Angiomyolipoma

Epidemiology and Etiology:

• 1% of surgically removed renal tumours
• Sporadic (~80% of surgically removed):
• 4:1 F:M
• No apparent sex predilection for TS patients
• ?hormonal influence
• Age mean 45-55
• Onset after puberty
• Tuberous sclerosis
• 25-50% of patients with tuberous sclerosis
• Age mean 25-35

o Association with lymphangioleiomyomatosis of the lung (also related to TS)

• Share many features histopathologically and genetically

Common sites:

• Cortex
• Medulla
• Extrarenal in retroperitoneal space with or without renal attachment

Gross features:

• Solitary (most)
• Multifocal (presumptive Dx of TS)
• Larger lesions typically detected in sporadic cases
• Distinctive pattern on CT due to high fat content which is present in most angiomyolipomas
• Well demarcated from adjacent kidney (usually)
• Bulge into (rather than infiltrate) the perirenal fat
• Yellow to pinkish tan
• May resemble clear cell RCC or leiomyoma depending on constituent components
• Cystic or pseudocystic change may be prominent (rarely)
• Epithelioid angiomyolipoma:
• Large
• Infiltrative growth
• Necrosis maybe
• Greyish-tan, white, brown, or hemorrhagic
• Extrarenal extension or involvement of the renal veins or venae cavae may occur

Histologic features:

• Variable proportions of adipose tissue, spindle cells, epithelioid smooth muscle cells, and abnormal thick-walled blood vessels
• Abnormal thick-walled poorly-organized blood vessels
• Lack the normal elastic content of arteries
• If prominent, may have appearance of vascular malformation
• smooth muscle cells
• spindle and/or epithelioid (less common)
• emanate from blood vessel walls in a radial pattern
• cells associated with a thin-walled branching vessels with a pattern similar to LAM is a variation
• some subcapsular AMLs are composed almost entirely of smooth muscle cells (capsulomas)
• rarely show striking nuclear atypia
• adipose tissue
• mature typically
• vacuolated adipocytes suggestive of lipoblasts maybe
• border with kidney is typically sharp
• some entrapped tubules at the periphery maybe
• with epithelial cysts maybe:
• mixed solid and cystic architecture characteristically
• cuboidal to hobnail epithelial-lined cysts (?entrapped renal tubular epithelium)
• compact subepithelial cambium-like layer of stromal cells
• vascular invasion; extension into intrarenal venous system (uncommon) (not evidence of malignancy)
• regional lymph node involvement is considered multifocal growth pattern rather than metastasis
• multifocality maybe (also not evidence of malignancy)
• microhamartomas often present in kidneys bearing AML
• small nodules with some features of angiomyolipoma
• intraglomerular lesions with features similar to those of AML have been reported
• oncocytoma-like AML (rare)

o epithelioid angiomyolipoma (rare – < 5% of resected AML):

§ at least 80% epithelioid cells

§ 2 different morphologic patterns:

· Carcinoma-like growth:

· Large polygonal cells arranged in cohesive nests and compartmentalized sheets separated by thin vascular-rich septa

· dense, deeply eosinophilic cytoplasm

· atypical nuclei with prominent nucleoli

· intranuclear inclusions common

· no mitoses or only 1 per 50 HPF usually

· some have >= 2 mitoses per 50 HPF

· multinucleate tumour giant cells often

· necrosis variable

· hemorrhage maybe

• epithelioid and plump spindled cells arranged in diffuse and densely packed sheets
• more homogenous growth pattern than carcinoma-like
• tumour cells relatively monomorphic epithelioid cells
• clear to granular, feathery eosinophilic cytoplasm
• smaller cell size
• nuclei relatively uniform and lack atypia
• intranuclear inclusions are uncommon
• multinucleate giant cells singly or in groups
• no mitotic activity usually
• microscopic foci of adipocyte differentiation maybe

Immunophenotype:

Marker:	Sensitivity:	Specificity:
HMB45
Melan-A
Microphthalmia transcription factor
Cathepsin K
PR	frequently
ER	maybe
Smooth muscle actin and muscle-specific actin	Variable in epithelioid
Calponin
CD68	Maybe
S100	Maybe
Desmin	Maybe Less common in epithelioid
Epithelial markers (neg)	Always
TFE3 (often weak) (Usually FISH neg.)	Some epithelioid Not mentioned in classic

• Differentiation towards perivascular epithelioid cells with no normal counterpart

Molecular features:

• TSC2 inactivation consistently (sporadic and TS-related):
• TSC2 mutations (often in sporadic)
• TSC2 gene LOH (16p13) (often) (sporadic and TS-related, classic and epithelioid)
• TSC1 gene LOH (9q34) (occasionally)
• TFE3 gene rearrangement (occasional cases of epithelioid) (extremely uncommon)
• TS (germline):
• TSC1 gene (9q34) alterations:
• Encodes hamartin
• TSC2 gene (16p13) alterations:
• Encodes tuberin, a GTP-ase-activating protein for RAS-related protein 1 and Rab protein 5
• Interacts with hamartin to form a cytoplasmic complex

Other features:

• PEComa
• Benign (classical angiomyolipoma)
• Only a few cases of sarcoma developing in sporadic (classic) angiomyolipoma have been reported (pulmonary mets, hepatic mets)
• Very small minority associated with complications and morbidity and mortality
• Epithelioid angiomyolipoma:
• Some can exhibit malignant behavior (variable percentages from 5-65%)
• Prognostic factors are largely undetermined. Suggested poor prognostic indicators are:
• Size > 7 cm
• Carcinoma-like morphologic pattern
• Perinephric fat and/or renal vein involvement
• Necrosis
• Older age
• Higher proportion of epithelioid component
• Severe atypia
• Higher percentage of atypical cells