MEN1, autosomal dominant, is characterized by combined tumours of the parathyroid glands, pancreatic islet cells, and the anterior pituitary, sometimes associated with other endocrine (adrenocortical, foregut carcinoid) and nonendocrine (lipoma, angiofibroma, collagenoma, ependymoma, meningioma) tumors. It is caused by inactivating mutations of the MEN1 tumour suppressor gene (chromosome 11q13), encoding menin. Menin, involved in activation of gene transcription, regulates PPARg-dependent adipocyte differentiation (Dreijerink Mol Cell Biol 2009), whereas PPARg is expressed in several MEN1-related tumor types.
We report two cases of unrelated obese male patients presenting with aggressive MEN1 and large either hibernoma or lipoma. Case 1, 39-year-old, without any family history, was diagnosed with ZollingerEllison syndrome with high gastrin, pancreatic polypeptide and glucagon level, invasive macroprolactinoma, groin angiofibromas, 5 cm adrenal mass and hyperparathyroidism. MEN1 gene analysis showed two not-indexed heterozygous mutations (exon 2AB: c105G>AA/exon 3: c737_740del). At 43 years old, increasing size of the pancreatic nodules, and pancreatic and right thigh PET-FDG uptake led to i) total pancreatectomy (13 neuroendocrine pancreatic tumors (pT2MN1: 11 G1, one G2, one G3)), ii) left adrenalectomy (Weiss 0), and iii) thigh hibernoma resection. Case 2, 25-year-old, belonging to a MEN1 family (c.1546dupC/pArg516ProfsX15), was diagnosed with severe hyperparathyroidism (with ectopic parathyroid gland), five pancreatic endocrine tumors (with hyperglucagonemia) and a 13 cm FDG-negative lipoma of the left iliac muscle.
In conclusion, hibernomas are benign tumors with morphological features resembling brown fat. Their PET-FDG uptake raises differential diagnosis issues with liposarcomas and metastasis. As lipomas (Vortmeyer J Natl Cancer Inst 1998), they consistently display cytogenetic rearrangements, involving chromosome band 11q13 (Gisselsson Am J Pathol 1999). MEN1 display a low expression in hibernomas whereas the expression of genes up-regulated in brown fat (PPARg, UCP1) is high (Nord PNAS 2011). These associations raise the question of the relationship between adipose tissue and cancer genesis or MEN1 aggressiveness.
27 Apr - 01 May 2013
European Society of Endocrinology