Neuroblastoma: stages, types and prognosis

Author: Zou Jizhen, Chief Physician, Children's Hospital, Capital Institute of Pediatrics

Reviewer: Meihua Park, Chief Physician, Peking University Third Hospital

In the field of pediatric oncology, neuroblastoma occupies a unique position with its complex and changeable characteristics. As the third most common childhood tumor after leukemia and brain tumors, neuroblastoma is not only challenging in clinical manifestations, but its pathological classification is also the focus of continuous research in the medical community.

1. Overview and types of neuroblastoma

Neuroblastoma originates from ganglion cells during embryonic development, and its lesions are widely distributed in the sympathetic nerve chain of the human body's central axis, from the neck to the pelvis. This malignant tumor is composed of primitive neuroblasts and neural stroma. The difference in the ratio of the two and the maturity stage of neuroblasts leads to diverse histological subtypes.

Figure 1 Original copyright image, no permission to reprint

The International Neuroblastoma Pathology Committee divides neuroblastoma into four major categories: neuroblastoma, ganglioneuroblastoma (including nodular and mixed types), and ganglioneuroma. These four types of tumors constitute a dynamic spectrum change, gradually transitioning from the initial primitive immature type to the mature type. It is worth noting that some subtypes of neuroblastoma, such as undifferentiated and poorly differentiated types, often have a poor prognosis due to their high degree of malignancy.

Clinical manifestations and diagnosis of neuroblastoma

The clinical manifestations of neuroblastoma vary, but they can be divided into two categories: compression symptoms caused by the mass and paraneoplastic syndrome caused by hormones or substances secreted by the tumor. The mass can compress surrounding tissues, such as constipation caused by pelvic tumors and dyspnea caused by thoracic or mediastinal tumors. Paraneoplastic syndrome may manifest as symptoms such as hypertension and Horner's syndrome caused by specific substances secreted by the tumor.

Figure 2 Original copyright image, no permission to reprint

However, the hidden nature of neuroblastoma makes it particularly difficult to detect it early. Most children do not seek medical treatment until they have obvious symptoms, which often means that the diagnosis is not in the early stage. Therefore, regular physical examinations and imaging examinations are particularly important for children with potential risks.

In addition to clinical symptoms and signs, laboratory tests also play an important role in the diagnosis process. Increased levels of neuron-specific enolase (NSE), lactate dehydrogenase (LDH), ferritin (SF), and changes in the ratio of vanillylmandelic acid (VMA) to homovanillic acid (HVA) in urine all provide clues for the suspected diagnosis of neuroblastoma. However, the final diagnosis still depends on pathological examination, which uses histological analysis and immunohistochemical staining of the removed lesion tissue specimens to clarify the tumor type.

3. Multiple considerations of prognosis and the importance of staging

The prognosis of neuroblastoma is affected by many factors, among which the age of onset, the site of the lesion, the histological type and the molecular pathological characteristics are particularly critical. Children under two years old have a better prognosis, and the origin outside the adrenal medulla indicates a better survival rate. Among the histological types, the undifferentiated type has a poor prognosis, while ganglioneuroma is benign. In terms of molecular pathology, N-MYC gene amplification, chromosome 1p36 and 11q loss, and 17q gain are all associated with a poor prognosis. DNA ploidy analysis shows that tumors with a polyploid tendency have a relatively good prognosis.

In addition, tumor staging is crucial for assessing prognosis. The International Neuroblastoma Staging System divides the tumor development stage into multiple stages, from limited resectable stage 1 to extensive metastatic stage 4. Among them, the special stage 4S has distant metastasis but a good prognosis. It is mainly seen in infants less than one year old, and the primary lesion is limited to stage 1 or 2.