What is DSRTC?
Desmoplastic small-round-cell tumor (DSRTC) is a very aggressive form of cancer that is classified as a soft tissue sarcoma. In general, sarcomas are cancers in bones, muscles, and connective tissue throughout the body. DSRTC is a rare malignant neoplasm that occurs primarily in adolescents and young adults. The most common symptoms include pain or a mass in the abdomen. Only 300 cases have been reported throughout the world, although this number is likely to continue increasing with time. Histologic diagnosis is difficult, given its rarity, and the disease is often recognized too late.
Masses are usually found in the abdomen, often affecting the perioneum (the serous membrane that forms the lining of the abdominal cavity) and the abdominal lymph nodes. Other areas affected may include the testicles, ovaries, diaphragm, spleen, liver, chest wall, skull, spinal cord, bladder, brain, lungs testicles, ovaries, and the pelvis. Reported sites of metastastic spread include the liver, lungs, lymph nodes, brain, skull, and bones.
What are the causes?
There are no known risk factors that have been identified as specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood 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 cell tumors.
DSRCT is associated with a unique chromosomal translocation t(11;22)(p13:q12) resulting in an EWS/WT1 transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.
The EWS/WT1 translocation product targets ENT4.[7] ENT4 is also known as PMAT.
Clinical 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. 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. More than 40% of patients have distant metastases at the time of diagnosis, mostly located in the liver, lungs, and lymph nodes
Diagnosis
DSRCTs often reach considerable size in the abdominal cavity prior to diagnosis: a mean size of 10 cm has been described. Macroscopically, they are solid, firm, multilobulated gray-white masses where cystic areas can also be found. Tissue sampling via open or needle core biopsies is the method most consistently described; however, the use of cytology-based diagnosis performed on fine needle aspiration samples as well as ascitic and pleural fluid is an attractive alternative. The correct diagnosis of DSRCT on fine needle aspiration specimens is challenging and requires expertise in the utilization of ancillary techniques such as immunocytochemistry and flow-cytometric immunophenotyping.
Imaging studies are often suggestive but non-specific. Abdominal ultrasounds, CAT scans, MRIs, chest X-rays, or bone scans may be performed. Further exams may also be necessary to localize the disease.
Treatment
DSRCT is a very aggressive neoplasm with a 5-year survival of less than 15%. Treatment options include surgery, radiotherapy, chemotherapy with or without stem cell transplantation, and recently introduced molecularly targeted therapies. Unfortunately there is no standard therapeutic regimen described since no modality is clearly superior to any other. Surgery is usually extensive and often includes excision of the omentum, splenectomy and lymph node resections. Due to the invasive nature of this tumor, complete resection with negative margins is usually not possible. Debulking surgery has been described as an attempt to eliminate 90% of the tumor bulk.
In addition to surgery and radiation therapy, local control options for DSRCT (particularly metastatic disease) include radiofrequency ablation, gammaknife, cryoablation, embolization and chemoembolization. These are usually performed in academic centers after careful consideration of individual cases.
Research
Current research aims to improve the results of treatment through identifying patient prognostic characteristics and studying more effective drugs.
The biological properties of the tumor cells are also being studied in hopes of finding new treatment options to stop their growth. At the Ospedale Bambino Gesu’ in Rome, Doctor Giuseppe Milano has been working specifically in this rare field of pediatric oncology. His aim is to evaluate if the desmoplastic tumor cells have an indicator that could help the body’s immune system (adequately equipped with the proper genetic engineering) identify, attack, and destroy them.
In addition, he is conducting a national study and analysis on the number of cases of this disease at the AIEOP (Associazione Italiana di Ematologia ed Oncologia Pediatrica).
A summary of his project, compiled by Dr. Milano himself and his colleagues at the OBG laboratories of San Paolo, has been published in a medical journal. You can access this document using the link below.
