Nephroblastoma, or renal embryonal tumor, is the most common malignant kidney tumor in children. It was first reported by Wilms, so it is also called Wilms tumor. In the past 20 years, due to the development of comprehensive treatment measures such as surgery, chemotherapy and radiotherapy, as well as the promotion and application of multicenter research results such as the American Nephroblastoma Study Group and the European International Society of Pediatric Oncology, the efficacy has been significantly improved, complications in low-risk patients have gradually decreased, and the long-term survival rate of high-risk patients has been further improved.
What are the causes of nephroblastoma?
The incidence of nephroblastoma in infants and children is approximately 1 to 2/1,000,000. the age at diagnosis is most often between l and 3 years, with 80% of cases seen before the age of 5 years, and the average age is 3 years. The tumor may originate from the posterior renal blastoderm and is an embryonal tumor that occurs in the residual immature kidney and may be combined with urogenital malformations. Tumorigenesis may involve several genes such as WT1 (Wilms, Tumor l, also known as Wilms tumor suppressor gene), WT2, and P53. Tumorigenesis may also be associated with congenital genetic factors, as seen in syndromes such as Denys-Drash, Beckwith-Wiedemann, and WAGR.
What is the staging of nephroblastoma?
Nephroblastoma can occur anywhere in the kidney and often appears as a round, ovoid or large nodular solid mass with a perithelium composed of fibrous tissue and compressed renal tissue. The tumor often destroys and compresses the renal tissues causing deformation of the renal pelvis and calyces. The tumor is grayish fish-like in cross-section and may be brown or yellow in color due to focal hemorrhage and infarction, interspersed with cystic cavity formation. The tumor is composed of germ, mesenchymal and epithelial components. The germ component is a nest-like distribution of medium-sized naive cells.
The mesenchymal tissue accounted for most of the tumor, and the mesenchymal tumor cells were spindle-shaped with slightly less cellular components than the germ type, within which more mature connective tissues such as transverse muscle, smooth muscle, fat and cartilage could be seen. The epithelial cells are similar to the germinal naive cells and arranged in a primitive renal tubular pattern. In late stage, the tumor may break through the renal peritoneum and invade nearby organs or tissues extensively. It may metastasize to the hilar or para-aortic lymph nodes via lymphatic tract, or form tumor emboli extending along the renal vein to the inferior vena cava or even the right atrium, or metastasize to other parts of the body via blood flow, with pulmonary metastasis being the most common.
The prognosis of nephroblastoma is related to the tissue structure that constitutes the tumor. According to its tissue structure, the tumor is classified as
1. Histological structures with good prognosis
(1) Typical nephroblastoma: with dense undifferentiated germinal base and varying degrees of epithelial variation in embryonic-like tubules separated by typical stroma into daisy doughnut-like and vasosphere-like structures. It consists of three components: germ, epithelial, and stromal cells.
(2) Multicystic nephroblastoma: It consists of diffuse multicompartmental cysts with poorly differentiated cells present only at the cystic interval, which can develop into typical nephroblastoma.
The above li type accounts for 89% and has good prognosis.
2.Histology with poor prognosis
Undifferentiated type: Mostly seen in older children, the tumor cells have large nuclei, chromatin, obvious heterogeneity, multipolar division, diffuse growth, and poor prognosis. Undifferentiated tumors are further divided into mesenchymal, rod cell and clear cell types. The rod cell and clear cell types are similar to sarcoma in their presentation. They are highly invasive and malignant and have the worst prognosis, with mortality rates of more than 50%.
What are the clinical manifestations of nephroblastoma?
1. Abdominal mass: Abdominal mass or abdominal enlargement is the most common manifestation. When the mass is small, it has no obvious symptoms and is easily ignored. The lump is located in the upper abdomen on the side of the ribs, with smooth surface, medium hardness and no pressure pain, and may have certain mobility in the early stage, and may cross the midline after rapid increase. When the tumor is huge, it may produce compression symptoms, shortness of breath, lack of appetite, emaciation, irritability and other manifestations.
2.Abdominal pain: About l/3 of children have abdominal pain, the degree of which ranges from local discomfort, mild pain to severe pain and colic, if accompanied by fever, anemia and hypertension, it often indicates subperitoneal hemorrhage of tumor. If accompanied with fever, anemia and hypertension, it often indicates subperitoneal hemorrhage.
Hematuria: About 25% of children have microscopic hematuria, 10% to l5 % have carnal hematuria. Hematuria is mostly induced by minor trauma to the enlarged kidney or related to the invasion of the renal pelvis by the tumor, and is not a late manifestation of the tumor.
4. Hypertension: About 30% of cases have increased blood pressure, which may be due to renin production by tumor cells or high renin and angiotensin caused by renal vascular embolism or renal artery compression and ischemia. After the tumor is removed, the blood pressure often returns to normal.
5. Complications: Acute renal failure, varicocele and hypoglycemia may be combined. Erythrocytosis is rare, and the reason may be related to the production of erythropoietin by the tumor. In combination with nephrotic syndrome, it is called Wilms’ nephritis.
6. Metastatic symptoms: Inferior vena cava obstruction can lead to hepatomegaly and ascites, such as invasion of the right atrium can lead to congestive heart failure. Hematogenous metastasis can spread to all parts of the body, and pulmonary metastasis is the most common, which can lead to cough, pleural effusion, chest pain, hypothermia, anemia and cachexia.
7. Systemic symptoms: fever, fatigue, irritability, lack of appetite and weight loss, etc.
Diagnosis
1. Clinical manifestations: familiar with the clinical features of the disease, “large mass in the abdomen of a weak infant” and “rotund belly” should be considered nephroblastoma.
2. Laboratory tests: routine blood and urine tests, urinary catecholamine metabolites, renal function tests. Bone marrow aspiration is feasible if it is not easy to distinguish from neuroblastoma.
3. Imaging tests: IVP, ultrasound, CT, MRI play an important role in the diagnosis of Wilms’ tumor.
Differential diagnosis
In addition to nephroblastoma, there are also hydronephrosis, teratoma and neuroblastoma. The key points of differentiation refer to Table 12-2. renal tumors are easily distinguished from non-renal tumors by ultrasound examination and IVP. Urine VMA (3-methoxy-4-hydroxy bitter amygdalic acid) test and bone marrow aspiration can help distinguish neuroblastoma; ultrasound and CT can help distinguish teratoma and malignant tumor.