How to Differentiate Benign from Malignant Adrenocortical Tumors?

Abstract

Adrenocortical carcinoma (ACC) is a rare cancer with a poor prognosis. Adrenal incidentalomas are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance considering the large differences in clinical behavior requiring different strategies. Diagnosis of ACC starts with a thorough physical examination, biochemical evaluation, and imaging. Computed tomography is the first-level imaging modality in adrenal tumors, with tumor size and Hounsfield units being important features for determining malignancy. New developments include the use of urine metabolomics, also enabling discrimination of ACC from adenomas preoperatively. Postoperatively, the Weiss score is used for diagnosis of ACC, consisting of nine histopathological criteria. Due to known limitations as interobserver variability and lack of accuracy in borderline cases, much effort has been put into new tools to diagnose ACC. Novel developments vary from immunohistochemical markers and pathological scores, to markers at the level of DNA, methylome, chromosome, or microRNA. Molecular studies have provided insights into the most promising and most frequent alterations in ACC. The use of liquid biopsies for diagnosis of ACC is studied, although in a small number of patients, requiring further investigation. In this review, current diagnostic modalities and challenges in ACC will be addressed.

Was It an Adrenocortical Adenoma or an Adrenocortical Carcinoma? Limitation of the Weiss Scoring System in Determining the Malignant Potential of Adrenocortical Tumor: Report on Two Cases

“…The presence of three or more of which was reported to be highly correlated with subsequent malignant behavior and is diagnostic of ACC [ 10 ]. The reported sensitivity and specificity were about 86–95% and 90%, respectively in expert hands [ 14 ]. However, borderline cases of adrenocortical neoplasm with uncertain malignant potential may challenge the reliability of the Weiss system, and these tumors often have a Weiss score of 1–3 [ 2 , 8 , 11 ].…”

“…Being easier to use in clinical practice and more reproducible, the modified Weiss score has a reported specificity of 96.9% (vs. 90.2% in the original score) [ 7 ]. More recently, the reticulin algorithm and the Helsinki score ( Table 3 ) have been validated and are shown to be highly accurate in differentiating between benign and malignant adrenocortical tumors with 100% or nearly 100% sensitivity and specificity [ 3 , 4 , 14 ]. The rationale of the reticulin algorithm relies on the histochemical assessment of the reticulin network, which is commonly disrupted in ACC [ 12 ].…”

“…Other histopathological algorithm and scoring system, namely, the reticulin algorithm and Helsinki score, are recently developed and validated [ 12 , 13 ]. They are shown to be highly accurate in differentiating between benign and malignant adrenocortical tumors with almost 100% or nearly 100% sensitivity and specificity, but their routine use is yet to be widely adopted [ 14 ]. Nevertheless, certain clinical, biochemical, and radiological features may provide physicians with important complementary information to predict the malignant potential of an adrenocortical tumor.…”

Association of Nrf2 expression and mutation with Weiss and Helsinki scores in adrenocortical carcinoma

“…[16][17][18][19] A high expression of Nrf2 was reported to be associated with poor prognosis in ACC, 20 and an increased accumulation of 18 F-FDG was seen in the disease. 21 However, to date few studies have investigated the relationship of Weiss criteria and Helsinki score with Nrf2 from a metabolic perspective. In the present study, we found an association between a…”

Tissue miRNA Combinations for the Differential Diagnosis of Adrenocortical Carcinoma and Adenoma Established by Artificial Intelligence

“…The histological examination of adrenal tumors (including the Weiss-score and modified Weiss-score) is difficult and requires great expertise. Moreover, significant interobserver variability and a lack of accuracy in borderline cases are known limitations [ 8 ]. Mainly due to the difficulty of histological examinations, a biopsy of adrenal tumors is not recommended in routine practice and according to the current guidelines [ 3 , 5 ], as it would be difficult to determine malignancy from a small amount of tissue obtained, and there is a potential risk of complications (bleeding, pneumothorax) and maybe tumor dissemination as well [ 9 , 10 ].…”