Angiomyolipoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Faizan Sheraz, M.D. [3], Rekha, M.D.

Angiomyolipoma is a benign renal neoplasm previously considered to be a hamartoma or choristoma, but now known to be neoplastic. It is composed of variable amounts of fat, vascular, and smooth muscle elements. The fat density of the tumor on CT scan has been regarded to be pathognomonic. The lesion is well demarcated and contains mature elements. It occurs in more than 50% of individuals with tuberous sclerosis, often bilaterally. On gross pathology, well circumscribed and uniform yellow mass is characteristic finding of angiomyolipoma. Angiomyolipoma is caused by a defect in the TSC1 gene. Angiomyolipoma must be differentiated from retroperitoneal liposarcoma, adrenal myelolipoma, and renal cell carcinoma. If left untreated, small angiomyolipomas and those without dilated blood vessels (aneurysms) cause few symptoms. Small angiomyolipomas are associated with the most favorable prognosis. Common complications of angiomyolipoma include infection, hematuria and hemorrhage. Abdominal CT scan may be diagnostic for angiomyolipoma. On CT scan, angiomyolipoma is characterized by smooth tumor margin with low intratumoral fat component and homogenous enhancement on both corticomedullary and excretory phase scans. Surgery is not the first-line treatment option for patients with angiomyolipoma. Transcatheter arterial embolization is usually reserved for patients with complicated disease.

Angiomyolipoma was first described as a tumor in 1911 by Fisher. He also noted and described its association with the Tuberous Sclerosis. It has been named as Angiomyolipoma by Morgan and associates in 1951.

Angiomyolipoma may be classified according to radiologic appearance into 7 subtypes: classic angiomyolipoma, triphasic angiomyolipoma, fat poor angiomyolipoma, hyperattenuating angiomyolipoma, isoattenuating angiomyolipoma, angiomyolipoma with epithelial cysts, and angiomyolipoma in lymphangioleiomyomatosis.

On gross pathology, well circumscribed and uniform yellow mass is characteristic finding of angiomyolipoma. The components of an angiomyolipoma include vascular cells, immature smooth muscle cells and fat cells. Angiomyolipoma is caused by a defect in TSC1 gene. Diseases associated with angiomyolipoma include von Hippel-Lindau syndrome and tuberous sclerosis. Cytologic features of angiomyolipoma include round nuclei and bland chromatin. Immunohistochemistry markers of angiomyolipoma include positive melanocytic markers.

Angiomyolipoma is caused by a mutation in the TSC1 gene. It can also be caused by a defect in TSC2 gene.

Angiomyolipoma must be differentiated from retroperitoneal liposarcoma, adrenal myelolipoma, and renal cell carcinoma.

The incidence of angiomyolipoma is approximately 30 per 100,000 individuals worldwide. Females are more commonly affected with angiomyolipoma than males. Angiomyolipoma commonly affects individuals older than 40 years of age.

Tuberous sclerosis is a risk factor for the development of angiomyolipoma. Approximately 50% of individuals with tuberous sclerosis develop bilateral angiomyolipomas.

Patients who have tuberous sclerosis should be screened for angiomyolipoma. Abdominal CT scan is recommended for screening angiomyolipoma. High fat content is suggestive of angiomyolipoma.

If left untreated, small angiomyolipomas and those without dilated blood vessels (aneurysms) cause few symptoms. Small angiomyolipomas are associated with the most favorable prognosis. Common complications of angiomyolipoma include infection, hemorrhage, and shock.

Symptoms of angiomyolipoma include fever, nausea, vomiting, and abdominal pain.

Common physical examination findings of angiomyolipoma include fever, flank tenderness, and palpable mass.

Laboratory findings consistent with the diagnosis of angiomyolipoma include presence of red blood cells in urine and elevated white blood cell count.

Abdominal CT scan may be diagnostic for angiomyolipoma. On CT scan, angiomyolipoma is characterized by smooth tumor margin with low intratumoral fat component and homogenous enhancement on both corticomedullary and excretory phase scans.

Abdominal MRI may be diagnostic of angiomyolipoma. On MRI, angiomyolipoma is characterized by high signal intensity on non-fat saturated sequences and loss of signal following fat saturation.

On abdominal ultrasound, angiomyolipoma is characterized by hyperechoic lesions and posterior acoustic shadowing in the cortex.

On digital subtraction angiography, angiolipoma is characterized by hypervascular lesions, microvascular aneurysms and absent AV shunting.

Treatment options include selective renal artery embolization,nephron sparing surgery( enucleation or partial nephrectomy), complete and radical nephrectomy, radio-frequency ablation and everolimus. Treatment and management of the Angiomyolipoma depends largely on

1. Size of the tumors
2. Signs and symptoms
3. Presence or absence of life threatening hemorrhage
4. Its association with the tuberous sclerosis and
5. The presence of the comorbidities.

Angiomyolipomas found incidentally,asymptomatic, < 4 cm in size, generally requires no intervention beside periodic evaluation. Medium sized lesion(4-8 cm) should be closely followed with the serial imaging studies(every 6 month and then yearly once stable) and elective intervention provided if the change in the size or symptoms noticed, to increases the chances of renal function salvage. Larger lesion(>8cm), shown to progress to the development of the complication so treated electively.

Surgery is not the first-line treatment option for patients with angiomyolipoma. Transcatheter arterial embolization is usually reserved for patients with complicated disease.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rekha, M.D.

Angiomyolipoma was first described as a tumor in 1911 by Fisher. Fisher also noted and described its association with the Tuberous Sclerosis. It has been named as Angiomyolipoma by Morgan and associates in 1951.

• Angiomyolipoma was first described as a tumor in 1911 by Fisher.^{[1][2][3][4][5]}
• Fisher also noted and described angiomyolipoma association with the tuberous sclerosis.
• It has been named as Angiomyolipoma by Morgan and associates in 1951.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Faizan Sheraz, M.D. [3],Rekha, M.D.

Angiomyolipoma may be classified according to radiologic appearance into 7 subtypes: classic angiomyolipoma, triphasic angiomyolipoma, fat poor angiomyolipoma, hyperattenuating angiomyolipoma, isoattenuating angiomyolipoma, angiomyolipoma with epithelial cysts, and angiomyolipoma in lymphangioleiomyomatosis.^[1]

Angiomyolipoma may be classified according to World Health Organization (WHO) into as follows:^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3], Faizan Sheraz, M.D. [4], Rekha, M.D.

On gross pathology, well circumscribed and uniform yellow mass is characteristic finding of angiomyolipoma. The components of an angiomyolipoma include vascular cells, immature smooth muscle cells and fat cells. Angiomyolipoma is caused by a defect in TSC1 gene. Diseases associated with angiomyolipoma include von Hippel-Lindau syndrome and tuberous sclerosis. Cytologic features of angiomyolipoma include round nuclei and bland chromatin. Immunohistochemistry markers of angiomyolipoma include positive melanocytic markers.

• Angiomyolipoma is a tumor of the kidney which is composed of three different cells. The cells of angiomyolipoma include the following:
  • Smooth muscle like cells
  • Adipocyte like cells
  • Epithelioid cells
• The cells composing angiomyolipoma are pericytes originated not endothelial.^[1]

• Angiomyolipoma can be a sporadic mutation or part of tuberous sclerosis syndrome.
• There are different variants of angiomyolipoma that are differentiated by biopsy. These variants include:^[2]
  • Classic variant
  • Epithelioid variant
  • Cystic variant which is characterized by solid and cystic regions.

Genes involved in the pathogenesis of angiomyolipoma include:^[3][4]

• TSC1 gene

• TSC2 gene

Conditions associated with angiomyolipoma include:^[5][6][7][8]

• von Hippel-Lindau syndrome
• Tuberous sclerosis

On gross pathology, well circumscribed and uniform yellow mass are characteristic findings of angiomyolipoma.

On microscopic histopathological analysis the following are characteristic findings of angiomyolipoma:^[10]

• Smooth muscles
• Adipose tissue
• Abundant blood vessels

• 
  Histopathologic slide of renal angiomyolipoma. Nephrectomy specimen. H & E stain.^[11]
• 
  Histopathologic slide of renal angiomyolipoma. Nephrectomy specimen. H & E stain.^[11]
• 
  Histopathologic slide of renal angiomyolipoma. Nephrectomy specimen. H & E stain.^[11]
• 
  Histopathologic image of renal angiomyolipoma. Nephrectomy specimen. HMB-45 immunostain.^[11]

Epithelioid angiomyolipoma

• There is a special variant called an epithelioid angiomyolipoma, composed of epithelial looking cells, often with nuclear atypia

Cytologic features of angiomyolipoma include:^[10]

• Nuclei – round/ovoid
• Chromatin – bland

Immunohistochemistry markers of angiomyolipoma include:

• Melanocytic markers positive^[12][13][14]
  • HMB-45 positive in all cases (15/15)^[15]
  • Melan A positive in ~87% of cases (13/15)
• Epithelial markers negative^[12]
  • EMA
  • AE1/AE3
• SMA positive
• CD117 positive/negative
• Ki-67:^[16]
  • Epithelioid variant of angiomyolipoma positive
  • Conventional angiomyolipoma negative

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2], Rekha, M.D.

Angiomyolipoma is caused by a mutation in the TSC1 gene. It can also be caused by a defect in TSC2 gene.

• Angiomyolipoma is caused by a mutation in the following genes:^[1][2][3]
  • TSC1 gene
  • TSC2 gene

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2],Rekha, M.D.

Angiomyolipoma must be differentiated from retroperitoneal liposarcoma, adrenal myelolipoma, and renal cell carcinoma.^[1][2]

Angiomyolipoma must be differentiated from the following:^{[1][3][4][5][6]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Faizan Sheraz, M.D. [3], Rekha, M.D.

The incidence of angiomyolipoma is approximately 30 per 100,000 individuals worldwide. Females are more commonly affected with angiomyolipoma than males. Angiomyolipoma commonly affects individuals older than 40 years of age.

• Angiomyolipoma occurs in more than 70% of cases with renal manifestations of tuberous sclerosis.^[1][2][3]

• The incidence of angiomyolipoma is approximately 30 per 100,000 individuals worldwide.

• Females are more commonly affected with angiomyolipoma than males. The female to male ratio is approximately 4 to 1.

• Angiomyolipoma commonly affects individuals older than 40 years of age.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2], Rekha, M.D.

Tuberous sclerosis is a risk factor for the development of angiomyolipoma. Approximately 50% of individuals with tuberous sclerosis develop bilateral angiomyolipomas.

• The most potent risk factor for the development of angiomyolipoma includes:^[1][2][3][4]
  • Tuberous sclerosis
    • Approximately 50% of individuals with tuberous sclerosis develop bilateral angiomyolipomas.
  • Genetic mutations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2],Rekha, M.D.

Patients who have tuberous sclerosis should be screened for angiomyolipoma. Abdominal CT scan is recommended for screening angiomyolipoma.

• Patients who have tuberous sclerosis should be screened for angiomyolipoma.^[1]
• Abdominal CT scan is recommended for screening angiomyolipoma.
• High fat content is suggestive of angiomyolipoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Faizan Sheraz, M.D. [3],Rekha, M.D.

If left untreated, small angiomyolipomas and those without dilated blood vessels (aneurysms) cause few symptoms. Small angiomyolipomas are associated with the most favorable prognosis. Common complications of angiomyolipoma include infection, hemorrhage, and shock.

• If left untreated, small angiomyolipomas and those without dilated blood vessels (aneurysms) cause few problems.
• Angiomyolipomas grow as rapidly as 4 cm in one year so regular surveillance is necessary depending upon the size of the tumour.^[1][2]
  • Angiomyolipoma, less than 2cm, surveillance every 3-4 years by renal ultrasound.
  • Angiomyolipoma 2-4 cm, annual renal ultrasound recommended.
  • Angiomyolipoma more than 4 cm, and of Epithelioid variant, renal ultrasound every 6 months initially and annual thereafter once stabilized, in case if it is not resected.
  • Angiomyolipoma with high risk of malignant transformation, should undergo whole body CT/MRI, 6 months post resection and then yearly for at least 5 years.

• It has been observed in some studies that the female sex hormones has positive impact on the size of the angiomyolipoma.
• There has been increased growth and hemorrhagic complications seen during the pregnancy as well as after treatment with exogenous hormonal therapy.^{[3][4][5][6][7]}
• Due to increased rate of growth of angiomyolipoma and increased risk of its rupture, it is advised to use estrogen carefully in these patients, and frequent imaging surveillance every six months initially and annual thereafter, once established, is recommended.

• Common complications of angiomyolipoma include:^[8]
  • Infections
  • Urinary obstruction
  • End stage renal failure, in case of bilateral angiomyolipoma
  • Intestinal obstruction
  • Shock
  • Hemorrhage
  • Rarely, it can transform into malignant angiomyolipoma, especially if related to Tuberous Sclerosis

• Small angiomyolipomas are associated with the most favorable prognosis. An angiomyolipoma larger than 5 cm and those containing an aneurysm pose a significant risk of rupture, which is a medical emergency as it is potentially life-threatening. Cumulative risk of hemorrhage is estimated to be:^[9]
  • 10% among males
  • 20% among females

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