Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma

Grading / Staging

Clinical staging classifies patients into low, intermediate and high risk groups based on:

International Neuroblastoma Pathology Classification

Classifies tumors into unfavorable and favorable histology based on

Mitosis-karyorrhexis index (MKI)

Not calculated overall for ganglioneuroblastoma or ganglioneuroma
- Should be calculated only for nodules of neuroblasts in ganglioneuroblastoma

Mitotic figures + karyorrhectic cells / 5000 neoplastic cells

Tumor Subtype	MKI	Patient Age
Undifferentiated NB	Any MKI	Any age
Poorly differentiated NB	High MKI	Any age
Poorly differentiated NB	Intermediate MKI	Age ≥ 1.5 yrs
Poorly differentiated NB	Low MKI	Age ≥ 1.5 yrs
Differentiating NB	High MKI	Any age
Differentiating NB	Intermediate MKI	Age ≥ 1.5 yrs
Differentiating NB	Not applicable	Age ≥ 5 yrs
Ganglioneuroblastoma, Nodular*	Not applicable	Any age

* At least one nodule of neuroblasts has unfavorable histology

Tumor Subtype	MKI	Patient Age
Poorly differentiated NB	Intermediate MKI	Age < 1.5 yrs
Poorly differentiated NB	Low MKI	Age < 1.5 yrs
Differentiating NB	Intermediate MKI	Age < 1.5 yrs
Differentiating NB	Low MKI	Age < 5 yrs
Ganglioneuroblastoma, Intermixed	Not applicable	Any age
Ganglioneuroblastoma, Nodular*	Not applicable	Any age
Ganglioneuroma	Not applicable	Any age

* All nodules of neuroblasts must have favorable histology

Stage 1	Complete gross excision of localized tumor, with or without positive microscopic margins	Negative ipsilateral non-adherent lymph node(s) (lymph node(s) attached to and removed with the primary tumor may be positive)
Stage 2A	Incomplete gross excision of localized tumor	Negative ipsilateral non-adherent lymph node(s) (lymph node(s) attached to and removed with the primary tumor may be positive)
Stage 2B	Complete or incomplete gross excision of localized tumor	Positive ipsilateral non-adherent lymph node(s); contralateral lymph node(s) negative for tumor
Stage 3	a. Unresectable unilateral tumor infiltrating across the midline OR b. Localized unilateral tumor OR c. Unresectable midline tumor with bilateral extension	a. Positive or negative regional lymph node(s) OR b. Contralateral positive regional lymph node(s) OR c. May be “unresectable” due to positive bilateral lymph node(s)
Stage 4	Any primary tumor with involvement of distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs (except 4S)
Stage 4S	Any localized primary tumor with involvement of skin, liver, and/or less than 10% of bone marrow cellularity (ONLY applies to children less than 1 year of age)