Table 3. The International Neuroblastoma Staging System (INSS)
mIBG = metaiodobenzylguanidine.
Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically (i.e., nodes attached to and removed with the primary tumor may be positive).
Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically.
Localized tumor with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically
Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement. The midline is defined as the vertebral column. Tumors originating on one side and crossing the midline must infiltrate to or beyond the opposite side of the vertebral column.
Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs, except as defined for stage 4S.
Localized primary tumor, as defined for stage 1, 2A, or 2B, with dissemination limited to skin, liver, and/or bone marrow (by definition limited to infants younger than 12 months).Marrow involvement should be minimal (i.e., <10% of total nucleated cells identified as malignant by bone biopsy or by bone marrow aspirate). More extensive bone marrow involvement would be considered stage 4 disease. The results of the mIBG scan, if performed, should be negative for disease in the bone marrow.
Controversy exists regarding the INSS staging system and the treatment of certain small subsets of patients.[16,17,18] Risk group assignment and recommended treatment are expected to evolve as additional outcome data are analyzed. For example, the risk group assignment for INSS stage 4 neuroblastoma in patients aged 12 to 18 months changed in 2005 for those whose tumors had single copy MYCN and all favorable biological features; these patients had been previously classified as high risk, but data from both POG and Children's Cancer Group studies suggested that this subgroup of patients could be successfully treated as intermediate risk.[19,20,21]