Retinoblastoma

Features and prognosis of retinoblastoma

Retinoblastoma is characterized by the spread of tumor cells via two main pathways: lymphogenic and hematogenous. Through lymphatic pathways, cells migrate to the cervical, submandibular, and parotid lymph nodes. The hematogenous pathway leads to secondary lesions in the liver, cranial bones, and tubular bones of the limbs. It is distant metastases that most frequently cause 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 salt deposition (calcification).

The prognosis depends directly on the timely detection of the pathology:

• Early diagnosis enables successful organ-preserving interventions, which helps preserve vision.
• Extension of tumor masses beyond the eyeball sharply reduces the chances of a favorable outcome.
• As a severe complication following a course of radiotherapy, cases of orbital osteosarcoma have been described.

Wilms tumor (nephroblastoma): general characteristics

Nephroblastoma, first described by the surgeon M. Wilms in the late 19th century, is the most common primary malignant renal tumor in pediatric practice. It accounts for about 6–7% of all pediatric oncology. The peak incidence is observed between the ages of two and three years, while in infants under six months and children older than five years it is diagnosed extremely rarely.

The pathology can be sporadic or familial, and may also be part of complex congenital syndromes. In the majority of patients, the karyotype remains within normal limits, but suppressor gene mutations play a key role in pathogenesis:

• Gene WT-1: located in locus 11p13. Encodes a transcription-regulating protein expressed in developing kidneys and gonads. Loss of both copies of this gene leads to renal agenesis.
• Gene WT-2: mutations are detected distally to the WT-1 locus on the short arm of chromosome 11.
• In a subset of patients, loss of heterozygosity on the long arm of chromosome 16 is detected.

Syndromes associated with nephroblastoma

The development of Wilms tumor is closely associated with a number of severe genetic abnormalities in which the risk of oncogenesis increases manifold.

1. WAGR syndrome. The name is formed from the initial letters of its main manifestations: Wilms tumor, aniridia (absence of the iris), genital anomalies, and mental retardation. The risk of tumor development reaches 33%. The genetic basis is a sporadic deletion in the 11p13 region, involving the autosomal dominant gene and the adjacent WT-1 gene.
2. Denys–Drash syndrome. Manifests as male pseudohermaphroditism (gonadal dysgenesis) and severe nephropathy resulting in renal failure. The tumor develops in the vast majority of such patients. Unlike WAGR, a dominant-negative mutation occurs here at the 11p13 locus.
3. Beckwith–Wiedemann syndrome. Characterized by visceromegaly, hemihypertrophy, cyst formation, and enlargement of adrenal cortex cells. In addition to nephroblastoma, the probability of hepatoblastoma and rhabdomyosarcoma is increased. Pathogenesis is associated with damage to the 11p15.5 locus (WT-2 gene) and genomic imprinting phenomena (loss of maternal alleles with paternal disomy).

Stages and morphology of Wilms tumor

Clinically and morphologically, five stages of nephroblastoma are distinguished:

• Stage 1: the node does not extend beyond the intact renal capsule and is completely excised.
• Stage 2: extension beyond the organ, but complete surgical removal within healthy tissue margins.
• Stage 3: residual masses in the abdominal cavity, peritoneal implantation metastases, involvement of regional lymph nodes, presence of tumor cells at resection margins.
• Stage 4: hematogenous dissemination or involvement of lymph nodes outside the abdominal cavity.
• Stage 5: bilateral renal involvement.

Survival in stages 1–2 exceeds 90%, dropping to 60% in stage 4. In stage 5, the prognosis remains relatively favorable.

Macroscopic appearance The tumor appears as a large, solitary, soft, grayish-pink node on cross-section. The tissue is clearly demarcated from healthy parenchyma. Secondary changes are frequent: hemorrhages, cysts, and areas of necrosis. Multifocal and bilateral forms are recorded in 10% of cases.

Microscopic appearance Nephroblastoma is formed from derivatives of nephrogenic tissue of varying degrees of maturity. A characteristic three-component structure is typical, including:

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

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of spontaneous regression of malignant tumors
• Genetic bases of genomic imprinting in Beckwith–Wiedemann syndrome
• The role of the WT-1 gene in normal renal embryogenesis
• Differential diagnosis of three-component embryonic tumors

Other topics in "Chapter 26. Pediatric Tumors"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.