0.75), p = 0.026]. Keratin/EMA expression strongly indicated SS [OR (95% CI) = 345.00 (29.44 - infinity), p = 0.00011. A ROC curve value of 0.94 indicated that keratin/EMA expression might be a promising biomarker for SS, while separate expression of FLI1 and CD99 did not support the diagnosis of SS. Similarly, myogenin expression in RMS might be a promising biomarker for RMS with a ROC curve value of 0.97.. Diagnosis of SRBCTs should be based on a comprehensive analysis involving morphology and immunoreactivity to a panel of markers.

Topics: 12E7 Antigen; Adolescent; Adult; Aged; Antigens, CD; Cell Adhesion Molecules; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neuroectodermal Tumors; Odds Ratio; Proto-Oncogene Protein c-fli-1; Reverse Transcriptase Polymerase Chain Reaction; Rhabdomyosarcoma; Sarcoma, Ewing; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms; Young Adult

Topics: Adamantinoma; Adult; Diagnosis, Differential; Female; Femur; Follow-Up Studies; Humans; Humerus; Ilium; Keratins; Male; Middle Aged; Mucin-1; Retrospective Studies; Sarcoma, Ewing; Sarcoma, Synovial; Tibia; Tomography, X-Ray Computed; Young Adult

Primary renal synovial sarcoma is rare and might be misdiagnosed as another renal tumor. This study demonstrates the clinicopathologic and immunohistochemical features, differential diagnosis, and prognosis of such tumors.. Histologic slides and clinical data were reviewed for 4 patients with primary renal synovial sarcoma and immunohistochemical staining was performed. Molecular analysis was performed on 2 cases to demonstrate the presence of the SYT-SSX gene fusion transcripts by reverse transcriptase polymerase chain reaction (RT-PCR).. The patients were 2 women and 2 men aged from 32 to 48 years. The tumors were 10.0-15.0 cm in diameter, grey-white and solid, and hemorrhage or necrosis was observed. Microscopically, the tumors consisted of mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Hypocellular myxoid areas and a prominent hemangiopericytomatous pattern were present in all cases. The average mitotic rate was 5-8 mitoses/10 high-power fields. Hemorrhage and tumor necrosis were easily found. Scattered small cysts lined with flat, cuboidal, or hobnailed epithelia were found in 3 cases. Tumor cells are immunoreactive for Vimentin (4/4), Bcl-2 (4/4), CD99 (4/4), and CD56 (3/4), and focally for EMA (3/4) and Cytokeratin (3/4). SYT-SSX1 gene fusion was detected in the 2 cases in which RT-PCR analysis was performed. One patient had tumor metastasis to the lung 6 months after surgery and died 5 months later. Multiple metastasis to the liver occurred in one patient and the patient died 13 months after the initial surgery. The other 2 patients had tumors recur at 8 and 15 months and died at 18 and 21 months, respectively, after the initial operation.. Primary renal synovial sarcoma is rare, with poor prognosis, characterized by SYT-SSX gene fusion, and needs to be differentiated from other renal sarcomas.

Topics: 12E7 Antigen; Adult; Antigens, CD; CD56 Antigen; Cell Adhesion Molecules; Female; Follow-Up Studies; Humans; Keratins; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mucin-1; Neoplasm Recurrence, Local; Nephrectomy; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-bcl-2; Sarcoma, Synovial; Survival Rate; Vimentin

Topics: Glossectomy; Humans; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Oncogene Proteins, Fusion; Sarcoma, Synovial; Tongue Neoplasms; Translocation, Genetic; Vimentin

Synovial sarcoma (SS) is characterized by the t(X; 18) (p11.2; q11.2) translocation resulting in the SYT-SSX fusion transcript, detectable by reverse transcriptase polymerase chain reaction (RT-PCR). Fine-needle aspiration (FNA) cytology diagnosis of SS is challenging. We evaluated the applicability of RT-PCR on FNAs and to perform a detailed cytomorphological analysis in unequivocal cases of SS.. A prospective and retrospective analysis was performed over 4 years (2003-2007). Prospectively, FNAs positive for the SYT-SSX fusion transcript by RT-PCR (n = 6) and, retrospectively, cases proven on histopathology and immunohistochemistry (ICC; positivity for vimentin and epithelial membrane antigen [EMA]/cytokeratin) as SS (n = 10) were included in the study. A detailed cytomorphological analysis was carried out.. There were 9 biphasic and 7 monophasic tumors. The aspirates from both biphasic and monophasic tumors were richly cellular in all cases with micro tissue fragments. Pericapillary arrangement of tumor cells was present in most cases. Attempted gland formation was seen in 7 of 9 biphasic tumors. The individual tumor cells were round, ovoid, or spindle shaped. Pleomorphism was mild; monophasic tumors displayed lesser pleomorphism as compared with the biphasic ones. Nuclear chromatin was bland in all cases except 1 and nucleolar prominence was seen in just 3 biphasic tumors. Mast cells were seen in 3 biphasic and 2 monophasic tumors. Scanty to moderate extracellular matrix material was seen in 5 cases.. FNA cytology of SS shows a spectrum of cytomorphological features; the diagnosis is confirmed by RT-PCR on the aspirated material for the SYT-SSX fusion transcript.

Topics: Adolescent; Adult; Aged; Base Sequence; Biopsy, Fine-Needle; Cytodiagnosis; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Oncogene Proteins, Fusion; Prospective Studies; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Synovial; Sequence Analysis, DNA; Synovial Membrane; Vimentin; Young Adult

Topics: Adenocarcinoma; Adult; Combined Modality Therapy; Diagnosis, Differential; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Sarcoma, Synovial; Vimentin

Synovial sarcoma is a high-grade soft tissue sarcoma that can be challenging to diagnose on the basis of histology alone. It is defined by a characteristic translocation t(X;18) that produces the fusion oncogene SYT-SSX. The current diagnostic gold standard for synovial sarcoma is the demonstration of the translocation by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or cytogenetics, in an appropriate histologic context. TLE1 encodes a transcriptional corepressor that is overexpressed in synovial sarcomas. Gene and tissue microarray studies have identified TLE1 as an excellent bio-marker for distinguishing the synovial sarcoma from other soft tissue malignancies. We prospectively evaluated incoming soft tissue tumor cases where the histology and clinical setting made synovial sarcoma a real consideration in the differential diagnosis. TLE1, Bcl2, epithelial membrane antigen, and cytokeratin expression were assessed using commercially available antibodies. TLE1 gave intense, diffuse nuclear staining in 35 of 35 molecularly confirmed synovial sarcoma cases, and was rare to absent in the 73 other soft tissue tumors examined (positive staining was found only in 1 of 43 malignant peripheral nerve sheath tumors, the 1 tested fibrosarcoma, and 1 pleomorphic sarcoma). TLE1 was more sensitive and specific for synovial sarcoma than other currently available immunohistochemical markers including Bcl2, epithelial membrane antigen and cytokeratins, and had a positive predictive value of 92% and a negative predictive value of 100% in this clinical setting. Our findings confirm, in a prospective diagnostic context, that TLE1 is more sensitive and specific for synovial sarcoma than any other currently available immunohistochemical stains, and in some cases may preclude the need for molecular testing.

Topics: Biomarkers, Tumor; Co-Repressor Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Mucin-1; Oncogene Proteins, Fusion; Predictive Value of Tests; Prospective Studies; Proto-Oncogene Proteins c-bcl-2; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms

Synovial sarcomas are aggressive malignant soft tissue tumors typically observed in adolescents and young adults. They are often characterized by the chromosomal translocation t(X;18)(p11.2;q11.2), which results in the expression of SYT-SSX fusion transcripts. We describe the first case of synovial sarcoma observed in a human fetus. The tumor occurred in the left upper arm and led to intrauterine fetal demise during gestational week 31. Grossly, the tumor measured 10 x 8 x 8 cm, appeared pinkish in color, and developed in the soft tissues of the left arm surrounding the humerus. Histologically, this large tumor showed a dense proliferation of homogeneous spindle cells with some necrotic areas. The positive detection of the SYT-SSX1 fusion transcripts with reverse-transcription polymerase chain reaction in formalin-fixed and paraffin-embedded tissue confirmed the synovial sarcoma diagnosis.

Topics: Adult; Arm; Biomarkers, Tumor; Fatal Outcome; Female; Fetal Diseases; Humans; Immunohistochemistry; Keratins; Oncogene Proteins, Fusion; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Synovial; Soft Tissue Neoplasms; Translocation, Genetic

Primary pulmonary and mediastinal synovial sarcoma is rare and poses a diagnostic challenge particularly when unusual histological features are present. We present 60 cases of primary pulmonary and mediastinal synovial sarcoma (29 male and 27 female subjects; mean age, 42 years) and compare our results with five prior series to better define unusual histological features. Clinically, patients with mediastinal synovial sarcoma were younger with a male gender bias. Radiologically, tumors were well delineated with distinctive magnetic resonance imaging features and little vascular enhancement. In all, 21/46 patients died of disease within 5 years. Histologically, all tumors had dense cellularity, interlacing fascicles, hyalinized stroma, and mast cell influx. Hemangiopericytoma-like vasculature (48/60), focal myxoid change (30/60), and entrapped pneumocytes (23/60) were seen. Calcification was not prevalent (10/60). Unusual histological features included Verocay body-like formations (7/60), vague rosettes (6/60), well-formed papillary structures (3/60), adenomatoid change (3/60), and rhabdoid morphology (2/60). Immunohistochemistry demonstrated expression of pancytokeratin (39/58), epithelial membrane antigen (29/53), cytokeratin 7 (26/40), cytokeratin 5/6 (5/7), calretinin (15/23), CD99 (19/23), bcl-2 (24/24), CD56 (11/11), S-100 (9/51), and smooth muscle actin (8/32). In total, 92% (36/39) of primary pulmonary and mediastinal synovial sarcomas studied were positive for t(x;18). In conclusion, our study confirms the clinical, histological, immunohistochemical, and molecular data from previous large series of primary pulmonary and mediastinal synovial sarcoma. Compared with soft tissue synovial sarcoma, primary pulmonary and mediastinal synovial sarcoma has less calcification, less obvious mast cell influx, and less radiologic vascularity, but similar magnetic resonance imaging features, percentage of poorly differentiated tumors, and number of t(x;18)-positive tumors. Awareness of focal unusual histology can prevent misdiagnosis particularly in t(x;18)-negative tumors.

Topics: 12E7 Antigen; Adult; Antigens, CD; Calbindin 2; CD56 Antigen; Cell Adhesion Molecules; Chromosomes, Human, Pair 18; Chromosomes, Human, X; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mediastinal Neoplasms; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-bcl-2; S100 Calcium Binding Protein G; S100 Proteins; Sarcoma, Synovial; Survival Rate; Translocation, Genetic

The cytological features of conventional monophasic spindle cell and biphasic synovial sarcoma have been defined in detail in several large series. The cytology of rare morphological variants, especially the subtypes of poorly differentiated synovial sarcoma, are insufficiently evaluated and diagnostically difficult to define. The objective of the present study was to call attention to the variable cytology of rare variants of synovial sarcoma. Furthermore, adjunctive diagnostic methods, necessary for a correct diagnosis, are discussed.. Aspirates from four synovial sarcomas, with cytological features, which differed from those of conventional synovial sarcoma and from each other, were retrieved from our files and re-evaluated.. In three of the cases a correct diagnosis was not obtained from routinely stained aspirates. In the fourth case, the correct diagnosis was established by a combination of cytomorphology, immunocytochemistry and fluorescence in situ hybridization (FISH) performed on the aspirated material.. Ancillary diagnostic methods are necessary in the examination of aspiration smears from synovial sarcoma, especially of morphological variants with a cytomorphology that differs from conventional spindle-cell monophasic and biphasic tumours. Immunocytochemistry and molecular genetic examinations (reverse transcriptase polymerase chain reaction or FISH) are the methods of choice.

Topics: Adolescent; Adult; Aged; Biopsy, Fine-Needle; Cytodiagnosis; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Mucin-1; Neoplasm Proteins; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Synovial; Synovial Membrane

To assess the diagnostic values of immunohistochemistry and SYT-SSX fusion gene detection for synovial sarcoma.. Based on clinical features, histological and immunohistochemical profiles, 195 cases of tumors were divided into three diagnostic categories: definitive synovial sarcoma, probable synovial sarcoma and possible synovial sarcoma. RT-PCR Detection of the SYT-SSX fusion gene was performed using paraffin embedded tissue samples. Comparison between RT-PCR and immunohistochemistry results was carried out and their diagnostic value was evaluated.. There were 62 (31.8%) definite synovial sarcomas, 49 (25.1%) probable synovial sarcomas and 84 cases (43.1%) possible synovial sarcomas. SYT-SSX fusion gene was detected in 140 (78.2%) cases overall, including 94.7% (54/57) definite synovial sarcomas, 86.0% (37/43) probable synovial sarcomas and 62.0% (49/79) possible synovial sarcomas. In tumors in the certain and probable synovial sarcoma categories, the positive rates of epithelial membrane antigen (EMA) were significantly higher in the SYT-SSX positive cases than SYT-SSX-negative cases (P = 0.022, P = 0.010, respectively). EMA was positively correlated with the presence of SYT-SSX (r(s) = 0.431, P = 0.001, r(s) = 0.463, P = 0.002, respectively). However, such a correlation was not seen in cytokeratin (CK), vimentin or S-100 protein immunostains (P > 0.05). In tumors of possible synovial sarcoma category, there were no significant differences of CK, EMA, vimentin or S-100 protein between SYT-SSX-positive and SYT-SSX-negative tumors.. SYT-SSX fusion gene detection is not needed when the conventional approaches are diagnostic. EMA positivity has a similar diagnostic value to that of SYT-SSX by RT-PCR for tumors in the probable synovial sarcoma category. However, detection of SYT-SSX is very important for diagnosis of the tumors in the category of possible synovial sarcoma.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Oncogene Proteins, Fusion; Reverse Transcriptase Polymerase Chain Reaction; S100 Proteins; Sarcoma, Synovial; Soft Tissue Neoplasms; Vimentin; Young Adult

Synovial sarcoma is a rare but distinct soft tissue neoplasm, most commonly occurring in para-articular regions of the extremities of young adults and also occurring in the head and neck region. To the best of our knowledge, only one case of primary synovial sarcoma of the thyroid has been previously reported. Here, we report a 15-yr-old man who had a chief complaint of a palpable neck mass. The neck computed tomography revealed a relatively well-demarcated solid mass in the left thyroid gland. After fine needle aspiration cytology, total thyroidectomy and lymph node dissection were performed. Grossly, the mass was covered by the same capsule as the thyroid gland, measuring 6X5X5 cm in dimensions and weighing 78 gm. The cut surface showed a well demarcated, lobulated, grayish tan, and rubbery solid tumor. Histologically, this tumor was a biphasic synovial sarcoma. Immunohistochemical, ultrastructural, genetic studies, and cytologic findings were all consistent with synovial sarcoma. When synovial sarcomas arise in this unusual site, recognition and differential diagnosis become more difficult. The differential diagnosis of a spindle epithelial tumor with thymus-like differentiation is very difficult due to their similar clinical, histological, and immunohistochemical features. Ultrastructural and cytogenetic studies for synovial sarcoma are necessary to establish a definitive diagnosis.

Topics: Adolescent; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron, Transmission; Sarcoma, Synovial; Thyroid Neoplasms; Vimentin

Differential diagnosis of monophasic synovial sarcoma requires the detection of specific biological markers. In this study we evaluated the presence of molecular alterations in 15 monophasic synovial sarcomas. Multiple changes affecting chromosome arms were detected by CGH-array in all microdissected cases available, and an association between gain or loss of specific regions harbouring cancer progression-associated genes and aneuploid status was found. The most frequent alteration was loss of 3p including 3p21.3-p23 region that, however, did not involve the promoter regions of the corresponding genes, RASSF1 and MLH1. Using Real-Time PCR, mRNA levels of both resulted moderately high compared to normal tissue; however, the weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation. Moreover, immunohistochemical analysis revealed that both mesenchymal and epithelial antigens were present in diploid tumours. These findings confirm the genetic complexity of monophasic synovial sarcoma and underline the need to integrate different analyses for a better knowledge of this tumour, essential to investigate new diagnostic and prognostic markers.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Biomarkers, Tumor; Carrier Proteins; Chromosome Deletion; Chromosomes, Human, Pair 3; DNA, Neoplasm; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Microsatellite Repeats; Middle Aged; Mucin-1; MutL Protein Homolog 1; Neoplasms, Connective Tissue; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Prognosis; RNA, Messenger; Sarcoma, Synovial; Transcription, Genetic; Tumor Suppressor Proteins; Vimentin

The term synovial sarcoma was first proposed for the histologically well defined entity by Knox in 1936. The name was proposed due to the fact that at least the cases reported in the early part showed some resemblance of the tumour to normal synovial tissue histologically. Thereafter, tumours have been diagnosed from areas without synovial tissue. The diagnosis of monophasic tumours can be difficult and immunostains appear to be a good diagnostic tool in those cases. The occurrence in the mandible is extremely rare. This is a case of synovial sarcoma arising in the condyle involving most of the ramus. The tumour was diagnosed as synovial sarcoma with predominant spindle cell component by correlation of histopathology with immunostains (cytokeratin, epithelial membrane antigen, actin and desmin). The patient has been treated with surgery and radiotherapy.

Topics: Actins; Adult; Desmin; Female; Follow-Up Studies; Humans; Keratins; Mandibular Condyle; Mandibular Neoplasms; Mucin-1; Sarcoma, Synovial

Topics: 12E7 Antigen; Adult; Antigens, CD; Cell Adhesion Molecules; Humans; Immunohistochemistry; Keratins; Male; Oncogene Proteins, Fusion; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Sarcoma, Synovial

Topics: Adult; Chromosomes, Human, Pair 18; Chromosomes, Human, X; Humans; Immunohistochemistry; Karyotyping; Keratins; Lung; Lung Neoplasms; Male; Neoplasms, Radiation-Induced; Radiotherapy; Sarcoma, Synovial; Translocation, Genetic; Wilms Tumor

Topics: Actins; Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratins; Neoplasms, Glandular and Epithelial; Sarcoma, Synovial; Thymoma; Thymus Gland; Thyroid Neoplasms; Vimentin

As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in the differential diagnosis, and analyzed the data with cluster analysis. Stain intensity was scored as none, weak, or strong. For CD99, tumors with membranous accentuation were independently categorized. Cluster analysis sorted five groups, with like tumors clustering together. Synovial sarcoma clustered into two groups: one cytokeratin and EMA positive (n = 11), the other mostly cytokeratin negative, EMA positive, bcl-2 positive and mostly CD56 positive (n = 9). Malignant peripheral nerve sheath tumor clustered into two groups: one S100 positive, with nestin and NGFR positivity in most (n = 10), the other mostly S100 negative, and variably but mostly weakly positive for nestin and NGFR (n = 11). Ewing sarcomas clustered into a single group driven by membranous CD99 staining. Thirteen cases failed to cluster (outliers), while three Ewing sarcomas clustered into groups of other tumor types. Paired antibodies for each tumor type determined by visual assessment of cluster analysis data and statistical calculations of specificity, sensitivity, and predictive values showed that EMA/CK7 for synovial sarcoma, nestin/S100 for malignant peripheral nerve sheath tumor, and membranous CD99/Fli-1 for Ewing sarcoma yielded high specificity and positive predictive values. Cluster analysis also highlighted aberrant staining reactions and diagnostic pitfalls in these tumors. Hierarchical cluster analysis is an effective method for analyzing high-volume immunohistochemical data.

Topics: 12E7 Antigen; Antigens, CD; Biomarkers, Tumor; Bone Neoplasms; CD56 Antigen; Cell Adhesion Molecules; Cluster Analysis; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mucin-1; Nectins; Nerve Sheath Neoplasms; Nerve Tissue Proteins; Proto-Oncogene Protein c-fli-1; Receptors, Nerve Growth Factor; S100 Proteins; Sarcoma, Ewing; Sarcoma, Synovial

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2. Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Topics: 12E7 Antigen; Adult; Antigens, CD; Antigens, CD1; Antigens, CD20; Antigens, CD34; Cell Adhesion Molecules; Choristoma; Diagnosis, Differential; Hamartoma; Humans; Keratins; Leukocyte Common Antigens; Male; Nerve Sheath Neoplasms; Sarcoma, Synovial; Soft Tissue Neoplasms; Thymoma; Thymus Neoplasms; Vimentin

Synovial sarcoma arising in the abdominal wall is a rare tumor. We report a case of a 38-year-old man who complained of abdominal pain. Physical examination revealed a firm mobile mass, 25 cm in diameter, in the left lower abdominal wall. The tumor was first thought to be a sarcoma arising from the omentum or mesentery. During surgery, a large tumor was found attached to the inner surface of the abdominal wall and compressing the gastrointestinal tract. On microscopic examination the tumor corresponded to a biphasic synovial sarcoma immunoreactive for cytokeratins (AE1/AE3, 7 and 19), epithelial membrane antigen and carcinoembryonic antigen in the epithelial tumor cells, for E-cadherin especially in their glandular structure, vimentin, CD99, and CD56 in the spindle cell component and for bcl-2 protein. The tumor recurred at the same site, and clinical course progressed to death 3 months after the initial diagnosis.

Topics: 12E7 Antigen; Abdominal Neoplasms; Abdominal Wall; Adult; Antigens, CD; Biomarkers, Tumor; Cadherins; Carcinoembryonic Antigen; Carcinosarcoma; CD56 Antigen; Cell Adhesion Molecules; Fatal Outcome; Humans; Keratins; Male; Neoplasm Recurrence, Local; Sarcoma, Synovial; Tomography, X-Ray Computed; Vimentin

Peripheral primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES) of the central nervous system is extremely rare and should be differentiated from central PNET and other small blue round cell tumors. We describe a case of a meningeal peripheral PNET/ES of the spinal cord in an 11-year-old boy. Immunohistochemically, the small blue round cell tumor showed expression of epithelial markers and of CD99, thus posing an important differential diagnostic problem with a poorly differentiated synovial sarcoma. Fluorescence in situ hybridization revealed rearrangement of the EWS gene, as seen in peripheral PNET/ES. Peripheral PNET/ES does occur in the central nervous system, but its diagnosis can be extremely difficult on morphologic and immunohistochemical grounds alone. Genetic analysis plays a key role in its distinction from other small blue round cell tumors.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Child; Diagnosis, Differential; Humans; Keratins; Laminectomy; Male; Meninges; Mucin-1; Neuroectodermal Tumors, Primitive; Sarcoma, Ewing; Sarcoma, Synovial; Spectral Karyotyping; Spinal Cord; Spinal Cord Neoplasms; Vimentin

A series of 15 cases of primary mediastinal neoplasms displaying histopathologic, immunohistochemical, and ultrastructural features of synovial sarcoma is presented. The patients' ages ranged from 3 to 83 years, with a male-to-female ratio of 2:1. Nine cases presented as anterior mediastinal masses with chest pain, shortness of breath, and pleural effusion, and 6 cases were in paravertebral location in the posterior mediastinum and presented with neck or back pain and pleural effusion. The tumors measured from 5 to 20 cm in greatest diameter and showed a tan white, soft to rubbery cut surface with areas of hemorrhage and necrosis and foci of gelatinous material. Four cases showed areas of cystic degeneration. In 7 cases, the tumors were well circumscribed; in 6 cases, the tumors grossly invaded the pleura, pericardium, heart, great vessels, chest wall, rib, and vertebra. Histologically, 5 cases displayed a biphasic growth pattern, with well-formed glandular elements admixed with a monotonous spindle cell population. Ten cases were exclusively composed of a monotonous atypical spindle cell proliferation. Immunohistochemical studies showed focal positivity of the tumor cells for cytokeratin and/or epithelial membrane antigen, and strong positivity for vimentin and bcl-2 in the spindle cells in all cases studied (10 of 10). Eight cases also showed focal positivity for CD99. Electron microscopic examination in 5 cases showed oval to spindle tumor cells with closely apposed cell membranes, abundant cytoplasmic intermediate filaments and rough endoplasmic reticulum, and immature desmosome-type cell junctions. Ten patients were treated by complete surgical excision and two by partial excision followed by radiation therapy. In 4 patients, the tumors were inoperable and treated with radiation therapy only. Clinical follow-up was available in 5 patients and showed local recurrence with metastases to lung, lymph nodes, and epidural space from 1 to 3 years in 4 cases and liver metastases and death due to tumor after 6 month in 1 case. Synovial sarcoma should be considered in the differential diagnosis of biphasic and monophasic spindle cell neoplasms of the mediastinum.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Nucleus; Child, Preschool; Combined Modality Therapy; Desmosomes; Female; Humans; Keratins; Male; Mediastinal Neoplasms; Microscopy, Electron, Transmission; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Radiography, Thoracic; Sarcoma, Synovial; Tomography, X-Ray Computed

To see the distribution of Calretinin, thrombomodulin, CK5/6 and HBME-1 markers in various subtypes of mesotheliomas and extend the published data on this topic. The positivity of adenocarcinoma specific markers (CEA and BerEP4) in malignant mesotheliomas have also been evaluated.. Various markers in 173 cases of malignant mesotheliomas received over a period of 8 years were evaluated by immunohistochemistry.. In majority of malignant mesotheliomas i.e., epithelioid and biphasic types, the positive staining patterns complement the gold standard histologic diagnosis. However, in a small minority mainly sarcomatoid variant, heavy reliance cannot be placed on these markers. CEA and BerEP4 are useful negative markers of mesotheliomas, although occasionally these are positive in clear cut mesotheliomas.. Specificity of various markers in malignant mesotheliomas should be assessed according to histologic subtypes. The existing generation of markers is not reliable in diagnosis of sarcomatoid mesotheliomas. Fortunately this forms only a small group of mesothelial malignancy. In common epithelioid and biphasic variants calretinin, thrombomodulin, CK5/6, HBME-1 are sensitive positive markers whereas CEA and BerEP4 are negative markers of malignant mesotheliomas.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Coloring Agents; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma, Synovial; Soft Tissue Neoplasms; Thrombomodulin

More than 90% of synovial sarcomas (SSs) possess a non-random chromosomal translocation t(X;18)(p11;q11) and express SYT-SSX fusion gene products originating from the translocation. To test whether it is possible to detect the SYT-SSX mRNA on archival formalin-fixed paraffin-embedded SS tissue sections using PCR-based in situ amplification technique, we performed reverse transcription-polymerase chain reaction in situ hybridization (RT-PCR ISH) for the SYT-SSX fusion gene mRNA. In three types of SSs, monophasic fibrous, biphasic and poorly differentiated, NBT/BCIP signals corresponding to SYT-SSX mRNA were uniformly and predominantly positive in the sarcoma cell cytoplasm. Our results indicated that SS cells uniformly possessed the SYT-SSX fusion genes and expressed their transcripts. Furthermore, our results were thought to support monoclonal origin of epithelial and spindle cell components of biphasic SSs. Thus, specific chromosomal translocation t(X;18) is likely to be an early event in the development of SSs, and the expression of SYT-SSX fusion gene products is thought to be crucial for the tumorigenesis of SSs.

Topics: Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mucin-1; Oncogene Proteins, Fusion; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoma, Synovial; Vimentin

There has been no report on useful immunohistological markers for epithelioid sarcoma (ES) so far. The purpose of this study is to evaluate the positivity and specificity of CA125 as a marker for the correct diagnosis of ES.. This study was performed in 11 patients with ES (nine men and two women; distal type: 10 cases; proximal type: one case), 78 patients with other soft tissue tumors and nine with benign granulomas. The other soft tissue tumors consisted of six synovial sarcomas, six clear cell sarcomas, eight leiomyosarcomas, six rhabdomyosarcomas, five malignant peripheral nerve sheath tumors, ten malignant fibrous histiocytomas, 17 desmoid tumors, 14 liposarcomas, six squamous cell carcinomas (cutaneous SCC of the distal extremities), two rheumatoid nodules and seven foreign body granulomas. Immunohistochemical analysis for CA125 was performed for these 89 soft tissue tumors and nine granulomas using a labeled streptavidin biotin method. Immunohistochemical analysis of epithelial membrane antigen, cytokeratin, carcinoembrionic antigen, vimentin and CD34 was performed only for the 11 ES patients.. CA125 was strongly expressed in 10 out of the 11 ES patients. EMA, cytokeratin and vimentin were also positive in all the cases. CEA was positive in two of the 11 patients. Immunohistochemical study in six ES patients showed expression of CD 34. The other 78 soft tissue tumors and nine granulomas did not express CA125.. This study clearly revealed the specificity and positivity of CA125 in ES. These data indicate that CA125 may be a useful tumor marker for diagnosing ES.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD34; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Sarcoma, Clear Cell; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms

The clinical, radiological and pathologic features of a biphasic synovial sarcoma in the left elbow joint of a two-year-old male Rottweiler are presented. The tumor showed positive immunoreactivity for vimentin, Epithelial Membrane Antigen (EMA), p53 and PCNA, while it was negative for the cytokeratin used, S-100, Rb and p21. Immunohistochemistry for EMA allowed the identification of epithelioid components of synovial sarcoma, and may, therefore, contribute in establishing a diagnosis of biphasic synovial sarcoma. Intratumoral variation in PCNA immunoreactivity was minimal, indicating that the various tumor components proliferate at more or less similar rates. Overall, the characterized immunohistochemical profile for canine synovial sarcoma, not defined previously, may provide clues to the histogenesis of the phenotypically mesenchymal and epithelial elements of the tumor, and may be of value in the differential diagnosis of challenging cases, decreasing the risk of under- and mis-diagnosis. Although more cases need to be studied to determine whether there is a consistent pattern of immunostaining in canine synovial sarcoma, its potential significance is discussed in relation to the histogenesis, molecular pathology and differential diagnosis of canine synovial sarcoma.

Topics: Animals; Dog Diseases; Dogs; Elbow Joint; Forelimb; Histocytochemistry; Immunohistochemistry; Keratins; Male; Mucin-1; Oncogene Protein p21(ras); Proliferating Cell Nuclear Antigen; Radiography; Retinoblastoma Protein; Sarcoma, Synovial; Soft Tissue Neoplasms; Tumor Suppressor Protein p53; Vimentin

To evaluate a series of synovial sarcomas arising in the abdomen, pelvic cavity, or retroperitoneum. Synovial sarcoma is rare within the abdomen. In this location, it can be confused with other biphasic tumours and with other spindle and round cell sarcomas.. Cases were retrieved from archives. There were 11 intra-abdominal tumours among 300 synovial sarcomas in two referral practices (3.7%). Three were pelvic (two midline, one sidewall) and eight were retroperitoneal. They occurred in six males and five females aged from 25 to 75 years (mean 49 years, median 46 years), and ranged in diameter from 65 to 470 mm (mean 210 mm, median 150 mm). Six examples were biphasic, five were monophasic and seven had poorly differentiated areas. Monophasic tumours displayed at least one epithelial marker. One biphasic tumour had a SYT-SSX2 fusion gene. Seven sarcomas were high-grade and four of intermediate grade malignancy. Follow-up data were available in 10 patients. In all but one case, tumour recurred or metastasized within the abdomen. The pelvic sarcomas also metastasized outside the abdomen. Eight of 10 patients (80%) died of disease with survival from 4 to 36 months (mean 17 months, median 18 months). Two patients were alive with disease at 43 and 48 months.. Synovial sarcomas rarely arise within the abdomen and pelvis. They occur mainly in middle age, attain a large size, are difficult to excise and recur locally. Pelvic tumours metastasize distantly. Retroperitoneal tumours remain confined to the abdomen and, unlike synovial sarcomas elsewhere, do not metastasize remotely, although mortality is high.

Topics: 12E7 Antigen; Abdominal Neoplasms; Adult; Aged; Antigens, CD; Cell Adhesion Molecules; DNA, Complementary; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Oncogene Proteins, Fusion; S100 Proteins; Sarcoma, Synovial; Sequence Analysis, DNA

Other authors have demonstrated earlier that cells of normal synovium contain metallothionein. The protein was also detected in several other normal cell types and in tumors derived from the cells. Metallothionein content is thought to reflect proliferative activity of neoplastic cells. Therefore, it was decided to demonstrate metallothionein expression in various types of synovial sarcoma. The present study aimed to determine metallothionein cellular expression by immunocytochemical techniques in nine cases of biphasic, six cases of monophasic (spindle cell), and five cases of poorly differentiated synovial sarcoma, and to compare the expression with those of vimentin and cytokeratin 19. Metallothionein expression was demonstrated in epithelioid cells in all cases of biphasic type sarcoma and in spindle cells in all cases of monophasic type tumors. In poorly differentiated tumors, metallothionein expression was detected in four of five cases (80%). Expression of cytokeratin 19 was typical for epithelioid cells and expression of vimentin for spindle cells of synovial sarcoma. A much less pronounced expression of the proteins was observed in poorly differentiated tumors. The results indicate that metallothionein expression may prove useful in differential diagnosis and for defining prognosis in cases of synovial sarcomas.

Topics: Adolescent; Adult; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Metallothionein; Middle Aged; Prognosis; Sarcoma, Synovial; Vimentin

Synovial sarcoma is a unique mesenchymal tumour characterized by the presence of epithelial differentiation, although the mechanism involved in the epithelial morphology is still unclear. The aim of this study was to evaluate the function of matrix metalloproteinase-2 (MMP-2) in synovial sarcoma, in order to assess whether MMP-2 expression plays an important role in epithelial differentiation, or whether it contributes to a poor clinical outcome.. Immunohistochemical stainings for MMP-2, cytokeratins (CKs) 7, 8, 18 and 19, and E-cadherin were performed for 58 (44 monophasic and 14 biphasic) cases of synovial sarcoma, and we compared the expression of these proteins with the histological and clinical findings. MMP-2 and E-cadherin expression was observed in 43 cases (74.1%) and in 18 cases (31.0%), respectively. Expression of these proteins was preferentially observed in the glandular components of biphasic tumours or the epithelioid areas of monophasic tumours. Statistically significant correlations were recognized between MMP-2 expression and E-cadherin expression of biphasic subtype. Moreover, there were statistically significant correlations between monophasic tumours with epithelioid areas and MMP-2 expression or E-cadherin expression. MMP-2 expression was correlated with epithelial differentiation as assessed by CK immunoreactivity. The expression of MMP-2 did not affect the overall survival rate in synovial sarcoma.. MMP-2 expression seemed to have an important role to play in the epithelial differentiation of tumour cells in synovial sarcoma, through remodelling of the extracellular matrix and by changing the cytoskeletal interaction between the extracellular matrix and tumour cells.

Topics: Cadherins; Epithelium; Humans; Immunohistochemistry; Keratins; Matrix Metalloproteinase 2; Sarcoma, Synovial

Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid-glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the spindle cell and in the solid-glandular component of biphasic synovial sarcomas. We also performed a double-immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in neoplastic cells expressing either vimentin or cytokeratin.. Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or chi2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P=0.0004, P=0.082, and P < 0.0001, respectively); on the other hand, the latter showed higher expression of bcl-2 and vimentin than the former (P=0.0281 and P=0.059, respectively). Double immunohistochemistry analysis revealed higher co-expression levels of cytokeratin/Ki67 and cytokeratin/bcl-2 than the spindle cell component (P=0.015 and P < 0.0001, respectively); conversely, the latter presented higher co-expression of vimentin/bcl-2 than the former (P=0.0007). All cases showed no more than 10% of cells coexpressing cytokeratin/bcl-2, cytokeratin/Ki67, and no case revealed cells coexpressing vimentin/Ki67.. Our findings indicate that in biphasic synovial sarcoma the acquisition of epithelial phenotype (solid/glandular component) is associated with a high expression of pro-apoptotic proteins and a high proliferative differentiation status, and conversely, mesenchymal phenotype (spindle cell component) is associated with a high expression of apoptosis-inhibitor bcl-2 and a low proliferative terminal-type differentiation status.

Topics: Adult; Aged; Aged, 80 and over; bcl-2-Associated X Protein; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Sarcoma, Synovial; Vimentin

Synovial sarcoma (SS) is a rare soft-tissue tumor that affects children and young adults. It is characterized by the chromosomal translocation t(X;18)(p11.2;q11.2), which results in the fusion of the SYT gene on chromosome 18 with a SSX gene on chromosome X. In the majority of cases, SYT is fused to exon 5 of SSX1 (64%), SSX2 (36%), or, rarely, SSX4. A novel fusion transcript variant deriving from the fusion of SYT to exon 6 of SSX4 gene (SYT/SSX4v) was found coexpressed in one of the previously reported SYT/SSX4 cases. In the present investigation, we describe a new SS case that was previously shown to be negative for SYT/SSX1 and SYT/SSX2 expression by conventional reverse transcription polymerase chain reaction (RT-PCR) methods. By redesigning and optimizing the RT-PCR protocol, we were able to detect SYT/SSX4v as the sole fusion transcript expressed in this tumor sample. This finding suggests that this novel fusion gene, which involves exon 6 of SSX only, is sufficient to keep the transforming function conferred by the SYT/SSX translocation of SS. In about 3% of morphologically, ultrastructurally, and immunohistochemically defined SS, the SYT/SSX fusion transcript is not detected using conventional RT-PCR. Here we demonstrate that optimization of the RT-PCR method is important for detecting different and unexpected SYT/SSX variants, which otherwise could be overlooked. Using nine cases of SS in which SYT/SSX fusion transcripts were not detected by conventional RT-PCR methods, we demonstrate the presence of SYT/SSX transcripts in two cases using the proposed RT-PCR approach. Applications of optimized RT-PCR can contribute to reduce false-negative SYT/SSX SS cases reported in literature.

Topics: Adult; Base Sequence; Cloning, Molecular; DNA, Complementary; Female; Humans; Immunohistochemistry; Keratins; Molecular Sequence Data; Oncogene Proteins, Fusion; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; S100 Proteins; Sarcoma, Synovial; Sequence Analysis, DNA; Vimentin

Keratin polypeptides of the nonhair type, numbered 1 through 20 in the Moll catalog, are selectively expressed in normal and neoplastic tissues. Keratin 1 (K1), the highest-molecular-weight keratin (67 kd), was generally considered specific for keratinizing squamous epithelia. However, recent studies have shown that it is an integral component of the multiprotein kininogen receptor of endothelial cells. A library of formalin-fixed, paraffin-embedded tissue samples was evaluated immunohistochemically (avidin-biotin peroxidase complex method) for K1 expression using a specific monoclonal antibody (Novocastra clone 34betaB4). The study group included a wide variety of normal tissues and 541 tumors of epithelial or mesenchymal derivation. The specificity of the antibody to K1 was verified in normal epithelial tissues, where the staining was essentially limited to the epidermis and Hassal corpuscles of the thymus and focally to other squamous epithelia. Among carcinomas, it was essentially limited to keratinizing squamous carcinomas. It was also regularly found in endothelial cells of normal capillaries, veins, and arteries. Capillary, cavernous, and venous hemangiomas often had endothelia with K1 positivity. Among the malignant vascular tumors, epithelioid hemangioendotheliomas were consistently positive (8 of 8). However, angiosarcomas had more variable expression (59 of 81 were positive), with well-differentiated tumors generally having greater reactivity than poorly differentiated examples. Mesenchymal tumors with K1 expression included schwannomas (10 of 16), epithelioid sarcomas (26 of 37), and synovial sarcomas (19 of 68). In the last 2 tumor types, K1 reactivity was detected in both epithelioid and spindled neoplastic populations. In addition to its specificity for keratinizing squamous epithelia, K1 can be immunohistochemically detected in normal vascular endothelial cells and a spectrum of vascular tumors. However, its expression in poorly differentiated vascular tumors is variable, suggesting that this marker is poorly conserved in highly transformed endothelia. The unexpected K1 immunoreactivity in nonvascular soft tissue tumors, such as synovial sarcoma, epithelioid sarcoma, and schwannomas, requires further study.

Topics: Adult; Carcinoma; Endothelium; Female; Fetus; Humans; Immunoenzyme Techniques; Keratins; Male; Mesoderm; Neoplasms; Sarcoma, Synovial; Vascular Neoplasms

An 8-month-old Ayrshire heifer had a rapidly growing mass in the axillary region of the left thoracic limb. The mass surrounded the distal humerus and entrapped nerves of the brachial plexus, causing an abnormal gait. Histologically, the mass was composed of clusters and cords of round to polygonal cells with scattered, spindle-shaped cells. The neoplastic cells stained positively for vimentin and cytokeratin. No staining was found with S-100 protein, kappa and lambda light chains, or T-cell markers by immunohistochemistry. On electron microscopic evaluation, the cytoplasm of the neoplastic cells contained few organelles, principally rough and smooth endoplasmic reticulum and mitochondria. This synovial sarcoma has histologic and ultrastructural features characteristic of the poorly differentiated subtype of synovial sarcoma in the human classification system.

Topics: Animals; Cattle; Cattle Diseases; Extremities; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Keratins; Microscopy, Electron; S100 Proteins; Sarcoma, Synovial; Vimentin

Monophasic synovial sarcoma (MSS) and malignant peripheral nerve sheath tumor (MPNST) are spindle cell sarcomas with overlapping histologic features, and their immunophenotypes may overlap, since MPNSTs express S-100 protein in only 50% to 60% of cases and rarely express epithelial markers, whereas MSSs can express S-100 protein in up to 40% of cases. We immunostained 29 cases of MSS and 29 cases of MPNST with antibodies to AE1/AE3, CAM 5.2, epithelial membrane antigen (EMA), S-100 protein, and cytokeratin subsets 7 and 19. Inclusion criteria for MSS included a consistent histology with expression of at least 1 epithelial marker. Inclusion criteria for MPNST included a tumor with a consistent histology arising in a patient with neurofibromatosis type 1 and/or in a plexiform neurofibroma, or ultrastructural confirmation of clear-cut schwannian differentiation. By definition, all cases of MSS were positive for at least 1 epithelial marker. Ten cases showed focal S-100 protein immunoreactivity, and 26 cases stained for cytokeratins 7 and 19. Twenty-three cases stained for both antigens, whereas only 2 cases were negative for both cytokeratins. Twenty-two MPNSTs demonstrated immunoreactivity for S-100 protein, and 11 stained focally for AE1/AE3 or EMA. Two cases of MPNST stained for cytokeratin 7, and only 1 case stained for cytokeratin 19. No cases of MPNST stained for both cytokeratins. Antibodies to cytokeratins 7 and 19 are useful adjuncts for the separation of MSS from MPNST. The majority of MSSs stain for one or both of these antigens, whereas most MPNSTs, including those that are EMA- or AE1/AE3-positive, do not express these cytokeratin subsets.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Nerve Sheath Neoplasms; Sarcoma, Synovial; Soft Tissue Neoplasms

We report a case of synovial sarcoma with extensive myxoid change diagnosed by fine-needle aspiration. The patient is a 46-year-old woman who presented with a right paratibial mass. Aspiration cytology demonstrated a spindle cell neoplasm consistent with a synovial sarcoma but containing a prominent myxoid matrix. The clinical suspicion and cytologic diagnosis of a synovial sarcoma was confirmed by histologic and immunohistochemical findings. The cytologic differential diagnosis of spindle cell neoplasms with extensive myxoid change should be broadened to include synovial sarcoma.

Topics: Biomarkers, Tumor; Biopsy, Needle; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucins; Sarcoma, Synovial; Soft Tissue Neoplasms

We report the development of a reverse-transcriptase polymerase chain reaction assay that detects (in paraffin-embedded, formalin-fixed tissue) the SYT-SSXchimeric RNA transcript resulting from the t(X;18) of synovial sarcoma. The primers chosen detect both of the SSX1 and SSX2 partners, and the target sequence is small enough (87 base pairs) to be reliably detected in archival and variably processed consultation material. To demonstrate its usefulness, we applied it to 14 problematic cases, including spindle cell tumors of the thoracic region, of the neck, and of subcutaneous tissue. For instance, we show that, depending on the location, synovial sarcoma can mimic malignant solitary fibrous tumor, the spindle epithelial tumor with thymus-like differentiation, or skin adnexal tumors. Molecular detection of the SYT-SSX chimeric RNA should allow the reclassification of difficult cases in which the morphologic features overlap different entities or in which tumor nosology is still evolving.

Topics: Adult; Aged; Chromosomes, Human, Pair 18; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Molecular Probe Techniques; Neoplasm Proteins; Paraffin Embedding; Polymerase Chain Reaction; Proteins; Proto-Oncogene Proteins; Recombinant Fusion Proteins; Repressor Proteins; RNA, Neoplasm; Sarcoma, Synovial; Skin Neoplasms; Thoracic Neoplasms; Transcription, Genetic; Translocation, Genetic; X Chromosome

Synovial sarcoma is a relatively common sarcoma in adults, which in its classic bimorphic form infrequently poses a diagnostic problem. Monomorphic spindled variants, as well as the less common poorly differentiated variants, may be confused with other soft-tissue sarcomas; the poorly differentiated variant (PDSS), in particular, may be histologically indistinguishable from other small, blue, round cell tumors, including primitive neuroectodermal tumors (PNETs). Detection of the synovial sarcoma-associated t(X;18) by either cytogenetic or molecular genetic approaches may be necessary to confirm the diagnosis of synovial sarcoma in difficult cases. We evaluated 10 cases of PDSS from eight patients using a panel of antibodies (including those to intermediate filament proteins, nerve-sheath associated markers, and neuronal and neuroectodermal associated markers) in order to better establish the immunophenotype of this tumor and to help distinguish it from the tumors with which it may be confused, particularly PNETs and high-grade malignant peripheral nerve sheath tumors (MPNSTs). Our results showed PDSS to have significant immunophenotypic overlap with both PNETs and MPNSTs. In most instances these three entities may be differentiated by a panel of antibodies that should include those to both low and high molecular weight cytokeratins, epithelial membrane antigen, type IV collagen, CD99, CD56, and S-100 protein. Our results also suggest that synovial sarcoma may be a tumor showing combined neuroectodermal and nerve sheath differentiation--perhaps because of translocation-associated expression of specific proteins--rather than a carcinosarcoma of soft tissues or a tumor of specialized arthrogenous mesenchyme.

Topics: 12E7 Antigen; Adolescent; Adult; Antigens, CD; Biomarkers, Tumor; Cell Adhesion Molecules; Child; Collagen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Middle Aged; Mucin-1; Nerve Sheath Neoplasms; Neuroectodermal Tumors, Primitive; Neurofilament Proteins; Peripheral Nervous System Neoplasms; Sarcoma, Synovial

Identification of the t(X;18)(p11.2;q11.2) translocation and detection of the resulting SYT-SSX1 or SYT-SSX2 fusion transcripts are useful diagnostic markers for synovial sarcoma. In this study, we developed a polymerase chain reaction (PCR) assay to amplify SYT-SSX fusion transcripts. The primer sequences were designed to generate small PCR products and to amplify sequences of all known SSX genes as fusion partners for the SYT gene. RNA was obtained from formaldehyde-fixed and paraffin-embedded tissues of 22 immunohistochemically characterized synovial sarcomas, 6 of them cytogenetically confirmed as t(X;18) positive. The SYT-SSX fusion transcripts were detected in 21 of the 22 analyzed cases. The type of the fusion was identified by the specific restriction enzyme digestion pattern as SYT-SSX1 in 13 cases and SYT-SSX2 in 7 cases; in 1 case, the type could not be assigned. None of the cases showed involvement of the SSX3, SSX4, or SSX5 genes, the other members of the SSX gene family. In seven cases, the SYT-SSX1 or SYT-SSX2 fusion transcripts were demonstrated in frozen tissue using a different PCR assay. The PCR products were confirmed as SYT-SSX sequences by sequencing in five randomly selected cases. Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts. The PCR assay used in this study performs well in formaldehyde-fixed and paraffin-embedded tissue, and it shows a high specificity. This assay can be used as an adjunct test for diagnostically difficult cases or in retrospective studies to refine the diagnosis of synovial sarcoma in archival material.

Topics: Adolescent; Adult; Antigens, Neoplasm; Base Sequence; Female; Frozen Sections; Humans; Immunoenzyme Techniques; Karyotyping; Keratins; Male; Middle Aged; Molecular Sequence Data; Mucin-1; Neoplasm Proteins; Oncogene Proteins, Fusion; Paraffin Embedding; Polymerase Chain Reaction; Proteins; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Synovial; Transcription, Genetic; Translocation, Genetic

We describe a case of synovial sarcoma occurring in a 36 year-old woman, 8 years after radiation therapy for Hodgkin's disease. The tumor showed histological, immunohistochemical, ultrastructural, and molecular features diagnostic of synovial sarcoma. To our knowledge, this is the first report of a fully documented case of radiation associated synovial sarcoma.

Topics: Adult; Biomarkers, Tumor; Female; Hodgkin Disease; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Mucin-1; Neoplasms, Radiation-Induced; Peripheral Nervous System Neoplasms; Sarcoma, Synovial; Translocation, Genetic

We report two cases of synovial sarcoma arising in the vulva. The patients were 30 and 37 years old and presented with a painless mass that was interpreted clinically as a cyst. The tumors were 2.0 and 1.2 cm in greatest diameter. Histologically, they were composed of epithelial cells forming solid nests and gland-like and papillary structures surrounded by spindle-shaped cells. Immunohistochemically, the epithelial cells stained for cytokeratin and the spindle-shaped cells for vimentin. Ultrastructurally, the epithelial cells had prominent intercellular junctions and narrow microvilli and were separated from the spindle-shaped cells by a basal lamina. The spindle-shaped cells were closely apposed with focal intercellular contacts. One tumor recurred locally 3.5 years after excision, but the patient was alive and well 1 year after a re-excision and radiation therapy. The other patient was alive and well 4 years after an excision. These tumors are the first reported examples of synovial sarcoma arising in the vulva.

Topics: Adult; Diagnosis, Differential; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Sarcoma, Synovial; Vimentin; Vulvar Neoplasms

A 46-year-old man presented with recurrent anemia and polyarthralgia. Investigations revealed a mass in the ileal mesentery, which was resected. Results of routine histologic examination suggested a diagnosis of synovial sarcoma, a rare malignancy usually not reported at this site.. Tissue was examined immunohistochemically, ultrastructurally, and by fluorescent in situ hybridization to confirm the diagnosis.. Immunohistochemical studies revealed widespread labeling for cytokeratins and focal labeling for desmin and vimentin in the epithelial component, with labeling for epithelial membrane antigen in the epithelial and spindle-cell components. Fluorescent in situ hybridization analysis showed the characteristic t(X;18) translocation of synovial sarcoma.. This is a unique case of synovial sarcoma in the small intestinal mesentery. Immunohistochemical labeling confirmed the diagnosis, although, to the authors' knowledge, the pattern of desmin labeling has not been described previously. The clinical association with polyarthralgia, which resolved after removal of the neoplasm, also has not been described previously.

Topics: Desmin; Humans; Ileum; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Mesentery; Middle Aged; Peritoneal Neoplasms; Sarcoma, Synovial; Vimentin

Topics: Adolescent; Adult; Antibodies, Monoclonal; Female; Humans; Immunophenotyping; Keratins; Macrophages; Male; Receptors, Cytoadhesin; Sarcoma, Synovial; Soft Tissue Neoplasms; Synovial Membrane; Uridine Diphosphate Glucose Dehydrogenase

Twenty-five synovial sarcomas were studied with a battery of antibodies directed against keratin and epithelial membrane antigen (EMA). The keratin antibody MNF 116 showed reactivity in 24 tumors. In addition, 22 tumors showed reactivity with the antibody Keratin Wide Spectrum, 20 with the antibody Keratin 56, 64, and 19 with CAM 5.2. Seventeen tumors showed reactivity with EMA. The keratin and EMA reactivity was present in cells lining obvious cleft-like structures in biphasic tumors. In the spindle cell areas of both biphasic and monophasic fibrous tumors, we found clusters of a few reacting cells apparently located around small clefts. In the synovioblastic tumors, clusters of plump tumor cells reactive for both the keratins and EMA were present. In conclusion, we found that proper identification of epithelial differentiation in synovial sarcomas is facilitated by an immunohistochemical application of anti-epithelial antibodies. In most tumors, there was immunoreactivity for the same type of keratins as are normally identified in simple epithelia (the antibody CAM 5.2), but also for those found in stratified squamous epithelia (the antibody Keratin 56, 64). The results indicate that screening for epithelial features on paraffin sections in the various types of synovial sarcoma, even the poorly differentiated synovioblastic tumors, is improved if epithelial antibodies with a broad spectrum of reactivity are chosen.

Topics: Antibodies; Antibodies, Monoclonal; Antigens, Neoplasm; Epithelium; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Retrospective Studies; Sarcoma, Synovial

Little attention has been paid to the composition of the extracellular matrix in synovial sarcoma, a tumour showing both epithelial and mesenchymal phenotypes. As extracellular matrix participates actively in interactions between epithelial and mesenchymal tissues, further knowledge of the pathogenesis of this tumour may be provided by the study of extracellular matrix components. Therefore, we have analysed the immunohistochemical distribution of type I, III, and IV collagen, fibronectin, laminin and tenascin in four cases of synovial sarcoma. The pattern of immunoreactivity for these molecules varied according to the tissue phenotype of the tumour. Mesenchymal tissue labelled mainly for type I and III interstitial collagen and fibronectin. The epithelial component was surrounded by a laminin and type IV collagen-positive basement membrane, but punctate pericellular reactivity for laminin and type IV collagen was also detected among some mesenchymal cells. Tenascin was strongly expressed in the mesenchymal tissue immediately around epithelial structures and weakly or not at all expressed in the monophasic tumours and in mesenchymal tissue distant from epithelial elements in the biphasic tumours. These results suggest some resemblances between synovial sarcoma and the embryonic development of epithelia from mesenchymal cells, providing further support for the concept of an epitheliogenesis from the mesenchyme in these tumours.

Topics: Adult; Cell Adhesion Molecules, Neuronal; Collagen; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fibronectins; Humans; Keratins; Laminin; Male; Middle Aged; Neoplasm Proteins; Sarcoma, Synovial; Tenascin; Vimentin

Routine paraffin-embedded sections from synovial sarcomas in 70 patients were stained immunohistochemically with monoclonal anti-cytokeratin antibody and serum against mesothelial cells. Positive reactions occurred in the epithelioid cells of biphasic tumors only. On the ground of the reaction with anti-mesothelial serum a hypothetical scheme of cell differentiation in synovial sarcoma was set up.

Topics: Antibodies, Monoclonal; Cell Differentiation; Diagnosis, Differential; Epithelium; Humans; Immune Sera; Immunohistochemistry; Keratins; Mesothelioma; Paraffin Embedding; Sarcoma, Synovial; Soft Tissue Neoplasms; Staining and Labeling

A 43-year-old man presented with decreased range of motion in his left knee and a painful medial joint mass that was grossly visible. Arthroscopy demonstrated a mobile, flat mass 3 cm in diameter in the knee joint that seemed to be loosely tethered to the synovium. The mass was excised, and light microscopic examination demonstrated a biphasic synovial sarcoma. There was no transition with the attached normal synovium. Immunohistochemically, the epithelial component was intensely positive for epithelial membrane antigen and cytokeratins (CAM 5.2 and AE 1/AE 3), and the spindle cell component was focally positive for these markers. The patient has no evidence of disease 9 years after only local excision. Although the term synovial sarcoma suggests a relationship to normal synovium, only rarely has truly intraarticular disease been reported.

Topics: Adult; Cartilage, Articular; Humans; Immunohistochemistry; Keratins; Knee Joint; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Connective Tissue; Sarcoma, Synovial

The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas.

Topics: Cytoskeletal Proteins; Desmoplakins; Desmosomes; Humans; Keratins; Leiomyosarcoma; Neurilemmoma; Peptides; Peripheral Nervous System Neoplasms; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms

Of 49 cases of synovial sarcoma, which represent 5.8% of all soft tissue sarcomas with confirmed diagnosis in the files of the Kiel Pediatric Tumor Registry (Kiel, Germany), 35 occurred in patients up to the age of 18 years. The lower extremities were the most common. The 35 cases included 21 biphasic and 14 monophasic fibrous synovial sarcomas. The different cell types constituting synovial sarcoma could be demonstrated by conventional light microscopic study, but more readily so by immunohistochemical study, particularly when antibodies against cytoskeletal components were applied. Aberrant antigen expression was noticed for the neural markers, protein S-100, and neuron-specific enolase. Moreover, four tumors were positive for Ki M7. Collagen type IV was found in all tumors tested. For the 20 patients enrolled in the Cooperative Soft Tissue Sarcoma Study of the German Society of Pediatric Oncology (GPO) the survival rate at 7 years is 63%. When five patients with initial recurrence are excluded, the survival rate is 72%. It is concluded that immunohistochemical study is useful in the diagnosis and differential diagnosis of synovial sarcomas despite certain limitations. Multimodality treatment approach has improved the overall prognosis. There is no relationship between histologic subtype and prognosis according to the classification scheme employed in this study.

Topics: Adolescent; Antigens, Neoplasm; Child; Child, Preschool; Collagen; Female; Humans; Immunohistochemistry; Infant; Keratins; Male; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma, Synovial; Survival Rate; Vimentin

Four new cases of ectopic hamartomatous thymoma are presented. The tumor occurred either superficially or deep in the area of the sternoclavicular joint and consisted of solid islands of squamous epithelium which blended with spindled cells. Cysts lined by squamous epithelium, small glands, and fat also occurred in variable amounts. Both the spindled and epithelial regions of the tumor expressed keratin and muscle actin, but neither desmin nor S100 protein. The tumor probably originates from thymic anlage associated with the third pharyngeal pouch (thymus III), although origin from other structures such as thymus IV and the cervical sinus of His are discussed. Our experience indicates that the large size and extreme cellularity of the spindled portion of some tumors may result in the mistaken diagnosis of sarcoma.

Topics: Actins; Adult; Aged; Carcinoma; Desmin; Diagnosis, Differential; Hamartoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sarcoma, Synovial; Thymoma; Thymus Neoplasms

Thirty-six cases of synovial sarcoma (13 biphasic and 23 monophasic) were subjected to a clinicopathologic study that included electron microscopy and immunohistochemistry. The group consisted of 21 males and 15 females ranging in age from 2 to 63 years. The majority of tumors (27 cases) were found in the hip and lower extremity. Immunohistochemical study revealed that keratin, which was detected in 92% of the biphasic and 57% of the monophasic tumors, was a more sensitive marker of epithelial differentiation than EMA or CEA. The overall 5-year survival of the patients was 64%. Male sex, older age, presence of tumor necrosis, monophasic pattern, and absence of keratin positivity had an unfavourable effect on survival but lacked statistical significance. Survival was significantly lower in patients with tumors exhibiting more than 15 mitoses per 10 HPF (P less than .02) and in those with tumors showing necrosis and a mitotic rate greater than 5 mitoses per 10 HPF (P less than .005).

Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Keratins; Leg; Male; Middle Aged; Mitotic Index; Necrosis; Prognosis; Sarcoma, Synovial; Survival Rate

Four cases of a biphasic mediastinal tumor histologically identical to synovial sarcoma of soft tissue were observed. The tumors presented as solitary mediastinal masses. Although the tumors were frequently adherent to adjacent pleura or pericardium, none appeared to be arising from a mesothelial surface. All cases were composed of an intimate admixture of keratin-positive epithelial cells and vimentin-positive spindle cells with areas of transition, hyalinization, and calcification. Follow-up was available on three patients, who died of their disease 10 months, 14 months, and 4 years after diagnosis, respectively. Although synovial sarcoma usually occurs in deep soft tissues near joints in the extremities, it has been reported in locations removed from synovial, tendon sheath, and bursal structures. This report adds a previously unrecognized location for synovial sarcoma, the mediastinum. Occurrence in this location further supports an origin from pluripotential mesenchyme as opposed to synovium. The differential diagnosis includes mesothelioma, thymoma, germ cell tumors, malignant peripheral nerve sheath tumor with glandular differentiation, and metastatic carcinoma.

Topics: Adult; Aged; Diagnosis, Differential; Humans; Keratins; Male; Mediastinal Neoplasms; Mesothelioma; Middle Aged; Sarcoma, Synovial; Thymoma; Vimentin

Histopathologic study of 20 cases of synovial sarcoma (S.S.) in children has been conducted to evaluate the usefulness of immunohistochemistry in the diagnostic assessment of this tumor. Two of the 6 antibodies studied have been found to be the most informative: staining for keratin and vimentin proteins has been observed in most cases, outlining the epithelial and sarcomatous components of this tumor. The results are in accordance with those already described for S.S. in adults. The presence of cytokeratins in S.S. is discordant with classical histogenetic conceptions.

Topics: Child; Child, Preschool; Female; Humans; Keratins; Male; Sarcoma, Synovial; Vimentin

Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions: firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas.

Topics: Antibodies; Biomarkers, Tumor; Breast Neoplasms; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Sarcoma, Synovial; Skin Neoplasms; Stomach Neoplasms; Synovial Membrane

The epithelial properties of the cells in six cases of synovial sarcoma, five biphasic and one monophasic, were examined. Epithelial cells formed well demarcated glandular nests with a multi- or single-layered lining, poorly defined nest-like clusters, or appeared as scattered single plump cells in a spindle-cell stroma. Keratinization was seen in multi-layered epithelia, and was suggested in single-layered epithelia from the presence of some enlarged eosinophilic cells. Immunohistochemically, epithelia lining glands showed reactivity for both low- and high-molecular-weight (MW) cytokeratins, and the reactions for both were strongest in keratinized cells. Clustered or single plump cells showed low-MW cytokeratin reactivity. All epithelial cells were negative for the largest cytokeratin (no. 1), and occasionally stained positively for vimentin. Spindle-shaped stromal cells usually stained positively for vimentin only. Type IV collagen was distributed linearly around well circumscribed epithelia, but not around poorly defined epithelia or plump cells. Epithelial membrane antigen was distributed linearly along glandular spaces and irregularly or granularly in clustered plump cells. The immunophenotypic epithelialization in synovial sarcoma was restricted, but showed considerable correlation with the histological grade of differentiation.

Topics: Adult; Aged; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Collagen; Desmin; Epithelium; Female; Humans; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Phenotype; S100 Proteins; Sarcoma, Synovial; Skin Neoplasms; Vimentin

The histogenesis of synovial sarcomas remains controversial. An origin from epithelium, synovium, or synovial-related cells and neural tissue has been advanced. Using a combination of a cytokeratin (epithelial marker) antibody and a vimentin (mesenchymal marker) antibody, this study suggests that a synovial sarcoma might be regarded as a carcinosarcoma. It also highlights the diagnostic utility of those antibodies in the diagnosis of synovial sarcomas.

Topics: Carcinosarcoma; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mesoderm; Sarcoma; Sarcoma, Synovial; Vimentin

Topics: Basement Membrane; Carcinosarcoma; Connective Tissue; Humans; Intercellular Junctions; Keratins; Microscopy, Electron; Neoplasm Proteins; Sarcoma, Synovial; Soft Tissue Neoplasms

Seven cases of synovial sarcoma (SS), two with biphasic and five with monophasic histology, were studied immunohistochemically using monoclonal antibodies to intermediate filaments, keratin, and vimentin. Slender spindle cells and plump cells were constant components of all the tumors. Epithelioid cells were present only in biphasic SS. Epithelioid cells and plump cells were positively stained by both keratin and vimentin. Slender spindle cells were stained positive for vimentin and negative for keratin. Staining manner of each cell type was similar irrespective of monophasic or biphasic pattern. Present immunohistochemical studies suggested that monophasic or biphasic patterns in SS should be regarded as a different expression of the same disease. In addition, immunohistochemistry proved to be a useful tool to detect plump cells which were difficult to find on routine staining.

Topics: Adolescent; Adult; Female; Foot; Hand; Humans; Immunoenzyme Techniques; Joint Diseases; Keratins; Knee Joint; Male; Sarcoma, Synovial; Soft Tissue Neoplasms; Vimentin

To analyze the purportedly epithelial features of synovial sarcoma, the antigenic profiles of 20 of these neoplasms (including 12 of the monophasic type) were studied by three different immunohistochemical techniques, and the results were correlated with ultrastructural observations in 10 cases. All of the biphasic tumors were immunoreactive for the epithelial markers epithelial membrane antigen (EMA) and cytokeratin (CK) and also had ultrastructural features of epithelial differentiation. In contrast, only one of five monophasic tumors had electron microscopic features suggestive of epithelial differentiation, but eight of the 12 were immunoreactive for CK or EMA by a procedure combining the peroxidase-antiperoxidase and avidin-biotin-peroxidase complex methods. It is concluded that synovial sarcoma, including the monophasic variant, is a mesenchymal tumor with epithelial features. Immunohistochemical studies are more sensitive than ultrastructural analysis for documenting epithelial differentiation.

Topics: Adult; Antigens, Neoplasm; Carcinoembryonic Antigen; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Sarcoma, Synovial

Two hundred and three sarcomas, 40 carcinomas, 10 carcinomas with spindle cell features, 27 malignant melanomas and one spindle cell melanoma were examined using CAM 5.2, a monoclonal antibody to cytokeratin. This antibody which was prepared against colorectal carcinoma cells and which identifies low molecular weight intermediate filament cytokeratin proteins is suitable for use in formalin fixed, paraffin embedded material. Seventeen of the 203 sarcomas showed positive staining. These included 15/21 synovial sarcomas, 1/5 epithelioid sarcomas and 1/18 malignant neural tumours. Five carcinosarcomas showed positive staining of their epithelial components but negative staining of their spindle cell components; three out of four pure spindle cell carcinomas stained positively; a metastasis from a spindle cell renal carcinoma was negative. A spindle cell thymoma also stained positively. Thirty-seven of the 40 carcinomas stained positively; the three negative carcinomas were a squamous cell carcinoma, a renal cell carcinoma and an oat cell carcinoma. All malignant melanomas were negative. These results are compared with those of other workers and the sensitivity and specificity of CAM 5.2 as an epithelial marker is assessed.

Topics: Antibodies, Monoclonal; Carcinoma; Histocytochemistry; Humans; Keratins; Melanoma; Sarcoma; Sarcoma, Synovial; Vimentin

For the purpose of clarifying cellular differentiation of epithelioid sarcoma, studies based on various methods were performed. Enzyme histochemical studies showed that epithelioid sarcoma tumor cells have characteristics intermediate between epithelial cells and the large plump cells of synovial sarcoma-incomplete epithelial differentiation. For alkaline phosphatase and adenosine triphosphatase particularly, positive cells and negative cells coexisted, as in the large plump cells of synovial sarcoma. Immunohistochemical studies for alpha 1-antitrypsin, alpha 1-antichymotrypsin, vimentin, and keratin also showed that epithelioid sarcoma tumor cells are very similar to the large plump cells of synovial sarcoma and have incomplete epithelial differentiation. For example, the examinations of serial sections and double staining methods revealed that keratin-positive cells are always vimentin-positive in epithelioid sarcoma and in the monophasic area of synovial sarcoma. Electron-microscopically, bundles of intermediate filaments and filopodia toward the intercellular lumen were observed, as in the monophasic area of synovial sarcoma. The results of enzyme-histochemical and immunohistochemical studies of non-neoplastic synovial lining cells, performed here for the first time, are also discussed.

Topics: Adenosine Triphosphatases; Adult; Alkaline Phosphatase; Cell Transformation, Neoplastic; Female; Fibroma; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Sarcoma; Sarcoma, Synovial; Staining and Labeling; Vimentin

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 tonofilaments 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.

Topics: Cell Differentiation; Cytoplasmic Granules; Cytoskeleton; Female; Forearm; Humans; Keratins; Metaplasia; Microscopy, Electron; Middle Aged; Organoids; Sarcoma, Synovial

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.

Topics: Antibodies; Antigens; Binding Sites; Cytoskeleton; Humans; Immunoenzyme Techniques; Keratins; Membrane Proteins; Microscopy, Fluorescence; Mucin-1; Receptors, Mitogen; Sarcoma, Synovial; Soft Tissue Neoplasms; Synovial Membrane; Synovitis, Pigmented Villonodular; Terminology as Topic; Vimentin

Monophasic synovial sarcomas of spindle-cell type and fibrosarcomas were studied by electron and immunofluorescence microscopy for their intermediate filament expression and the binding of peanut agglutinin (PNA). In monophasic synovial sarcomas of spindle-cell type (two cases), frequent cell-to-cell junctions, irregular cytoplasmic processes, and occasional cytoplasmic, tonofilament-like bundles of intermediate filaments were seen by electron microscopy. These features were absent from fibrosarcomas. Immunohistologically, the monophasic synovial sarcomas showed arrays of prekeratin-positive cells in the midst of the vimentin-positive spindle cells. By double fluorescence microscopy, the prekeratin-positive cells also bound PNA, like the epithelial-like cells of the classical biphasic synovial sarcoma. In contrast to monophasic synovial sarcomas, prekeratin-positive cells and arrays of PNA-binding cells, were not seen by immunofluorescence microscopy in fibrosarcomas (seven cases). Thus the prekeratin-content, the binding of PNA lectin, and certain ultrastructural features suggesting early epithelial differentiation, help to distinguish monophasic synovial sarcomas of spindle-cell type from other spindle cell sarcomas.

Topics: Adult; Binding Sites; Cytoskeleton; Elbow Joint; Female; Fibrosarcoma; Finger Joint; Histocytochemistry; Humans; Intermediate Filament Proteins; Joint Diseases; Keratins; Lectins; Male; Microscopy, Electron; Protein Precursors; Sarcoma, Synovial; Vimentin

Four cases of classical biphasic synovial sarcoma were studied for intermediate filaments of keratin and vimentin type. Epithelial-like cells lining gland-like slits were strongly positive for keratin but negative for vimentin, whereas the spindle cell stroma was negative for keratin but positive for vimentin. The observations indicate epithelial differentiation in the glandular elements of biphasic synovial sarcomas, and are consistent with earlier ultrastructural observations suggesting epithelial properties of these cells.

Topics: Adolescent; Adult; Aged; Cell Differentiation; Cytoskeleton; Female; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Sarcoma, Synovial; Vimentin