Search Results
Search for other papers by Eleanor Fewings in
Google Scholar
PubMed
Search for other papers by Serena Khoo Sert Kim in
Google Scholar
PubMed
Search for other papers by Alexey Larionov in
Google Scholar
PubMed
Search for other papers by Alison Marker in
Google Scholar
PubMed
Search for other papers by Olivier Giger in
Google Scholar
PubMed
Search for other papers by Ashley Shaw in
Google Scholar
PubMed
Search for other papers by Graeme R Clark in
Google Scholar
PubMed
Search for other papers by Vasilis Kosmoliaptsis in
Google Scholar
PubMed
Search for other papers by Benjamin G Challis in
Google Scholar
PubMed
East Anglian Medical Genetics Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Search for other papers by Marc Tischkowitz in
Google Scholar
PubMed
Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Search for other papers by Ruth T Casey in
Google Scholar
PubMed
Background
Malignant oncocytic adrenocortical neoplasms (OANs) are rare tumours with a distinctive biological behaviour compared to conventional adrenocortical carcinoma (ACC). The current prognostic systems overestimate the malignant potential of these tumours, and guidance for surveillance and treatment strategies are lacking.
Aim
To evaluate the utility of clinical, pathological and molecular markers in predicting the biological behaviour and outcomes of malignant OANs.
Methods
A retrospective clinicopathological review of 10 histologically confirmed OANs was carried out. Whole exome sequencing (WES) of germline and paired tumour samples was performed for four of the ten OAN cases and compared to WES data from five cases of conventional ACC and data from The Cancer Genome Atlas. We reviewed all the cases of malignant OAN reported in the literature and compared to our case series.
Results
Eight (80%) tumours were classified as malignant, one borderline and one benign (Lin–Weiss–Bisceglia criteria, LWB). The malignant OAN were larger tumours and had higher MIB index and Helsinki scores. Molecular profiling identified a pathogenic germline variant in MSH6 in an individual in the OAN group. The OAN samples had a lower mutation burden compared to the ACC samples. Somatic driver variants were identified in OAN and ACC samples including a pathogenic missense variant in CTNNB1.
Conclusion
In this study, the LWB classification demonstrated sensitivity for the differentiation of benign from malignant OAN. Molecular profiling identified dysregulation in DNA repair and Wnt signalling pathways in both OAN and ACC samples, suggesting a molecular overlap between OAN and conventional ACC.
