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

Abstract

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.

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

“…For tumours of the adrenal cortex, the chance on malignant behaviour increases with tumour size. The differentiation between ACC and ACA on histopathological grounds can be challenging, by both a poor reproducibility and by tumours classified as being of uncertain malignant behaviour (Pohlink et al 2004, Tan et al 2005, Klibanski et al 2006, Giordano 2010. Mitotane treatment is given to prevent disease recurrence in patients with malignant adrenal tumours but is associated with serious toxicity (Lacroix 2010, Fassnacht et al 2013.…”

Adrenocortical cancer: pathophysiology and clinical management

“…Since the initial paper of Weiss (1984), it is assumed that a score above 3 is most likely to be associated with a malignant tumor. However, there is often a strong doubt for malignancy for scores at 3 and even in some rare cases 2 (Pohlink et al 2004). Since the Weiss score has limitations and it is dependant on the experience of the pathologist, there is an effort to develop molecular markers of malignancy.…”

Bilateral Primary Adrenal Non-Hodgkin's Lymphoma and Primary Adrenocortical Carcinoma - Review of the Literature Preoperative Differentiation of Adrenal Tumors

“…Nevertheless, there are still special types of ACC to which Weiss criteria are not fully applicable (e.g. pediatric adrenocortical tumors, oncozytomas, aldosterone-producing tumors of pure zona glomerulosa type) [30,32]. Important additional in-formation is gained from immunohistochemical stainig.…”