Poorly differentiated monophasic synovial sarcoma of the mediastinum

Poorly differentiated synovial sarcoma is a diagnostically challenging neoplasm. Most commonly they occur in the soft tissue of the extremities and are rare in the mediastinum. They can be indistinguishable from other "round cell tumors" based on the morphology alone or at times by immunohistochemical studies. Here in, we report an extremely rare case of metastatic poorly differentiated monophasic synovial sarcoma of the mediastinum without a known primary in a 30-year-old man. The imaging studies on admission showed 10 × 9.5 cm anterior mediastinal mass with multiple nodules in the lung and pleura along with multiple enlarged mediastinal and axillary lymph nodes. Histopathologic and immunohistochemical analysis supported the diagnosis of poorly differentiated synovial sarcoma, which was further confirmed by molecular genetic analysis.     

Monophasic, glandular, synovial sarcomas and carcinomas of the soft tissues

In soft tissues, malignant tumors with epithelial qualities are usually metastatic carcinomas. A rare, primary, soft-tissue tumor that is uniformly carcinoma-like is the monophasic, glandular, synovial sarcoma. We studied three cases of carcinoma-like neoplasms of soft tissue. In one primary tumor and two recurrent tumors of soft tissue, the histologic patterns were uniformly glandular. For the two recurrent tumors, the primary lesions were a classic, synovial sarcoma and a biphasic, synovial sarcoma with a histiocytic, stromal component. By inference, the third tumor, a primary "carcinoma" of soft tissue, may represent a de novo, monophasic, glandular, synovial sarcoma. Synovial sarcoma should be considered in the differential diagnosis of carcinoma like tumors discovered in the soft tissues.     

Monophasic synovial sarcoma of the liver

We report a hepatic monophasic synovial sarcoma in a 60-year-old woman who presented with right upper quadrant pain subsequent to an intrahepatic bleed from a highly vascular tumor mass. Imaging studies showed a dominant tumor mass in the right hepatic lobe with multiple satellite nodules. A detailed physical examination and radiologic workup failed to reveal a primary tumor elsewhere. A right partial hepatectomy was performed with a preoperative differential diagnosis of angiosarcoma versus hepatocellular carcinoma. The morphologic, immunophenotypic, and cytogenetic findings (t(X;18)(p11.2;icq11.2)) were consistent with a monophasic synovial sarcoma. Postoperative clinical evaluation of the extremities and a positron emission tomographic scan performed 4 weeks after surgery showed no evidence of recurrent or metastatic disease. The patient was started on an aggressive 4-drug chemotherapy regimen, but died 3 months thereafter from widespread metastatic disease. No autopsy was performed. The presence of multiple lesions in the liver certainly suggests the possibility of metastatic disease. It would, however, be very unusual for a synovial sarcoma to present as an occult primary, and the negative radiologic workup 1 month after the partial hepatectomy also argues against this possibility. The clinical presentation, radiographic findings, and subsequent course in this patient was therefore most consistent with a primary monophasic synovial sarcoma of the liver.     

Intraneural synovial sarcoma: two cases.

We report two cases of intraneural synovial sarcoma. The first patient is a 46-year-old female who presented for several months with soft-tissue mass in the right infra-auricular region. The second patient is a 11-year-old girl who fell and then presented with pain in the area innervated by the right C7 spinal root and a nodule identified in the nerve root foramina. Both lesions were of small size and presented with features of synovial sarcoma. A biphasic variant was found in case 1 and a monophasic variant was present in case 2. Immunohistochemical studies were performed to confirm the diagnosis, excluding the main differential diagnoses, namely schwannoma and malignant peripheral nerve sheath tumor. Ultrastructural study was performed in case 2 allowing exclusion of other possible diagnoses. Molecular studies were performed on paraffin-embedded tissue in both cases and revealed the known characteristic t(X;18)(SYT-SSX) translocation.     

Epithelioid Monophasic Synovial Sarcoma

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

Paraganglioma of the vulva: a case report and review of the literature

Paraganglioma is a neuroendocrine neoplasm, which is extremely rare in the vulva and only one case has been reported. Here we present a case of vulvar paraganglioma in a 48-year-old woman and a literature review. The patient found a lump located in the genitals below the symphysis pubis 3 months before presentation when she complained that the lump was increasing in size. A 3.2 cm x 2.3 cm x 1.5 cm nodule was excised from subcutaneous soft tissue in the vulva. Microscopy showed a diversity of cell morphologies and structures in the rich vascular network of the tumor separated the chief cells into round cell nests (Zellballen pattern). Some areas of the tumor presented epithelioid and spindle-shaped cells with increased cell density and indistinct structural characteristics. Hyaline degeneration of collagen fibers or mucoid degeneration was found in tumor interstitium. Immunohistochemical staining showed diffused expression of synaptophysin in the chief cells, focal expression of S-100 protein in the sustentacular cells and high expression of CD34 in the vascular components. Based on morphological and immunohistochemical results, a rare paraganglioma of the vulva was diagnosed.     

Primary biphasic synovial sarcoma of the orbit.

Synovial sarcoma is one of the most common soft tissue malignancies of adolescents and young adults. Despite its name, it is no longer thought to be histogenetically derived from the synovium. What seems to be the first case of synovial sarcoma to arise in the orbit presented in a 21 year old woman as a slowly enlarging subconjunctival mass. Although this tumour was typically biphasic, the monophasic spindle cell variant arising at this site could easily be confused with less aggressive orbital connective tissue neoplasms.     

SYNOVIAL SARCOMA

This clinicopathologic study concerns 42 cases of synovial sarcoma (13 biphasic and 29 monophasic), including electron-microscopic examination of five cases, among 753 cases of soft tissue sarcomas. The age of the patients ranged from 9 to 70 years, with a median of 35 years. Tumors occurred most commonly on the extremities with 31 on the lower extremities. Histologically the monophasic type on this occasion included tumors with focal or minimal biphasic differentiation (9 cases) in addition to totally monophasic tumor (20 cases). A comparative light microscopy revealed otherwise inappreciable differences in histologic characteristics between the monophasic synovial sarcoma and certain other spindle cell sarcomas. Ultrastructurally, the cells composing the spindle-cell area of the synovial sarcoma contained basically the same elements as did the cells forming epithelioid or gland-like structures, and as the cells in the areas of gradual transitions of the two. One exception was that the cells lining the gland-like lumina had microvillar projections. Characteristic secretory-like granules, similar to those seen in the synovial type B cell of the normal human synovium, were evident in all five cases studied electron microscopically. In contrast to the findings of others, patients with monophasic tumors had a better prognosis, 58% surviving 5 years compared to 36% for those with biphasic tumors.     

SYT-SSX2 variant of primary pulmonary synovial sarcoma with focal expression of CD117 (c-Kit) protein and a poor clinical outcome

Pulmonary synovial sarcoma is a rare neoplasm recently recognized as a distinct entity and characterized by t(X;18) translocation and production of at least 2 fusion genes, SYT-SSX1 and SYT-SSX2. We report a case of primary pulmonary synovial sarcoma with the SYT-SSX2 phenotype and a rapidly progressive downhill course. Previous reports have suggested that the soft tissue synovial sarcomas with SYT-SSX2 phenotype have a favorable clinical outcome. To the best of our knowledge, this is also the first report of CD117 (c-Kit) expression in a pulmonary synovial sarcoma. A 45-year-old woman presented with left chest pain and was found to have a left lower lobe tumor that was originally diagnosed as a sarcomatoid carcinoma. After the patient underwent chemotherapy and brachytherapy, the specimen from a left pneumonectomy showed a large spindle cell tumor, which was reclassified as a synovial sarcoma based on the results of immunophenotyping and molecular genetic studies. Differentiation between sarcoma and carcinosarcoma is crucial for implementing appropriate therapy. Furthermore, if the tumor expresses c-Kit, it may respond to target-based therapy.     

Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors

Nineteen synovial sarcomas, six biphasic and 13 monophasic tumors, were examined by light and electron microscopy and immunohistochemically for the presence of the epithelial markers keratin and epithelial membrane antigen (EMA). Ultrastructurally, intercellular spaces with processes are present to varying degrees in the spindle cell component of all synovial sarcomas, and junctional specializations occur in most cases. Tumors of the two types differ in their content of external (basal) lamina, which encloses the epithelial component of all biphasic tumors and is detectable in the spindle cell component of two thirds of them, but is absent from the majority of monophasic tumors. Keratin and EMA were demonstrated in both components of all six biphasic tumors. Of the 13 monophasic tumors, keratin was present in nine, EMA in eight, and at least one epithelial marker in ten. Synovial sarcoma is regarded as a distinctive soft tissue tumor with variable epithelial-like differentiation. The use of electron microscopy can increase the specificity of immunohistochemical studies of soft tissue sarcomas and allow more accurate differentiation of monophasic synovial sarcoma from other spindle cell tumors, particularly those that do not express markers.     

Aggressive "breast-like" adenocarcinoma of vulva.

A case of vulvar adenocarcinoma seen in a 42-year-old woman is reported. The tumor involved the right labium majus and diffusely spread into the surrounding soft tissues as well as the inguinal lymph nodes and was histologically composed of nests, cords, and tubular formations recalling an aggressive duct carcinoma of breast. Likewise, tumor cells exhibited positivity for common breast tumor markers, such as epithelial membrane antigen, carcinoembryonic antigen, and glandular keratins. The possible origin of the neoplasm from mammary ectopic tissue in vulva or from vulvar skin adnexa is briefly discussed.     

Primary pulmonary synovial sarcoma. Apropos of 1 case with cytogenetic study

Synovial sarcoma most commonly occurs in the peri-articular regions of the extremities. We report a case of primary pulmonary monophasic synovial sarcoma. This tumor is extremely rare and shows a particular immunohistochemical pattern of great help for the diagnosis. Cytogenetic study confirm the diagnosis by showing the specific t (X; 18) chromosomal translocation, characteristic of synovial sarcoma in all anatomic locations.     

Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases.

Synovial sarcoma in its classic biphasic form can be distinguished readily from other soft tissue lesions; however, monophasic and poorly differentiated forms are diagnostically more problematic. For this reason, we assessed the efficacy of immunostaining for SYT and SSX1 proteins, the gene products resulting from unique synovial sarcoma translocation, to distinguish synovial sarcoma from other soft tissue lesions. A total number of 146 cases were analyzed, including 47 synovial sarcoma cases (all of which were verified by FISH to have t(X; 18) translocation and SYT-SSX fusion gene) and 99 soft tissue tumors of various types. A polyclonal IgG antibody against SYT was used to stain formalin-fixed paraffin embedded tissues. Forty-one out of 47 (87%) synovial sarcoma displayed strong positive nuclear staining (ranging from 80 to 90% of the tumor cells) for SYT antibody. Nineteen of 99 (19%) non-synovial sarcoma cases showed variable nuclear and cytoplasmic staining with SYT, which ranged from 20 to 60% of tumor nuclei, and included malignant peripheral nerve sheath tumor (5/25), solitary fibrous tumor (2/14), Ewing sarcoma (2/6), low grade fibromyxoid tumor (2/4), extraskeletal mesenchymal chondrosarcoma (2/6), gastrointestinal tumor (4/17), epithelioid sarcoma (2/2). The remaining non-synovial sarcomas were negative. This is the first study demonstrating SYT protein expression in tissue sections of synovial sarcoma. This method could provide an easy, rapid and widely applicable means of assisting in the diagnosis of synovial sarcoma, particularly when material and/or resources are unavailable for PCR or FISH-based testing. However, as variable weak staining for SYT may be encountered in a small percentage of non-synovial sarcoma sarcomas, a positive interpretation should be made only when the staining is strong, nuclear and present in the majority of cells.     

Role of electron microscopy in the evaluation of soft tissue neoplasms, with emphasis on spindle cell and pleomorphic tumors

The current significant role of transmission electron microscopy in the evaluation of soft tissue tumors when correlated with conventional histological and immunohistochemical studies is discussed for the following entities: myxofibrosarcoma, storiform-pleomorphic fibrosarcoma (malignant fibrous histiocytoma), and myofibrosarcoma; dermatofibrosarcoma protuberans; hemangiopericytoma; monophasic synovial sarcoma; extrarenal rhabdoid tumor; soft tissue perineurioma; and gastrointestinal stromal tumors, notably the so-called autonomic nerve variant.     

Synovial sarcoma. Inter-relationship of the biphasic and monophasic subtypes.

In order to assess minimum diagnostic criteria for synovial sarcoma, particularly the monophasic variety, and the inter-relationship between the monophasic and biphasic types, 32 examples were studied histologically, immunohistochemically (26 cases), and ultrastructurally (13 cases). Of the six biphasic synovial sarcomas examined by electron microscopy, the spindle cell component did not show evidence of epithelial differentiation or resemble the epithelial phase, but did appear fibroblastic; no tumor cells transitional between the spindle and epithelial component were evident. In contrast, all of the seven monophasic lesions had ultrastructural growth patterns and some cellular features approximating the epithelial cells of the biphasic variant. In 11 biphasic synovial sarcomas, epithelial membrane antigen was detected in the glandular epithelium of all cases and cytokeratins in eight cases; in no case were these antigens detected in the spindle cell regions of biphasic lesions. Of the 15 monophasic synovial sarcomas, two were positive for cytokeratins and four for epithelial membrane antigen. Thus, the detection of epithelial markers either immunohistochemically or by electron microscopy (or both) should be the minimal diagnostic criteria for monophasic synovial sarcomas. Based on these findings, it is suggested that monophasic synovial sarcomas do not represent the spindle cell or "stromal" phase of biphasic synovial sarcomas, but are a poorly differentiated variant of the latter. As others have suggested, these tumors are, in fact, carcinosarcomas and carcinomas of the soft tissues and the designation synovial sarcoma is inappropriate for this tumor class.     

Subcutaneous Ewing sarcoma/PNET as a second cancer in a previously irradiated young patient. an uncommon type of post-irradiation soft tissue sarcoma

Soft tissue sarcomas account for a small proportion of second cancers, with an estimated frequency of < 10%. The most common histologic type of soft tissue sarcomas as second cancers include mostly high-grade sarcomas, such as rhabdomyosarcoma, malignant peripheral nerve sheath tumour, fibrosarcoma, leiomyosarcoma, synovial sarcoma, alveolar soft part sarcoma and Ewing sarcoma/primitive neuroectodermal tumour (PNET). We report a case of superficial soft tissue Ewing sarcoma/PNET as a second cancer in a young patient previously treated for Hodgkin's disease (HD). To the best of our knowledge and based on a literature search, this is the first reported case of post-irradiation soft tissue Ewing sarcoma/PNET as a second cancer arising in the same area irradiated for cure of HD.