Neuroblastoma

About 8-9 per million per year.
black ~ white
~10% of childhood CA
In order of maturation: neuroblastoma -> ganglioneuroblastoma -> ganglioneuroma
A small blue round cell tumor (others: Ewing's sarcoma, NHL, PNET, rhabodomyosarcoma, undifferentiated soft tissue sarcomas)

Can be differentiated by staining and histology

Differential Staining of SBRCTs
Mono-Ab	NB	NHL	EW	Rhabdo	PNET
Neurofilament	+	-	+/-	-	-
Synaptophysin	+	-	-	-	-
Neuron-specific enolase	+	-	-^*	-^*	+
b2 microglobulin	-	-	-	-	+
Leucocyte common Ag	-	+	-	-	-
Vimentin	-	+/-	+	+	+
Myoglobin	-	-	-	+	-
Myosin	-	-	-	+	-
Actin	-	-	-	+	-
Desmin	-	-	-	+	-

^*Extraosseus Ewing/Rhabdo may stain NSE +

Shimada/Joshi Histopathological Classification

Favorable
Shimada	Stroma-rich, all ages, no nodular patern
	Stroma-poor, age 1.5-5y, differentiated, MKI < 100
	Stroma-poor, age < 1.5y, MKI < 200
Joshi	Grade 1, all ages; Grade 2 < 1 yr
Unfavorable
Shimada	Stroma-rich, all ages, nodular pattern
	Stroma-poor, age > 5 y
	Stroma-poor, age 1.5-5y, undifferentiated
	Stroma-poor, age 1.5-5, differentiated, MKI > 100
	Stroma-poor, age < 1.5y, MKI > 200
Joshi	Grade 2, age > 1y; Grade 3, all ages

Grade 1	Low mitotic rate (<10 mitotic figures per 10 HPF) and calcifications present
Grade 2	Either low mitotic rate or calcification present
Grade 3	Neither low mitotic rate nor calcification present

Associated Syndromes

Pepper: Massive liver involvement
Horner: Unilateral proptosis, myosis, anhydrosis. Not reversible.
Hutchinson: Limp, irritability; assoc with bone or marrow mets.
Opsomyoclonus (dancing eyes, dancing feet): May be associated with cerebellar ataxia. Sx may not resolve after tumor removal.
Kerner-Morrison Syndrome: Secretory diarrhea from paraneoplastic vasoactive intestinal peptide secretion.
Racoon Eyes: Periorbital hemorrhage from metastatic tumor.

Criteria for diagnosis:

Histological diagnosis from tumor by LM, with or without immunohistology, EM, or catecholamines.
BM Aspirate/Bx of unequivocal tumor cells AND urine/serum catecholamines.

Positive catecholamines must be more than 3 SD for age.

Staging primary

CT or MRI; MIBG (metaiodobenzylguanidine) scan

Testing for metastasis

MIBG scan
bilateral BM aspirate/bx
Bone radiograph/scintigraphy
CXR: AP and lateral; CT/MRI if either chest radiograph positive or if lymph node disease extends to chest.

Staging of Neuroblastoma (INSS)
Stage 1	Localized tumor confined to the area of origin; complete gross resection, with or without microscopic residual disease; identificable ipselateral and contralateral lymph node negative for tumor.
Stage 2A	Unilateral with incomplete gross resection; identifiable ipselateral and contralateral lymph node negative for tumor.
Stage 2B	Unilateral with complete or incomplete gross resection; with ispilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor.
Stage 3	Tumor infilatrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midlnie tumor with bilateral lymph node involvement.
Stage 4	Dissemination of tumor to distant lymph nodes, bone marrow, liver or other organs except as defined by stage 4S.
Stage 4S	Localized primary tumor as defined in stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10% of nucleated BM cells are tumor).

Negative Prognostic Markers

N-myc amplifications
1p deletion
low ploidy

INSS Stage	Age (y)	N-myc	Shimada	Ploidy	Risk Group
1	0-21	Any	Any	Any	Low
2A and 2B	< 1	Any	Any	Any	Low
	1-21	Not Amp	Any	NA	Low
	1-21	Amp	Favorable	NA	Low
	1-21	Amp	Unfavorable	NA	High
3	<1	Not Amp	Any	Any	Intermediate
	<1	Amp	Any	Any	High
	1-21	Not Amp	Favorable	NA	Intermediate
	1-21	Not Amp	Unfavorable	NA	High
	1-21	Amp	Any	NA	High
4	<1	Not Amp	Any	Any	Intermediate
	<1	Amp	Any	Any	High
	1-21	Any	Any	NA	High
4S	<1	Not Amp	Favorable	> 1	Low
	<1	Not Amp	Any	1	Intermediate
	<1	Not Amp	Unfavorable	Any	Intermediate
	<1	Amp	Any	Any	High

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Last modification: July 8, 2000