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1.  A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy 
Oncology Letters  2011;3(1):30-34.
Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive and malignant tumor that predominantly affects young males. No standard therapy is currently available for patients with DSRCT and the prognosis remains extremely poor. In this study, we report a thought-provoking DSRCT case. A 24-year-old male was admitted to our hospital with a chief complaint of hematemesis. Computed tomography revealed a retrovesical mass with a splenic hilar tumor, multiple lung and liver tumors and marked lymph node swellings. The source of hematemesis was gastric varices caused by the compression of the splenic vein by a splenic hilar tumor. The patient was provided with a histological diagnosis of DSRCT based on needle biopsy from the liver tumors and the pelvic mass was thought to be the primary lesion. This is a long-term survival case of metastatic DSRCT treated with multimodal therapy including 15 courses of multiagent chemotherapy, radiation therapy for the hepatic portal region using 42.5 Gy, and four instances of therapeutic endoscopy. The prolonged progression-free survival period (15 months) obtained following chemotherapy suggests the chemosensitive feature of the disease. We used a modified P6 regimen (cyclophosphamide, pirarubicin, vincristine, ifosfamide and etoposide) and a modified PAVEP regimen (cyclophosphamide, pirarubicin, etoposide and cisplatin) to decrease severe adverse events and to improve the completion rate of chemotherapy. DSRCT is an aggressive but chemo-sensitive disease, and continuous chemotherapy using an appropriate regimen with possible supportive care is essential for long-term survival. This case report may represent a treatment option for this rare disease.
doi:10.3892/ol.2011.457
PMCID: PMC3362338  PMID: 22740851
desmoplastic small round cell tumor; multimodal therapy; P6 regimen; PAVEP regimen
2.  Desmoplastic Small Round Cell Tumor of Stomach 
Desmoplastic small round cell tumor (DSRCT) is an extremely uncommon, highly aggressive, and malignant mesenchymal neoplasm of undetermined histogenesis. Less than 200 case reports have been documented in literature so far. Herein, we report a 26-year-old otherwise healthy female patient who presented with a 1-month history of epigastric pain. On physical examination, a palpable, slightly mobile, and tender epigastric mass was detected. All laboratory tests were normal. A chest, abdominal, and pelvic contrast-enhanced computed tomography (CT) scans showed a 3.8 × 7.2 × 8.7 cm ill-defined mass, involving gastric fundus and extending into gastric cardia and lower gastroesophageal junction. It was associated with multiple enlarged gastrohepatic lymph nodes; the largest measured 1.2 cm. There was no evidence of ascites or retroperitoneal or mesenteric lymphatic metastases. Patient underwent total gastrectomy with D2 lymphadenectomy, splenectomy, and antecolic Roux-en-Y esophagojejunal anastomosis. Histopathological examination revealed coexpression of mesenchymal, epithelial, and neural markers. The characteristic chromosomal translocation (t(11; 22)(p13; q12)) was demonstrated on fluorescence in situ hybridization (FISH) technique. Diagnosis of DSRCT of stomach was confirmed. Patient received no postoperative radiotherapy or chemotherapy. A postoperative 3-month followup failed to show any recurrence. In addition, a literature review on DSRCT is included.
doi:10.1155/2013/907136
PMCID: PMC3690222  PMID: 23840979
3.  Desmoplastic small round cell tumor: impact of 18F-FDG PET induced treatment strategy in a patient with long-term outcome 
Rare Tumors  2009;1(1):e19.
The desmoplastic small round cell tumor (DSRCT) is an uncommon and highly aggressive cancer. The role of 18F-FDG PET in management of DSRCT is little reported. We report a case of metastasized abdominal DSRCT detected in a 43-year old patient whose diagnostic and therapeutic approaches were influenced by 18F-FDG PET-CT. The patient is still alive ten years after diagnosis. 18F-FDG PET-CT seems to be a useful method for assessing therapeutic efficiency and detecting early recurrences even in rare malignancies such as DSRCT.
doi:10.4081/rt.2009.e19
PMCID: PMC2994440  PMID: 21139890
4.  Desmoplastic Small Round Cell Tumor: Current Management and Recent Findings 
Sarcoma  2012;2012:714986.
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 [90Y]Yttrium microsphere liver embolization.
doi:10.1155/2012/714986
PMCID: PMC3329898  PMID: 22550424
5.  Primary desmoplastic small round cell tumor of the testis: A case report and review of the literature 
Oncology Letters  2013;6(2):565-567.
Desmoplastic small round cell tumors (DSRCTs) are extremely rare and mainly affect adolescents and young adults. The tumors are usually involved with the abdominal area and/or the pelvic peritoneum. Only a small number of cases have been reported concerning DSRCTs of the testicular region. The present study reports a case of DSRCT of the testis with radical orchectomy and systemic chemotherapy, leaving the patient disease-free for 14 months. However, the patient died of multiple metastasis 12 months later. Furthermore there is a review of the English literature to analyze the incidence, site of origin, imaging and pathological characteristics of DSRCT.
doi:10.3892/ol.2013.1421
PMCID: PMC3789079  PMID: 24137371
desmoplastic small round cell tumor; testis
6.  Desmoplastic small round cell tumor (DSRCT) xenografts and tissue culture lines: Establishment and initial characterization 
Oncology Letters  2013;5(5):1453-1456.
Desmoplastic small round cell tumor (DSRCT) is an extremely rare and aggressive neoplasm, which mainly affects young males and generally presents as a widely disseminated tumor within the peritoneal cavity. Due to the rarity of the tumor, its younger and overall healthier patient population (compared with other tumor types) and the fact that it lacks definitive histological and immunohistological features, the diagnosis of DSRCT may be frequently delayed or the tumor may be entirely misdiagnosed as a different type of abdominal sarcoma. The present study aimed to rectify the lack of models that exist for this rare neoplasm, through the development of several DSRCT tissue cultures and xenograft lines. Samples were received from surgeries and biopsies from patients worldwide and were immediately processed for xenograft development in nude mice. Tumor tissues were minced and fragments were injected into the dorsal flanks of nude mice. Of the 14 samples received, nine were established into xenograft lines and five into tissue culture lines. Xenografts displayed the microscopic histology of their parent tumors and demonstrated two different growth rates among the established xenograft lines. Overall, the establishment of these xenograft and tissue culture lines provides researchers with tools to evaluate DSRCT responses to chemotherapy and to investigate DSRCT-specific signaling pathways or mechanisms.
doi:10.3892/ol.2013.1265
PMCID: PMC3678573  PMID: 23759995
desmoplastic small round cell tumor; sarcoma; xenograft; nude mice; tissue culture techniques
7.  Removal of an intra-abdominal desmoplastic small round cell tumor by repetitive debulking surgery: A case report and literature review 
Oncology Letters  2014;7(5):1464-1468.
In the current study, a case of recurrent desmoplastic small round cell tumor (DSRCT) is presented, which was successfully treated by repetitive debulking surgery. In May 2010, a 39-year-old male, with a history of surgical resection of intra-abdominal DSRCT, visited the Ibaraki Medical Center, Tokyo Medical University Hospital (Ami, Japan) with severe lower abdominal discomfort. Abdominal computed tomography revealed a large tumor in the pouch of Douglas with a small number of nodules in the abdominal cavity. The recurrent DSRCT was diagnosed and removed via lower anterior resection; however, complete resection was impossible due to multiple peritoneal metastases. One year later, the patient developed pain in the right groin due to the growth of metastasized tumor cells in the groin lymph nodes. The affected lymph nodes were removed utilizing an extra-peritoneal approach. At the time of writing, the patient continues to survive without any symptoms 60 months since the initial surgery. In conclusion, surgical debulking is a significant procedure for relieving patient symptoms as well as improving the survival time of patients with metastatic and recurrent DSRCT.
doi:10.3892/ol.2014.1913
PMCID: PMC3997734  PMID: 24765157
desmoplastic small round cell tumor; prognosis; debulking surgery
8.  Desmoplastic Small Round Cell Tumor of the Abdomen and Pelvis: Clinicopathological Characters of 12 Cases 
The Scientific World Journal  2014;2014:549612.
Purpose. To study the clinical, radiological, and pathological characteristics of abdominal desmoplastic small round cell tumor (DSRCT) and investigate the optimal therapy modalities. Patients and Methods. A retrospective cohort study was performed on 12 abdominal DSRCT patients; all pathological, radiological, and prognostic data were analyzed. There were 3 patients (25%) with metastatic disease at presentation. In all 12 cases, 6 cases underwent operation and adjuvant chemotherapy (group 1, 6/12, 50%). The other 6 cases were diagnosed by fine needle aspiration or exploratory laparotomy biopsy (group 2, 6/12, 50%); all cases received four to six courses of multiple agents chemotherapy, respectively. Results. All cases were finally diagnosed as DSRCT pathologically. Among group 1, all cases underwent en bloc resection (2/6, 33%) or tumor debulking (4/6, 67%) and, following four courses of multiple agents chemotherapy, Kaplan-Meier analysis revealed that 3-year survival was 50% in group 1 versus 16.7% in group 2 (P < 0.05). Gross tumor resection was highly significant in prolonging overall survival; patients with localized solitary lesion have a better prognosis, most likely due to increased feasibility of resection. Conclusions. DSRCT is a rare malignant tumor with poor prognosis. Surgical excision with combination chemotherapy as an adjunct is mandatory for nonmetastatic cases because these modalities used in isolation may have less impact.
doi:10.1155/2014/549612
PMCID: PMC4060500  PMID: 24987737
9.  An Unusual Presentation of Desmoplastic Small Round Cell Tumour of the Abdomen: Morphological, Immunohistochemical, Ultrastructural, and Molecular Studies 
Desmoplastic small round cell tumour (DSRCT) is an aggressive and a rare neoplasm. We report on a 34-year-old male who had abdominal discomfort with a large intraperitoneal mass. Histological examination of the tumour biopsy revealed sheets of small round cells. The cells were positive with vimentin and desmin (with occasional dot positivity) and negative for WT1 and CD 99 with immunohistochemistry. Cytogenetics showed a translocation disrupting the EWSR 1 gene on 22 q 12 consistent with DSRCT. Electron microscopic examination showed sparse cytoplasmic organelles. The patient succumbed 34 months from disease presentation after multiple chemotherapies and thereafter radiotherapy. In summary, our case exemplifies that it is crucial to combine clinical, histological, and molecular aspects in diagnosing DSRCT especially when characteristic dot positivity with desmin is weak along with deficient marking of WT1 and CD99 by immunohistochemistry. Histology was also less clear than published examples of this entity with a poor desmoplastic response. A multidisciplinary approach including early referral to specialised centres is recommended in these cases as tertiary referral centres will be required to substantiate the diagnosis.
doi:10.1155/2011/183938
PMCID: PMC3350138  PMID: 22606441
10.  Intra-abdominal desmoplastic small round cell tumor: Presentation of four cases and review of the literature 
Desmoplastic small round cell tumor (DSRCT) of the abdomen is a recently identified aggressive neoplasm. Very few cases have been reported in the literature. Thus, the treatment guidelines are yet to be defined. The role of chemotherapy, radiotherapy and surgery is evolving. We treated four cases of DSRCT involving the abdomen using combination chemotherapy and/or tumor cytoreductive surgery. There were two men and two women. The chemotherapy drugs consisted of cisplatin, adriamycin, etoposide, ifosphamide, vincristine and cyclophsophamide. All patients achieved meaningful partial response to chemotherapy, which maintained for 6–9 months. There were very minimal chemotherapy-related complications. At the time of reporting, the median survival time was 15 months. Thus, DSRCT is an aggressive intra-abdominal tumor with excellent chemoresponsiveness, but relapse is frequent.
doi:10.4103/0971-5851.68849
PMCID: PMC2941599  PMID: 20931017
Abdomen; chemotherapy; desmoplastic small round cell tumor; management and prognosis; radiotherapy; surgery
11.  Clinicopathological investigation of four cases of desmoplastic small round cell tumor 
Oncology Letters  2012;4(3):423-428.
The purpose of this study was to perform clinicopathological and immunohistochemical analysis and to investigate the Ewing sarcoma gene (EWS)-Wilms' tumor suppressor gene (WT1) fusion within desmoplastic small round cell tumors (DSRCTs). Histology slides and clinical data were reviewed for four patients with DSRCT. A variety of immunohistochemical staining was performed. Fluorescence in situ hybridization (FISH) was performed to detect the EWS-WT1 fusion transcripts resulting from the chromosomal translocation t(11;22)(p13;q12). The patients consisted of four males aged from 26 to 52 years old (mean, 33.5). In three of these patients, the tumors were situated in the abdominal cavity and the tumor from the other patient was located in the pelvic cavity. The tumors were 8–15 cm in diameter (mean tumor diameter, 13), solid and gray-white, with an appearance of nodosity or sublobes, and hemorrhage or necrosis was observed. Microscopically, the tumors consisted of small round cell nests of unequal size. Hyperplastic and thick fibrous connective tissue surrounding the neoplastic cell nests was present in all cases. The tumor nuclei were hyperchromatic and contained inconspicuous nucleoli with a high level of karyokinesis. Immunohistochemical staining revealed diffuse and strong staining for CK, vimentin, desmin and CAM5.2 in all cases. Certain cases also expressed WT-1, EMA, NSE, CD56, CD99 and CK5/6. Staining was negative for myogenin, MyoD1, calretinin, CD117, CD34, HMB45 and CEA. EWS-WT1 fusion transcripts were detected in 3 out of 4 cases, but not in any other tumor types studied as controls using paraffin-embedded tissue by FISH. DSRCT is a highly maligant tumor occuring predominantly in the abdominal or pelvic cavity of young males with multiphenotypic differentiation. Basic morphological features, clinical manifestations and the detection of the EWS-WT1 fusion transcript within the tumor aid the recognition and diagnosis of the tumor.
doi:10.3892/ol.2012.750
PMCID: PMC3673645  PMID: 23741244
desmoplastic small round cell tumor; clinicopathological features; immunophenotype; gene fusion
12.  Clinical and computed tomography features of adult abdominopelvic desmoplastic small round cell tumor 
To investigate the clinical and computed tomography (CT) features of desmoplastic small round cell tumor (DSRCT), we retrospectively analyzed the clinical presentations, treatment and outcome, as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology. The CT manifestations of DSRCT were as follows: (1) multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis, with the dominant mass usually located in the pelvic cavity; (2) masses without an apparent organ-based primary site; (3) mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT; and (4) secondary manifestations, such as ascites, hepatic metastases, lymphadenopathy, hydronephrosis and hydroureter. The prognosis and overall survival rates were generally poor. Commonly used treatment strategies including aggressive tumor resection, polychemotherapy, and radiotherapy, showed various therapeutic effects. CT of DSRCT shows characteristic features that are helpful in diagnosis. Early discovery and complete resection, coupled with postoperative adjuvant chemotherapy, are important for prognosis of DSRCT. Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.
doi:10.3748/wjg.v20.i17.5157
PMCID: PMC4009557  PMID: 24803835
Desmoplastic small round cell tumor; Peritoneum; Pathology; Computed tomography; Clinical features
13.  Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor 
PLoS ONE  2008;3(6):e2353.
Background
Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive malignancy that affects mainly adolescents and young adults. A defining characteristic of DSRCT is a specific chromosomal translocation, t(11;22)(p13;q12), that fuses EWS with WT1, leading to a production of two isoforms of chimeric transcription factor, EWS/WT1(−KTS) and EWS/WT1(+KTS). The chimeric proteins are thought to play critical roles in various stages of oncogenesis through aberrant transcription of different genes, but only a few of these genes have been identified.
Methodology/Principal Findings
We report the identification of a new target of EWS/WT1, ENT4 (equilibrative nucleoside transporter 4) which encodes a pH-dependent adenosine transporter. ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses. Furthermore, ENT4 is highly and specifically expressed in primary tumors of DSRCT as well as in a DSRCT cell line, JN-DSRCT-1. Treatment of JN-DSRCT-1 cells with adenosine analogs, such as 2-chloro-2′-deoxyadenosine (2-CdA), resulted in an increased cytotoxic response in dose- and pH-dependent manner.
Conclusions/Significance
Our detailed analyses of a novel target of EWS/WT1 in DSRCT reveal an insight into the oncogenic mechanism of EWS-fusion chromosomal translocation gene products and provide a new marker for DSRCT. Furthermore, identification of ENT4 as a highly expressed transcript in DSRCT may represent an attractive pathway for targeting chemotherapeutic drugs into DSRCT.
doi:10.1371/journal.pone.0002353
PMCID: PMC2394657  PMID: 18523561
14.  Combined resection and multi-agent adjuvant chemotherapy for desmoplastic small round cell tumor arising in the abdominal cavity: Report of a case 
Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.
doi:10.3748/wjg.v12.i5.800
PMCID: PMC4066136  PMID: 16521199
Desmoplastic small round cell tumor; Surgery; Chemotherapy
15.  Symptomatic Hypoglycemia Related to Inappropriately High IGF-II Serum Levels in a Patient with Desmoplastic Small Round Cell Tumor 
Case Reports in Medicine  2010;2010:684045.
A 45-year old man was diagnosed with desmoplastic small round cell tumor (DSRCT) with involvement of the peritoneum and pelvis. Disease progression was observed despite systemic chemotherapy. Six months after diagnosis, he developed severe hypoglycemia presented with seizures. He received intravenous glucose infusion and hydrocortisone with poor glycemic control, but with seizures resolution. The investigation excluded insulinoma, adrenal, liver and GH deficiencies. Laboratory showed slight rise of IGF-II and significant increase of the ratio IGF-II : IGF-I, which is pathognomonic of non-islet cell tumor hypoglycemia (NICTH). He received the diagnoses of NICTH related to IGF-II inappropriate production by DSRCT. Despite the attempt to control tumor mass and hypoglycemia, the patient died 9 months after diagnosis. NICTH related to inappropriate IGF-II secretion should be investigated in all cancer patients with refractory hypoglycemia whom insulinoma and other metabolic abnormalities were excluded from.
doi:10.1155/2010/684045
PMCID: PMC2892690  PMID: 20592985
16.  Retroperitoneal desmoplastic small round cell tumor: Pediatric patient treated with multimodal therapy 
A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intra-abdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.
doi:10.3748/wjg.15.4212
PMCID: PMC2738824  PMID: 19725162
Retroperitoneum; Desmoplastic small round cell tumor; Multimodal therapy
17.  Desmoplastic Small Round Cell Tumor: Report of 2 Cases Treated with Chemotherapy Alone or in Combination with Bevacizumab 
Case Reports in Oncology  2014;7(1):102-108.
Here, we present 2 case reports of patients with desmoplastic small round cell tumor (DSRCT), a very rare and aggressive mesenchymal cancer, and we discuss 2therapeutic options for this sarcoma. This report focuses on men aged 22 and 37 years, respectively. The first patient presented with an abdominopelvic mass which was not suitable for surgery. He underwent chemotherapy (adriblastina and cisplatin) with a brief partial remission and survival time of 13 months. The second patient presented with an abdominal mass and underwent partial resection. He received chemotherapy and bevacizumab, resulting in a partial remission and a survival time of 34 months. The extent of surgery and monoclonal antibody use probably had a positive impact on survival. It is necessary to include specific targeted therapies in an attempt to improve survival. Surprisingly, positron emission tomography was not effective in restaging of the second patient, emphasizing the importance of computed tomography or magnetic resonance in DSRCT.
doi:10.1159/000359997
PMCID: PMC3975756  PMID: 24707256
Desmoplastic small round cell tumor; Chemotherapy; Abdominal tumor; Bevacizumab
18.  Expression of connective tissue growth factor (CCN2) in desmoplastic small round cell tumour 
Journal of Clinical Pathology  2004;57(4):422-425.
Background: Desmoplastic small round cell tumour (DSRCT) is a rare and often fatal abdominal tumour that is distinguished by well defined islands of cells, surrounded by prominent desmoplastic stroma. As in certain other tumours, the function of the Wilms’s tumour protein (WT1) in repressing gene transcription is lost in DSRCT.
Aims: To assess the expression and localisation of connective tissue growth factor (CCN2) in DSRCT because this protein is transcriptionally repressed by WT1 and is associated with the production of abundant extracellular matrix.
Methods: CCN2 was assessed by in situ hybridisation and immunohistochemistry.
Results: CCN2 mRNA and protein were colocalised to the tumour cells themselves, in addition to stromal fibroblasts and vascular endothelial cells.
Conclusions: These data show that CCN2 is produced in high amounts by several cell types in DSRCT, and highlight a potential role for this factor in the autocrine and paracrine regulation of tumour cell growth, matrigenesis, and angiogenesis.
doi:10.1136/jcp.2003.012344
PMCID: PMC1770275  PMID: 15047749
fibrosis; stroma; connective tissue growth factor; desmoplasia; tumour
19.  Imaging of desmoplastic small round cell tumour in adults 
The British Journal of Radiology  2012;85(1010):187-192.
Desmoplastic small round cell tumour (DSRCT) belongs to the histological descriptive category of small round blue cell tumours. DSRCT primarily occurs in adolescents and young adults between the ages of 15 and 25 years and has a male predominance. DSRCT is an aggressive disease with a poor prognosis; timely diagnosis is therefore critical to the management of these patients. Although their radiographic appearances overlap with other aggressive malignancies, there are certain imaging features that can suggest the diagnosis and expedite the initiation of appropriate therapy. The aim of our pictorial review is to describe the imaging findings of primary and metastatic DSRCT in adults.
doi:10.1259/bjr/57186741
PMCID: PMC3473944  PMID: 22128126
20.  Morphoproteomic Profiling of the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Desmoplastic Small Round Cell Tumor (EWS/WT1), Ewing’s Sarcoma (EWS/FLI1) and Wilms’ Tumor(WT1) 
PLoS ONE  2013;8(7):e68985.
Background
Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing’s sarcoma (EWS) gene with the Wilms’ tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing’s sarcoma (EWS-FLI1) and Wilms’ tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies.
Methodology
This pilot study assessed patients with DSRCT, Wilms’ tumor and Ewing’s sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls.
Principal Findings
In DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing’s sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm’s tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing’s sarcoma, but not in the DSRCT.
Conclusion
Morphoproteomic tumor analyses revealed constitutive activation of the mTOR pathway as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic assessments of these tumors are warranted.
doi:10.1371/journal.pone.0068985
PMCID: PMC3726753  PMID: 23922674
21.  A practical approach to the clinical diagnosis of Ewing’s sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue 
Journal of Clinical Pathology  2005;58(10):1051-1056.
Background: Over 90% of Ewing’s sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis.
Aims: To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS.
Methods: Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe.
Results: One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls.
Conclusions: Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.
doi:10.1136/jcp.2004.025502
PMCID: PMC1770737  PMID: 16189150
Ewing’s sarcoma/primitive neuroectodermal tumour; desmoplastic small round cell tumour; clear cell sarcoma; fluorescence in situ hybridisation; formalin fixed paraffin wax embedded
22.  ONCOGENE MUTATION PROFILING OF PEDIATRIC SOLID TUMORS REVEALS SIGNIFICANT SUBSETS OF EMBRYONAL RHABDOMYOSARCOMA AND NEUROBLASTOMA WITH MUTATED GENES IN GROWTH SIGNALING PATHWAYS 
Clinical Cancer Research  2011;18(3):748-757.
Compared to the numerous broad screens for oncogene mutations in adult cancers, very few have been performed in pediatric solid tumors. To identify novel mutations and potential therapeutic targets in pediatric cancers, we performed a high-throughput Sequenom-based analysis in large sets of several major pediatric solid cancers, including neuroblastoma (NB), Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and desmoplastic small round cell tumor (DSRCT).
Experimental Design
We designed a highly multiplexed Sequenom-based assay to interrogate 275 recurrent mutations across 29 genes. Genomic DNA was extracted from 192 NB, 75 ES, 89 RMS, and 24 DSRCT samples. All mutations were verified by Sanger sequencing.
Results
Mutations were identified in 13% of NB samples, 4% of ES samples, 21.1% of RMS samples, and no DSRCT samples. ALK mutations were present in 10.4% of NB samples. The remainder of NB mutations involved the BRAF, RAS, and MAP2K1 genes and were absent in samples harboring ALK mutations. Mutations were more common in embryonal RMS (ERMS) samples (28.3%) than alveolar RMS (ARMS) (3.5%). In addition to previously identified RAS and FGFR4 mutations, we report for the first time PIK3CA and CTNNB1 (Beta-Catenin) mutations in 4.9% and 3.3% of ERMS, respectively.
Conclusions
In ERMS, ES, and NB, we identified novel occurrences of several oncogene mutations recognized as drivers in other cancers. Overall, NB and ERMS contain significant subsets of cases with non-overlapping mutated genes in growth signaling pathways. Tumor profiling can identify a subset of pediatric solid tumor patients as candidates for kinase inhibitors or RAS-targeted therapies.
doi:10.1158/1078-0432.CCR-11-2056
PMCID: PMC3271129  PMID: 22142829
mutation; rhabdomyosarcoma; neuroblastoma; Ewing sarcoma; desmoplastic small round cell tumor
23.  Desmoplastic small round cell tumor: a case report and review of the literature 
Desmoplastic small round cell tumor is a rare malignant tumor that has a poor prognosis. It affects predominantly young males. In the current report, a 14-year-old male patient was admitted to the hospital for evaluation of abdominal distension, and abdominal pain. Imaging examination revealed a high prevalence of multiple intraperitoneal and liver parenchymal cystic and solid tumors. After an explorative surgery, the pathological findings confirmed the presentation of desmoplastic small round cell tumor. Diagnosis of desmoplastic small round cell tumor could easily have been overlooked since there was no specific evidence for this condition available in the clinical and imaging examinations. In the present study, ultrasound examination detected solid cystic masses, which suggested the presence of necrosis and hemorrhage. Immunohistochemistry and cytogenetic studies confirmed the diagnosis of desmoplastic small round cell tumor in this patient.
doi:10.1186/1477-7819-12-9
PMCID: PMC3976550  PMID: 24410799
Desmoplastic small round cell tumor; Imaging; Pathology
24.  ThinPrep Cytological Findings of Desmoplastic Small Round Cell Tumor with Extensive Glandular Differentiation: A Case Study 
Korean Journal of Pathology  2013;47(2):182-187.
Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm. The cytological diagnosis of this tumor has only been reported in a few cases. In most of these cases, the diagnosis was made using fine-needle aspiration cytology. Most DSRCTs resemble disseminated carcinomatoses in their clinical manifestation as well as cytomorphologically, even in young-adult patients. These authors report a case of using peritoneal-washing and pleural-effusion ThinPrep cytology to diagnose DSRCT, with extensive glandular differentiation and mucin vacuoles. We found that fibrillary stromal fragment, clinical setting, and adjunctive immunocytochemical staining were most helpful for avoiding misdiagnosis.
doi:10.4132/KoreanJPathol.2013.47.2.182
PMCID: PMC3647133  PMID: 23667380
Desmoplastic small round cell tumor; Gland; Mucin content; Desmin; ThinPrep
25.  Desmoplastic small round cell tumour: the radiological, pathological and clinical features 
Insights into Imaging  2013;4(1):111-118.
Objectives
Desmoplastic small round cell tumours (DSRCTs) are rare aggressive tumours of young adults that present late and have poor prognosis. This review discusses distinctive radiological features, histopathology and clinical course of this soft-tissue sarcoma.
Methods
From 1991 to 2012, the radiology of 20 patients with pathologically proven DSRCT was independently reviewed by two experienced radiologists. The clinical presentation, treatment and outcome were recorded.
Results
Patients: 16 men, four women; mean age 28.3 years. Computed tomography (CT) demonstrated peritoneal/omental masses without an organ of origin (94 %), with the majority of cases demonstrating large (>5 cm) dominant soft-tissue deposit (80 %) with multiple smaller foci. CT and magnetic resonance imaging (MRI) typically demonstrated heterogeneous soft-tissue enhancement with cystic degeneration. A minority (20 %) demonstrated calcification. Lymph node enlargement occurred in 50 % of cases. Distant metastatic disease occurred in 25 %. Painful abdominal masses were clinically predominant. Treatment strategies include combination chemotherapy with debulking surgery and/or radiotherapy. Median survival from diagnosis was 22.8 months.
Conclusion
Features of multifocal peritoneal/omental masses, usually in combination with a dominant soft tissue deposit, are distinctive in this rare sarcoma. CT/MRI defines the extent of disease and characterises supporting imaging findings. Prolific desmoplastic reaction histologically separates DSRCT from similar subtypes. Combination treatment strategies can infer a survival benefit but prognosis remains poor.
Teaching Points
• DSRCTs are rare tumours of young adults (mean age 28.3 years) with a male predominance (4:1).
• Painful abdominal masses clinically predominate. Non-specific features of malignancy can be present.
• Multifocal peritoneal masses with a dominant soft tissue lesion is a distinctive imaging finding.
• A large desmoplastic reaction differentiates DSRCTs from histologically similar round cell subtypes.
• Despite debulking surgery with adjuvant chemotherapy, median survival from diagnosis is 22.3 months.
doi:10.1007/s13244-012-0212-x
PMCID: PMC3579986  PMID: 23307783
Desmoplastic small round cell tumour; DSRCT; Radiology; Pathology; Clinical features; Imaging; Treatment

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