Tuberous sclerosis complex (TSC) can present itself as five different lesions in the kidneys: angiomyolipomas, cysts, malignant angiomyolipomas, oncocytomas, and renal cell carcinoma.
Benign angiomyolipomas are the most common TSC lesion, occurring in 70 percent to 80 percent of adults and older children. Accurate noninvasive ultrasound, CT, or MRI diagnosis of these lesions is highly dependent on their fat content. It can sometimes be difficult to tell the difference between a small or low-fat-content benign angiomyolipoma and a malignant tumor. When tumors become larger than 4 cm, bleeding of the angiomyolipoma, the primary complication of this lesion, increases in frequency. Pain may also become a significant problem with angiomyolipomas.
Renal angiomyolipomas—made up of vascular tissue (angio), smooth muscle (myo), and fat (lipoma)—are benign hamartomas. These hamartomas are well circumscribed groups of cells that multiply excessively, growing as tumors that may or may not cause symptoms. The prevalence of TSC-related renal angiomyolipomas increases with age, and in adults bilateral tumors or multiple tumors in one kidney are common. Angiomyolipomas begin in childhood in many individuals with TSC, but they usually grow very slowly and may not be problematic until young adulthood. Individuals with TSC should have their kidneys imaged at the time of diagnosis and then regularly throughout their lives.
TSC renal cysts are commonly multiple and bilateral. They are the second most frequently occurring kidney manifestation of TSC. Single or multiple renal cysts occur less often in individuals with TSC than do angiomyolipomas, but they may appear earlier. Some cysts may collapse and disappear.
One important research finding was the discovery of the TSC2 gene in close proximity to the gene for polycystic kidney disease (PKD1) on chromosome 16. A small group of individuals with TS have a large segment of chromosome 16 deleted which means that both the TSC2 and PKD1 genes are also removed. These individuals most often will have polycystic kidneys from birth and will require close monitoring and treatment throughout the childhood years.
Individuals with TSC and renal angiomyolipomas have a greater risk of developing malignant kidney tumors than do individuals with renal angiomyolipomas who do not have TSC. As a result, patients with TSC must have their kidney images carefully reviewed by a physician who is knowledgeable about TSC and who can differentiate between angiomyolipomas and other types of kidney tumors. The physician should work closely with a radiologist who can differentiate between malignant and benign angiomyolipomas. Malignant angiomyolipomas should be removed as soon as possible after their detection.
Oncocytomas are tumors only occasionally seen in individuals with TSC.
Renal cell carcinoma, or cancer in the kidney, is also rarely seen in individuals with TSC, but when these tumors are present, they often are multi-centric and bilateral. These tumors should also be removed as soon as possible after their detection to prevent metastasis.
Both renal angiomyolipomas and cysts are often asymptomatic and may not require treatment; however, both should be followed closely with imaging every 1 to 2 years because aggressive treatment can preserve kidney function with minimal trauma to the individual or the kidney. If the tumors are allowed to grow, they may lead to obstructive uropathy or displacement of much of the normal kidney tissue. There is also a significant risk of hemorrhage if the angiomyolipomas or cysts grow larger than 4 cm. Hematuria, back or abdominal pain, or internal hemorrhage may be the initial signs of kidney problems.
The renal lesions that appear in many individuals with TSC may remain stable and require no specific treatment. Renal tumors must sometimes be removed, however, if they grow rapidly, if there is an indication that they may be malignant (i.e., a solid tumor with little or no fat content), or to alleviate obstruction. Less-invasive methods of removing the angiomyolipomas, such as embolization, reduces kidney trauma and helps preserve as much normal kidney as possible. With more frequent imaging of the kidneys and good clinical care, an individual with TSC should not have to lose an entire kidney or experience hemorrhaging from an angiomyolipoma. Early and aggressive treatment is much better for most individuals with TSC.
Unfortunately, some individuals with TSC who also have polycystic kidney disease will also have problems maintaining normal blood pressure levels. Their blood pressure usually can be controlled with medication early in the disease process; however, dialysis, and sometimes even renal transplantations, may eventually be necessary. Renal transplantation has been performed successfully in individuals with TSC; there does not appear to be a recurrence of angiomyolipomas in transplanted kidneys.