Pheno-MYCN maps the morphological footprint of MYCN amplification in paediatric neuroblastoma
Year: 2026
Type: preprint
Abstract: MYCN amplification and segmental chromosomal abnormalities have long been prognostic markers in paediatric neuroblastoma, and are often accompanied by morphological changes that portend high-risk disease. Yet quantitative morphological assessment is limited to countable features, such as the mitosis-karyorrhexis index. Other high-risk features, such as nuclear size, pleomorphism and anaplasia, lack formal criteria. This leaves a gap: current simple pathology metrics cannot capture, or localise, the full morphological landscape of high-risk biology, such as disease driven by MYCN. Seeking high-risk cases that standard criteria may miss, we developed Pheno-MYCN, a weakly supervised framework linking slide-level MYCN prediction on 189 H&E whole-slide images to interpretable phenotypic sub-populations that expert review mapped to neuroblastoma morphologies. The aim is not a stronger classifier, but to reveal the morphological basis of MYCN prediction. Cell-level profiling found MYCN-associated differences across sub-populations. Amplified tumour was densely cellular but disorganised, with less connected networks, lower cellular diversity and greater abundance of haemorrhagic and acellular necrotic regions. MYCN-amplified-like tissue was identifiable per slide from these features alone (AUC 0.93-1.00, leave-one-slide-out) and traced as a continuous gradient within tumours. Thus MYCN amplification leaves a concrete, interpretable footprint, readable and localisable on routine H&E.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7203923740