Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene.

The objective of this study was to describe a familial screening for AIP
mutations in the context of aggressive prolactinoma in childhood. A 12-year-old
boy, presented headaches and bilateral hemianopsia. He had adequate height and
weight for his age (50(th) percentile), Tanner stage G1 P1. His bone age was 10
years. Prolactin was 10.560 ng/mL (3-25), FSH and LH were undetectable, IGF-1,
TSH, Free T4, ACTH, and cortisol were within normal ranges. MRI showed a
pituitary macroadenoma, 5.3 X 4.0 X 3.5 cm with compression of the optic chiasm,
bilateral cavernous sinus invasion, encasement of carotids, and extension to
clivus. Surgical debulking was performed. Resistance to cabergoline was
characterized and he was submitted to two surgeries and radiotherapy.
Immunohistochemical evaluation included prolactin, ACTH, GH, FSH, LH,AIP, c-erb
B2, Ki-67, and p53. Genomic DNA was isolated from the index case and 48
relatives, PCR and sequencing were performed.A germline A195V mutation in AIP was
identified in the index case and in five asymptomatic relatives. Germline
mutations in the AIP gene may be involved in the predisposition to pituitary
adenoma formation, as cause or co-factor in pathogenesis of aggressive tumors in
young patients.