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 histologic diagnosis from tumor 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 standardize 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: localized tumor not involving vital structures, as defined by the list of IDRFs (below), and confined to one body compartment

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

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

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

• Neck:

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

  • Tumor extending to skull base

  • Tumor compressing trachea

• Cervicothoracic junction:

  • Tumor encasing brachial plexus roots

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

  • Tumor compressing trachea

• Thorax:

  • Tumor encasing aorta and/or major branches

  • Tumor compressing trachea and/or principal bronchi

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

• Thoracoabdominal junction:

  • Tumor encasing aorta and/or vena cava

• Abdomen and pelvis:

  • Tumor infiltrating porta hepatis and/or hepatoduodenal ligament

  • Tumor encasing branches of superior mesenteric artery at mesenteric root

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

  • Tumor invading one or both renal pedicles

  • Tumor encasing iliac vessels

  • Pelvic tumor crossing sciatic notch

• Intraspinal tumor extension:

  • Intraspinal tumor 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)[57]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 tumor and MYCN amplification.

• Stage MS disease in patients ages <12 months with no MS tumor-related symptoms, no MYCN amplification, and all favorable biology.

Intermediate risk

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

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

• Stage MS disease in patients ages <12 months with either MS symptoms or no MS symptoms with no MYCN amplification and any unfavorable biology, or in patients ages 12 to <18 months with no MYCN amplification and all favorable 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 ages 18 months to <5 years with unfavorable histology or ages ≥5 years with INPC undifferentiated or poorly differentiated type.

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

• Stage MS disease in patients ages <12 months with no MS tumor-related symptoms and MYCN amplification, or in patients ages 12 to <18 months with either MYCN amplification or no MYCN amplification with any unfavorable 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 utilized:

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

• Stage 2a: localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically.

• Stage 2b: localized tumor with or without complete gross excision; with ipsilateral nonadherent lymph nodes positive for tumor; enlarged contralateral lymph nodes must be negative microscopically.

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

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

• Stage 4S: localized primary tumor (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).