Ovarian lesions in Carney complex: Clinical genetics and possible predisposition to malignancy

Carney complex (CNC) is a familial multiple neoplasia and lentiginosis synd rome (OMIM 160980, http ://www.ncbi.nlm.nih.gov/omim) with features overlap ping those of other multiple endocrine neoplasias and hamartomatoses, Peutz -Jeghers syndrome (PJS) in particular. Although a number of patients with C NC and ovarian tumors have been described in individual patient reports, it is unclear whether ovarian lesions constitute a component of the syndrome or are coincidental events. We investigated 18 women with CNC [age at first evaluation, 31.3 +/- 12.1 yr (mean +/- SD)] prospectively for the developm ent of ovarian tumors over a period of 35.7 +/- 30.6 months by physical exa mination and pelvic ultrasonography. They were compared with 11 women (age at first evaluation, 32.9 +/- 17 yr) who were enrolled under the same proto col (follow up, 32.3 +/- 25.1 months) and served as a control group. In add ition, a registry of 178 women from among a total of 309 patients with CNC was searched retrospectively for any having ovarian tumors. Seven available histological specimens were rereviewed. None of the CNC patients had ovari an tumors analogous to those of PJS. Two patients with CNC in the prospecti ve group developed ovarian tumors and were operated upon. One had bilateral oophorectomy for asynchronous serous cystadenomas. The second patient had a unilateral serous cystadenoma. Resected tumor tissue from both patients w as tested for genetic abnormalities of the chromosomal regions to which CNC genetic loci have been mapped. Both showed genomic amplification of chromo somal region 2p16. An additional 10 patients had at least 1 sonogram positi ve for ovarian cysts. Only 1 of the patients in the control group was found to have a persistent, simple ovarian cyst by ultrasonography. The registry of 178 CNC patients included 4 who had undergone surgery for ovarian tumor s. The diagnoses included endometrioid adenocarcinoma (1 patient) and metas tatic mucinous adenocarcinoma (the primary site was probably ovarian; 1 pat ient). In addition, 7 of 12 patients (58%) with CNC, who died of other caus es, had ovarian lesions at autopsy. In conclusion, although the same stroma l tumor, large-cell calcifying Sertoli cell tumor; affects the testes in CN C and PJS, we did not find such tumors in a small population of CNC patient s that was studied prospectively or a larger group of CNC patients that was studied retrospectively. The results of our study also suggested that wome n with CNC commonly develop ovarian cysts and may be at risk for ovarian ca rcinoma. The chromosome 2p16 CNC locus was involved in ovarian pathology wi th apparent copy number gain, suggesting that at least molecularly there is some involvement of the CNC gene(s) in these lesions. Although ovarian tum ors do not seem to be a major manifestation of CNC, sonography of the ovari es may be part of the initial evaluation for this genetic syndrome in women with CNC; follow-up of any identified lesion is recommended because of the possible risk for malignancy.