Cause:Retinoblastoma, in 10-15%, is genetic, autosomal recessive; other neuroblastoma is rarely genetic
Pathophys:Retinoblastoma originates in retina; acts autosomal dominant but really is recessive; develops tumor when normal arm of chromosome 13 is dropped (Nejm 1984;310:550) (“2-hit” theory)
Adrenal medulla origin
Malignancy correlates with the number of N-myconcogene chromosome copies (Nejm 1996;334:231; 1993;328:847) as well as allelic loss of chromosome 1p (Nejm 1996;334:225)
Both, like Wilm’s tumor of childhood, associated with in utero radiation exposure (Nejm 1985;312:541). Retinoblastoma possibly assoc w IVF? (Lancet 2003;361:309)
Other neuroblastoma, male/female = 2:1 (Ped Hematol Oncol 1994;11:91)
Sx:Positive family hx in 10% w retinoblastoma
In other neuroblastomas, 50% are under age 1 yr; 75% are <3 yr (75%)
Si:In retinoblastoma, strabismus; “cat’s eye” light reflex; bilateral in 30%
In other neuroblastomas, abdominal mass; Horner’s syndrome; thoracic mass; hepatomegaly
In retinoblastoma, peak mortality at age 2-3 yr; 81% survival; rarely metastatic
In other neuroblastoma: stage I: localized to organ of origin; stage II: node negative or ipsilateral node positive beyond organ of origin; stage III: beyond midline; stage IV-S: small primary tumors and metastases in liver, bone, skin often spontaneous regression; stage IV: mets to bone or distant nodes, survival <15% (Onc 1997;11:1857, 1869, 1875)
In retinoblastoma, osteosarcoma in 30% of genetic type from the same oncogene (Ann IM 1990;113:781); overall 2nd primary incidence is 50% in 50 yr, contrast controls where = 5% (Jama 1997;278:1262)
Lab:
Chem:Urine VMA and HVA elevation in neuroblastomas if distant metastases present often (Nejm 1972;286:1123)
Path:Recombinant DNA and chromosomal studies to ascertain risk group.
Xray:MRI helps distinguish neuroblastoma stage IV from IV-S stages
Rx:
of retinoblastoma: if no mets present, surgical excision or radiation; if mets present, partial surgical excision; 6% operative mortality; then radiation rx and chemo rx, eg, with cyclophosphamide, prednisone, actinomycin D, vincristine, and chlorambucil
of neuroblastoma: screening infants for urinary catechols incr detection rate but not survival rate (Nejm 2002;346:1041, 1047, 1084)
chemo rx with cyclophosphamide, doxorubicin, carboplatin, etoposide combos q1 month for 4 (intermediate risk) to 8 (high risk) cycles (Nejm 2010;363:1313)
autologous hematopoetic stem cell transplantation superior to conventional therapy in retrospective, single-arm studies (Haematologica 2000;85[suppl 11]:66)