Case Report

Ovarian Fibromas in Pediatric Patients With Basal Cell Nevus(Gorlin) Syndrome

Allison Ball MSc, MD *, Joan Wenning MD, FRCSC, Nancy Van Eyk MD, FRCSCDepartment of Obstetrics and Gynaecology, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada

a b s t r a c t

Background: Gorlin syndrome is a rare genetic condition consistin

g of multiple basal cell nevi associated with other entities such asmedulloblastoma, skeletal abnormalities, and ovarian fibromas.Case: A 15-year-old girl presented with abdominal discomfort. Magnetic resonance imaging showed multiple bilateral solid adnexalmasses, the largest measuring 5.5 cm � 6.1 cm � 5.6 cm. At laparoscopy, 10 ovarian fibromas, ranging from 3 mm to 7 cm in size, wereremoved from each ovary. Concurrent with her gynecologic course, she was found to have maxillary sinus cysts and multiple basal cellnevi. The patient’s history was also significant for a medulloblastoma as an infant. Given this constellation of findings, a diagnosis of Gorlinsyndrome was made.Conclusion: The development of ovarian fibromas in the pediatric population is rare. When diagnosed, the possibility of Gorlin syndromemust be considered. Furthermore, females with Gorlin syndrome would benefit from regular gynecologic surveillance.Key Words: Gorlin syndrome, Ovarian fibroma, Basal cell carcinoma, Nevoid basal cell carcinoma syndrome, Pediatric gynecology

Case

A 15-year-old girl presented to her family physicianwith generalized abdominal discomfort. An ultrasoundidentified what appeared to be a 6-cm anterior wall fibroid.She was referred to a pediatric gynecologist for furtherinvestigation and treatment. A repeat ultrasound 6 monthslater was unable to determine the nature of the mass,however, magnetic resonance imaging (MRI) showedmultiple enhancing bilateral adnexal masses, the largestmeasuring 5.5 cm � 6.1 cm � 5.6 cm. There was also note ofsignificant free fluid in the pelvis. Serum tumor markerswere negative.

The patient’s medical history was significant fora medulloblastoma at age 2 that was treated with surgeryand chemotherapy, followed by radiation 1 year later fora recurrence. Subsequently, she developed partial pituitaryfailure, requiring thyroid and growth hormone replace-ment. At age 5, she developed central precocious pubertyrequiring a GnRH agonist until age 11. At age 13, with nosigns of spontaneous puberty, she was commenced onhormone replacement therapy.

Concurrent with her gynecologic assessment, the patienthad a routine MRI of her head as follow-up for her medul-loblastoma. An incidental finding was noted of a leftmaxillary sinus cyst. A computed tomography (CT) scanfound bilateral cystic lesions in her maxillary sinuses andcalcification of her falx cerebri and tentorium cerebelli. She

* Address correspondence: Allison Ball, MSc, MD, 5850/5980 University Avenue,PO Box 9700, Halifax, Nova Scotia, Canada B3K 6R8; phone: (902) 470-8888.

E-mail address: Allison.ball@dal.ca (A. Ball).

1083-3188/$ - see front matter � 2011 North American Society for Pediatric and Adolesdoi:10.1016/j.jpag.2010.07.005

underwent enucleation of the maxillary cysts via a LeFort Iosteotomy.

Three months later, the patient underwent laparoscopicbilateral cystectomies. She was found to have multiplebilateral ovarian fibromas, approximately 10 on each side,ranging from 3 mm to 7 cm in size (Figure 1). Most ofthe fibromas were exophytic and completely excised;however, a portion of a large fibroma on the rightremained because of its intimate nature with the ovaryand the desire to maintain fertility. Other pelvic andabdominal structures appeared normal. The pathologyreport confirmed benign fibromas, and cytology of thepelvic fluid was negative.

Given the constellation of findings in this patient, shewas referred to medical genetics as well as to dermatology,who confirmed multiple basal cell nevi. Clinical criteria andgenetic testing confirmed a diagnosis of basal cell nevus(Gorlin) syndrome.

Background

Gorlin syndrome is a rare genetic syndrome of multiplebasal cell carcinomas associated with other pathologicentities, such as jaw cysts, skeletal abnormalities, medul-loblastomas, and ovarian fibromas.1 It was first reported in1894 but more clearly described by dentist Robert Gorlinand dermatologist Robert Goltz in 1960, who describedseveral coexisting features suggestive of a unifyingsyndrome.2 Gorlin syndrome is also known as Gorlin-Goltzsyndrome, nevoid basal cell carcinoma syndrome (NBCCS),and basal cell nevus syndrome (BCNS). It is a rare entity, andthe frequency is estimated at 1/50,000-150,000. Over

cent Gynecology. Published by Elsevier Inc.

Fig 1. Intraoperative laparoscopic photographs. Bilateral ovarian fibromas are seen in the left and right adnexae.Ă

A. Ball et al. / J Pediatr Adolesc Gynecol 24 (2011) e5ee7e6

a hundred clinical features have been associated withGorlin syndrome, but the diagnostic criteria have beennarrowed to those features outlined in Table 1.3 When indoubt, genetic correlation may be used to confirm thediagnosis.

The gene responsible for Gorlin syndrome has beenidentified on chromosome 9q22.3.4 This mutation is mostcommonly inherited, but it can also arise anew. The muta-tion occurs in the PTCH (patched) tumor suppressor gene,which modifies the hedgehog signaling pathway, a complexpathway responsible for cell cycle regulation. Although thegene mutation is inherited in an autosomal dominantfashion with high penetrance, it has highly variableexpression, which is responsible for its variable clinicalphenotype.

The development of ovarian tumors in the pediatricpopulation is rare. It is estimated that only 1.5% of ovariantumors in the pediatric population are fibromas.5 Whenidentified, the possibility of basal cell nevus (Gorlin)syndrome must be considered. The association of ovarianfibromas with Gorlin syndrome was first described in 1963by Clendenning et al.6 Since that time, there have been veryfew published cases of pediatric Gorlin syndrome patientswith ovarian fibromas. They are listed in Table 2. Though the

Table 1Diagnostic Criteria for Basal Cell Nevus (Gorlin) Syndrome. Diagnosis Requires 2Major or 1 Major and 2 Minor Criteria

Major Criteria:More than 2 BCC or 1 BCC in a person younger than 20 yearsOdontogenic keratocysts of the jawThree or more palmar or plantar pitsCalcification of the falx cerebriBifid, fused, or splayed ribsFirst-degree relative with NBCC syndrome

Minor Criteria:Childhood medulloblastomaMacrocephalyCraniofacial malformations (ie, cleft lip/palate, frontal bossing,

or hypertelorism)Ovarian and/or cardiac fibromasOther skeletal abnormalities such as sprengel deformity, pectus deformity,

or syndactylyRadiologic abnormalities (ie bridging of the sella turcica, vertebral

anomalies, flame-shaped lucencies of hands/feet)

Abbreviations: BCC, basal cell carcinoma; NBCC, nevoid basal cell carcinoma.

true frequency of fibromas in Gorlin syndrome patients ishard to estimate, and early estimates were as high as 75%,approximately 2%-25% of females with Gorlin syndromewill develop ovarian fibromas.1,2 In contrast to fibromas notassociated with Gorlin syndrome, they are usually bilateraland often calcified.1 Furthermore, recurrence is likely ifcomplete bilateral oophorectomies are not performed.7,8

Despite the possibility of recurrence, ovarian conservationin the pediatric population is of great importance, asreproductive potential does not seem to be affected byGorlin syndrome. The decision for further surgery requirescase-specific discussion and counseling, as ovarian functionmay be compromised or lost. Furthermore, there remainsa small risk of malignant pathology.

Ovarian pathologies other than fibromas have beenidentified in patients with Gorlin syndrome. There havebeen case reports of a fibrosarcoma in an 8-year-old girl,9

and a 20-year old with a primary ovarian leiomyosarcomafollowing ovarian fibroma excision.10 Concurrent endome-trial cancer and ovarian fibroma in awoman of reproductiveage has also been described.11

There have been 3 reports published on pregnant womenwith Gorlin syndrome who manifest unusual ovarianpathology. One of these women had bilateral virilizingsclerosing stromal ovarian tumors that developed in preg-nancy following treatment with clomiphine citrate.12 Sherequired surgical management and had postoperativeresolution of her virilization. The 2 others had renin-secreting ovarian fibrothecomas developed in early preg-nancy in women known to have Gorlin syndrome. Bothrequired oophorectomy owing to refractory hypertensionand had postoperative resolution of symptoms.13,14

In patients in whom the diagnosis of Gorlin syndrome issuspected, referral to a medical geneticist is recommended.For those patients with a confirmed diagnosis, regularmultidisciplinary surveillance is required. Periodic dentalx-rays, regular dermatologic exams, and periodic echocar-diograms are among the routine recommendations. Giventhe risk of ovarian pathology in female Gorlin syndromepatients, they also benefit from increased gynecologicsurveillance. Furthermore, in a pediatric patient in whomovarian fibromas are diagnosed, the diagnosis of Gorlinsyndrome must be considered.

Table 2Confirmed Cases of Pediatric Gorlin Syndrome Patients With Ovarian Pathology

Year Publication Age at presentationof ovarianpathology (y)

Pathology Intervention

1968 Rater CJ15 5 Unilateral ovarian fibroma Unknown1983 Raggio M8 7 Recurrent bilateral ovarian fibromas First surgery: bilateral ovarian cystecomies

Second surgery: right salpingoophorectomy,left ovarian cystectomy

1984 Kraemer BB9 8 Bilateral ovarian fibrosarcoma Bilateral salpingoophorectomy1986 Johnson AD5 3 Bilateral ovarian fibromas First surgery: left salpingoophorectomy, right

ovarian wedge resectionSecond surgery: right ovarian cystectomyThird surgery: right salpingoophorectomy

2001 Seracchioli R7 17 Recurrent bilateral ovarian fibromas First surgery: bilateral ovarian cystectomiesSecond surgery: bilateral ovariancystectomies

2002 Smith LM16 12 Ovarian fibroma Right oophorectomy2003 Seracchioli R10 16 Primary leiomyosarcoma of ovary after

previous bilateral ovarian fibromasFirst surgery: right salpingoophorectomy with

left ovarian cystectomySecond surgery: left salpingoophorectomy

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References

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13. Yoshizumi J, Vaughan RS, Jasani B: Pregnancy associated with Gorlin’ssyndrome. Anaesthesia 1990; 45:1046e8

14. Fox R, Eckford S, Hirschowitz L, et al: Refractory gestational hypertention due toa renin-secreating ovarian fibrothecoma associated with Gorlin’s syndrome. BrJ Obstet Gynaecol 1994; 101:1015e7

15. Rater CJ, Selke AC, Van Epps EF: Basal cell nevus syndrome. Am J RoentgenolRadium Ther Nucl Med 1968; 103:589e94

16. Smith LM, Hu P, Meyer LJ, et al: Complex karyotypic abnormality in ovarianfibroma associated with Gorlin syndrome. Am J Med Genet 2002; 112:61e4