Epithelioid Angiomyolipoma: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
July 18, 2026

Epithelioid angiomyolipoma is a rare kidney tumor and an uncommon type of angiomyolipoma. A classic angiomyolipoma is a noncancerous tumor made of a mixture of fat, muscle, and blood vessels. Epithelioid angiomyolipoma is different: it is built mostly from a single kind of cell, the epithelioid cell, which makes up at least 80% of the tumor, and it contains little or none of the fat that gives classic angiomyolipoma its name.

The most important thing to understand about this tumor is that it does not fit neatly into “benign” or “cancer.” Most epithelioid angiomyolipomas are cured by surgery and never cause further trouble. A minority behave like a cancer, growing into nearby tissue, coming back after surgery, or spreading to other parts of the body. For this reason it is described as a tumor with malignant potential, and the main job of your pathology report is to look for the specific features that separate the tumors likely to behave well from the smaller number that may not.

This article will help you understand the findings in your pathology report for epithelioid angiomyolipoma, what each term means, and why it matters for your care.

What causes epithelioid angiomyolipoma?

Most epithelioid angiomyolipomas, a rare kidney tumor, develop because of a change in a gene called TSC2 (and sometimes the related gene TSC1). These genes normally act as a brake on cell growth by controlling a growth-signaling system inside the cell called the mTOR pathway. When the brake is lost, the mTOR pathway stays switched on and the cells keep growing. This mechanism matters beyond simply explaining the tumor, because drugs that block the mTOR pathway are the main treatment when this tumor spreads, as described in the biomarker and treatment sections below.

Epithelioid angiomyolipoma belongs to a family of tumors called PEComas (perivascular epithelioid cell tumors), which arise from a specialized cell normally found wrapped around small blood vessels. Other members of this family are found in the uterus, liver, lungs, and soft tissues, and they share the same mTOR biology.

Inherited conditions associated with epithelioid angiomyolipoma

Many epithelioid angiomyolipomas happen by chance, with no inherited condition. Some occur in people with tuberous sclerosis complex, an inherited condition caused by a change in the TSC1 or TSC2 gene present from birth. Tuberous sclerosis affects cell growth throughout the body and causes tumors and other changes in the kidneys, brain, skin, heart, and lungs. It is also the condition most associated with classic angiomyolipoma. A rarer inherited disorder involving both the TSC2 and PKD1 genes, called TSC2/PKD1 contiguous gene syndrome, combines kidney cysts with these tumors. Because of these links, a person found to have epithelioid angiomyolipoma, particularly at a young age or with more than one kidney tumor, may be asked about features of tuberous sclerosis and, in some cases, referred for genetic assessment.

What are the symptoms of epithelioid angiomyolipoma?

Many epithelioid angiomyolipomas, a rare kidney tumor, are found by chance when imaging is done for another reason. When symptoms occur, they may include:

Pain or discomfort in the flank or abdomen.
Blood in the urine, which can make the urine look pink, red, or brown.
A lump that can be felt in the abdomen or side.

On imaging, epithelioid angiomyolipoma often looks like a renal cell carcinoma, because it usually lacks the fat that makes a classic angiomyolipoma easy to recognize on a scan. This overlap is the reason the diagnosis usually cannot be made from imaging alone and requires a tissue sample.

Who gets epithelioid angiomyolipoma?

Epithelioid angiomyolipoma is uncommon, making up fewer than 5 out of every 100 angiomyolipomas removed by surgery. The average age at diagnosis is about 50 years, with a wide range from about 30 to 80 years, and men and women are affected equally.

How is the diagnosis made?

The diagnosis of epithelioid angiomyolipoma is made when a pathologist examines the tumor under a microscope and confirms it with special stains. Because imaging cannot reliably tell this tumor apart from kidney cancer, a tissue sample is needed, obtained either by a needle biopsy or, more often, by surgery to remove the tumor. Under the microscope, the tumor is made up mostly of epithelioid cells, which are round to many-sided cells with abundant cytoplasm, rather than the long, thin muscle cells of a classic angiomyolipoma. These cells are typically larger and plumper than normal muscle cells and make up at least 80% of the tumor.

Pathologists recognize two growth patterns, which may be named in your report. In the carcinoma-like pattern, the cells grow in nests and clusters separated by thin bands of small blood vessels, resembling a carcinoma even though the tumor does not come from epithelial cells; the cells often have abundant pink cytoplasm, prominent nucleoli, and small round intranuclear inclusions, and some resemble large nerve-related cells called ganglion cells based on shape alone. In the diffuse epithelioid and spindle cell pattern, the cells grow in sheets and may be epithelioid or spindle-shaped, usually with milder abnormality. Other findings that may be described include multinucleated giant cells, small areas of fat, and thick-walled blood vessels.

The diagnosis is confirmed with immunohistochemistry, a test that uses special stains to detect proteins inside cells. Epithelioid angiomyolipoma is characteristically positive for markers normally found in pigment-producing cells, including HMB-45, Melan-A, and MITF, and for a protein called cathepsin K, while showing variable staining for smooth muscle actin. This combination is what separates epithelioid angiomyolipoma from the kidney cancers it can resemble, above all clear cell renal cell carcinoma and urothelial carcinoma, which do not carry these pigment-cell markers. Because these stains establish what the tumor is rather than guiding treatment, they belong here in the diagnosis rather than in the biomarker section.

One test requires caution. A protein called TFE3 is sometimes positive in these tumors, but most epithelioid angiomyolipomas that stain for TFE3 do not have a true change in the TFE3 gene. A small number of PEComas do carry a genuine TFE3 rearrangement and are now regarded as a distinct tumor, so when the stain is positive, a genetic test may be added to sort out which situation applies.

Risk features and how this tumor behaves

Because epithelioid angiomyolipoma sits between benign and malignant, your pathology report does not simply call it one or the other. Instead, it describes a set of features that, taken together, estimate the risk that the tumor will come back or spread. Understanding these features is key to reading the report, because a tumor with none of them is very likely to behave benignly, while a tumor with several is the kind that warrants closer follow-up.

The features associated with a higher risk of recurrence or spread are:

Large tumor size — Tumors larger than 7 cm carry a higher risk.
A high proportion of atypical cells — Cells with marked nuclear atypia, meaning they look strikingly abnormal.
Increased mitotic activity — A higher number of dividing cells, or mitotic figures, than expected. Two or more per a defined area of tissue is one of the thresholds used.
Atypical mitotic figures — Dividing cells with an abnormal shape.
Tumor necrosis — Areas where tumor cells have died.
Growth into surrounding structures — Extension into the fat around the kidney or into blood vessels such as the renal vein.
A carcinoma-like growth pattern — The nested pattern described above, which is associated with more concerning behavior than the diffuse pattern.

Pathologists have proposed formal systems that count these features and sort tumors into low-, intermediate-, and high-risk groups; the systems developed by Brimo and by Nese are the ones most often referenced. There is no universally agreed-upon set of criteria, so your report may describe individual features rather than assign a single risk label. A related marker, Ki-67, which measures how many cells are actively dividing, and loss of the smooth muscle actin stain have both been linked to more concerning behavior and may be mentioned as well.

Surgical margins

A margin is the cut edge of the tissue removed during surgery for epithelioid angiomyolipoma. Your pathologist examines these edges under the microscope to see whether any tumor cells reach them.

Negative margin — No tumor cells are seen at the cut edge. This suggests the entire tumor was removed and is associated with a lower chance of it returning in the same place.
Positive margin — Tumor cells are present at the cut edge, which means some tumor may have been left behind and is associated with a higher chance of it 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.

Is epithelioid angiomyolipoma staged?

Epithelioid angiomyolipoma is not staged using the TNM system that is applied to kidney cancers such as renal cell carcinoma. Because it is a tumor of uncertain behavior rather than a confirmed cancer, there is no formal stage number. Its outlook is judged instead from the risk features described above, together with whether it was completely removed and whether it had already grown outside the kidney or spread at the time of diagnosis.

Biomarker and molecular testing

Biomarkers are features of a tumor, usually proteins or gene changes, that provide information beyond the diagnosis itself. For most epithelioid angiomyolipomas, no molecular testing is needed, because surgery removes the tumor and no further treatment is required. Testing becomes relevant in the minority of cases that behave like a cancer, and epithelioid angiomyolipoma is unusual among kidney tumors in having a biomarker that directly points to a treatment.

The mTOR pathway (TSC1 and TSC2)

As described earlier, these tumors are driven by loss of TSC1 or TSC2, which leaves the mTOR growth pathway switched on. This is not only the cause of the tumor but also its treatment target. Drugs that block the mTOR pathway, called mTOR inhibitors, work particularly well in tumors driven this way. For a tumor that has been completely removed, this biology usually stays in the background. For a tumor that has spread or cannot be fully removed, drug treatment becomes the basis, as described in the next section. Testing of the TSC1 and TSC2 genes by next-generation sequencing is generally reserved for those situations, or when an inherited condition is suspected.

TFE3 testing

As noted in the diagnosis section, a positive TFE3 stain does not necessarily indicate a true TFE3 gene change. When the distinction matters, a genetic test such as FISH or sequencing is used to confirm the presence of a genuine TFE3 rearrangement, because a PEComa with a real TFE3 rearrangement is considered a separate tumor. This testing clarifies the diagnosis rather than selecting a treatment.

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

What is the prognosis?

Prognosis means the expected course of a disease. For epithelioid angiomyolipoma, the outlook varies more than for almost any other kidney tumor, which is exactly why the risk features above matter so much. Most tumors, especially small ones without concerning features, are cured by surgery and never return. A minority, particularly larger tumors with several high-risk features, come back after surgery or spread to other parts of the body, most often the liver, lungs, or nearby lymph nodes. The tumors reported to behave in a cancer-like way have usually carried more than one of the high-risk features rather than a single one.

Because behavior cannot be predicted with certainty from the microscope alone, follow-up is tailored to the risk features on your report. A tumor with none of them may need only limited imaging follow-up, while a tumor with several is followed more closely and for longer. Your treatment team will explain where your tumor falls and what that means for the follow-up plan.

What happens after the diagnosis?

Once epithelioid angiomyolipoma has been confirmed, the findings on your pathology report, above all the risk features and whether the tumor was completely removed, shape the next steps. Care usually involves a urologist, a pathologist, and a radiologist, with a medical oncologist becoming involved if the tumor has spread or carries high-risk features.

Surgery — Surgery to remove the tumor is the main treatment and cures most epithelioid angiomyolipomas. Depending on the size and location, this may be a partial nephrectomy, which preserves the rest of the kidney, or removal of the whole kidney. Complete removal with clear margins is the goal.
mTOR inhibitor drugs — For a tumor that has spread or cannot be completely removed, drugs that block the mTOR pathway are the main treatment, reflecting the biology described above. Nab-sirolimus (Fyarro) is approved specifically for advanced PEComas that behave in a malignant way, based on a trial in which the tumor shrank in a meaningful proportion of patients, and a related drug, everolimus, has also been used with response in this setting. These drugs are far more effective here than traditional chemotherapy, which works poorly against this tumor and is generally not used.
Follow-up — After surgery, imaging of the abdomen, and sometimes the chest, is used to watch for the tumor returning or spreading, on a schedule matched to the risk features on your report. Because a tumor with high-risk features can return later, follow-up in that situation continues for a number of years.
Genetic assessment — If tuberous sclerosis or another inherited condition is suspected, a referral to a genetics clinic may be arranged so that the condition can be looked for and family members supported if needed.

Questions to ask your doctor

Is this tumor an epithelioid angiomyolipoma, and how was it told apart from a kidney cancer?
Which of the high-risk features, if any, were present in my tumor?
How large was the tumor, and did it grow outside the kidney or into a blood vessel?
Was tumor necrosis, atypia, or increased mitotic activity seen?
Was the tumor completely removed, and were the surgical margins clear?
Would my tumor be considered low, intermediate, or high risk?
Could this tumor be related to tuberous sclerosis or another inherited condition?
Should I be referred for genetic counseling, and should my family be assessed?
Do I need any treatment beyond surgery?
If the tumor were to spread, would an mTOR inhibitor such as nab-sirolimus be an option?
How often will I need imaging follow-up, and for how many years?
What symptoms should prompt me to seek medical attention?