Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations.
BACKGROUND
The von Hippel-Lindau (VHL) syndrome is an inherited multitumour disorder characterized by clinical heterogeneity and high penetrance. Pheochromocytoma (Pheo) is present in 10%-15% of cases and can be isolated or associated with other lesions such as haemangioblastomas, kidney cysts or cancer and pancreatic lesions. In VHL patients, Pheos generally secrete norepinephrine and are located in the adrenals. Extra-adrenal Pheos (paragangliomas, PGLs) are rare.


OBJECTIVE
While performing genetic testing in patients affected by apparently sporadic Pheos or PGLs, we found two novel different VHL germline mutations in two females who presented with two distinct very uncommon clinical pictures. One patient was studied for the presence of an adrenal incidentaloma and the other for the presence of a neck tumour.


RESULTS
Patients coding regions and exon-intron boundaries of RET (exons 10, 11, 13-15), VHL, SDHD, SDHB and SDHC genes were amplified and sequenced. We identified two novel VHL point mutations: a L198V missense mutation in a 32-year-old female affected by a right adrenal compound and mixed tumour constituted by an epinephrine secreting Pheo, a ganglioneuroma and an adrenocortical adenoma, and a T152I missense mutation in a 24-year-old female affected by a left carotid body tumour. No other lesions were found in the patients or in the VHL mutation positive relatives.


CONCLUSIONS
These cases enlarge the list of VHL mutations and add new insights in the clinical variability of VHL disease, thus confirming the importance of genetic testing in patients affected by apparently sporadic Pheos or PGLs.
Ercolino
Tonino
T
Department of Clinical Physiopathology, Division of Endocrinology, University of Florence, Florence, Italy.
Becherini
Lucia
L
Valeri
Andrea
A
Maiello
Michele
M
Gaglianò
Maria Sole
MS
Parenti
Gabriele
G
Ramazzotti
Matteo
M
Piscitelli
Elisa
E
Simi
Lisa
L
Pinzani
Pamela
P
Nesi
Gabriella
G
Degl'Innocenti
Donatella
D
Console
Nico
N
Bergamini
Carlo
C
Mannelli
Massimo
M
D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; C108825:VBP1 protein, human