Angiomyolipomas are the most common benign tumour of the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
. Although regarded as benign, angiomyolipomas may grow such that
kidney function is impaired or the blood vessels may
dilate
Dilation (or dilatation) may refer to:
Physiology or medicine
* Cervical dilation, the widening of the cervix in childbirth, miscarriage etc.
* Coronary dilation, or coronary reflex
* Dilation and curettage, the opening of the cervix and surgic ...
and burst, leading to bleeding.
Angiomyolipomas are strongly associated with the genetic disease
Tuberous Sclerosis
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...
, in which most individuals have several Angiomyolipomas affecting both kidneys. They are also commonly found in women with the rare lung disease
lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare, progressive and systemic disease that typically results in cystic lung destruction. It predominantly affects women, especially during childbearing years. The term sporadic LAM is used for patients with LAM ...
. Angiomyolipomas are less commonly found in the liver and rarely in other organs. Whether associated with these diseases or sporadic, Angiomyolipomas are caused by mutations in either the ''
TSC1
Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the ''TSC1'' gene.
Function
TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and de ...
'' or ''
TSC2
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene.
Function
Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is a ...
''genes, which govern cell growth and proliferation. They are composed of blood vessels, smooth muscle cells, and fat cells.
Large Angiomyolipomas can be treated with
embolisation
Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (t ...
. Drug therapy for Angiomyolipomas is at the research stage. The Tuberous Sclerosis Alliance has published guidelines on diagnosis, surveillance, and management.
Signs and symptoms
![CT of angiomyolipoma, before and after radiocontrast](https://upload.wikimedia.org/wikipedia/commons/d/d3/CT_of_angiomyolipoma%2C_before_and_after_radiocontrast.jpg)
Most people with benign Angiomyolipomas do not show signs or have symptoms. However, some people can have symptoms If the dilated blood vessels in an Angiomyolipoma rupture, this is called a
retroperitoneal hemorrhage
Retroperitoneal bleeding is an accumulation of blood in the retroperitoneal space. Signs and symptoms may include abdominal or upper leg pain, hematuria, and shock. It can be caused by major trauma or by non-traumatic mechanisms.
Signs and sympto ...
. This can cause pain in the back, nausea and vomiting. Some long-term effects are anemia, hypertension, and chronic kidney disease. Up to 20% of patients who present symptoms, and are brought into the
emergency department
An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pati ...
, are in
shock
Shock may refer to:
Common uses Collective noun
*Shock, a historic commercial term for a group of 60, see English numerals#Special names
* Stook, or shock of grain, stacked sheaves
Healthcare
* Shock (circulatory), circulatory medical emerge ...
.
[
]
Pathophysiology
Angiomyolipomas are tumours consisting of perivascular Mural cells are the vascular smooth muscle cells (vSMCs), and pericytes, of the microcirculation. Both types are in close contact with the endothelial cells lining the capillaries, and are important for vascular development and stability. Mural cell ...
epithelioid cells (cells which are found surrounding blood vessels and which resemble epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
). A tumour of this kind is known as a PEComa
Perivascular epithelioid cell tumour, also known as PEComa or PEC tumour, is a family of mesenchymal tumours consisting of perivascular epithelioid cells (PECs). These are rare tumours that can occur in any part of the human body.
The cell type ...
, from the initials of perivascular epithelioid cell. Older literature may classify them as hamartomas
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...
(benign tumours consisting of cells in their correct location, but forming a disorganised mass) or choristoma Choristomas, a form of heterotopia, are masses of normal tissues found in abnormal locations. In contrast to a neoplasm or tumor, the growth of a choristoma is normally regulated.
It is different from a hamartoma. The two can be differentiated a ...
(benign tumours consisting of normal cells in the wrong location). PEComas are themselves a kind of mesenchymal tumour
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...
which involves cells that form the connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
, cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
, and lymphatic
Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...
systems.[
An Angiomyolipoma is composed of varying proportions of vascular cells, immature ]smooth muscle cell
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
s, and fat cell
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
s.[ These three components respectively give rise to the components of the name: angio-, myo-, and lip-. The -oma suffix indicates a tumour.
Angiomyolipomas 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. The Maclean imaging classification system for renal Angiomyolipomas is based on the location of the Angiomyolipoma within the kidney.][D. F. W. Maclean, R. Sultana, R. Radwan, L. McKnight, and J. Khastgir]
Is the follow-up of small renal angiomyolipomas a necessary precaution?
Clinical Radiology, vol.69, no.8, pp.822–826, 2014
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 cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
that developed the common second-hit mutation.[
]
Diagnosis
Three methods of scanning can detect Angiomyolipomas: ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Ultrasound is standard and is particularly sensitive to the fat in Angiomyolipomas, but less so to the solid components. However, accurate measurements are hard to make with ultrasound, particularly if the Angiomyolipoma is near the surface of the kidney (grade III). 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. 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 is not diagnostic. Distinguishing a fat-poor angiomyolipoma from a ]renal cell carcinoma
Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, resp ...
(RCC) can be difficult. Both minimal fat AMLs and 80% of the clear-cell type of RCCs display signal drop on an out-of-phase MRI sequence compared to in-phase. Thus, a lesion growing at greater than 5 mm per year may warrant a biopsy for diagnosis.[
Incidental discovery of angiomyolipomas (AML) should trigger consideration of ]tuberous sclerosis
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...
complex (TSC), especially those who aged 18 to 40 years, and those with bilateral angiomyolipomas. Those with AML and TSC has 20 to 50% chance of having haemorrhage from AML, and of those having haemorrhages, 20% of them have life-threatening haemorrhages. Screening for TSC includes a detailed physical exam, including dermatologic and ophthalmologic evaluations, by TSC expert clinicians and a CT or MRI of the brain. Screening for LAM includes a high-resolution CT of the lung and pulmonary function testing.
Treatment
Everolimus
Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.
It is the 40 ...
is FDA approved for the treatment of Angiomyolipomas. Treatment should be considered for asymptomatic, growing AMLs measuring larger than 3 cm in diameter.
Angiomyolipomas do not normally require surgery unless life-threatening bleeding is present.[ Some centers may perform preventative selective ]embolisation
Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (t ...
of the Angiomyolipoma if it is more than 4 cm in diameter, due to the risk of hemorrhage.
People with Tuberous Sclerosis are advised to have yearly renal scans, though 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, typically, many Angiomyolipomas affect each kidney. Not uncommonly, more than one intervention may be required during lifetime. Since kidney function may already be impaired (up to half the kidney may be lost before function loss is detectable), preserving as much kidney as possible is vital when removing any lesion. Large Angiomyolipomas are treated by embolization, which reduces the risk of hemorrhage and can also shrink the lesion. A side effect of this treatment is postembolisation syndrome, severe pain and fever, but this is easily managed and lasts only a few days.][
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 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 with oral rehydration therapy (drinking), intravenous ...
). Therefore, removal of the affected kidney (nephrectomy
A nephrectomy is the surgical removal of a kidney, performed to treat a number of kidney diseases including kidney cancer. It is also done to remove a normal healthy kidney from a living or deceased donor, which is part of a kidney transplant pro ...
) is strongly discouraged, though may occur if the emergency department is not knowledgeable about Tuberous Sclerosis.[
Embolisation involves inserting a ]catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
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
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s are used. The destroyed kidney tissue often causes postembolisation syndrome, which manifests as nausea, vomiting, fever, and abdominal pain, and lasts a few days. Embolisation (in general) has an 8% rate of morbidity
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
and a 2.5% rate of mortality
Mortality is the state of being mortal, or susceptible to death; the opposite of immortality.
Mortality may also refer to:
* Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
, 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 intravenous 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 angiomyolipomas have caused ]chronic kidney disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
, dialysis is required.[
Robotic assisted partial nephrectomy has been proposed as a surgical treatment of a ruptured Angiomyolipoma combining the advantages both of a kidney preservation procedure and the benefits of a minimal invasive procedure without compromising the safety of the patient.]
Follow-up
It is suggested that no follow-up is needed for Angiomyolipoma-like incidental imaging finding
In medical or research imaging, an incidental imaging finding (also called an incidentaloma) is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental medical findings, they may represen ...
s measuring less than 1 or 2 cm. Alternatively, a renal ultrasonography
Renal ultrasonography (Renal US) is the examination of one or both kidneys using medical ultrasound.
Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most ...
every 3 or 4 years has been suggested for angiomyolipoma-like masses measuring less than 2 cm.[ This topic last updated: Dec 30, 2017.] For those measuring 2 to 4 cm, annual ultrasonography is recommended.[ Those over 4 cm are usually surgically removed, but for those that are not, it is recommended to perform an ultrasonography after 6 months, and then annually if stable.][
]
Prognosis
Small Angiomyolipomas and those without dilated blood vessels (aneurysms
An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus (s ...
) cause few problems, but Angiomyolipomas have been known to grow as rapidly as 4 cm in one year. Angiomyolipomas 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 hemorrhage to be 10% in males and 20% in females.[
A second problem occurs when the renal Angiomyolipomas take over so much kidney that the function is impaired, leading to chronic kidney disease. This may be severe enough to require ]dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
. A population survey of patients with TSC and normal intelligence found 1% were on dialysis.[
]
Epidemiology
Angiomyolipomas are the most common benign tumor 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
A longitudinal study (or longitudinal survey, or panel study) is a research design that involves repeated observations of the same variables (e.g., people) over short or long periods of time (i.e., uses longitudinal data). It is often a type of obs ...
found 80% will have some form of renal lesion by around 10 years of age. Of these, 75% are Angiomyolipomas and 17% are cysts. The Angiomyolipomas increased in size in around 60% of these children. An autopsy study and TSC clinic survey found a prevalence of 67 and 85%, respectively, for patients with TSC. Both genders are affected equally.[Bissler JJ, Henske EP. Renal Manifestations of Tuberous Sclerosis Complex. In: Kwiatkowski DJ, Wiittlemore DJ, Thiele EA, editors. Tuberous Sclerosis Complex: Genes, Clinical Features and Therapeutics. Wiley-VCH Verlag GmbH; 2010. p. 321–325. .]
References
External links
{{Urologic neoplasia
Benign neoplasms
Urological neoplasia
Benign renal neoplasms