Fig.7.33A ).Mitoticactivity,nuclearbreakdown(“karyorrhexis”),andpleomorphismmaybeprominent.Thebackgroundoftendemonstratesafaintlyeosinophilicfibrillarymaterial(neuropil)thatcorrespondstoneuriticprocessesoftheprimitiveneuroblasts.Typically,so-calledHomer-Wright pseudorosettes canbefound,inwhichthetumorcellsareconcentricallyarrangedaboutacentralspacefilledwithneuropil(theabsenceofanactualcentrallumengarnersthedesignationpseudo-).Otherhelpfulfeaturesincludeimmunochemicaldetectionofnerualmarkers,suchasneuron-specific enolase,anddemonstrationonultra-structuralstudiesofsmall,membrane-bound,cytoplasmiccatecholamine-containingsecretorygranules.
Someneoplasmsshowsignsofmaturation,eitherspontaneousortherapy-induced.Largercellshavingmoreabundantcytoplasmwithlargevesicularnucleiandaprominentnucleolus,representingganglion cells invariousstagesofmaturation,maybefoundintumorsadmixedwithprimitiveneuroblasts(ganglioneuroblastoma). Lesionsthatareevenbetterdifferentiatedcontainmanymorelargecellsresemblingmatureganglioncellsintheabsenceofresidualneuroblasts;suchneoplasmsmeritthedesignationganglioneuroma (
Fig.7.33B ).MaturationofneuroblastsintoganglioncellsusuallyisaccompaniedbytheappearanceofSchwanncells.
Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient.
• Staging of neuroblastomas (
Table 7.10 ) assumes great importance in establishing a prognosis. Special note should be taken of stage 4S (S means special), because the outlook for these patients is excellent, despite the spread of disease. As noted in
Table 7.10 , the primary tumor would be classified as stage 1 or 2 but for the presence of metastases, which are limited to liver, skin, and bone marrow, without bone involvement. Infants with 4S tumors have an excellent prognosis with minimal therapy, and it is not uncommon for the primary or metastatic tumors to undergo spontaneous regression. The biologic basis for this welcome behavior is not clear. Unfortunately, most (60% to 80%) children
Fig. 7.33 (A)Neuroblastoma.Thistumoriscomposedofsmallcellsembeddedinafinelyfibrillarmatrix(neuropil).AHomer-Wrightpseudorosette(tumorcellsarrangedconcentricallyaroundacentralcoreofneuropil)isseenintheupperrightcorner.(B)Ganglioneuromas,arisingfromspontaneousortherapy-inducedmaturationofneuroblastomas,arecharacterizedbyclustersoflargeganglioncellswithvesicularnucleiandabundanteosinophiliccytoplasm(arrow).Spindle-shapedSchwanncellsarepresentinthebackgroundstroma.
present with stage 3 or 4 tumors, and only 20% to 40% present with stage 1, 2A, 2B, or 4S neuroblastomas.
Age is the other important determinant of outcome. The outlook for children younger than 18 months is much more favorable than for older children at a comparable stage of disease. Most neoplasms diagnosed in children during the first 18 months of life are stage 1 or 2, or stage 4S (“low” risk category in
Table 7.10), whereas neoplasms in older children fall into the “intermediate” or “high” category of risk.
Histology is an independent prognostic variable in neuroblastic tumors; evidence of schwannian stroma and gangliocytic differentiation is indicative of a favorable prognosis.