The “neuro” of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder

Abstract

Neuroblastoma is a childhood cancer derived from cells of neural crest origin. The hallmarks of its enigmatic character include its propensity for spontaneous regression under some circumstances and its association with paraneoplastic opsoclonus, myoclonus, and ataxia. The neurodevelopmental underpinnings of its origins may provide important clues for development of novel therapeutic and preventive agents for this frequently fatal malignancy and for the associated paraneoplastic syndromes.

Sequence-dependent trafficking and activity of GDE2, a GPI-specific phospholipase promoting neuronal differentiation

“…Enforced GDE2 expression led to altered Rho GTPase signaling, upregulation of neuronal differentiation markers, neurite outgrowth and resistance to neurite retraction through an as-yet-unknown transmembrane effector pathway (Matas-Rico et al, 2016). Moreover, GDE2 expression strongly correlated with positive clinical outcome in neuroblastoma (Matas-Rico et al, 2016), an often lethal neurodevelopmental malignancy characterized by impaired differentiation (Ratner et al, 2016). Importantly, Gde2-knockout in mice leads to progressive neurodegeneration with pathologies reflecting human neurodegenerative disease, which was accompanied by reduced glypican release, implicating dysregulated GPI-anchored protein activity in neurodegeneration (Cave et al, 2017).…”

Síndrome de opsoclonus mioclonus secundario a neuroblastoma abdominal. Presentación de un caso clínico pediátrico

“…El síndrome opsoclonus mioclonus (SOM), también denominado síndrome de los ojos danzantes (dancing eye syndrome) por los movimientos oculares caóticos y rápidos, es una entidad rara en los pacientes pediátricos. [1][2][3] Su incidencia se estima en 0,27-0,40 casos por millón de niños 4 y se presenta entre el primer año de vida y los tres años con una media entre 18 y 22 meses. 5 Su diagnóstico es clínico y debe cumplir tres de estos criterios:…”

“…6,7 Se cree que es de origen autoinmune, dada la presencia de autoanticuerpos descritos tanto en los adultos como en los niños. 1,8 Puede ser la manifestación de un síndrome paraneoplásico (el neuroblastoma es el tumor con mayor asociación -hasta en el 50 % de los casos-) o presentarse como un cuadro clínico posinfeccioso (virus coxsackie, sarampión, rubéola, varicela zóster, influenza, enterovirus, rotavirus, virus de Epstein-Barr, virus de la inmunodeficiencia humana -VIH-, rickettsias, tuberculosis, citomegalovirus, enfermedad de Lyme, hepatitis A y B). 9,10 Se presenta el caso de un varón de 2 años con diagnóstico de SOM secundario a un neuroblastoma suprarrenal izquierdo.…”

Therapeutic plasma exchange for a case of refractory opsoclonus myoclonus ataxia syndrome

“…Opsoclonus myoclonus ataxia syndrome (OMAS) is thought to be an antibody‐mediated, autoimmune syndrome targeting the central nervous system. While often idiopathic, OMAS also occurs as a paraneoplastic syndrome affecting 2–3% of children with neuroblastoma, an embryonal tumor of sympaticoadrenal origin . Despite the favorable prognosis of the neuroblastoma in cases with OMAS, the OMAS itself often has a chronic, relapsing‐remitting course associated with significant long‐term morbidity .…”

“…While often idiopathic, OMAS also occurs as a paraneoplastic syndrome affecting 2-3% of children with neuroblastoma, an embryonal tumor of sympaticoadrenal origin. [1][2][3][4][5][6] Despite the favorable prognosis of the neuroblastoma in cases with OMAS, [1][2][3]5,6 the OMAS itself often has a chronic, relapsing-remitting course associated with significant long-term morbidity. 2,4,[6][7][8][9] Typical treatment for paraneoplastic OMAS involves escalating immune suppression and modulation.…”