top of page

Neuroblastoma

Contents

  1. Introduction

  2. Presentation

  3. Staging

  4. Risk Stratification

  5. Investigations

  6. Management 

  7. Surgical Steps

  8. Followup

  9. The Future

Introduction

The clinical incidence of neuroblastoma is 1 in 7500 to 1 in 10000 children. Neuroblastoma is responsible for 10% of all childhood tumours and 15% of all cancer deaths. At the time of diagnosis 50% of the patients are 24 months of age and 40% are 12 months of age. Mothers of neonates with congenital neuroblastoma occasionally experience flushing and hypertension during pregnancy as a result of catecholamine released from the fetal tumour in situ. Male infants have a predilection for central nervous system tumours, neuroblastoma and retinoblastoma. In female infants the commonly occurring tumours are teratoma and hepatoblastoma. Neuroblastoma is one of the most common solid tumours in infancy and childhood. It is a neoplasm of the neural crest origin. It commonly arises in the adrenal medulla and along the sympathetic ganglion chain from the neck to the pelvis. This neoplasm exhibits great heterogeneity in its behaviour. Primitive neuroblasts can be seen in the fetal adrenal gland in the 10th and 12th intrauterine week. They increase in number by the 20th intrauterine week and diminish in number by the third trimester. Neuroblastoma in situ occurs in 1 in 260 neonates dying of congenital heart disease and 1 in 39 in neonates who die of other causes. Mass screening programme was discontinued by the Ministry of Health, Japan, in April 2004. mass screening provides important information about the natural history of the tumour and about biologically favourable tumours that regress. However, it causes medical and psychological distress to parents because of its high false-positive rates. Overdiagnosis of neuroblastoma has led to unnecessary therapy. Therefore mass screening programmes have been abandoned in Japan, North America, Europe and Canada.

Presentation

Screenshot 2026-04-14 at 1.35.40 PM.png

Presents in the first two years of life. 

Associated with HD, central hypo, BWS, Fetal alcohol syndrome

Primitive neuroblasts can be seen in the fetal adrenal glands in the 10th and 12th week of intrauterine life, they increase in number by the 20th week and diminish in number by the 3rd trimester. 

  • Adrenal medulla 50%

  • Paraspinal 25%

  • Neck and Pelvis 2.5% each

  • Mediastinal 20%: A posterior mediastinal mass in a child has a high likelihood of being a neurogenic tumor, such as neuroblastoma or ganglioneuroma. The differential diagnoses include congenital pulmonary airway malformations, such as sequestrations, and bronchopulmonary foregut malformations, such as bronchogenic cysts or esophageal duplications. Approximately three-quarters of patients who present with neuroblastoma-associated acute cerebellar ataxia, the opsoclonus myoclonus syndrome, have thoracic lesions.

  • Pelvic organ of Zuckerkandl (Chromaffin body derived from the neural crest cells at the bifurcation of the aorta) 2.5%

  • Spread: Direct, Lymph, hematogenous

  • Tumor markers: Neuron specific enolase, LDH, S/Ferratin.

​

Special Examination

Proptosis (retro-orbital metastasis) or raccoon eyes (periorbital metastasis) and signs of Horner ’ s (ptosis, miosis, and anhydrosis).

Skin exam may reveal the blueberry muffin lesions indicating skin metastases. Abdominal exam should screen for hepatomegaly or any palpable masses.

​

Staging

Screenshot 2026-04-14 at 1.38.56 PM.png

LC LI-P UC D S

1-LC - Localized Complete 

2A-LI - Localized Incomplete 

2B-P - Ipsilateral Lymphnodes 

3-UC Unresectable / infiltrating the midline / contralateral lymphnodes 

4-D- Disseminated 

4- S - limited to skin/liver/marrow

Screenshot 2026-04-14 at 1.40.14 PM.png

bone marrow involvementshould be limited to <10% of total nucleated cells on smears or biopsy to classify as 4S disease

Screenshot 2026-04-14 at 1.41.25 PM.png

Risk Stratification

Low-Risk:
Localized tumor, MYCN negative, age <18 mo.
→ Cure rate >90–95% with surgery alone or limited chemo.

Intermediate-Risk:
L2 stage, age <18 mo, MYCN negative, favorable histology.
→ Survival 70–90% with chemo + surgery.

High-Risk:
MYCN amplified, stage M, or age >18 mo.
→ Survival 40–60% even with multimodal therapy (chemo + surgery + transplant + immunotherapy + retinoic acid).

Special group: Stage MS (<12 mo, limited metastasis)
Often spontaneous regression; managed conservatively or with mild chemo.

Screenshot 2026-04-14 at 1.45.08 PM.png
Screenshot 2026-04-14 at 1.45.41 PM.png

DNA ploidy is checked by flow cytometry and cytogenetics NMYC amplification is checked by FISH/PCR/Immunohistochemistry

 

MKI refers to nuclear fragmantation and is determined by the sum of the number of the number of necrotic tumor cells (Mitotic Karyorrhexis index)

Investigations

Investigations:

  • CBC with differentials 

  • S/Electrolytes

  • Serum levels of lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) should be checked

  • 24hr catecholamine urinary: VMA (Mature), HVA (Immature), NE, Metanephrine 

  • X ray abdomen will show calcifications and displacement of bowel gas by mass (Stippled Calfications, irregular, gritty clacifications - present in more than 80-90%)

  • CXR for mediastinal masses (calcifications and mediastinal widening)

  • USG Doppler Solid vs Cystic mass, site, size and vascularity, also comment on IVC obstruction or involvement 

  • CT with IV contrast (chest, abdomen and pelvis) shows calcifications (80%) and is helpful in staging 

  • MRI Helpful to assess spinal extension. MRI is preferred, especially if neuroblastoma is suspected, as it will demonstrate potential intraspinal extension, as well as the extent of tumor in the intervertebral foramina. 

  • Metaiodobenzylguanidine (MIBG scan): Most sensitive scan for staging, images both soft tissue and bone. Response to therapy. Analogue of NE and its specifically taken up and stored in the tumor. Metaiodobenzylguanidine (MIBG) scanning will confirm the diagnosis, as well as identify potential metastatic sites. Bone scan done if MIBG equivocal.  

  • Bone marrow biopsy should be done (can show rosette of tumor cells, round blue cells) from B/L iliac crests.

  • Genetic testing: NMYC amplification, DNA ploidy and TrkA Expression. 

  • TruCut biopsy: Biopsy stains (only in neuroblastoma): Synaptophysin, Neuron specific enolase, Neurofilament protein S100, Chromogranin A, Tyrosine Hydoxylase y

  • Tumor markers: NSE, LDH and Serum Ferratin (High levels indicate bad prognosis)

image.png

Management

Screenshot 2026-04-14 at 1.52.58 PM.png

Tumor volume < 16ml in  solid and <65ml in cystic 

Observe for any increase in size, if regresses then ok if not then surgery

 

If conservative +ve then

  • Observe with Utrasound and Urine HVA/VMA every 3 months, as most regress spontaneously and differentiate into benign histology, if size increased/markers raised then proceed to surgery.

  • Localised tumors not meeting observation criteria should be resected 

​

B/L neuroblastoma 

Uncommon 

Familial

Treatment options include Observation alone, unilateral resection and observation of other lesions/enucleation 

B/L adrenelectomy and hormone replacement.

 

Stage 4S

Low dose radiotherapy (600-1200Gy) to reduce tumor size 

Cyclophosphamide chemotherapy 5mg/kg/day

Decompressive laparotomy in case of compartment syndrome.

​

CHEMOTHERAPY

4-5 cycles of VCD | Vincristine, Cyclophosphamide and Dacarbazine if fails then Doxorubacin and etoposide. [40% complete response, 30% partial response, 30% no response]

 

RADIOTHERAPY

Neuroblastoma is radiosensitive - High risk after induction chemotherapy and surgery 

As palliation treatment in advanced metastatic disease (low dose)

Dose 2100cGy hyperfractionated radiotherapy to primary site

Recently targeted radiotherapy with Iodine-131-targetted radiotherapy 

 

Treatment for High Risk

Induction chemotherapy is used to decrease tumour burden, eliminate metastasis and facilitate safer surgical resection. Various induction regimens are used, in the UK we use Rapid COJEC. Following induction, peripheral blood stem cell harvest is performed followed by surgical excision of the tumour. Surgical resection (Consolidation) of the primary tumour is usually planned for the end of induction chemotherapy, as long as there is a good response. MRI and CT scan are required for planning and assessing operative IDRF. Recent evidence has shown that CT is superior to MRI for safe surgical planning as MRI can underestimate the extent of the disease compared to CT. Following surgery patients will then undergo myeloablative therapy with autologous stem cell transplantation, and radiation to the primary tumour bed. Maintenance therapy: 13-cis-retinoic acid/isotretinoin promotes tumour cell differentiation and slows the growth of neuroblastoma cells. Patients also receive immunotherapy with a monoclonal antibody called anti-GD2 antibody. Other agents include irinotecan, topotecan that help in remission. Treatment duration is approximately 18 months or longer if there are delays, and patients are followed up for 5 years following successful treatment.

​

IS-S MAA-M Followed for 5 years

 

Newer agents: Recently targeted radiotherapy with Iodine-131-targetted radiotherapy 

​

Summary of management is as follows:

Screenshot 2026-04-14 at 1.58.20 PM.png

SURGERY

Remnants of neuroblastoma at the vertebral foramina do not adversely affect the outcome. The excision of spinal extension is controversial.

 

Abdominal

Open/Laparoscopic 

 

Goal: Complete removal of tumor (if possible) + lymph node biopsy

If densely adherent to kidney → Nephrectomy

Gentle handling to prevent rupture/spill → Catecholamine release 

Monitor BP during surgery 

Good IV access (Highly vascular tumor)

Apply titanium clips to margins → guide radiotherapy 

 

Thoracic 

Posterolateral thoracotomy/thoracoscopy 

 

If neurological symptoms → urgent MRI → emergency laminectomy (intrathoracic resection - excise ectodermal tumor + release cord compression)

 

If extradural tumor on imaging but asymptomatic but asymptomatic → chemotherapy to shrink tumor (this may avoid laminectomy) → if size shrinks then only thoracic approach, if it doesn’t shrink then do laminectomy followed by thoracic dissection. 

 

Cervical/Upper Mediastinal 

Good outcome 

Prognosis on image defined risk factors

May involve stellate gangion

Risk of postop horners syndrome 

Parents should be counselled 

Protect brachial plexus, vagus nerve, RLN, 

 

Risk factors that increase morbidity

Adherent to vascular structures 

Tumor size

Friability

Dumbbell tumors 

 

Upper abdominal lesion

Thoracoabdominal exposure, complete dissection of the vasculature including primary site in addition to all regional lymph nodes 

 

Steps

 

Routine formal lymph node dissection is not required, suspicious lymph nodes are sampled

Operations are undertaken in case of critical neurosurgical symptoms 

Or in a small subset of patients who may be spared chemotherapy with a curative operation. 

Surgical Steps

Principles

​

  1. Work in quadrants; create planes: sharp dissection on the tumor pseudocapsule; preserve normal envelopes (Gerota’s fascia, pancreas capsule).

  2. Subadventitial (“intimal”) dissection on encased vessels: peel tumor off arterial adventitia under loupe magnification; use fine bipolar, peanut dissectors, and microclips.

  3. Avoid capsular rupture: no traction on the mass; use counter-traction with sponges rather than graspers.

  4. Lymph nodes: sample/en bloc regional nodal basin (para-aortic/caval, renal hilar, celiac/para-caval depending on location).

​

Exposure

  1. Incision: generous midline laparotomy (extend to xiphoid/pubic as needed). Consider limited thoracoabdominal extension if tumor reaches crus/hiatus.

  2. Systematic exploration: peritoneal surfaces, liver, spleen, omentum; document and biopsy unexpected lesions if oncologically indicated.

  3. Mobilize the colon on the involved side first to enter the retroperitoneum on an avascular plane (Toldt’s). Pack bowel away with moist pads.

 

Vascular Orientation & Early Control Options

  1. Identify great vessels early: aorta, IVC, renal vessels, celiac axis, SMA/SMV—loop with vessel loops for orientation, not tension.

  2. Plan venous control but avoid blind early ligation—handle adrenal vein thoughtfully (see side-specific steps).

Side-Specific Maneuvers

 

Right adrenal/para-caval tumor

  1. Liver mobilization: divide right triangular/coronary ligaments; pack liver cephalad.

  2. Kocher maneuver: mobilize duodenum to expose IVC, renal hilum, and aorto-caval groove.

  3. Right colon/Cattell–Braasch: if more exposure needed, mobilize right colon and hepatic flexure.

  4. Identify the right adrenal vein entering the IVC; control it once you have safe circumferential dissection (usually early, after exposure) with clip/ligature.

  5. Dissect along IVC wall (subadventitial) to free tumor from cava and renal vein; protect short hepatic/retro-hepatic veins.

  6. Renal preservation: skeletonize right renal artery/vein; preserve unless tumor truly invades the pedicle or kidney parenchyma non-reconstructably.

 

Left adrenal/para-aortic tumor

  1. Left colon mobilization: incise white line of Toldt; reflect colon medially.

  2. Spleen/pancreas (Mattox-type) mobilization: mobilize spleen and tail of pancreas medially; protect splenic vessels.

  3. Identify left adrenal vein (usually to left renal vein); clip/ligate once safe.

  4. Dissect along aorta and left renal pedicle with subadventitial technique around celiac/SMA origins if encased; preserve critical branches.

  5. Protect pancreas tail—keep dissection outside its capsule to prevent fistula.

 

Midline/para-aortic “inter-renal” or celiac/SMA root tumors

  1. Expose supracolic compartment: open lesser sac if needed; elevate stomach/colon to view celiac axis and SMA.

  2. Loop celiac, SMA, and left gastric/splenic/hepatic trunks for orientation only.

  3. Shave tumor off arterial origins subadventitially; avoid thermal injury—short, cool bipolar bursts.

  4. Protect cisterna chyli & major lymphatics over aorta/SMA—clip visible lymphatics to prevent chyle leak.

 

Pelvic/iliac extension (rare)

  1. Track along iliac vessels with meticulous subadventitial dissection; preserve hypogastric branches where possible.

 

Paraspinal/foraminal extension

  1. Neurosurgery coordination if intraspinal component: laminectomy is staged or pre-done after chemo.

  2. At foramina: avoid avulsion of nerve roots; gentle piecemeal shaving is safer than traction.

 

Tumor Delivery & Hemostasis

  1. Final attachments: divide remaining small feeders with clips/energy. Keep a blood-less field to spot adventitial tears early.

  2. Specimen handling: en bloc; avoid capsular breach. Orient and label margins/nodes.

  3. Hemostasis: fine bipolar; micro-clips on adventitial bleeders; topical agents as needed.

 

Reconstruction & Closure

  1. Check perfusion of kidney, bowel, spleen, liver before closing.

  2. Lymphatic control: systematically clip/seal open lymphatics near SMA/aorta/renal hilum to reduce chylous ascites.

  3. Drains: place closed-suction drains selectively (large dead space, raw lymphatic bed, pancreatic hazard).

Close fascia with non-absorbable/slow-absorbable; skin per preference.

ICU monitoring: BP lability, glucose, electrolytes; analgesia with epidural/locoregional if placed. Adrenal considerations: if bilateral manipulation, watch for adrenal insufficiency.

Renal care: monitor urine output, creatinine; renal Doppler if pedicle was manipulated .

Chyle surveillance: milky drain output → triglycerides; initiate MCT diet/octreotide if needed. Pathway: early mobilization,

NG off when bowel sounds return, feeds as tolerated.

Oncology handoff: pathology with nodal status, margin description, % necrosis/chemo response → guides further therapy.

Followup

Screenshot 2026-04-14 at 2.02.12 PM.png

The patient will be followed at regular intervals with physical exam andurinary catecholamine metabolites. Any increase in metabolites will triggeran MIBG to detect recurrence and MRI to define its extent.

The Future

Therapeutic MIBG in neuroblastoma means using radioactive iodine-labeled MIBG, usually ¹³¹I-MIBG, as a targeted radiotherapy for MIBG-avid tumor cells. Neuroblastoma is MIBG-avid in about 90% of cases, and current NCI guidance lists ¹³¹I-MIBG alone or in combination, sometimes followed by stem-cell rescue, as an option for recurrent or refractory high-risk neuroblastoma.

  • Confirm avidity first
    The child must have an MIBG-positive tumor on diagnostic imaging before therapeutic use is considered. Non-avid tumors generally will not benefit and are usually assessed with other modalities such as FDG-PET.

  • Select the usual clinical setting
    Therapeutic ¹³¹I-MIBG is mainly used for relapsed/refractory neuroblastoma, and in some centers/trials it has also been explored in newly diagnosed high-risk disease as part of intensive multimodal therapy.

  • Give thyroid blockade before treatment
    Because free radioactive iodine can accumulate in the thyroid, thyroid protection is required before treatment. This is a standard safety step with iobenguane-based therapy/imaging and remains important in therapeutic practice.

  • Administer ¹³¹I-MIBG intravenously in a radiation-protected setting
    The drug is given by IV infusion in a specialized nuclear medicine/radiation-therapy unit with radiation-safety precautions for staff, patient, and caregivers. The treatment works because MIBG is taken up through the norepinephrine transporter in neuroblastoma cells, delivering internal radiation to tumor deposits.

  • Supportive care during admission
    Practical care usually includes hydration, monitoring, antiemetics as needed, and attention to radiation isolation precautions until exposure levels fall. Blood counts are followed closely because myelosuppression is a major toxicity. This is why some treatment plans include autologous stem-cell support/rescue, especially at higher intensities. NCI specifically notes use “followed by stem cell rescue” in some regimens.

  • Consider combination therapy in selected patients
    ¹³¹I-MIBG has been studied with agents such as vincristine and irinotecan, and randomized phase II work compared single-agent MIBG with MIBG-based combinations in relapsed/refractory disease. These are usually center- and protocol-dependent decisions rather than a one-size-fits-all approach.

Source: https://www.cancer.gov/types/pheochromocytoma/patient/pheochromocytoma-treatment-pdq

Important Points

  • thoracic tumors are more likely than abdominal tumors to be localized at diagnosis, thoracoscopy has frequently been used to resect these tumors.

  • The goals of the procedure should be complete gross resection, avoidance of tumor spill or hemorrhagic complications, and adequate lymph node sampling if possible.

  • The parents should be informed of the high likelihood of postoperative Horner ’ s syndrome given the tumor ’ s superior extent

  • nterestingly, the site of origin is often associated with level of aggressiveness, with extra-abdominal tumors more likely to present as localized tumors with a more favorable biologic profile. Neuroblastoma is one of the classic small round blue cell tumors of childhood, the others being Ewing ’ s sarcoma, lymphoma, rhabdomyosarcoma, hepatoblastoma, Wilms tumor, and retinoblastoma.

  • Any child with new onset ataxia and non-rhythmic nystagmus should undergo a chest x-ray and abdominal ultrasound to screen for neuroblastoma.

  • These tumors typically have an excellent oncologic outcome, but the syndrome usually continues after tumor resection and requires treatment with steroids, immunoglobulins, and potentially chemotherapy.

  • Neuroblastomas can secrete VIP: VIP acts as a major mediator in the gut, inducing smooth muscle relaxation (including in the lower esophageal sphincter), promoting water and electrolyte secretion, and regulating digestion.

  • MIBG should be performed preoperatively to both obtain a baseline for future patient monitoring, as well as assess for metastases including the bone and bone marrow. A bone scan is no longer routinely required for staging, but should still be performed if the tumor is not MIBG-avid.

  • Risk stratification depends upon: histology, MYCN amplification status, DNA ploidy, and the presence or absence of chromosomal aberrations DMCH. 

  • The MKI is determined by calculating the number of mitoses and karyorrhectic cells per 5,000 neuroblastic cells.

  • Many patients with extensive retroperitoneal disease respond dramatically to chemotherapy and can undergo a complete resection, which is typically carried out after the fourth cycle of chemotherapy. The tumor response may be most profound after the first two cycles and subsequently plateau

Screenshot 2026-04-16 at 1.24.25 PM.png

The adrenal gland has a very rich arterial supply from three sets of arteries:

1. Superior suprarenal arteries

  • Usually multiple small branches

  • Arise from the inferior phrenic artery

2. Middle suprarenal artery

  • Usually a single branch

  • Arises directly from the abdominal aorta

3. Inferior suprarenal artery

  • Arises from the renal artery

 

Venous drainage

Each adrenal gland usually has one main vein:

  • Right suprarenal vein → drains directly into the inferior vena cava

  • Left suprarenal vein → drains into the left renal vein (often after joining the inferior phrenic vein)

image.png

© 2035 by paedsurg.net

University Avenue New Muslim Town, Lahore

Tel: 92 322 418 5076

  • White Facebook Icon
  • White Twitter Icon
bottom of page