WILMS TUMOR

Wilms tumor (nephroblastoma) contributes to ~5-6% of childhood malignancies, being one of the commonest solid tumor in under-five children.

Epidemiology: Wilms' tumor is typically a tumor of preschool children with ~75% cases diagnosed by 4 years.

Etiologically, while most cases are sporadic, 1-2% of Wilms tumors are familial, more common in younger age with bilateral disease. Genetic mutations have been identified in ~20% cases, specially involving WT1 gene on 11p13.

Wilms tumor is frequently associated with other congenital anomalies, e.g., aniridia, hemihypertrophy or genitourinary malformations; or specific syndromes, e.g., Beckwith-Wiedemann syndrome (with macrosomia), Denys- Drash syndrome (with genital abnormalities) and WAGR syndrome (Wilms tumor, Aniridia, Genital abnormalities, mental Retardation).

Pathology: Over 90% of Wilms tumors are unilateral, arising as a solitary mass from any part of kidney, leading to distortion of renal outline and compression of residual normal kidney as a thin rim. Wilms' tumor probably originates from incompletely differentiated renal mesenchyme. Histologically, two broad groups are recognized with prognostic significance:

a. Favorable triphasic histology with three cell types— epithelial, blastemal, and stromal elements (90%), and

b. Unfavorable histology with anaplasia, rhabdoid tumors and clear cell sarcoma (10%).

Tumor may spread locally as an invasive thrombus into renal vein and inferior vena cava (seen in 4-10% cases), or metastasize via lymphatics and blood. Lung is the commonest site of extrarenal metastasis.

Clinically, Wilms tumor presents with a triad of—(a) unilateral abdominal mass, (b) painless hematuria and/ or (c) hypertension.

Rare cases present with abdominal pain and vomiting (d/d surgical abdomen), paraneoplastic syndromes, e.g., polycythemia (due to excess erythropoietin secretion) or bleeding diathesis (acquired VonWillebrand like syndrome).

Diagnosis rests on USG, followed by CT-scan to confirm intrarenal origin (d/d neuroblastoma), to assess extent of spread and to evaluate functional status of other kidney. Bone scan, neuroimaging and chest X-ray/CT scan is required to detect metastasis.

Immediate total/radical nephrectomy is indicated in all unilateral tumors for staging (Table 20.12) and histological classification, along with CT chest and bone scan to exclude metastasis.

Management depends on staging and histological type (Table 20.13) of tumor and includes radical nephrectomy in all cases except bilateral tumors, followed by chemotherapy, with/without radiotherapy. Bilateral tumors should receive pre-operative chemotherapy before partial nephrectomy.

TABLE 20.12: National Wilms' tumor staging system

I. Tumor limited to kidney and completely excised

II. Tumor extends through the perineal capsule but is completely excised

III. Residual non-hematogenous tumor confined to the abdomen

IV. Hematogenous metastasis to lung, liver, bone, brain, bone, etc

V. Bilateral renal involvement at diagnosis

For chemotherapy, generally two drugs are used (vincristine + actinomycin), every 1-3 weeks in stage I/ II, while a third one-doxorubicin is added in advanced stages or unfavorable histology.

Wilms tumor is highly radiosensitive and postoperative radiotherapy is indicated in all cases except stage I and II disease, along with simultaneous irradiation of metastatic lesions in lungs in stage IV disease.

In very large tumors, which are either unresectable or too risky to resect, preoperative chemotherapy followed by delayed surgery is preferred.

Prognosis is generally excellent in appropriately treated cases with 4-year survival of gt;90%, except in bilateral tumors or unfavorable histology (Table 20.13). Younger age, lower stage and lower tumor weight suggest more favourable outcome, while those with genetic mutations have higher risk of recurrence.

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