Casey Allison Seideman, MD
Ganesh V. Raj, MD, PhD, FACS
BASICS
DESCRIPTION
• Angiomyolipoma (AML): Benign renal tumor composed of vascular tissue (angio), muscle (myo), and adipose (lipoma) tissue elements
• Tumors <4 cm are less likely to be symptomatic
• Tumors >4 cm have increased risk of spontaneous bleeding
• Can be sporadic, but is associated with tuberous sclerosis (TS) and lymphangioleiomyomatosis (LAM)
• Can be a cause of Wunderlich syndrome:
– Spontaneous, nontraumatic renal hemorrhage
– Bleeding usually confined to renal capsule
EPIDEMIOLOGY
Incidence
• 20–30% of cases are seen in patients with tuberous sclerosis (TS)
• Mean age:
– Sporadic AML: 5th or 6th decade
– Tuberous sclerosis complex (TSC) patients: Age 30
• Female > male (4:1) overall; 2:1 in TS patients
• Right side more common
Prevalence
Prevalence 0.13%, 2–3% of all renal tumors
RISK FACTORS
• TSC (50% develop AML)
• LAM (40% develop AML)
• Patients with TC tend to develop larger, bilateral, multicentric, tumors which grow more rapidly, and tend to have more spontaneous bleeds
Genetics
• TSC, AD with variable expression
• 2/3 result from sporadic mutations
• 2 genes: TSC1 (9q34), TSC2 (16p13)
PATHOPHYSIOLOGY
In rare cases, can cause: Renal failure (large volume of tumor, or solitary kidney)
ASSOCIATED CONDITIONS
• TS (1)
– 50–80% of patients with TS develop AML
– TS: Autosomal dominant condition, comprised of mental retardation, epilepsy, angiofibromas of the face (adenoma sebaceum), hamartomas in the kidney, brain (subependymal giant-cell astrocytomas [SEGAs]), eye (retinal phakomas), heart, lung, and bone
• LAM—rare lung disease, associated with TS
– Characterized by smooth muscle growth in the lungs, resulting in obstruction of small airways. Also occurs with TS
DIAGNOSIS
HISTORY
• Most asymptomatic, discovered incidentally
• Occasionally diagnosed by flank pain, hypotension, and spontaneous hemorrhage
• History of LAM, TSC
• GI complaints due to mass effect
• Hematuria, hypertension, anemia
PHYSICAL EXAM
• Hypertension, or hypotension (in the setting of hemorrhage)
• TSC: Mental retardation, adenoma sebaceum, ungula/subungual fibromas, lung disease
• Flank pain/mass
– Up to 50% of patients who are symptomatic may have a palpable mass
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Anemia
• Gross/micro hematuria
• Renal insufficiency
• Genetic testing if TS is suspected
Imaging
• CT: AML is commonly diagnosed on CT scans that reveal solid masses with areas of fat density (Hounsfield units below −20); most reliable imaging modality; IV contrast not necessary
• Fat density is not identified on CT in some cases with reduced fat content (1)[C]
• Rare reported cases of RCC containing fat densities (finding of calcification in mass is suspicious for RCC) (2)[C]
– US: Well-circumscribed, hyperechoic mass with shadowing (other RCTs may also be echogenic)
– IVP: Similar appearance to other RCTs
– Angiogram: Increased vascularity (also seen in many malignant renal lesions); 50% of AMLs are found to have aneurysmal dilation
– MRI: Adipose tissue has high signal intensity on T1-weighted images and lower on T2-weighted images
Pathologic Findings
• Pathology findings:
– Thick-walled vessels, smooth muscle, and adipose tissue with spindle and epithelioid cells
– The amount of each component varies
• Epithelioid AMLs
– Variant of AML characterized by epithelioid cells that are cytokeratin negative and HMB-45 positive. More aggressive clinical course
DIFFERENTIAL DIAGNOSIS (2)
• Renal masses:
– Oncocytoma
– Renal and retroperitoneal liposarcoma
– Renal cell carcinoma
– Renal cysts
– Renal lipoma
– Sarcoma (including fibrosarcoma, leiomyosarcoma, and liposarcoma)
– Teratoma
– Upper-tract urothelial carcinoma
– Wilms tumor
– Xanthogranulomatous pyelonephritis
• Renal/retroperitoneal hemorrhage:
– Arteriovenous malformation
– Coagulopathy
– Hemorrhage of other renal mass such as renal cell carcinoma
– Iatrogenic
– Ruptured aneurysm
– Traumatic injury
– Vasculitis
TREATMENT
GENERAL MEASURES (3)
• Benign renal masses, rarely transform to malignant entities
• Observation unless large, or symptomatic
MEDICATION
First Line
• Medical management is not currently standard
• Everolimus (4)
– Approved in adults with renal AML and TSC not requiring immediate surgery
– May benefit other TSC-associated disease manifestations, such as skin manifestations, pulmonary LAM, cardiac rhabdomyomas, and epilepsy
– An inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway
– 10 mg once daily with or without food
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Indications: Diagnostic uncertainty, hemorrhage causing significant symptoms, pain, hematuria, risk of rupture
• Asymptomatic AML <4 cm:
– Observation with serial imaging at 12-mo intervals
• Asymptomatic AML >4 cm:
– Treatment should be considered; observation with serial imaging
– The risk of spontaneous hemorrhage appears greatest in masses >4 cm
– Women of childbearing age may consider proactive treatment
• Symptomatic AML/lesion >4 cm:
– Selective arterial embolization or nephron-sparing surgery
• Acute hemorrhage:
– Initially treated with embolization (stabilizes patient and often eliminates need for more intervention)
– If explored emergently, total nephrectomy usually necessary
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Limited reports of treatment using cryoablation and radiofrequency ablation
• In patients with LAM or TS, mTOR inhibitors such as sirolimus/temsirolimus have been shown to decrease mass size by 30%
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Local recurrence rare after removal.
• Extrarenal lesions are multicentric and not metastatic.
• Extended follow-up is necessary after selective embolization due to complications and recurrence risk.
• Extremely rare case reports of malignant transformation.
COMPLICATIONS
• Flank/abdominal pain
• Hematuria
• Hemorrhage (may cause anemia or shock)
• Mass effect on surrounding organs
FOLLOW-UP
Patient Monitoring
• Controversial in patients with newly diagnosed AML; screen for TS
• Conservative management: Serial imaging (usually with CT or US) every 6–12 mo
• Growth rate typically 5% per yr for solitary AML
• TSC patients and those with multicentric AMLs have growth rate of 20% per yr
Patient Resources
• TS alliance www.tsalliance.com
• LAM Foundation www.theLAMfoundation.com
REFERENCES
1. Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urol. 1994;152:1988–1991.
2. Margulis V, Matin SF, Wood CG. Chapter 51: Benign Renal Tumors. In: Campbell-Walsh Urology. Philadelphia, PA: Elsevier; 2010:1492–1505.
3. Nelson CP, Sanda MG. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002;168:1315–1325.
4. Dabora SL, Franz DN, Aswal S, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: Kidney angiomyolipomas and other tumors regress and VEGF-D levels decrease. PLoS One. 2011;6(9):e23379.
ADDITIONAL READING
• Folpe AL, Mentzel T, Lehr HA, et al. Perivascular epitheliod cell neoplasms of soft tissue and gynecological origin: A clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29(12):1558–1575.
• Moavero R, Coniglio A, Garaci F, et al. Is mTOR inhibition a systemic treatment for tuberous sclerosis? Ital J Pediatr. 2013;39:57.
• Rakowski SK, Winterkorn EB, Paul E, et al. Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors. Kidney Int. 2006;70(10):1777–1782.
• Roy C, Tuchmann C, Lindner V, et al. Renal cell carcinoma with a fatty component mimicking angiomyolipoma on CT. Br J Radiol. 1998;71:977–979.
• Steiner MS, Goldman SM, Fishman EK, et al. The natural history of renal angiomyolipoma. J Urol. 1993;150:1782–1786.
See Also (Topic, Algorithm, Media)
• Renal Angiomyolipoma Image 
• Renal Cell Carcinoma, General
• Renal Mass
• Retroperitoneal Hematoma
• Tuberous sclerosis
CODES
ICD9
• 223.0 Benign neoplasm of kidney, except pelvis
• 593.81 Vascular disorders of kidney
• 759.5 Tuberous sclerosis
ICD10
• D17.71 Benign lipomatous neoplasm of kidney
• N28.89 Other specified disorders of kidney and ureter
• Q85.1 Tuberous sclerosis
CLINICAL/SURGICAL PEARLS
• Benign renal tumor characterized by presence of vascular, muscle, and adipose components.
• Larger lesions have increased risk of spontaneous hemorrhage.
• Diagnosis is usually made by imaging.
• Observation for small masses, consider embolization for larger masses.
• Everolimus (mTOR inhibitor) can shrink large multifocal lesions in patients with tuberous sclerosis (TS) and lymphangioleiomyomatosis (LAM).