Neuroblastoma Tip.
Neuroblastoma (neuroblastoma) is the most common extracranial malignant solid tumor in pediatric patients, and the most common malignant tumor in infants and children, accounting for 7% to 10% of childhood tumors.
Etiology Neuroblastoma is an embryonal tumor of sympathetic nerve, which is associated with abnormal neural crest development. According to the degree of sympathetic differentiation of neural crest, neuroblastoma is classified into: hypodifferentiated neuroblastoma, undifferentiated and differentiated mature ganglion cells co-exist, and relatively mature differentiated ganglion cell tumor. Because this developmental process can be reversed, neuroblastoma is clinically manifested as a spontaneous regression of neuroblastoma. Neuroblastoma cases can be complicated by diseases associated with abnormal embryonic neural crest development, such as congenital megacolon, neurofibromatosis, and Beckwith-Wiedemann syndrome.
Clinical manifestations
1.Non-specific systemic symptoms Low fever, lack of appetite, pallor, emaciation, weight loss, local mass, pain, etc.
2.Symptoms related to the site of the mass
(1)Head and neck: one side of the neck mass is found, local lymph node enlargement, Homer syndrome.
(2) Orbit: orbital hemorrhage, protrusion of the eyeball, ptosis. Brain damage may present with retinal hemorrhage, mild bruising of the motoneurial muscles, and the appearance of strabismus.
(3) Chest: The presence of masses in the upper chest may cause dyspnea, dysphagia, and induce lung infection. If the mass appears in the lower chest, it is often asymptomatic.
(4) Abdomen: abdominal pain, lack of appetite, vomiting, palpable abdominal masses, and pressure pain. Neonatal neuroblastoma often leads to liver metastasis, which may result in diaphragm elevation and cause dyspnea and respiratory distress.
(5) Pelvis: urinary retention, constipation, and pre-sacral masses can be palpated on rectal finger examination.
(6) Paravertebral: localized pain and tenderness in the back, weakness of lower limbs, claudication, hypotonia, urinary and fecal incontinence.
3.Other clinical manifestations
(1) Abnormalities in catecholamine metabolism (VMA/HVA) and corresponding complicating symptoms, such as pallor, excessive sweating, headache, palpitations, and hypertension due to increased renin secretion.
(2) Refractory watery diarrhea, wasting, and hypokalemia caused by increased vasoactive substances. Neuroblastoma secretes gastrointestinal hormones (vasoactive intestinal peptides).
Clinical staging
INSS staging.
Stage I The tumor is limited to the primary tissue or organ, complete removal of the tumor by the naked eye, and negative lymph node microscopy.
Stage II Ⅱa tumor with incomplete sarcoid resection and negative ipsilateral lymph nodes.
Stage IIb complete or incomplete resection of the tumor by the naked eye, positive ipsilateral lymph nodes.
Stage III Tumor beyond the midline, ipsilateral lymph node microscopy negative or positive; tumor not beyond the midline, contralateral lymph node
The tumor does not go beyond the midline, but the contralateral lymph nodes are positive on microscopic examination.
Stage IV Distant metastasis to bones, lymph nodes, bone marrow, liver or other organs.
Stage IV-S or special stage IV, age ≤ 1 year, liver, skin or bone metastases only.
Treatment
The main treatment for neuroblastoma is surgery and chemotherapy, and radiation therapy if necessary.
1.Surgical treatment
(1) Complete resection of the tumor is the best treatment for neuroblastoma. In stage I and II cases, complete resection of tumor should be performed, so that no tumor tissue visible to the naked eye remains. In stage III cases, if more than 90% of the tumor can be excised, stage I surgery should be performed. If stage I resection cannot be performed, 2-3 courses of chemotherapy can be given before surgery to suppress and reduce the tumor blood vessels and reduce the size of tumor, so that the tumor can be easily separated for surgery and create conditions for complete resection of tumor in stage II.
(2) Primary organ treatment: If it is possible to remove the primary tumor organ without endangering life, for example, if the lesion involves one side of kidney, it should be removed in principle.
(3) Removal of tumor tissues to further clarify the diagnosis and clinical staging and successfully complete the treatment.
2.Chemotherapy
Stage I and II cases Surgical treatment + postoperative chemotherapy.
Stage III and IV cases Pre-operative 2-4 courses of chemotherapy + surgical treatment + post-operative chemotherapy.
Risk factors affecting chemotherapy: five indicators of neuroblastoma stage, age of the child at diagnosis, MYCN gene copy number, Shimada histopathological classification and DNA index. Based on these five indicators, neuroblastoma was divided into low-risk, intermediate-risk and high-risk groups.
The treatment principles for each group are as follows.
Low-risk group: complete resection of the tumor was used as treatment, and chemotherapy was given only in case of recurrence. Chemotherapy drugs: cyclophosphamide, adriamycin.
Intermediate risk group: mild chemotherapy regimen after surgical resection of the primary tumor.
High-risk group: high-dose consolidation chemotherapy regimen.
The following chemotherapy drugs are used in the intermediate risk group and high risk group: cisplatin, etoposide, cyclophosphamide, adriamycin.
3.Radiotherapy is not done for cases with complete tumor resection. Radiotherapy should be done if the tumor is not completely resected or there is lymph node infiltration. The dose of radiotherapy for children with bone metastasis should be increased appropriately according to the condition.
Prognosis]
It mainly depends on the following factors.
(1) Age: infants less than 1 year old have the best prognosis and high rate of complete tumor resection.
(2) Primary tumor site: above the diaphragm is less likely to spread and has a good prognosis; tumors outside the adrenal gland are better than adrenal tumors.
((3) Clinical stage: Stage I, II and IVS have good prognosis, stage III and IV have poor prognosis.
(4) High expression of MYCN gene and poor prognosis.
(5) Shimada histopathological classification: good prognosis type with good outcome.
(6) DNA index: heteroploidy, good prognosis.