Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clear cell sarcoma of tendons and aponeuroses (CCS) is an uncommon malignancy characterized by a t(12;22)(q13;q12) causing a fusion of the EWS and ATF1 genes. We describe the cytogenetic and molecular genetic analyses of two lung metastases from a CCS patient. Both lesions presented the defining t(12;22) and a type 1 EWS/ATF1 chimeric transcript. The additional cytogenetic changes present in the two lesions allowed us to obtain some insight into the pathogenetic basis of disease progression. Four related clones were identified in the right lung metastasis, permitting a partial reconstitution of the stepwise clonal evolution, whereas the left lung metastasis presented yet another subclone. The comparison of the two karyotypes enabled us to pinpoint which changes occurred in the primary tumor and which emerged independently after the two metastases had been established. We conclude that both clonal divergence and convergence may be operative during tumor progression of CCS.
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PMID:Karyotypic divergence and convergence in two synchronous lung metastases of a clear cell sarcoma of tendons and aponeuroses with t(12;22)(q13;q12) and type 1 EWS/ATF1. 1293 23

Clear cell sarcoma of tendons and aponeuroses is a unique sarcoma initially described by Dr Franz M. Enzinger. The tumor has a proclivity to involve the tendons and aponeuroses of distal extremities of relatively young individuals and is characterized by multiple local recurrences with late metastases and a high rate of tumor deaths. Since its seminal description in 1965, there have been many studies verifying the uniqueness of this entity and probing its differentiation. Ultrastructural and immunohistochemical studies have shown melanocytic differentiation, whereas molecular genetic studies have shown cytogenetic rearrangements resulting in a EWSR1-ATF1 fusion gene that is characteristic but not entirely unique for clear cell sarcoma (similar fusion genes are also seen in angiomatoid fibrous histiocytoma). Detection of this fusion gene and the absence of BRAF gene mutations clearly distinguish clear cell sarcoma from cutaneous melanoma. Adverse prognostic factors identified to date include larger tumor size and any microscopic tumor necrosis. Surgery is the mainstay of treatment for this high grade sarcoma, with chemotherapy having little effect. Although the melanocytic differentiation of clear cell sarcoma is indisputable, its precise lineage remains unclear. Thus, clear cell sarcoma maintains the status of a unique yet enigmatic clinicopathologic entity of ever increasing complexity 40 years after its original description by an extraordinarily gifted man.
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PMID:Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. 1707 94

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low malignant potential and uncertain differentiation. Only three genetically investigated cases of AFH have been reported. Two of them displayed a FUS-ATF1 fusion gene and one showed an EWSR1-ATF1 chimera. Using RT-PCR analysis, we have identified the EWSR1-ATF1 fusion transcript, and delineated the genomic breakpoints, in two new cases of AFH. Previously, the EWSR1-ATF1 fusion protein has been suggested to activate expression of the MITF-M transcript, and therefore the expression pattern of the MITF gene was studied. The MITF-M transcript was not detected in either AFH, in line with the finding that the co-activator SOX10 was not expressed. Thus, of the five AFH that have been molecularly analyzed to date, two have displayed a FUS-ATF1 fusion gene and three have shown an EWSR1-ATF1 chimera. There is no apparent correlation between the type of fusion gene and clinicopathologic features. Nonetheless, RT-PCR for these fusion transcripts remains a valuable diagnostic adjunct in the distinction between AFH and other soft tissue tumors or metastases that may simulate it.
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PMID:Fusion genes in angiomatoid fibrous histiocytoma. 1718 28

Clear cell sarcoma of tendons and aponeuroses, also referred to as malignant melanoma of soft parts, is a rare malignancy derived from neural crest cells. It usually presents in the distal lower extremities of young adults, frequently attached to tendons or aponeuroses. It behaves like a high-grade soft tissue sarcoma and is associated with poor overall survival. Magnetic resonance imaging studies of the lesion reveal T1 hypointensity, T2 hyperintensity, and gadolinium uptake. Grossly, the tumor is usually circumscribed with a histologic pattern of uniform polygonal to fusiform cells with clear to pale eosinophilic cytoplasm divided into variably sized clusters by fibrous septa. Immunohistochemical studies in most cases show that the neoplastic cells are positive with HMB-45 and react with antibody against S100 protein. Most cases show a reciprocal cytogenetic translocation t(12;22)(q13;q12) that creates a unique chimeric fusion EWSR1/ATF1 gene transcript. Metastasis occurs mainly to regional lymph nodes and lungs. Poor prognostic indicators include a tumor size equal to or more than 5 cm, presence of metastasis, and necrosis. The mainstay of treatment is wide excision of the tumor. The use of sentinel lymph node biopsy may become an important procedure in detecting occult regional metastasis and guiding the extent of surgery. The beneficial effects of adjuvant chemotherapy and radiotherapy have not been fully evaluated. This article provides a short overview of the current knowledge of clear cell sarcoma of tendons and aponeuroses.
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PMID:Clear cell sarcoma of tendons and aponeuroses: a review. 1722 18

Clear cell sarcoma (CCS) of soft tissue is a rare sarcoma with morphologic similarities to malignant melanoma but a distinct genetic background including a chromosomal translocation, t(12;22)(q13;q12), or a resultant EWSR1-ATF1 fusion gene. In addition, the tumors occurring in the gastrointestinal tract may have a variant fusion gene EWSR1-CREB1. This study analyzed the clinicopathologic and molecular genetic features of 33 CCSs of soft tissue. The patients' ages ranged from 13 to 73 years (median, 30 y), and there was a male predominance (20 males, 13 females). The tumors were located in the deep soft tissues of the extremities (N=25) or in the trunk or limb girdles (N=8). The median tumor size was 4 cm (range, 1 to 15 cm). The tumor cells were either spindle or epithelioid, and they were arranged predominantly in a short fascicular (N=19) or a solid sheetlike growth pattern (N=14). Minor histologic variations included the existence of rhabdoid cells (N=8), bizarre pleomorphic cells (N=6), alveolar structures due to loss of cellular cohesion (N=3), and a seminomalike pattern (N=2). Tumor necrosis was evident in 14 tumors, and the mitotic activity ranged from 0 to 43 mitotic figures (MF)/10 high-power fields (HPF) (mean: 4 MF/10 HPF). Immunohistochemically, the tumors were consistently positive for S-100 protein (33/33) and variably or focally for HMB45 (32/33), microphthalmia transcription factor (26/32), Melan A (23/32), CD57 (25/33), bcl-2 (30/32), synaptophysin (14/32), CD56 (7/32), epithelial membrane antigen (12/33), cytokeratin (AE1/AE3) (1/32), CD34 (3/32), c-erbB-2 (10/32), c-kit (5/32), and c-met (5/32). alpha-Smooth muscle actin, desmin, and cytokeratin (CAM5.2) were negative. Reverse transcription-polymerase chain reaction using RNA extracted from formalin-fixed, paraffin-embedded tissues demonstrated transcripts of the EWSR1-ATF1 (31/33) or EWSR1-CREB1 fusion gene (2/33). In 26 cases with available clinical information, local recurrences and metastases developed in 2 and 15 patients, respectively. Ten patients were dead of the disease, and the overall survival rate was 63% at 5 years. However, no clinicopathologic or molecular variables associated with the patients' prognosis were identified. This study confirms that CCS is an aggressive soft tissue tumor with a melanocytic phenotype and wider morphologic variations than had been generally considered. In cases with unusual histologic findings, molecular detection of the EWSR1-ATF1/CREB1 fusion genes provides critical information regarding the diagnosis of the tumor.
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PMID:Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. 1830 Aug 4

Clear cell sarcoma of soft tissue (CCSST) is a rare soft tissue neoplasm with marked variable tumor progression and prognosis. Although morphologically similar to malignant melanoma, CCSST can be distinguished by the presence of a t(12; 22)(q13; q12) and/or associated EWSR1-ATF1 chimeric gene. CCSST has an affinity for the extremities and is capable of metastasizing to a wide variety of sites including bone, lung, and lymph nodes and rarely to skin, liver, heart, muscle, and brain. Metastases have been known to occur as late as 29 years after initial presentation. We report a case of a 33-year-old woman who presented with bilateral ovarian cystic tumors, ascites, and pulmonary nodules. Her past medical history was significant for clear cell sarcoma of the left foot 2 years earlier. Bilateral salpingo-oophorectomy was performed and the light microscopic and immunohistochemical findings coupled with the detection of an EWSR1 rearrangement by fluorescence in situ hybridization were compatible with a diagnosis of CCSST metastases to the ovaries. To the best of our knowledge, this is the first reported case of CCSST metastatic to the ovaries.
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PMID:Clear cell sarcoma of soft tissue metastatic to the ovaries: a heretofore unreported occurrence. 1962 Sep 41

Clear cell sarcoma (CCS) of tendons and aponeuroses/malignant melanoma (MM) of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract that may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with MM and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0.97 cm (range, 0.4 to 1.7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis, prima vista mimicking junctional nests of melanocytes. The specific translocation pattern was confirmed in all cases by fluorescence in situ hybridization. Local recurrences and metastases developed in 2 and 3 patients, respectively, and 1 patient died of the disease.
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PMID:Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma. 2008 59

Hyalinizing clear cell carcinoma (HCCC) is a unique low-grade tumor composed of cords and nests of clear cells in a hyalinized stroma that was first reported by Milchgrub et al. It was recognized as a separate entity from clear cell variants of epithelial-myoepithelial carcinoma, myoepithelial carcinoma and mucoepidermoid carcinoma. HCCC is included in a long list of clear cell-containing tumors of salivary gland, as well as odontogenic tumors and metastases (renal cell carcinoma). Up until now, it has been considered a diagnosis of exclusion, despite its very distinctive appearance, and labeled as "not otherwise specified" by the World Health Organization. The emergence of molecular data in salivary gland tumors, including HCCC now allow for a more rigorous appraisal of its spectrum. The EWSR1-ATF1 fusion has proven the concept of a "mucinous HCCC" and removes mucin as an exclusion criterion for this tumor. It has also proven a genetic link between clear cell odontogenic carcinoma and HCCC. Molecularly-proven cases have also highlighted variant morphologies and shown that cases with overt squamous differentiation are true HCCC. This gives further weight to the classification of this tumor as squamous or adenosquamous in differentiation and as a specific entity rather than an "NOS" tumor.
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PMID:What the EWSR1-ATF1 fusion has taught us about hyalinizing clear cell carcinoma. 2345 38

Cutaneous myoepithelial tumors demonstrate heterogenous morphologic and immunophenotypic features. We previously described, in brief, 7 cases of cutaneous myoepithelioma showing solid syncytial growth of ovoid, spindled, or histiocytoid cells. We now present the clinicopathologic features in a series of 38 cases of this distinctive syncytial variant, which were diagnosed between 1997 and 2012 (mostly seen in consultation). There were 27 men and 11 women, with a median age of 39 years (range, 2 mo to 74 y). Primary anatomic sites were the upper extremity (11, including 2 on the hand), upper limb girdle (3), lower extremity (14; 3 on the foot), back (6), face (2), chest (1), and buttock (1); the typical presentation was as either a polypoid or papular lesion. Tumors were well circumscribed and centered in the dermis and ranged in size from 0.3 to 2.7 cm (median 0.8 cm). Microscopically all tumors showed a solid sheet-like growth of uniformly sized ovoid to spindled or histiocytoid cells with palely eosinophilic syncytial cytoplasm. Nuclei were vesicular with fine chromatin and small or inconspicuous nucleoli and exhibited minimal to no atypia. Mitoses ranged from 0 to 4 per 10 HPF; 28 tumors showed no mitoses. Necrosis and lymphovascular invasion were consistently absent. Adipocytic metaplasia, appearing as superficial fat entrapped within the tumor, was seen in 12 cases. Chondro-osseous differentiation was seen in 1 tumor. All tumors examined were diffusely positive for EMA, and the majority showed diffuse staining for S-100 protein (5 showing focal staining). Keratin staining was focal in 1 of 33 tumors and seen in rare cells in 3 other cases. There was also positivity for GFAP (14/33), SMA (9/13), and p63 (6/11). Most lesions were treated by local excision. The majority of tumors tested (14/17; 82%) were positive by fluorescence in situ hybridization for EWSR1 gene rearrangement; testing for potential fusion partners (PBX1, ZNF444, POU5F1, DUX4, ATF1, CREB1, NR4A3, DDIT3, and NFATc2) was negative in all EWSR1-rearranged tumors. No FUS gene rearrangement was detected in 2 tumors lacking EWSR1 rearrangement. Follow-up information is available for 21 patients (mean follow-up 15 mo). One patient with a positive deep margin developed a local recurrence 51 months after initial biopsy. All other patients with available follow-up information, including 11 who had positive deep margins, are alive with no evidence of disease and no reported metastases. In summary, cutaneous syncytial myoepithelioma is a morphologically distinct variant that more frequently affects men, occurs over a wide age range, and usually presents on the extremities. Tumors are positive for S-100 protein and EMA, and, unlike most myoepithelial neoplasms, keratin staining is infrequent. EWSR1 gene rearrangement is present in nearly all tumors tested and likely involves a novel fusion partner. Prior reports describe some risk of recurrence and metastasis for cutaneous myoepithelial tumors; however, the syncytial variant appears to behave in a benign manner and only rarely recurs locally.
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PMID:Cutaneous syncytial myoepithelioma: clinicopathologic characterization in a series of 38 cases. 2358 65

Clear cell sarcoma shares features with melanoma, but frequently shows EWSR1 rearrangements. It is an aggressive tumor typically occurring in the soft tissues of the extremities, with a gastrointestinal variant with less consistent melanocytic differentiation. It is extremely rare in the head and neck region, with no reported cases in the oral cavity. We report a case of an 82-year-old woman with a clear cell sarcoma arising in the tongue, with cervical lymph node metastases. Histologically, the tumor showed some features of gastrointestinal clear cell sarcoma. No osteoclast-type giant cells were present. The tumor cells were positive for S100 protein and negative for other melanocytic markers. Fluorescence in situ hybridization showed rearrangements of EWSR1 and ATF1. This case expands the spectrum of clear cell sarcoma with a gastrointestinal-like variant in a novel site, emphasizing the need to consider it as a differential diagnosis to melanoma in mucosal sites.
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PMID:Primary clear cell sarcoma of the tongue. 2416 10


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