Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of adrenocortical tumors?

Adrenal incidentalomas are detected more frequently with high-resolution imaging modalities. It is difficult to distinguish between benign and malignant lesions despite the so-called histologic Weiss criteria, imaging features, and molecular studies. We here present a 52 yr-old man who was found to have an adrenal incidentaloma during an annual check-up at his urologist. An 8 cm large adrenal lesion was detected on ultrasound, computed tomography, and magnetic resonance imaging with imaging features suggestive of malignancy. The lesion was hormonally inactive. A left-sided adrenalectomy was performed and histologic grading revealed a Weiss score of 2, suggesting a benign tumor. However, on further follow-up, the patient developed a local recurrence and pulmonary metastases diagnosed 6 yr after initial presentation. After repeat surgery in the left adrenal bed adrenocortical tumor tissue had a Weiss score of 8, clearly suggesting histologic malignancy. The patient received adjuvant mitotane therapy. Under this therapy, he developed a right-sided adrenal mass (contralateral from the primary tumor) of 2 cm size which disappeared during the following 9 months, whereas the pulmonary metastases remained unchanged, suggesting tumor clones with a variable response to treatment or spontaneous apoptosis. This case suggests that adrenal incidentalomas larger than 6 cm with imaging features such as intratumoral necrosis suggestive of malignancy, should be managed as potential cancers independent of the so-called Weiss criteria. In such patients, close follow-up examinations including high-resolution imaging (preferably 3 monthly) are needed and should be carried out by a physician familiar/specialized in endocrine oncology.