Desmoplastic small round cell tumor (ORPHA:83469)
An aggressive soft tissue cancer that typically arises in serous lined surfaces of the abdominal or pelvic peritoneum, and spreads to the omentum, lymph nodes and hematogenously disseminates especially to the liver. Extraserous primary location has been reported in exceptional cases.
Epidemiology
DSRCT is extremely rare. Only a few hundred cases have been reported worldwide since the first description in 1989. It usually affects males, during adolescence or young adulthood, with a male-to-female ratio of 4:1.
Clinical description
Clinical signs and symptoms of DSRCT are non-specific. DSRCT presents with abdominal pain, enlarged abdomen, dyspepsia, and/or vomiting and weight loss depending on the stage of the disease. Other signs can be observed such as a palpable abdominal mass, gastrointestinal occlusion, ascites, and hepatomegaly. Sometimes, DSRCT can arise from other primary sites such as the brain, thorax, lung, paratesticular region, ovaries and nasal cavity, without characteristic clinical signs.
Etiology
DSRCT seems to originate from the mesothelium. In almost all cases, a specific translocation t(11;22)(p13;q12) is found that juxtaposes the EWSR1 gene to the WT1 tumor suppressor gene. However, the underlying molecular mechanism remains unknown. Several other associated chromosomal translocations have been described (t(5;19), t(X;16) and t(4;10)).
Diagnostic methods
The diagnosis is difficult due to the rarity of the tumor and its similarities with other small round cell tumors. Diagnosis is based on clinical signs, endoscopic examination (laparoscopy) and/or imaging techniques (radiography, chest-abdominal-pelvic computed tomography (CAP-CT)). Biopsy of the mass shows nests of poorly differentiated small round cells with little cytoplasm and hyperchromatic nuclei that are surrounded by desmoplastic stroma. Cells can present an epithelial, mesenchymal, or neuronal differentiation. The diagnosis is confirmed by the presence of a polyphenotypic immunoprofile (tumor cells express several cytokeratins (KL1, AE1/AE3), desmin, and neuron-specific enolase), and by molecular identification (FISH, RT-PCR) of the EWSR1/WT1 translocation.
Differential diagnosis
Differential diagnoses include all the small round cells tumors: Ewing sarcoma and other peripheral neuroectodermal tumors (PNET), Wilms tumor, rhabdomyosarcoma and undifferentiated carcinoma (see these terms).
Management and treatment
Management is multidisciplinary and must be discussed by a panel of physicians in a specialized center. Up to 30% of DSRCT cases are misdiagnosed leading to incorrect management. There are currently no validated recommendations on clinical management and no cytotoxic agents have been granted a European Marketing Authorization (MA) in this indication. Some teams have proposed treatment based on aggressive multiagent chemotherapy (off-label use), followed by optimal cytoreductive surgery and abdominal radiotherapy. Prospective studies are underway to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC), maintenance chemotherapy and targeted therapy.
Prognosis
Prognosis is poor. Median overall survival is 17 months and less than 20% of patients live more than 5 years after diagnosis.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Gwenaël FERRON  - Pr François-Noël GILLY