Rhabdoid tumour of the kidney is an exceptionally rare and aggressive childhood cancer that primarily strikes infants and toddlers, often before they reach their second birthday. Despite its rarity, understanding this disease is crucial for families facing this devastating diagnosis.

Epidemiology

Rhabdoid tumour of the kidney represents one of the rarest forms of childhood cancer. According to medical estimates, this disease affects fewer than one person per million in the general population, making it extraordinarily uncommon.^[1] In children specifically, rhabdoid tumours account for only 0.9 to 2 percent of all kidney tumours, highlighting just how unusual this cancer truly is.^[5]

The disease shows a very distinct pattern regarding age. Rhabdoid tumours mainly affect babies and very young children, with the highest occurrence observed in infants between 11 and 18 months old.^[1] The average age at diagnosis is approximately 15 months.^[2] The peak incidence spans from one to four years of age, though the disease can occasionally affect older children and even adults in extremely rare circumstances.^[4]

In the United States, approximately 20 to 25 new cases of malignant rhabdoid tumours are diagnosed each year across the entire country.^[2] This incredibly small number reflects the extreme rarity of the condition. The United Kingdom registry has estimated an age-standardized annual incidence of extra-central nervous system rhabdoid tumour at about one case per two million children, though this figure might actually underestimate the true occurrence.^[7]

Rhabdoid tumours can occur in different locations throughout the body. When specifically affecting the kidneys, they are called rhabdoid tumours of the kidney. These tumours can also develop in other soft tissues such as the liver, lungs, and skin, or in the central nervous system including the brain and spinal cord.^[1] Among infants under one year of age, rhabdoid tumours may account for roughly 20 percent of all kidney cancers and 15 percent of soft tissue tumours, making them proportionally more significant in this very young age group.^[7]

Causes

The root cause of rhabdoid tumour of the kidney lies in genetic changes that occur within cells. Most cases result from a mutation in a gene called SMARCB1, which is also known by other names including INI1, SNF5, and BAF47.^[1] This gene plays an essential role in protecting the body from cancer development. Understanding how this gene works helps explain why these tumours form.

The SMARCB1 gene is what scientists call a tumour suppressor gene, meaning it produces proteins that help control how cells grow and divide. When this gene functions normally, it acts like a brake system that prevents cells from growing out of control. However, when the SMARCB1 gene becomes mutated or damaged, it loses its ability to regulate cell growth properly. This loss of control allows tumour cells to multiply rapidly and aggressively.^[1]

In nearly all rhabdoid tumours, including those affecting the kidney, the SMARCB1 gene is turned off or mutated.^[2] Less commonly, mutations in another tumour suppressor gene called SMARCA4 can cause rhabdoid tumours, though this occurs rarely.^[1]

Research has shown that the current understanding suggests rhabdoid tumours are driven by epigenetic dysregulation rather than problems with a specific biological pathway.^[4] Epigenetic changes affect how genes are turned on or off without altering the DNA sequence itself. The SMARCB1 gene is part of a larger complex that helps remodel chromatin, the structure that packages DNA inside cells. When this remodeling process goes wrong, it can lead to cancer development.

There is no clear environmental cause or lifestyle factor that has been identified as contributing to rhabdoid tumour development. The disease does not appear to result from anything parents did or did not do during pregnancy or child-rearing. The genetic mutations that cause these tumours happen at the cellular level for reasons that remain incompletely understood by medical science.

Risk Factors

Unlike many other cancers, rhabdoid tumour of the kidney does not have typical risk factors related to lifestyle, diet, or environmental exposures. The primary known risk factor is genetic, specifically related to mutations in the SMARCB1 or SMARCA4 genes.

The most significant risk factor is having an inherited mutation in the SMARCB1 gene. While the majority of rhabdoid tumours occur in children with no family history of the condition due to spontaneous new mutations, some children are born with an inherited gene change passed down from a parent.^[1] When a child inherits this mutation, they have a condition sometimes called rhabdoid predisposition syndrome, which increases their risk of developing these tumours.

Children with germline mutations (mutations present in all cells of the body from birth) affecting the SMARCB1 gene are predisposed to developing rhabdoid tumours. These same mutations also increase the risk of developing another genetic condition called schwannomatosis, which involves the growth of noncancerous tumours on nerves.^[4]

Children who are born with or develop one rhabdoid tumour may be at increased risk of developing additional tumours in different locations. Children in their first year of life may sometimes present with more than one primary rhabdoid tumour simultaneously, which is consistent with a genetic predisposition to cancer.^[4] These infants typically develop tumours in multiple sites, such as both the central nervous system and the kidney, or in the brain along with the liver or lung.

Very young age, particularly being under three years old and especially between 11 and 18 months, represents a demographic risk factor simply because the disease occurs most frequently during this developmental period.^[1] However, this should not be confused with a modifiable risk factor, as age itself cannot be changed.

Importantly, rhabdoid tumours do not run in families in the traditional sense for most cases. The condition typically does not show a hereditary pattern, and most families have no prior history of the disease.^[1] When genetic changes do occur, they happen spontaneously during cell development rather than being passed down through generations.

As part of medical care, children diagnosed with rhabdoid tumours may undergo genetic evaluation to determine whether they carry a germline mutation. This testing helps doctors understand the likelihood of the child developing additional tumours and whether the mutation could potentially affect other family members or be passed to future children.^[1]

Symptoms

The symptoms of rhabdoid tumour of the kidney vary depending on the child’s age and where the tumour is located within the body. Because these tumours grow and spread very rapidly, symptoms often develop quickly and worsen over a period of just days or weeks. This fast progression makes it particularly important for parents and caregivers to seek medical attention promptly when concerning signs appear.^[1]

For tumours located in the kidney, one of the most common first signs is the discovery of a lump or mass in the child’s abdomen. Parents or doctors may feel this mass during routine examination or when touching the child’s belly area.^[2] The presence of an abdominal mass often prompts further medical investigation. Because rhabdoid tumours most frequently affect infants, recognizing symptoms can be challenging since very young children cannot verbally communicate their discomfort. The child may appear fussy or irritable, but they might not show obvious signs of pain beyond general crankiness, potentially making early diagnosis difficult.^[2]

Blood in the urine, medically called hematuria, is another symptom that may occur.^[1] Parents might notice that their child’s urine appears pink, red, or cola-colored. Some children may also experience difficulty urinating or show signs of discomfort when trying to pass urine.^[2] These urinary symptoms occur because the growing tumour affects kidney function and the urinary tract system.

General symptoms that affect the whole body are also common. Many children with rhabdoid tumours develop fever that may come and go or persist.^[1] The child may experience nausea and vomiting, particularly if the tumour is putting pressure on surrounding organs or affecting normal bodily functions. A decreased appetite is frequently observed, with the child showing less interest in eating than usual. This can lead to noticeable weight loss over time.^[1]

Symptoms related to where the tumour grows and how it affects nearby structures include abdominal pain and swelling of the abdomen, which may become visibly distended.^[5] In some cases, parents notice that their infant or toddler appears more tired than normal, displaying unusual sleepiness or lethargy.^[1] The child may also develop swollen lymph nodes, which are small glands that can be felt under the skin in areas like the neck, armpits, or groin.^[1]

If the tumour has spread to other parts of the body, additional symptoms may appear depending on which organs are affected. Respiratory issues such as difficulty breathing may occur if the tumour has spread to the lungs.^[1] Some children develop headaches, particularly if there is involvement of the nervous system. Loss of balance or trouble walking can indicate that the tumour has affected areas of the brain that control movement and coordination.^[1]

In infants, an increase in head size may be noticeable if the tumour or related complications cause fluid buildup in the brain.^[1] Other neurological symptoms might include nerve paralysis, affecting the child’s ability to move certain parts of their body normally. Some children may experience high blood pressure as a consequence of kidney involvement.^[7]

A case report described a three-month-old infant who presented with fever, diarrhea, and abdominal distension. Upon examination, the infant appeared dehydrated and lethargic, and doctors could feel a palpable mass in the right side of the abdomen.^[5] This example illustrates how symptoms can initially seem like common childhood illnesses, making diagnosis challenging without proper medical investigation.

Prevention

Currently, there are no known methods to prevent rhabdoid tumour of the kidney from developing. Because the disease results from genetic mutations that occur either spontaneously or are inherited, there are no lifestyle changes, dietary modifications, or environmental precautions that can reduce the risk of these tumours forming.

Unlike some other cancers that can be prevented through avoiding certain risk factors like tobacco use, sun exposure, or dietary habits, rhabdoid tumours arise from genetic changes at the cellular level that are beyond anyone’s control. Parents should understand that nothing they did or failed to do caused their child’s tumour to develop. There are no known preventable causes or risk factors that could have been avoided.

For families with a known history of SMARCB1 gene mutations or for children who have been diagnosed with one rhabdoid tumour, genetic counseling becomes an important consideration rather than a prevention strategy. Genetic counseling involves meeting with specially trained healthcare professionals who can help families understand the genetic aspects of the disease, assess the risk of additional tumours developing, and discuss implications for other family members and future children.^[1]

Children who carry germline SMARCB1 mutations have an increased risk of developing multiple rhabdoid tumours. For these children, regular medical surveillance becomes important for early detection rather than prevention. Brain and spine imaging studies should always be performed when a child is newly diagnosed with a kidney or other soft tissue rhabdoid tumour to check for tumours in the central nervous system.^[4] Similarly, imaging to check for kidney tumours is recommended for children diagnosed with brain rhabdoid tumours.

Because rhabdoid tumours spread rapidly and can be fatal if not treated promptly, early detection through awareness of symptoms is crucial. Parents and caregivers should seek immediate medical attention if they notice any concerning signs such as an abdominal mass, blood in the urine, persistent fever, unexplained weight loss, or other worrying symptoms in their infant or young child. While this does not prevent the tumour from forming, early detection allows for prompt treatment, which is essential for the best possible outcome.

There are no screening tests recommended for the general population to detect rhabdoid tumours before symptoms appear, as the disease is extremely rare. Even for families with known genetic mutations, routine screening protocols are not well established due to the rarity of the condition. Medical management focuses primarily on prompt diagnosis and aggressive treatment once symptoms appear rather than preventive screening.

Pathophysiology

Understanding the pathophysiology of rhabdoid tumour of the kidney means exploring how the normal processes of cell growth and division become disrupted, leading to aggressive cancer development. The story begins at the molecular level with genes that normally protect the body from uncontrolled cell growth.

In healthy tissues, the SMARCB1 gene produces a protein that forms part of a larger molecular machine called the SWI/SNF chromatin-remodeling complex.^[4] This complex plays a critical role in controlling which genes are turned on or off in cells. Think of chromatin as tightly wound packaging material that wraps around DNA. The SWI/SNF complex acts like a molecular tool that can loosen or tighten this packaging, making certain genes more or less accessible for activation. This remodeling process is essential for normal cell development, growth, and specialization.

When the SMARCB1 gene functions properly, it works as a tumour suppressor, meaning its protein product helps prevent cells from becoming cancerous. The protein made by this gene helps control cell growth by regulating the expression of many other genes involved in cell division and survival. In rhabdoid tumours, this gene becomes inactivated through mutation, deletion, or other mechanisms.^[4]

In the vast majority of rhabdoid tumours, the SMARCB1 gene is not functioning—it has been “turned off.”^[2] When both copies of this gene become inactivated (since humans have two copies of most genes, one from each parent), the protective brake on cell growth is removed. Without functional SMARCB1 protein, the chromatin remodeling complex cannot work properly, leading to widespread disruption of normal gene expression patterns throughout the cell.

The current scientific hypothesis suggests that rhabdoid tumours are driven primarily by epigenetic dysregulation rather than the alteration of a specific biological signaling pathway.^[4] Epigenetic changes affect how genes are expressed without changing the actual DNA sequence. When the SWI/SNF complex cannot function normally due to missing SMARCB1 protein, widespread epigenetic changes occur throughout the cell’s genome, affecting the expression of hundreds or thousands of genes simultaneously.

These disrupted gene expression patterns cause cells to lose their normal identity and growth controls. The cells begin dividing rapidly and uncontrollably, forming a tumour. The resulting rhabdoid cells have distinctive features when examined under a microscope—they are large cells with unusual characteristics. The tumours are named “rhabdoid” because the cancer cells resemble rhabdomyoblasts, which are cells that normally develop into muscles, even though rhabdoid tumours are not actually related to muscle tissue.^[1]

Histologically (when examined under a microscope), rhabdoid tumours display characteristic rhabdoid cells that are large with eccentrically located nuclei and abundant, eosinophilic (pink-staining) cytoplasm.^[6] These cells contain distinctive structures visible under the microscope that help pathologists identify the tumour type. One case report described tumour tissue composed of solid sheets showing unusual proliferation of epithelioid cells with eosinophilic cytoplasm and atypical features.^[5]

Mechanically and physically, rhabdoid tumours cause problems through several mechanisms. As the tumour grows rapidly within the kidney, it can invade surrounding structures including blood vessels, the kidney’s collecting system, and nearby organs. The tumours commonly arise from primitive medullary cells (cells from the inner part of the kidney) and can invade both the hilum (where vessels enter and exit the kidney) and the collecting system (the tubes that drain urine).^[5]

These tumours are highly malignant, meaning they are cancerous and aggressive.^[1] They grow much faster than normal tissue and have a strong tendency to spread or metastasize to other parts of the body. Cancer cells can break away from the original kidney tumour and travel through the bloodstream or lymphatic system to establish new tumours in distant organs such as the lungs, liver, brain, or other locations. This rapid spread is one reason why rhabdoid tumours are so difficult to treat successfully.

Biochemically, the loss of SMARCB1 function appears to affect multiple cellular processes. Studies have shown that rhabdoid tumours may have abnormalities in chromosome 22, where the SMARCB1 gene is located.^[6] The inactivation can occur through deletion (physical loss of the gene), mutation (changes in the gene’s sequence), or acquired uniparental disomy (inheritance of two copies of the chromosome from one parent).^[6]

At the tissue level, rhabdoid tumours disrupt normal kidney architecture and function. As the tumour grows, it compresses and destroys normal kidney tissue. This can lead to kidney dysfunction, affecting the organ’s ability to filter blood and produce urine properly. The compression of surrounding structures can cause swelling, pain, and other symptoms. When tumours grow large, they can cause the abdomen to swell visibly.

The body’s immune system typically struggles to recognize and fight rhabdoid tumours effectively. These cancer cells have ways of evading immune detection and destruction, allowing them to continue growing despite the body’s natural defense mechanisms. The tumours also develop their own blood supply through a process called angiogenesis, where new blood vessels grow to feed the rapidly dividing cancer cells.

Rare mutations in another gene called SMARCA4 can also cause rhabdoid tumours through similar mechanisms, as this gene also encodes a component of the SWI/SNF chromatin-remodeling complex.^[1] When either SMARCB1 or SMARCA4 is lost, the entire chromatin remodeling apparatus becomes dysfunctional, leading to the characteristic aggressive behavior of rhabdoid tumours.