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

Section Editor: Trevor Flood MD FRCPC
July 17, 2026

Succinate dehydrogenase-deficient renal cell carcinoma, often shortened to SDH-deficient RCC, is a rare type of kidney cancer. It is caused by the loss of a group of proteins called the succinate dehydrogenase complex, which the cell uses to turn food into energy. Fewer than 1 in 200 kidney cancers are of this type, and it tends to affect people much younger than other kidney cancers, often in their thirties or forties.

Two features set this diagnosis apart. The first is reassuring: most of these tumors grow slowly and are cured by surgery. The second is the reason the diagnosis matters so much. Almost everyone with this tumor was born with the gene change that caused it, which means the diagnosis identifies an inherited condition that also raises the risk of tumors elsewhere in the body, and that close relatives may share.

This article will help you understand the findings in your pathology report for SDH-deficient renal cell carcinoma, what each term means, and why it matters for your care and for your family.

What causes succinate dehydrogenase-deficient renal cell carcinoma?

Succinate dehydrogenase-deficient renal cell carcinoma, a rare kidney cancer, is caused by the loss of the succinate dehydrogenase complex, a machine built from four parts encoded by four genes: SDHA, SDHB, SDHC, and SDHD. The complex sits inside the mitochondria, the parts of the cell that produce energy, and it performs one step in the chain of reactions that converts food into fuel. Damage to any one of the four genes causes the whole complex to fall apart. A substance called succinate then builds up inside the cell, changes which genes the cell switches on and off, and tricks the cell into behaving as though it is starved of oxygen. In the kidney, that combination can produce a tumor. SDHB is by far the gene most often responsible, followed by SDHC, SDHA, and rarely SDHD.

Nearly everyone with this tumor was born with a change in one copy of one of these genes, and the second copy was lost later in a kidney cell. Cases in which both copies were damaged in the kidney alone are very rare. This is the key difference between this cancer and the common kidney cancers, and it is why the diagnosis itself, on its own, is a reason to be referred for genetic testing.

Inherited conditions associated with SDH-deficient renal cell carcinoma

A change in an SDH gene present from birth is inherited in an autosomal dominant pattern, meaning a parent who carries it has a 1 in 2 chance of passing it to each child. Carriers are at risk of several tumors, not only kidney cancer. Most carriers never develop a kidney tumor at all.

Paraganglioma and pheochromocytoma — The tumors most commonly associated with these gene changes. Paragangliomas arise from cells of the nervous system that help regulate blood pressure and the body’s response to stress, and can occur in the head and neck, chest, abdomen, or pelvis. A pheochromocytoma is a tumor arising in the adrenal gland, which sits on top of the kidney. Some of these tumors release hormones and cause high blood pressure, headaches, sweating, or a racing heart, which is why carriers are monitored for them.
Gastrointestinal stromal tumor (GIST) — SDH-deficient GIST is a tumor of the wall of the digestive tract, almost always the stomach. When GIST and paraganglioma occur in the same person or family due to an inherited SDH gene mutation, the combination is called Carney-Stratakis syndrome.
Pituitary tumors — Reported in a small number of carriers, though much less often than the tumors above.

Which gene is involved shapes the risk. SDHB carriers, the group most likely to develop this kidney cancer, also have a higher risk of paragangliomas that spread, so the gene named in your genetic test result guides the follow-up plan that is built for you.

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

Most people with succinate dehydrogenase-deficient renal cell carcinoma, a rare kidney cancer, have no symptoms. These tumors are usually found by accident during an ultrasound, CT scan, or MRI performed for an unrelated reason, or during imaging performed because an inherited SDH gene change is already known. When symptoms do occur, they may include:

Blood in the urine, which can make the urine look red, pink, or brown.
Pain or a dull ache in the back or the side of the abdomen.
A lump or fullness in the abdomen or side.
Weight loss that was not intended, or fatigue.

Some people are diagnosed with a paraganglioma or a GIST first, and the kidney tumor is found later during the imaging that follows. If the tumor has spread to another part of the body (a process called metastasis), the symptoms depend on where it has spread.

How is the diagnosis made?

The diagnosis of succinate dehydrogenase-deficient renal cell carcinoma is made when a pathologist examines kidney tissue under a microscope and uses a special stain to confirm that the protein is missing. The tumor is usually first seen as a mass in the kidney on imaging. Tissue is most often obtained by surgery to remove the tumor, although a needle biopsy may be done first in some situations.

Under the microscope, this tumor has a distinctive and, importantly, a calm appearance. The cells are uniform and cuboidal with pink (eosinophilic) interiors, and they grow in solid sheets or compact nests. The feature that points to the diagnosis is inside the cell: bubbly spaces, called vacuoles, and pale inclusions filled with wispy material, which give the cytoplasm a bubbled look. Other common findings are small cysts, benign kidney tubules trapped within the tumor, and scattered immune cells called mast cells. The nuclei are round and bland, with no prominent nucleoli, and this low-grade appearance is characteristic of the tumor rather than an incidental detail. The pink cytoplasm means the tumor is often mistaken at first glance for an oncocytoma or a chromophobe renal cell carcinoma, and the presence of vacuoles often prompts a pathologist to order a confirmatory stain.

That stain is part of a test called immunohistochemistry, which uses special stains to detect proteins inside cells. The key stain is SDHB. Because damage to any of the four SDH genes causes the whole complex to break down, the SDHB protein disappears regardless of which gene is at fault, making this one stain a test for all of them. In this tumor the cancer cells lose SDHB while the normal cells and blood vessels around them keep it, and that internal comparison is what makes the result reliable. A second stain, SDHA, is often added: when both SDHA and SDHB are lost, SDHA is the likely cause, whereas loss of SDHB alone points to one of the other three genes. Other stains help distinguish this tumor from its look-alikes, as it is typically positive for PAX8, which confirms it originated in the kidney, and negative for CD117 and CK7, both of which are usually positive in oncocytoma and chromophobe renal cell carcinoma. Once the diagnosis is confirmed, imaging is used to assess for spread and, because of the syndrome, to identify tumors elsewhere.

Histologic grade and high-risk features

Most kidney cancers are given a grade, a number from 1 to 4 describing how abnormal the cells look, using the WHO/ISUP system based on how easily the nucleoli can be seen. That system was developed and validated for clear cell and papillary renal cell carcinoma, so a numeric grade may or may not appear on a report for succinate dehydrogenase-deficient renal cell carcinoma. What matters more is the description of the nuclei.

The great majority of these tumors have bland, low-grade nuclei, and those tumors behave well. A minority contain areas where the tumor has changed character, and three findings identify that minority. They are the most important things to look for on your report:

High-grade nuclei — Areas where the nuclei become enlarged and irregular with prominent nucleoli, in contrast to the bland nuclei found in the rest of the tumor.
Coagulative necrosis — Areas where tumor cells have died, usually because the tumor outgrew its blood supply.
Sarcomatoid change — Areas where the tumor cells are replaced by long, thin, spindle-shaped cells that resemble a soft tissue cancer rather than a carcinoma.

If none of these three appears on your report, the tumor falls into the group with an excellent outlook. If one or more is present, the risk that the cancer will return or spread is meaningfully higher, and follow-up is planned accordingly.

Tumor size

Your pathology report will state the size of the succinate dehydrogenase-deficient renal cell carcinoma, measured in centimeters, from the tissue removed at surgery. This measurement is more accurate than the size estimated on imaging beforehand, so the two numbers may not match exactly. Size is part of the tumor stage (pT), with thresholds of 4 cm, 7 cm, and 10 cm. These tumors are often several centimeters across when found, because they cause no symptoms and grow slowly, and a larger size in this tumor does not carry the concern it would in other kidney cancers when the high-risk features described above are absent.

Multifocal and bilateral tumors

Because the gene change that causes succinate dehydrogenase-deficient renal cell carcinoma is present in every kidney cell from birth, more than one tumor can develop. When more than one tumor is found in the same kidney, it is called multifocal; when tumors are present in both kidneys, they are called bilateral. Roughly a quarter of people with this diagnosis have more than one tumor.

Multiple tumors do not mean the cancer has spread. Each one started independently. Your report will describe each tumor separately, with its own size and features, and the stage is based on the largest. Finding more than one tumor strengthens the case for an inherited condition and affects surgical planning, because preserving kidney function becomes a long-term concern when new tumors may appear over a lifetime.

Tumor extension

Tumor extension describes whether a succinate dehydrogenase-deficient renal cell carcinoma has grown outside the kidney and, if so, how far. The kidney is surrounded by a layer of fat, and outside that fat is a tough envelope called Gerota’s fascia. The adrenal gland sits on top of the kidney, and the renal vein carries blood away from the kidney into the largest vein in the body, the inferior vena cava. Your pathologist examines all of these structures in the tissue removed at surgery.

The report may describe growth into the fat around the kidney (perinephric fat), into the fat in the middle of the kidney where the blood vessels enter (renal sinus fat), into the collecting system that drains urine (the pelvicalyceal system), into the renal vein or the inferior vena cava, into the adrenal gland, or through Gerota’s fascia into other organs. Most of these tumors remain confined to the kidney. When growth outside the kidney is present, it raises the tumor stage and is associated with a higher risk of the cancer returning.

Lymphovascular invasion

Lymphovascular invasion means that cells from the succinate dehydrogenase-deficient renal cell carcinoma are seen inside small blood vessels or lymphatic channels within or around the tumor. Blood vessels carry blood throughout the body, and lymphatic channels carry a fluid called lymph toward the lymph nodes. Tumor cells inside these vessels can be carried elsewhere, so lymphovascular invasion is associated with a higher risk of the cancer returning or spreading. It is uncommon in this tumor.

Lymphovascular invasion is not the same as growth into the renal vein, which is a large named vessel and is reported separately as part of tumor extension and stage. It does not change the pT stage on its own, but it is one of the findings your treatment team considers when deciding how closely to follow you after surgery.

Surgical margins

A margin is the cut edge of the tissue removed during surgery for succinate dehydrogenase-deficient renal cell carcinoma. Your pathologist examines these edges under the microscope to see whether any tumor cells reach them. Which margins are examined depends on the operation. In a partial nephrectomy, where only the tumor and a rim of surrounding tissue are removed, the margins are the kidney tissue and fat around the tumor. In a radical nephrectomy, where the whole kidney is removed, the margins include the fat around the kidney, the renal vein, and the ureter (the tube carrying urine to the bladder).

Negative margin — No tumor cells are seen at the cut edge. This suggests the whole tumor was removed and is associated with a low risk of the cancer coming back in the same place.
Positive margin — Tumor cells are present at the cut edge. This means tumor cells may have been left behind, and it is associated with a higher risk of the cancer returning at that site. A positive margin is one of the findings the surgical team uses when deciding whether more surgery or closer imaging follow-up should be considered.

Partial nephrectomy is used often in this tumor. Because a carrier may need more than one kidney operation over a lifetime, preserving as much working kidney as possible is weighed alongside removing the tumor completely.

Lymph nodes

Lymph nodes are small immune organs found throughout the body, including around the large blood vessels near the kidney. Cells from a succinate dehydrogenase-deficient renal cell carcinoma can travel through lymphatic channels and settle in a lymph node, although this is uncommon. Lymph nodes are not removed routinely during kidney cancer surgery. They are usually removed only when they look enlarged on imaging or feel abnormal during the operation, so many reports for this cancer will say that no lymph nodes were submitted.

If lymph nodes were removed, your report will state how many were examined, how many contained cancer, and the size of the largest deposit of tumor within a node. It may also state whether extranodal extension is present, meaning that cancer cells within a lymph node have broken through the node’s outer capsule into the surrounding tissue. Cancer in even one lymph node places the tumor in a higher stage group and is associated with a higher risk of the cancer returning.

Examination of the non-tumor kidney

When kidney tissue is removed for succinate dehydrogenase-deficient renal cell carcinoma, your pathologist also examines the kidney tissue away from the tumor. Two kinds of findings may be described. The first are changes that affect how well the remaining kidney will work, such as scarring from long-standing high blood pressure or diabetes. The second are additional small tumors, which matter here because a carrier can develop more than one over time. Because most people with this diagnosis are young and may face further kidney surgery in the future, the condition of the kidney away from the tumor is worth asking about.

Biomarker and molecular testing

Biomarkers are features of a tumor, usually a protein or a change in a gene, that provide information beyond the diagnosis itself. In some cancers, biomarker results decide which drug a person receives. That is not the case here: no biomarker test currently selects treatment for this cancer. The testing described below matters for another, equally important reason. In succinate dehydrogenase-deficient renal cell carcinoma, the finding that establishes the diagnosis, the loss of the SDHB protein described above, is also the strongest signal of an inherited condition of any kidney cancer, and that condition affects your lifelong care and your family.

Inherited (germline) SDH testing

Germline testing looks for a gene change a person was born with, using a blood or saliva sample rather than the tumor itself. A diagnosis of SDH-deficient renal cell carcinoma is a reason to offer this testing to every patient, regardless of age and regardless of whether anyone in the family has had a tumor. This is different from most kidney cancers, where testing is reserved for people who are young, have several tumors, or have a family history. The reason is that almost every one of these tumors turns out to be caused by an inherited gene change, and the pathologist cannot tell from the tumor alone. The genes tested are SDHB, SDHA, SDHC, and SDHD, and the SDHA stain result described above helps direct which is examined most closely.

Results are reported in one of three ways: a pathogenic (disease-causing) variant, which confirms the inherited condition; no variant identified, which is uncommon in this tumor and means the gene changes were confined to the kidney; or a variant of uncertain significance, which means a change was found but it is not yet known whether it matters. A pathogenic result changes the plan for you and for your family. It means lifelong monitoring not only of your kidneys but for paraganglioma, pheochromocytoma, and GIST, and it means your parents, siblings, and children can be offered testing of their own, called cascade testing, through a genetics clinic. Because tumors in this syndrome can appear in childhood and adolescence, testing and monitoring in relatives generally begin at a young age.

Comprehensive genomic profiling (next-generation sequencing)

Next-generation sequencing reads many genes at once from the tumor tissue. In this cancer it is generally performed only when the diagnosis remains uncertain after the stains, or when the cancer has spread and a clinical trial is being considered. These tumors carry very few mutations besides the SDH gene change itself, so panels usually return little. Molecular testing of the tumor alone cannot reliably tell you whether a gene change was inherited; only the germline test described above can do that.

Mismatch repair, microsatellite instability, and tumor mutational burden

These tests identify tumors that respond to immunotherapy regardless of where the cancer started, an idea called a tumor-agnostic approval. Mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) are tested by immunohistochemistry and reported as intact or retained, which is the normal result, or as deficient (dMMR) when one or more proteins are lost. The related test for microsatellite instability is reported as stable (MSS) or high (MSI-H). Tumor mutational burden counts the number of mutations in the tumor and is reported as mutations per megabase, with 10 or more considered high. All three findings are rare in this cancer, so a normal result is expected. When one is present, it can make a person eligible for the immunotherapy drug pembrolizumab under approvals that apply across cancer types.

You can learn more about the tests described here in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage of a succinate dehydrogenase-deficient renal cell carcinoma describes how far the cancer had grown at the time of surgery. It is written using the TNM system created by the American Joint Committee on Cancer (AJCC), currently in its 8th edition, and it is the same system used for all renal cell carcinomas. T describes the size of the tumor and how far it has grown outside the kidney, N describes whether cancer is found in nearby lymph nodes, and M describes whether the cancer has spread to a distant part of the body. The letter “p” in front means the category was assigned by a pathologist after examining the tissue. The M category is almost always determined by imaging rather than by the pathologist, so it may not appear on your report at all. When more than one tumor is present, the stage is based on the largest.

Tumor stage (pT)

pT1a — The tumor is 4 cm or smaller and remains inside the kidney.
pT1b — The tumor is larger than 4 cm but not more than 7 cm and remains inside the kidney.
pT2a — The tumor is larger than 7 cm but not more than 10 cm and remains inside the kidney.
pT2b — The tumor is larger than 10 cm and remains inside the kidney.
pT3a — The tumor has grown into the renal vein or one of its branches, into the fat around the kidney or in the renal sinus, or into the collecting system that drains urine, but not beyond Gerota’s fascia.
pT3b — The tumor has grown into the inferior vena cava below the diaphragm.
pT3c — The tumor has grown into the inferior vena cava above the diaphragm, or into the wall of the vena cava.
pT4 — The tumor has grown beyond Gerota’s fascia, including growth into the adrenal gland on the same side.

Nodal stage (pN)

pN0 — No cancer was found in any of the lymph nodes examined.
pN1 — Cancer was found in one or more nearby lymph nodes.
pNX — No lymph nodes were removed or they could not be assessed. This is a common and expected result in kidney cancer surgery.

What is the prognosis?

Prognosis means the expected course of a disease. For most people with succinate dehydrogenase-deficient renal cell carcinoma, the outlook is good. The typical tumor, with bland low-grade nuclei and no necrosis or sarcomatoid change, is confined to the kidney and is cured by surgery, and spread to other parts of the body occurs in only about 1 in 10 people. The tumors that do spread are almost always those carrying one or more of the three high-risk features described earlier, which is why those findings matter more on your report than the tumor’s size.

One quality of this cancer shapes follow-up more than any other: it can return very late. Spread has been reported more than a decade after the kidney was removed, well beyond the period over which most cancers are watched. Combined with the risk of new kidney tumors and of tumors elsewhere from the inherited condition, this is why follow-up here is measured in decades rather than years. The features on your report associated with a higher risk of the cancer returning are high-grade nuclei, coagulative necrosis, sarcomatoid change, growth outside the kidney, lymphovascular invasion, a positive surgical margin, and cancer in lymph nodes.

What happens after the diagnosis?

Once succinate dehydrogenase-deficient renal cell carcinoma has been confirmed, the findings on your pathology report, particularly whether any of the three high-risk features are present, the stage, and the margin status, shape the next steps. This diagnosis involves a wider team than other kidney cancers, usually including a urologist, a pathologist, a radiologist, a genetic counselor, and often an endocrinologist for other tumors associated with the syndrome. Because the tumor is rare, review at or in consultation with a center that sees it regularly is worth asking about.

Surgery — Surgery is the main treatment and is usually curative. A partial nephrectomy, which preserves the rest of the kidney, is favored where the tumor allows, because a carrier may need further kidney surgery over a lifetime. A radical nephrectomy removes the whole kidney and is considered for larger tumors or tumors involving the renal vein.
Treatment after surgery (adjuvant therapy) — No drug treatment given after surgery has been shown to help in this cancer. The immunotherapy options approved after kidney cancer surgery, including pembrolizumab and the pembrolizumab and belzutifan combination approved in June 2026, were studied in and approved for renal cell carcinoma with a clear cell component and do not apply here. Follow-up is by imaging.
Treatment for cancer that has spread — No treatment has been tested in a trial devoted to this cancer, and there is no established standard. Options are drawn from studies of kidney cancers other than clear cell, and a clinical trial is discussed more often here than for common kidney cancers. Chemotherapy is not effective and is not used. Surgery or radiation may be considered for a single site of spread. One point sometimes causes confusion: belzutifan, a drug that blocks the same oxygen-sensing pathway this tumor switches on, was approved in May 2025 for advanced paraganglioma and pheochromocytoma. That approval covers those tumors, not this kidney cancer, although the shared biology is one reason the drug is of research interest here.
Genetic assessment — A referral to a genetics clinic is part of standard care for everyone with this diagnosis, not only those with a family history. If an inherited SDH gene change is confirmed, your relatives can be tested, and those who carry it enter a monitoring program.
Lifelong surveillance — If an inherited gene change is confirmed, monitoring covers more than the kidneys. It typically includes periodic imaging of the abdomen and, depending on the gene involved, whole-body imaging and blood or urine tests that detect the hormones some paragangliomas release. Your genetics and endocrine teams will build the schedule around the specific gene, and it continues for life.

Questions to ask your doctor

Was the diagnosis confirmed with the SDHB stain, and was SDHA also tested?
Has genetic testing been arranged for me, and when will I see a genetic counselor?
Which SDH gene is involved, and what does that mean for my risk of other tumors?
If the gene change is inherited, which of my relatives should be tested, and at what age?
Did my tumor show high-grade nuclei, necrosis, or sarcomatoid change?
How large was my tumor, and what was the pathologic stage (pT and pN)?
Was there more than one tumor in my kidney, or tumors in both kidneys?
Were the surgical margins negative or positive, and if positive, where?
Did the tumor grow outside the kidney, into the fat, the renal sinus, or the renal vein?
Was as much of my kidney preserved as possible, and how well is my kidney function now?
Will I be monitored for paraganglioma, pheochromocytoma, and GIST as well as for kidney tumors?
How often will I need imaging, what type of scans, and for how many years?
Should my care be reviewed at a center that specializes in rare and inherited kidney cancers?
Are there clinical trials I should know about?