Adrenocortical Neoplasms 429 429 Departments of Laboratory Medicine and Pathology (LAE, LJ, TJS, RVL), Health Sciences Research (CL, VSP), and Surgery (MLK, JAvH, GBT, CSG) Mayo Clinic and Mayo Foundation, Rochester, Minnesota Address correspondence to: Dr. Ricardo V. Lloyd, Depart- ment of Laboratory Medicine and Pathology, Hilton 11, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Endocrine Pathology, vol. 12, no. 4, 429–435, Winter 2001 © Copyright 2001 by Humana Press Inc. All rights of any nature whatsoever reserved. 1046–3976/98/12:429–435/ $11.75 Pathologic Features and Expression of Insulin-like Growth Factor-2 in Adrenocortical Neoplasms Lori A. Erickson, MD, Long Jin, MD, Thomas J. Sebo, MD, PHD, Christine Lohse, BS , V. Shane Pankratz, P HD, Michael L. Kendrick, MD, Jon A. van Heerden, MD, Geoffrey B. Thompson, MD, Clive S. Grant, MD, and Ricardo V. Lloyd, MD, PHD Abstract We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic fea- tures and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carci- nomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expres- sion of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). In patients with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was associ- ated with decreased survival. Expresssion of IGF-2 was higher in adrenocortical carcino- mas than in adenomas (p < 0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic fea- tures are needed to establish the diagnosis in difficult cases. Key Words: Adrenocortical adenoma; adrenocortical carcinoma; insulin-like growth factor-2. Introduction Adrenocortical carcinomas are rare tumors that are associated with a high mortality. Although no single criterion other than metastasis or regional invasion is diagnostic of malignancy in adrenocor- tical neoplasms, a variety of clinical and pathologic criteria have been proposed for diagnosis, grading, and prognosis in adrenocortical neoplasms [1–5]. Clinical features include weight loss, urinary 17-ketosteroid levels, response to adreno- corticotropic hormone stimulation tests, and the presence of Cushing syndrome. Gross features include tumor size and tumor weight. Histologic features included diffuse growth pattern, eosinophilic tumor cell cytoplasm, vascular invasion (venous and/or sinusoidal invasion), necrosis, broad fibrous bands, capsular invasion, mitotic rate, atypical mitotic figures, and nuclear plenomorphism. T he systems suggested for Clinical Research