Clear cell sarcoma of the kidney (CCSK) is a rare type of kidney cancer that happens mostly in young children, usually under 5 years of age. It grows from the supporting (mesenchymal) tissue inside the kidney, not from the usual kidney filtering cells. Doctors see it in about 3–5 out of every 100 childhood kidney tumors, so it is uncommon but still one of the main kidney cancers in children after Wilms tumor.
Clear cell sarcoma of the kidney (CCSK) is a rare, aggressive kidney cancer that mainly affects young children, usually under 3 years of age. It starts from the tissues of one kidney and often looks similar to Wilms tumor under the microscope, but it behaves more aggressively and has a higher risk of spreading (metastasis), especially to the bones, brain, and lungs. Because of this, CCSK is treated as a “high-risk” kidney tumor in pediatric oncology protocols.
In most children, CCSK is treated with a combination of surgery, intensive multi-drug chemotherapy, and sometimes radiation therapy to the tumor area or other sites. International treatment groups such as the National Wilms Tumor Study Group and SIOP (International Society of Pediatric Oncology) have developed regimens that combine drugs like vincristine, doxorubicin, cyclophosphamide, etoposide, and actinomycin D, often together with flank or whole-abdomen radiation, depending on the stage.
This tumor usually appears as a single mass in one kidney. Under the microscope, it can show many different patterns, which is why it was called a “tumor with many faces” in pathology studies. Even though it is called “clear cell,” it is a completely different disease from clear cell renal cell carcinoma, which is the common adult kidney cancer. CCSK behaves differently and needs special treatment plans designed for children.
A special feature of clear cell sarcoma of the kidney is its strong tendency to spread (metastasize) to bones, much more often than Wilms tumor. Studies report that 40–60% of children with CCSK who develop spread have bone metastases, while bone spread in Wilms tumor is only around 2%. Because of this, doctors always look carefully at the bones when they stage this cancer.
Modern treatment uses a combination of surgery, chemotherapy, and sometimes radiotherapy. With these combined treatments, long-term survival has improved a lot. Recent large studies show 4–5-year overall survival around 80–90%, especially in children whose tumor is found at an early stage. However, high-stage disease and relapse still carry a worse outlook, so early diagnosis and complete treatment are very important.
Other names
Clear cell sarcoma of the kidney has been described in the medical literature under a few different names. The current preferred name is “clear cell sarcoma of the kidney” and the short form is “CCSK.”
In older papers, CCSK was sometimes called the “bone-metastasizing renal tumor of childhood” because doctors noticed very early that this tumor often spreads to bones. This older name highlights its strong bone-seeking behavior but is less used now, because it can be confusing and does not describe all its features.
It is important not to confuse CCSK with “clear cell sarcoma of soft tissue,” which is a different cancer that usually grows in tendons and soft tissues of the arms or legs. Even though both contain the words “clear cell sarcoma,” they have different genetic changes, appear in different body sites, and are treated as separate conditions.
Types
When pathologists look at CCSK under a microscope, they see several patterns. These are not separate diseases but different “looks” that the same tumor can have. Recognizing them helps confirm the diagnosis.
Classic type – This is the most common pattern. The tumor cells are small to medium-sized, arranged in cords or nests, with pale (clear) areas between them and thin fibrous bands. This pattern is reported in the majority of cases and is usually present at least in some part of the tumor.
Myxoid type – In this type, the tumor has a lot of jelly-like (myxoid) material in the background. The cells float in this mucoid substance. Myxoid change is seen in about half of tumors and can sometimes make the tumor resemble other myxoid soft-tissue sarcomas, which can complicate diagnosis.
Sclerosing type – Here, thick collagen bands separate the tumor cells, making the tissue look scar-like and dense. This sclerosing pattern is reported in about one-third of cases and can be very striking in some tumors.
Cellular type – The cellular pattern shows more crowded, densely packed tumor cells with less background stroma. This can make the tumor appear more aggressive under the microscope and may mimic other small round blue cell tumors of childhood.
Epithelioid (trabecular or acinar) type – In this pattern, cells form cord-like or gland-like structures that can mimic epithelial tumors. Pathologists must use special stains to avoid misdiagnosing it as carcinoma because CCSK is a mesenchymal tumor, not a true epithelial cancer.
Palisading / Verocay-body-like pattern – Some areas may show rows of tumor cell nuclei lined up in parallel (palisading), similar to patterns seen in nerve sheath tumors. This is less common but is a recognized variant.
Spindle-cell pattern – In some tumors, the cells become more elongated and spindle-shaped. This variant can resemble other spindle-cell sarcomas, which is why immunohistochemistry and molecular tests are so important for a correct diagnosis.
Anaplastic type – Rarely, CCSK shows very abnormal (anaplastic) cells with huge, dark nuclei and bizarre mitoses. This anaplastic variant may be linked with a more aggressive behavior, so its recognition has prognostic value.
Causes and risk factors
For most children with clear cell sarcoma of the kidney, doctors cannot find a clear external cause. The disease seems to result mainly from random genetic changes that happen during kidney development. Below are factors and mechanisms thought to play a role. Some are well proven; others are still under study and should be seen as possible contributors, not definite causes.
Sporadic genetic changes during kidney development – Most CCSK cases occur in children with no family history and no known exposure, suggesting new mutations in kidney precursor cells that happen by chance in early life.
BCOR internal tandem duplication (BCOR-ITD) – Many CCSK tumors carry a specific change in the BCOR gene on the X chromosome. In this change, a small piece of DNA in the gene is repeated back-to-back (internal tandem duplication), which alters how the BCOR protein controls other genes and promotes tumor growth.
YWHAE–NUTM2B/E gene fusion – A smaller group of tumors shows a fusion between YWHAE and NUTM2B/E genes. This fusion produces an abnormal protein that changes cell signaling. It usually does not occur together with BCOR-ITD; the two alterations tend to be mutually exclusive.
BCOR pathway dysregulation – BCOR helps regulate gene expression through a polycomb repressive complex. When BCOR is altered, many downstream developmental genes may become abnormally activated or silenced, favoring uncontrolled cell division in kidney mesenchymal cells.
Embryonal origin of kidney tissue – The kidney develops from embryonal blastemal tissue. Errors in the maturation of this tissue can lead to several pediatric renal malignancies, including CCSK, suggesting that disruptions in very early kidney development are a key underlying cause.
Epigenetic changes – Altered methylation and chromatin states associated with BCOR and related complexes can change how genes are switched on or off without changing the DNA sequence. Such epigenetic changes have been reported in CCSK and are thought to support tumor cell survival.
Male sex (slight predominance) – Some series show a small male predominance, suggesting that sex-linked genetic or hormonal factors may slightly increase risk, although the exact reason is not known.
Very young age – CCSK is mainly seen in toddlers and preschool children. The concentration in this age group supports the idea that disturbances in early developmental windows are important in its cause.
General pediatric renal cancer predisposition – While strong links between CCSK and specific inherited cancer syndromes are not clearly proven, children with certain congenital conditions may have a higher general tendency to develop kidney tumors; CCSK is part of this broader group of embryonal renal cancers.
DNA repair problems – Some researchers suspect that subtle defects in DNA repair pathways might allow mutations like BCOR-ITD or gene fusions to persist in dividing kidney cells, although this has not been fully mapped for CCSK.
Abnormal cell-cycle control – Overexpression of proteins such as cyclin D1 has been described in CCSK. These proteins drive cells through the cell cycle and, when overactive, may help tumor cells divide faster.
Disordered signaling pathways (e.g., Wnt / growth factor pathways) – Gene expression studies show that several growth and developmental pathways are altered in CCSK, which may help cells grow even when they should stop.
Random prenatal events – Some tumors may begin from mutations that occur before birth, while the baby is still in the womb. These events are random and not caused by anything the parents did, but they can start the path toward future tumor development.
Lack of strong environmental links – Unlike some adult cancers, no strong association has been proven between CCSK and environmental exposures such as smoking or adult-type toxins, which supports a mainly genetic and developmental origin.
Possible role of prenatal growth factors – Because CCSK arises in a developing organ, disturbances in the balance of growth factors that shape the kidney may contribute, although current research is still exploratory in this area.
Tumor microenvironment changes – The supporting tissue around tumor cells, including blood vessels and stromal cells, shows special patterns in CCSK and may provide signals that help the tumor grow and spread, especially to bone.
Bone-seeking biology – The strong tendency to metastasize to bone suggests that CCSK cells express molecules that allow them to home to bone marrow and grow there; this is still under investigation.
Potential shared pathways with other BCOR-rearranged tumors – CCSK shares BCOR changes with some other rare sarcomas. This suggests that common BCOR-driven molecular programs may predispose certain cell types, including kidney stromal cells, to become malignant.
Stochastic (chance) events in small cell populations – Because the number of precursor cells in the developing kidney is limited, a single harmful mutation in one cell can have a big impact. Chance events in this small cell pool are therefore an important part of CCSK causation.
Unknown factors still to be discovered – Research continues, and it is very likely that new genetic or molecular abnormalities will be found in CCSK. For now, doctors consider the cause largely unknown, with BCOR alterations as the main known driver.
Symptoms and signs
Painless abdominal mass – The most common sign is a firm swelling or lump in the child’s abdomen that parents or doctors can feel. Often it does not hurt at first, so it may be found during bathing, dressing, or a routine exam.
Abdominal pain or discomfort – As the tumor grows, it can stretch the kidney capsule or press on nearby organs, causing vague belly pain, a feeling of fullness, or tenderness when the area is touched.
Blood in the urine (hematuria) – Some children may pass urine that looks pink, red, or cola-colored. Sometimes the blood is microscopic and only detected on a urine test, but it still suggests kidney involvement.
High blood pressure (hypertension) – The tumor can affect kidney blood flow and hormone production (such as renin), leading to elevated blood pressure. This might be noticed during routine measurements at the clinic.
Fever – Some children have unexplained fevers. These can be due to tumor-related inflammation or occasional tumor necrosis and are often mistaken for simple infections at first.
Loss of appetite – A growing abdominal mass and the body’s inflammatory response can reduce appetite, so the child may eat less than usual or refuse food.
Weight loss or poor weight gain – Over time, reduced appetite and increased energy use by the tumor may lead to weight loss or failure to gain weight along normal growth curves.
Tiredness and low energy (fatigue) – Tumor growth, possible anemia, and the body’s response to cancer can make the child more tired, less active, or less interested in play than before.
Pale skin (pallor) – If the tumor causes blood loss in urine or affects bone marrow over time, the child may become anemic and appear pale, especially on the lips, tongue, and inside the eyelids.
Nausea and vomiting – Pressure on the stomach or intestines, or disturbance of body chemistry from kidney involvement, may cause nausea or vomiting, especially when the mass is large.
Constipation or change in bowel habit – A large tumor can compress the intestines, slowing movement of stool and leading to constipation or changes in bowel pattern.
Shortness of breath – If the cancer spreads to the lungs or if a large abdominal mass pushes up against the diaphragm, breathing can become harder. The child may breathe faster, get tired easily, or have a cough.
Bone pain – Because CCSK often spreads to bones, children can develop bone pain, tenderness over bones, or limping if the legs or spine are affected. This symptom is particularly suspicious in a child with a known renal mass.
Swelling or fractures in bone metastases – In advanced cases, areas of metastatic bone disease may cause visible swelling or even pathologic fractures after minimal trauma.
Headache or neurological symptoms (rare) – If the tumor spreads to the brain, the child may develop headaches, vomiting, seizures, or behavior changes. This is uncommon but reported in some advanced cases.
Diagnostic tests –
Physical examination
General pediatric physical examination – The doctor checks the child’s overall condition, including weight, height, temperature, heart rate, and breathing pattern. This helps detect signs like fever, weight loss, or tiredness that support the suspicion of a serious underlying illness.
Abdominal inspection and palpation – The doctor looks at the abdomen for swelling or uneven shape and gently feels (palpates) the belly with both hands. A firm, irregular mass on one side of the abdomen is a key physical clue that a kidney tumor like CCSK may be present.
Blood pressure measurement – A simple cuff is placed on the arm or leg to measure blood pressure. High readings can suggest that the kidney tumor is affecting the renin-angiotensin system, which helps regulate blood pressure.
Examination for bone tenderness and gait – Because CCSK can spread to bones, the doctor may gently press along the spine and limbs and watch how the child walks or stands. Pain, limping, or refusal to bear weight can indicate possible bone involvement.
Manual and bedside tests
Bedside urine dipstick test – A small plastic strip is dipped into a fresh urine sample. Color changes on the strip can quickly show the presence of blood or protein in the urine, which supports the suspicion of kidney damage or tumor.
Manual abdominal percussion – The doctor gently taps on the abdomen to listen for changes in sound that suggest a solid mass instead of normal air-filled bowel. This simple bedside technique helps confirm that the swelling is solid and may be coming from an organ like the kidney.
Growth chart assessment – The child’s height and weight are plotted on a pediatric growth chart. Slowed growth or weight loss for age can be a subtle sign of chronic illness such as a kidney tumor, even before the mass is obvious.
Laboratory and pathological tests
Complete blood count (CBC) – This blood test measures red cells, white cells, and platelets. It can show anemia from blood loss or chronic disease, and sometimes mild changes in white cells or platelets related to illness or treatment.
Kidney function tests (serum creatinine and urea) – These tests show how well the kidneys are cleaning waste from the blood. In many children with a single kidney tumor, kidney function may still be normal, but these tests are important for planning surgery and chemotherapy.
Liver function and electrolytes – These blood tests check if the liver and body salts are normal. They help assess the child’s general health and fitness for anesthesia and chemotherapy and can reveal complications from widespread disease.
Detailed urinalysis – A laboratory looks at the urine under a microscope and does chemical tests. This can confirm microscopic blood, detect protein loss, and look for casts or other changes that occur with kidney damage.
Tumor biopsy and histopathology (usually after nephrectomy) – The most important diagnostic step is removal of the kidney mass (nephrectomy) and careful examination under the microscope. Pathologists look for the characteristic patterns of CCSK and distinguish it from Wilms tumor and other pediatric renal cancers.
Immunohistochemistry (IHC) – including BCOR and cyclin D1 – Special stains highlight certain proteins in tumor cells. Diffuse strong staining for BCOR and cyclin D1 has been shown to be a sensitive and specific marker pattern for CCSK among pediatric kidney tumors, helping confirm the diagnosis.
Molecular testing for BCOR-ITD or YWHAE–NUTM2 fusion – Genetic tests such as PCR or sequencing can detect BCOR internal tandem duplications or YWHAE–NUTM2B/E fusions. Finding one of these changes strongly supports the diagnosis of CCSK and can help when the histology is unusual.
Electrodiagnostic tests
Electrodiagnostic tests are not used to find the kidney tumor itself, but they are often part of the full work-up and treatment planning, especially because therapy can affect the heart and other organs.
Electrocardiogram (ECG or EKG) – This test records the electrical activity of the heart. It is important before and during anthracycline-based chemotherapy (such as doxorubicin), which is commonly used in CCSK treatment and can affect heart function. A baseline ECG helps doctors detect any heart rhythm problems early.
Echocardiography (heart ultrasound with Doppler) – While technically an imaging test, it is often grouped with electrodiagnostic cardiac assessment. It uses ultrasound and sometimes Doppler to see heart structure and measure pumping function. Because intensive chemotherapy is given for CCSK, echocardiography is usually done before treatment to make sure the heart is strong enough.
Imaging tests
Abdominal ultrasound – Ultrasound is usually the first imaging test. It uses sound waves to show a mass in the kidney, its size, and its relation to other organs. It does not use radiation, so it is safe for children and helps decide whether more detailed scans are needed.
Contrast-enhanced CT scan of abdomen and pelvis – CT uses X-rays and computer processing to create detailed cross-section images of the abdomen and pelvis. With contrast dye, it clearly shows the kidney mass, nearby lymph nodes, blood vessels, and possible spread within the abdomen, helping stage the disease and plan surgery.
MRI of abdomen (and sometimes spine) – MRI uses magnetic fields instead of X-rays and gives excellent soft-tissue contrast. It can better define tumor extension into veins or surrounding structures and is useful in children to limit radiation exposure, especially if repeated scans are needed.
Chest CT and bone imaging (bone scan, PET/CT, or MRI of bones) – Because CCSK often spreads to lungs and bones, imaging of the chest and skeletal system is crucial. Chest CT detects small lung nodules, and bone scans or MRI can show active bone lesions. These tests help determine the stage and guide decisions about the intensity of chemotherapy and radiotherapy..
Non-pharmacological treatments
1. Multidisciplinary tumor board planning
For CCSK, a team of pediatric oncologists, surgeons, radiation oncologists, radiologists, and pathologists meet together to design the treatment plan. This “tumor board” approach helps match the child’s stage, age, and health to the best evidence-based protocol and reduces the chance of missing important details such as lymph node involvement or metastatic sites.
2. Pre-operative assessment and staging work-up
Before surgery, doctors use imaging tests like ultrasound, CT, or MRI plus chest imaging to check the size of the tumor, involvement of blood vessels, lymph nodes, and spread to lungs, bone, or brain. Accurate staging is essential because the chemotherapy intensity and radiation fields depend on how far the tumor has spread.
3. Careful radical nephrectomy planning
Although surgery is a “procedure,” planning it is a key non-drug step. Surgeons plan how to remove the whole tumor and kidney safely, avoid rupture, and sample lymph nodes. Good surgery with clean margins and lymph node sampling lowers the risk of local relapse and may allow less radiation in some patients.
4. Rehabilitation after surgery (physiotherapy)
After nephrectomy and early chemotherapy, children may be weak, tired, and in pain. Physiotherapists use gentle exercises, breathing training, and mobility work to help the child move safely, maintain muscle strength, and prevent chest infections and blood clots.
5. Occupational therapy for daily activities
Occupational therapists support children and families with positioning, feeding, dressing, and play after surgery and during chemotherapy. They may suggest adaptive tools, safe lifting methods, and energy-saving strategies so that the child can participate in home and school life as much as possible.
6. Child-life and play therapy
Child-life specialists use play, drawing, and age-appropriate education to explain what is happening and prepare the child for tests, surgery, and chemotherapy. This reduces fear, increases cooperation during procedures, and can lower anxiety and behavioral problems.
7. Psychological counseling for child and family
A cancer diagnosis is very stressful for parents and siblings. Psychologists or counselors provide coping strategies, grief support, and help with sleep problems, fear, or depression. Early psychological support can improve adherence to treatment and quality of life during and after therapy.
8. Social work and practical support
Social workers help families handle financial issues, transport, housing near the hospital, and work or school disruptions. They may connect families to charities, insurance resources, and legal support, which reduces stress and allows caregivers to focus on the child’s treatment.
9. Nutrition counseling
Dietitians assess weight, growth, and lab values, then design meal plans that provide enough calories, protein, fluids, and micronutrients despite nausea or poor appetite. Good nutritional status improves wound healing, tolerance of chemotherapy, and immune function.
10. Non-drug pain management
In addition to prescribed medicines, non-pharmacological pain methods such as relaxation breathing, distraction, music therapy, warm packs, and gentle massage can reduce discomfort from surgery, injections, and bone pain. These methods support lower doses of opioids and fewer side effects.
11. Infection-control education at home
Families are taught handwashing, safe food handling, avoiding sick contacts, and watching for fever when blood counts are low. Simple measures like daily temperature checks and quick reporting of fever can prevent minor infections from becoming life-threatening sepsis during chemotherapy-induced neutropenia.
12. School liaison and educational planning
Teachers and school nurses are informed about the child’s diagnosis, expected absences, and any physical limits. Educational plans may include home tutoring or online lessons, so the child keeps up academically and socially. This support helps long-term quality of life and reintegration after treatment.
13. Exercise and activity pacing
Gentle physical activity, like walking and light play, is encouraged between chemotherapy cycles. Activity pacing means balancing movement with rest to fight fatigue and keep muscles strong without over-exertion. This may reduce long-term deconditioning and cardiometabolic risks after therapy.
14. Sleep hygiene strategies
Hospital routines, steroids, and anxiety can disturb sleep. Non-drug approaches include regular sleep schedules, limiting screen time before bed, creating a quiet dark environment, and using calming bedtime routines. Better sleep improves mood, behavior, concentration, and coping.
15. Spiritual or cultural support
Many families draw strength from religious or cultural practices. Chaplains or spiritual care workers offer non-judgmental support, help with rituals, and assist families in making difficult decisions about treatment goals that match their values.
16. Palliative care and symptom-focused support
Palliative care is not only for end of life. In CCSK, palliative teams help control pain, nausea, breathlessness, and emotional distress throughout the illness. Early palliative care is linked to better symptom control and family satisfaction, even when the goal is cure.
17. Survivorship and late-effects clinic follow-up
After treatment, survivors of CCSK need long-term follow-up for heart problems, second cancers, fertility issues, kidney function, and growth disturbances due to chemotherapy and radiation. Survivorship clinics track these late effects, arrange screening, and give guidance on healthy lifestyles.
18. Telemedicine and remote monitoring
Video visits and remote symptom reporting platforms allow families to discuss side effects, lab results, and imaging without always traveling to the hospital. Telemedicine reduces burden, improves access to specialists for rare tumors, and supports quick triage of urgent problems.
19. Clinical trial participation and registry enrollment
Because CCSK is rare, many children are treated in clinical trials or registries that collect data on survival and side effects. Enrolling in such studies helps refine future protocols and sometimes gives access to new imaging, radiation approaches, or supportive-care innovations.
20. Peer and parent support groups
Talking with other parents or survivors who faced CCSK or similar childhood cancers can reduce isolation and provide practical coping tips. Hospitals or charities may offer online or in-person groups, mentorship programs, and family camps that support emotional recovery.
Drug treatments
Clear cell sarcoma of the kidney is usually treated with combinations of standard chemotherapy drugs originally developed for other cancers (such as Wilms tumor or sarcomas). These medicines are almost always given in a specialized pediatric oncology center, through a central venous line, and according to protocol doses calculated from body surface area (mg/m²) or weight (mg/kg).
Doses below are typical ranges from prescribing information or common oncology protocols and are not instructions for self-treatment. Actual doses, schedules, and combinations must be decided by the treating oncologist.
1. Vincristine sulfate
Vincristine is a vinca alkaloid that stops tumor cells from dividing by blocking formation of microtubules in the mitotic spindle. In pediatric cancer protocols, the usual dose is about 1.5–2 mg/m² (maximum 2 mg) given intravenously once weekly. Major side effects include peripheral neuropathy (weakness, tingling), constipation, hair loss, and bone marrow suppression. Intrathecal (spinal) use is strictly forbidden because it is almost always fatal.
2. Doxorubicin hydrochloride
Doxorubicin is an anthracycline antibiotic that intercalates into DNA and inhibits topoisomerase II, causing breaks in tumor cell DNA and generation of free radicals. When used with other chemotherapy drugs, the recommended dose is roughly 40–75 mg/m² given intravenously every 21–28 days, with lower doses in heavily pretreated or higher-risk patients. Important side effects include dose-dependent heart damage (cardiomyopathy), bone marrow suppression, mouth sores, nausea, and hair loss.
3. Cyclophosphamide
Cyclophosphamide is an alkylating agent that cross-links DNA, preventing cell division and leading to tumor cell death. It is used in CCSK regimens at varying doses (for example, several hundred mg/m² to about 1–1.5 g/m² per cycle) as intravenous infusion. Side effects include bone marrow suppression, nausea, hair loss, and hemorrhagic cystitis (bleeding from the bladder), which is reduced by hydration and uro-protective agents like mesna.
4. Etoposide / etoposide phosphate
Etoposide is a topoisomerase II inhibitor that causes DNA strand breaks in rapidly dividing cells. Typical dosing in combination regimens is around 100 mg/m² per day given intravenously for 3–5 days in each cycle. Common side effects include low blood counts, infection risk, hair loss, nausea, and sometimes low blood pressure during infusion.
5. Dactinomycin (actinomycin D)
Dactinomycin is a cytotoxic polypeptide antibiotic that binds to DNA and blocks RNA synthesis, stopping cell growth. It is widely used in pediatric solid tumors such as Wilms tumor and sarcomas and may be part of CCSK-like protocols. Doses are usually calculated in micrograms/kg or mg/m² as short intravenous injections. Major side effects include severe bone marrow suppression, mucositis, nausea, and liver toxicity, so it must be given only under close supervision.
6. Carboplatin
Carboplatin is a platinum compound that cross-links DNA and triggers apoptosis in cancer cells. It is often used in relapse or high-risk regimens for pediatric solid tumors, including metastatic CCSK, usually at doses based on area under the curve (AUC) or mg/m² every 3–4 weeks. Its key side effect is thrombocytopenia (low platelets), along with anemia, neutropenia, nausea, and less kidney and hearing damage than cisplatin.
7. Ifosfamide
Ifosfamide is another alkylating agent closely related to cyclophosphamide that forms DNA cross-links. In sarcoma-style regimens, it may be given at doses like 1.2 g/m² per day for 3–5 days every 3 weeks, always with strong hydration and mesna to protect the bladder. Important toxicities are bone marrow suppression, kidney injury, bladder bleeding, and central nervous system toxicity such as confusion or seizures.
8. Mesna (uro-protectant)
Mesna is not an anti-cancer drug but is crucial when using high-dose ifosfamide or cyclophosphamide. It binds and neutralizes acrolein, a toxic metabolite in the urine, preventing hemorrhagic cystitis and long-term bladder damage. Mesna dosing is usually proportional to the dose of the alkylating drug and given intravenously or orally at intervals during and after chemotherapy. Side effects are usually mild and may include nausea or allergic reactions.
9. Growth-factor support (filgrastim / pegfilgrastim)
Filgrastim (G-CSF) and pegfilgrastim are injected growth factors that stimulate the bone marrow to produce neutrophils faster. They are used after intensive chemotherapy to shorten the duration of neutropenia and lower the risk of serious infections. Typical doses are weight-based or fixed (for pegfilgrastim) and given subcutaneously; side effects include bone pain and rare splenic complications.
10. Anti-nausea medicines (ondansetron and others)
Serotonin-antagonist antiemetics such as ondansetron are standard with CCSK chemotherapy to prevent nausea and vomiting. Doses are usually weight-based and given intravenously or orally before chemotherapy and then at intervals afterward. Side effects can include constipation, headache, and, rarely, heart rhythm changes, so ECG monitoring may be needed in high-risk patients.
11. Corticosteroids (dexamethasone)
Dexamethasone is often added as part of antiemetic regimens and to reduce brain swelling in patients with brain metastases. It decreases inflammation in tissues and around tumors but can cause side effects such as high blood sugar, mood changes, muscle weakness, and infection risk, especially with long use.
12. Broad-spectrum antibiotics
When CCSK patients develop neutropenic fever, broad-spectrum intravenous antibiotics are started immediately as life-saving treatment. Regimens are chosen according to hospital guidelines and local bacterial resistance patterns. Side effects depend on the antibiotic but may include allergic reactions, kidney or liver test changes, and gastrointestinal upset.
13. Antifungal prophylaxis
In very intensive regimens or prolonged neutropenia, oncologists may add antifungal medicines (such as azoles or echinocandins) to prevent invasive fungal infections. These drugs interfere with fungal cell membranes and reduce life-threatening infections but can interact with chemotherapy through liver enzyme pathways, so levels and liver tests must be monitored.
14. Proton-pump inhibitors or H₂-blockers
Acid-suppressing drugs, such as omeprazole or ranitidine, may be used to protect the stomach from stress ulcers and steroid-related irritation. They reduce gastric acid production and help children tolerate oral medicines and food, but long-term use may affect mineral absorption or infection risk, so they are used for the shortest effective time.
15. Analgesics (acetaminophen, opioids)
Pain control often requires a ladder from paracetamol (acetaminophen) to stronger opioid medicines such as morphine, especially after surgery or with bone metastases. Doses are carefully tailored to weight and response, and side effects like constipation, drowsiness, and risk of respiratory depression are closely monitored by the care team.
16. Anticonvulsants
If CCSK spreads to the brain or if chemotherapy causes seizures, anticonvulsant drugs are used to stabilize neuronal firing. Choices depend on age, organ function, and interactions with chemotherapy. Side effects can include drowsiness, behavioral changes, and liver enzyme elevation, so regular monitoring is needed.
17. Anticoagulants in selected patients
Children with central lines, immobility, or certain chemotherapy regimens may have a higher risk of blood clots. In these high-risk cases, low-molecular-weight heparin or similar drugs can be used to prevent or treat thrombosis. They work by inhibiting clotting factors but can cause bleeding, so doses are carefully adjusted.
18. Radioprotective planning (care around radiation)
While not a “drug,” careful dosing and field planning of radiation is closely integrated with chemotherapy. For stage II–III disease, flank radiation is often used, while some stage I patients may safely omit radiation when lymph nodes are sampled, helping reduce long-term side effects such as growth problems and secondary cancers.
19. Rescue agents for chemo toxicity (e.g., leucovorin in certain regimens)
In regimens that include antifolate drugs (less common in CCSK but used in other sarcomas), leucovorin “rescue” is used to protect normal cells by bypassing folate blockade. It is given at specific times after chemotherapy infusion, according to protocol, and reduces mucositis and bone marrow toxicity.
20. Investigational or targeted agents in clinical trials
Because outcomes for relapsed CCSK are still suboptimal, some patients may enter trials using targeted therapies or new combinations. These agents may act on specific growth factor receptors or DNA repair pathways. Their dosing, safety, and benefits are still being studied, so they are only given within controlled research protocols.
Dietary molecular supplements
There is no supplement that cures clear cell sarcoma of the kidney. However, some nutrients are studied for general immune and nutritional support during cancer therapy. Doses below are typical ranges from general nutrition or adult oncology literature, not personal medical advice.
1. Vitamin D
Vitamin D helps regulate calcium balance, bone health, and immune function. Many children on chemotherapy have low levels, so doctors may prescribe cholecalciferol at doses such as 400–1000 IU/day or as individualized high-dose replacement if levels are very low. Too much vitamin D can cause high calcium and kidney problems, so blood levels must be monitored.
2. Calcium
Cancer treatment and reduced activity can weaken bones, especially after nephrectomy and corticosteroid use. Calcium supplements (for example 500–1000 mg/day total dietary plus supplement in older children or adults) may be advised if intake is low. They must be balanced with vitamin D status and kidney function to avoid kidney stones or calcifications.
3. Omega-3 fatty acids (EPA/DHA)
Omega-3 fats from fish oil or algae may help with inflammation, appetite, and weight maintenance during chemotherapy. Typical studied doses are around 1–2 g/day of combined EPA/DHA in older children or adults, but pediatric doses are strictly weight-based. Side effects include a fishy aftertaste and, rarely, increased bleeding tendency at high doses.
4. Probiotics (with caution)
Probiotics aim to support gut microbiota and may reduce diarrhea or antibiotic-associated imbalance. However, in severely neutropenic patients there is a theoretical risk of bloodstream infection from live bacteria. For this reason, any probiotic use must be cleared by the oncology team.
5. Zinc
Zinc is important for wound healing, taste, and immune function. Supplement doses are typically 5–20 mg/day depending on age and diet; long-term high doses can cause copper deficiency and anemia. Oncologists may prescribe zinc if tests or diet suggest deficiency, especially in children with poor appetite or chronic diarrhea.
6. Selenium
Selenium is a trace mineral involved in antioxidant enzymes. Small supplemental doses (for example, 50–100 mcg/day in older patients) have been studied for their possible role in reducing chemotherapy-related oxidative stress, but evidence is still limited. High doses can be toxic, so supplements should only be taken under medical supervision.
7. Glutamine
Glutamine is an amino acid used by rapidly dividing cells and may support gut and muscle health. Some studies in oncology suggest it may reduce mucositis and neuropathy, but evidence is mixed. Typical adult doses are several grams per day, but pediatric dosing must be individualized; excessive amounts may be harmful in certain metabolic states.
8. Whey or plant protein supplements
When appetite is low, liquid protein supplements or shakes can help reach daily protein needs for healing and immune function. Intake is usually calculated as grams of protein per kilogram of body weight per day, adjusted for kidney function (only one kidney remains). Dietitians guide brand choice and amount to avoid excessive sugar or phosphorus.
9. Multivitamin (age-appropriate)
A simple age-appropriate multivitamin can cover small gaps in intake caused by nausea or food aversions. It is important to avoid high-dose “mega vitamins” or overlapping products that multiply certain nutrients, especially fat-soluble vitamins and minerals that can accumulate and harm the liver or kidneys.
10. Curcumin or plant antioxidants (experimental)
Curcumin and other plant-derived antioxidants are sometimes discussed by families. Laboratory studies show antioxidant and anti-inflammatory effects, but clinical data in children with CCSK are lacking. These compounds can interact with chemotherapy metabolism, so they should only be used, if at all, under guidance in a research or clinical setting.
Immunity-booster, regenerative and stem-cell-related drugs
These medicines do not treat the tumor directly but help the bone marrow and blood system recover from intensive chemotherapy. They must be prescribed and monitored by oncology specialists.
1. Filgrastim (G-CSF)
Filgrastim is a recombinant granulocyte colony-stimulating factor that binds to G-CSF receptors in the bone marrow and speeds production of neutrophils. It is usually given as a daily subcutaneous injection starting 24–72 hours after chemotherapy until neutrophils recover. Common side effects are bone pain and injection-site discomfort; rare complications include splenic enlargement.
2. Pegfilgrastim
Pegfilgrastim is a PEGylated, long-acting G-CSF that stays in the body longer and is often given as a single injection per chemotherapy cycle. It has a similar mechanism to filgrastim but more convenient dosing. Side effects are similar, and doses are weight-based in children.
3. Sargramostim (GM-CSF)
Sargramostim is a granulocyte-macrophage colony-stimulating factor that boosts several white blood cell lines, including neutrophils and monocytes. It may be used in some protocols or after stem cell transplantation to speed bone marrow recovery. Side effects include fever, bone pain, and occasionally fluid retention or capillary leak in high doses.
4. Epoetin alfa (erythropoietin)
Epoetin alfa is a synthetic form of the hormone erythropoietin, which stimulates red blood cell production in the bone marrow. It may be used in selected patients with chemotherapy-associated anemia to reduce transfusion needs, though use in children is carefully weighed due to potential risks such as hypertension and thrombosis. Dosing is weight-based and given subcutaneously several times per week.
5. Thrombopoietin receptor agonists (e.g., eltrombopag)
Thrombopoietin receptor agonists stimulate platelet production and can be considered in refractory thrombocytopenia, particularly in research or specialized contexts. They bind to c-Mpl receptors on megakaryocytes and increase platelet counts, but may cause liver enzyme elevations and, rarely, clotting problems, so they are used with caution.
6. Hematopoietic stem cell transplantation (HSCT) support drugs
In very high-risk or relapsed CCSK, some centers may consider high-dose chemotherapy followed by autologous or allogeneic HSCT. This involves using conditioning regimens with alkylating agents and sometimes total body irradiation, followed by infusion of stem cells and intensive supportive drugs such as anti-infectives, growth factors, and immunosuppressants. HSCT remains experimental in CCSK and is generally reserved for clinical trials or selected cases.
Surgeries
1. Radical nephrectomy with lymph node sampling
The primary surgery for CCSK is radical nephrectomy, where the entire affected kidney, tumor, surrounding fat, and nearby lymph nodes are removed. This procedure aims to completely excise the tumor, prevent rupture, and provide accurate staging information. Lymph node sampling is essential because node involvement changes chemotherapy and radiation plans.
2. Partial nephrectomy (selected cases)
In rare situations, such as bilateral tumors or solitary kidneys, surgeons may consider partial nephrectomy to preserve renal tissue. The goal is to remove all visible tumor while keeping as much healthy kidney as possible, but this is less common in CCSK due to its aggressive nature and high relapse risk if margins are not clear.
3. Resection of metastatic lesions (metastasectomy)
If CCSK spreads to the lungs, bone, or brain, and chemotherapy and radiation have reduced but not eliminated disease, surgeons may remove remaining metastatic nodules. Metastasectomy is done to achieve complete remission when systemic therapy alone cannot clear all disease and may improve survival in selected patients.
4. Central venous catheter or port placement
Long-term chemotherapy requires stable, safe venous access. Surgeons or interventional specialists place tunneled central lines or implanted ports under the skin, usually in the chest. These devices allow blood draws and chemotherapy infusions with less pain and fewer peripheral IV attempts, but they need careful care to avoid infection or clotting.
5. Neurosurgical procedures for brain metastases
For patients with CCSK spread to the brain, neurosurgery may be used to remove accessible lesions, reduce pressure, and obtain tissue for diagnosis. Surgery is usually combined with radiation and systemic therapy and is considered when the lesion is causing symptoms or is large and resectable.
Prevention
Because CCSK is a rare pediatric cancer with no clear environmental cause, there is no proven way to fully prevent it. Prevention focuses on reducing treatment complications and improving long-term health.
Early evaluation of abdominal masses or swelling – Parents should seek medical care quickly if they notice a firm belly mass, persistent abdominal swelling, or blood in the urine, so tumors can be found and treated at an earlier stage.
Prompt imaging and referral – Health workers should refer children with suspected kidney masses to centers experienced in pediatric renal tumors, so correct diagnosis and staging happen without delay.
Avoiding unnecessary radiation exposure – Using ultrasound and MRI when appropriate and limiting CT scans helps reduce lifetime radiation dose, which is important because these children already receive radiation as part of treatment.
Following protocol-based chemotherapy – Adhering to standardized evidence-based regimens reduces the risk of under- or over-treatment and supports the best chance of cure.
Strict infection-control practices – Good hand hygiene, neutropenia precautions, and prompt treatment of fever prevent sepsis, which is a major cause of treatment-related death.
Cardiac monitoring during and after anthracyclines – Echocardiograms before, during, and after doxorubicin therapy help detect heart problems early, allowing dose adjustments and cardioprotective strategies.
Kidney protection strategies – Avoiding dehydration, unnecessary nephrotoxic drugs, and large doses of NSAIDs helps protect the remaining kidney, lowering the risk of chronic kidney disease.
Lifelong survivorship follow-up – Scheduled visits to late-effects clinics allow early detection of second cancers, growth problems, or endocrine issues, which can then be managed promptly.
Healthy lifestyle habits – Encouraging smoke-free homes, balanced diet, physical activity, and healthy weight in survivors may reduce cardiovascular and metabolic complications after treatment.
Participation in registries and research – Sharing anonymized data in CCSK registries helps improve risk-stratification, which may later allow more precise, less toxic treatments for future patients.
When to see a doctor
Families should contact the oncology team or seek urgent care if the child:
Develops fever, especially if on chemotherapy or known to have low neutrophils.
Has sudden abdominal pain, vomiting, or swelling that is new or much worse than before.
Shows blood in the urine, very reduced urine output, or swelling in legs or face that may signal kidney or heart issues.
Complains of strong headache, seizures, vision changes, or weakness suggesting possible brain involvement or treatment complications.
Has shortness of breath, chest pain, or severe cough, which can indicate infection, lung metastases, or clot.
Experiences severe mouth sores, inability to drink, or rapid weight loss, which may require nutritional or intravenous support.
Diet: what to eat and what to avoid
Eat energy-dense, protein-rich foods – Eggs, lean meat, fish, beans, lentils, yogurt, and nut butters help repair tissues and maintain weight during chemotherapy.
Choose soft, easy-to-swallow foods during mucositis – Soups, smoothies, mashed potatoes, and soft fruits can reduce pain when the mouth is sore.
Encourage small, frequent meals – Many children feel full quickly or nauseated; frequent snacks often work better than three big meals.
Focus on safe food hygiene – Fully cooked meats, pasteurized dairy, and washed fruits and vegetables lower the risk of foodborne infection in neutropenic periods.
Limit ultra-processed and very salty foods – Excess salt can stress the remaining kidney and contribute to high blood pressure; processed meats add little nutritional value.
Avoid raw or undercooked meats, eggs, and unpasteurized products – These foods increase infection risk, which is dangerous with low white cell counts.
Be cautious with herbal supplements and “immune boosters” – Many products interact with chemotherapy or affect the liver and kidneys; always discuss them with the oncologist before use.
Encourage adequate fluids – Water, oral rehydration solutions, and suitable juices help protect kidney function and reduce chemotherapy-related bladder irritation, unless fluid is restricted by the doctor.
Limit sugary drinks and sweets – While some extra calories are helpful, high sugar intake can worsen dental problems and blood sugar control, especially with steroid use.
Follow individualized diet plans from the oncology dietitian – Each child’s kidney function, growth pattern, and treatment schedule are different, so personalized diet plans are more accurate than generic advice.
Frequently asked questions
1. Is clear cell sarcoma of the kidney the same as Wilms tumor?
No. Both are childhood kidney cancers, but CCSK is biologically and clinically different from Wilms tumor. CCSK usually has a higher tendency to spread to bone and brain and therefore requires more intensive chemotherapy and sometimes radiation.
2. What causes CCSK?
The exact cause is unknown. Unlike some Wilms tumors, CCSK is not strongly linked to known inherited syndromes, and most cases appear “sporadic.” Researchers are studying genetic and molecular changes in tumor cells to understand why they become malignant.
3. How is CCSK usually found?
Most children present with a painless abdominal mass, belly swelling, or sometimes blood in the urine. Doctors confirm the diagnosis with imaging and then by examining the tumor tissue after surgery, using special stains and molecular tests.
4. Can CCSK be cured?
Many children, especially those with early-stage disease who get protocol-based treatment, can be cured. However, relapse risk is higher than in Wilms tumor, especially in advanced stages, so long-term follow-up and intensive therapy are needed.
5. Why is chemotherapy so intensive in CCSK?
Studies from large trials showed that CCSK responds better and relapse rates are lower when multi-drug regimens like vincristine, doxorubicin, cyclophosphamide, and etoposide are used, often along with radiation, compared to milder regimens.
6. Does every child with CCSK need radiation therapy?
Not always. Some recent data suggest that children with completely resected stage I CCSK and sampled lymph nodes may avoid radiation without losing cure rates, while children with higher-stage disease still benefit from flank or whole-abdomen radiation. Decisions are made by the tumor board.
7. What are the main long-term side effects to watch for?
Long-term effects can include reduced heart function from anthracyclines, growth and spine problems from radiation, chronic kidney disease in the remaining kidney, hormonal or fertility issues, and increased risk of second cancers, so survivorship follow-up is essential.
8. Will my child live a normal life after treatment?
Many survivors of CCSK can attend school, work, and have families, though some may have chronic health issues that need monitoring. Early rehabilitation, healthy lifestyle, and regular follow-up help maximize long-term quality of life.
9. Can CCSK come back years later?
Relapses most often occur within the first few years after treatment, but late relapses have been reported, sometimes in the brain or bone. This is why long-term follow-up with periodic imaging and symptom review is recommended.
10. Are there targeted therapies specifically for CCSK?
As of now, there is no widely used targeted drug that is specific for CCSK, but researchers are studying its molecular pathways and testing targeted and immunotherapy agents in early-phase trials for relapsed or refractory disease.
11. Is genetic testing needed for my child?
Some centers perform genetic or genomic testing on the tumor to look for characteristic changes and potential targets, and they may offer germline testing if there is a strong family history or syndromic features. Your oncologist will advise whether testing is useful in your situation.
12. Can parents or siblings do anything to lower their own cancer risk because of this diagnosis?
In most cases, CCSK is not inherited, so the risk to siblings is low and routine screening is not needed unless a genetic syndrome is discovered. General healthy lifestyle choices—no smoking, balanced diet, exercise—are still important for the whole family.
13. How important is treatment at a specialized pediatric center?
Very important. Outcomes for rare tumors like CCSK are better when care is provided by experienced teams that follow international protocols, have access to pediatric surgery, radiation oncology, intensive care, and clinical trials.
14. What kind of emotional support is available?
Most children’s cancer centers offer psychologists, social workers, child-life specialists, and support groups for parents and survivors. Using these services early can improve coping, reduce anxiety and depression, and help with school and social reintegration.
15. Where can families find reliable information and research updates?
Reliable information comes from pediatric cancer centers, national cancer institutes, peer-reviewed journals, and recognized charities focused on childhood cancer. Your oncology team can point to trusted resources and registries specific to CCSK and other pediatric kidney tumors.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 28, 2025.
