Investigating the clinical, pathological and molecular profile of oncocytic adrenocortical neoplasms: a case series and literature review

Eleanor Fewings; Serena Khoo Sert Kim; Alexey Larionov; Alison Marker; Olivier Giger; Ashley Shaw; Graeme R Clark; Vasilis Kosmoliaptsis; Benjamin G Challis; Marc Tischkowitz; Ruth T Casey

doi:10.1530/EO-21-0011

Investigating the clinical, pathological and molecular profile of oncocytic adrenocortical neoplasms: a case series and literature review

Endocr Oncol. 2021 Aug 16;1(1):33-44. doi: 10.1530/EO-21-0011. eCollection 2021 Jan.

Authors

Affiliations

¹ Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
² Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
³ Department of Histopathology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
⁴ Department of Pathology, University of Cambridge, Cambridge, UK.
⁵ Department of Radiology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
⁶ Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁷ East Anglian Medical Genetics Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.

Abstract

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.

Keywords: Lin-Weiss-Bisceglia system; malignant; oncocytic adrenocortical neoplasms; oncocytic tumours.