|Year : 2013 | Volume
| Issue : 1 | Page : 61-66
Multiple keratocystic odontogenic tumors in a non-syndromic minor patient: Report of an unusual case
Shalu Rai1, AS Rana2, Puneet Kalra2, Deepak Gupta2, Sumit Goel3
1 Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Kadrabad, Modinagar, India
2 Department of Oral and Maxillofacial Surgery, Institute of Dental Studies and Technologies, Kadrabad, Modinagar, India
3 Department of Oral Medicine and Radiology, Subharti Dental College, Meerut, Uttar Pradesh, India
|Date of Web Publication||20-Jun-2013|
Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Kadrabad, Modinagar - 201 201, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Keratocystic odontogenic tumor (KCOT) is developmental odontogenic cysts of epithelial origin known for their potentially aggressive behavior and significant rate of recurrences. Single odontogenic cysts are very well documented in the literature. Multiple (KCOT) are principle features of nevoid basal cell carcinoma syndrome (naevoid basal cell carcinoma syndrome; Gorlin-Goltz syndrome). We report an intriguing case of multiple KCOT in a non-syndromic patient simultaneously occurring in maxilla as well as in mandible with brief highlight on molecular data and the treatment modality.
Keywords: Gorlin-Goltz syndrome, multiple keratocystic odontogenic tumor, non-syndromic
|How to cite this article:|
Rai S, Rana A S, Kalra P, Gupta D, Goel S. Multiple keratocystic odontogenic tumors in a non-syndromic minor patient: Report of an unusual case. J Orofac Sci 2013;5:61-6
|How to cite this URL:|
Rai S, Rana A S, Kalra P, Gupta D, Goel S. Multiple keratocystic odontogenic tumors in a non-syndromic minor patient: Report of an unusual case. J Orofac Sci [serial online] 2013 [cited 2022 May 26];5:61-6. Available from: https://www.jofs.in/text.asp?2013/5/1/61/113708
| Introduction|| |
According to World Health Organization's 2005 edition of its histological classification of odontogenic tumors keratocystic odontogenic tumor (KCOT) also known as odontogenic keratocyst (OKC) has been defined as "A benign uni- or multicystic intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potentially aggressive, infiltrative behavior.  World Health Organization (WHO) recommends the term KCOT because of its aggressive and infiltrative nature. This lesion shows the features both of cyst and benign neoplasm. It may be solitary or multiple. The latter is usually one of the stigmata of the inherited naevoid basal cell carcinoma syndrome (NBCCS). 
Multiple KCOTs usually occur as a component of NBCCS or Gorlin-Goltz syndrome,  orofacial digital syndrome,  Ehler-Danlos syndrome,  Noonan syndrome,  Simpson-Golabi-Behmel syndrome More Details  or can be non-syndromic. ,, Brahnon in his analysis of clinical features of 312 cases of OKC found that 5.8% of patient with the multiple OKC had no other features of syndrome. 
KCOTs associated with NBCCS occur earlier in life and exhibit a greater tendency to recur and are more aggressive than non-syndromic OKCs,  and occasionally been reported to transform into aggressive neoplasms such as ameloblastomas, and squamous cell carcinoma. 
Occurrence of multiple KCOT is rare and to date only few cases have been reported in literature until 2011. Here, we report a case of the multiple KCOT involving both the jaws with the maxillary canine pushed high up near the orbit and mandibular canine lying near the lower border of mandible in a non-syndromic 14-year-old patient with hypertelorism, strabismus, and polydactyl thus, presenting a partial expression of NBCCS.
| Case Report|| |
A 14-year-old male patient presented with his parents with the chief complaint of pain and swelling in the right side of the face since 20 days (with an informed consent from his parents). His past medical and dental history was unremarkable. On examination, he was thin built. There was obvious hypertelorism with an increased intercanthal distance along with strabismus [Figure 1]. His gait was normal. However, he exhibited polydactyl of hand and feet [Figure 2]. Extraoral swelling was present on the right side of the face extending from the medial acanthus of the eye to the corner of the mouth, obliterating the nasolabial angle [Figure 1]. On intraoral examination, a vestibular swelling, which was firm, tender, and non-fluctuant was observed extending from 13 to 16 region with over retained deciduous canine [Figure 3]. No significant palatal expansion was noted.
|Figure 1: Patient with hypertelorism and strabismus along with an extraoral swelling on the right side of the face extending from medial acanthus of the eye to the corner of the mouth, obliterating the nasolabial angle|
Click here to view
|Figure 3: A vestibular swelling is seen extending from 13 to 16 region with over retained deciduous canine|
Click here to view
Radiographical investigations performed for the patient were orthopantomogram, Skull views, chest radiograph, hand wrist radiograph, and Computerized Tomography (CT). Panoramic radiography revealed four large bony defects showing a large radiolucency with the sclerotic border resembling cysts associated with impacted 13, 43, 38, and 48 [Figure 4]. Chest and skull radiographs were unremarkable. Axial CT showed a large expansile space occupying lesion in the right maxillary sinus area, involving pterygoid plates, nasal floor, anterior, and lateral maxillary wall on the right side [Figure 5]. 3D CT reconstruction showed erosion of maxillary bone, nasal floor, and medial wall of the orbit.
|Figure 4: Orthopantomogram showing four large bony defects resembling cysts associated with impacted 13, 43, 38, and 48 in right maxillary and mandibular canine region and bilateral mandibular ramus region respectively|
Click here to view
|Figure 5: Axial computed tomography showing a large expansile region involving pterygoid plates, nasal floor, anterior and lateral maxillary wall on right side not crossing the midline|
Click here to view
Hematological investigations were within normal limits. Under General Anesthesia, the patient underwent marsupialization for the lesion in the right maxillary canine region with 23 left in situ, and enucleation and curettage with Carnoy's solution was carried out for the remaining three cystic lesions along with the removal of impacted 43, 38, and 48. All the lesions were sent for histopathologic examination. Patient had an uneventful post-operative course and was discharged the next day. Follow-up for 20 days showed good healing at surgical sites without any paresthesia. The patient is under follow-up since last 6 months.
H and E stained sections of two cystic lesions (right mandibular ramus and right mandibular canine) showed features of classical parakeratinized OKC with underlying connective tissue showing mild to moderate inflammatory infiltrate [Figure 6]a. Tissue obtained from right maxillary canine region showed parakeratinized epithelium along with the mural thickening on the lining with few areas showing features of mild cellular dysplasia. This lesion was diagnosed as OKC with dysplastic changes [Figure 6]b. Tissue obtained from left mandibular ramus region showed typical OKC like parakeratinized epithelial lining with connective tissue showing islands of epithelial cells along with dense collagenous fibrous stroma. This lesion was diagnosed as desmoplastic ameloblastoma in the wall of parakeratinized OKC.
| Discussion|| |
NBCCS is characterized by multiple OKCs, nevoid basal cell carcinoma of skin, calcification of falx cerebri, bifid ribs, and other features.  Gorlin first described these features associated with this syndrome in the year 1960 hence it is also called as Gorlin-Goltz syndrome.  Multiple cyst formations occur typically in association with a Gorlin's syndrome and rarely with other syndromes mentioned previously. There is no specific test to diagnose NBCCS and the diagnosis is made clinically using the criteria suggested by Evans et al.  and Kimonis et al. [Table 1].  Some studies show that affected patients with NBCCS may have high levels of cyclic adenosine monophosphate and impaired phosphate diuresis on parathormone challenge.  Our patient was apparently healthy and had no significant features suggestive of above syndromes except for the presence of multiple OKCs, hypertelorism, strabismus, and polydactyl of hand and feet. Lindboom has reported a case with hypertelorism, mental retardation, strabismus, calcification of falx cerebri, and medulloblastoma. 
The multiple cysts does not necessarily mean the patient will have more than one cyst at a given time. However, refers to occurrence of cyst over a life time of patient.  Thus, the dentist might be the first one to detect this syndrome.
OKCs of the jaws is considered as the developmental cysts and account for 10-15% of all jaw cysts. ,, arising from cell rests of the dental lamina and occurring over a wide age group with peak incidence in second and third decade of life. , Clinically, they generally present as a swelling, with or without pain. The cyst classically grows within the medullary spaces of the bone in an anteroposterior direction, causing expansion that is at first minimal. Buccal expansion is noted in approximately 30% of maxillary and 50% of mandibular lesions. ,
They are twice as common in the mandible than maxilla  with a predilection for the angle and ascending ramus.  Rare examples of these cysts arising from the temporomandibular joint have been reported.  Although most (OKCs) are encountered as intraosseous lesions, peripheral manifestations have been reported,  primarily involving the buccal gingival soft-tissue in the canine area of the mandible.  In the present case, multiple OKCs were associated with impacted 13, 43, 38, and 48 in the right maxillary and mandibular canine region and bilateral mandibular ramus region respectively.
The radiographic features of OKC are not pathognomonic, and the presentation can be similar to that of other odontogenic cysts and tumors. The radiographic features characteristic of OKCs are  a distinctly corticated, often scalloped, border, expansion, especially, toward the lingual (medial) side, and growth along the length of the mandibular bone with displacement of developing teeth or resorption of the roots of erupted teeth and extrusion of erupted teeth. a radiolucent lumen, and occasionally a cloudy or milky appearance of the lumen on the panoramic radiograph. In 25-40% of cases, there is an unerupted tooth involved with the lesion, adjacent teeth may be displaced. However, root resorption is rarely seen. An important feature that helps to distinguish the OKC is stated by White and Pharoah  that it exhibit a "propensity to grow along the internal aspect of the jaws, causing minimal expansion."
In the present case, two cystic lesions presented as well-defined radiolucencies associated with impacted teeth (38,48) with thin sclerotic border, whereas, the remaining two showed an ill-defined border with displacement of impacted teeth (13,33). Overall, a range of different imaging modalities was used to help the diagnosis and to evaluate the extension of the lesion in different sites. In our case, CT scan was helpful in showing the extent of the lesion. This is in agreement with Janse van Rensburg et al.,  who stated that CT displays aspects of bone morphology not seen in plain films, and demonstrated the importance of the combination of several imaging modalities to improve the diagnosis of the nevoid basal cell carcinoma syndrome.
The cyst lining seen in the NBCSS-related OKC is classically parakeratinized. OKCs associated with NBCCS are more aggressive and have higher recurrence rates than those associated without syndrome. The keratocysts in patients with this syndrome tend to have more satellite cysts, solid islands of epithelial proliferation, and odontogenic epithelial rests within the fibrous capsule than do isolated keratocysts.  They have higher tendencies to transform in to aggressive neoplasms. ,,, Although, satellite cysts were not seen in the present case. However, cystic lining was parakeratinized in all the four lesions of our case. One of our cystic lesions showed dysplastic changes while one showed the presence of desmoplastic ameloblastoma in the cystic wall, thus, revealing their aggressive nature [Table 2].
|Table 2: The variations in all the four cystic lesions of the present case|
Click here to view
Various gene have been postulated to play a role in the pathogenesis, recurrence and in deciding the treatment modality of OKC. THE gene For Gorlin has been identified as the human homologue of the Drosophilia segment polarity gene "patched" known as PTCH gene, have been isolated in patient with both sporadic or NBCC syndrome.  The increased proliferation of epithelial cells have been reported in the lesion as Cytokeratin 6B.  Various other overexpressed genes found include epidermal growth factor receptor 3, glioma-associated oncogene homolog 1, P53 genes and disruption of fragile histidine traid (FHIF). , Kuroyanagi et al.,  suggested the presence of Ki-67 expression in OKC, which might be helpful for considering the alternative surgical procedure to avoid recurrence and might be used as a prognostic indicator. In recent studies, the hypothesis that suppression of sonic hedgehog (SHH) signaling pathway might be effective for the treatment of OKC. 
Treatment of OKCs remains controversial, and management modalities can be categorized as either "conservative" or "aggressive," based on the multiple factors including lesion size, anatomic relationship, recurrence pattern, and the cyst's association with the NBCCS. Multiple surgical management techniques have been reported, including marsupialization, enucleation, enucleation with the use of Carnoy's solution, decompression, marginal or radical surgical resection, and the bone implantation. , Cystic lesions in the present case were treated by marsupialization (maxillary canine region) so that the eruption of the canine can be guided along with the development of the jaw could be maintained, and enucleation and curettage with Carnoy's solution (remaining three) along with the removal of impacted 43, 38, and 48.
The occurrence of multiple OKCs may be the first and only manifestation of NBCCS. Multiple OKCs can occur a decade before other symptoms associated with NBCCS and in patient younger than those with the single OKC. The possibility of our young patient developing other features of NBCCS in the future cannot be excluded.
It emphasizes the need for a thorough examination of patients with recurrent OKCs to detect other features of the NBCCS syndrome, which is known for its variability of expression. OKC associated with NBCC having higher recurrence rate of 82% as compared to the recurrence rate for solitary OKC, which is 61%.  Our patient is under regular follow-up.
| Conclusion|| |
In any patient with the multiple OKCs, possibility of NBCCS must be considered. Although our patient did not completely fulfilled major and minor diagnostic criteria of this syndrome, but in view of the clinical findings (multiple OKCs simultaneously occurring in both jaws, early age of occurrence, hypertelorism, strabismus and polydactyly) and histological correlations (parakeratinized lining and aggressive behavior), we suggest our case to be a partial expression of NBCCS. Thus, our case adds to the other numbers of such cases of non-syndromic OKC. It is important to high-light the importance of diagnosing this entity so that a stringent follow-up be enforced in such cases.
| Acknowledgment|| |
Department of Oral Pathology, I.D.S.T. Dental College, Kadrabad, Modinagar, Uttar Pradesh - 201 201, India. The author would like to thank the patient for providing consent to use his photograph in this article.
| References|| |
|1.||Philipsen HP. Keratocystic odontogenic tumour. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. WHO classification of keratocystic odontogenic tumour. Pathology and genetics of tumours of the head and neck. lyon: International Agency for Research on Cancer (IARC); 2005. p. 306-7. |
|2.||McGrath CJ, Myall RW. Conservative management of recurrent keratocysts in Basal-cell naevus syndrome. Aust Dent J 1997;42:399-403. |
|3.||Lindeboom JA, Kroon FH, de Vires J, van den Akker HP. Multiple recurrent and de novo odontogenic keratocysts associated with oral-facial-digital syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:458-62. |
|4.||Carr RJ, Green DM. Multiple odontogenic keratocysts in a patient with type II (mitis) ehlers-danlos syndrome. Br J Oral Maxillofac Surg 1988;26:205-14. |
|5.||Connor JM, Evans DA, Goose DH. Multiple odontogenic keratocysts in a case of the Noonan syndrome. Br J Oral Surg 1982;20:213-6. |
|6.||Krimmel M, Reinert S. Multiple odontogenic keratocysts in mental retardation-overgrowth (Simpson-Golabi-Behmel) syndrome. Br J Oral Maxillofac Surg 2000;38:221-3. |
|7.||Auluck A, Suhas S, Pai KM. Multiple odontogenic keratocysts: Report of a case. J Can Dent Assoc 2006;72:651-6. |
|8.||Parikh NR. Nonsyndromic multiple odontogenic keratocysts: Report of case. J Adv Dent Res 2010;1:71-4. |
|9.||São Paulo. Non-syndromic keratocystic odontogenic tumor involving the maxillary sinus: Case report. Intl Arch Otorhinolaryngol 2010;14:364-7. |
|10.||Brannon RB. The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part I. Clinical features. Oral Surg Oral Med Oral Pathol 1976;42:54-72. |
|11.||González-Alva P, Tanaka A, Oku Y, Yoshizawa D, Itoh S, Sakashita H, et al. Keratocystic odontogenic tumor: A retrospective study of 183 cases. J Oral Sci 2008;50:205-12. |
|12.||Reisner KR, Riva RD, Cobb RJ, Magidson JG, Goldman HS, Sordill WC. Treating nevoid basal cell carcinoma syndrome. J Am Dent Assoc 1994;125:1007-11. |
|13.||Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA. Complications of the naevoid basal cell carcinoma syndrome: Results of a population based study. J Med Genet 1993;30:460-4. |
|14.||Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299-308. |
|15.||Bakaeen G, Rajab LD, Sawair FA, Hamdan MA, Dallal ND. Nevoid basal cell carcinoma syndrome: A review of the literature and a report of a case. Int J Paediatr Dent 2004;14:279-87. |
|16.||Woolgar JA, Rippin JW, Browne RM. The odontogenic keratocyst and its occurrence in the nevoid basal cell carcinoma syndrome. Oral Surg Oral Med Oral Pathol 1987;64:727-30. |
|17.||White SC, Pharoah MJ. Cysts of the jaws. In: White SC, Pharoah MJ, editors. Oral radiology: Principles and interpretation. 5 th ed. St. Louis, MO: Mosby; 2004. p. 384-409. |
|18.||Habibi A, Saghravanian N, Habibi M, Mellati E, Habibi M. Keratocystic odontogenic tumor: A 10-year retrospective study of 83 cases in an Iranian population. J Oral Sci 2007;49:229-35. |
|19.||Blanas N, Freund B, Schwartz M, Furst IM. Systematic review of the treatment and prognosis of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:553-8. |
|20.||MacDonald-Jankowski DS. Keratocystic odontogenic tumour: Systematic review. Dentomaxillofac Radiol 2011;40:1-23. |
|21.||Eryilmaz T, Ozmen S, Findikcioglu K, Kandal S, Aral M. Odontogenic keratocyst: An unusual location and review of the literature. Ann Plast Surg 2009;62:210-2. |
|22.||Chi AC, Owings JR Jr, Muller S. Peripheral odontogenic keratocyst: Report of two cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:71-8. |
|23.||Janse van Rensburg L, Nortje CJ, Thompson I. Correlating imaging and histopathology of an odontogenic keratocyst in the nevoid basal cell carcinoma syndrome. Dentomaxillofac Radiol 1997;26:195-9. |
|24.||Neville BW, Damm DD, Allen CM, Bouquet JE. In: Oral and maxillofacial pathology. 3 rd ed. Missouri; Elsevier; 2004. p. 648-50. |
|25.||Dominguez FV, Keszler A. Comparative study of keratocysts, associated and non-associated with nevoid basal cell carcinoma syndrome. J Oral Pathol 1988;17:39-42. |
|26.||Sun LS, Li XF, Li TJ. PTCH1 and SMO gene alterations in keratocystic odontogenic tumors. J Dent Res 2008;87:575-9. |
|27.||Rogers MA, Edler L, Winter H, Langbein L, Beckmann I, Schweizer J. Characterization of new members of the human type II keratin gene family and a general evaluation of the keratin gene domain on chromosome 12q13.13. J Invest Dermatol 2005;124:536-44. |
|28.||Heikinheimo K, Jee KJ, Morgan PR, Nagy B, Knuutila S, Leivo I. Genetic changes in sporadic keratocystic odontogenic tumors (odontogenic keratocysts). J Dent Res 2007;86:544-9. |
|29.||Malciæ A, Jukiæ S, Aniæ I, Paveliæ B, Kapitanoviæ S, Kruslin B, et al . Alterations of FHIT and P53 genes in keratocystic odontogenic tumor, dentigerous and radicular cyst. J Oral Pathol Med 2008;37:294-301. |
|30.||Kuroyanagi N, Sakuma H, Miyabe S, Machida J, Kaetsu A, Yokoi M, et al. Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): Analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation. J Oral Pathol Med 2009;38:386-92 |
|31.||Zhang L, Sun ZJ, Zhao YF, Bian Z, Fan MW, Chen Z. Inhibition of SHH signaling pathway: Molecular treatment strategy of odontogenic keratocyst. Med Hypotheses 2006;67:1242-4. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]