Primary intravascular synovial sarcoma: A disease of young adult women? report of a case diagnosed by aspiration biopsy and review of the literature

Intravascular synovial sarcoma (IVSS) is an extremely rare tumor with only four well-documented cases in the English literature. All tumors were located in large veins of the lower extremities or trunk in young women except for one case occurring in a 54-yr-old woman. We report here an additional case of IVSS arising from the superior vena cava in a 32-yr-old woman who presented with a cervical mass and superior vena cava syndrome. A fine-needle aspiration biopsy (FNAB) was performed and showed a malignant biphasic tumor with spindle cell and epithelioid components. The tumor cells were negative for CD31, CD34, factor VIII, desmin, smooth muscle actin, and S-100 protein, and had positive staining for vimentin and cytokeratin (AE1/AE3) predominantly in the spindle and epithelial components, respectively. A diagnosis of synovial sarcoma was made and confirmed in a subsequent transvascular biopsy demonstrating chromosomal translocation t(X, 18) by fluorescence in situ hybridization using a dual color, break-apart-style probe for SYT. Although clinically similar to previously reported IVSS, this is the first case arising in large veins of the upper portion of the trunk and diagnosed by FNAB.     

Subcutaneous leiomyosarcoma with lymphomatous elements: histogenetic implications of an unusual sarcoma

A 49-year-old woman had an unusual sarcoma that recurred three times in four years. The tumor manifested initially as a subcutaneous abdominal wall nodule composed of lymphohistiocytic malignant lymphoma and spindle cell sarcoma with epithelioid and clear cell elements. The neoplasm recurred first as a spindle cell sarcoma in the lumbar area, second as a malignant lymphoma in the subcutaneous tissue of the right shoulder, and third as a spindle cell sarcoma with lymphohistiocytic areas in the abdominal wall. Ultrastructural studies of this last tumor nodule demonstrated the unequivocal smooth muscle features of the spindle cells. Histogenetic implications of this neoplasm are discussed. It is proposed that the tumor represents an unusual variant of malignant mesenchymoma of soft tissues.     

Malignant solitary fibrous tumor of pleura with focal expression of cytokeratin

Solitary fibrous tumor is a rare circumscribed neoplasm involving usually the pleura and now described in many organs and in the soft tissues with a favorable outcome when completely excised. We report herein a malignant solitary fibrous tumor of the pleura occurring in a 59-year-old woman. The tumor cells strongly expressed vimentin and CD 34. In addition a weak positive staining was obtained using CD 99 and bcl 2. A disconcerting focal immunoreactivity with cytokeratin was observed. Solitary fibrous tumor is composed of loosely arranged spindle cells of variable density and may occasionally mimic malignant mesothelioma, an hemangiopericytoma or synovial sarcoma. Immunohistochemical study is helpful demonstrating a strong positivity for vimentin and CD 34 and absence of staining for epithelial markers and S-100 protein.     

低分化滑膜肉瘤临床病理及分子遗传学研究

目的：研究低分化滑膜肉瘤的临床病理学特点及其分子遗传学表现。方法：收集低分化滑膜肉瘤标本121例，采用形态学观察和免疫组化染色，并用RT－PCR方法在石膜包埋组织中检测SYT－SSX融合mRNA表达。结果：12例低分化滑膜肉瘤中细胞型4例，大细胞型6例，高度恶性梭形细胞型2例。8例有随访资料其中4例死于肿瘤，平均生存时间18个月。免疫组化表现为CK和（或）EMA阳性，以EMA阳性率较高，同时vimentin阳性。S－100蛋白也有较高阳性率，多呈局灶或散在阳性。RT－PCR方法均可检测到SYT－SSXmRNA表达，对照组12例肿瘤包括恶性周围神经 鞘膜瘤、尤因肉瘤和恶性血管外皮瘤SYT－SSX检测全部阴性。结论：低分化滑膜肉瘤有其形态学及免疫表型特点，分子遗传学检测SYS－SSX融合mRNA有助于诊断和鉴别诊断。     

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.     

Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.     

Immunohistochemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms

A sizable proportion of pleural malignant mesotheliomas are sarcomatoid (22%) or biphasic (24%) and may need to be distinguished from other spindle cell neoplasms that occur as primary or metastatic tumors of the chest wall or lungs. To determine the utility of immunohistochemistry in the differentiation of sarcomatoid malignant mesotheliomas from other spindle cell neoplasms, the authors studied the immunostaining patterns of nine antibodies in four sarcomatoid mesotheliomas, one desmoplastic mesothelioma, two epithelial mesotheliomas, four spindle cell squamous carcinomas, and eight sarcomas of various differentiation. Three of the four sarcomatoid mesotheliomas and the desmoplastic mesothelioma had positive results for cytokeratin, which distinguishes them from sarcomas but not from spindle cell squamous carcinomas. The immunostaining pattern of 14 examples of benign spindle cell mesothelial proliferation was similar to that of the sarcomatoid mesotheliomas, which supports the theory that these tumors are mesothelial in origin. Although other antibodies occasionally may be helpful, depending on the differentiation of the sarcoma, cytokeratin immunostaining appears to be the best method to discriminate sarcomatoid mesotheliomas from sarcomas.     

Malignant ameloblastoma,spindle cell variant

In this report, we document the histologic and clinical features of a previously undefined spindle cell variant of ameloblastoma that eventually behaved in a malignant fashion during a protracted course. The predominant histologic pattern was a well-differentiated, cellular, spindled epithelial proliferation arising in the maxilla of a 14-year-old African American girl. Over 19 years, the patient experienced numerous local recurrences, metastases to distant bones after 15 years, and finally bulky local recurrence with intracranial extension resulting in death. This ameloblastic malignancy histologically simulates a low-grade true sarcoma or an ameloblastic sarcoma, but differs in that the extensive spindle cell proliferation is epithelial, characterized by strong cytokeratin immunoreactivity and negative vimentin staining.     

Pheochromocytoma Combined with Malignant Schwannoma: Unusual Neoplasm of the Adrenal Medulla

A 38-year-old woman was operated on to remove a large tumor that replaced the left adrenal gland. The tumor was encapsulated and showed small areas typical of pheochromocytoma, and spindle cell or undifferentiated round cell sarcoma in most areas. Metastases of primitive round cell appearance were operated from the abdominal cavity and abdominal wall shortly after the initial surgery. Eighteen months after the first operation, the patient was alive with metastases in liver and retroperitoneal space. The pheochromocytomalike component showed a typical ultrastructural and immunohistochemical profile of pheochromocytoma and was positive for neurofilaments, synaptophy-sin, neuron-specific enolase, and S-100 protein in the sustentacular cells. The sarcomatous areas showed fibroblastoid spindle cells that were often surrounded by a basal lamina. Immunohisto-chemistry revealed S-100 protein positivity in many spindle cells, but markers of pheochromocytoma or epithelial differentiation were absent. The metastases lacked all markers except for vimentin, and the cells were undifferentiated by electron microscopy. These findings suggest that the neoplasm was a compound tumor with a typical pheochromocytoma component and a sarcoma resembling a malignant schwannoma. Neoplastic proliferation of the S-100 protein-positive Schwann-cell-like sustentacular cells of the pheochromocytoma would be an explanation for the genesis of this sarcoma associated with pheochromocytoma.     

Pheochromocytoma Combined with Malignant Schwannoma: Unusual Neoplasm of the Adrenal Medulla

A 38-year-old woman was operated on to remove a large tumor that replaced the left adrenal gland. The tumor was encapsulated and showed small areas typical of pheochromocytoma, and spindle cell or undifferentiated round cell sarcoma in most areas. Metastases of primitive round cell appearance were operated from the abdominal cavity and abdominal wall shortly after the initial surgery. Eighteen months after the first operation, the patient was alive with metastases in liver and retroperitoneal space. The pheochromocytomalike component showed a typical ultrastructural and immunohistochemical profile of pheochromocytoma and was positive for neurofilaments, synaptophy-sin, neuron-specific enolase, and S-100 protein in the sustentacular cells. The sarcomatous areas showed fibroblastoid spindle cells that were often surrounded by a basal lamina. Immunohisto-chemistry revealed S-100 protein positivity in many spindle cells, but markers of pheochromocytoma or epithelial differentiation were absent. The metastases lacked all markers except for vimentin, and the cells were undifferentiated by electron microscopy. These findings suggest that the neoplasm was a compound tumor with a typical pheochromocytoma component and a sarcoma resembling a malignant schwannoma. Neoplastic proliferation of the S-100 protein-positive Schwann-cell-like sustentacular cells of the pheochromocytoma would be an explanation for the genesis of this sarcoma associated with pheochromocytoma.     

SYT在诊断单相纤维型滑膜肉瘤中的价值

目的 探讨SYT在单相纤维型滑膜肉瘤(monophasic fibrous synovial sarcoma,MFSS)的诊断及与其它梭形细胞肿瘤鉴别诊断中的作用.方法 收集MFSS 36例、其它梭形细胞肿瘤32例,其中包括恶性外周神经鞘膜瘤7例、纤维肉瘤6例、平滑肌肉瘤4例、恶性纤维组织细胞瘤7例和孤立性纤维性肿瘤8例,检测sYT蛋白在上述病例中的表达.结果 SYT在MFSS中的阳性表达率为91.67%(33/36),其中15例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),12例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性表达.SYT在其他梭形细胞间叶肿瘤中的阳性表达率为59.37%(19/32),其中6例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),7例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性.结论 SYT蛋白在MFSS和其他梭形细胞肿瘤中均有较强的阳性表达,提示SYT抗体在MFSS与其他梭形细胞肿瘤的鉴别诊断中作用有限.     

Fine-needle aspiration biopsy of pleomorphic (giant cell) carcinoma of the pancreas. Cytologic, immunocytochemical, and ultrastructural findings

Four cases of pleomorphic (giant cell) carcinoma (PGC) of the pancreas, diagnosed by fine-needle aspiration biopsy, are presented. Ancillary immunocytochemical studies were also performed on the smears (four cases) and cell blocks (three cases), along with ultrastructural (electron microscopic) examination of the aspirated specimen (two cases). Three of the four patients were elderly (age range: 44-65 years), and all had large pancreatic masses. A spectrum of cytomorphologic features was encountered, including poorly cohesive bizarre mononuclear cells, many multinucleated tumor giant cells, and associated malignant spindle cells. Prominent cellular cannibalism and cytophagocytosis also were seen. Immunoperoxidase studies demonstrated dual staining of the malignant cells for cytokeratin and vimentin in two cases and exclusive staining for vimentin in the remaining two cases. Ultrastructural examination demonstrated epithelial features in both cases studied. One of the cases demonstrated intracytoplasmic whorled bundles of intermediate filaments, corresponding to pale eosinophilic globular material, appreciated both in the Diff-Quik- and Papanicolaou-stained smears and staining with positive results for vimentin. The immunocytochemical studies suggest that the coexpression of vimentin and cytokeratin within the cells is consistent with a pleomorphic malignancy of epithelial origin. It is speculated that the staining of two of the cases exclusively for vimentin can be seen in either epithelial malignancies with sarcomatoid transformation or, less likely, a pure sarcoma of the pancreas.     

Prostatic stromal sarcoma with rhabdoid features

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis).     

Cystic synovial sarcoma

A case of synovial sarcoma of the paraspinal region showing massive cystic changes is described. The tumor presented in a 53-year-old white woman who noticed a lump on the upper aspect of her back. Magnetic resonance imaging of the cervical spine showed a heterogeneous paraspinal mass with well-defined margins and a multilocular quality with foci of hemorrhage. Fine needle aspiration of the mass showed clusters of polygonal cells admixed with a scattered spindle cell component. Surgical excision of the mass showed a well-circumscribed but nonencapsulated tumor that showed multiple small cystic structures on cross-section. Histologic examination showed a biphasic neoplasm characterized by bland-appearing glandular elements embedded in a moderately cellular spindle cell stroma. The tumor contained multiple cysts of varying size. Immunohistochemical studies showed the glandular component to be positive for cytokeratin and epithelial membrane antigen. The spindle cell component was immunoreactive for cytokeratin, vimentin, bcl-2, and CD99. Stains for muscle-specific actin, smooth muscle actin, S-100 protein, and CD34 were negative. Cytogenetic analysis showed a balanced reciprocal translocation involving chromosomes X and 18, in addition to other clonal abnormalities. Synovial sarcoma should be considered in the differential diagnosis of cystic lesions involving the soft tissues. Magnetic resonance imaging is considered the procedure of choice for the evaluation of soft tissue tumors because of its superior soft tissue contrast and multiplanar imaging capability. While the imaging features of soft tissue tumors are often nonspecific, magnetic resonance imaging may provide helpful clues, thus narrowing the differential diagnosis. Immunohistochemical studies and cytogenetic analysis may be very helpful for establishing the correct diagnosis in cases with this unusual presentation. Ann Diagn Pathol 5:48-56, 2001.     

Benign and malignant neoplasms of myoepithelial cells: Cytologic findings

We report two myoepithelial cell neoplasms; a salivary gland tumor was malignant and a breast neoplasm was benign. Both were studied histologically, immunohistochemically, cytologically, and ultrastructurally. The malignant myoepithelioma recurred twice and metastasized to one regional lymph node. This tumor was infiltrative with areas of necrosis and hemorrhage. It was composed of malignant-appearing spindle and plasmacytoid cells. Both types of cells were immunoreactive to muscle specific actin, S-100 protein, cytokeratin, vimentin, and neuron-specific enolase. Ultrastructurally, features of myoepithelial cells were seen. Fine-needle aspirate smears showed spindle and plasmacytoid cells, numerous mitoses, and malignant-appearing nuclei. Spindle-cell adenomyoepithelioma of the breast, a small well-circumscribed firm nodule, featured multiple lobules of spindle cells associated with clear-cell glands at the tabular periphery. Histologically and cytologically, the lesion was cellular but appeared benign. The differential diagnosis of myoepithelial neoplasms is discussed.     

Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review

Synovial sarcomas arising in unexpected locations may lead to diagnostic challenges. In this report, we describe 3 cases of synovial sarcoma that manifested clinically as primary pericardial lesions. All 3 cases occurred in men in their fourth decade. Fever, cough, chest pain, and chest distress were the most common symptoms. Histologically, 2 of the tumors were spindle cell monophasic, and 1 tumor was biphasic. By immunohistochemical studies, the tumor cells were positive for cytokeratins and epithelial membrane antigen. In addition, the tumor cells displayed focal immunoreactivity for calretinin, cytokeratin 5/6, and HBME-1, resulting in the initial interpretations of malignant mesotheliomas. None of the 3 cases were diagnosed correctly until subsequent molecular cytogenetic assays demonstrated the presence of SYT gene rearrangements. As there are overlapping morphologic features between pericardial synovial sarcoma and mesothelioma, molecular analysis is essential for differential diagnoses.     

Chordomas with malignant spindle cell components. A DNA flow cytometric and immunohistochemical study with histogenetic implications.

The authors studied four chordomas with malignant spindle cell components (SCs) and 12 conventional chordomas (CCs) by DNA flow cytometry using paraffin-embedded tissue. In addition, immunohistochemical stains for a variety of epithelial and mesenchymal markers were performed. The four SCs contained areas histologically identical to conventional chordomas, as well as a high-grade malignant spindle cell component. All four (100%) SCs had an aneuploid-multiploid DNA content. Of interest, the conventional chordoma areas in these tumors had DNA contents different from those containing the high-grade malignant spindle cells. In contrast, only three (27%) of the 11 conventional chordomas with analyzable histograms had an aneuploid-multiploid DNA content. Immunohistochemical studies performed on the four SCs showed the high-grade malignant spindle cells to stain strongly for vimentin and weakly for cytokeratin, S-100 protein, and epithelial membrane antigen (EMA), whereas the areas of conventional chordoma in these same neoplasms stained moderately for vimentin and S-100 protein, and strongly for cytokeratin and EMA. In two cases, the staining for EMA and cytokeratin highlighted a gradual transition between the areas of conventional chordoma and the spindle cell areas. The immunohistochemical staining pattern of the 12 conventional chordomas was similar to that seen in the conventional chordoma components of the four chordomas with malignant spindle cell components. These results suggest that: 1) aneuploidy is more common in SCs than in CCs, and 2) some SCs are multipotential neoplasms in which the neoplastic cells are capable of differentiation along both epithelial and mesenchymal pathways.     

Pericardial malignant mesothelioma: Case report and discussion of immunohistochemical and histochemical findings

An extremely rare case of malignant mesothelioma of the pdcardium is reported. The tumor appeared to be the Uphasic type of diffuse malignant mesothetioma which presgnt many small to tine lipid droplets in the cytoplasm, particularly that of the epithelial cell, and a positive immunohistochemical reaction with antibodies to low molecular weight cytokeratin (45–50 kDa) in all of the tumor cells. The literature is also reviewed and the presence of lipid droplets and the importance of the immunohistochemical positivity to low molecular weight cytokeratin for differential diagnosis from other malignant tumors, such as invasive adeno-carcinoma or primary sarcoma of the pleura, or soft tissue sarcoma involving the pleura is discussed.