Succinate Dehydrogenase-Deficient Renal Cell Carcinoma: Understanding Your Pathology Report

Jason Wasserman MD PhD FRCPC
June 15, 2025

Succinate dehydrogenase-deficient renal cell carcinoma (often called SDH-deficient RCC) is a rare type of kidney cancer. It occurs when a gene called succinate dehydrogenase (SDH) doesn’t function properly due to mutations. SDH is important for normal cell function and energy production. When this gene isn’t working, it can cause cells in the kidney to grow into a tumour. Although rare, SDH-deficient RCC can behave aggressively, meaning it may grow rapidly or metastasize (spread) to other parts of the body.

What are the symptoms of succinate dehydrogenase-deficient renal cell carcinoma?

Many people with SDH-deficient RCC do not experience noticeable symptoms at first. These tumours are usually discovered during imaging tests (such as CT or MRI scans) done for unrelated reasons. However, if symptoms occur, they might include:

• Blood in the urine, causing it to appear pink, red, or brown.

• Pain or discomfort in the side or lower back.

• A lump or mass felt in the abdomen.

• Unexplained weight loss or fatigue.

Symptoms might become more noticeable if the tumour grows large or spreads to other parts of the body.

What causes succinate dehydrogenase-deficient renal cell carcinoma?

SDH-deficient RCC develops when there are changes (mutations) in genes called SDH genes, especially the SDHB, SDHA, or SDHC genes. Usually, these mutations are inherited, meaning they’re passed down through families. People with inherited mutations have a genetic condition that increases their risk of developing SDH-deficient RCC, as well as other types of tumours.

Genetic conditions associated with SDH-deficient renal cell carcinoma

Many cases of SDH-deficient RCC are associated with inherited genetic conditions. People who inherit these genetic changes (mutations) in the SDH genes are more likely to develop this type of tumour. These individuals might also develop other related conditions, such as:

• Tumours in other parts of the body, known as paragangliomas or pheochromocytomas, are related to the adrenal gland or the nervous system.

• Gastrointestinal stromal tumours (GIST), which occur in the digestive system.

• Tumours in the pituitary gland in the brain.

Doctors recommend genetic counselling and genetic testing for patients diagnosed with SDH-deficient RCC and their family members to identify and manage these risks early.

How is succinate dehydrogenase-deficient renal cell carcinoma diagnosed?

Doctors often find SDH-deficient RCC when they perform imaging tests, such as ultrasound, CT, or MRI scans, for other reasons. On these scans, SDH-deficient RCC typically appears as a mass in the kidney.

Your doctor might suggest surgery to remove the tumour. After removal, the tumour is examined by a pathologist under a microscope. Special laboratory tests, including genetic testing and immunohistochemistry (explained below), help confirm that the tumour is SDH-deficient RCC.

What does succinate dehydrogenase-deficient renal cell carcinoma look like under the microscope?

Under the microscope, SDH-deficient RCC has specific features that help pathologists recognize it. Tumour cells are usually arranged into tight groups (clusters), small tubes, or cyst-like spaces filled with clear fluid. These tumour cells often have abundant, pinkish-red (eosinophilic) cytoplasm. The centers of the tumour cells (nuclei) are irregularly shaped, with large and prominent internal structures called nucleoli. Sometimes, the tumour cells have tiny inclusions (small structures) in their cytoplasm.

These microscopic features help pathologists identify SDH-deficient RCC and distinguish it from other types of kidney tumours.

What other tests may be performed to confirm the diagnosis?

In addition to examining the tumour under the microscope, pathologists often use a special laboratory test called immunohistochemistry. Immunohistochemistry uses special stains that help identify proteins inside tumour cells.

For SDH-deficient RCC, pathologists specifically look for a protein called SDHB. Tumour cells typically lose the expression of SDHB protein (meaning SDHB is negative in tumour cells), whereas normal cells around the tumour will still have this protein. This pattern confirms that the tumour is SDH-deficient RCC. Another protein, called 2-succinocysteine (2SC), is often present in tumour cells and helps confirm the diagnosis.

How is succinate dehydrogenase-deficient RCC different from other types of kidney cancer?

SDH-deficient RCC differs from other kidney cancers in several ways:

• Genetic mutation: This involves a specific mutation in the SDH genes, which is usually inherited and uncommon in most other types of kidney cancer.

• Microscopic features: The tumour cells exhibit characteristic appearances, including large, prominent nucleoli and distinctive growth patterns, which help pathologists recognize it.

• Association with genetic syndromes: Many cases are linked to inherited conditions that cause tumours in other parts of the body, unlike most other kidney cancers.

• Behavior and prognosis: SDH-deficient RCC can be aggressive, but prognosis varies significantly. Early identification helps in appropriate treatment and follow-up.

What does tumour extension mean, and why is it important?

Tumour extension describes how far the tumour has grown beyond the kidney into surrounding tissues or organs, such as nearby fat, large veins, or other structures. This is carefully evaluated and reported by pathologists. Tumour extension is important because it affects the stage of the cancer, influences treatment decisions, and can determine the prognosis. Tumours confined within the kidney generally have a better outlook than tumours that extend beyond the kidney.

What are surgical margins, and why are they important?

Surgical margins are the edges of healthy tissue that are removed along with the tumour during surgery. Pathologists carefully examine these edges to ensure no tumour cells remain behind.

• Negative margins: No tumour cells are found at the edges of the tissue. This means the entire tumour was likely removed, reducing the chance of recurrence.

• Positive margins: Tumour cells are present at the edges of the tissue. Positive margins mean some tumour may remain, and additional treatment might be necessary.

Your pathology report will clearly state the margin status, helping your doctor determine whether further treatment is necessary.

What is lymphovascular invasion, and why is it important?

Lymphovascular invasion means tumour cells have entered small blood vessels or lymphatic vessels (channels that carry fluid called lymph to lymph nodes). Tumours with lymphovascular invasion have a higher risk of spreading to other parts of the body. Pathologists carefully examine for lymphovascular invasion, as its presence may influence treatment decisions and monitoring.

Were lymph nodes examined, and what do the results mean?

Lymph nodes are small, bean-shaped immune organs throughout your body. Tumour cells can spread to lymph nodes through lymphatic vessels.

If lymph nodes were removed during surgery, pathologists carefully examine them under the microscope to check for tumour cells.

• Negative lymph nodes: No tumour cells were found in the lymph nodes examined. This indicates the tumour likely hasn’t spread.

• Positive lymph nodes: Tumour cells were found in one or more of the lymph nodes examined. Positive lymph nodes indicate that the tumour has spread, which may require additional treatments, such as chemotherapy or immunotherapy.

Your pathology report will detail how many lymph nodes were examined, whether tumour cells were found, and the size of any tumour deposits.

Prognosis and treatment for succinate dehydrogenase-deficient renal cell carcinoma

Most SDH-deficient RCC tumours have a favourable prognosis if detected and treated early. However, they can be aggressive, especially if certain high-risk features are present. These tumours may spread to other parts of the body or recur after treatment. Regular follow-up and surveillance are important, especially for those with inherited genetic changes.

Doctors typically recommend genetic counselling and genetic testing for individuals diagnosed with SDH-deficient RCC and their family members. Lifelong monitoring may be recommended due to the possibility of developing other related tumours.

Pathologic staging (TNM system) for succinate dehydrogenase-deficient renal cell carcinoma

Your doctor uses the TNM staging system to clearly describe how advanced your tumour is. The TNM system helps determine treatment decisions and your prognosis.

Tumour stage (T)

• T1: Tumour is 7 cm or smaller, entirely within the kidney.

• T2: Tumour is larger than 7 cm but confined to the kidney.

• T3: Tumour has grown into the surrounding fat or a large vein attached to the kidney.

• T4: Tumour has extended outside the kidney into adjacent structures or through Gerota’s fascia (the protective layer around the kidney).

Lymph node stage (N)

• N0: No tumour cells found in lymph nodes.

• N1: Tumour cells found in lymph nodes.

• NX: No lymph nodes were examined.

Metastatic stage (M)

• M0: Tumour has not spread to distant body parts.

• M1: Tumour has spread (metastasized) to distant parts of the body.

• MX: Spread to distant body parts cannot be determined.

Higher stages indicate more advanced tumours that may require more extensive treatments and monitoring.

Questions to ask your doctor

• Do I need genetic counselling or genetic testing for myself and my family members?

• What treatment options are best for my tumour?

• How often will I need follow-up tests or imaging?

• What is the likelihood of the tumour returning or spreading?

• Are lifestyle changes or dietary adjustments recommended after treatment?

• What signs or symptoms should I watch for and report immediately?