Retinoblastoma and Wilms Tumor

Clinical Features and Prognosis of Retinoblastoma

Retinoblastoma typically spreads via two main pathways: lymphatic and hematogenous. Through lymphatic routes, tumor cells migrate to the cervical, submandibular, and parotid lymph nodes. The hematogenous route leads to secondary lesions in the liver, cranial bones, and long tubular bones. Distant metastases are the most common cause of patient mortality.

An interesting feature of the disease is the tumor's ability to undergo spontaneous regression. This process is accompanied by marked inflammation and calcium deposition (calcification).

Prognosis directly depends on early detection:

• Early diagnosis allows for successful eye-sparing interventions that preserve vision.
• Extension of tumor masses beyond the eyeball drastically reduces the chances of a favorable outcome.
• Orbital osteosarcoma has been described as a severe late complication following radiotherapy.

Wilms Tumor (Nephroblastoma): General Characteristics

Nephroblastoma, first described by surgeon M. Wilms in the late 19th century, is the most frequent primary malignant renal tumor in pediatric practice. It accounts for about 6–7% of all childhood cancers. The peak incidence occurs between the ages of two and three years, while it is extremely rare in infants under six months and children over five years old.

The condition can be sporadic or familial, and may present as part of complex congenital syndromes. In most patients, the karyotype remains normal, but suppressor gene mutations play a key role in pathogenesis:

• The WT1 gene: Located at locus 11p13. It encodes a transcription-regulating protein expressed in developing kidneys and gonads. Loss of both copies of this gene leads to renal agenesis.
• The WT2 gene: Mutations are identified distal to the WT1 locus on the short arm of chromosome 11.
• A subset of patients exhibits loss of heterozygosity on the long arm of chromosome 16.

Syndromes Associated with Nephroblastoma

The development of Wilms tumor is closely linked to several severe genetic disorders that significantly increase the risk of oncogenesis.

1. WAGR syndrome. Named after its primary features: Wilms tumor, aniridia (absence of the iris), genital anomalies, and intellectual disability. The risk of tumor development reaches 33%. The genetic basis is a sporadic deletion at 11p13 involving the autosomal dominant gene and the adjacent WT1 gene.
2. Denys–Drash syndrome. Manifests as male pseudohermaphroditism (gonadal dysgenesis) and severe nephropathy progressing to renal failure. Tumors develop in the vast majority of these patients. Unlike WAGR, this involves a dominant-negative mutation at the 11p13 locus.
3. Beckwith–Wiedemann syndrome. Characterized by visceromegaly, hemihypertrophy, cyst formation, and adrenocortical cytomegaly. In addition to nephroblastoma, there is an increased risk of hepatoblastoma and rhabdomyosarcoma. Pathogenesis involves alterations at locus 11p15.5 (the WT2 gene) and genomic imprinting phenomena (loss of maternal alleles with paternal uniparental disomy).

Stages and Morphology of Wilms Tumor

Clinically and morphologically, nephroblastoma is classified into five stages:

• Stage I: The tumor is limited to the kidney within an intact capsule and is completely excised.
• Stage II: Tumor extends beyond the organ, but complete surgical resection is achieved with negative margins.
• Stage III: Residual tumor remains in the abdomen, peritoneal implant metastases, regional lymph node involvement, or positive surgical margins.
• Stage IV: Hematogenous dissemination or extra-abdominal lymph node involvement.
• Stage V: Bilateral renal involvement.

Survival exceeds 90% for stages I and II, dropping to 60% for stage IV. For stage V, the prognosis remains relatively favorable with modern therapy.

Macroscopic Appearance Appears as a large, solitary, soft, grayish-pink nodule on cross-section. The tissue is sharply demarcated from the healthy parenchyma. Secondary changes such as hemorrhage, cysts, and necrosis are common. Multicenter and bilateral forms occur in 10% of cases.

Microscopic Appearance Nephroblastoma arises from nephrogenic derivatives of varying degrees of maturity. It features a characteristic triphasic structure, including:

• Blastemal component (small round cells with large hyperchromatic nuclei and scant cytoplasm);
• Epithelial component (various tubules mimicking embryonic tubules);
• Stromal component.