Differential Diagnosis of Malignant Tumors in Children
In pediatric oncology, the diagnosis of neoplasms such as osteosarcoma often requires the exclusion of other aggressive tumors. A significant proportion of such pathologies consist of small round blue cell tumors. This is a heterogeneous group of neoplasms that, at the light-microscopic level, consist of undifferentiated small cells with hyperchromatic blue nuclei.
In complex cases where the characteristic architecture of the tumor is not apparent, the diagnosis is established only through additional methods. These tumors include various soft tissue sarcomas (e.g., rhabdomyosarcoma) and neuroblastoma.
Additionally, the following malignant and mixed tumors are common in childhood:
- Nephroblastoma (Wilms tumor): has a specific embryonal origin and characteristic histological structure.
- Retinoblastoma: an intraocular neoplasm with its own pathways and features of metastasis.
- Hepatoblastoma: a malignant liver tumor of early childhood.
- Teratomas: tumors with complex morphological structures arising in typical anatomical locations.
Rhabdomyosarcoma as an Object of Differential Diagnosis
Soft tissue sarcomas, specifically rhabdomyosarcoma, are essential comparators when suspecting malignant processes of the musculoskeletal system. Several prognostically and morphologically distinct variants of this tumor are recognized.
Embryonal Rhabdomyosarcoma
Includes spindle cell and botryoid subtypes. Despite their histological features, these variants are distinguished by a more favorable prognosis.
- Botryoid rhabdomyosarcoma: characterized by the formation of a so-called cambium layer. Under the microscope, a compact layer of hyperchromatic tumor cells is identified directly beneath the epithelial lining, visually resembling a layer beneath tree bark.
Alveolar Rhabdomyosarcoma
Distinguished by a more aggressive clinical course and specific morphology.
- Architecture: the tumor is divided into cellular clusters by prominent stromal fibrovascular septa. This exact structure gives the tissue a honeycombed, "alveolar" appearance.
- Cluster center: cells lose connection with the septa, desquamate, and lie freely.
- Periphery: tumor cells retain a strong connection to the stroma, lining up along the septa in a distinctive pallisading arrangement.
- Cytology: the majority of the population consists of undifferentiated cells. Multinucleated forms or cells with eosinophilic cytoplasm are only occasionally encountered, indicating myoblastic differentiation.
Immunohistochemistry and Molecular Genetics
To accurately verify sarcomas, especially when lymph node metastases are detected or clear morphological features are absent, high-tech methods are employed.
Immunohistochemistry (IHC): The main marker of skeletal muscle differentiation is myogenin, as well as the MyoD protein. In rhabdomyosarcoma tumor cells, prominent positive nuclear staining is observed upon reaction with these antibodies.
Molecular Genetic Testing: In ambiguous situations, a search for specific chromosomal translocations is performed. Alveolar rhabdomyosarcoma is typified by the formation of chimeric genes due to rearrangements of transcription regulator genes (which normally regulate early stages of muscle tissue development):
- t(2;13)(q35;q14) leads to fusion and formation of the PAX3/FOXO chimeric gene.
- t(1;13)(p36;q14) forms the PAX7/FOX1 chimeric gene.
Risk Factors and Prognostic Criteria
To determine the treatment strategy, all sarcomas of this type are classified into three prognostic groups: low, intermediate, and high risk.
Patient assignment to a specific group is determined by the following factors:
- Patient age.
- Disease stage (depending on location, dissemination, surgical radicality, and lymph node involvement).
- Morphological variant of the neoplasm.
- Survival rates:
The use of modern combined therapy protocols achieves a 3-year survival rate of 86% for localized forms (without distant metastases). However, in the high-risk group, the prognosis remains extremely grave: survival does not exceed 30%. Furthermore, the most significant adverse prognostic factor is the presence of metastatic involvement in regional lymph nodes.