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Disease

Desmoplastic small-round-cell tumor is classified as a soft tissue sarcoma. It is an aggressive and rare tumor that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metatastic spread include the liver, lungs, lymph nodes, brain, skull, and bones. The tumor is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer. Research has indicated that there is a chimeric relationship between desmoplastic small-round-cell tumor (DSRCT) and Wilms' tumor and Ewing's sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small or B cell tumors. DSRCT is associated with a unique chromosomal translocation (t11;22)(p13:q12) resulting in a EWS/WT1 transcriptthat is diagnostic of this tumor  This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.
Desmoplastic small round cell tumor (DSRCT) was first described in 1989 by Gerald and Rosai who described a distinct type of small round blue cell tumor with a predilection for serosal surfaces such as the peritoneum and the tunica vaginalis that affected mostly Caucasian males in the second or third decade of life (1). DSRCT is generally associated with aggressive features and a poor prognosis. Tumor cells co-express epithelial, mesenchymal and neuronal markers and are thought to originate from a mesothelial or submesothelial progenitor cell with the potential to undergo multilineage differentiation.
                           Clincal Manifestations
In most cases, DSRCT presents as an abdominal mass with peritoneal and omental implants. Associated symptoms may include crampy abdominal pain, weight loss and constipation. The most common presentation is bulky abdominal disease present in a young adult, often males. Other reported sites of disease include pleura, ethmoid sinuses, scalp, hand, posterior cranial fossa, pancreas, ovary, paratesticular and kidney. Symptoms related to extra-abdominal tumors vary, and include scoliosis, chronic sinusitis, and pain. Erectile dysfunction has also been described (1-3, 5-9). DSRCT is regional; the major bulk of these tumors is intraabdominal. Liver metastases are common at diagnosis and relapse; other distant sites include lymph nodes, lung and bones. Interestingly, DSRCT has been documented as an incidental finding during a cesarean section. Another peculiar sign on presentation is known as a "Sister Mary Joseph nodule," which is an occasionally painful lump in the umbilicus secondary to metastatic cancer in this location
                             Diagnosis
Imaging studies are often suggestive but non-specific. Abdomen CT usually demonstrates bulky, heterogeneous masses located in the abdomen and pelvis with a peritoneal component
Once an intra-abdominal tumor is found, histologic diagnosis should be established .
Histologic examination shows small cells that can be round, ovoid or spindled usually grouped in clumps, cords, nests or sheets. These cells contain hyperchromatic nuclei with condensed chromatin and eosinophilic cytoplasm. Mitotic figures are common. The extensive collagenous stroma is characteristic, and desmoplasia (from the Greek desmos, "a band or felter" and plassein, "to form or to mold"), is a distinctive feature to this tumor.
A polyphenotypic pattern of immunohistochemical markers has been described. DSRCT express antigens related to different cell lineages, including:
1.   Epithelial: cytokeratin, epithelial membrane antigen.
2.   Mesenchymal: desmin (characteristic dot-like pattern), vimentin.
3.   Neural: neuron-specific enolase, synaptophysin.
Molecular Analysis
DSRCT seems to originate from an undifferentiated cell with multilineage potential.
The molecular hallmark of DSCRT is the EWS-WT1 reciprocal. This chimeric protein functions as an aberrant transcription factor involved in the pathogenesis of DSCRT. The EWS-WT1 translocation product plays a role in the regulation of the expression of several genes potentially involved with oncogenesis, including IGF-1 receptor, PDGFα, PAX2-2, WT-1, ENT4, TALLA-1 and IL-2/15Rβ ,CCN2 (connective tissue growth factor) has been shown to be highly expressed in DSRCT, and could have an autocrine or paracrine role in disease progression
Differential Diagnoses
Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for Ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.
Treatment
DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.
There is no standard protocol for the disease however, recent journals and studies have reported that some patients respond to high dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation Therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.
Although DSRCTs are generally sensitive to chemotherapy, the response is not enough to achieve cure since patients almost invariably relapse. This could potentially be a reflection of the heterogeneity of the cells within the tumor; where a distinct population of cells ("cancer stem cells") that are less sensitive to chemotherapy and radiotherapy possess the ability to self-renew and retain the capacity to regenerate the tumor bulk after it has been eradicated.
Prognosis
The prognosis for DSRCT remains poor.[8] The 5-year survival rate of DRSCT is only approximately 15%
Conclusion
In summary, DSRCT is a highly aggressive sarcoma with a dismal prognosis for which the ideal therapeutic modality is yet to be determined. Current therapeutic approaches remain highly toxic and have not achieved complete disease control. The development of molecularly targeted agents, likely in combination with conventional approaches, could potentially have significant impact on the treatment of this disease.