Desmoplastic small round cell tumour is a rare and aggressive type of cancer that typically develops in the abdomen, predominantly affecting young males between the ages of 10 and 30.

Understanding Desmoplastic Small Round Cell Tumours

Desmoplastic small round cell tumour, often shortened to DSRCT, represents one of the rarest forms of cancer known to medical science. This condition belongs to a broader category called soft tissue sarcomas, which are cancers that begin in the tissues that connect, support, and surround other body structures. In the case of DSRCT, these include fat, muscles, tendons, lymph and blood vessels, and nerves.^[1]

The tumours characteristically develop in the peritoneum, which is the thin membrane lining the inside of the abdomen and pelvis. Rather than appearing as a single growth, DSRCT usually manifests as multiple tumours spread throughout the abdominal cavity. In some cases, dozens or even hundreds of tumour nodules may be present at the time of diagnosis. Often, there is one very large dominant mass in the omentum, with additional large clusters of tumours in the pelvis and right side of the abdomen.^[9]

These fast-growing tumours can quickly spread to other nearby organs, including the bladder, colon, and liver. In more than 40 percent of patients, the cancer may also spread beyond the abdomen to more distant sites such as the lymph nodes, lungs, bones, and other parts of the body.^[6]

Epidemiology

DSRCT stands as an exceptionally rare condition. Since researchers first identified and described this cancer in 1989, only approximately 200 cases have been recorded worldwide according to some reports.^[1] The condition affects about 1 in 1 billion people globally, making it one of the rarest cancers encountered in medical practice.^[3]

The disease shows a striking pattern in who it affects. DSRCT occurs most often in young white males between the ages of 10 and 30 years.^[1] Some sources indicate that males between ages 20 and 30 are particularly vulnerable, though the condition can occur at any age.^[3] The median age at diagnosis is 23 years old.^[8]

In England, an average of 12 cases of DSRCT are diagnosed every year, further highlighting how uncommon this cancer truly is.^[8] The overwhelming majority of patients—approximately 90 percent—are Caucasian males.^[6] While the disease can affect anyone regardless of gender or ethnicity, it remains much more common in males than females.^[8]

Causes

The exact causes of desmoplastic small round cell tumour remain unclear to researchers and doctors. What is known is that cancer begins when a cell develops changes in its DNA, which contains all the instructions that tell a cell what to do. These changes tell the cell to multiply quickly, creating a clump of cancer cells called a tumour. The cancer cells can then invade and destroy healthy body tissue and eventually break away and spread to other parts of the body.^[2]

Scientists have discovered that DSRCT happens when changes occur in certain chromosomes—the structures in cells that contain all genes. Specifically, chromosomes can break apart and rejoin together in the wrong way, causing cells to not function as they should. In DSRCT, this chromosomal rearrangement creates an abnormal gene known as EWS-WT1.^[3]

This abnormal gene results from a specific translocation, which is when pieces of two different chromosomes swap places. In DSRCT, a gene called EWS (Ewing sarcoma gene) on chromosome 22 wrongly joins with a region called WT1 (Wilms tumour gene) on chromosome 11. This creates a fusion gene expressed as t(11;22)(p13;q12).^[10] This fusion is considered a defining molecular feature of DSRCT and plays a crucial role in the disease’s development.^[10]

The EWS-WT1 fusion protein functions as an oncogenic transcription factor, meaning it can turn certain genes on or off in ways that promote cancer growth. The zinc finger domain of WT1 interacts with certain promoter regions, influencing the expression of various downstream proteins such as PDGFA, PAX2, insulin-like growth factor 1 receptor, and epidermal growth factor receptor.^[10]

Importantly, researchers do not yet understand what triggers these chromosomal changes in the first place. The condition does not appear to be inherited, and because there are so few people with DSRCT, doctors cannot determine whether it runs in families.^[1]

Risk Factors

Healthcare professionals have not identified many clear risk factors for developing desmoplastic small round cell tumours. Unlike some cancers where lifestyle choices, environmental exposures, or family history play a significant role, DSRCT appears to develop without obvious external triggers.^[23]

The most consistent demographic pattern is that being a young male appears to increase risk. The disease predominantly affects males over females, and typically strikes during adolescence and young adulthood. However, this is more of an observation about who gets the disease rather than a modifiable risk factor that individuals can control.^[1]

The cancer affects people who are otherwise healthy. There is no evidence linking it to smoking, diet, physical activity levels, or other lifestyle factors that influence risk for more common cancers. Similarly, there is no known connection to environmental toxins, radiation exposure, or occupational hazards.^[6]

Scientists believe a genetic abnormality involving chromosomes 11 and 22 may play a part in this cancer, but this chromosomal change appears to occur randomly rather than being inherited from parents.^[6] Because the genetic changes happen within individual cells rather than being passed down through families, having a family member with DSRCT does not appear to increase risk for other family members.

Symptoms

One of the challenges with desmoplastic small round cell tumour is that many people do not develop symptoms when the cancer first starts. The tumours can grow to a substantial size before a person notices anything wrong. This delay in symptom onset often means the cancer is already advanced by the time it is discovered.^[1]

Patients may not develop symptoms until tumours become large enough to affect the abdomen and digestive system. The main symptom of DSRCT is often a solid mass or hard lump in the abdomen. This lump can grow very quickly and is often painful to the touch.^[6][8]

As the disease progresses, common symptoms include abdominal pain, which can range from mild discomfort to severe cramping. The abdomen may become noticeably swollen or distended, sometimes to the point where clothes no longer fit properly. This swelling can also cause visible changes to the belly’s appearance.^[2][3]

Digestive symptoms are frequent and troublesome. Patients may experience persistent nausea and vomiting that interferes with normal eating. Changes in bowel habits are common, including both constipation and diarrhoea. Some individuals find it difficult to urinate normally due to pressure from abdominal tumours.^[1][3]

Unexplained weight loss often occurs, partly due to the cancer itself and partly because digestive symptoms make it difficult to eat normally. Some patients experience persistent fatigue that does not improve with rest. A painful lump may appear in or around the belly button area.^[3][6]

Despite the often overwhelming number of abdominal tumours present at diagnosis, symptoms of bowel obstruction are surprisingly rare. Some patients may have fluid accumulation in the abdomen, called ascites. In later stages of the disease, patients may develop pleural effusions (fluid around the lungs), pleural implants, enlarged lymph nodes in the mediastinum (chest area) or above the collarbone, or bone metastases.^[9]

Many of these symptoms—such as constipation, diarrhoea, nausea, and vomiting—are common complaints that happen for many different reasons and may not indicate serious illness. However, if these symptoms persist, worsen, or last for more than a few days, it is important to consult a healthcare provider for evaluation.^[3]

Prevention

Given the rarity of desmoplastic small round cell tumour and the lack of understanding about what causes it, there are currently no established prevention strategies. Unlike some cancers where lifestyle modifications such as avoiding tobacco, maintaining a healthy weight, or limiting alcohol consumption can reduce risk, DSRCT does not appear to be linked to any modifiable behaviours or exposures.

Because the genetic changes that lead to DSRCT occur spontaneously within cells rather than being inherited, there are no screening programmes available for individuals or families. The chromosomal translocation that causes the disease appears to happen randomly, without clear triggers that could be avoided.

The best approach for individuals, particularly young males in the typical age range, is to be aware of persistent or unusual symptoms and to seek medical attention promptly if concerning signs develop. Early medical consultation when symptoms such as persistent abdominal pain, unexplained swelling, or a palpable mass occur may help with earlier diagnosis, though this does not constitute true prevention.

Healthcare providers emphasize the importance of seeking medical evaluation for any persistent signs and symptoms that cause concern, particularly those that worsen over time or do not resolve on their own. While most cases of abdominal pain or digestive issues are not caused by cancer, persistent symptoms warrant proper medical investigation.^[2]

Pathophysiology

The pathophysiology of desmoplastic small round cell tumour involves complex changes at the cellular and molecular level that transform normal cells into aggressive cancer cells. Understanding these changes helps explain why DSRCT behaves the way it does and guides treatment approaches.

At the microscopic level, DSRCT has a distinctive appearance that pathologists recognize. The tumour consists of nests or clusters of small, round, undifferentiated cells separated by abundant desmoplastic stroma, which is dense fibrous connective tissue. This characteristic pattern of small round blue cells surrounded by fibrous tissue gives the tumour its name.^[9][10]

One of the unique features of DSRCT is its multi-phenotypic differentiation, meaning the tumour cells show characteristics of multiple different cell types. When pathologists perform immunohistochemical staining—special tests that identify specific proteins in tissue samples—DSRCT cells stain positive for markers from different cell lineages. They show mesenchymal markers (like desmin), epithelial markers (like cytokeratin), and neural markers (like S100). This unusual combination of markers is highly characteristic of DSRCT and helps distinguish it from other similar tumours.^[9]

The defining molecular feature of DSRCT is the EWS-WT1 fusion gene created by the chromosomal translocation. This fusion protein acts as a powerful transcription factor, meaning it can turn certain genes on or off in ways that promote cancer development. The EWS portion of the fusion protein provides a strong transcriptional activation domain, while the WT1 portion provides DNA-binding capability through its zinc finger domains.^[10]

The fusion protein influences the expression of various downstream genes involved in cell growth, survival, and differentiation. For example, it affects genes encoding platelet-derived growth factor A (PDGFA), PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, and others. These proteins promote cell proliferation, inhibit programmed cell death, and support tumour growth and spread.^[10]

The specific organ or tissue type from which DSRCT originates has yet to be identified, which is unusual for a cancer. What is known is that these tumours have mesenchymal cell origin, meaning they arise from cells that give rise to connective tissue.^[9]

DSRCT rarely arises as a single tumour. In most cases, dozens to hundreds of abdominal peritoneal tumours are present at diagnosis. The cancer cells have a strong tendency to seed throughout the peritoneal cavity—the space inside the abdomen—creating multiple tumour deposits. This pattern of spread is similar to how some ovarian cancers behave and presents significant treatment challenges.^[9]

The tumours are highly aggressive and grow rapidly. They have a propensity for local invasion, growing into nearby organs and structures. They also readily spread to distant sites through the lymphatic system and bloodstream, with common sites of metastasis including lymph nodes, lungs, liver, and bones.

If the EWS-WT1 fusion protein cannot be identified in the tissue through molecular testing, the diagnosis of DSRCT cannot be definitively made. This fusion is so characteristic of the disease that it serves as the gold standard for diagnosis.^[9]