Clinical and genetic characteristics of patients with adrenocortical carcinoma and lynch syndrome

MD Avilasha Sinha,; MD Katherine I. Wolf,; MS, CGC Jenae Osborne,; MD, PhD Anthony J. Scott,; NP Elizabeth A. Hesseltine,; MD Francis P. Worden,; MD, PhD Thomas Giordano,; MD, PhD Gary D. Hammer,; MD Tobias Else,

doi:10.1530/endoabs.107.008

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Endocrine Abstracts (2024) 107 008 | DOI: 10.1530/endoabs.107.008

IACS9 9th International Adrenal Cancer Symposium 2024 Abstracts (18 abstracts)

Clinical and genetic characteristics of patients with adrenocortical carcinoma and lynch syndrome

Avilasha Sinha, MD¹, Katherine I. Wolf, MD², Jenae Osborne, MS, CGC³, Anthony J. Scott, MD, PhD³, Elizabeth A. Hesseltine, NP^2,4, Francis P. Worden, MD⁴, Thomas Giordano, MD, PhD⁵, Gary D. Hammer, MD, PhD^2,4 & Tobias Else, MD^2,3,4

Author affiliations

¹Department of Internal Medicine, University of Michigan, USA ²Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, USA ³Division of Medical Genetics, Department of Internal Medicine, University of Michigan, USA ⁴Endocrine Oncology Program, Rogel Cancer Center, University of Michigan, USA ⁵Department of Pathology, University of Michigan, USA

Background: Lynch syndrome (LS), caused by MMR gene pathogenic variants (PVs), is the most common hereditary cancer syndrome observed in patients with ACC, but little is known about the clinical and genetic characteristics of patients with ACC and LS.

Objectives: To describe the clinical and genetic characteristics of ACC in patients with LS.

Methods: The EMR and local registries of patients at the University of Michigan were searched using defining keywords (e.g., ‘Lynch Syndrome’, ‘adrenocortical carcinoma’) and provider names through the EMERSE software. Patients with ACC and rare MMR germline variants were included in the study.

Results: 31 patients with ACC and rare MMR germline variants were identified, of which, 30 patients (97%) had rare germline variants in one MMR gene, (20 [65%] PV [12 MSH2, 1 MLH1, 7 MSH6], 9 [29%] variants of uncertain significance/VUS [3 MSH2, 3 MSH6, 3 PMS2], and 1 patient had rare variants in 2 MMR genes (MSH6 [VUS] and PMS2 [benign variant]). 21 patients (68%) were diagnosed at stages I-III vs. 10 patients (32%) at stage IV. 18 patients (58%) had tumor mitotic rates > 20/50 per HPF and 16 patients (52%) had tumor Ki67 > 20%. 18 patients (58%) had hormone excess (5 cortisol, 5 androgen, 2 aldosterone, 6 cortisol and androgen). 5 patients (16%) had other LS-associated malignancies (4 of these patients with PV, 1 with VUS) and 22 patients (71%) had a family history of LS-associated malignancies (16 with PV, 5 patients with VUS, 1 patient with a benign variant). Only 3 patients (10%) met Amsterdam I criteria (all 3 with PV). 13 patients (42%) met Amsterdam II criteria, including ACC as a Lynch-associated cancer (12 PV, 1 VUS). The prevalence of LS in ACC patients was estimated as 3 - 4%.

Discussion: This analysis further supports the association of ACC with Lynch syndrome. Only a minority of patients fulfilled classical diagnostic criteria (Amsterdam I & II), justifying a general testing recommendation for all ACC patients regardless of family history.