What Is Esthesioneuroblastoma?

The prognosis of patients with different neuroblastomas is very different, that is, there is extensive tumor heterogeneity among neuroblastomas. According to different high-risk factors, neuroblastoma can be divided into low-risk group, intermediate-risk group and high-risk group. For patients with neuroblastoma in the low-risk group (most common in infants and young children), simple observation or surgery can often achieve good results; but patients with neuroblastoma in the high-risk group, even if integrated with various intensive treatment options The prognosis is still not ideal. Olfactory groove neuroblastoma is generally thought to originate from the olfactory nerve epithelium; its classification is still controversial. Because it does not belong to the sympathetic nervous system, olfactory sulcus neuroblastoma should be a separate type of tumor, which is different from the neuroblastoma described below.

Lin Qingtang	(Deputy Chief Physician)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University
Du Jianxin	(Chief physician)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University

Neuroblastoma is the most common extracranial tumor in children and the most common tumor in infants and young children. Nearly half of neuroblastomas occur in infants younger than two years of age. Neuroblastoma accounts for approximately 6-10% of childhood tumors and 15% of childhood tumor mortality. For children under 4 years old, the mortality rate is 10 per million people; for children 4-9 years old, the death rate is 4 per million people. Neuroblastoma is a neuroendocrine tumor that can originate from any nerve ridge in the sympathetic nervous system. The most common site is the adrenal gland, but it can also occur in the nervous tissue of the neck, chest, abdomen, and pelvis. There are currently a few known human tumors that spontaneously degenerate from undifferentiated malignancies to completely benign tumors. Neuroblastoma is one of them.

Western Medicine Name: Neuroblastoma
Affiliated Department: Surgery-Neurosurgery
Disease site: brain

Multiple groups: Infants under 2 years
Contagious: Non-contagious
Whether to enter health insurance: Yes

Neuroblastoma disease profile

Neuroblastoma symptoms and signs

The initial symptoms of neuroblastoma are atypical, making early diagnosis difficult. The more common symptoms include fatigue, loss of appetite, fever, and joint pain. The symptoms caused by a tumor depend on the organ in which the tumor is located and whether metastasis has occurred.

Neuroblastoma in the abdominal cavity generally manifests as abdominal distension and constipation; Thoracic neuroblastoma generally manifests as dyspnea; Spinal neuroblastoma generally exhibits reduced strength in the trunk and limbs, and patients often have difficulty standing and walking; Neuroblastomas of the bones such as the hips and hips can manifest as bone pain and claudication; the destruction of bone marrow can make patients' skin pale due to anemia. Most neuroblastomas (50-60%) have extensive metastases before they appear clinically. The most common site of primary neuroblastoma is the adrenal gland (about 40%); other primary organs include the neck (1%), thorax (19%), abdominal cavity (30%), and pelvic cavity (1%) . In other rare cases, the primary lesion was not found. Rare but characteristic clinical manifestations include transected spinal cord disease (spinal compression, 5%), refractory diarrhea (tumor secretes vasoactive intestinal peptide, 4%), Horner syndrome (neck tumor, 2.4%) ), Ataxia (caused by paracrine tumors, 1.3%), and hypertension (compressed renal arteries or catecholamine secretion, 1.3%).

Causes of neuroblastoma

The true etiology of neuroblastoma is unknown. Some genetic susceptibility factors have been found to be associated with the pathogenesis of neuroblastoma. Familial neuroblastoma has been shown to be caused by somatic mutations of anaplastic lymphoma kinase (ALK). In addition, many molecular mutations have been found in neuroblastoma. N-myc gene amplification mutations are also common in neuroblastoma. The amplification type is bidirectionally distributed: 3-10 times amplification at one extreme and 100-300 times amplification at the other extreme. N-myc gene amplification mutations are often associated with tumor spread. The LMO1 gene has been shown to be related to the degree of malignancy of the tumor.

Because neuroblastoma often occurs in infants and young children, many studies have focused on investigating the impact of environmental risk factors on pregnancy and pregnancy. For example, whether you are exposed to chemical dangers, smoking, alcohol, drugs, infections, etc. during pregnancy. However, these studies have not yet yielded clear results.

Neuroblastoma diagnosis

The final diagnosis depends on the postoperative pathology, but at the same time, the clinical manifestations of the patient and other auxiliary examination results must be considered.

Neuroblastoma biochemical examination

Nearly 90% of neuroblastoma patients have significantly higher concentrations of catecholamines and their metabolites (dopamine, homovanillic acid, vanillyl mandelic acid) in the blood or urine compared with the normal population.

Neuroblastoma imaging

Another method for detecting neuroblastoma is a meta-iodobenzylguanidine (mIBG) scan. The molecular mechanism of this test is that meta-benzylguanidine is a functional analog of norepinephrine and can be taken up by sympathetic neurons. When meta-stilbeneguanidine is coupled with a radioactive substance such as iodine-131 or iodine-123, it can be used as a radiopharmaceutical for the diagnosis and efficacy monitoring of neuroblastoma. The half-life of iodine-123 is 13 hours, which is often used as the preferred method of detection; the half-life of iodine-131 is 8 days. When used in large doses, it can be used to treat relapse and refractory neuroblastoma.

Neuroblastoma immunohistochemical examination

Under the microscope, neuroblastomas appear as small blue-stained round cells arranged in a chrysanthemum pattern. Tumor cells are arranged in a chrysanthemum pattern around neuropils, which is different from other tumors (such as optic neuroblastoma) in a chrysanthemum pattern around blood vessels. Others also have immunohistochemical staining specific to neuroblastomas to differentiate them from other tumors (Ewing's sarcoma, lymphoma, etc.). ^[1]

Neuroblastoma tumor staging

The International Neuroblastoma Staging System (INSS) was established in 1986 and revised in 1988. The system is based on the tumor's primary organ and metastasis.

Phase 1: limited to primary organs, no metastases;

Stage 2A: Subtotal resection of unilateral tumors; no metastasis on ipsilateral and contralateral lymph nodes;

Stage 2B: Subtotal or total resection of unilateral tumors; ipsilateral lymph nodes have clear metastasis, while contralateral lymph nodes have no clear metastasis;

Stage 3: tumor invasion across the midline, with or without local lymph node metastasis; or unilateral tumor with contralateral lymph node metastasis; or tumor growing across the midline with bilateral lymph node metastasis;

Stage 4: The tumor spreads to distant lymph nodes, bone marrow, liver, or other organs (except the organs defined in stage 4S).

Stage 4S: Children less than 1 year old; tumors are limited to primary organs; tumor spread is limited to liver, skin, or bone marrow (tumor cells have less than 10% of bone marrow nucleated cells). ^[2]

Beginning in 2005, several major child cancer research collaboration groups around the world began a retrospective comparison study of 8,800 neuroblastoma cases treated in Europe, Japan, the United States, Canada, and Australia between 1990 and 2002. Based on the results of this retrospective study, neuroblastomas are restaged (INRGSS) according to the degree of risk. This retrospective study found that children with neuroblastoma at 12-18 months have a good prognosis; accordingly, the new classification system will remove children with 12--18 months without N-myc mutation from the previous high-risk group , Reclassified to the intermediate-risk group. The risk classification system is as follows:

Stage L1: The lesion is limited and there are no risk factors identified by imaging;

Stage L2: lesions are limited but have risk factors determined by imaging;

Stage M: metastasis occurs;

MS stage: specific metastasis of the lesion (same as 4S stage above);

The new risk stratification system will divide neuroblastoma patients into: extremely low-risk groups based on the new INRGSS staging system, age at onset, tumor grade, N-myc amplification status, unbalanced mutations in the 11q chromosome, and multikaryotype factors , Low-risk group, intermediate-risk group, and high-risk group.

Neuroblastoma treatment

According to the above risk stratification, the treatment is also different:

Neuroblastoma low-risk group

Observation is allowed, and intervention is not made until the disease has progressed or changed; or surgery is performed, which is often curable.

Neuroblastoma intermediate-risk group

Resection with chemotherapy.

Neuroblastoma high-risk group

High-dose chemotherapy, surgical resection, radiotherapy, bone marrow / hematopoietic stem cell transplantation, 13-cis-retinoic acid-based biotherapy, and granulocyte colony-stimulating biological factors and interleukin-2 immunotherapy ^[3]

Neuroblastoma prognosis

After treatment, the cure rate of patients in the low-risk group was more than 90%, and the cure rate of patients in the intermediate-risk group was between 70-90%. However, the cure rate for patients in the high-risk group is only about 30%. In recent years, with the advent of immunotherapy and new drugs, the prognosis of patients in the high-risk group has improved to some extent.