Mutiple keratocystic odontogenic tumors (KCOT) in a patient with Gorlin syndrome: a case report with late presentation and absence of skin manifestations

To our knowledge this is the first reported case of Gorlin syndrome in our country. One of the characteristic features of this syndrome is the presence of multiple jaw cysts which may appear in very early life and thus can lead to its recognition at that time. Our case is unique in this aspect that the patient presented in the fourth decade of life and yet there was no skin lesion which can be clinically suspected to be of basal cell carcinoma. One of the explanations may be that the patient is dark skinned not very much involved in outdoor activities which led to his protection from basal cell carcinoma. Another distinctive feature of our case was quite a larger number of cysts compared to most of the case reports where average number of jaw cysts was three. Falx cerebral calcification is another pathognomonic characteristic of Gorlin syndrome which was demonstrated in our case. Saulite et al. reported a case with incidental finding of falx cerebral calcification leading to the diagnosis of Gorlin syndrome [8]. Other characteristic facial features of Gorlin syndrome like cleft lip/palate, micropthalmia were not present in our case.

KCOT occurring in Gorlin syndrome have a higher recurrence rate as compared to nonsyndromic solitary keratocysts [9]. This aggressive behavior may be explained by the presence of daughter and satellite cysts in syndromic keratocysts [10]. In our case daughter cysts were not observed. In addition, two of the cysts were heavily inflamed with focal calcification and giant cell reaction. Biologically, it is believed that in syndromic KCOT epithelial remnants are left behind which give rise to recurrence of cysts and therefore it is suggested that overlying mucosa should be excised before bone grafting [11].

Although it is firmly established that multiple KCOT are linked to Gorlin syndrome, i.e. mutation of PTCH gene, a few case reports of multiple KCOT without other manifestations of Gorlin syndrome were also reported in literature [12, 13]. Raghavendra et al. explained this occurrence by partial expression of PTCH gene [14]. This may also explain our case in which no skin lesions were observed and jaw cysts occurred in late adulthood.

In our case, based on clinical and radiologic findings, surgical excision was planned, however ideally such patients should first be biopsied to establish a diagnosis before embarking on definitive surgical management as complete removal of all cysts is key to prevent recurrence. Woolgar et al. compared the histologic features of KCOTs associated with Gorlin syndrome with those of solitary KCOTs. Syndromic KCOTs were found to be more significantly associated with satellite cysts, solid islands of epithelial proliferations, odontogenic rests within the capsule and in the number of mitotic figures in the lining epithelium [15]. Several authors have reported a higher recurrence rate of KCOTs particularly those associated with Gorlin syndrome. There are many reasons of this occurrence; for instance, by incomplete removal of the original cyst lining, by retention of daughter cysts, from epithelial islands in the wall of original cysts and by the development of new KCOTs from epithelial buds of the basal layer of oral epithelium [16]. This reinforces the importance of biopsy and proper surgical management.

Multidisciplinary clinical approach is needed to manage patients with Gorlin syndrome with the involvement of geneticists and maxillofacial surgeons. Moreover, dermatologists may also be involved to ensure early detection and treatment of basal cell carcinomas. KCOTs are hallmark of this disease and should always lead to its suspicion even in the absence of other clinical manifestations.

The two key features of Gorlin syndrome are basal cell carcinoma and KCOTs, both of which usually start to occur during 1st and 2nd decade of life. On the contrary, in our case, there was no evidence of basal cell carcinoma and there was even late occurrence of KCOTs. This may be explained by both genetic and environmental factors. Yaser et al. described nine genetic variants which modify the age of onset of basal cell carcinoma in Gorlin syndrome [17]. In addition, environmental factors like sunlight exposure and amount of skin pigmentation may also modify the age of presentation. Therefore a diagnosis of Gorlin syndrome should always be suspected in any patient presenting with KCOTs especially if multiple or recurring even if at a late age of onset. As in cases of Gorlin syndrome a more vigilant clinical approach would be needed including assessment of any developing skin lesions, aggressive surgical approach for the management of KCOTs, more closer clinical follow-up to deal with any recurring KCOTs and genetic counseling.