Neuroblastoma

American Society of Clinical Oncology diagnostic criteria[27]Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993 Aug;11(8):1466-77. http://www.ncbi.nlm.nih.gov/pubmed/8336186?tool=bestpractice.com

Definitive diagnosis requires one of the following:

• Unequivocal histological diagnosis from tumour tissue by light microscopy.

• Unequivocal evidence of neuroblastoma cells on bone marrow aspiration and biopsy in the setting of increased urine catecholamines.

International Neuroblastoma Risk Group Staging System (INRGSS)[2]Brisse HJ, McCarville MB, Granata C, et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology. 2011 Oct;261(1):243-57. http://pubs.rsna.org/doi/full/10.1148/radiol.11101352 http://www.ncbi.nlm.nih.gov/pubmed/21586679?tool=bestpractice.com

In order to internationally standardise staging irrespective of surgery, the INRG, a collective of investigators from the major cooperative groups in the US, Australia, New Zealand, Japan, China, Germany, and Europe, developed a staging system based on image-defined risk factors (IDRFs). The IDRFs are determined at the time of diagnosis, prior to surgery.

Patients are divided into four main categories:

• L1: localised tumour not involving vital structures, as defined by the list of IDRFs (below), and confined to one body compartment

• L2: local-regional tumour with presence of one or more IDRFs

• M: distant metastatic disease (except stage MS tumour)

• MS: metastatic disease in children younger than 18 months, with metastases confined to the skin, liver, and/or bone marrow

IDRFs

• Multiple body compartments:

  • Ipsilateral tumour extension within two body compartments (i.e., neck and chest, chest and abdomen, or abdomen and pelvis)

• Neck:

  • Tumour encasing carotid artery, vertebral artery, and/or internal jugular vein

  • Tumour extending to skull base

  • Tumour compressing trachea

• Cervicothoracic junction:

  • Tumour encasing brachial plexus roots

  • Tumour encasing subclavian vessels, vertebral artery, and/or carotid artery

  • Tumour compressing trachea

• Thorax:

  • Tumour encasing aorta and/or major branches

  • Tumour compressing trachea and/or principal bronchi

  • Lower mediastinal tumour infiltrating costovertebral junction between T9 and T12 vertebral levels

• Thoracoabdominal junction:

  • Tumour encasing aorta and/or vena cava.

• Abdomen and pelvis:

  • Tumour infiltrating porta hepatis and/or hepatoduodenal ligament

  • Tumour encasing branches of superior mesenteric artery at mesenteric root

  • Tumour encasing origin of celiac axis and/or origin of superior mesenteric artery

  • Tumour invading 1 or both renal pedicles

  • Tumour encasing iliac vessels

  • Pelvic tumour crossing sciatic notch

• Intraspinal tumour extension:

  • Intraspinal tumour extension (whatever the location), provided that more than one third of the spinal canal in the axial plane is invaded, the perimedullary leptomeningeal spaces are not visible, or the spinal cord signal intensity is abnormal

• Infiltration of adjacent structures and organs:

  • Pericardium, diaphragm, kidney, liver, duodenopancreatic block, and mesentery

Revised Children’s Oncology Group Neuroblastoma Risk Classification System (COG version 2)[58]Irwin MS, Naranjo A, Zhang FF, et al. Revised neuroblastoma risk classification system: a report from the Children's Oncology Group. J Clin Oncol. 2021 Oct 10;39(29):3229-41. http://www.ncbi.nlm.nih.gov/pubmed/34319759?tool=bestpractice.com

Uses the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporates segmental chromosome aberrations as an additional biomarker. This risk classification system has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.

Low risk

• Stage L1 disease, unless in patients with incomplete resection of tumour and MYCN amplification.

• Stage MS disease in patients aged <12 months with no MS tumour-related symptoms, no MYCN amplification, and all favourable biology.

Intermediate risk

• Stage L2 disease in patients with no MYCN amplification and either aged <18 months, aged 18 months to <5 years with favourable histology, or aged ≥5 years with International Neuroblastoma Pathology Classification (INPC) differentiating type.

• Stage M disease in patients with no MYCN amplification and either aged <12 months or aged 12 to <18 months with all favourable biology.

• Stage MS disease in patients aged <12 months with either MS symptoms or no MS symptoms with no MYCN amplification and any unfavourable biology, or in patients aged 12 to <18 months with no MYCN amplification and all favourable biology.

High risk

• Stage L1 disease in patients with incomplete resection and MYCN amplification.

• Stage L2 disease in patients with MYCN amplification, or in patients with no MYCN amplification and either aged 18 months to <5 years with unfavourable histology or aged ≥5 years with INPC undifferentiated or poorly differentiated type.

• Stage M disease in any patient aged ≥18 months, patients aged <18 months with MYCN amplification, or patients aged 12 to <18 months with no MYCN amplification and any unfavourable biology.

• Stage MS disease in patients aged <12 months with no MS tumour-related symptoms and MYCN amplification, or in patients aged 12 to <18 months with either MYCN amplification or no MYCN amplification with any unfavourable biology.

International Neuroblastoma Staging System (INSS)[27]Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993 Aug;11(8):1466-77. http://www.ncbi.nlm.nih.gov/pubmed/8336186?tool=bestpractice.com

Neuroblastoma has historically been staged by the INSS, a primarily surgical staging system where staging depends on the aggressiveness of the surgical approach utilised:

• Stage 1: localised tumour with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumour microscopically (nodes attached to and removed with the primary tumour may be positive).

• Stage 2a: localised tumour with incomplete gross excision; representative ipsilateral non-adherent lymph nodes negative for tumour microscopically.

• Stage 2b: localised tumour with or without complete gross excision; with ipsilateral non-adherent lymph nodes positive for tumour; enlarged contralateral lymph nodes must be negative microscopically.

• Stage 3: unresectable unilateral tumour infiltrating across the midline (beyond the opposite side of the vertebral column) with or without regional lymph node involvement, or localised unilateral tumour with contralateral regional lymph node involvement, or midline tumour with bilateral extension via infiltration (unresectable) or lymph node involvement.

• Stage 4: any primary tumour with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs (except as defined for stage 4S disease).

• Stage 4S: localised primary tumour (as defined for stage 1, 2A, or 2B disease), with dissemination limited to skin, liver, and/or bone marrow (limited to infants <1 year of age, marrow involvement <10% of total nucleated cells, 123-iodine-metaiodobenzylguanidine [MIBG] scan findings negative in the marrow).