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A Case Report in Favor of a Multistep Adrenocortical Tumorigenesis

Laboratoire d’Explorations Fonctionnelles Endocriniennes (C.G., V.G., Y.L.B.), Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France; Services d’endocrinologie (M.-H.B.), d’anatomopathologie (N.B.), et de chirurgie viscérale (J.-L.P.) des Hôpitaux de Lyon, 69321 Lyon, France; and Department of Molecular Medicine (S.S., D.J.M., B.G.R.), Kolling Institute of Medical Research and University of Sydney, St. Leonards, 2065 NSW Australia

Address all correspondence and requests for reprints to: Dr. Christine Gicquel, Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, 26 Avenue Arnold Netter, 75012 Paris, France. E-mail: christine.gicquel{at}trs.ap-hop-paris.fr.

Abstract

The mechanisms of adrenocortical tumorigenesis are still not fully understood. Data from clonal analysis, comparative genomic hybridization, and allelotyping suggest that it involves a multistep process during which several genetic defects are progressively acquired, leading to the malignant transformation. The events involved in the first steps of this process are not well known, and most of the abnormalities described in adrenocortical tumors to date are associated with the malignant phenotype. We report a case that suggests that adrenocortical tumorigenesis may be a multistep process. A 43-yr-old patient underwent surgery for an incidentally discovered adrenal mass. Pathological analysis showed that this tumor consisted of two parts: a central part with features of malignancy surrounded by another part with a strictly benign appearance. These data were confirmed by molecular analysis and comparative genomic hybridization that were consistent with either a malignant or benign presentation. The apparently malignant part of the tumor exhibited molecular abnormalities [17p13 loss of heterozygosity (LOH), 11p15 uniparental disomy and overexpression of the IGF-II gene] as well as chromosomal gains and losses (comparative genomic hybridization) that have been previously described in malignant tumors. No abnormalities were found in the surrounding benign tissues. Although this observation is not definitive proof that adrenocortical tumorigenesis occurs via a multistep process, it suggests that there is a progressive change from the benign to the malignant state in some adrenocortical tumors.

Footnotes

This work was supported by the Assistance Publique Hôpitaux de Paris, the University Paris VI, Institut National de la Santé et de la Recherche Médicale (U515), and Programme Hospitalier de Recherche Clinique Grant AOM 95201 for the Comete Network.

Abbreviations: CGH, Comparative genomic hybridization; CT, computerized tomography; LOH, loss of heterozygosity.

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