Definition/General
Introduction:
Renal angiomyolipoma is a benign mesenchymal tumor
Belongs to PEComa family
Composed of blood vessels, smooth muscle, and adipose tissue
Excellent prognosis
Associated with tuberous sclerosis complex.
Origin:
Arises from perivascular epithelioid cells (PEC)
Shows melanoma markers positivity
mTOR pathway involvement
Associated with TSC1/TSC2 mutations.
Classification:
WHO 2022: Angiomyolipoma
Classic triphasic
Epithelioid angiomyolipoma
Fat-poor angiomyolipoma
Part of PEComa tumor family.
Epidemiology:
Peak incidence 4th-5th decades
Female predominance (4:1)
Sporadic (80%) vs TSC-associated (20%)
Bilateral/multiple in TSC
Most common benign kidney tumor.
Clinical Features
Presentation:
Asymptomatic (50%)
Flank pain
Retroperitoneal hemorrhage (large tumors >4 cm)
Hematuria
Palpable mass
Wunderlich syndrome.
Symptoms:
Abdominal/flank pain
Sudden severe pain (hemorrhage)
Hematuria
Hypovolemic shock
Nausea/vomiting
Constitutional symptoms (bleeding).
Risk Factors:
Tuberous sclerosis complex
Female gender
Estrogen exposure
Pregnancy (growth acceleration)
LAM syndrome
TSC1/TSC2 mutations.
Screening:
CT/MRI imaging
Fat-containing lesion
Heterogeneous enhancement
Aneurysm formation
TSC screening
Family history.
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Gross Description
Appearance:
Well-circumscribed
Yellow-gray color
Soft consistency
Heterogeneous cut surface
Prominent fat
Vascular spaces.
Characteristics:
Lobulated surface
Variegated appearance
Yellow fatty areas
Gray smooth muscle
Vascular channels
Hemorrhage (ruptured).
Size Location:
Variable size (0.5-30 cm)
Cortical location
Exophytic growth
Multiple/bilateral (TSC)
Unilateral/solitary (sporadic).
Multifocality:
Solitary (sporadic)
Multiple/bilateral (TSC)
Synchronous lesions
Variable sizes
Progressive growth.
Microscopic Description
Histological Features:
Three components: blood vessels, smooth muscle, adipose tissue
Thick-walled vessels
Spindle cells (smooth muscle)
Mature fat
Variable proportions.
Cellular Characteristics:
Spindle-shaped smooth muscle cells
Epithelioid cells
Mature adipocytes
Endothelial cells
Melanoma-like cells (epithelioid type).
Architectural Patterns:
Fascicular smooth muscle
Thick-walled vessels
Mature adipose tissue
Perivascular distribution
Epithelioid nests (epithelioid type).
Grading Criteria:
Benign tumor
Epithelioid AML: Uncertain malignant potential
Assessment: Cellular atypia
Mitotic activity
Necrosis.
Immunohistochemistry
Positive Markers:
Melanoma markers: HMB-45+, Melan-A+
Smooth muscle actin - positive
Smooth muscle myosin - positive
Cathepsin K - positive
TFE3 - positive.
Negative Markers:
Desmin - negative
S-100 - negative
Cytokeratins - negative
CD68 - negative
RCC marker - negative.
Diagnostic Utility:
HMB-45 positivity diagnostic
Melanoma markers distinguish from other mesenchymal tumors
SMA confirms smooth muscle
Desmin negative typical.
Molecular Subtypes:
Classic AML: HMB-45+, SMA+
Epithelioid AML: Strong melanoma markers
Fat-poor AML: Same markers, less fat
All types: mTOR pathway involvement.
Molecular/Genetic
Genetic Mutations:
TSC1/TSC2 mutations
mTOR pathway activation
Loss of heterozygosity (chromosome 16p)
TFE3 translocations (rare)
Simple karyotype.
Molecular Markers:
mTOR/S6K1 activation
Tuberin/hamartin loss
Autophagy dysregulation
Cell growth pathways
Melanocyte markers.
Prognostic Significance:
Benign behavior (classic)
Hemorrhage risk (>4 cm)
Epithelioid type: Uncertain malignant potential
Size predicts complications
Excellent prognosis overall.
Therapeutic Targets:
mTOR inhibitors (everolimus, sirolimus)
Observation (<4 cm)
Embolization
Partial nephrectomy
Ablative techniques.
Differential Diagnosis
Similar Entities:
Renal cell carcinoma with fat
Liposarcoma
Leiomyosarcoma
Epithelioid PEComa
Melanoma metastasis
Clear cell RCC.
Distinguishing Features:
AML: HMB-45+, RCC markers-
RCC: PAX8+, CA9+
Liposarcoma: MDM2+, CDK4+
Leiomyosarcoma: Desmin+, high grade
Melanoma: S-100+, clinical correlation.
Diagnostic Challenges:
Fat-poor AML
Epithelioid AML
RCC with hemorrhage
Small biopsies
Crush artifact.
Rare Variants:
Epithelioid angiomyolipoma
Angiomyolipoma with epithelial cysts
Lymphangioleiomyomatosis-associated AML.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Partial nephrectomy/enucleation] with well-circumscribed mass
Tumor Description
Angiomyolipoma measuring [X] cm with heterogeneous yellow-gray appearance
Three Components
Contains blood vessels ([prominent/moderate]), smooth muscle ([prominent/moderate]), and adipose tissue ([prominent/moderate/minimal])
Microscopic Features
Thick-walled blood vessels, spindle smooth muscle cells, and mature adipocytes in variable proportions
Epithelioid Features
Epithelioid features: [absent/present - uncertain malignant potential]
Immunohistochemistry
HMB-45: Positive, Melan-A: Positive, SMA: Positive, Desmin: Negative
TSC Association
[Multiple lesions suggest TSC - genetic counseling recommended / Solitary sporadic lesion]
Hemorrhage Risk
Size [>4 cm - increased hemorrhage risk / <4 cm - low risk]
Final Diagnosis
Angiomyolipoma, [X] cm, [classic/epithelioid/fat-poor] type
Management
[Observation recommended for lesions <4 cm / Consider intervention for large lesions >4 cm / mTOR inhibitors may be beneficial]