Angiomyolipomas, the prototype of the PEComa family of tumors, exhibit immunoreactivity for both melanocytic markers (as detected by the HMB-45 and melanin-A antibodies) and smooth-muscle markers (actin and desmin). All components of angiomyolipomas, including the vascular cells, immature smooth-muscle-like spindle cells, epithelioid cells, and fat cells contain somatic mutations that, combined with their germline mutation, render the cells deficient in either tuberin or hamartin. Presumably, this deficiency disrupts the integrated control of cell growth leading to the angiomyolipoma [12
]. A cross-sectional study of TSC patients revealed an increase in angiomyolipomas during childhood and adolescence that then stabilized throughout adulthood [13
]. In a longitudinal study of children with TSC, 55% of children (mean age 6.9 years) had some type of renal abnormality, and at follow-up 80% (mean age 10.5 years) had abnormalities [6
], with the most common form of involvement being angiomyolipomas. Based on their findings, the authors concluded that renal involvement begins in infancy and increases with age.
Angiomyolipomas significantly affect the lives of TSC patients because these lesions are at risk for hemorrhage and can invade adjacent normal renal parenchyma (fig. ) leading to chronic kidney disease and even end-stage renal disease. In addition to macroscopic disease, kidney tissue that is radiologically normal may, on cut section, contain both microscopic angiomyolipomas and cysts. These findings beg the question that such microscopic lesions may grow and become identifiable as the patient ages. The vascular component of larger angiomyolipomas frequently develop aneurysms (fig. ) that can rupture causing the hemorrhage [14
]. The hemorrhage risk of renal angiomyolipomas in TSC patients is between 25 and 50% [18
], and between 20–30% of patients with hemorrhages present to the emergency room in shock [20
]. The hemorrhage risk is significantly increased for aneurysms larger than 5 mm [21
According to traditional urological tenets, if doubt exists regarding the nature of a renal lesion in routine practice, then nephrectomy is justified. Because familiarity with the renal manifestations of TSC is generally only found in specialized TSC centers, TSC patients with suspected retroperitoneal hemorrhage or atypical renal lesions may undergo elective or emergent, but most often avoidable, nephrectomy in centers with limited TSC experience. Such procedures hasten the requirement for renal replacement therapy. Considering the relentless progression of CKD and the inherent increased risk in morbidity and mortality, these lesions pose a significant burden for patients with TSC [22
]. Given the frequent existence of microscopic angiomyolipomas, the most logical intervention is to treat hemorrhage, or reduce its risk, and not to actually remove the angiomyolipoma. It is critical to note that due to the bilateral nature of the renal lesions in TSC, and in order to preserve functional renal mass, nephrectomy should not be undertaken without a very careful risk-benefit analysis. The current standard of care to both control active bleeding as well as to prevent lesions with aneurysms from bleeding in the future is embolization [15
], and corticosteroid therapy can greatly reduce the subsequent postembolization syndrome [15
]. Although embolization is preferable, surgical intervention may be contemplated in selected patients who have cortical or exophytic lesions that have not hemorrhaged. The goal of surgical therapy, as it is for embolization, is to do the least invasive procedure directed at a specifically targeted lesion, with the minimum risk to the remainder of the kidney. Less invasive surgical methods such as laparoscopy have reduced the overall impact of the surgery, and partial nephrectomy or ablative therapy with cryotherapy or radiofrequency treatment can be acceptable treatment options in such selected patients by properly trained urologists.