Angiomyolipoma
Encyclopedia
Angiomyolipoma are the most common benign tumour of the kidney and are composed of blood vessels, smooth muscle cells and fat cells. Angiomyolipoma are strongly associated with the genetic disease tuberous sclerosis
, in which most individuals will have several angiomyolipoma affecting both kidneys. They are also commonly found in women with the rare lung disease lymphangioleiomyomatosis
. Angiomyolipoma are less commonly found in the liver and rarely in other organs. Whether associated with these diseases or sporadic, angiomyolipoma are caused by mutations in either the TSC1
or TSC2
genes, which govern cell growth and proliferation.
Although regarded as benign, angiomyolipoma may grow such that kidney function is impaired or the blood vessels may dilate
and burst leading to haemorrhage. Large angiomyolipoma can be treated with embolisation. Drug therapy for angiomyolipoma is at the research stage.
cells (cells which are found surrounding blood vessels and which resemble epithelial cells). A tumour of this kind is known as a PEComa
, from the initials of perivascular epithelioid cell. Older literature may classify them as hamartoma
(benign tumours consisting of cells in their correct location but forming a disorganised mass) or choristoma (benign tumours consisting of normal cells in the wrong location). PEComas are themselves a kind of mesenchymal tumour which involves cells that form the connective tissue
, cardiovascular and lymphatic
systems.
An angiomyolipoma is composed of varying proportions of vascular cells, immature smooth muscle cells and fat cells. These three components respectively give rise to the components of the name: angio-, myo- and lip-. The -oma suffix is indicates a tumour.
Angiomyolipoma are typically found in the kidney but have also been commonly found in the liver and less commonly the ovary, fallopian tube, spermatic cord, palate and colon.
causes sudden pain, accompanied with nausea and vomiting. When the patient presents in the emergency department
, up to 20% will be in shock.
that suffered the common second hit mutation.
and a lesion growing at greater than 5 mm per year may warrant a biopsy in order to distinguish it from a from this form of cancer.
People with tuberous sclerosis are advised to have yearly renal scans, though it is possible that patients with very stable lesions could be monitored less frequently. The research in this area is lacking. Even if no angiomyolipoma is found, one can develop at any life stage. The angiomyolipoma can grow rapidly.
In tuberous sclerosis, there are typically many angiomyolipoma affecting both kidneys. It is not uncommon for more than one intervention to be required during lifetime. Since kidney function may already be impaired (up to half the kidney may be lost before function loss is detectable), it is vital to preserve as much kidney as possible when removing any lesion. Large angiomyolipoma are treated by embolisation which reduces the risk of haemorrhage and can also shrink the lesion. A side effect of this treatment is postembolisation syndrome: severe pain and fever, possibly for many weeks.
A ruptured aneurysm in an angiomyolipoma leads to blood loss that must be stopped (though embolisation) and compensated for (through intravenous fluid replacement
). Therefore, removal of the affected kidney (nephrectomy
) is strongly discouraged though may occur if the emergency department is not knowledgeable about tuberous sclerosis.
Embolisation involves inserting a catheter
along the blood vessels to the tumour. The blood vessels are then blocked
, typically by injecting ethanol or inert particles. The procedure can be very painful, so analgesic
s are used. The destroyed kidney tissue often causes post-embolisation syndrome, which manifests as nausea, vomiting, fever and abdominal pain, and lasts a few days. Embolisation (in general) has an 8% rate of morbidity and a 2.5% rate of mortality
, so is not considered lightly.
Patients with kidney loss should be monitored for hypertension (and treated for it if discovered) and avoid nephrotoxic drugs such as certain pain relievers and IV contrast agents. Such patients who are unable to communicate effectively (due to age or intellectual disability) are at risk of dehydration. Where multiple or large angiomyolipoma have caused chronic kidney disease, dialysis is required.
Rapamycin and related drugs have been studied for their effect on angiomyolipoma due to their action on the pathways that are disrupted when TSC1 and TSC2 genes are broken. Small studies showed the lesions shrank but that the drugs were often toxic. The use of these drugs remains at the research stage.
blood vessels (aneurysms) cause few problems, but angiomyolipoma have been known to grow as rapidly as 4 cm in one year. An angiomyolipoma larger than 5 cm and those containing an aneurysm pose a significant risk of rupture, which is a medical emergency as it is potentially life threatening. One population study found the cumulative risk of haemorrhage to be 10% in males and 20% in females.
A second problem occurs when the renal angiomyolipoma take over so much kidney that the function is impaired leading to chronic kidney disease. This may be severe enough to require dialysis
. A population survey of patients with TSC and normal intelligence found 1% were on dialysis.
In patients with TSC, a longitudinal study
found 80% will have some form of renal lesion by around 10 years-of-age. Of these, 75% are angiomyolipoma and 17% cysts. The angiomyolipoma increased in size in around 60% of these children. An autopsy study and TSC clinic survey found an prevalence of 67% and 85% respectively for patients with TSC. Both genders are affected equally.
Tuberous sclerosis
Tuberous sclerosis or tuberous sclerosis complex is a rare multi-system genetic disease that causes non-malignant tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, developmental delay, behavioral...
, in which most individuals will have several angiomyolipoma affecting both kidneys. They are also commonly found in women with the rare lung disease lymphangioleiomyomatosis
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis is a rare lung disease that results in a proliferation of disorderly smooth muscle growth throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways and lymphatics...
. Angiomyolipoma are less commonly found in the liver and rarely in other organs. Whether associated with these diseases or sporadic, angiomyolipoma are caused by mutations in either the TSC1
TSC1
Tuberous sclerosis protein 1, also known as TSC1 or hamartin, is a human protein and gene.- Function :This peripheral membrane protein was implicated as a tumor suppressor...
or TSC2
TSC2
Tuberous sclerosis protein 2, also known as TSC2 and Tuberin, is a human protein and gene.-Interactions:TSC2 has been shown to interact with FOXO1, GSK3B, Peptidylglycine alpha-amidating monooxygenase, RAP1A, MAPK1, AKT1, AXIN1, TSC1, PTK2, Protein kinase, AMP-activated, alpha 1, YWHAZ, RPS6KA1,...
genes, which govern cell growth and proliferation.
Although regarded as benign, angiomyolipoma may grow such that kidney function is impaired or the blood vessels may dilate
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
and burst leading to haemorrhage. Large angiomyolipoma can be treated with embolisation. Drug therapy for angiomyolipoma is at the research stage.
Classification
Angiomyolipoma are tumours consisting of perivascular epithelioidEpithelioid
An epithelioid cell is a cell that resembles epithelial cells in that it directly contacts its neighboring cells via cell surface molecules or junctions. Unlike epithelial cells, however, epithelioid cells make contacts over their entire surface, rather than at restricted portions. The term...
cells (cells which are found surrounding blood vessels and which resemble epithelial cells). A tumour of this kind is known as a PEComa
PEComa
In oncology, PEComa, also PEC tumour and perivascular epithelioid cell tumour, is a family of mesenchymal tumours consisting of perivascular epithelioid cells . These are rare tumours that can occur in any part of the human body....
, from the initials of perivascular epithelioid cell. Older literature may classify them as hamartoma
Hamartoma
A hamartoma is a benign, focal malformation that resembles a neoplasm in the tissue of its origin. This is not a malignant tumor, and it grows at the same rate as the surrounding tissues. It is composed of tissue elements normally found at that site, but which are growing in a disorganized mass...
(benign tumours consisting of cells in their correct location but forming a disorganised mass) or choristoma (benign tumours consisting of normal cells in the wrong location). PEComas are themselves a kind of mesenchymal tumour which involves cells that form the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
, cardiovascular and lymphatic
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...
systems.
An angiomyolipoma is composed of varying proportions of vascular cells, immature smooth muscle cells and fat cells. These three components respectively give rise to the components of the name: angio-, myo- and lip-. The -oma suffix is indicates a tumour.
Angiomyolipoma are typically found in the kidney but have also been commonly found in the liver and less commonly the ovary, fallopian tube, spermatic cord, palate and colon.
Symptoms
If the dilated blood vessels in an angiomyolipoma rupture, the resulting retroperitoneal haemorrhageRetroperitoneal hemorrhage
Retroperitoneal hemorrhage refers to an accumulation of blood found in the retroperitoneal space.It can present with Grey Turner's sign .Causes include:* anticoagulation* a ruptured aortic aneurysm...
causes sudden pain, accompanied with nausea and vomiting. When the patient presents in the emergency department
Emergency department
An emergency department , also known as accident & emergency , emergency room , emergency ward , or casualty department is a medical treatment facility specialising in acute care of patients who present without prior appointment, either by their own means or by ambulance...
, up to 20% will be in shock.
Pathophysiology
Since all three components of an angiomyolipoma (vascular cells, immature smooth muscle cells and fat cells) contain a "second hit" mutation, they are believed to have derived from a common progenitor cellProgenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
that suffered the common second hit mutation.
Diagnosis
There are three methods of scanning that detect angiomyolipoma: ultrasound, CT and MRI. Ultrasound is standard and is particularly sensitive to the fat in angiomyolipoma but less so to the solid components. However it is hard to make accurate measurements with ultrasound. Computed tomography (CT) is very detailed and fast and allows accurate measurement. However, it exposes the patient to radiation and the dangers that a contrast dye used to aid the scanning may itself harm the kidneys. Magnetic resonance imaging (MRI) is safer than CT but many patients (particularly those with the learning difficulties or behavioural problems found in tuberous sclerosis) require sedation or general anaesthesia and the scan cannot be performed quickly. Some other kidney tumours contain fat, so the presence of fat isn't diagnostic. It can be difficult to distinguish a fat-poor angiomyolipoma from a renal cell carcinomaRenal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
and a lesion growing at greater than 5 mm per year may warrant a biopsy in order to distinguish it from a from this form of cancer.
Treatment
Angiomyolipoma do not normally require surgery unless there is life threatening bleeding. Some centres may perform preventative selective embolisation of the angiomyolipoma if it is more than 4 cm in diameter, due to the risk of haemorrhage.People with tuberous sclerosis are advised to have yearly renal scans, though it is possible that patients with very stable lesions could be monitored less frequently. The research in this area is lacking. Even if no angiomyolipoma is found, one can develop at any life stage. The angiomyolipoma can grow rapidly.
In tuberous sclerosis, there are typically many angiomyolipoma affecting both kidneys. It is not uncommon for more than one intervention to be required during lifetime. Since kidney function may already be impaired (up to half the kidney may be lost before function loss is detectable), it is vital to preserve as much kidney as possible when removing any lesion. Large angiomyolipoma are treated by embolisation which reduces the risk of haemorrhage and can also shrink the lesion. A side effect of this treatment is postembolisation syndrome: severe pain and fever, possibly for many weeks.
A ruptured aneurysm in an angiomyolipoma leads to blood loss that must be stopped (though embolisation) and compensated for (through intravenous fluid replacement
Fluid replacement
Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced via oral administration , intravenous administration, rectally, or hypodermoclysis, the direct injection...
). Therefore, removal of the affected kidney (nephrectomy
Nephrectomy
Nephrectomy is the surgical removal of a kidney.-History:The first successful nephrectomy was performed by the German surgeon Gustav Simon on August 2, 1869 in Heidelberg. Simon practiced the operation beforehand in animal experiments...
) is strongly discouraged though may occur if the emergency department is not knowledgeable about tuberous sclerosis.
Embolisation involves inserting a catheter
Catheter
In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...
along the blood vessels to the tumour. The blood vessels are then blocked
Vascular occlusion
Vascular occlusion is a sudden blockage of a blood vessel, usually with a clot. It differs from thrombosis in that it can be used to describe any form of blockage, not just one formed by a clot. When it occurs in a major vein, it can, in some cases, cause deep vein thrombosis. The condition is...
, typically by injecting ethanol or inert particles. The procedure can be very painful, so analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s are used. The destroyed kidney tissue often causes post-embolisation syndrome, which manifests as nausea, vomiting, fever and abdominal pain, and lasts a few days. Embolisation (in general) has an 8% rate of morbidity and a 2.5% rate of mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
, so is not considered lightly.
Patients with kidney loss should be monitored for hypertension (and treated for it if discovered) and avoid nephrotoxic drugs such as certain pain relievers and IV contrast agents. Such patients who are unable to communicate effectively (due to age or intellectual disability) are at risk of dehydration. Where multiple or large angiomyolipoma have caused chronic kidney disease, dialysis is required.
Rapamycin and related drugs have been studied for their effect on angiomyolipoma due to their action on the pathways that are disrupted when TSC1 and TSC2 genes are broken. Small studies showed the lesions shrank but that the drugs were often toxic. The use of these drugs remains at the research stage.
Prognosis
Small angiomyolipoma and those without dilatedVasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
blood vessels (aneurysms) cause few problems, but angiomyolipoma have been known to grow as rapidly as 4 cm in one year. An angiomyolipoma larger than 5 cm and those containing an aneurysm pose a significant risk of rupture, which is a medical emergency as it is potentially life threatening. One population study found the cumulative risk of haemorrhage to be 10% in males and 20% in females.
A second problem occurs when the renal angiomyolipoma take over so much kidney that the function is impaired leading to chronic kidney disease. This may be severe enough to require dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
. A population survey of patients with TSC and normal intelligence found 1% were on dialysis.
Epidemiology
Angiomyolipoma are the most common benign tumour of the kidney and are found either in patients with tuberous sclerosis or sporadically. About 80–90% of cases are sporadic and these are most commonly found in middle-aged women.In patients with TSC, a longitudinal study
Longitudinal study
A longitudinal study is a correlational research study that involves repeated observations of the same variables over long periods of time — often many decades. It is a type of observational study. Longitudinal studies are often used in psychology to study developmental trends across the...
found 80% will have some form of renal lesion by around 10 years-of-age. Of these, 75% are angiomyolipoma and 17% cysts. The angiomyolipoma increased in size in around 60% of these children. An autopsy study and TSC clinic survey found an prevalence of 67% and 85% respectively for patients with TSC. Both genders are affected equally.