Page 6

Answer:

4. Angiomyolipomas

Discussion: Tuberous Sclerosis

Tuberous sclerosis is one of several neurocutaneous syndromes (phakomatoses), hereditary disorders characterized by abnormal differentiation of neuroectodermal tissues. Additional phakomatoses include Neurofibromatosis, Sturge-Weber, Von Hippel Lindau, and Ataxia Telangectasia. These diseases demonstrate dysplastic and neoplastic lesions in the CNS, in addition to cutaneous manifestations.

Tuberous Sclerosis is an autosomal dominant disorder, linked to the genes TSC 1 and TSC 2, which code for the proteins hamartin and tuberin, respectively.

Clinical:

The classic triad of tuberous sclerosis is Vogt's triad (adenoma sebaceum, seizures, and mental retardation):

• Adenoma Sebaceum -- facial angiofibromas, reddish hamartomas that occur in a malar distribution. Additional skin lesions include Ash-leaf macules, Shagreen patches, and ungual fibromas.
  
  
• Seizures: effects 70-80% of patients. Requires medication, although resection of cortical tubers may help control seizures in some patients.
  
  
• Mental Retardation: effects 60-70% of patients.
  
  

Imaging findings:

CNS lesions:

• Subependymal hamartomas: Occur along the ventricular surface of the caudate nucleus. They appear as nodules portruding into the ventricle, initially isodense to brain, calcifiying with age.
  
  
• Tubers: Cortical and subcortical hamartomas resulting from abnormal neuronal migration, resulting in smooth, firm, raised nodules. Calcification occurs with age. Enhancement may occur in degenerated nodules. MRI is preferable to CT, and MRI FLAIR images are sensitive. The number of tubers appears to correlate to the severity of disease.
  
  
• Subependymal Giant Cell Astrocytomas (SEGA): Histologically benign, with abnormal enlarged glial cells and multinucleated cells; identical on microscopic examination to subependymal hamartomas. Although they do not metastasize and rarely degenerate, SEGAs typically occur adjacent to the foramen of Monro, frequently producing obstructive hydrocephalus. This may be fatal in up to 25%.
  
  

• Retinal hamartomas: Hamartomatous astrocyte proliferation, may cause leukocoria. Asymptomatic unless complicated by vitreous hemorrhage or macular involvement.
  
  
• Renal angiomyolipomas (AML): Benign hamartomas composed of vascular, smooth muscle, and fat components. Fat content is characteristic. Renal lesions not containing fat are non-specific, likely requiring further evaluation. AML's greater than 4 cm are at risk for severe hemorrhage.
  
  
• Renal cysts: 20-30% of patients with TS have renal cysts.
  
  
• Cardiac Rhabdomyomas: Benign striated muscle hamartomas that may cause murmurs and arrhythmias. Cardiac rhabdomyomas are commonly detected by fetal ultrasound. They regress in the first few years of life in 80% of patients.
  
  
• Lymphangeiomyomatosis: Uncommon, ocurring in 1% of TS patients. Hamartomatous proliferation of smooth muscles along airways produce cystic changes. Cysts typically appear relatively regular and uniform in size; may progress to honeycombing.
  
  

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