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Horm Metab Res 2020; 52(11): 784-787
DOI: 10.1055/a-1186-0790
Endocrine Care

Pancreatic Neuroendocrine Neoplasm Associated with a Familial MAX Deletion

Sandrine Petignot
1   Department of Endocrinology, Liège Université, Liège, Belgium
,
Adrian F. Daly 
1   Department of Endocrinology, Liège Université, Liège, Belgium
,
Emilie Castermans
2   Department of Human Genetics, Liège Université, Liège, Belgium
,
Esther Korpershoek
3   Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Irène Scagnol
4   Department of Pathology, Liège Université, Liège, Belgium
,
Pablo Beckers
2   Department of Human Genetics, Liège Université, Liège, Belgium
,
Vinciane Dideberg
2   Department of Human Genetics, Liège Université, Liège, Belgium
,
Vincent Rohmer
1   Department of Endocrinology, Liège Université, Liège, Belgium
,
Vincent Bours
2   Department of Human Genetics, Liège Université, Liège, Belgium
,
Albert Beckers
1   Department of Endocrinology, Liège Université, Liège, Belgium
› Author Affiliations Funding Information This work was funded by grants from the FIRS 2018–2019, CHU de Liège, and from the JABBS Foundation, UK (to Albert Beckers).
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Abstract

Most pancreatic neuroendocrine neoplasms (pNEN) occur sporadically but they can also occur as part of multiple endocrine neoplasia type 1 (MEN1). MAX was originally described as an inherited pheochromocytoma-paraganglioma risk gene, but also has recently been implicated in pituitary tumorigenesis. Here we describe the first case of a pNEN associated with an inherited MAX gene deletion in a family with endocrine tumors. The patient was a male carrier of an intragenic exon 3 deletion inherited from his father who had recurrent pheochromocytomas and a macroprolactinoma. The patient underwent screening and hormonal studies but no pheochromocytoma-paraganglioma, pituitary or renal tumors were identified. However, abdominal magnetic resonance imaging (MRI) identified a 1 cm lesion in body of the pancreas. The lesion was hyperintense on T2-weighted signal, and there was hyperfixation of the tumor on 68Ga-DOTANOC PET-CT images. No biochemical evidence of pancreatic hormone excess was identified. Following a guided biopsy, a pathological diagnosis of a low grade pNEN was made and immunohistochemistry showed loss of MAX nuclear staining. Genetic analysis of the tumor tissue indicated copy number neutral loss of heterozygosity consistent with uniparental disomy. This is the first reported case of a MAX deletion associated pNEN and strengthens the argument that MAX may represent an inheritable multiple endocrine neoplasia risk gene. Further analysis of germline and somatic MAX mutations/deletions in large cohorts of unexplained NEN cases could help clarify the potential role of MAX in NEN etiology.

Key words

familial - MAX - pancreatic neuroendocrine neoplasm - pituitary - pheochromocytoma


Publication History

Received: 09 March 2020

Accepted after revision: 18 May 2020

Article published online:
10 June 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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