- Email: [email protected]
Bilateral keratocystic odontogenic tumor of mandible – A unique pediatric lesion: Case report and review
International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case Report
Bilateral keratocystic odontogenic tumor of mandible – A unique pediatric lesion: Case report and review Reena Radhikaprasad Sarkar a,*, G.P. Rathod b a b
Professor and Head, Department of Oral and Maxillofacial Pathology and Microbiology, National Dental College, Derabassi, Mohali, Punjab, India Professor, Head and Postgraduate Teacher, Oral Pathology, PDM Dental College, Bahadurgarh, Haryana, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 17 June 2013 Received in revised form 8 September 2013 Accepted 10 September 2013 Available online 19 September 2013
The keratocystic odontogenic tumor (KCOT) is the most common cystic neoplasm in the maxillofacial region. Multiple odontogenic keratocyst are usually associated with Nevoid Basal Cell Carcinoma (NBCC) syndrome. A variant of this neoplasm is the sporadic multiple KCOT in pediatric population. Presented here is a case of bilateral keratocystic odontogenic tumor in a fourteen year old. Multiple keratocysts in the pediatric population is rare, aggressive, and recurrent and the first sign of NBCC or the solo presentation of human homologue of the PTCH (Drosophila segment polarity gene Patched) gene mutation. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Neoplasm Keratocystic odontogenic tumor Juvenile Nevoid Basal Cell Carcinoma syndrome
1. Introduction The keratocystic odontogenic tumor (KCOT) is the most common cystic neoplasm in the maxillofacial region. Formerly known as odontogenic keratocyst (OKC), it constitutes about 3– 21.5% of all odontogenic cysts. The peak incidence is second to fourth decades of life and usually shows a male predilection [1]. Majority of lesions occur in the mandible mainly in posterior body and ascending ramus region. Multiple odontogenic keratocyst are usually associated with Nevoid Basal Cell Carcinoma or Goltz Gorlin (NBCC) syndrome. Histopathological studies show that presence of parakeratinization, intramural epithelial remnants and satellite cysts are more among NBCCS associated OKC [2]. A variant of this neoplasm is the sporadic multiple KCOT in pediatric population. Multiple KCOTs have a propensity to recur. All clinicians need to be alert to clinicopathologic markers of recurrence namely younger age, parakeratinization, inflammation, daughter cysts, subepithelial split, sub epithelial hyalinization. Also, such a sporadic incidence may be the first sign Of Nevoid Basal Cell Carcinoma syndrome. 1.1. Case report A 14-year-old male patient reported to the department with a 15-day-old right sided painful swelling. A 10 cm 3 cm hard * Correspondence to: 1357 Sector 26, Panchkula, Haryana, India. Tel.: +91 09988222449/08558058355. E-mail addresses: [email protected] (R.R. Sarkar), [email protected] (G.P. Rathod). 1871-4048/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pedex.2013.09.001
diffuse swelling was evident at right mandibular parasymphyseal region. No lymph nodes were palpable. Intraorally, an intraosseous lesion was seen in relation to teeth 31–85, 4 cm 2 cm irregular with draining sinus in vestibule corresponding to 84 (Fig. 1). The teeth 41, 83, 84, 85 were mobile. Orthopantomogram showed radiolucency extending in the region of 31–85 with impacted 42, 43, 44, 45 (Fig. 2). An additional radiolucency was detected in left ramus in relation to impacted 38. Aspiration fluid from right parasymphyseal region was a serosanguinous yield and that of the ramus region was creamy semisolid type. Provisionally diagnosis was of multiple odontogenic keratocyst and dentigerous cyst was considered as a differential. Family history was noncontributory. Excisional biopsy (with subsequent usage of Carnoy’s solution) yielded from ramus region; a 4 cm 2 cm 3 cm enucleated cystic lining attached at the cervical portion of 38. Biopsy from the right parasymphyseal cyst was of dimension 1 cm 1 cm 1 cm (Fig. 3a–c). Marsupalization was carried out leaving the impacted teeth intact so as to allow them to erupt. A consultation with physician failed to add to the medical history. Hematoxylin and eosin stained serial sections were evaluated histologically. Both the lesions showed cystic lining which was incomplete, parakeratinized stratified squamous epithelium showing folding. Keratin layer was thin and corrugated. Lumen showed almost nil keratin content. Basal cells were low columnar to cuboidal with palisaded nucleus (Fig. 4). Intraluminal epithelial plaques could be seen with basal cells hyper plastic, hyper chromatic, low cuboidal at places (Fig. 5). Mitosis could be seen both suprabasally and basally. Epithelial connective tissue
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
141
Fig. 1. Intraosseous swelling in region of 84 with draining sinus. Fig. 4. Basal cells were low columnar to cuboidal with palisaded nucleus. Hematoxylin and eosin (450).
2. Discussion
Fig. 2. Orthopantomogram parasymphyseal cyst is massive, crossing midline with several impacted permanent teeth, unilocular ramus cyst with scalloped margin and impacted 38.
interface was flat showing both sub-basal and supra-basal split (Fig. 6). At certain areas epithelium was effaced or atrophic in many areas and typical features were lost (Fig. 7). Capsule was composed of loosely arranged collagen bundles with generalized chronic inflammation in both the cysts. Early hyalinization could be seen subepithelially. Numerous daughter cysts could be detected (Fig. 8a and b). In the parasymphyseal cyst, parakeratinized stratified squamous gingival epithelium corresponding to the draining sinus could be seen. The ramus cyst may have shown the inflammation due to the preceding aspiration biopsy procedure. Upon correlating clinico-pathologically, final diagnosis was of multiple sporadic Keratinizing Cystic Odontogenic Tumor: Juvenile, massive, envelopmental (right) and follicular (left).
The term keratocystic odontogenic tumor (KCOT) 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. It may be solitary or multiple. The latter is usually the stigmata of the inherited Nevoid Basal Cell Carcinoma Syndrome (NBCCS) [3]. Owing to its clinical features, its potential for locally destructive behavior, high recurrence rate and tendency to multiplicity, the formerly cystic lesion was termed as a tumor [4]. There exists 43 cases of previously reported patients of multiple OKCs occurring in nonsyndromic patients out of which the pediatric population is involved only in 17 cases (Auluck et al., Parikh, Nirwan et al., Bartake et al., Meara et al.) (Table 1) (upper age limit being 15 years). Reports say that sporadic KCOTs involve a 2 hit mechanism with allelic loss at9q22. The 2 hit mechanism is process by which a tumor suppressor gene is inactivated. The first hit leads to mutation in one allele which has no phenotypic effect although it can be dominantly inherited. The second hit refers to loss of heterozygosity. In case of KCOT it leads to dysregulation in cyclin D1 and p53 [15–17]. 5%of cases of multiple KCOTs in children are indicative of multiple cysts without Goltz Gorlin syndrome [18]. Recurrence rate of such cysts is greater than solitary cyst by a value of 30%. This is of clinical importance and will influence the follow up of the case [6,7].
Fig. 3. Excised tissue from parasymphyseal region (a); from ramus region (b and c). 3c-Cusp imprint of impacted third molar crown cyst, dentigerous relation with tooth crown, root is underdeveloped.
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
142
Table 1 summarizing reported cases of multiple sporadic KCOT. S. no.
Investigator(s)
Year of report
Case report or study
Pediatric population involved
Reference
1 2 3 4 5 6 7 8 9 10 11
Yeo and Loh Meara et al. Auluck et al. Gonzalez-Alva et al. Sholapurkar et al. Rudagi et al. Bartake et al. Guruprasad and Chauhan Parikh Singh et al. Nirwan et al.
1989 1999 2006 2008 2008 2010 2011 2012 2012 2013 2013
Case 11 positive cases Case report-22 years old 183 cases total 11 positive 24-Year-old patient 21-Year-old girl 20-Year-old girl 16 years old 12 years old 186 patients 14 patients positive Three siblings (10, 13, 17 years age)
– 11 cases Yes, history since 7 years old – – – Yes, since age of nine years – Yes – Two cases
[5] [6] [7] [8] [1] [9] [10] [11] [12] [13] [14]
Fig. 5. Intraluminal epithelial plaques could be seen with basal cells hyper plastic, hyper chromatic, low cuboidal at places (450).
Fig. 6. Epithelial connective tissue interface was flat showing supra-basal split (450).
Fig. 7. At certain areas epithelium was effaced or atrophic in many areas and typical features were lost (100).
Fig. 8. (a and b) Satellite cyst 100.
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
Mandible is more involved than maxilla (65–83%) posterior regions were more involved [8]. The lumen of the keratocyst may be filled with a thin straw colored fluid or with a thicker creamy material [18]. Our findings showed thin watery fluid in the parasymphyseal cyst and thick pultaceous aspirate in the ramus cyst. Nevoid Basal Cell Carcinoma syndrome is characterized by multiple OKCs, Nevoid Basal Cell Carcinomas of the skin, bifid ribs, and calcification of the falx cerebri [11]. The systemic features were not present in our case. Both the cysts were unilocular with scalloped margins and associated with unerupted teeth. The ramus KCOT was in true dentigerous relation with the impacted teeth and parasymphyseal KCOT was of envelopmental variety. True dentigerous relation was confirmed in the gross specimen. This conforms to the 25–40% incidence of KCOT associated with impacted teeth [11]. Histologically parakeratinized low columnar palisaded stratified squamous epithelial lining existed. Certain areas showed very thin lining and intraluminal epithelial plaque especially in the parasymphyseal cyst. Smaller epithelial height, fewer total basal nuclei, inflammation in the capsule, presence of islands and daughter cysts were noted. According to Neville et al., 7–26% of cases showed satellite cysts [19]. According to Forssell, who studied serial section of OKC, micro cysts had a 20% incidence rates and epithelial islands had a rate of occurrence of 50% [18]. Also daughter cyst are associated with higher frequency of allelic loss [20]. In our case; younger age, association with impacted tooth, parakeratinization, presence of inflammation, separation of epithelium from capsule and presence of satellite cyst and epithelial islands were pointing to an aggressive lesion [21–23]. In my opinion this case is a partial expression of NBCC. The clinicopathologic features such as early age, multiple cysts, inflammation, presence of daughter cysts, smaller epithelial height, sub and supra epithelial split are all harbingers of NBCC associated recurrent KCOT. The absence of family history and other features of syndrome can be due to variation in penetration and expression of different mutations within same gene.33-50% cases show new mutations. NBCC patients are known to carry nine variants of mutation and a decade may pass before systemic signs set in clinically [7]. Future scope will be in the form of extensively investigating PTCH gene mutation and mandatory genetic counseling. Successful treatment methods are enucleation and Carnoy’s solution in small lesions and marsupalization for large lesions [24]. Our case was similarly treated. So far only two cases reports which term multiple KCOT as partial expression of NBCCS [5,6]. Multiple KCOT in pediatric population is rare and such reports add to the world literature. The oral pathologist may serve as the whistle blower and sound an alert toward possible recurrences and emergence of dieases associated with NBCC, in patients and their off springs.
143
References [1] A.A. Sholapurkar, M.V. Reddy, M.P. Keerthilatha, V. Geetha, Nonsyndromic multiple odontogenic keratocyst: report of case, Rev. Clin. Pesq. Odontol. 4 (3) (2008) 193–199. [2] J.A. Regezi, J.J. Sciubba, Odontogenic tumors, in: J.A. Regezi, J.J. Sciubba (Eds.), Oral Pathology: Clinical Pathologic Correlations, 6th ed., WB Saunders, Philadelphia, USA, 2012, pp. 246–255. [3] D.S. MacDonald-Jankowski, Keratocystic odontogenic tumour: systematic review, Dentomaxillofac. Radiol. 40 (2011) 1–23. [4] A. Shuster, B. Shlomi, V. Reiser, I. Kaplan, Solid keratocystic odontogenic tumor— report of a nonaggressive case, J. Oral Maxillofac. Surg. 70 (April (4)) (2012) 865– 870. , http://dx.doi.org/10.1016/j.joms.2011.02.140. [5] J.F. Yeo, F.C. Loh, Multiple odontogenic keratocysts of the jaws. Case report, Aust. Dent. J. 34 (December (6)) (1989) 503–506. [6] J.G. Meara, K.K. Li, S.S. Shah, M.J. Cunningham, Odontogenic keratocysts in the pediatric population, Arch. Otolaryngol. Head Neck Surg. 122 (July (7)) (1996) 725–728. [7] A. Auluck, S. Suhas, K.M. Pai, Multiple odontogenic keratocysts: report of a case, J. Can. Dent. Assoc. 72 (September (7)) (2006) 651–656. [8] P. Gonzalez-Alva, A. Tanaka, Y. Oku, D. Yoshizawa, S. Itoh, H. Sakashita, et al., Keratocystic odontogenic tumors: a retrospective study of 183 cases, J. Oral. Sci. 50 (June (2)) (2008) 205–212. [9] B.M. Rudagi, V.R. Kharkar, Y. Kini, Multiple odontogenic keratocyst with diverse histologic features in a nonsyndromic patient, Pravara Med. Rev. 2 (3) (2010) 35–37. [10] A. Bartake, N. Shreekanth, S. Prabhu, K. Gopalkrishnan, Nonsyndromic recurrent multiple odontogenic keratocyst: a case report, J. Dent. (Tehran) 8 (Spring (2)) (2011) 96–100. [11] Y. Guruprasad, D.S. Chauhan, Multiple odontogenic keratocysts in a nonsyndromic patient, J. Cranio Max Dis. 1 (2012) 36–40. [12] D.R. Parikh, Nonsyndromic multiple odontogenic keratocysts: a case report, NJIRM 3 (4) (2012) 142–145. [13] H.P. Singh, A. Nayyar, A. Raj, P. Kumar, Are all odontogenic keratocysts keratocystic odontogenic tumors? Correlation between imaging features and epithelial cell proliferation, J. Clin. Imaging Sci. (2013), http://dx.doi.org/10.4103/21567514.106616, 3/1/3/106616. [14] A. Nirwan, S.P. Wanjari, R. Saikhedkar, K. Vinayak, Multiple nonsyndromic odontogenic keratocysts in three siblings, BMJ Case Rep. March (2013), http:// dx.doi.org/10.1136/bcr-2012-007503, pii: bcr2012007503. [15] J. Madras, H. Lapointe, Keratocystic odontogenic tumor: reclassification of the odontogenic keratocyst from cyst to tumor, J. Can. Dent. Assoc. 74 (March (2)) (2008) 165–1165. [16] A.R. Casaroto, D.C. Loures, E. Moreschi, V.C. Veltrini, V.D. Gottardo, V.S. Lara, Early diagnosis of Gorlin-Goltz syndrome: case report, Head Face Med. 25 (7) (2011) 1– 5. , http://dx.doi.org/10.1186/1746-160X-7-2. [17] G.D. Rabelo, J.C.G. Henriques, J.H. Macedo, C.J. Silva, S.V. Cardoso, A.M. Loyola, et al., Non-syndromic keratocystic odontogenic tumor involving the maxillary sinus: case report, Int. Arch. Otorhinolaryngol. 14 (3) (2010) 364–367. [18] R. Rajendran, Chapter 4, cysts and tumors of odontogenic origin, in: R. Rajendran, B. Sivapathasundaram (Eds.), Shafer’s Textbook of Oral Pathology, 6th ed., Elsevier Inc., 2009, pp. 254–297. [19] B.W. Neville, D.D. Damm, C.M. Allen, J.E. Buoquot, Chapter 15, odontogenic cysts and tumors, in: Oral and Maxillofacial Pathology, 3rd ed., Elsevier Inc., Saunders, 2009, pp. 670–700. [20] N. Kuroyanagi, H. Sakuma, S. Miyabe, J. Machida, A. Kaetsu, M. Yokoi, 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. 38 (2009) 386–392. , http://dx.doi.org/ 10.1111/j.1600-0714.2008.00729.x. [21] P.J. Boyne, D. Hou, C. Moretta, T. Pritchard, The multifocal nature of odontogenic keratocysts, J. Calif. Dent. Assoc. 33 (December (12)) (2005) 961–965. [22] T. Goichi, T. Makino, T. Kikuchi, K. Kishimoto, A. Nishiyama, A. Sasaki, et al., A comparative analysis of odontogenic keratocysts associated with and not associated with an impacted mandibular third molar, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 94 (August (2)) (2002) 272–275. [23] H.E. Cottom, F.I. Bshena, P.M. Speight, G.T. Craig, A.V. Jones, Histopathological features that predict the recurrence of odontogenic keratocysts, J. Oral Pathol. Med. 41 (2012) 408–414. , http://dx.doi.org/10.1111/j.1600-0714.2011.01113.x. [24] N. Guler, K. Sencift, O. Demirkol, Conservative management of keratocystic odontogenic tumors of jaws, Scientific World J. 2012 (2012) 680397, http:// dx.doi.org/10.1100/2012/680397.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case Report
Bilateral keratocystic odontogenic tumor of mandible – A unique pediatric lesion: Case report and review Reena Radhikaprasad Sarkar a,*, G.P. Rathod b a b
Professor and Head, Department of Oral and Maxillofacial Pathology and Microbiology, National Dental College, Derabassi, Mohali, Punjab, India Professor, Head and Postgraduate Teacher, Oral Pathology, PDM Dental College, Bahadurgarh, Haryana, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 17 June 2013 Received in revised form 8 September 2013 Accepted 10 September 2013 Available online 19 September 2013
The keratocystic odontogenic tumor (KCOT) is the most common cystic neoplasm in the maxillofacial region. Multiple odontogenic keratocyst are usually associated with Nevoid Basal Cell Carcinoma (NBCC) syndrome. A variant of this neoplasm is the sporadic multiple KCOT in pediatric population. Presented here is a case of bilateral keratocystic odontogenic tumor in a fourteen year old. Multiple keratocysts in the pediatric population is rare, aggressive, and recurrent and the first sign of NBCC or the solo presentation of human homologue of the PTCH (Drosophila segment polarity gene Patched) gene mutation. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Neoplasm Keratocystic odontogenic tumor Juvenile Nevoid Basal Cell Carcinoma syndrome
1. Introduction The keratocystic odontogenic tumor (KCOT) is the most common cystic neoplasm in the maxillofacial region. Formerly known as odontogenic keratocyst (OKC), it constitutes about 3– 21.5% of all odontogenic cysts. The peak incidence is second to fourth decades of life and usually shows a male predilection [1]. Majority of lesions occur in the mandible mainly in posterior body and ascending ramus region. Multiple odontogenic keratocyst are usually associated with Nevoid Basal Cell Carcinoma or Goltz Gorlin (NBCC) syndrome. Histopathological studies show that presence of parakeratinization, intramural epithelial remnants and satellite cysts are more among NBCCS associated OKC [2]. A variant of this neoplasm is the sporadic multiple KCOT in pediatric population. Multiple KCOTs have a propensity to recur. All clinicians need to be alert to clinicopathologic markers of recurrence namely younger age, parakeratinization, inflammation, daughter cysts, subepithelial split, sub epithelial hyalinization. Also, such a sporadic incidence may be the first sign Of Nevoid Basal Cell Carcinoma syndrome. 1.1. Case report A 14-year-old male patient reported to the department with a 15-day-old right sided painful swelling. A 10 cm 3 cm hard * Correspondence to: 1357 Sector 26, Panchkula, Haryana, India. Tel.: +91 09988222449/08558058355. E-mail addresses: [email protected] (R.R. Sarkar), [email protected] (G.P. Rathod). 1871-4048/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pedex.2013.09.001
diffuse swelling was evident at right mandibular parasymphyseal region. No lymph nodes were palpable. Intraorally, an intraosseous lesion was seen in relation to teeth 31–85, 4 cm 2 cm irregular with draining sinus in vestibule corresponding to 84 (Fig. 1). The teeth 41, 83, 84, 85 were mobile. Orthopantomogram showed radiolucency extending in the region of 31–85 with impacted 42, 43, 44, 45 (Fig. 2). An additional radiolucency was detected in left ramus in relation to impacted 38. Aspiration fluid from right parasymphyseal region was a serosanguinous yield and that of the ramus region was creamy semisolid type. Provisionally diagnosis was of multiple odontogenic keratocyst and dentigerous cyst was considered as a differential. Family history was noncontributory. Excisional biopsy (with subsequent usage of Carnoy’s solution) yielded from ramus region; a 4 cm 2 cm 3 cm enucleated cystic lining attached at the cervical portion of 38. Biopsy from the right parasymphyseal cyst was of dimension 1 cm 1 cm 1 cm (Fig. 3a–c). Marsupalization was carried out leaving the impacted teeth intact so as to allow them to erupt. A consultation with physician failed to add to the medical history. Hematoxylin and eosin stained serial sections were evaluated histologically. Both the lesions showed cystic lining which was incomplete, parakeratinized stratified squamous epithelium showing folding. Keratin layer was thin and corrugated. Lumen showed almost nil keratin content. Basal cells were low columnar to cuboidal with palisaded nucleus (Fig. 4). Intraluminal epithelial plaques could be seen with basal cells hyper plastic, hyper chromatic, low cuboidal at places (Fig. 5). Mitosis could be seen both suprabasally and basally. Epithelial connective tissue
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
141
Fig. 1. Intraosseous swelling in region of 84 with draining sinus. Fig. 4. Basal cells were low columnar to cuboidal with palisaded nucleus. Hematoxylin and eosin (450).
2. Discussion
Fig. 2. Orthopantomogram parasymphyseal cyst is massive, crossing midline with several impacted permanent teeth, unilocular ramus cyst with scalloped margin and impacted 38.
interface was flat showing both sub-basal and supra-basal split (Fig. 6). At certain areas epithelium was effaced or atrophic in many areas and typical features were lost (Fig. 7). Capsule was composed of loosely arranged collagen bundles with generalized chronic inflammation in both the cysts. Early hyalinization could be seen subepithelially. Numerous daughter cysts could be detected (Fig. 8a and b). In the parasymphyseal cyst, parakeratinized stratified squamous gingival epithelium corresponding to the draining sinus could be seen. The ramus cyst may have shown the inflammation due to the preceding aspiration biopsy procedure. Upon correlating clinico-pathologically, final diagnosis was of multiple sporadic Keratinizing Cystic Odontogenic Tumor: Juvenile, massive, envelopmental (right) and follicular (left).
The term keratocystic odontogenic tumor (KCOT) 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. It may be solitary or multiple. The latter is usually the stigmata of the inherited Nevoid Basal Cell Carcinoma Syndrome (NBCCS) [3]. Owing to its clinical features, its potential for locally destructive behavior, high recurrence rate and tendency to multiplicity, the formerly cystic lesion was termed as a tumor [4]. There exists 43 cases of previously reported patients of multiple OKCs occurring in nonsyndromic patients out of which the pediatric population is involved only in 17 cases (Auluck et al., Parikh, Nirwan et al., Bartake et al., Meara et al.) (Table 1) (upper age limit being 15 years). Reports say that sporadic KCOTs involve a 2 hit mechanism with allelic loss at9q22. The 2 hit mechanism is process by which a tumor suppressor gene is inactivated. The first hit leads to mutation in one allele which has no phenotypic effect although it can be dominantly inherited. The second hit refers to loss of heterozygosity. In case of KCOT it leads to dysregulation in cyclin D1 and p53 [15–17]. 5%of cases of multiple KCOTs in children are indicative of multiple cysts without Goltz Gorlin syndrome [18]. Recurrence rate of such cysts is greater than solitary cyst by a value of 30%. This is of clinical importance and will influence the follow up of the case [6,7].
Fig. 3. Excised tissue from parasymphyseal region (a); from ramus region (b and c). 3c-Cusp imprint of impacted third molar crown cyst, dentigerous relation with tooth crown, root is underdeveloped.
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
142
Table 1 summarizing reported cases of multiple sporadic KCOT. S. no.
Investigator(s)
Year of report
Case report or study
Pediatric population involved
Reference
1 2 3 4 5 6 7 8 9 10 11
Yeo and Loh Meara et al. Auluck et al. Gonzalez-Alva et al. Sholapurkar et al. Rudagi et al. Bartake et al. Guruprasad and Chauhan Parikh Singh et al. Nirwan et al.
1989 1999 2006 2008 2008 2010 2011 2012 2012 2013 2013
Case 11 positive cases Case report-22 years old 183 cases total 11 positive 24-Year-old patient 21-Year-old girl 20-Year-old girl 16 years old 12 years old 186 patients 14 patients positive Three siblings (10, 13, 17 years age)
– 11 cases Yes, history since 7 years old – – – Yes, since age of nine years – Yes – Two cases
[5] [6] [7] [8] [1] [9] [10] [11] [12] [13] [14]
Fig. 5. Intraluminal epithelial plaques could be seen with basal cells hyper plastic, hyper chromatic, low cuboidal at places (450).
Fig. 6. Epithelial connective tissue interface was flat showing supra-basal split (450).
Fig. 7. At certain areas epithelium was effaced or atrophic in many areas and typical features were lost (100).
Fig. 8. (a and b) Satellite cyst 100.
R.R. Sarkar, G.P. Rathod / International Journal of Pediatric Otorhinolaryngology Extra 8 (2013) 140–143
Mandible is more involved than maxilla (65–83%) posterior regions were more involved [8]. The lumen of the keratocyst may be filled with a thin straw colored fluid or with a thicker creamy material [18]. Our findings showed thin watery fluid in the parasymphyseal cyst and thick pultaceous aspirate in the ramus cyst. Nevoid Basal Cell Carcinoma syndrome is characterized by multiple OKCs, Nevoid Basal Cell Carcinomas of the skin, bifid ribs, and calcification of the falx cerebri [11]. The systemic features were not present in our case. Both the cysts were unilocular with scalloped margins and associated with unerupted teeth. The ramus KCOT was in true dentigerous relation with the impacted teeth and parasymphyseal KCOT was of envelopmental variety. True dentigerous relation was confirmed in the gross specimen. This conforms to the 25–40% incidence of KCOT associated with impacted teeth [11]. Histologically parakeratinized low columnar palisaded stratified squamous epithelial lining existed. Certain areas showed very thin lining and intraluminal epithelial plaque especially in the parasymphyseal cyst. Smaller epithelial height, fewer total basal nuclei, inflammation in the capsule, presence of islands and daughter cysts were noted. According to Neville et al., 7–26% of cases showed satellite cysts [19]. According to Forssell, who studied serial section of OKC, micro cysts had a 20% incidence rates and epithelial islands had a rate of occurrence of 50% [18]. Also daughter cyst are associated with higher frequency of allelic loss [20]. In our case; younger age, association with impacted tooth, parakeratinization, presence of inflammation, separation of epithelium from capsule and presence of satellite cyst and epithelial islands were pointing to an aggressive lesion [21–23]. In my opinion this case is a partial expression of NBCC. The clinicopathologic features such as early age, multiple cysts, inflammation, presence of daughter cysts, smaller epithelial height, sub and supra epithelial split are all harbingers of NBCC associated recurrent KCOT. The absence of family history and other features of syndrome can be due to variation in penetration and expression of different mutations within same gene.33-50% cases show new mutations. NBCC patients are known to carry nine variants of mutation and a decade may pass before systemic signs set in clinically [7]. Future scope will be in the form of extensively investigating PTCH gene mutation and mandatory genetic counseling. Successful treatment methods are enucleation and Carnoy’s solution in small lesions and marsupalization for large lesions [24]. Our case was similarly treated. So far only two cases reports which term multiple KCOT as partial expression of NBCCS [5,6]. Multiple KCOT in pediatric population is rare and such reports add to the world literature. The oral pathologist may serve as the whistle blower and sound an alert toward possible recurrences and emergence of dieases associated with NBCC, in patients and their off springs.
143
References [1] A.A. Sholapurkar, M.V. Reddy, M.P. Keerthilatha, V. Geetha, Nonsyndromic multiple odontogenic keratocyst: report of case, Rev. Clin. Pesq. Odontol. 4 (3) (2008) 193–199. [2] J.A. Regezi, J.J. Sciubba, Odontogenic tumors, in: J.A. Regezi, J.J. Sciubba (Eds.), Oral Pathology: Clinical Pathologic Correlations, 6th ed., WB Saunders, Philadelphia, USA, 2012, pp. 246–255. [3] D.S. MacDonald-Jankowski, Keratocystic odontogenic tumour: systematic review, Dentomaxillofac. Radiol. 40 (2011) 1–23. [4] A. Shuster, B. Shlomi, V. Reiser, I. Kaplan, Solid keratocystic odontogenic tumor— report of a nonaggressive case, J. Oral Maxillofac. Surg. 70 (April (4)) (2012) 865– 870. , http://dx.doi.org/10.1016/j.joms.2011.02.140. [5] J.F. Yeo, F.C. Loh, Multiple odontogenic keratocysts of the jaws. Case report, Aust. Dent. J. 34 (December (6)) (1989) 503–506. [6] J.G. Meara, K.K. Li, S.S. Shah, M.J. Cunningham, Odontogenic keratocysts in the pediatric population, Arch. Otolaryngol. Head Neck Surg. 122 (July (7)) (1996) 725–728. [7] A. Auluck, S. Suhas, K.M. Pai, Multiple odontogenic keratocysts: report of a case, J. Can. Dent. Assoc. 72 (September (7)) (2006) 651–656. [8] P. Gonzalez-Alva, A. Tanaka, Y. Oku, D. Yoshizawa, S. Itoh, H. Sakashita, et al., Keratocystic odontogenic tumors: a retrospective study of 183 cases, J. Oral. Sci. 50 (June (2)) (2008) 205–212. [9] B.M. Rudagi, V.R. Kharkar, Y. Kini, Multiple odontogenic keratocyst with diverse histologic features in a nonsyndromic patient, Pravara Med. Rev. 2 (3) (2010) 35–37. [10] A. Bartake, N. Shreekanth, S. Prabhu, K. Gopalkrishnan, Nonsyndromic recurrent multiple odontogenic keratocyst: a case report, J. Dent. (Tehran) 8 (Spring (2)) (2011) 96–100. [11] Y. Guruprasad, D.S. Chauhan, Multiple odontogenic keratocysts in a nonsyndromic patient, J. Cranio Max Dis. 1 (2012) 36–40. [12] D.R. Parikh, Nonsyndromic multiple odontogenic keratocysts: a case report, NJIRM 3 (4) (2012) 142–145. [13] H.P. Singh, A. Nayyar, A. Raj, P. Kumar, Are all odontogenic keratocysts keratocystic odontogenic tumors? Correlation between imaging features and epithelial cell proliferation, J. Clin. Imaging Sci. (2013), http://dx.doi.org/10.4103/21567514.106616, 3/1/3/106616. [14] A. Nirwan, S.P. Wanjari, R. Saikhedkar, K. Vinayak, Multiple nonsyndromic odontogenic keratocysts in three siblings, BMJ Case Rep. March (2013), http:// dx.doi.org/10.1136/bcr-2012-007503, pii: bcr2012007503. [15] J. Madras, H. Lapointe, Keratocystic odontogenic tumor: reclassification of the odontogenic keratocyst from cyst to tumor, J. Can. Dent. Assoc. 74 (March (2)) (2008) 165–1165. [16] A.R. Casaroto, D.C. Loures, E. Moreschi, V.C. Veltrini, V.D. Gottardo, V.S. Lara, Early diagnosis of Gorlin-Goltz syndrome: case report, Head Face Med. 25 (7) (2011) 1– 5. , http://dx.doi.org/10.1186/1746-160X-7-2. [17] G.D. Rabelo, J.C.G. Henriques, J.H. Macedo, C.J. Silva, S.V. Cardoso, A.M. Loyola, et al., Non-syndromic keratocystic odontogenic tumor involving the maxillary sinus: case report, Int. Arch. Otorhinolaryngol. 14 (3) (2010) 364–367. [18] R. Rajendran, Chapter 4, cysts and tumors of odontogenic origin, in: R. Rajendran, B. Sivapathasundaram (Eds.), Shafer’s Textbook of Oral Pathology, 6th ed., Elsevier Inc., 2009, pp. 254–297. [19] B.W. Neville, D.D. Damm, C.M. Allen, J.E. Buoquot, Chapter 15, odontogenic cysts and tumors, in: Oral and Maxillofacial Pathology, 3rd ed., Elsevier Inc., Saunders, 2009, pp. 670–700. [20] N. Kuroyanagi, H. Sakuma, S. Miyabe, J. Machida, A. Kaetsu, M. Yokoi, 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. 38 (2009) 386–392. , http://dx.doi.org/ 10.1111/j.1600-0714.2008.00729.x. [21] P.J. Boyne, D. Hou, C. Moretta, T. Pritchard, The multifocal nature of odontogenic keratocysts, J. Calif. Dent. Assoc. 33 (December (12)) (2005) 961–965. [22] T. Goichi, T. Makino, T. Kikuchi, K. Kishimoto, A. Nishiyama, A. Sasaki, et al., A comparative analysis of odontogenic keratocysts associated with and not associated with an impacted mandibular third molar, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 94 (August (2)) (2002) 272–275. [23] H.E. Cottom, F.I. Bshena, P.M. Speight, G.T. Craig, A.V. Jones, Histopathological features that predict the recurrence of odontogenic keratocysts, J. Oral Pathol. Med. 41 (2012) 408–414. , http://dx.doi.org/10.1111/j.1600-0714.2011.01113.x. [24] N. Guler, K. Sencift, O. Demirkol, Conservative management of keratocystic odontogenic tumors of jaws, Scientific World J. 2012 (2012) 680397, http:// dx.doi.org/10.1100/2012/680397.