Dsrct: Symptoms, Types, Causes and Treatment

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive cancer most often affecting adolescents and young adults. Despite advances in medicine, DSRCT remains challenging to diagnose and treat, with most patients facing a poor prognosis. By understanding the symptoms, types, causes, and treatment options for DSRCT, patients, families, and clinicians can make more informed decisions and advocate for improved care. This article synthesizes up-to-date research to provide a comprehensive overview of DSRCT.

Symptoms of Dsrct

Recognizing the symptoms of DSRCT is crucial, given its aggressive nature and tendency to present late. The tumor’s location often determines the initial symptoms, and many signs can be vague or overlap with other conditions. Early identification can lead to more timely interventions and potentially better outcomes.

Symptom	Description	Typical Presentation	Sources
Abdominal pain	Persistent or severe pain in abdomen	Most common, often sudden	3 4 9
Ascites	Accumulation of fluid in abdomen	Swelling, distension	3 4 9
Weight loss	Unintentional, sometimes rapid	Accompanies other symptoms	3
Chest pain	Pain in chest or pleural area	Especially with pleural DSRCT	2 5
Respiratory	Shortness of breath, cough	With lung or pleural tumors	2 5
Hypertension	High blood pressure	In rare paraneoplastic cases	1
Hypokalemia	Low potassium in blood	Accompanies hypertension	1

Table 1: Key Symptoms

Common Presenting Symptoms

Most DSRCT cases begin with vague, non-specific symptoms. Abdominal pain is the hallmark, often accompanied by a distended abdomen due to ascites or the sheer mass of tumor growth. Patients may report:

• Persistent or severe abdominal discomfort
• Visible or palpable abdominal swelling
• Nausea and vomiting, especially if the tumor presses on the gastrointestinal tract
• Unintentional weight loss over weeks or months 3 4 9

Respiratory and Chest Symptoms

When DSRCT arises in the chest, pleura, or lung, patients present with:

• Chest pain
• Shortness of breath
• Cough
• Pleural effusions (fluid around the lungs) 2 5

These cases are rare but highlight the tumor’s potential to appear outside the abdomen.

Paraneoplastic and Rare Presentations

In extremely rare scenarios, DSRCT may produce hormones or hormone-like substances, leading to paraneoplastic syndromes. One reported patient had severe hypertension and hypokalemia due to the tumor secreting renin, a hormone that regulates blood pressure 1. Such presentations can easily be mistaken for other diseases, complicating the diagnostic process.

Disease Progression Symptoms

As DSRCT advances, symptoms may include:

• Fatigue and weakness
• Evidence of metastasis (e.g., bone pain, lymph node swelling, supraclavicular adenopathy)
• In late stages, symptoms related to widespread disease, such as pleural effusions and respiratory compromise 9

Types of Dsrct

DSRCT is most commonly found in the abdomen but can manifest in various body regions, each with unique challenges. Understanding the types helps guide diagnosis and treatment.

Type	Primary Location	Notable Features	Sources
Abdominal	Peritoneum, omentum	Multiple peritoneal tumors	4 9
Pelvic	Pelvis, reproductive	Ovarian/testicular masses	3 4
Pleural/Thoracic	Pleura, lung	Chest pain, pleural effusion	2 5
Extra-abdominal	Pancreas, other sites	Rare, diagnostic challenge	4 5

Table 2: DSRCT Types and Locations

Abdominal and Pelvic DSRCT

The classic and most common form is intra-abdominal DSRCT, presenting as numerous tumor nodules scattered throughout the peritoneum. Often, a dominant large mass is found in the omentum, with additional conglomerates in the pelvis and right peritoneum 4 9. In females, DSRCT may involve the ovary and mimic gynecologic malignancies 3.

Pleural and Thoracic DSRCT

DSRCT can rarely originate in the pleura or lungs. These types present with:

• Chest pain
• Pleural effusion
• Respiratory complaints

This presentation is uncommon and can be mistaken for other pleural or pulmonary tumors 2 5.

Extra-abdominal DSRCT

There are exceptional reports of DSRCT originating in locations such as the pancreas 4. These cases are challenging to diagnose and often require advanced molecular testing to confirm the diagnosis.

Multiphenotypic Features

Regardless of location, DSRCT tumors consistently display nests of small round blue cells within a desmoplastic (fibrous) stroma and often show evidence of epithelial, mesenchymal, and neural differentiation on immunohistochemistry 3 4 5 9. This unique multiphenotypic pattern is a key diagnostic clue.

Causes of Dsrct

While the precise cause of DSRCT remains unclear, recent research has shed light on its genetic and cellular origins. Understanding these underlying factors guides both diagnosis and the development of new treatments.

Cause	Detail/Mechanism	Significance	Sources
Genetic translocation	t(11;22)(p13;q12) EWSR1-WT1 fusion	Diagnostic hallmark	4 8 10
Mesothelial origin	Thought to arise from mesothelium	Explains common sites	4 5 9
Molecular pathways	PDGF, VEGF, IGF-1, EGFR activation	Therapeutic targets	10
Unknown triggers	Environmental or stochastic factors	Largely speculative	9 10

Table 3: Key Causes and Mechanisms

Genetic Abnormalities

Virtually all DSRCT cases harbor a specific chromosomal translocation: t(11;22)(p13;q12), resulting in the fusion of the EWSR1 gene with the WT1 gene 4 8 10. This unique genetic event is both diagnostic and central to the tumor’s biology.

• The EWSR1-WT1 fusion protein acts as an abnormal transcription factor, driving the cancer’s aggressive behavior.
• Detection of this fusion via molecular testing (e.g., RT-PCR) is considered the gold standard for diagnosis 4 8.

Proposed Cell of Origin

DSRCT is believed to originate from mesothelial cells, explaining its predilection for the peritoneum, pleura, and other serosal surfaces 4 5 9. However, the precise tissue of origin remains uncertain. Rare cases in organs like the pancreas support the theory that DSRCT can arise wherever mesothelial tissue or its derivatives exist 4.

Molecular and Cellular Pathways

The EWSR1-WT1 fusion triggers a cascade of molecular events, activating several signaling pathways important for tumor growth and survival:

• Platelet-derived growth factor (PDGF)
• Vascular endothelial growth factor (VEGF)
• Insulin-like growth factor (IGF-1)
• Epidermal growth factor receptor (EGFR)
• Androgen receptor, c-KIT, MET, and TGF-beta pathways

These pathways are under investigation as potential drug targets 10.

Non-genetic and Environmental Factors

There is currently no strong evidence linking DSRCT to environmental exposures, inherited syndromes, or lifestyle factors. Its occurrence appears sporadic, with a strong male predominance and peak incidence in young males 4 9 10.

Treatment of Dsrct

Treating DSRCT is complex and requires a coordinated, multidisciplinary approach. While survival has improved with aggressive therapy, most patients still face a guarded prognosis. Research into new treatments and targeted therapies offers hope for the future.

Treatment	Key Elements	Outcomes/Challenges	Sources
Chemotherapy	ES-based, multi-agent regimens	Essential, improves survival	3 4 8 9 10
Cytoreductive surgery	Complete tumor resection	Improves survival, rarely curative	6 7 8 9
HIPEC (intraperitoneal chemo)	Heated chemo after surgery	May increase survival, for selected cases	6 7 8
Radiation therapy	Whole abdominal or targeted	Adjunct, unclear impact	8
Targeted therapies	Multikinase/other inhibitors	Under investigation	10
Palliative/supportive	Symptom control	Important for advanced cases	3 4 9

Table 4: Main DSRCT Treatments

Chemotherapy

High-dose, multi-agent chemotherapy is the cornerstone of DSRCT treatment. Regimens are typically modeled after Ewing sarcoma protocols, such as:

• VAC/IE: Vincristine, doxorubicin (adriamycin), cyclophosphamide, ifosfamide, etoposide 1 3 4 8 9
• P6 protocol: An intensive combination used in some centers 3

Chemotherapy can shrink tumors, improve resectability, and prolong survival. However, side effects are significant, and not all patients respond. Chemotherapy alone is rarely curative 3 4 8.

Cytoreductive Surgery

Complete cytoreductive surgery (CCS)—the removal of all visible tumor—is a critical component of therapy. Studies show that patients who undergo CCS have significantly better survival than those with incomplete surgery or inoperable disease 7 8 9. Despite aggressive surgery, microscopic disease frequently remains, contributing to high recurrence rates.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

HIPEC involves circulating heated chemotherapy drugs within the abdominal cavity after tumor removal. Recent studies suggest that HIPEC may:

• Improve disease-free and overall survival for selected patients with limited peritoneal disease 6 7 8
• Reduce peritoneal recurrence, especially when there are no liver or portal metastases 7
• Carry risks, including renal insufficiency and gastroparesis, but is generally safe in experienced hands 6

HIPEC is generally reserved for patients with disease confined to the abdomen and who achieve complete cytoreduction 6 7 8.

Radiation Therapy

Whole abdominal radiation therapy (WART) or targeted radiotherapy may be used as adjuncts to surgery and chemotherapy. The benefit of radiation remains unclear, and its use is often limited by toxicity concerns 8.

Targeted and Novel Therapies

Given DSRCT’s unique molecular profile, targeted therapies are an active area of research. Potential agents include:

• Multityrosine kinase inhibitors (e.g., pazopanib, imatinib, sorafenib)
• mTOR inhibitors
• Agents targeting the PDGF, VEGF, and IGF-1 pathways 10

To date, these therapies have yet to demonstrate consistent, long-term benefit, but clinical trials are ongoing 10.

Palliative and Supportive Care

For patients with advanced, refractory, or relapsed disease, palliative care is essential for symptom management and quality of life. Supportive interventions may include:

• Pain management
• Nutritional support
• Management of ascites or pleural effusions
• Psychological and social support 3 4 9

Conclusion

DSRCT is a rare but devastating cancer, mainly affecting adolescents and young adults. Despite its aggressive nature, multidisciplinary care has led to incremental improvements in survival, particularly for those who can undergo complete tumor removal and intensive chemotherapy. Ongoing research into targeted therapies and improved supportive care is critical for future progress.

Key Points Covered:

• DSRCT typically presents with abdominal pain, ascites, weight loss, and, less commonly, chest or paraneoplastic symptoms.
• Most cases are abdominal, but DSRCT can arise in the pelvis, pleura, or rarely in organs like the pancreas.
• The hallmark cause is a specific chromosomal translocation (EWSR1-WT1 fusion), with tumor origin likely from mesothelial cells.
• Treatment is multimodal: chemotherapy, complete cytoreductive surgery, and, in some cases, HIPEC and radiation.
• Targeted therapies are being explored but are not yet standard of care.
• Early diagnosis, individualized treatment plans, and supportive care remain essential for optimizing outcomes.