Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.
BACKGROUND
Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD (SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene). Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent.


METHODS
An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1.


RESULTS
Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL.


CONCLUSIONS
Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.
Boedeker
Carsten C
CC
Department of Otorhinolaryngology, Albert-Ludwigs-University, Freiburg D-79106, Germany.
Erlic
Zoran
Z
Richard
Stéphane
S
Kontny
Udo
U
Gimenez-Roqueplo
Anne-Paule
AP
Cascon
Alberto
A
Robledo
Mercedes
M
de Campos
José M
JM
van Nederveen
Francien H
FH
de Krijger
Ronald R
RR
Burnichon
Nelly
N
Gaal
José
J
Walter
Martin A
MA
Reschke
Kirsten
K
Wiech
Thorsten
T
Weber
Johannes
J
Rückauer
Klaus
K
Plouin
Pierre Francois
PF
Darrouzet
Vincent
V
Giraud
Sophie
S
Eng
Charis
C
Neumann
Hartmut P H
HP