American Journal of Medical Genetics 112:61–64 (2002) Clinical Report Complex Karyotypic Abnormality in Ovarian Fibroma Associated With Gorlin Syndrome Lynn M. Smith, 1 Ping Hu, 2 Larry J. Meyer, 3 and Cheryl M. Coffin 4 * 1 Department of Radiation Oncology, University of Utah Health Sciences Center, Salt Lake City, Utah 2 University of Utah School of Medicine, Geriatrics Research Education and Clinical Center, Salt Lake City, Utah 3 VAMC and Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah 4 Division of Pediatric Pathology, University of Utah Health Sciences Center and Primary Children’s Medical Center, Salt Lake City, Utah Nevoid basal cell carcinoma (NBCC) syn- drome is an autosomal dominant disorder characterized by distinctive congenital mal- formations and a variety of benign and malignant neoplasms, including ovarian fibromas. We describe pathologic and cyto- genetic findings in a large unilateral ovarian fibroma from a 12-year-old female with NBCC syndrome. The pathologic findings were characteristic for ovarian fibroma, but were unusual for the ovarian fibromas associated with NBCC syndrome because of the absence of calcification, the lack of bilaterality, and the presence of focal hypercellularity. The karyotype of tumor tissue showed complex numerical and structural abnormalities. Al- though there is frequent loss of heterozygo- sity of 9q22.3 and mutations in the PTCHgene in Gorlin syndrome, the ovarian fibroma in this case did not have cytogenetically detect- able abnormalities of chromosome 9. ß 2002 Wiley-Liss, Inc. KEY WORDS: ovarian fibroma; Gorlin syn- drome; nevoid basal cell car- cinoma syndrome INTRODUCTION Gorlin syndrome or nevoid basal cell carcinoma (NBCC) syndrome is a highly variable autosomal domi- nant disorder characterized by congenital malforma- tions and susceptibility to basal cell carcinoma (BCC) and occasionally other neoplasms early in life, including ovarian fibromas, medulloblastoma, cardiac fibroma, fetal rhabdomyoma, and rhabdomyosarcoma [Kraemer et al., 1984; Farndon et al., 1992; Shanley et al., 1994; Kimonis et al., 1997]. There is considerable variability in the phenotypic expression of the syndrome both within and between different families with Gorlin syndrome [Evans et al., 1993; Chidambaram et al., 1996; Shimkets et al., 1996; Wicking et al., 1997]. The gene for Gorlin syndrome or NBCC has been localized to 9q22.3 and subsequently cloned [Farndon et al., 1992; Hahn et al., 1996; Johnson et al., 1996]. The tumor suppressor gene, patched (PTCH), is a trans- membrane protein that activates intracellular proteins that control development and growth [Chidambaram et al., 1996; Hahn et al., 1996; Johnson et al., 1996; Shimkets et al., 1996; Wicking et al., 1997]. Evidence that mutation of the PTCH gene causes Gorlin syn- drome includes point mutations in families that cose- gregate with the disease and new mutations in PTCH in sporadic cases. By standard criteria, it seems to function as a tumor suppressor gene [Bale et al., 1998]; there is frequently loss of heterozygosity (LOH) at 9q22.3 in basal cell tumor tissue, compared to somatic tissue [Hahn et al., 1996]. In one case, a new mutation was found in the PTCH gene in one tumor, while LOH was noted in other cutaneous BCCs in the same patient. PTCH gene mutations have also been detected in odontogenic keratocysts [Barreto et al., 2000]. Other genetic abnormalities in neoplasms arising in the con- text of Gorlin syndrome have not been well characteriz- ed. This report illustrates an example of an ovarian fibroma with a complex karyotypic abnormality in an adolescent female with Gorlin syndrome. CLINICAL REPORT Clinical History The patient was diagnosed with hereditary Gorlin syndrome at the age of 9 years after a biopsy of a BCC. *Correspondence to: Cheryl M. Coffin, M.D., Division of Pediatric Pathology, Primary Children’s Medical Center, Salt Lake City, Utah 84132. E-mail: pcccoffi@ihc.com Received 30 April 2001; Accepted 17 April 2002 DOI 10.1002/ajmg.10607 ß 2002 Wiley-Liss, Inc.