Fibroblastoma

Nephroblastoma is a congenital embryonic malignant tumor of the kidney.

[1], [2], [3], [4], [5], [6], [7], [8]

Epidemiology

Incidence of nephroblastoma. Compared with other malignant solid tumors of childhood, relatively high - 7-8 cases per 1 million children under the age of 14 years per year. The risk of contracting nephroblastoma has 1 in 8000-10 000 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 nephroblastoma is diagnosed. The defeat of the second kidney is not the result of metastasis, but the manifestation of a primary-multiple tumor. Bilateral nephroblastomas manifest earlier than one-sided: the average age of diagnosis is 15 months and 3 years, respectively.

[9], [10], [11], [12], [13]

Causes of the nephroblastoma

Nephroblastoma occurs during embryogenesis as a result of violations of the bookmark and differentiation of the renal tissue. Up to a third of patients with nephroblastoma also have developmental defects associated with other disorders of embryogenesis, while nephroblastoma can act as an integral part of some hereditary syndromes. The emergence of nephroblastoma and developmental defects is associated with the effect during embryogenesis of one factor on which the fetal tissues react with various disorders.

Nephroblastoma and hereditary syndromes

Congenital malformations are recorded in 12-15% of cases of nephroblastoma. The most common findings are anomalies such as aniridia, hemigipertrophy, Beckwith-Wiedemann syndrome, malformations of the genitourinary system (WAGR syndrome, Denys-Drash syndrome), malformations of the musculoskeletal system, hamartomas (hemangiomas, multiple nevuses, "coffee stains" skin), etc.

Congenital aniridia is recorded in 1 of 70 patients with nephroblastoma. In this case, a third of children with spontaneous aniridia subsequently develops a nephroblastoma. With nephroblastoma, cataracts, congenital glaucoma, microcephaly, delayed psychomotor development, craniofacial dysmorphism can also be detected. Anomalies of the auricles, growth retardation, cryptorchid, hypospadias, horseshoe kidney. Chromosomal abnormalities in such cases are manifested by deletion in the short arm of chromosome 11 (Pr13) - WT-1 gene.

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

Beckwith-Wiedemann syndrome is manifested by fetal hyperplastic visceralogalia of the kidneys, adrenal cortex, pancreas, gonads and liver, macroglossia, developmental defects of the anterior abdominal wall (omphaloceles, umbilical hernia, diastasis of the rectus abdominis muscles), hemygypertrophy, microcephaly, psychomotor development delay,  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. 20% of individuals with Beckwith-Wiedemann syndrome develop a bilateral nephroblastoma with synchronous or metachronous growth of the tumor. The locus of the gene responsible for Beckwith-Wiedemann syndrome is located on chromosome 11p5 (WT-2 gene).

Children who are predisposed to nephroblastoma (congenital aniridia, congenital hemihypertrophy, Beckwtth-Wiedetnann syndrome) should be screened every 3 months until they reach the age of six.

Anomalies in the development of the genitourinary system (horseshoe kidney, kidney dysplasia, hypospadias, cryptorchidism, doubling 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, malformations of the genitourinary system, delayed psychomotor development) is associated with the deletion of the chromosome 11p13 (WT-1 gene). A feature of the WAGR syndrome is the development of renal failure.

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

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

Syndromes Ferlmann, Sotos, Stmpson-Golaby-Behemel - the so-called syndromes of excessive growth, manifest accelerated prenatal and postnatal development in the form of macroglossia, nephromegalia, macrosomia. With these syndromes, both nephroblastoma and nephroblastomatosis can develop - the persistence of embryonic renal tissue (blastema), which is more often bilateral. The frequency of nephroblastomatosis is approximately 20-30 times higher than the incidence of nephroblastoma. Nephroblasmosis can potentially develop into a nephroblastoma, a dynamic ultrasound screening is necessary.

[14], [15], [16]

Symptoms of the nephroblastoma

Nephroblastoma can be hidden for a long time. For months or years, there are no abnormalities in the development of the child - during this period, the tumor grows slowly. Then the rate of tumor progression increases - from this moment the rapid growth of nephroblastoma begins. The leading symptom is the presence of a palpable formation in the abdominal cavity.

As a rule, the subjective well-being of the child remains satisfactory. Since before reaching a certain size nefroblastoma does not cause discomfort, the child may not pay attention to the tumor or hide it from the parents. Usually parents themselves, as a rule, during bathing and changing clothes, discover the asymmetry of the abdomen and the palpable tumor in the child. However, even a large tumor, until it causes asymmetry and an increase in the abdomen, can go unnoticed.

The marked intoxication is noted, as a rule, only in neglected cases. Not more than 25% of patients observe such symptoms as macrogematuria caused by the subcapsular rupture of the nephroblastoma, and hypertension associated with hypereneniaemia.

Nephroblastoma is characterized by hematogenous and lymphatic metastasis. While lymphogenous metastasis is early. Lymph nodes are damaged in the gates of the kidneys, para-aortic nodes and lymph nodes of the liver gates. With nephroblastoma, you can see a tumor thrombus in the inferior vena cava.

Forms

Histological structure and histological classification

Nephroblastoma originates from a primitive metanephalic blastema and is characterized by histological heterogeneity. About 80% of all cases of nephroblastoma constitute the so-called classical, or three-phase variant of the tumor, consisting of cells of three types: epithelial, blastema and stromal. Also, the epithelial type is predominantly predominant, predominantly the blastema and predominantly stroma-containing type of this tumor, while the content of one of the components should be at least 65%. Some tumors can be biphasic and even monophasic.

Histological staging for Smldr / Harms involves the allocation of three degrees of malignancy of kidney tumors in children associated with the prognosis of the disease (Table 66-1).

[17], [18], [19], [20]

Clinical staging

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

• I stage - the tumor is localized within the kidney, possibly complete removal.
• II stage - the tumor spreads beyond the kidneys, possibly complete removal;
  • germination of the capsule of the kidney with spreading to the pericardial cellulose and / or the kidneys:
  • defeat of regional lymph nodes (stage IIN +);
  • defeat of the adrenal vessels;
  • ureteral involvement.
• III stage - the tumor spreads beyond the kidney, possibly incomplete
  • delete:
  • in case of incisional or aspiration biopsy;
  • pre- or intraoperative rupture;
  • metastases per peritoneum:
  • lesion of intra-abdominal lymph nodes, with the exception of regional (stage III N +):
  • tumor effusion into the abdominal cavity;
  • non-radical removal.
• Stage IV - the presence of distant metastases.
• V stage - bilateral nephroblastoma.

[21]

Diagnostics of the nephroblastoma

Palpation of the abdomen in case of a tumor-like formation revealed in it should be carried out cautiously, because as a result of excessive traumatization, the tumor pseudocapsule may break with the development of intra-abdominal bleeding and total seeding of the abdominal cavity by tumor cells. For the same reason, a child with a nephroblastome needs to observe a protective regime (rest, prevention of falls and bruises).

The most common mask nefroblasgomy - rickets. Common symptoms of rickets and nephroblastoma are an increase in the abdomen and the unfolding of the lower aperture of the thorax. Symptoms of tumor intoxication (pallor, capriciousness, poor appetite, weight loss) can also be mistaken for signs of rickets.

As with all other malignant tumors, the diagnosis of nephroblastoma is based on morphological findings. However, with regard to nephroblastoma, an exception can be made to the rule of biopsy before the initiation of chemoradiotherapy. During the biopsy, the integrity of the pseudocapsule appears, and the tumor detritus encapsulated in the pseudocapsule is porous, dispersing over 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 up to the age of 16, the diagnosis of nephroblastoma is established with a conservative examination that excludes 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, the American protocols of NWTS suggest an initial removal of the kidney from the tumor or a biopsy, even with a questionable resectability of the tumor. In accordance with the NWTS strategy, this approach avoids the error of conservative diagnosis and conducts a thorough revision of the abdominal organs, eliminating or detecting metastatic lesions and a tumor of the opposite kidney (according to NWTS, in 30% of cases of bilateral nephroblastoma, the tumor of the second kidney can not be visualized by methods conservative diagnosis).

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

Laboratory and instrumental research

Ultrasound of the abdominal cavity. When ultrasound is detected, the non-uniform formation originating from the kidney is closely related to the remains of the destroyed kidney. A tumor thrombus in the inferior vena cava can be visualized. With tumors originating from other organs, the kidney will be mixed, deformed. When hydronephrosis with ultrasound revealed expansion of the collection system of the kidney, thinning of its parenchyma.

Excretory urography reveals in the survey a shadow of tumor formation, pushing the bowel loops. In the subsequent pictures, either a "mute" kidney or a deformity, a displacement of the calyxal and pelvic system of the kidney and a delay in the evacuation of the contrast medium are detected. In the case of a tumor that does not emerge from the kidney, excretory urography has a "mute" kidney

Do not detect, the contrast of contrast medium is not typical, but typically the mixing of the calyxal and pelvic system of the kidney and ureter. With hydronephrosis, the expansion of the cup-and-pelvis system and the "coin-like" deformation of the cups are often noted, often combined with a megaureter and vesicoureteral reflux.

Computer or magnetic resonance imaging reveals the presence of tumor formation originating from the kidney, and provides additional information about the prevalence and association of the tumor with surrounding organs.

Angiography is performed in case of doubt in the diagnosis. Angiograms reveal a pathological network of blood vessels, reveal the source of blood supply - the renal artery (with the main type of blood supply).

Angiographically and with color duplex Doppler angioscanning, a tumor thrombus can be visualized in the inferior vena cava.

Radioisotope study of kidneys - renoscintigraphy - allows to evaluate both the total kidney function, and separately the functions of each of them.

Especially important is the differential diagnosis between nephroblastoma and neuroblastoma. Since the clinical and diagnostic picture for these tumors may be very similar in some cases. Therefore, in all patients with primary diagnosis, a myelogram is examined in order to exclude metastases of neuroblastoma into the bone marrow, and also examine the excretion of catecholamines in the urine.

Diagnosis of possible metastases includes chest X-ray (if necessary - X-ray computed tomography (RT)), 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 diagnosis of effusion into the abdominal cavity .

[22], [23], [24]

Mandatory and additional studies in patients with suspected nephroblastoma

Mandatory studies

• Full fiscal survey with assessment of local status
• Clinical blood test
• Clinical analysis of urine
• Biochemical blood test (electrolytes, total protein, liver tests, creatinine, urea, latdehydrogenase, alkaline phosphates, phosphoric-calcium metabolism) Coagulogram
• UEI of the abdominal cavity and retroperitoneal space
• RCC (MRI) of the abdominal cavity and retroperitoneal space with intravenous contrast
• Radiography of the chest cavity in five projections (straight, two side, two oblique)
• Bone puncture from two points
• Renoscintigraphy examination of urine ECG catecholamines
• Echocardiography

Additional diagnostic tests

• If there is a suspected metastasis in the lungs and prolapse of the tumor through the diaphragm - PKT of the thoracic cavity
• If there is a suspicion of metastases in the brain, as well as in the case of a light-cell sarcoma and a rhabdoid tumor of the kidney - EchoEG and PKT of the brain
• Ultrasound colors duplex venous scans of the abdominal cavity and retroperitoneal space
• Angiography
• With the difficulty of differential diagnosis with neurogenic tumors - MIBG-scintigraphy.
• With a clear cell sarcoma of the kidney - sclerografy of the skeleton

[25], [26]

Treatment of the nephroblastoma

Nephroblastoma was the first solid malignant tumor in children, whose treatment in pediatric oncology received encouraging results. At present, complex treatment of nephroblastoma is being used. The treatment plan includes chemotherapy, a radical operation in the volume of tumor nephroureterectomy and radiation therapy.

The tumor is removed from the medial laparotomy access. The choice of any other access is a gross mistake, since only the mid-laparotomy provides sufficient opportunities for revision of the abdominal cavity, tumor-neuroneuretectomy and removal of lymph nodes affected by metastases. When a tumor of large size, sprouting into neighboring organs (diaphragm, liver), requires thoracophrenicoparotomy. The tumor is removed with a single block. We must pay special attention to the prevention of intraoperative rupture of the tumor, the early ligation of the kidney vessels. Bandaging (sewing) and crossing the ureter should be performed after it is mobilized as distally as possible. It is necessary to audit the contralateral kidney in order to exclude its tumor lesion. If signs of enlarged lymph nodes in the retroperitoneal space, para-aortic, mesenteric, in the portal of the liver, iliac nodes, they should be biopsy.

Modern approaches to the program treatment of nephroblastoma in Europe and North America are similar in the part of conducting tumor neuronephrectectomy and adjuvant chemotherapy and radiation therapy. Differences between them consist in carrying out preoperative (neoadjuvant) chemotherapy (the basic combination of cytotoxic drugs is a combination of vincristia and dactinomycin.) Preoperative chemotherapy is administered to patients older than 6 months.

In the USA and Canada, treatment of nephroblastoma is traditionally initiated with surgery, without preoperative chemotherapy. An exception is an unresectable tumor and a tumor thrombus in the inferior vena cava. In these cases, incision or aspiration transcutaneous biopsy is performed.

Treatment of stage V nephroblastoma

Traditionally, with bilateral nephroblastoma, the indication for surgery is 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. The necessary condition for performing the second stage of surgical treatment is the confirmation of sufficient functions of the least affected kidney after resection.

Treatment of nephroblastoma with distant metastases

The most common are metastases in the lungs. With their resectability after chemoradiotherapy, sterno- or thoracotomy is performed with the removal of pulmonary metastases. In the case of radiological and RCT signs of complete regression of pulmonary metastases, an operation is performed with a lung biopsy in suspicious locations.

Forecast

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

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