Adrenal cortical carcinomas are not usually graded on histologic grounds. Severe nuclear atypia, high mitotic count, vascular invasion, tumor necrosis, and other microscopic features may, in combination, support a diagnosis of adrenal cortical carcinoma and should be recorded. When several malignant features are present together (eg, highly atypical nuclei, trabecular growth, necrosis, and many mitoses), the risk of distant metastases is increased. In some studies, specific combinations of features, such as mitotic rates of >5 per 50 high-power fields (HPF) along with atypical mitosis and venous invasion, have been found to correlate with metastasis or recurrence of adrenal cortical carcinomas. Other studies have shown that mitotic rates greater than 20 per 50 HPF are associated with decreased survival, suggesting that a high mitotic index may be an important adverse prognostic factor.
The criteria used in adults to separate benign from malignant cortical tumors are not entirely applicable to adrenocortical tumors in pediatric age groups. Further, pediatric adrenocortical neoplasms showing histologic features worrisome for malignancy in adults (eg, capsular invasion, vascular invasion, increased mitotic activity, atypical mitoses, necrosis) may not be predictive of biologic behavior; such a pediatric adrenocortical neoplasm exhibiting such histologic features may have a clinically benign course. A number of classification schemes attempting to separate benign from malignant pediatric adrenocortical tumors have been proposed. One of these studies is based on the presence (carcinoma) or absence (adenoma) of 4 histologic features (modified Weiss system) including high nuclear grade, necrosis, mitotic rate greater than 5 per 50 HPF, and atypical mitoses; another study found that tumor weight was the only reliable predictor of behavior, with tumors weighing over 500 g being malignant; and another study correlated tumor volume of greater than 200 cm3 and weight greater than 80 g associated with an adverse outcome. Subsequent to these studies, another study proposed classifying pediatric adrenocortical neoplasms based on a series of 9 criteria including tumor weight greater than 400 g, tumor size greater than 1.5 cm, extension into periadrenal soft tissues and/or adjacent organs, invasion into the vena cava, venous invasion, capsular invasion, presence of tumor necrosis, mitotic rate greater than 15 per 20 HPF, and the presence of atypical mitoses; based on this study, the presence of up to 2 of these criteria was associated with a benign outcome, 3 criteria were considered indeterminate for malignancy, and 4 or more criteria were associated with malignant behavior.
Although this protocol does not cover medullary tumors, it should be noted that pheochromocytoma is usually diagnosed preoperatively by clinical and laboratory means. Metastatic disease is considered the standard proof of malignancy, but recently a constellation of histologic features that can be used to predict malignant has been proposed.
Although this protocol does not cover medullary tumors, it should be noted that pheochromocytoma is usually diagnosed preoperatively by pharmacologic means. No pathologic criteria for differentiation of benign from malignant pheochromocytomas have been defined. Metastatic disease is considered the only irrefutable proof of malignancy.
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