Pediatric Desmoplastic Small Round Cell Tumor - Clinical Features, Diagnosis, and Management

Introduction

Desmoplastic small round cell tumor (DSRCT) is a rare cancer that primarily affects young individuals between 10 and 15 years, and males are mostly affected. It is most commonly observed in the pelvic and abdominal regions. DSRCT falls under soft tissue sarcomas, cancer originating in soft tissues such as tendons, muscles, lymph nodes, blood vessels, nerves, and fat. Individuals afflicted by this condition typically present with an intra-abdominal mass accompanied by scattered small tumor deposits throughout the peritoneal cavity. Furthermore, lung, liver, bone, or spleen metastases often occur. Unfortunately, the overall survival rate for DSRCT is low.

What Is Pediatric Desmoplastic Small Round Cell Tumor?

Desmoplastic small round cell tumor is a type of cancer that develops in the soft tissues and belongs to the category of soft tissue sarcomas. They exhibit aggressive behavior. These cancers are characterized by the presence of small, round cancer cells that are surrounded by fibrous tissue known as desmoplasia.

What Are the Clinical Features of Pediatric DSRCT?

The clinical features of pediatric desmoplastic small round cell tumors include:

• Abdominal symptoms such as abdominal discomfort. Abdominal distension and pain.
• A palpable abdominal mass can be detected during physical examination.
• Due to the size and location of the tumor, changes in bowel and urinary habits may occur, such as diarrhea, constipation, urgency, or increased frequency of urination.
• Unexplained weight loss and enlarged lymph nodes.
• General weakness and fever.
• In advanced stages, the tumor can metastasize to other areas, leading to symptoms related to the metastasized area.

What Are the Genetic Changes Noted in Pediatric DSRCT?

Pediatric desmoplastic small round cell tumor is linked to an abnormality in the gene known as the EWS-WT1 (Ewing's sarcoma breakpoint region 1 - Wilms tumor 1) fusion gene, which arises due to chromosomal translocation. In this genetic anomaly, there is a rearrangement of genetic material between the EWS and WT1 genes. The EWS gene on chromosome 22 becomes fused with the WT1 gene on chromosome 11. This fusion leads to the production of a fusion protein that drives the progression of DSRCT. However, other genetic alterations can also be associated with this cancer.

What Is the Diagnosis of Pediatric DSRCT?

The diagnosis of pediatric DSRCT includes:

• Clinical Evaluation: This includes the patient's medical history, symptoms, and physical examination, which also encompasses the presence of an abdominal mass.

• Imaging Studies: This category covers ultrasound, CT (computed tomography), and MRI (magnetic resonance imaging) scans. These imaging techniques aid in visualizing the tumor, and its cross-sectional images help assess its location and relationship with neighboring tissues. PET (positron emission tomography) scans are utilized to evaluate the tumor's metabolic activity and identify areas of metastases. The liver is the most common site of metastasis. Other common locations include the lungs, mediastinum, and pleura. Imaging might reveal lesions spread throughout the peritoneal cavity or a 'sheet' of sarcomatosis, indicating widespread distribution of tumor deposits.

• Biopsy: This procedure involves removing tissue for further examination under a microscope.

• Histopathology: These tumors are characterized by nests of small round cells separated by desmoplastic stroma, which is fibrous. Additionally, immunohistochemical staining can assist in further diagnosing these tumors. The tumor is positive for desmin (a mesenchymal marker), cytokeratin (an epithelial marker), and S100 (a neural marker).

• Genetic Testing: This includes the detection of EWSR1-WT1 rearrangement, along with a specific staining technique called selective WT1 carboxy-terminus immunoreactivity. This staining detects the presence of a specific protein called WT1, located in the carboxy terminus or C-terminus. This testing is one of the most significant diagnostic tools for detecting DSRCT.

What Is the Management of Pediatric DSRCT?

Due to the rarity of the cancer, there are no standard protocols for its management. Some treatment options include:

• Surgery: In cases where multiple tumor growths, known as abdominal sarcomatosis, are present with sizes ranging from 0.039 inches to 15.7 inches, and patients exhibit spread to various areas such as the spleen, diaphragm, abdominal wall, peritoneum, pelvis, and small bowel mesentery, peritonectomy (removal of cancer cells from the peritoneal cavity) are preferred. However, generally, DSRCT is more responsive to chemotherapy. Therefore, surgical treatment should not be initiated within four to six months of chemotherapy. Surgical reduction, cytoreduction, and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved outcomes.

• Chemotherapy: Chemotherapy helps decrease the vascularity of the tumor and is effective against malignant ascites, a condition where fluid in the peritoneal cavity increases due to cancer. Ewing's type of chemotherapy demonstrates higher efficacy, using alkylating agents such as Ifosfamide or Cyclophosphamide along with Doxorubicin and Vincristine. This chemotherapy, surgical resection, and post-operative whole abdominal radiation have improved outcomes. Another approach involving Vincristine, Ifosfamide, and Etoposide, followed by aggressive surgical resection and 30 grays of radiotherapy to the whole abdomen, along with Irinotecan and Temozolomide for a total of twelve cycles, has demonstrated further improved outcomes.

• Radiation Therapy: A specialized technique called intensity-modulated radiation therapy (IMRT) delivers a targeted dose to cancerous tumors while minimizing exposure to healthy cells. This technique is more effective and associated with fewer side effects.

• Hyperthermic Intraperitoneal Chemotherapy (HIPEC): HIPEC is a specialized treatment involving cytoreductive surgery, which removes visible tumors as much as possible. Then, a heated solution containing chemotherapy drugs is delivered into the peritoneal cavity. The temperature is elevated from 105.8 to 109.4 degrees Fahrenheit, enhancing drug penetration. This solution circulates in the peritoneal cavity for about one to two hours. After treatment, the solution is drained, and incisions are sutured. This treatment has improved outcomes.

• Intraperitoneal Antibody Instillation: This innovative approach involves delivering antibodies into the peritoneal cavity, allowing immune system-produced proteins to target specific cells. This targeted approach aims to eliminate cancer cells.

Conclusion

Desmoplastic small round cell tumor is a rare and aggressive tumor that primarily affects males in their young adulthood or adolescence. The core treatment modalities encompass chemotherapy, surgical resection, and radiation therapy. Emerging techniques like HIPEC have enhanced survival rates, yet ongoing research explores novel approaches. The overall prognosis for this cancer remains notably grim, with a mere five-year survival rate.