Pathological and Genetic Characterization of Bilateral Adrenomedullary Hyperplasia in a Patient with Germline MAX Mutati
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Pathological and Genetic Characterization of Bilateral Adrenomedullary Hyperplasia in a Patient with Germline MAX Mutation Pauline Romanet 1 & Carole Guerin 2 & Pascal Pedini 1 & Wassim Essamet 3 & Frédéric Castinetti 4 & Fréderic Sebag 2 & Philippe Roche 5 & Alberto Cascon 6 & Arthur S. Tischler 7 & Karel Pacak 8 & Anne Barlier 1 & David Taïeb 9
# Springer Science+Business Media New York 2016
Abstract In recent years, familial pheochromocytoma (PHEO) with germline mutations in the MAX (MYC associated factor X) gene has been reported in a few cases. Here, we investigated a 25–year-old patient with multiple PHEOs associated with a nonsense germline MAX mutation. Preoperative 18F-FDOPA PET/ CT revealed bilateral adrenal involvement with multiple tumors. In addition, both adrenal glands were found to have diffuse or nodular adrenal medullary hyperplasia (AMH), a histopathological feature previously described as a precursor of MEN2- and SDHB-related PHEOs but not MAX. After bilateral adrenalectomy, different paraffin-embedded and frozen samples were analyzed for allelic imbalances of the MAX gene using allelic quantification by pyrosequencing. The expression of the protein MAX was studied by immunohistochemistry. All PHEOs but also nodular AMH exhibited a loss of the normal allele. By contrast, the diffuse AMH did not show loss-of-heterozygosity. Nevertheless, immunohistochemistry demonstrated loss of
protein MAX expression in all samples including diffuse hyperplasia, suggesting a causative role of MAX mutation for both PHEOs and AMH. The present case shows that both nodular and diffuse AMH belongs to the spectrum of MAX-related disease. These data support the possible continuum between nodular AMH and PHEO, expanding the qualification of microPHEO to nodular AMH. Keywords Pheochromocytoma . MYC-associated factor X . MAX . Adrenal medullary hyperplasia
Introduction Pheochromocytomas (PHEOs) are neural crest-derived catecholamine-secreting tumors arising from the adrenal medulla. They belong to the family of pheochromocytoma/
Electronic supplementary material The online version of this article (doi:10.1007/s12022-016-9460-5) contains supplementary material, which is available to authorized users. * David Taïeb [email protected] 1
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Laboratory of Molecular Biology, Aix Marseille University CNRS, CRN2M, Marseille, France & APHM Conception, 13385 Marseille, France
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
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Department of Endocrine Surgery, Aix-Marseille University Marseille, France & APHM Conception, 13284 Marseille, France
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA
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Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA
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Department of Nuclear Medicine, La Timone University Hospital & CERIMED & Inserm UMR1068 Marseille
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