Nephroblastoma

Metastasis and stages of neuroblastoma

Neuroblastoma is characterized by a high propensity for early dissemination. The frequency of metastasis detection directly correlates with the patient's age: in children under one year of age, metastases are found in 50% of cases, whereas in older age groups, this figure reaches 70%. Typical metastatic sites include lymph nodes, bone marrow, bone tissue, liver, and subcutaneous adipose tissue.

To assess the extent of the disease, an international classification based on the pathomorphological examination of resected tissues is used:

• Stage 1: The neoplasm is localized within the organ, no metastases are present, and the tumor has been completely excised.
• Stage 2a: The tumor node extends beyond the organ boundaries, but is located on one side and does not cross the midline. Most of the mass has been resected, with no metastases.
• Stage 2b: Unilateral involvement of any size, completely or partially excised. A distinctive feature is the presence of metastases in regional lymph nodes.
• Stage 3: The tumor cannot be completely resected, crossing the midline (with or without lymph node involvement). This stage also includes unilateral tumors with contralateral lymph node metastases, or midline tumors with bilateral lymph node involvement.
• Stage 4: Presence of distant hematogenous metastases and distant lymph node involvement.
• Stage 4S: A specific variant occurring exclusively in infants under 1 year of age. The primary tumor corresponds to stage 1 or 2, but there are hematogenous metastases to the skin, liver, and bone marrow.

Diagnosis and prognostic factors of neuroblastoma

Diagnosis is based on the clinical presentation and morphological verification. Cytogenetic and biochemical tests are supportive. However, 90% of patients exhibit elevated blood levels of catecholamines. In clinical practice, the gold standard is the assessment of 24-hour urinary excretion of their metabolites — homovanillic and vanillylmandelic acids.

Prognosis is based on the Shimada classification, which takes into account histological structure, proliferation and apoptosis indices, age, and stage. The most favorable prognosis is observed in children under 1 year of age (85–90% survival regardless of stage) and in stages 1–2 (up to 98%). Age over one year and the presence of metastases critically reduce survival (to less than 10%).

Genetic markers:

1. Deletion of the short arm of chromosome 1 (distal to p32): leads to the loss of a tumor suppressor gene, associated with an unfavorable prognosis.
2. N-myc and N-ras amplification: associated with a poor prognosis (up to 300 copies of N-myc in disseminated cases). It is important to consider not only the copy number but also the expression level.
3. Ploidy: hyperdiploidy worsens the prognosis, while aneuploidy improves it.
4. Trk expression: a high level of nerve growth factor receptor stimulates differentiation into mature ganglion cells and increases survival.

Elevated serum markers—neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and ferritin—are also poor prognostic signs.

Retinoblastoma: etiology and genetics

Retinoblastoma is a malignant neuroepithelial neoplasm of the retina, accounting for 2.5–4.5% of all pediatric malignancies (1 in 20,000 newborns). It manifests predominantly in the first 3 months of life (peaking up to 4 years). A unique feature of the tumor is its ability to undergo spontaneous regression.

Two clinical forms are distinguished:

• Familial (hereditary): accounts for about 50%, characterized by multifocal and bilateral involvement.
• Sporadic: always monofocal and unilateral.

The cornerstone of pathogenesis is a mutation in the Rb tumor suppressor gene located on chromosome 13 (locus 13q14). The protein encoded by this gene normally blocks cell cycle exit from the G1 phase and controls differentiation. According to Knudson's classical "two-hit" hypothesis, two mutations in the Rb gene are required for tumor development. In the hereditary form, the first mutation is inherited from the parents, while the second occurs in somatic retinal cells. In the sporadic form, both mutations occur in a single somatic cell. Today, this process is viewed as multifactorial, requiring the involvement of other genes (suppressors and proto-oncogenes).

Morphology and pathways of spread in retinoblastoma

The tumor develops in the posterior chamber of the eye, appearing macroscopically as a pinkish-white mass with foci of necrosis and calcification.

Microscopically, the tissue consists of small round cells with scant cytoplasm and hyperchromatic nuclei capable of forming ribbon-like structures. In more differentiated tumors, "true rosettes" are formed—palisade-like clusters of columnar or cuboidal cells surrounding a central microcavity.

Dynamics of invasive growth:

1. Development within the retina.
2. Destruction of the vitreous membrane.
3. Invasion into the vitreous body and choroid.
4. Filling of the posterior chamber and extension through the eyeball wall.
5. Destruction of orbital bone structures.
6. Spread into the cranial cavity along the optic nerve.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of spontaneous regression in embryonal tumors
• Comparison of hereditary and sporadic forms of retinoblastoma
• Knudson's hypothesis and modern perspectives on multifactorial carcinogenesis
• Morphological characteristics and differential diagnosis of rosettes in oncopathology
• Biochemical methods for determining catecholamines and their metabolites

Other topics in "Chapter 26. Pediatric Tumors"

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