title: Somatic RET mutation in a patient with pigmented adrenal pheochromocytoma.
abstract: Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic 'black' pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed.
  
  
  CONCLUSIONS
  Pheochromocytoma is a rare neuroendocrine tumor.Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin.
authors: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München , Munich , Germany.
authors: Nicole
authors: N
authors: Maison
authors: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam , Rotterdam , The Netherlands.
authors: Esther
authors: E
authors: Korpershoek
authors: Department of Medicine III, Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden , Dresden , Germany.
authors: Graeme
authors: G
authors: Eisenhofer
authors: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER) , Madrid , Spain.
authors: Mercedes
authors: M
authors: Robledo
authors: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands.
authors: Ronald
authors: R
authors: de Krijger
authors: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München , Munich , Germany.
authors: Felix
authors: F
authors: Beuschlein