Delayed diagnosis of Gorlin syndrome: Learning from mistakes!

Gorlin syndrome (GS) is a rare inherited multisystem disorder with predisposition to basal cell carcinomas and various other neoplasms. Characteristic features include falx calcification, multiple odontogenic keratocysts (OKCs), early onset medulloblastoma, craniofacial and skeletal malformations, cardiac and ovarian fibroma. We present a case of GS in a 9-year-old girl with recurrent dental infections which was overlooked for 8 years. Diagnosis was finally suggested by the incidental detection of multiple OKCs and ovarian fibromas on follow-up magnetic resonance imaging performed for surveillance of previous operated brain tumor.

Introduction

Gorlin syndrome (GS), also known as basal cell nevus syndrome (BCNS) is a rare hereditary multisystem disorder, characterized by a series of multiple developmental anomalies and increased risk of developing various benign and malignant tumors. The major risk is the development of multiple basal cell carcinomas (BCCs).[1] Here we report a case of GS overlooked for 8 years in a child with recurrent dental infections and prior history of medulloblastoma. Diagnosis was first suggested by the radiologist on follow-up magnetic resonance imaging (MRI), performed for the surveillance of brain tumor based on the incidental detection of odontogenic keratocysts (OKCs) and ovarian fibromas.

Case Report

A 9-year-old girl presented to pediatric neurology clinic for periodic follow-up of her cerebellar medulloblastoma, operated at 6 months of age. Multiple follow-up MRI did not show any recurrence or new problems. The patient or the parents did not complain of any new symptoms except for recurrent dental infections for which they had over the counter antibiotics and analgesics. Physical examination revealed mentally retarded quiet child with facial dysmorphism in the form of large head and hyperteleorism. Oral examination was remarkable for multiple caries tooth.

MRI brain and spine was ordered in the current visit which showed gliotic changes from prior surgery with no residual/recurrent mass. Multiple calcifications were seen in the falx cerebri and tentorium [Figure 1]. The inferior cuts of brain included portion of the face which revealed multiple cystic lesions along the maxillary and mandibular alveolus [Figure 2]. On retrospective review, these cystic lesions were also seen on prior MRI performed immediately after surgery 7 years back. MRI spine did not show any drop metastasis but lumbar spine images showed mass like lesions in the pelvis. Further evaluation with MRI pelvis demonstrated multiple bilateral solid adnexal masses showing predominant T2-hypointensity suggestive of ovarian fibromas [Figure 3]. Considering the history of medulloblastoma, multiple dental cysts and adnexal lesions, probable diagnosis of GS was suggested by the radiologist. Surgical excision of dental cysts confirmed the diagnosis of OKC. Focussed physical examination did not reveal any skin lesions. Genetic counseling has been given and patient is now planned for laparoscopic excision of ovarian fibromas with ovarian preservation.

Figure 1

(a) Axial T2-weighted magnetic resonance imaging reveals gliotic changes in vermis and adjacent superior cerebellum (arrow) from prior excision of medulloblastoma. (b) Axial susceptibility weighted images shows tentorial calcification (arrows). (c) Axial susceptibility weighted images shows falx calcification (short arrows), parenchymal calcification (long arrow) and ventriculoperitoneal shunt (arrowhead)

Figure 2

Multiple odontogenic keratocysts in the maxillary and mandibular alveolus. (a) Coronal T2-weighted magnetic resonance imaging shows cystic lesion (arrow) in the right maxillary alveolus. (b) Coronal T2-weighted magnetic resonance imaging reveals two cystic lesions in the maxillary alveolus at the base of maxillary sinuses (arrows). (c) Coronal T2-weighted magnetic resonance imaging reveals cystic lesions in left mandibular alveolus (arrow), one of them showing impacted tooth (arrowhead)

Figure 3

Coronal T2-weighted magnetic resonance imaging reveals multiple T2-hypointense bilateral adnexal masses (arrows), largest in the right adnexa showing central necrosis (asterisk)

Discussion

GS is an autosomal dominant disorder with near complete penetrance but variable expressivity and an estimated birth incidence of 1 in 19,000 individuals.[2] Recent consensus statement from the first international colloquium on BCNS proposed less stringent criteria for diagnosis [Table 1]: (1) One major criterion and molecular confirmation; or (2) two major criteria; or (3) one major and two minor criteria.[3]

Table 1

Revised criteria for diagnosis of GS

Our index case meets three major (medulloblastoma, OKCs of the jaw and calcification of the falx cerebri) and two minor (ovarian fibroma and macrocephaly) diagnostic criteria for GS. Our patient did not have any BCC skin lesions, which typically develop between puberty and age 35 years and are most commonly located on the face, neck and upper trunk.

Childhood medulloblastoma develops in approximately 5% of individuals with GS with peak incidence at 2 years.[4] Medulloblastoma is almost always the first tumoral manifestation of this syndrome. Imaging features include: midline cerebellar mass appearing hyperdense on noncontrast computed tomography, intermediate signal intensity on T2-weighted MRI due to high cellularity, shows intense and homogenous enhancement, causes obstructive hydrocephalus and CSF seeding to spinal cord and meninges seen in 30% of cases.[5] One of the most common intracranial abnormalities in GS is lamellar calcification of the falx before 20 years of age seen in 90% of patients.

Multiple OKCs develop in approximately 90% of patients with GS now renamed as keratocystic odontogenic tumor with peak occurrence in the adolescence. They present as painless swellings.[6] OKCs are typically seen as a solitary, lucent, unilocular lesion with smooth corticated borders on orthopantomogram (OPG). Literature is scanty on MRI features and includes T1-hypointensity and T2-hyperintensity in keeping with cystic nature of the lesion.[7]

Cardiac and ovarian fibromas occur, respectively, in approximately 2% and 20% of females. Ovarian fibromas are the most common gynecological manifestation in GS and are more likely to develop before puberty, most often bilateral, multinodular, multifocal, and calcified. Treatment involves surgical excision of the tumor with attempt at ovarian tissue preservation for fertility. MRI features are characteristic and include diffuse T2-hypointensity of solid component due to fibrous nature of the tumor.[8]

This case is interesting and educational for few reasons.

Childhood brain tumor is a common association for GS. However, this was not considered by the treating neurosurgeons and the reason put forth was absence of skin lesions. Although the number of BCC lesions of the skin can be very high, it is important to note that 10% of patients over the age of 30 years do not have skin lesions.[9]

Recurrent dental infections in this child was not paid appropriate attention, partly because of treating physicians underestimating the dental infections and the parents relying on over the counter medications. Diagnosis could have been made early if a dentist has seen the child and asked for an OPG.

Most importantly, cystic lesions round the maxilla and mandible were overlooked by the radiologist in the prior MRI as the study was focused on brain and not maxillofacial region.

To the best of our knowledge, this is the first case of GS diagnosed solely based on various MRI features. This case clearly shows the important role of radiologist in making the diagnosis of GS as it was not suspected by treating physicians. Radiologists should be aware of spectrum of imaging features in GS and should be suspicious of incidental findings such as falx calcification, skeletal anomalies, and jaw cysts. The same is also stressed by the recent consensus statement which recommended educating neurosurgeons, gynecologists, and radiologists for early diagnosis of GS.[3]

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