Rare MYC-amplified Neuroblastoma With Large Cell Histology

Abstract

Background Although MYCN (aka N-myc) amplification is reported in ∼20% of neuroblastomas, MYC (aka C-myc) amplification appears to be a rare event in this disease. As of today, only 2 MYC-amplified neuroblastomas have been briefly mentioned in the literature. Methods We studied here the clinicopathological features of 3 MYC-amplified neuroblastomas. Results All 3 patients (2 females and 1 male) had stage 4 disease. One female is currently alive and well 52 months after the diagnosis, while the other female and male patients died of disease 24 and 20 months after the diagnosis, respectively. Further analysis on 2 tumors revealed unfavorable histology with MYC protein overexpression but with neither MYCN amplification nor MYCN protein overexpression. Both of these tumors exhibited "large cell neuroblastoma" histology with enlarged, uniquely open nuclei and nucleolar hypertrophy, along with "aberrant" desmin expression. Conclusions MYC-amplified neuroblastomas are extremely rare and seem to present with distinct clinicopathological features.

Adult‐onset neuroblastoma: Report of seven cases with molecular genetic characterization

“…We also found one case with gain of MYCN , a finding that has not been reported by others, but may not have been documented as this genetic change carries no prognostic significance . Overexpression of the oncogene MYC is seen in ~10% of pediatric neuroblastoma and is associated with unfavorable histology and a poor prognosis . MYC expression is mutually exclusive of MYCN expression due to MYCN amplification.…”

“…Neuroblastoma is unusual among malignancies in that it is characterized by a striking heterogeneity of histology and genetic aberrations resulting in a widely variable clinical behavior . Genetic changes that impart a negative prognostic effect include: amplification of the MYCN gene, expression of MYC, deletion or loss of heterozygosity of chromosome 1p and gain of chromosome 17q and maintenance of telomeres through ATRX mutations or rearrangements of the TERT gene . Genetic changes comprise one parameter, along with stage, age, and histology, for risk stratification systems that are used for children with neuroblastoma, in order to tailor therapy more precisely for each patient …”

Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma

“…In line with this, a recent study shows that a subset of high-risk neuroblastomas display upregulated cMyc due to enhancer hijacking, and overexpression of cMyc under the DβH promoter induced tumor mass growth in vivo in zebrafish (61). cMyc amplification is extremely rare in neuroblastoma, but a case study reports undifferentiated morphology, poor survival, and low levels of MycN expression in these tumors (62). These studies further support our hypothesis that physiological rather than overexpressed cMyc levels are associated with the better outcome of the disease.…”

Pathology of Peripheral Neuroblastic Tumors

“…Due to the presence of prominent nucleoli, indicative of hyperactive rRNA synthesis and protein translation, MYC-driven neuroblastomas are morphologically distinguishable from the conventional neuroblastomas with so-called "saltand-pepper" nuclei. In contrast to n-MYC overexpressing neuroblastoma, it is extremely rare to see the gene amplification in c-MYC overexpressing neuroblastoma [59]. In this regard, other molecular mechanisms for high c-MYC protein expression independent of the genomic amplification, such as the oncogene activation through enhancer hijacking by translocations, focal enhancer amplification near to the c-MYC-coding region (8q24) or MK2-mediated OCT4 transcriptional activation of the c-MYC gene, have been reported [60,61].…”