Fig. 7.34 (A)FISHusingafluorescein-labeledcosmidprobeforN-myc onatissuesectioncontainingneuroblastomaattachedtothekidney.Notetheneuroblastomacellsontheupperhalfofthephotowithlargeareasofstaining(yellow-green);thiscorrespondstoamplifiedN-MYC intheformofhomogeneouslystainingregions.Renaltubularepithelialcellsinthelowerhalfofthephotographshownonuclearstainingandbackground(green) cytoplasmicstaining.(B)AKaplan-Meiersurvivalcurveofinfantsyoungerthan1yearofagewithmetastaticneuroblastoma.The3-yearevent-freesurvivalofinfantswhosetumorslackedMYCN amplificationwas93%,whereasthosewithtumorsthathadMYCN amplificationhadonlya10%event-freesurvival.(A, Courtesy Dr. Timothy Triche, Children’s Hospital, Los Angeles, California. B, Reproduced with permission from Brodeur GM: Neuroblastoma: biological insights into a clinical enigma, NatRevCancer3:203–216, 2003.) from an abdominal mass, fever, and weight loss. In older children the neuroblastomas may remain unnoticed until metastases cause hepatomegaly, ascites, and bone pain. Neuroblastomas may metastasize widely through the hematogenous and lymphatic systems, particularly to liver, lungs, bones, and the bone marrow. In neonates, disseminated neuroblastomas may manifest with multiple cutaneous metastases associated with deep blue discoloration to the skin (earning the rather unfortunate moniker of “blueberry muffin baby”). About 90% of neuroblastomas, regardless of location, produce catecholamines (similar to the catecholamines associated with pheochromocytomas), which constitutes an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]). Despite the elaboration of catecholamines, hypertension is much less frequent with these neoplasms than with pheochromocytomas (Chapter 20).
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Neuroblastomasandrelatedtumorsarisefromneuralcrest–derivedcellsinthesympatheticgangliaandadrenalmedulla.
Neuroblastomasareundifferentiated,whereasganglioneuroblastomasandganglioneuromasdemonstrateevidenceofdifferentiation(schwannianstromaandganglioncells).Homer-Wrightpseudorosettesarecharacteristicofneuroblastomas.
Age,stage,andMYCN amplificationandploidyarethemostimportantprognosticfeatures;childrenyoungerthan18monthsusuallyhaveabetterprognosisthanolderchildren,whereaschildrenwithhigher-stagetumorsorMYCN amplificationfareworse.AhighfrequencyofrelapsedneuroblastomashavemutationsintheRAS-MAPkinasepathway.
Neuroblastomassecretecatecholamines,whosemetabolites(VMA/HVA)canbeusedforscreeningpatients.