Neuroblastoma (NB) is a malignant tumor originating from neural crest cells of the embryonic sympathetic nervous system, capable of secreting various neurogenic derivatives (such as catecholamines and neuron-specific enolase). The etiology and pathogenesis remain unclear, but recent studies suggest that the loss of heterozygosity on the short arm of chromosome 1 (deletion of tumor suppressor genes) and amplification of the N-myc oncogene play significant roles in the disease mechanism. It ranks as the third most common malignant solid tumor in children, predominantly affecting those under 5 years old, though cases in older children also occur. The disease progresses rapidly, metastasizes early, and has a poor prognosis. Tumors in infants under 1 year old may exhibit a tendency for spontaneous regression.

bubble_chart Clinical Manifestations

1. Systemic manifestations: Often include irregular fever, pallor, poor appetite, lack of strength, pain, and irritability. Rarely, symptoms of increased catecholamine metabolism such as profuse sweating, palpitation, tachycardia, and elevated blood pressure may occur. Chronic watery diarrhea may be present. Occasionally, eye-myoclonus syndrome may be observed.
2. Primary lesion manifestations: In more than half of the cases, the primary follicular tumor is located in the abdomen, most commonly in the adrenal medulla. The tumor mass is often situated in one hypochondrium region, may cross the midline, and presents as a painless, hard, irregular nodule. Abdominal pain may occur. If the tumor is small and lacks abdominal symptoms or signs, it can be easily misdiagnosed and is referred to as the occult type. Primary follicular tumors can occur anywhere along the sympathetic nerve axis, including the neck, mediastinum, abdominal cavity, and pelvic cavity. Tumors in the upper mediastinum or neck may cause cough, dyspnea, Horner's sign, and other compressive symptoms. Paravertebral tumors extending into the spinal canal through the intervertebral foramen, forming a dumbbell shape, may lead to constipation, urinary retention, flaccid paralysis, and other symptoms.
3. Metastatic lesion manifestations: At the time of diagnosis, 75% of cases already have metastases, commonly involving the liver, bones, bone marrow, lymph nodes, orbits, and skin. Bone pain in the limbs, arthralgia, proptosis, periorbital ecchymosis, and petechiae suggest bone metastases. Liver metastases are more common in infants under 1 year of age and may present with jaundice. Skin metastases are more frequently observed in neonates and infants.

TCM's treatment of atopic dermatitis is more comprehensive, fundamental, non-toxic and effective than Western medicine's symptomatic treatment

bubble_chart Auxiliary Examination

1. The blood picture often shows anemia, with normal white blood cell differential or the presence of immature cells or tumor cells. Platelet counts may be normal or decreased.
2. Bone marrow findings: In more than half of the cases, tumor cells can be observed in bone marrow smears. Typically, these tumor cells aggregate in Chrysanthemum Flower-like clusters, exhibiting diverse morphologies. When only cell clusters are present, specific monoclonal antibodies can be used to detect their phenotype and identify NB tumor cells.
3. Urinary catecholamine metabolite testing: Elevated levels of VMA (vanillylmandelic acid) and HVA (homovanillic acid) in 24-hour urine provide important diagnostic evidence for this disease. Repeated measurements can increase the positive rate. For cases where collecting 24-hour urine is difficult, random urine samples can be tested for creatinine, VMA, and HVA levels to determine their relative ratios (VMA, HVA g/mg creatinine).
4. Imaging diagnosis: B-ultrasound, X-ray, CT, and magnetic resonance imaging (MRI) can detect tumor lesions in the chest, abdomen, bones, or spinal canal. Approximately 50% of abdominal tumors exhibit punctate or speckled calcifications. Observing the characteristics of intravenous pyelography can help differentiate these tumors from other retroperitoneal tumors.
5. Histopathological examination: Tumor tissue or lymph node biopsy specimens show diffuse proliferation of small blue round cells forming syncytial aggregates, typically arranged in Chrysanthemum Flower-like clusters. Immunohistochemical examination provides reliable evidence for definitive diagnosis and differential diagnosis.
6. Prognostic factor testing: (1) Poor prognostic factors: In addition to age ≥1 year and advanced-stage tumors, the following factors should be assessed: - Amplification of the N-myc oncogene (≥10 copies); - Deletion in the short arm of chromosome 1; - Aneuploid DNA content in tumor cells; - Serum ferritin ≥150 mg/L; - Serum neuron-specific enolase (NSE) ≥1500 IU/L or ≥100 ng/ml; - Positive expression of MRP (multidrug resistance-associated protein); - Histopathological classification (Shimada method) indicating an unfavorable prognosis. (2) Favorable prognostic factors: - High expression of the TRK-A (neurotrophic tyrosine kinase receptor type 1) gene in tumor cells; - Hyperdiploid DNA content (DNA index ≥1.0) in infant cases.

For influenza, enterovirus, and various viral colds, TCM is more refined, non-toxic, and effective than modern medicine

bubble_chart Diagnosis

(1) Diagnosis can be confirmed if one of the following criteria is met:

1. Histopathological examination of tumor tissue definitively identifies it as neuroblastoma;
2. Bone marrow specimens reveal definitive characteristic neuroblastoma syncytia or immunologically identified positive cell clusters, accompanied by elevated urinary VMA and HVA levels (VMA and HVA levels exceeding the normal mean for the age group by 3 standard deviations per gram of creatinine).

(2) Tumor staging diagnosis (International NB Staging System)
Stage I: The tumor is confined to the original site and can be completely resected.
Stage II: The tumor extends beyond the original site but does not cross the midline, with complete or incomplete resection. Further divided into Stage IIa (lymph node biopsy negative) and Stage IIb (ipsilateral lymph node biopsy positive, contralateral negative).
Stage III: The tumor infiltrates beyond the midline, with bilateral regional lymph node involvement.
Stage IV: Distant metastasis to bones, solid organs, soft tissues, distant lymph nodes, or bone marrow.
Stage IV-s: Infants under 1 year of age with Stage I or II primary follicular tumor may exhibit metastasis to one or more distant sites (liver, skin, or bone marrow) but no bone metastasis.

(3) For cases primarily presenting as retroperitoneal tumors, differentiation from Wilms' tumor, teratoma, lymphoma, etc., is necessary. Early occult cases should be distinguished from acute leukemia, acute osteomyelitis, wind-dampness arthritis, osteomyelitis, histiocytosis, etc.

bubble_chart Treatment Measures

(1) Staging System Treatment Management

Although in recent years, both domestically and internationally, risk grouping (low, intermediate, high risk) based on clinical and tumor biological characteristics and the formulation of treatment strategies according to risk groups have emerged, there is still a lack of universally recognized unified grading standards. The following only introduces the staging system treatment management.

1. Stage I: No further treatment is required after complete tumor resection, but regular follow-up is necessary.
2. Stage II: For tumors completely resected without unfavorable prognostic factors, postoperative two-drug combination chemotherapy for 12 months is recommended. For tumors partially resected or with microscopic residual lesions and significant unfavorable prognostic factors, treatment follows the #-stage postoperative residual lesion protocol, but radiotherapy is generally not performed.
3. Stage III: For tumors completely resected, postoperative radiotherapy is administered to the tumor bed area, along with multi-drug combination chemotherapy for 12 months. For Stage III tumors partially resected, postoperative radiotherapy to the tumor bed area is combined with chemotherapy for 3–6 months. If subsequent ultrasound and CT examinations confirm tumor disappearance and normalization of VMA, HVA, SF, NSE, etc., chemotherapy is continued for 2 years. If tumors persist, regional lymph nodes remain, or VMA/SF levels remain elevated, a second surgical exploration and treatment are required, followed by continued chemotherapy for 18–24 months.
4. Stage III tumors that cannot be surgically resected and Stage IV patients require induction chemotherapy with 3–4 drugs for 3–6 months to localize and shrink the tumor and eliminate metastases, supplemented with radiotherapy if necessary. Delayed surgery is then performed to achieve as complete a resection as possible, followed by postoperative radiotherapy and consolidation chemotherapy for 2 years, with a second surgery if necessary during seasonal epidemics. For refractory cases and Stage III/IV (≥1 year old) cases with poor prognostic factors such as N-MYC amplification, postoperative intensive treatment (chemotherapy, radiotherapy) plus autologous bone marrow transplantation can improve efficacy.
5. Stage IV-S: For cases with spontaneous calcification, normal VMA and SF, and no unfavorable prognostic factors, surgery may be omitted, and regular follow-up is sufficient. For cases with complications (e.g., massive liver causing lung or kidney compression symptoms) or bone marrow metastasis, or those in poor general condition, chemotherapy (e.g., VCR and CTX) may be administered first, possibly supplemented with radiotherapy (150 cGy/day × 3 days). Delayed surgery is performed after 3–6 months based on tumor regression, followed by chemotherapy for 3–6 months as appropriate. Strengthen symptomatic and supportive treatment.

TCM can effectively treat dry eye syndrome, floaters, retinopathy, and various chronic eye diseases

(2) Chemotherapy Protocol Introduction

1. Induction regimen: <1歲的Ⅲ、Ⅳ期用兩藥聯合方案:一線方案:CTX(環磷酰胺)150mg/( m2‧d),iv，第1～7天;ADM(阿黴素)35mg/ m2, .m，第8天，每3周為一個療程。二線方案:DDP(順鉑)3mg/kg, iv，第1天;VP-16(依托泊甙)5Omg/m2, iv，第3天。每3周為1療程。此方案也適用於Ⅱ期術後化療，化療間隔時間酌情調整。
   For patients aged ≥1 year with stage III or IV, consider the following multi-drug combination regimens: (1) OPEC regimen: CTX 600mg/m², IV, Day 1; VCR 1.5mg/m², IV, Day 1; DDP 90mg/m², Day 2; VP-16 (Vm-26) 150mg/m², IV, Day 4. Repeat every 3 weeks as one course. (2) CDEC regimen: DDP 60mg/m², IV, Day 1; VP-16 100mg/m², IV, Days 3–6; ADM 30mg/m², IV, Day 3; CTX 900mg/m², IV, Days 4–5. Repeat every 3–4 weeks as one course. (3) PECA regimen: DDP 90mg/m², IV, Day 1; VP-16 100mg/m², IV, Day 3; CTX 150mg/m²/day, IV (PO), Days 7–13; ADM 35mg/m², IV, Day 14. Repeat every 3–4 weeks as one course. (4) CIDE regimen: DDP 40mg/m², IV, Days 1–4; IFD (ifosfamide) 2500mg/m², IV, Days 1–4 (must be combined with Mesna); ADM 10mg/m², IV, Days 1–4; VP-16 125mg/m², IV, Days 1–4.
2. Postoperative radiotherapy: Radiotherapy to the tumor bed begins on the 8th day after surgery. During the radiotherapy period, CTX 150mg/(m2‧d) may be administered orally from days 8 to 14 as appropriate; VP-16 120-150mg/m2 on days 15, 16, and 17.
3. Consolidation therapy: Continue chemotherapy with effective induction regimens until the total treatment course reaches two years. After discontinuing chemotherapy drugs, administer all-trans retinoic acid at 30μg/(m2‧d) for 20 days per month for a total of 6 months to conduct induction differentiation therapy and eliminate minimal residual disease. For stage IV-S patients requiring chemotherapy, use a CTX-VCR combination regimen: the dose should be 50-70% of the conventional dose. DDP should be dissolved in 3% sodium chloride solution and administered intravenously over 2-4 hours. Strong antiemetics should be given during administration, and appropriate hydration therapy should be provided before and after administration, with the addition of magnesium ions, mannitol, and furosemide as needed. During medication, strengthen monitoring and protection against nephrotoxicity and hearing damage, and pay attention to correcting typical electrolyte disturbances. For precautions and supportive treatment regarding the use of high-dose CTX, IFO, and other intensive induction regimens, refer to the treatment protocols for acute leukemia, etc.

bubble_chart Prognosis

With modern comprehensive treatment, the long-term survival rates are 75-90% or higher for stages I, II, and IV-S; 80-90% for stage III and 60-75% for stage IV in children under 1 year old; and 15-50% for stages III and IV in children aged 1 year or older. Emerging biological therapies and targeted therapies under research offer hope for further improving treatment outcomes.