Your pathology report for epithelioid angiomyolipoma

by Jason Wasserman MD PhD FRCPC
January 12, 2026

Epithelioid angiomyolipoma is a rare type of kidney tumour and a variant of angiomyolipoma. Unlike classic angiomyolipoma, which contains a mixture of fat, muscle, and blood vessels, epithelioid angiomyolipoma is made up mostly of epithelioid cells (at least 80%). Because of these cells, this tumour can sometimes behave more aggressively than classic angiomyolipoma.

This article explains the pathology report for epithelioid angiomyolipoma, including how it is diagnosed, what features pathologists look for, and how these findings relate to prognosis and treatment.

Where does epithelioid angiomyolipoma develop?

Epithelioid angiomyolipoma develops in the kidney. In some cases, the tumour can:

• Extend outside the kidney into the surrounding tissues.

• Involve nearby blood vessels, such as the renal vein.

What symptoms can epithelioid angiomyolipoma cause?

Many epithelioid angiomyolipomas are discovered incidentally during imaging performed for another reason. When symptoms occur, they may include flank or abdominal pain, blood in the urine, or a palpable mass.

On imaging studies, epithelioid angiomyolipoma often looks similar to renal cell carcinoma, which is why biopsy or surgical removal is frequently needed to make a definite diagnosis.

Who gets epithelioid angiomyolipoma?

The average age at diagnosis is about 50 years, with a wide age range from 30 to 80 years. Men and women are affected equally. Epithelioid angiomyolipoma is uncommon, accounting for less than 5% of all surgically removed angiomyolipomas.

What causes epithelioid angiomyolipoma?

Some cases occur in people with tuberous sclerosis, a genetic condition that affects cell growth and can cause tumours in multiple organs. Epithelioid angiomyolipoma has also been reported in people with TSC2/PKD1 contiguous gene syndrome, a rare inherited disorder involving both kidney cysts and tumours.

However, many cases occur sporadically, meaning there is no known inherited condition.

How does epithelioid angiomyolipoma develop?

Most epithelioid angiomyolipomas show changes involving the TSC2 gene, which normally helps regulate cell growth. When this gene does not function properly, it can lead to uncontrolled cell growth by activating the mTOR pathway.

These tumours belong to a group of related tumours called PEComas (perivascular epithelioid cell tumours), which arise from specialized cells found around blood vessels.

How is the diagnosis made?

The diagnosis is made by examining tumour tissue under the microscope and using immunohistochemistry. Because imaging alone cannot reliably distinguish epithelioid angiomyolipoma from kidney cancer, tissue examination is essential.

Microscopic (pathologic) features

Under the microscope, epithelioid angiomyolipoma is defined by the presence of large numbers of epithelioid cells, comprising at least 80% of the tumour.

Epithelioid cells are tumour cells that look round to polygonal, with more abundant cytoplasm, rather than long and spindle-shaped. In epithelioid angiomyolipoma, these cells are larger and plumper than the smooth muscle cells seen in classic angiomyolipoma.

Two main microscopic growth patterns may be seen: carcinoma-like and diffuse epithelioid and spindle cell.

Carcinoma-like pattern

In this pattern, the tumour cells grow in nests or clusters, as many cancers called carcinomas do. This appearance is why the term carcinoma-like is used, although the tumour does not arise from epithelial cells.

The cells often have abundant pink (eosinophilic) cytoplasm, prominent nucleoli (small structures inside the nucleus that help make proteins), and intranuclear inclusions (small round areas inside the nucleus). Some of these cells resemble ganglion cells, which are large nerve-related cells normally found in the nervous system. This resemblance is based on size and shape only and does not mean the tumour comes from nerves.

The nests are separated by thin tissue containing many small blood vessels. In most cases, only a few dividing cells (mitoses) are seen.

Diffuse epithelioid and spindle cell pattern

In this pattern, the tumour grows as sheets of cells rather than distinct nests. The cells may be epithelioid or spindle-shaped (elongated cells that taper at the ends). The cells usually show moderate atypia, meaning they look somewhat abnormal but not extremely aggressive. Mitotic activity is typically low, and intranuclear inclusions are uncommon.

Additional microscopic features that may be seen include:

• Multinucleated giant cells (large cells with more than one nucleus).

• Small areas of fat.

• Thick-walled blood vessels, which may be less obvious than in classic angiomyolipoma.

Immunohistochemistry

Immunohistochemistry is a laboratory test that uses special stains to detect proteins inside tumour cells. These stains help confirm the diagnosis and distinguish epithelioid angiomyolipoma from kidney cancers.

Epithelioid angiomyolipoma typically shows:

• Positivity for melanocytic markers such as HMB45, melan-A, and MITF.

• Expression of cathepsin K.

• Variable expression of smooth muscle markers.

This staining pattern helps distinguish epithelioid angiomyolipoma from clear cell renal cell carcinoma and urothelial carcinoma, which do not share this immunophenotype. There is some overlap with certain rare kidney cancers, but additional markers (such as PAX8 and CD68) help resolve these cases.

Molecular testing

Molecular testing looks for changes in the DNA of tumour cells. Routine molecular testing is not required for diagnosis.

Rarely, rearrangements involving the TFE3 gene have been reported. However, most epithelioid angiomyolipomas that show TFE3 staining lack a true TFE3 gene rearrangement, so these findings must be interpreted with caution.

How is epithelioid angiomyolipoma staged?

Epithelioid angiomyolipoma is not staged using standard cancer staging systems.

Is epithelioid angiomyolipoma cancer?

This is an important and often confusing question.

Epithelioid angiomyolipoma is not typically considered a cancer, but in some cases, it behaves like cancer. Because of this unpredictable behaviour, it is often described as a tumour with malignant potential.

Most classic angiomyolipomas are clearly benign and do not spread. In contrast, epithelioid angiomyolipoma can sometimes:

• Grow aggressively.

• Come back after surgery.

• Spread (metastasize) to other parts of the body.

However, not all epithelioid angiomyolipomas behave this way. Many remain localized and do not cause serious problems after removal.

Pathologists cannot label all epithelioid angiomyolipomas as cancer because:

• Some tumours show no aggressive features and behave in a benign manner.

• Others show features under the microscope that are linked to a higher risk of spread or recurrence.

For this reason, your pathology report focuses on specific high-risk features, such as tumour size, cell appearance, mitotic activity, necrosis (areas of dead tumour), and invasion into nearby tissues or blood vessels. These features help doctors estimate the risk of aggressive behaviour and decide how closely to follow the patient after treatment.

What is the prognosis for a person with epithelioid angiomyolipoma?

Unlike classic angiomyolipoma, epithelioid angiomyolipoma can behave aggressively and, in some cases, is considered malignant. Reported behaviour ranges widely, from indolent tumours to those that recur or metastasize.

Certain features have been associated with a higher risk of aggressive behaviour, including:

• A high percentage of atypical epithelioid cells.

• Increased mitotic activity.

• Atypical mitotic figures.

• Tumour necrosis.

• Large tumour size (greater than 7 cm).

• Growth into surrounding fat or blood vessels.

• A carcinoma-like growth pattern.

Some studies have proposed risk stratification systems that divide tumours into low-, intermediate-, and high-risk groups based on these features. Tumours with multiple high-risk features are more likely to progress or metastasize and require closer follow-up.

Questions to ask your doctor

• Is this tumour an epithelioid angiomyolipoma or another type of kidney tumour?
• Do any features in my pathology report suggest a higher risk of aggressive behaviour?
• Is this tumour related to tuberous sclerosis or another genetic condition?
• Do I need additional treatment or imaging follow-up?
• What symptoms should prompt urgent medical attention?