Angiomyolipoma of the left and right kidney

Among benign tumors, there is such a specific neoplasm as angiomyolipoma, which can be accidentally detected during imaging of the abdominal organs. Although, reaching a certain size, this tumor can cause a number of symptoms and complications.

The first most frequent localization of angiomyolipoma is the kidneys, the  [1]second is the liver; rarely, such a tumor forms in the spleen, retroperitoneal space, lungs, soft tissues, ovaries, fallopian tubes.

Epidemiology

Angiomyolipoma of the kidneys - the most common benign tumor of this organ - develops sporadically in 0.2-0.6% of people after 40 years, and women predominate among patients. [2]

According to clinical statistics, in 80% of cases, single formations occur.

Angiomyolipoma is less common in children than in adults. According to research, in 75% of children with tuberous sclerosis at the age of ten, renal angiomyolipoma is found, and its size increases in more than 50% of cases. [3], [4]

Causes of the angiomyolipomas

The exact causes of angiomyolipoma are unknown, and it can occur sporadically in middle-aged adults. But the version of the genetically determined origin of these tumors has strong evidence. So, most often, kidney angiomyolipoma is associated with a hereditary genetic disease -  tuberous sclerosis , which is caused by a mutation of one of two tumor suppressor genes: TSC1 (on the long arm of chromosome 9q34) or TSC2 (on the short arm of chromosome 16p13) and in which - due to excessive proliferation cells - benign neoplasias of various localization are formed, including multiple renal angiomyolipomas.

Angiomyolipoma of the renal parenchyma with cystic changes is detected in almost one third of patients with such a progressive systemic disease as pulmonary  lymphangioleiomyomatosis  (LAM), as well as in its fairly common combination with tuberous sclerosis. [5]

In children, there is a connection between the appearance of numerous angiomyolipomas with the presence of congenital encephalotrigeminal angiomatosis (Sturge-Weber syndrome), caused by random mutations in the GNAQ gene (encoding guanine nucleotide binding protein G), or with type I neurofibromatosis (the result of neurofibromin 1 protein NF-1).

Risk factors

Experts consider tuberous sclerosis to be the most serious risk factor for the development of this neoplasm: bilateral angiomyolipomas - angiomyolipoma of the left kidney and simultaneously angiomyolipoma of the right kidney - are detected in 50-80% of patients.

Among the general factors that increase the risk of these tumors, there are genetic mutations that are inherited or occur spontaneously during intrauterine development, as well as the presence of certain systemic syndromes.

Pathogenesis

Angiomyolipomas are defined as mesenchymal tumors, that is, they are neoplasms of  mesenchymal stem cells  - adult pluro or multipotent stem cells of adipose, muscle and vascular tissues.

It is assumed that the pathogenesis of tumor formation is due to the increased ability of these cells to proliferate, self-renewal by dividing and differentiating into cells of various tissues (including adipose, muscle and connective tissues). And the morphological feature of classical angiomyolipoma is the presence of adipose tissue cells (adipocytes), smooth muscle cells and blood vessels (with thickened walls and abnormal lumens) in its composition.

In addition, this tumor is considered a perivascular epithelioid cell neoplasm, which, according to many researchers, originates from epithelioid cells (epithelioid histiocytes) adjacent to the vessel walls. Being derivatives of activated macrophages, these cells resemble epithelial cells, but have a modified cytoskeleton, denser cell membranes, and an increased ability to aggregate and adhere. [6]

Symptoms of the angiomyolipomas

In the presence of this tumor more than 30-40 mm in diameter, the main symptoms - in cases of localization of the formation in the kidneys - appear in the form of sudden pain (in the abdomen, side or back); nausea and vomiting; fever, hypotension / hypertension, anemia. Occasionally, larger angiomyolipomas can bleed spontaneously, leading to  hematuria .

But the distinct first signs are always manifested by abdominal pain of varying intensity.

An extremely rare tumor - liver angiomyolipoma - is asymptomatic in most patients and is detected by chance; may assert itself with minor pain in the right hypochondrium and abdominal discomfort. But intratumoral hemorrhage with bleeding into the abdominal cavity is also possible. [7]

Very rare neoplasms include adrenal angiomyolipoma (with a prevalence of 0.5-5%). As a rule, it does not manifest itself in any way, however, when it is large, it causes pain in the abdomen. [8], [9]

Splenic angiomyolipoma can be isolated, but is more often associated with renal angiomyolipoma and tuberous sclerosis; education grows slowly and asymptomatic. With angiomyoipoma of the mediastinum against the background of tuberous sclerosis, shortness of breath, chest pains, nausea and vomiting develop, pleural effusions are noted.

Angiomyolipoma of soft tissues behaves differently, which can form, for example, in the anterior abdominal wall (in the form of a dense node), in the skin of any localization, in deep muscle tissues.

Angiomyolipoma and pregnancy. If a pregnant woman has a timely undetected renal angiomyolipoma, her hemorrhagic rupture, causing bleeding, can have fatal consequences for both the mother and the fetus. [10], [11]

Forms

In the absence of a unified classification, the types or types of angiomyolipomas are distinguished not so much by localization as by their histology and visualized characteristics.

Kidney angiomyolipomas are divided into sporadic (isolated) and hereditary (associated with tuberous sclerosis). According to histological features, isolated angiomyolipomas are divided into three-phase (typical) and single-phase (atypical).

In addition, using the methods of computer and magnetic resonance imaging, the three-phase type is divided into tumors with a high content of adipose tissue and, accordingly, with a low; Also, specialists take into account how fat cells are distributed in the tumor mass.

Tumors with a low content of adipocytes and a predominance of smooth muscle cells are called epithelioid or atypical, referring to them as potentially malignant neoplasms.

Complications and consequences

The main consequences and complications of angiomyolipoma include:

• spontaneous retroperitoneal bleeding, which can lead to shock;
• dilation of the blood vessels of the tumor (aneurysm);
• destruction of the renal parenchyma, leading to a decrease in renal function and end-stage renal failure (with the threat of the need for dialysis or nephrectomy).

Epithelioid angiomyolipoma - in rare cases - can transform into a malignant tumor with metastases to the lymph nodes. [12]

Diagnostics of the angiomyolipomas

Imaging, that is, instrumental diagnostics, plays a key role in the detection of renal angiomyolipomas. [13]

And analyzes (microscopic examination) of a tumor tissue sample obtained by a percutaneous renal biopsy are  [14]necessary to differentiate a benign mesenchymal tumor with low adipocyte count from renal cell carcinoma. With epithelioid angiomyolipoma, an additional immunohistochemical analysis of a tumor tissue sample may be required. [15]

A classical, with a sufficient amount of adipose tissue, an angiomyolipoma on ultrasound shows a hyperechoic mass, and formations less than 30 mm can produce acoustic shading. The echogenicity is the lower, the less fatty cells are in the composition of the neoplasm, therefore, experts note the lack of diagnostic reliability of ultrasonography (especially for small tumors).

The density of adipocytes in the renal tumor clearly shows angiomyolipoma on CT - in the form of dark (hypodense) foci. [16]

If there are too few adipose tissue cells in the tumor, angiomyolipoma is examined on MRI to visualize and locate areas of fat in the mass by comparing T1-weighted images with and without frequency selective fat suppression. [17]

Differential diagnosis

Differential diagnosis is extremely important. If the number of adipocytes in the tumor is low, that is, it is closer to the epithelioid formation, angiomyolipoma or kidney cancer (renal cell carcinoma, sarcoma, etc.) should be differentiated.

Differentiation is also carried out with retroperitoneal liposarcoma with kidney damage, oncocytoma, Williams' tumor, adrenal myelolipoma.

Treatment of the angiomyolipomas

For each patient, the treatment of angiomyolipoma is carried out taking into account the size of the tumor and the clinical picture. Its purpose is to protect the renal parenchyma while preserving their functions. [18]

Methods range from active surveillance (from the moment a tumor is detected) to medication and surgery. Observation of small angiomyolipomas of the kidneys (the size of which does not exceed 40 mm) includes an annual ultrasound of the kidneys, and with an increase in the formation (usually by 5% per year) - CT of the kidneys.

The criteria for eligibility for treatment, according to the recommendations of the European Association of Urology (EAU), are large tumors and the presence of symptoms.

Although pharmacological therapy for angiomyolipomas is in the research phase, the main drugs used for renal angiomyolipomas associated with tuberous sclerosis and / or lymphangioleiomyomatosis are rapamycin protein-blocking (mTOR) immunosuppressants that stop cell proliferation: Rapamycin (Sirolimus) (, Zotarolimus.

The use of these drugs is long-term, therefore, one should bear in mind the high risk of their side effects, including a decrease in the number of leukocytes and platelets and an increase in blood cholesterol levels, arterial hypertension, pain in the abdominal region and intestinal disorders, increased frequency of infections (bacterial, viral, fungal). [19]

With large sizes of neoplasms in the kidneys, surgical treatment is performed:

• selective vascular embolization; [20]
• radiofrequency or cryoablation of the tumor; [21]
• partial or complete nephrectomy. 

Patients with decreased kidney function are additionally recommended nutritional therapy -  diet No. 7 .

Prevention

Preventive measures include early detection of angiomyolipomas, and arterial embolization is used as a preventive treatment for symptomatic or large tumors (due to the risk of bleeding).

Forecast

If angiomyolipomas do not enlarge rapidly and do not have dilated blood vessels, the prognosis is good. Otherwise, severe renal failure develops, requiring removal of the kidney or constant dialysis.