Nephroblastoma

Nephroblastoma is a congenital embryonic malignant tumor of the kidney.

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Epidemiology

The incidence of nephroblastoma is relatively high compared to other malignant solid tumors of childhood - 7-8 cases per 1 million children under 14 years of age per year. The risk of developing nephroblastoma is 1 in 8,000-10,000 children. The tumor is detected mainly at the age of 1-6 years. Patients over 6 years of age make up about 15%.

In 5-10% of cases, bilateral nephroblastomas are diagnosed. The damage to the second kidney is not the result of metastasis, but a manifestation of a primary multiple tumor. Bilateral nephroblastomas manifest earlier than unilateral ones: the average age of diagnosis is 15 months and 3 years, respectively.

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Causes nephroblastomas

Nephroblastoma occurs during embryogenesis as a result of disturbances in the formation and differentiation of renal tissue. Up to a third of patients with nephroblastoma also have developmental defects associated with other embryogenesis disorders, and nephroblastoma can be a component of some hereditary syndromes. The occurrence of nephroblastoma and developmental defects is associated with the action of one factor during embryogenesis, to which fetal tissues react with various disorders.

Nephroblastoma and hereditary syndromes

Congenital malformations are registered in 12-15% of cases of nephroblastoma. The most frequently detected anomalies are aniridia, hemihypertrophy, Beckwith-Wiedemann syndrome, malformations of the genitourinary system (WAGR syndrome, Denys-Drash syndrome), malformations of the musculoskeletal system, hamartomas (hemangiomas, multiple nevi, "coffee stains" on the skin), etc.

Congenital aniridia is registered in 1 out of 70 patients with nephroblastoma. At the same time, one third of children with spontaneous aniridia subsequently develop nephroblastoma. In nephroblastoma, cataracts, congenital glaucoma, microcephaly, delayed psychomotor development, craniofacial dysmorphism, anomalies of the auricles, growth retardation, cryptorchidism, hypospadias, horseshoe kidney can also be detected. Chromosomal abnormalities in such cases are manifested by a deletion in the short arm of chromosome 11 (Pr13) - the WT-1 gene.

Congenital hemihypertrophy is most often associated with nephroblastoma, but can also be associated with adrenal cortex tumors, liver tumors, hamartomas, neurofibromatosis, and Russell Silver syndrome (dwarfism).

Beckwith-Wiedemann syndrome is characterized by fetal hyperplastic visceromegaly of the kidneys, adrenal cortex, pancreas, gonads and liver, macroglossia, malformations of the anterior abdominal wall (omphalocele, umbilical hernia, diastasis recti), hemihypertrophy, microcephaly, delayed psychomotor development, hypoglycemia, postnatal somatic gigantism, malformations of the auricle. This syndrome is combined not only with nephroblastoma, but also with other embryonic tumors: neuroblastoma, rhabdomyosarcoma, hepatoblastoma, teratoblastoma. In 20% of individuals with Beckwith-Wiedemann syndrome, bilateral nephroblastoma with synchronous or metachronous tumor growth develops. The gene locus responsible for Beckwith-Wiedemann syndrome is located on chromosome 11p5 (WT-2 gene).

Children predisposed to nephroblastoma (congenital aniridia, congenital hemihypertrophy, Beckwtth-Wiedetnann syndrome) should undergo screening ultrasound every 3 months until they reach 6 years of age.

Developmental anomalies of the genitourinary system (horseshoe kidney, renal dysplasia, hypospadias, cryptorchidism, duplication of the renal collecting system, cystic kidney disease) are also associated with a mutation in chromosome 11 and can be combined with nephroblastoma.

WAGR syndrome (nephroblastoma, aniridia, genitourinary malformations, psychomotor retardation) is associated with a deletion of chromosome 11p13 (WT-1 gene). The peculiarity of WAGR syndrome is the development of renal failure.

Denys-Drash syndrome (nephroblastoma, glomerulopathy, genitourinary malformations) is also associated with a point mutation in the 11p13 locus (WT-1 gene).

Developmental defects of the musculoskeletal system (clubfoot, congenital hip dislocation, congenital rib pathology, etc.) are detected in 3% of patients with nephroblastoma.

Ferlmann, Sotos, Stimpson-Golaby-Behemel syndromes - the so-called syndromes of excessive growth, are manifested by accelerated prenatal and postnatal development in the form of macroglossia, nephromegaly, macrosomia. With these syndromes, both nephroblastoma and nephroblastomatosis - the persistence of embryonic renal tissue (blastema), often having a bilateral character, can develop. The frequency of nephroblastoma is approximately 20-30 times higher than the frequency of nephroblastoma. Nephroblastomatosis can potentially develop into nephroblastoma, dynamic ultrasound screening is necessary.

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Symptoms nephroblastomas

Nephroblastoma can be latent for a long time. No developmental abnormalities are detected in the child for months or years - during this period, the tumor grows slowly. Then the tumor progression rate increases - from this moment, the rapid growth of nephroblastoma begins. In this case, the leading symptom is the presence of a palpable formation in the abdominal cavity.

As a rule, the child's subjective well-being remains satisfactory. Since nephroblastoma does not cause discomfort until it reaches a certain size, the child may not pay attention to the tumor or hide it from parents. Usually, parents themselves, as a rule, when bathing and changing clothes, discover abdominal asymmetry and a palpable tumor in the child. However, even a large tumor, as long as it does not cause asymmetry and abdominal enlargement, may remain unnoticed.

Severe intoxication is usually observed only in advanced cases. No more than 25% of patients experience symptoms such as macrohematuria caused by subcapsular rupture of nephroblastoma and arterial hypertension associated with hyperreninemia.

Nephroblastoma is characterized by hematogenous and lymphogenous metastasis. Lymphogenous metastasis is early. The lymph nodes in the renal hilus, paraaortic nodes and lymph nodes of the liver hilus are affected. With nephroblastoma, a tumor thrombus can be found in the inferior vena cava.

Forms

Histological structure and histological classification

Nephroblastoma originates from primitive metanephric blastema and is characterized by histological heterogeneity. About 80% of all cases of nephroblastoma are the so-called classic or three-phase variant of the tumor, consisting of three types of cells: epithelial, blastemal and stromal. There are also predominantly epithelial, predominantly blastemal and predominantly stromal types of this tumor, with the content of one of the components being at least 65%. Some tumors can be biphasic and even monophasic.

Histological staging according to Smldr/Harms provides for the identification of three degrees of malignancy of kidney tumors in children, associated with the prognosis of the disease (Table 66-1).

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Clinical staging

Currently, the SIOP (Europe) and NWTS (North America) groups use a single staging system for nephroblastoma.

• Stage I - the tumor is localized within the kidney, complete removal is possible.
• Stage II - the tumor spreads beyond the kidney, complete removal is possible;
  • germination of the renal capsule with spread into the perirenal tissue and/or renal hilum:
  • damage to regional lymph nodes (stage IIN+);
  • extrarenal vascular lesions;
  • ureteral lesion.
• Stage III - the tumor spreads beyond the kidney, possibly incomplete
  • removal:
  • in case of incisional or aspiration biopsy;
  • pre- or intraoperative rupture;
  • peritoneal metastases:
  • damage to the intra-abdominal lymph nodes, with the exception of regional ones (stage III N+):
  • tumor effusion into the abdominal cavity;
  • non-radical removal.
• Stage IV - presence of distant metastases.
• Stage V - bilateral nephroblastoma.

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Diagnostics nephroblastomas

Palpation of the abdomen in case of a tumor-like formation detected in it should be carried out carefully, since excessive trauma may result in a rupture of the tumor pseudocapsule with the development of intra-abdominal bleeding and total seeding of the abdominal cavity with tumor cells. For the same reason, a child with nephroblastoma needs to follow a protective regimen (rest, prevention of falls and bruises).

The most common mask of nephroblastoma is rickets. Common symptoms of rickets and nephroblastoma are abdominal enlargement and expansion of the lower thoracic aperture. Symptoms of tumor intoxication (paleness, moodiness, poor appetite, weight loss) can also be mistaken for signs of rickets.

As with all other malignant tumors, nephroblastoma diagnostics is based on the morphological conclusion. However, in relation to nephroblastoma, an exception to the rule of conducting a biopsy before the start of chemoradiation therapy is allowed. During the biopsy, the integrity of the pseudocapsule is violated, and the tumor detritus enclosed in the pseudocapsule, which has a mushy character, is scattered throughout the abdominal cavity, which increases the prevalence of the tumor, changes the clinical stage of the disease (automatically transfers to stage III) and worsens the prognosis of the disease. Therefore, in patients under 16 years of age, the diagnosis of nephroblastoma is established during a conservative examination, excluding aspiration and incisional biopsy. This is facilitated by the presence of clear diagnostic signs of nephroblastoma, reducing diagnostic errors to an insignificant minimum.

At the same time, American NWTS protocols suggest initial removal of the kidney with the tumor or its biopsy, even if the tumor resectability is questionable. In accordance with the NWTS strategy, this approach allows avoiding the error of conservative diagnostics and conducting a thorough revision of the abdominal organs, excluding or detecting lymph nodes affected by metastases and a tumor in the opposite kidney (according to NWTS, in 30% of cases of bilateral nephroblastoma, the tumor in the second kidney cannot be visualized by conservative diagnostic methods).

Diagnosis of the primary tumor focus is based on the search for typical signs of nephroblastoma and exclusion of other diseases. The range of differential diagnoses includes kidney malformations, hydronephrosis, neurogenic tumors and other tumors of the retroperitoneal space, liver tumors.

Laboratory and instrumental studies

Ultrasound of the abdominal cavity. Ultrasound reveals a heterogeneous formation coming from the kidney, closely associated with the remains of the destroyed kidney. A tumor thrombus in the inferior vena cava may be visualized. In tumors originating from other organs, the kidney will be displaced and deformed. In hydronephrosis, ultrasound reveals expansion of the renal collecting system and thinning of its parenchyma.

Excretory urography reveals on the survey image a shadow of a tumor formation displacing the intestinal loops. Subsequent images reveal either a “silent” kidney or deformation, displacement of the renal pelvis and calyceal system and delayed evacuation of the contrast agent. In the case of a tumor originating not from the kidney, excretory urography reveals a “silent” kidney

They are not detected, the delay of the contrast agent is not typical, but the mixing of the renal pelvis and ureter is typical. In hydronephrosis, the renal pelvis and ureter system are dilated and the calyces are deformed in a coin-shaped manner, often combined with megaureter and vesicoureteral reflux.

Computerized tomography or magnetic resonance imaging reveals the presence of a tumor originating from the kidney and provides additional information about the spread and relationship of the tumor to surrounding organs.

Angiography is performed when there are doubts about the diagnosis. Angiograms reveal a pathological network of vessels, identify the source of blood supply - the renal artery (with the main type of blood supply).

Angiographically and with color duplex Doppler angioscanning, it is possible to visualize a tumor thrombus in the inferior vena cava.

Radioisotope examination of the kidneys - renoscintigraphy - allows one to evaluate both the overall function of the kidneys and the functions of each of them separately.

Of particular importance is the differential diagnosis between nephroblastoma and neuroblastoma, since the clinical and diagnostic picture of these tumors can be very similar in some cases. Therefore, in all patients, during the primary diagnosis, a myelogram is examined to exclude metastases of neuroblastoma to the bone marrow, and the excretion of catecholamines in the urine is also examined.

Diagnosis of possible metastases includes chest X-ray (if necessary - X-ray computed tomography (CT)], ultrasound of the abdominal cavity and retroperitoneal space also serves to assess possible metastases in regional lymph nodes, liver, other organs and tissues, as well as to diagnose effusion in the abdominal cavity.

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Mandatory and additional studies in patients with suspected nephroblastoma

Mandatory research

• Full fiscal audit with local status assessment
• Clinical blood test
• Clinical urine analysis
• Biochemical blood test (electrolytes, total protein, liver function tests, creatinine, urea, lactate dehydrogenase, alkaline phosphate, phosphorus-calcium metabolism) Coagulogram
• UEI of abdominal organs and retroperitoneal space
• CT (MRI) of the abdominal organs and retroperitoneal space with intravenous contrast
• X-ray of the chest organs in five projections (straight, two lateral, two oblique)
• Bone marrow puncture from two points
• Renal scintigraphy urine catecholamine study ECG
• EchoCG

Additional diagnostic tests

• If metastases to the lungs and prolapse of the tumor through the diaphragm are suspected - CT of the chest organs
• In case of suspected metastases to the brain, as well as in case of clear cell sarcoma and rhabdoid tumor of the kidney - EchoEG and CT of the brain
• Ultrasound color duplex venoscanning of the abdominal cavity and retroperitoneal space
• Angiography
• In case of difficulty in differential diagnosis with neurogenic tumors - MIBG scintigraphy.
• In case of clear cell sarcoma of the kidney – skeletal scingiography

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Treatment nephroblastomas

Nephroblastoma was the first solid malignant tumor in children, the treatment of which in pediatric oncology yielded encouraging results. Currently, complex treatment of nephroblastoma is used. The treatment plan includes chemotherapy, radical surgery in the amount of tumor nephroureterectomy and radiation therapy.

The tumor is removed through a midline laparotomy approach. Choosing any other approach is a gross mistake, since only a midline laparotomy provides sufficient opportunities for revision of the abdominal cavity, tumor nephroureterectomy, and removal of lymph nodes affected by metastases. In case of a large tumor growing into adjacent organs (diaphragm, liver), a thoracophrenicolaparotomy is necessary. The tumor is removed as a single block. Particular attention should be paid to preventing intraoperative tumor rupture and timely ligation of the renal vessels. Ligation (suturing) and intersection of the ureter should be performed after its mobilization as distally as possible. It is necessary to revise the contralateral kidney in order to exclude its tumor lesion. If there are signs of enlarged lymph nodes in the retroperitoneal space, paraaortic, mesenteric, in the porta hepatis, iliac nodes, they should be biopsied.

Modern approaches to program treatment of nephroblastoma in Europe and North America are similar in terms of tumor nephroureterectomy and adjuvant chemotherapy and radiation therapy. The differences between them are in the implementation of preoperative (neoadjuvant) chemotherapy (the basic combination of cytostatic drugs is a combination of vincristine and dactinomycin. Preoperative chemotherapy is performed in patients over 6 months of age).

In the United States and Canada, treatment of nephroblastoma traditionally begins with surgery, without preoperative chemotherapy. The exceptions are unresectable tumors and tumor thrombi in the inferior vena cava. In these cases, incisional or aspiration transcutaneous biopsy is performed.

Treatment of stage V nephroblastoma

Traditionally, in case of bilateral nephroblastoma, the indication for surgery is considered to be the possibility of resection of the least affected kidney. Surgical treatment is performed in two stages. Initially, resection is performed within the healthy tissues of the least affected kidney with the tumor, and after a few weeks, the second, most affected kidney is removed. A necessary condition for performing the 2nd stage of surgical treatment is confirmation of sufficient functions of the least affected kidney after resection.

Treatment of nephroblastoma with distant metastases

Most often, metastases are detected in the lungs. If they are resectable, after chemoradiation therapy, sterno- or thoracotomy is performed with removal of pulmonary metastases. In this case, in the case of radiological and CT signs of complete regression of pulmonary metastases, an operation with lung biopsy in suspicious places is performed.

Forecast

The prognosis for nephroblastoma depends on the histological variant (there are favorable and unfavorable morphological forms), age (the younger the child, the better the prognosis) and stage of the disease. With favorable histological variants, up to 95% of patients survive at stage I, up to 90% at stage II, up to 60% at stage III, and up to 20% at stage IV. The prognosis for unfavorable histological variants is significantly worse. The prognosis for stage V depends on the possibility of resection of one of the affected kidneys.

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