3. The International Neuroblastoma Staging System (INSS).

Stage	Definition
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)
2A	Localised tumour with incomplete gross excision; representative ipsilateral non‐adherent lymph nodes negative for tumour microscopically
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.
3	Unresectable unilateral tumour infiltrating across the midline,1 with or without regional lymph node involvement; or localised unilateral tumour with contralateral regional lymph node involvement; or midline tumour with bilateral extension by infiltration (unresectable) or by lymph node involvement
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)
4S	Localised primary tumour (as defined for stages 1, 2A, or 2B), with dissemination limited to skin, liver, and/or bone marrow2 (limited to infants < 1 year of age)

Reference: Brodeur 1993

Note: Multifocal primary tumours (e.g. bilateral adrenal primary tumours) should be staged according to the greatest extent of disease, as defined above, and followed by a subscript letter 'M' (e.g. 3_M).
 ¹The midline is defined as the vertebral column. Tumours originating on one side and crossing the midline must infiltrate to or beyond the opposite side of the vertebral column.
 ²Marrow involvement in stage 4S should be minimal (i.e. < 10% of total nucleated cells identified as malignant on bone marrow biopsy or on marrow aspirate). More extensive marrow involvement would be considered to be stage 4. An MIBG (metaiodobenzylguanidine) scan (if performed) should be negative in the marrow.