156	4 Renal Tumors in Children

•Neoadjuvant chemotherapy has been shown to decrease the size and stage of RCC and this allow it to be surgically removed. This may be useful in those with large non resectable tumors but the effectiveness of this approach is still being assessed.

•Immunotherapy with interferon or interleukin for the treatment of advanced RCC have been reported, but the benefits of these are uncertain in children.

•The role of new agents such as tyrosine kinase inhibitors is not well established in children with RCC.

•Metastatic renal cell carcinoma:

–Metastatic renal cell carcinoma has a poor prognosis.

–The tumor is extremely resistant to chemotherapy, rendering metastatic disease difficult to treat.

–25–30 % of patients with RCC have metastatic spread at the time of diagnosis.

–The most common sites for metastasis are the lymph nodes, lung, bones, liver and brain.

–The 5 year survival rate for metastatic renal cell carcinoma remains under 10 % and 20–25 % of these patients remain unresponsive to all treatments and the disease progress rapidly.

–Interleukin-2 is considered a standard treatment for those with advanced renal cell carcinoma.

–Other new treatments specifically designed for metastatic renal cell carcinoma include:

•Sunitinib

•Temsirolimus

•Bevacizumab

•Sorafenib

•Everolimus

•Pazopanib

•Axitinib

–These new treatments inhibit the growth of new blood vessels in the tumors, slow the growth and in some cases reduce the size of the tumors.

–Side effects are common with these treatments and include:

•Gastrointestinal side effects: Nausea, vomiting, diarrhea, anorexia

•Respiratory side effects: Coughing, difficulty in breathing

•Cardiovascular side effects: Hypertension

•Neurological side effects: Intracranial hemorrhage, thrombosis in the brain

•Skin and mucus membranes side effects: Rashes, hand-foot syndrome, stomatitis

•Bone marrow suppression

•Renal side effects: Impaired kidney function

•Fatigue

–Radiotherapy and chemotherapy are more commonly used to treat metastatic RCC.

–These are not curative but are useful to relief symptoms related to the metastasis.

4.6.8Prognosis

•The prognosis for renal cell carcinoma is largely influenced by a variety of factors, including:

–Tumor size

–Degree of invasion

–Metastasis

–Histologic type

–Nuclear grade

•The prognosis is influenced most by the stage at presentation, with an overall survival rate of approximately 64 %.

•Renal cell carcinoma does not generally respond to chemotherapy or radiation.

•For those that have tumor recurrence after surgery, the prognosis is generally poor.

4.7Angiomyolipoma of the Kidney

4.7.1Introduction

•Angiomyolipomas are the most common benign tumor of the kidney.

•They are classically composed of blood vessels, smooth muscle cells and fat cells.

•It has an incidence of about 0.3–3 %.

4.7 Angiomyolipoma of the Kidney	157

•About 80 % of cases are sporadic and these are most commonly found in middle-aged women (mean age of presentation 43 years).

•There is a strong female predilection (F: M of 4:1) in sporadic angiomyolipomas.

•The remaining 20 % are seen in association with tuberous sclerosis, although they have also been described in Von Hippel-Lindau syndrome (VHL) and neurofibromatosis type

1(NF1).

•In patients with tuberous sclerosis, 67–85 % will have renal angiomyolipoma by around

10years of age.

•In these cases they present earlier (usually identified by the age of 10 years), are larger, fat-poor and are far more numerous.

•Angiomyolipomas are strongly associated with tuberous sclerosis.

•Patients with tuberous sclerosis tend to have several angiomyolipomas affecting both kidneys.

•Angiomyolipomas are also commonly found in women with the rare lung disease lymphangioleiomyomatosis.

•They can spontaneously hemorrhage, which can be fatal.

•The classic microscopic features of angiomyolipoma is myoid cells with clear cytoplasm spinning off of large vessels in a background of mature fat.

•Angiomyolipomas are caused by mutations in either the TSC1 or TSC2 genes, which govern cell growth and proliferation.

•Angiomyolipomas are usually benign but they may grow in size to an extent that the kidney function is impaired or leads to hemorrhage.

4.7.2Histopathology

•Angiomyolipomas are members of the perivascular epithelioid cells tumour group (PEComas).

•They are composed of variable amounts of three components:

–Blood vessels (-angio)

–Plump spindle cells (-myo)

–Adipose tissue (-lipo)

•Almost all classic angiomyolipomas are benign.

•They have the risk of rupture with bleeding or secondary damage/destruction of surrounding structures as they grow.

•There is a special variant called an epithelioid angiomyolipoma.

–This is composed of more plump, epithelial looking cells, often with nuclear atypia.

–These have a risk of malignant behavior.

–They mimic renal cell carcinoma.

–Metastases from this type have also been described.

4.7.3Classification

•Angiomyolipomas are known as a PEComa, from the initials of perivascular epithelioid cell.

•They consist of perivascular epithelioid cells (cells which are found surrounding blood vessels and which resemble epithelial cells).

•In the past, these tumors were considered as hamartomas (benign tumors consisting of cells in their correct anatomical location but forming a disorganized mass).

•They were also considered as a choristoma (benign tumors consisting of normal cells but in the wrong location).

•Angiomyolipomas are considered as mesenchymal tumors 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-, myoand lip-. The -oma suffix indicates a tumor.

•Angiomyolipomas are typically found in the kidney but have also been found in the liver and less commonly the ovary, fallopian tube, spermatic cord, palate and colon.

•Angiomyolipomas occur in young women with lymphangiomyomatosis without other stigmata of tuberous sclerosis.

•Angiomyolipoma is also associated with neurofibromatosis and von Hippel–Lindau syndrome.

•In children, angiomyolipomas are rare in the absence of tuberous sclerosis.

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•Eighty percent of children with tuberous sclerosis may be expected to develop angiomyolipomas by the age of 10 years.

•There are two types of angiomyolipoma:

–Sporadic (isolated) angiomyolipoma

•This accounts for 80 % of the cases.

•Usually solitary.

•The mean age at presentation is 43 years.

•It is four times more common in women than in men.

•80 % of the cases involve the right kidney.

–Angiomyolipoma associated with tuberous sclerosis

•This accounts for 20 % of the cases.

•The lesions are typically larger than isolated angiomyolipomas.

•They are often bilateral and multiple

•They occur equally in males and females

•Angiomyolipomas occur in 80 % of patients with tuberous sclerosis.

4.7.4Clinical Features

•Angiomyolipomas are often found incidentally when the kidneys are imaged for other reasons, or as part of screening in patients with tuberous sclerosis.

•Symptomatic presentation is most frequently with spontaneous retroperitoneal hemorrhage.

•The risk of bleeding being proportional to the size of the lesion (>4 cm diameter).

•Shock due to severe hemorrhage from rupture is described as Wunderlich syndrome.

•An angiomyolipoma larger than 5 cm and those containing an aneurysm pose a significant risk of potentially life-threatening rupture.

•Sometimes, the renal angiomyolipomas affect both kidneys to the extent that the renal function is impaired leading to chronic renal disease and renal failure.

•The retroperitoneal hemorrhage causes sudden pain, accompanied with nausea and vomiting.

•Up to 20 % of those with who present with retroperitoneal hemorrhage will be in shock.

•Patients may also present with numerous other symptoms and signs including:

–A palpable mass

–Flank pain

–Urinary tract infections

–Hematuria

–Renal failure

–Hypertension

4.7.5Investigations

•CBC

•Electrolytes, BUN and creatinine

•PT and PTT

•Abdominal ultrasound:

–This reveals hyperechoic lesions located in the renal cortex and with posterior acoustic shadowing.

–In those with tuberous sclerosis, angiomyolipomas may be so numerous that the entire kidney is affected, appearing echogenic with loss of normal cortico-medullary differentiation.

•Abdominal CT-scan:

–This reveals lesions involving the renal cortex and demonstrate macroscopic fat (less than -20 HU).

–It is important to realize that a proportion of angiomyolipomas are fat-poor.

–This is seen in those with tuberous sclerosis.

–Calcification is rare in these tumors.

•Abdominal MRI:

–MRI is excellent to diagnose angiomyolipomas because of their high fat content.

–It can be difficult to distinguish a fat-poor angiomyolipoma from a renal cell carcinoma.

–The presence of fat is not pathognomonic of angiomyolipomas and it is important to note that rarely renal cell carcinomas may have macroscopic fat components.

–The absence of calcification on CT-scan or MRI favors the diagnosis of angiomyolipomas.

•Angiography:

–Angiomyolipomas are hypervascular lesions demonstrating often characteristic features: