Virilizing sclerosing-stromal tumor of the ovary in a young woman with McCune Albright syndrome: clinical, pathological, and immunohistochemical studies.
BACKGROUND
McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait skin pigmentations, and gonadotropin-independent sexual precocious puberty, resulting from a somatic postzygotic activating mutation of the GNAS1 gene.


METHODS
We report a virilizing sclerosing-stromal tumor of the ovary in a young female with MAS.


METHODS
She presented polyostotic fibrous dysplasia of the left upper and lower limbs and a café-au-lait skin spot in the posterior area of the neck. She had a history of precocious puberty, diagnosed at the age of 6 years and treated with cyproterone acetate until the age of 10 years; then she developed central puberty with severe oligomenorrhea. At the age of 23 years, she was hospitalized for a virilization syndrome including hirsutism, acne, deepening of the voice, amenorrhea, and clitoromegaly. Serum levels of T were dramatically increased (1293 ng/dl; normal range, 10-80). The abdominal computed tomography scan revealed a solid mass located on the left ovary.


METHODS
An ovariectomy was performed, and histological examination revealed a sclerosing-stromal tumor with pseudolobular pattern.


RESULTS
Immunohistochemical studies revealed that the tumor cells expressed all steroidogenic enzymes involved in androgen synthesis. Molecular analysis revealed that ovarian tumor cells harbored the Arg 201 activating mutation in the GNAS1 gene. After surgery, T levels returned to normal, the patient retrieved a normal gonadal function, and she was able to become pregnant.


CONCLUSIONS
This observation extends the clinical spectrum of ovarian pathology of women with MAS. However, the mechanisms causing this ovarian tumor remain unclear, even if the gsp oncogene has been implicated in the pathogenesis of some gonadal tumors.
Department of Endocrinology and Metabolic Diseases, Centre Hospitalier Universitaire Rangueil-Larrey, 24 Chemin de Pourvouville, TSA 30030, 31059 Toulouse Cedex 9, France.
Kahina
K
Boussaïd
Geri
G
Meduri
Jean-Christophe
JC
Maiza
Isabelle
I
Gennero
Ghislaine
G
Escourrou
Arnaud
A
Bros
Pierre
P
Leguevaque
Antoine
A
Bennet
Philippe
P
Caron
D000293:Adolescent; D002648:Child; D002864:Chromogranins; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts; D011629:Puberty, Precocious / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014770:Virilism / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D002864:Chromogranins; D010936:Plant Extracts; C500217:younggaechulgam-tang; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs