Gorlin-Goltz syndrome: A series of three cases.

The Gorlin-Goltz syndrome (GGS) is also known as nevoid basal cell carcinoma syndrome. It is characterized by multiple keratocystic odontogenic tumors (KCOTs) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. The syndrome may be diagnosed early by a dentist during the routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article reports the series of 3 cases, emphasizing its clinical and radiographic manifestations of GGS.

INTRODUCTION

Gorlin-Goltz syndrome (GGS) is an autosomal dominant disorder characterized by a predisposition to neoplasms and other developmental abnormalities.[1] It was first described by Jarisch and White in 1894. In 1960 Gorlin and Goltz described the classical triad composed of multiple basal cell carcinomas, keratocystic odontogenic tumours (KCOTs) in the jaws and bifid ribs that characterized the diagnosis of this syndrome. In addition to this triad, calcification of the falx cerebri, palmar and plantar epidermal pits, spine and rib anomalies, relative macrocephaly, facial milia, frontal bossing, ocular malformation, medulloblastomas, cleft lip and/or palate and developmental malformations were also established as features of the syndrome.[123]

The prevalence of GGS has been estimated from 1 in 57,000 to 1 in 164,000, but there is now general agreement that the prevalence is about 1/60,000. This syndrome probably presents itself in all ethnic groups and affects both men and women in the same way.[4]

During the last few years very important advances have taken place in the knowledge about the genetic characteristics of this syndrome. The tumor suppressor gene called patched (PTCH), located in the 9q22.3 chromosome and has been identified as the main cause of GGS.[5]

In the case of GGS, it is of great importance to make an early diagnosis since the severity of complications, such as malignant skin and brain tumors can be reduced and maxillofacial deformities related to the jaw cysts can be avoided. The treatment of which involves a therapeutic approach to its clinical findings. The present report describes patients with some typical features of GGS.

CASE REPORTS

Case 1

The first case was about a 15-year-old female patient who reported to our college with the complaint of malaligned teeth and difficulty in chewing from the right side. She was referred to the Department of Orthodontics. In their routine radiographic investigations, they found multiple cystic lesions in upper and lower jaw, associated with unerupted teeth. She was referred to the Department of Maxillofacial Surgery for further management. On intraoral examination, there were displaced crowns of 41 and 42, consistent with the finding of underlying cystic lesion. Investigations included routine blood investigations, orthopantomogram (OPG), lateral cephalogram, computed tomography (CT) scan with 3-D reconstruction and chest X-ray. Her past medical and dental history did not reveal any significant finding.

The OPG showed multiple lytic lesions in the upper and lower jaws associated with unerupted permanent teeth. The chest radiograph showed second bifid rib on right and third bifid ribs on the left side. Cortical expansion was evident on the right side of the mandible (lower jaw). In addition, a radiolucent lesion was also noted in the premolar region on the right side. Based on the clinical and radiological findings, a provisional diagnosis of GGS was considered. Palmar-plantar keratosis was present. Syndactility was present in both feet. No skin lesions in the form of basal cell nevi were present. The parents and siblings of the patient were also examined clinically and radiographically; however, none of them showed any characteristics of this syndrome.

Treatment

The treatment done was as follows:

3rd molar extraction of bilateral mandibular teeth with enucleation, peripheral ostectomy and use of Carnoy's solutions

Mandibular molars were surgically removed, followed by enucleation of mandibular cystic lining. This was followed by peripheral osteotomy and chemical cauterization with Conroy's solution

Extraction of 41, 42 with marsupialization

41, 42 were extracted which was followed with marsupialization with roller gauze impregnated with idoform

Enucleation of cysts in maxilla

The enucleation of cysts in maxilla was done through Caldwell Luc approach.

This case is being followed since last 5 years.

Case 2

This was a case report of a 13-year-old girl patient who presented with a complaint of mild swelling and pus like discharge from the maxillary canine and left mandibular premolar region for over a month in February 2006. She did not complain of pain, facial swelling or foul odor and was apparently healthy. On intraoral examination revealed the absence of tooth numbers 13, 14, 15, 23, 34, 35, 44 and 45 with retention of deciduous molars. There was a slight expansion of the buccal cortical plate in the right and left maxillary canine regions. With pressure, white creamy exudates oozed out of the area, but there was no tenderness or bleeding. A panoramic radiograph revealed multiple radiolucencies in all 4 quadrants.

The patient's chest radiograph revealed the presence of bifid ribs. On dermatologic examination, palmar pitting was seen. Hematologic investigations were however within the normal limits. These findings led us to the diagnosis of GGS in the patient. The parents and siblings of the patient were also examined clinically and radiographically; in which the mother of the patient was found to have syndactyly of the right hand. She also gave a history of being operated for oral cystic lesions 20 years back.

The treatment done was as follows:

Surgical management was planned under general anesthesia

Two maxillary lesions were enucleated via the Caldwel Luc approach and chemical cauterization done using Carnoy's solution, which was applied to the osseous margins

Two mandibular lesions were marsupialized with the removal of deciduous teeth 53, 54, 55, 74, 75, 84 as there was a good chance of eruption of succedaneous teeth

Specimens were sent for histopathologic examination. The histopathologic reports revealed that the cystic lining of all 4 lesions was parakeratinized stratified squamous epithelium of uniform 6-8-cell thickness depicting KCOT. The lining epithelium consisted of well-defined columnar basal cells in a palisade arrangement and with polarized nuclei. The height of the epithelial cells and the number of nuclei they contained were reduced

Follow-up after 18 months showed both enucleated sites in the maxilla were healed, without signs of cyst recurrence. In mandible marsupialized sites showed maintenance of the window created and tooth number 34, 35, 44 in erupting position.

The case is being followed since last 9 years.

Case 3

A 29-year-old man reported to our department with the chief complaint of foul smelling discharge from left mandibular molar region. On examination, there was a swelling seen along the left mandibular surface, which could also be seen intraorally along the vestibule. There was mild tenderness on palpation, associated with crepitus and pus discharge. 37 was found to be mobile. An OPG was taken, which showed the presence of multiple cystic lesions in all the four quadrants. The size of the cysts was varying. All third molars were unerupted and were housed in cystic cavities. The multilocular cyst on left mandibular quadrant had produced buccal cortical expansion and was infected. The patient also depicted frontal bossing, palmar pitting and keratosis. On CT scan, a bifid spinal process could be seen. The findings led us to diagnosing the patient with GGS.

The treatment done was as follows:

Surgical management was planned under general anesthesia

Two maxillary lesions were enucleated through the Caldwel Luc approach and chemical cauterization was done using Carnoy's solution, which was applied to the osseous margins. Later the cystic lesions were connected with bilateral nasal antrostomies and packed using iodoform impregnated roller gauze

The largest cyst extending from 43 to the left coronoid process was marsupialized and packed open. An acrylic stent was later fabricated, which covered the marsupialization window and allowed for irrigation

A cyst in the Rt mandibular molar ramus region measured 3 cm × 4 cm and was enucleated and Carnoy's solution applied to peripheral osseous walls. The wound was then primarily closed.

The case is being followed since last 2 years [Figures 1-5].

Figure 1

Crowding of teeth

Figure 5

Lateral cephalogram showing frontal bossing

Orthopantamogram showing crowding of teeth and multiple cystic lesions in mandible

syndactylity of 2nd and 3rd toe

Chest X ray showing bifid rib

DISCUSSION

According to Manfredi et al., the diagnostic criteria of nevoid basal cell carcinoma syndrome (NBCCS) require the presence of two major/one major and two minor criteria. Major criteria include the presence of more than two basal cell carcinomas or one under the age of 20 years, histologically-proven KCOT of the jaw, cutaneous palmar or plantar pits and bifid, fused ribs. Minor criteria, includes congenital malformations (cleft lip or palate, frontal bossing or moderate or severe hypertelorism), skeletal and radiological abnormalities (bridging of sella turcica and vertebral anomalies), ovarian fibroma and medulloblastoma.

In the present case report the patient presented with multiple KCOTs in the maxilla and mandible, rib anomalies, syndactylity and palmar-plantar keratosis confirming the diagnosis of NBCCS or GGS. One of the features found in this syndrome and mentioned in literature is the development of multiple basal cell carcinomas, especially in the head and neck region. In this case, it has not been possible to identify the presence of basal cell carcinomas. This fact can be explained by the patient's age. Possibly, these carcinomas may develop in the future mostly in second or third decade of life.

According to Marotto et al., some of the most common clinical findings of the syndrome are discovered through radiography commonly used in orthodontic treatment. In the case described in this study, OPG taken for orthodontic purposes showed radiolucent areas in the maxilla and mandible, suggesting the presence of KCOTs.

KCOTs are among the most consistent and common features of NBCCS. The lesions are characterized by aggressive growth and a tendency to recur after surgical treatment. The epithelial cells of the basal layer show increased mitotic activity, together with a potential for budding and the presence of daughter cysts in the wall. It has been reported that the presence of daughter cysts was related to the recurrence of KCOT. The mandible is involved more frequently than the maxilla and the posterior regions are the most commonly affected sites.

There are two methods for the treatment of KCOT, a conservative and an aggressive. In the conservative method, simple enucleation with or without curettage and marsupialization are suggested. Aggressive methods include peripheral ostectomy, chemical curettage with Carnoy's solution and resection.

Serious consideration should be given to en bloc resection in the following cases: (1) When KCOT recurs despite previous enucleation with an adjunctive procedure; (2) when KCOT recurs despite previous marsupialization followed by enucleation with an adjunctive procedure; (3) in cases of multilocular aggressive intraosseous KCOT; (4) in cases of multiple non-syndromic and syndromic KCOTs or (5) in a diagnosed KCOT exhibiting particularly aggressive clinical behavior (e.g. growth, destruction of adjacent tissues) that should require resection as the initial surgical treatment.

If the patient is in the first decade and has unerupted permanent teeth involving KCOTs, it would be difficult to make a decision of aggressive surgery over conservative management. In children who have unerupted teeth, conservative management should be considered first because an aggressive operation can have an adverse effect on tooth development, the eruption process and the development of the involved jaw. Thus, younger patients usually receive more conservative than aggressive treatment.

Some authors believe that simple enucleation might be the most appropriate conservative method for the treatment of KCOT. Others have shown that successful treatment of large or multiple KCOTs can be achieved using marsupialization followed by enucleation. Furthermore, it has been reported that marsupialization followed by enucleation results in the lowest recurrence rate among the conservative treatment. Moreover, considering the reconstructive and rehabilitative issues associated with radical surgery, marsupialization followed by enucleation has been suggested as the conservative option for treatment of KCOT in younger patients.

Histopathological examination of the removed tumors should be performed to provide a definitive diagnosis. In this case, histopathological examination confirmed the diagnosis of KCOT and thus need for monitoring the disease. Suggested follow-up periods are long for these cases. In order to minimize recurrences after the treatment, patients with KCOT should be observed carefully by radiographic imaging particularly during the 1st year.