Determining Epithelioid Component in Renal Angiomyolipoma
Epithelioid angiomyolipoma is definitively diagnosed by histopathologic examination showing ≥80% epithelioid cells, requiring tissue biopsy or surgical resection for confirmation. 1
Histopathologic Criteria for Epithelioid Component
The diagnosis of epithelioid angiomyolipoma (EAML) requires microscopic examination of tissue with specific quantitative and qualitative features:
Quantitative Threshold
- Tumors with ≥80% epithelioid cells are classified as epithelioid angiomyolipoma according to the 2016 WHO classification. 1
- Any angiomyolipoma containing an epithelioid component (even <80%) warrants special attention, as these occur in approximately 7.7% of all angiomyolipomas. 2
Cellular Morphology
The epithelioid tumor cells are categorized into three types based on cell size: 2
- Small cell type
- Intermediate cell type
- Large cell type
Key Histologic Features Suggesting Epithelioid Component
- Extreme cytological atypia (present in 93% of EAML cases) 2
- Histiocytoid appearance of cells 3
- Coagulative tumor necrosis (seen in 27% of EAML) 2
- Increased mitotic activity (present in 47% of EAML) 2
- Solid architecture without frequent alveolar patterns 3
Immunohistochemical Markers
Positive melanocytic markers are essential for confirming the diagnosis: 4
- HMB45 positivity
- MelanA positivity
Strong p53 staining may suggest the presence of an epithelioid component, even in otherwise classic-appearing angiomyolipomas. 1
When to Obtain Tissue for Diagnosis
Indications for Biopsy
- Fat-poor angiomyolipomas with growth rate >5 mm per year 5
- Lesions failing to respond to 12 months of mTOR inhibitor therapy 5
- Atypical imaging features that raise concern for malignancy 6
Important Caveat
Routine percutaneous kidney biopsy is NOT recommended for all fat-poor angiomyolipomas. 5 Biopsy should be reserved for specific clinical scenarios as outlined above.
Imaging Limitations
Imaging alone cannot definitively identify epithelioid histology: 6, 1
- CT and MRI cannot reliably distinguish fat-free angiomyolipoma (which may be epithelioid) from renal cell carcinoma 6
- Fatty appearance on imaging is MORE commonly observed in tumors WITHOUT an epithelioid component 1
- MRI is preferred for characterization and surveillance but cannot determine epithelioid features 5, 7
Clinical Significance and Prognostic Features
Malignant Potential Indicators
Eight features suggest malignant behavior when ≥5 are present: 4
- Size ≥5 cm
- Metastasis
- Infiltration
- Necrosis
- ≥50% atypical epithelioid cells
- Cytologic atypia
- Atypical mitosis
- Vessel invasion
Association with Tuberous Sclerosis Complex
Epithelioid component is more common in TSC-associated angiomyolipomas (25%) compared to sporadic cases (6.2%). 2 The presence of epithelioid component, epithelial cysts, and microscopic AML foci together should raise strong suspicion for TSC. 2
Practical Algorithm
- If imaging shows fat-poor lesion with growth >5 mm/year: Consider percutaneous core biopsy 5
- If lesion requires intervention: Obtain tissue via nephron-sparing surgery (enucleation preferred) 5
- Submit tissue for: Standard histopathology with quantification of epithelioid cells, immunohistochemistry (HMB45, MelanA, p53), and assessment of mitotic activity 1, 2, 4
- If ≥80% epithelioid cells: Diagnose as epithelioid angiomyolipoma and assess for malignant features 1, 4
Critical Pitfall to Avoid
Do not rely on imaging characteristics alone to exclude epithelioid histology. Fat-poor appearance on imaging does not automatically indicate epithelioid variant, and conversely, some epithelioid angiomyolipomas may contain fat. 1 Tissue diagnosis is mandatory for definitive characterization.