Context: Adrenocortical cancer (ACC) is a rare disease with an often fatal outcome. The clinical and pathological diagnosis of a malignant vs. benign adrenocortical tumors is sometimes challenging. Telomere maintenance mechanisms (TMM) are critical for the persistence of the malignant phenotype, but little is known about these mechanisms or their diagnostic value in adrenocortical lesions.

Objective: Tissue samples of diagnostically known adrenocortical neoplasms were evaluated for parameters of known TMMs, telomerase activity (TA) and alternative telomere lengthening (ALT).

Design: The study analyzed retrospectively collected frozen adrenocortical tissue samples from the University of Michigan Health System.

Patient Samples: 24 ACCs, 11 adrenocortical adenomas (ACAs), 3 normal adrenal tissues (NATs).

Main outcome measures: Telomerase activity (TRAP assay), alternative telomere lengthening (telomere restriction fragment analysis, telomere associated PML bodies)

Results: 22/24 (96%) ACCs could be definitively assigned to a TMM. The TMM classification was: 19/24 (79%) TA positive, two of which displayed very long telomeres, 1/24 (4%) ALT positive and 2/24 (8%) positive for both TA and ALT. Results of 2/24 (8%) were inconclusive (1 negative for TA and positive in one ALT assay, 1 negative in all assays). None of the NAT (0/3) or ACA (0/11) samples had signs of an active TMM.

Conclusions: TA is the main TMM in the majority of ACCs, but subsets of ACCs additionally or exclusively exhibit signs of ALT. Determination of telomere maintenance mechanisms in diagnostically challenging adrenocortical tumors might be of additional diagnostic value in the pathological diagnosis of malignant vs. benign lesions.