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
