Trends of Presentation and Clinical Outcome of Treated Renal Angiomyolipoma

Angiomyolipoma (AML) is a relatively rare benign tumor of the kidney consisting of fat, blood vessels, and smooth muscle. According to previous literature, AML is predominant in women and approximately 20% occurs in patients with tuberous sclerosis complex (TSC), in which 80% is bilateral or multiple.1-3 TSC is an autosomal disease entity with various features such as mental retardation, adenoma sebaceum, seizure, and renal manifestations. Renal manifestations include AML, benign cyst, and renal cell carcinoma (RCC), which is the leading cause of morbidity and mortality in these patients.4 Although clinically-insignificant AMLs can be safely observed, intervention is recommended for intractable pain, large size, suspicion of malignancy, and risk of life-threatening hemorrhages.5-7 Given the benign nature of AML, renal preserving treatment modalities such as nephron-sparing surgery (NSS) or selective renal artery angioembolization are preferred.6 To set a strategy for AML management, clinical prognosis according to tumor size, association with TSC, multiplicity, radiologic finding, and treatment modality were investigated.

AMLs are recognized as hamartomatous lesions composed of heterogenous tissue components including blood vessels, smooth muscles, and fat. Renal AMLs occupy 1-3% of renal tumors and occur in 2 clinical spectrums: sporadic and those associated with TSC.8 TSC is an autosomal disease entity with various characteristics such as mental retardation, adenoma sebaceum, seizure, renal manifestations, and loss of heterozygosity of TSC1 and TSC2 genes.4, 9 Although AML is uncommon among the general population, previous studies has shown that 20% of patients with TSC are known to develop AML while on the other hand, more than 50% of AMLs are associated with TSC.7 In this rare setting, tumors tend to be larger, develop earlier in life, and are more often multiple or bilateral.3

Our study demonstrated a relatively low prevalence rate for TSC-associated AMLs (9.3%) compared with 20% reported by Lendvay and Marshall.10 However, significant differences in the clinical spectrum of TSC-association according to age at presentation, tumor size, symptom, and multiplicity correlated with those of previous studies.7 TSC-associated AMLs tended to be more symptomatic, multiple, and bilateral. Therefore, active surveillance is strongly recommended for asymptomatic tumors < 4 cm, while angioembolization or surgical interventions with maximal parenchymal preservation including partial nephrectomy, enucleation, or wedge resection should be an alternative option for symptomatic tumors ≥ 4 cm. We reported a relatively large average tumor size for TSC-associated AML patients (7.6 cm, range, 1.1-16 cm) compared with 6.6 cm reported by Harabayashi, et al.11 Our experience of 4 TSC-associated patients with tumors ≥ 8 cm who finally ended up with receiving a radical nephrectomy demonstrated that, although angioembolization could be a primary option in controlling existing or impending hemorrhages in spontaneous ruptured AMLs, a prophylactic radical nephrectomy is relatively recommended for tumors ≥ 8 cm or those refractory to angioembolization.

Among TSC-associated AMLs, epitheliod components were pathologically observed in 9 patients. These tumors are thought to originate from common progenitor perivascular epitheloid cells, recognized as members of the perivascular epithelioid clear cell tumors (PEComas).12 Unlike classic AMLs, PEComas are distinctively characterized by local recurrence, lymph node involvement, and metastasis, thus demonstrating a substantial diagnostic challenge in differentiation with RCC.12-14 Brecher, et al.15 reported their results with AML with lymph node involvement, that no recurrence was noted during the follow-up and that it represents a multicentric growth pattern rather than metastasis. In addition, prognosis was considered to depend on remaining renal function rather than lymph node involvement.15 However, our study included one 16 year-old female patient who was an exception to this thesis. She presented with a 7 cm solid fat-containing parenchymal mass with multiple lymph node involvement along with facial adenoma sebaceum and multiple pulmonary lymphangioleiomatosis. Although NSS was performed due to her young age and disease trait, a radical nephrectomy was eventually performed after the 23 month follow-up due to a spontaneous rupture of the recurred tumor in the ipsilateral kidney. Although the patient remained asymptomatic for a follow-up period of 49 months, angioembolization or a radical nephrectomy is currently being considered for a 16 cm-sized recurred tumor on the contralateral kidney.

With the advancement of noninvasive radiological imaging techniques, the detection of fat poor AMLs has recently surged in line with increased detection of incidental and asymptomatic small sized renal tumors.16 Although the diagnosis of AML is typically based upon presence of fat component on CT scans, many AMLs with a scant fat component may evade radiographic diagnosis.17, 18 Fergany, et al.19 described that solid renal tumors ought to be primarily considered as RCCs and surgical intervention are performed, due to the fact that solid tumors originating from renal parenchyma are mostly malignant and that 85-90% are RCCs.20 McCullough, et al.21 also recommended surgical treatment for tumors that are undistinguishable from RCC or those that contain calcification, a feature implying malignancy. Also, Lemaitre, et al.17 stated that 14% of AMLs demonstrate low fat content on radiographic imaging. However, of 129 AMLs in our series, 41 (31.7%) had radiographic features prompting surgical management based on clinical suspicion of RCC; all 41 cases were surgically managed based on the previously established principle.

Through our retrospective review of clinical outcomes of AML, we noticed a treatment trend based on tumor characteristics along with its associated symptoms. Although surgical intervention such as NSS or radical nephrectomy was the mainstay in the management of most renal tumors, our study demonstrated an surging number of angioembolization in patients with TSC-association. Several factors led to this conservative approach in recent years. Repeated nephrectomy reduces management options for the remaining kidney, subsequently mandating only a conservative approach. Regardless, characteristics of TSC-associated AMLs such as large size and multiplicity have limited the role of NSS. Angioembolization and NSS for renal AMLs both offer long-term renal function preservation with low complication rates. However, to better define the advantages of these two modalities a prospective head-to-head, comparisons will be needed.7, 22, 23

In conclusion, significant differences in clinical manifestations and treatment outcomes of AML were noted according to tumor size, association with TSC, multiplicity, radiologic characteristics, and treatment modalities. However, most patients treated for AML remained symptom-free with preservation of renal function. The fact that smal-sized AMLs with scant fat components and those associated with TSC may evade radiographic diagnosis is of clinical significance. Therefore, additional areas of research need to address the role of conventional imaging in identifying a fat component that would better differentiate AML from malignancy.