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

The occurrence of Ewing sarcoma-peripheral primitive neuroectodermal tumor as a primary intracranial tumor is very rare, with only 29 cases reported in the literature, 19 of which have included molecular studies. We present the clinical, radiologic and pathologic findings of an intracranial Ewing sarcoma in a 22-year-old woman arising from the dura over the right frontal convexity. The patient underwent craniotomy with gross total excision of the tumor. The tumor showed atypical histology and the diagnosis was confirmed by detection of a rearrangement of the EWSR1 gene by fluorescent in situ hybridization and identification of the diagnostic t(11;22)(q24;q12) translocation by reverse transcription-polymerase chain reaction. Additional features were detected in this tumor that are known to be associated with an unfavorable prognosis, including loss of p16 expression and gains of chromosomes 1q and 12. The patient experienced the most rapid downhill course reported to date for intracranial Ewing sarcoma, developing multiple extracranial metastases at 2 months and dying 6 months after the initial operation.
 ...
PMID:Primary intracranial Ewing sarcoma with an unusually aggressive course: a case report and review of the literature. 2200 64

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive mesenchymal tumor that develops in the abdominal cavity of young men adults. Patients typically present with symptoms of abdominal sarcomatosis. Diagnosis is based on histological analysis of biopsies which typically show small round blue cells in nests separated by an abundant desmoplastic stroma. DSRCT is associated with a unique chromosomal translocation t(11:22) (p 13; q 12) that involves the EWSR1 and WT1 genes. The prognosis is particularly poor; median survival ranges from 17 to 25 months, largely due to the presentation of the majority of patients with metastatic disease. Management of DSRCT remains challenging and current schemes lack a significant cure rate despite the use of aggressive treatments such as polychemotherapy, debulking surgery and whole abdominal radiation. Several methods are being evaluated to improve survival: addition of chemotherapy and targeted therapies to standard neoadjuvant protocol, completion of surgical resection with HIPEC, postoperative IMRT, treatment of hepatic metastases with [(90)Y]Yttrium microsphere liver embolization.
 ...
PMID:Desmoplastic small round cell tumor: current management and recent findings. 2255 Apr 24

Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15-76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37-82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs.
 ...
PMID:NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma. 2256 67

Angiomatoid fibrous histiocytoma is a rare soft tissue tumor of intermediate biologic potential, predominantly arising in superficial extremities of children and young adults. Less than 5% metastasize. We describe a case of angiomatoid fibrous histiocytoma in the scalp of an 8-year-old boy, which metastasized to a postauricular lymph node 3 years after primary tumor excision. Histologically, primary and metastasis comprised nodules of bland ovoid cells, with primary additionally showing hemorrhagic cavities, fibrous capsule, and lymphoplasmacytic inflammation. Both strongly expressed desmin, with focal epithelial membrane antigen. Reverse transcription-polymerase chain reaction showed EWSR1-CREB1 fusion transcripts in both primary and metastasis. This is, to our knowledge, the first description of genetically proven metastatic angiomatoid fibrous histiocytoma. Angiomatoid fibrous histiocytoma can mimic both benign and malignant lesions, and although most behave indolently, it is important to recognize their metastatic potential.
 ...
PMID:Metastatic angiomatoid fibrous histiocytoma of the scalp, with EWSR1-CREB1 gene fusions in primary tumor and nodal metastasis. 2319 25

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.
 ...
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.
 ...
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.
...
PMID:Primary clear cell sarcoma of the tongue. 2416 10

Angiomatoid "malignant fibrous histiocytoma" (AMFH) is a tumor of intermediate malignancy and undefined lineage, mostly arising in the extremities of young patients. Examples with a prominent myxoid matrix are very uncommon. Twenty-one cases of myxoid AMFH (among a total of 414) identified in consult files are described, including clinicopathologic features, fluorescence in situ hybridization analysis in a subset of cases, and follow-up. Thirteen patients were female and 8 male, ranging in age from 2 to 51 y (median 17 y). These circumscribed tumors arose in subcutaneous or deep somatic soft tissue, with a median size of 2.5 cm (range, 1 to 8 cm), being located in the extremities (14/21), trunk (4/21), and upper limb girdle (3/21). Characteristic features included a fibrous pseudocapsule (20/21), peritumoral lymphoplasmacytic infiltrates (20/21), blood-filled cystic spaces (17/21), and prominent myxoid morphology comprising 60% to 100% of the tumor surface area examined. Histiocytoid or spindled tumor cells exhibited vesicular nuclei, inconspicuous nucleoli, palely eosinophilic cytoplasm, and multinodular growth without necrosis. Mucin pools and scattered multinucleate giant cells were observed in a subset of cases. Mild to moderate atypia was observed in 4 cases; 1 tumor showed a pseudochondroid matrix. Immunohistochemically, 14/21 cases expressed desmin, 12/21 expressed EMA, and 4/7 exhibited EWSR1 rearrangement. Follow-up, available for 11 patients (median, 43 mo), revealed that 3 developed local recurrence after 2, 7, and 48 months, respectively. All patients were alive without metastases. AMFH may present with prominent myxoid features making diagnosis difficult and causing possible confusion with other myxoid tumors including low-grade fibromyxoid sarcoma, extraskeletal myxoid chondrosarcoma, and myxoid liposarcoma.
...
PMID:Myxoid variant of so-called angiomatoid "malignant fibrous histiocytoma": clinicopathologic characterization in a series of 21 cases. 2450 54

The next WHO classification should abandon "salivary duct carcinoma"; conventional salivary duct carcinoma should be classified as "high-grade salivary duct carcinoma". Low-grade salivary duct carcinoma should replace the current nosology of "low-grade cribriform cystadenocarcinoma". Cystadenocarcinoma should be classified with the descriptor "Not Otherwise Specified" and should be considered an exclusionary diagnostic category. On the other hand, "Not Otherwise Specified" does not fit for hyalinizing clear cell carcinoma (HCCC). The EWSR1-ATF1 fusion is specific for HCCC within the context of salivary neoplasia. We recommend adding "hyalinizing" even though this feature is not present in all cases; the benefit of which is the mental association with a salivary clear cell malignancy. Sinonasal Renal Cell-like Adenocarcinoma (SNRCLA) is a distinct clear cell neoplasm and should be added to the next WHO classification. Future studies will bear out whether SNRCLA is even a low-grade carcinoma, or may be reclassified as "adenoma". Lastly, the next WHO monograph should include the Risk Model in the general introductory statements on oral squamous cell carcinoma, under a subheading of "Histological Prognosticators". The positive predictive value for developing locoregional recurrence in patients with low-stage oral cavity squamous carcinoma (OSCC) and "worst pattern of invasion type-5" (WPOI-5) is 42 %. Low-stage high-risk OSCC with a combination of features other than WPOI-5 is associated with 32 % likelihood for locoregional progression. WPOI-5 also predicts occult metastatic disease (p = 0.0001, Chi squared, 2 DF). Thus the Risk Model can also be used to make decisions regarding staged elective neck dissections.
 ...
PMID:Envisioning the next WHO head and neck classification. 2459 18

Ewing sarcoma, the second most common bone tumor in children and young adults, is an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is characterised by translocations encoding fusion transcription factors with an EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs are post-transcriptional regulators of gene expression and aberrantly expressed microRNAs have been identified as tumor suppressors or oncogenes in most cancer types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the putative cellular origin of Ewing sarcoma, from 6 healthy donors. Of the 35 differentially expressed microRNAs identified (fold change >4 and q<0.05), 19 were higher and 16 lower expressed in Ewing sarcoma. In comparisons between Ewing sarcoma samples with EWS-FLI or EWS-ERG translocations, with differing dissemination characteristics and of primary samples and metastases no significantly differential expressed microRNAs were detected using various stringency criteria. For miR-31, the microRNA with lowest expression in comparison to mesenchymal stem cells, functional analyses were performed to determine its potential as a tumor suppressor in Ewing sarcoma. Two of four miR-31 transfected Ewing sarcoma cell lines showed a significantly reduced proliferation (19% and 33% reduction) due to increased apoptosis in one and increased length of G1-phase in the other cell line. All three tested miR-31 transfected Ewing sarcoma cell lines showed significantly reduced invasiveness (56% to 71% reduction). In summary, we identified 35 microRNAs differentially expressed in Ewing sarcoma and demonstrate that miR-31 affects proliferation and invasion of Ewing sarcoma cell lines in ex vivo assays.
...
PMID:Differentially expressed miRNAs in Ewing sarcoma compared to mesenchymal stem cells: low miR-31 expression with effects on proliferation and invasion. 2466 36


<< Previous 1 2 3 4 5 6 7 8 Next >>