Renal angiomyolipoma (RAML) is the most common form of angiomyolipoma, a benign neoplasm of largely unknown etiology. Patients suffering from tuberous sclerosis or sporadic lymphangioleiomyomatosis are predisposed for developing RAML. Most RAML grow slowly and don't require any specific therapy, but regular surveillance. If treatment is deemed necessary, the application of everolimus, cryoablation, radiofrequency ablation, embolization of the renal artery, and nephrectomy may be considered.
Most RAML patients are asymptomatic. The mean size of tumors at the time of detection is 4 to 6 cm and the smaller the tumor, the lower the likelihood of it causing any complaints . Occasionally, these benign renal neoplasms provoke back and flank pain. Furthermore, RAML may cause hematuria. It has been estimated that a palpable mass may be detected during a physical examination of the kidneys in about 10% of those individuals presenting with RAML-related hematuria. Additionally, these patients are predisposed for spontaneous retroperitoneal hemorrhages, a condition also known as Wunderlich syndrome. Pregnant women are particularly susceptible to this complication and may even suffer from life-threatening hemorrhagic shock  .
In patients suffering from tuberous sclerosis or lymphangioleiomyomatosis, symptoms caused by RAML are usually not the reason why medical attention is sought. Tuberous sclerosis is typically associated with mental retardation and epilepsy, which may manifest during infancy. Affected individuals are prone to a variety of mesenchymal tumors, with facial angiofibromas distributed in a butterfly-like pattern being the most characteristic ones. Angiomyolipomas may not only develop in the kidneys, but also in the liver and possibly in other organs. Lymphangioleiomyomatosis is usually part of the tuberous sclerosis complex, but may rarely occur as a sporadic disease not related to tuberous sclerosis. Lymphangioleiomyomatosis manifests in form of unspecific respiratory symptoms like chest pain, dyspnea, and cough.
Entire Body System
- Flank Mass
Shock due to a grave haemorrhage from AML rupture is called Wunderlich syndrome that is clinically characterized by the Lenk's triad: acute flank pain, a flank mass and hypovolemic shock.Other symptoms and signs may be present: haematuria, palpable mass [ncbi.nlm.nih.gov]
- Developmental Delay
We present the case of a 12 year-old male with past medical history of tuberous sclerosis, characterized by developmental delay, tonic and clonic seizures, and cutaneous abnormalities. He presented with macroscopic hematuria and abdominal pain. [ncbi.nlm.nih.gov]
- Acute Onset of Symptoms
Such a patient presented to us with acute onset of symptoms, and on account of severe anemia with active bleeding, transarterial embolization was performed. This was followed by elective nephrectomy without any complications. [ncbi.nlm.nih.gov]
- Acute Abdomen
This case highlights the presentation in the form of an acute abdomen in the immediate post-partum period. This is important as acute abdomen following delivery can be attributed to a number of other causes. [ncbi.nlm.nih.gov]
Three of these were known to be symptomatic: intermittent flank pain and gross hematuria for 2 months; recurrent hematuria both before and after flank trauma and a third patient with acute abdomen due to a ruptured tumor blood vessel. [thedoctorsdoctor.com]
Solitary sporadic tumors may cause an acute abdomen and shock as a result of spontaneous hemorrhage in the tumor. [emedicine.medscape.com]
- Abdominal Fullness
The 22-year-old man was admitted due to bilateral flank pain, gross hematuria, and abdominal fullness. He had history of epilepsy, mental retardation, and delayed development during childhood. He had angiofibroma on his face since 10 years ago. [ncbi.nlm.nih.gov]
- Back Pain
We report a case of a pregnant woman with 18 weeks of gestation admitted in the emergency room with an acute right low back pain with no other symptoms. [ncbi.nlm.nih.gov]
Clinical History: 59-year old woman with right lower back pain for more than one year Diagnosis: Right renal angiomyolipoma MR Technique: Upper abdominal imaging was performed on a 3T MR system. [clinical-mri.com]
In this situation, the signs and symptoms could be nausea, vomiting, back pain, sudden drop in blood pressure, and palpitations. [dovemed.com]
These symptoms most commonly included abdominal or back pain, nausea and vomiting and fever. For the individual who is non-verbal, this may be present as irritability and vomiting. [tsalliance.org]
- Flank Pain
flank pain, urinary tract infections, renal failure or hypertension. [ncbi.nlm.nih.gov]
Although life-threatening complications related to retroperitoneal bleeding and massive hematuria are possible, it is often detected incidentally. Pulmonary embolism as the first symptom is extremely rare. [ncbi.nlm.nih.gov]
- Cesarean Section
At 35 weeks of gestation, it was performed elective cesarean section without complications for both mother and fetus. [ncbi.nlm.nih.gov]
- Bilateral Flank Pain
We present a case of 13-year female patient who was referred to Civil Hospital, Karachi, with bilateral flank pain, cutaneous nodule and low intelligence. [ncbi.nlm.nih.gov]
Because patients don't usually present symptoms related to the disease, most RAML are incidental findings. They are rather easily detected on images obtained by means of sonography, radiography, computer tomography and magnetic resonance imaging . Their distinction from other renal neoplasms is largely facilitated by their increased content of fat, which accounts for their characteristic, heterogeneous appearance. However, proportions of vascular tissue, smooth musculature, and proliferating adipocytes vary and atypical, minimal-fat RAML have been described. Up to 5% of all cases fall into this category . Contrary to typical, triphasic RAML, these tumors present as homogeneous masses and resemble renal cell carcinoma on images. Several studies have been conducted to define parameters that may help to distinguish both types of neoplasms.
A detailed comparison of imaging findings characteristic of minimal-fat RAML and distinct types of renal cell carcinoma has recently been published by Lim et al. . These authors have proposed the combination of hypointensity on T2-weighted images, low apparent diffusion coefficients, and avid early enhancement and washout on contrast-enhanced computer tomography or magnetic resonance imaging have been proposed as valuable for recognizing RAML . Elsewhere, it has been stated that calcified areas are to be expected in renal cell carcinomas only , although statements to the contrary can also been found in the literature . Still, these conclusions have not yet been validated on a larger scale and it may occasionally not be possible to reliably distinguish RAML from renal cell carcinoma if only imaging data are available.
Anamnestic data, results obtained during the histological examination of percutaneous biopsy specimens, and those of genetic analyses may support a tentative diagnosis of RAML. RAML are typically found in young women, while renal cell carcinomas are most commonly diagnosed in patients aged 40 to 60 years, unless they are related to hereditary diseases predisposing for tumor growth. Those patients previously diagnosed with tuberous sclerosis or lymphangioleiomyomatosis are much more likely to repeatedly develop RAML than renal cell carcinomas. With regards to the histological examination of tissue samples, due to the heterogeneity of RAML, it may be difficult to obtain representative specimens. Immunohistochemical staining for specific tumor markers, e.g., smooth muscle actin and HMB-45 for RAML and CD10 and CD34 for renal cell carcinoma, may nevertheless yield conclusive results . Finally, the presence of mutations of tumor suppressor genes TSC1 or TSC2, which are associated with tuberous sclerosis and lymphangioleiomyomatosis and may be revealed by means of molecular biological techniques, indicate RAML.
Periodic clinical and imaging assessments are recommended in cases of asymptomatic RAML and small tumor size, if malignancy is not suspected. Generally, patients are to be re-examined yearly. Sporadic RAML are expected to grow slowly, but rapid growth may be observed in tuberous sclerosis-related cases. It is important to remember to realize regular blood pressure measurements, because renal neoplasms may interfere with the kidney's function in blood pressure regulation. At the same time, renal parameters should be evaluated by means of blood sample analysis .
Few years ago, everolimus, an inhibitor of the mTOR pathway, has been approved to treat tuberous sclerosis- and lymphangioleiomyomatosis -associated RAML. The mTOR pathway has been shown to play a crucial role in the pathogenesis of those diseases  . Cryoablation, radiofrequency ablation, and embolization of the renal artery have also been carried out to treat RAML, irrespective of their association to multi-system pathologies. The latter is of particular importance to avert the risk of hemorrhages and hemorrhagic shock; the former are typically considered in cases of small, but symptomatic RAML . While low complication rates and a good preservation of renal function have been reported for cryoablation , the risk of re-intervention was significantly higher after embolization than in patients that underwent any other treatment .
Surgical interventions have been recommended for patients with symptomatic RAML, for those with tumors that measure more than 4 cm in diameter or that contain aneurysms of more than 5 mm in diameter, for women of childbearing age, and if malignancy cannot be excluded . However, alternative treatment options should be seriously considered before opting for surgery because of the high incidence of complications and an increased risk of future renal insufficiency and end-stage renal failure . Partial, total, or radical nephrectomy may be conducted. If the situation warrants surgery but a patient's general condition renders them ineligible for surgery, either of the aforementioned approaches may be chosen to delay tumor growth and to avoid possibly life-threatening ruptures of aneurysms until general improvement.
RAML are benign neoplasms and are generally associated with a good prognosis. However, literature contains isolated reports of spread to adjacent tissues, to the renal vein and inferior vena cava, to regional lymph nodes and even to the large intestine . Presumably, such growth behavior is more likely in RAML of the epithelioid variant, a rare form of RAML that has also been designated atypical or oncocytoma-like RAML . Epithelioid RAML differ from typical, triphasic RAML in that they are missing the characteristic vascular structures and adipocytes.
RAML have originally been classified as hamartomas because they were thought to develop due to an abnormal proliferation of certain components of renal tissue. This classification has been revised and RAML are now listed as perivascular epithelioid cell tumors or PEComas. These tumors may grow at a variety of visceral and soft tissue sites and arise from clonal proliferation of epithelioid cells surrounding blood vessels . While tuberous sclerosis and sporadic lymphangioleiomyomatosis have been related to mutations in either of the two tumor suppressor genes TSC1 or TSC2, little is known about the causes of sporadic RAML.
RAML are the most common solid, benign kidney tumors. RAML and other perivascular epithelioid cell tumors are more common in women . The female-to-male ratio is approximately 2:1, as has been confirmed in a large screening study for renal neoplasms conducted in Japan: Almost 18,000 individuals have been screened and RAML were detected in 0.22% of females and 0.1% of males . The overall prevalence of RAML has been calculated to 0.13% .
RAML develop within the renal parenchyma and are well-circumscribed tumors that usually don't spread to the renal capsule or the perirenal space . They are mesenchymal neoplasms typically composed of abnormal, eccentric and thick-walled vessels, smooth muscle cells of different maturation stages and adipocytes. While hemorrhages may be visible macroscopically or upon histological examination, necrotic foci are not characteristic of RAML. However, necrotic foci are not uncommon in the rare epithelioid subtype of RAML. This subtype is further characterized by an increased number of mitotic figures per microscopic field, which may be atypical . The histological hallmark of epithelioid RAML is the near absence of vascular structures and adipocytes. Malignant potential has been ascribed to about a third of all cases of epithelioid RAML, which distinguishes this subtype from all other forms of RAML .
Few recommendations can be given to prevent RAML: About 80% of all cases are sporadic and while one in five RAML patients does suffer from tuberous sclerosis, a hereditary disorder, this disease is often triggered by de novo mutations.
However, those affected by tuberous sclerosis are recommended to undergo regular imaging assessments to detect RAML at an early stage . This way, therapy can be initiated in a timely manner and the risk of possibly life-threatening hemorrhages can be reduced. This also applies for patients with lymphangioleiomyomatosis.
An angiomyolipoma is a benign neoplasm of mesenchymal origin that mainly consists of dysmorphic blood vessels, smooth muscle cells, and mature adipose tissue - the name of this tumor derives from that particular composition of tissues . Angiomyolipomas most commonly develop in the kidneys, but they may also be detected in the liver and, very rarely, in other organs. It has been estimated that about 80% of these tumors are sporadic, while the remaining 20% are developed by patients suffering from tuberous sclerosis or sporadic lymphangioleiomyomatosis . At the same time, most individuals affected by tuberous sclerosis and about 60% of lymphangioleiomyomatosis patients eventually develop RAML .
It is important to distinguish between sporadic RAML and cases associated to the pathological conditions mentioned above: The course of the disease varies considerably depending on its etiology. In sporadic cases, solitary tumors are much more common. By contrast, tuberous sclerosis patients usually develop multiple RAML that affect both kidneys . Also, tuberous sclerosis-related RAML tend to grow more rapidly and a reach larger size and than those affecting the general population. Large size is associated with an increased risk of hemorrhages and possibly hemorrhagic shock. Therefore, it is important to assess, and possibly re-assess, a tumor's size and vascularization. Besides imaging and histological data, these parameters are most important when deciding on one of several treatment options: surveillance, pharmacotherapy, cryoablation, radiofrequency ablation, embolization of the renal artery, or nephrectomy.
Renal angiomyolipoma (RAML) is a benign tumor of the kidney. Most cases are sporadic, i.e., they are not associated with any hereditary condition or pre-existing diseases. Sporadic RAML grow very slowly and don't usually cause any symptoms. Indeed, they are most commonly detected when individuals undergo diagnostic imaging of the abdomen for non-related reasons. By contrast, patients suffering from tuberous sclerosis or lymphangioleiomyomatosis should undergo regular imaging assessments because those disorders are known to predispose for RAML. About one in five RAML cases is not sporadic but related to either of the aforementioned pathologies. In individuals suffering from tuberous sclerosis or lymphangioleiomyomatosis, RAML tend to grow faster and reach larger sizes. Because large RAML often contain abnormal blood vessels that may eventually rupture, causing possibly life-threatening hemorrhages, alternative therapeutic approaches may be chosen: In case of sporadic RAML, patients are generally recommended for surveillance and periodic re-imaging, but larger tumors like those frequently found in those affected by tuberous sclerosis or lymphangioleiomyomatosis may require pharmacological treatment, minimally invasive or conventional surgery. The patient's prognosis is generally good, even more so in case of sporadic RAML. Tuberous sclerosis and lymphangioleiomyomatosis predispose for the development of certain types of tumors and while the current problem may be solved, recurrence is more likely.
- Lienert AR, Nicol D. Renal angiomyolipoma. BJU Int. 2012; 110 Suppl 4:25-27.
- Katada Y, Umehara I, Ohki T, Kishino M, Shibuya H. Bilateral renal angiomyolipoma in a patient with tuberous sclerosis treated with resection of one kidney and transarterial embolization of other kidney using CT during selective arteriography: a case report. Cases J. 2009; 2:6351.
- Ugwumba FO, Nnakenyi EF, Okafor OC, Onuh AC, Ezechukwu PC, Urube S. Renal Angiomyolipoma in Pregnancy: Surgical Management with Fetal Preservation - Approach in a Developing Setting. Clin Pract. 2016; 6(4):893.
- Jinzaki M, Tanimoto A, Narimatsu Y, et al. Angiomyolipoma: imaging findings in lesions with minimal fat. Radiology. 1997; 205(2):497-502.
- Lim RS, Flood TA, McInnes MDF, Lavallee LT, Schieda N. Renal angiomyolipoma without visible fat: Can we make the diagnosis using CT and MRI? Eur Radiol. 2017.
- Schieda N, Hodgdon T, El-Khodary M, Flood TA, McInnes MD. Unenhanced CT for the diagnosis of minimal-fat renal angiomyolipoma. AJR Am J Roentgenol. 2014; 203(6):1236-1241.
- Flum AS, Hamoui N, Said MA, et al. Update on the Diagnosis and Management of Renal Angiomyolipoma. J Urol. 2016; 195(4 Pt 1):834-846.
- Kufer V, Schwab SA, Büttner M, Agaimy A, Uder M, Amann K. Incidental monotypic (fat-poor) renal angiomyolipoma diagnosed by core needle biopsy. Case Rep Med. 2012; 2012:906924.
- Samuels JA. Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis Complex. Clin J Am Soc Nephrol. 2017; 12(7):1196-1202.
- Brakemeier S, Bachmann F, Budde K. Treatment of renal angiomyolipoma in tuberous sclerosis complex (TSC) patients. Pediatr Nephrol. 2017; 32(7):1137-1144.
- Makki A, Graumann O, Hoyer S, et al. Cryoablation of Renal Angiomyolipoma: An Evaluation of Safety and Efficacy. J Endourol. 2017; 31(11):1117-1122.
- Kuusk T, Biancari F, Lane B, et al. Treatment of renal angiomyolipoma: pooled analysis of individual patient data. BMC Urol. 2015; 15:123.
- Krueger DA, Northrup H. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4):255-265.
- Sun DZ, Campbell SC. Atypical Epithelioid Angiomyolipoma: A Rare Variant With Malignant Potential. Urology. 2017.
- Armah HB, Parwani AV. Perivascular epithelioid cell tumor. Arch Pathol Lab Med. 2009; 133(4):648-654.
- Fujii Y, Ajima J, Oka K, Tosaka A, Takehara Y. Benign renal tumors detected among healthy adults by abdominal ultrasonography. Eur Urol. 1995; 27(2):124-127.
- Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int. 2004; 66(3):924-934.