Case Report/Clinical Techniques
Orthokeratinized Odontogenic Cysts Presenting as a Periapical Lesion: Report of a Case and Literature Review Jo~ ao Paulo Silva Servato, MS,* Sergio Vitorino Cardoso, PhD,* Marcelo Caetano Parreira da Silva, MS,† Mirna Scalon Cordeiro, PhD,† Paulo Rogerio de Faria, PhD,‡ and Adriano Mota Loyola, PhD* Abstract Introduction: Inflammatory cysts, granulomas, abscesses, and fibrous scars represent most periapical radiolucencies. However, other less common lesions, such as orthokeratinized odontogenic cysts (OOCs), can be found at this region, and they deserve to be discussed because the prognosis for an OOC is different from that expected for the ordinary inflammatory periapical diseases. Methods: An interesting case of OOC associated with a nonvital tooth in a 40-year-old woman is described. After a previous clinical diagnosis of a radicular cyst, the tooth was extracted, and the lesion was enucleated and submitted to microscopy examination. Results: Because of the detection of an orthokeratinized epithelium lining, a diagnosis of OOC was concluded. After 2 years of periodic follow-up, no signs of recurrence were detected. Conclusions: The presence of keratin in radicular lesions must be carefully evaluated to eliminate the diagnosis of lesions with more aggressive behavior, such as an OOC or even a keratocystic odontogenic tumor. Hence, histopathologic examination is mandatory to confirm the type of lesion and to differentiate other pathologic conditions, therefore establishing patients’ prognoses precisely. (J Endod 2014;40:455–458)
Key Words Differential diagnosis, odontogenic cysts, orthokeratinized odontogenic cyst, radicular cyst
From the *Oral and Maxillofacial Pathology Area, School of Dentistry, Federal University of Uberl^andia, Uberl^andia; † Department of Oral Surgery, UNITRI–Centro Universitario do Tri^angulo, Uberl^andia; and ‡Department of Morphology, Biomedical Science Institute, Federal University of Uberl^andia, Uberl^andia, Minas Gerais, Brazil. Address requests for reprints to Prof Dr Adriano Mota Loyola, Universidade Federal de Uberl^andia, Faculdade de Odonto logia–Area de Patologia, Av. Para, 1720 Campus Umuarama, CEP 38400-902 Uberl^andia, MG, Brazil. E-mail address: [email protected] 0099-2399/$ - see front matter Copyright ª 2014 American Association of Endodontists. http://dx.doi.org/10.1016/j.joen.2013.09.044
JOE — Volume 40, Number 3, March 2014
T
he diagnosis of apical radiolucencies associated with devitalized teeth poses a great challenge for both clinicians and pathologists. Although the most prevalent diagnosis in these cases is either radicular cyst (RC) or granuloma, other entities with much more aggressive behavior, including orthokeratinized odontogenic cyst (OOC) and keratocystic odontogenic tumor (KCOT), may develop in the same region, therefore requiring the attention of oral pathologists during the examination of the specimens to avoid an improper diagnosis (1–4). Thus, differentiation from an indolent to a life-threatening disease growing in the periapical region, although uncommon, is potentially real (3, 4). Hence, the faster the diagnosis, the better the prognosis will be, especially for those patients affected by tumors (3, 4). Whatever the lesion may be, microscopic examination remains the gold standard tool for making the correct diagnosis of such lesions and should be used for any soft tissues removed during surgical procedures. In this article, we describe a rare case of OOC mimicking a radicular cyst and present a pertinent review of the literature discussing different aspects of this odontogenic lesion, including its clinicopathologic and biological behavior, histopathologic features, and the prognosis and treatment of the affected patient.
Case Report A 40-year-old woman was referred to the Oral Medicine Department of Centro Universitario do Tri^angulo (UNITRI); she was complaining about spontaneous pain and swelling in the oral cavity. Her medical history was noncontributory. The patient’s dental history showed no previous buccal or facial pain, traumatic dental injury, or other abnormalities at the periodontal region. Clinical examination revealed a swelling in the region of tooth #8. It presented a large dental restoration and complete absence of vitality, as demonstrated by using tetrafluoroethane spray. No tooth mobility was detected. On palpation, both buccal and palatal structures surrounding the tooth were painless. Periapical radiography was taken and exhibited a unilocular, well-circumscribed, round-shaped radiolucent lesion measuring about 25 mm that was closely associated with the root of the right upper central incisor. The lesion appeared to slightly displace the adjacent tooth’s root, without provoking root resorption (Fig. 1A and B). On the basis of the dimension of the radiographic image and the close association with nonvital teeth, a hypothesis of radicular cyst was raised, and endodontic treatment was indicated. Because of finances and the poor prognosis for periodontal status, the patient refused to submit to this conservative treatment and preferred to remove all periodontally compromised teeth in conjunction with the lesion to further use a total dental prosthesis. After surgery, the lesion was immediately submerged in 10% neutral buffered formalin and sent to the laboratory to be examined microscopically. At the oral pathology laboratory, a brownish cystic lesion measuring 27 19 9 mm was cut into small pieces, processed according to standardized histotechnical methods, and then embedded in paraffin. Sections 5-mm-thick were obtained from the paraffin block and stained with hematoxylin-eosin. Microscopically, a keratinized, stratified epithelium was observed lining the lesion. In some areas of this epithelium, a predominance of orthokeratin intermixing with a small area of parakeratin could be noted (Fig. 1C). In general, the lining was composed of layers 4–7 cells in thickness, but other regions were thicker than this, especially in
Periapical Orthokeratinized Odontogenic Cyst
455
Case Report/Clinical Techniques
Figure 1. (A) Periapical radiography exhibited a unilocular, well-circumscribed, radiolucent cyst, measuring about 25 mm, associated with the root of the right upper central incisor (distal view). (B) Periapical radiography exhibited a unilocular, well-circumscribed, radiolucent cyst (mesial view). (C) Hematoxylin-eosin stain; original magnification, 40. Cystic lesion showing orthokeratinized stratified squamous epithelium, with 7–10 cell layers thick. The capsule was composed of a fibrous connective tissue wall that contained severe chronic inflammatory cells. (D) Hematoxylin-eosin stain; original magnification, 400. Cystic stratified epithelium exhibiting orthokeratinization; the basal cells are hyperchromatic and show little tendency to palisade or polarize.
those areas intensively infiltrated by inflammatory cells. In general, a well-defined, non-palisaded basal layer was seen in the whole extension of the epithelium, and the correspondent cells usually exhibited basophilic nuclei (Fig. 1D). Likewise, parts of the epithelium showed stratification as well as a slight or even complete absence of keratin on the surface, notably when associated with the underlying inflammatory foci in the cystic wall, resembling a typical radicular cyst. Moreover, the cystic wall was composed of fibrous connective tissue exhibiting a multifocal, intense, chronic inflammatory infiltrate, and odontogenic epithelial rests without forming satellite cysts were seen as well. The final diagnosis was OOC. After 2 years of follow-up, complete bone formation was observed, and there was no recurrence of the lesion.
Discussion In the present study, we described a rare case of OOC developing close to the radicular root of tooth #8, mimicking a radicular cyst. In contrast to radicular cysts that are primarily associated with the inflammatory process, OOCs are admitted to have a developmental origin as a result of PTCH gene mutation. They represent 10% of all cases previously diagnosed as odontogenic keratocyst (OK) (5–11). Payne (5) first described OOC in 1972, followed by Wright (6), who classified the lesion as a variant of the OK because of the presence of an orthokeratinized layer on the epithelium surface and less tendency of recurrence. For a long time, OOC has been recognized by the World Health Organization as an entity derived from OK (12, 13). However, in its last edition launched in 2005, the World Health Organization reclassified OK as KCOT, and OOC was recognized as a distinct entity different from KCOT (14). Taking into consideration and evaluating the pertinent literature, there have been few published series reporting clinical, histologic, and immunohistochemical profiles of OOC (5–11, 15–17). Clinically, OOC presents as a painless solitary lesion, occurring predominantly at the posterior region of the mandible in young males (10). Radiographically, 90% of OOCs are unilocular and exhibit a welldefined limit, buccolingual expansion, and complete absence of root resorption (11). However, in some circumstances, this lesion may develop to show different aspects and epicenters, including its rare association with Gorlin syndrome (11). In contrast to a radicular cyst, an OOC is a cystic lesion with great growth potential, and in some cases huge dimensions have been reported (5–11, 18). In the present reported case, the occurrence in the periapical region in close association with a nonvital tooth, the small dimension, and the absence of any kind of symptoms made it difficult to promptly recognize the precise nature of the lesion. Because of this, histologic 456
Silva Servato et al.
examination was crucial to conclude the diagnosis. Microscopically, OOC is characterized by the presence of medium-thickness orthokeratinized epithelium with non-palisaded cells in the basal layer. Sometimes parakeratinization and hyperplasia can be focally observed. Skin appendages (ie, hair follicles, sebaceous and sweat glands) and satellite cysts have not been described for these lesions (8, 10, 11). In radicular cysts, keratinizing epithelium has been observed in less than 2% of cases (orthokeratinization is predominant), representing a metaplastic process, and usually it is a focal phenomenon (19–22). In addition, Browne (22, 23) showed that the presence of keratin in RC was significantly associated with the age of patients, with higher incidence between the second and third decades of life (mean, 32.1 years), lower than that seen in non-keratinized radicular cysts (mean of 40.2 years and incidence peak above the third decade) (22, 23). Similar ages are described for OOCs. Even when these microscopic characteristics are actually considered as gold standard parameters to ultimately establish a differential diagnosis between OOC and keratinized RC, this is not an easy task. In fact, there are no specific criteria to distinguish keratinized RCs from OOCs and KCOTs. Although it might be made histologically, there are some instances in which a complete examination of the lining is mandatory to confirm the presence of orthokeratin covering the OOC’s epithelium completely (5–11, 19). On the other hand, as pointed out elsewhere (9, 23), a differential diagnosis among them may be difficult, particularly when there is a secondary infection and keratin is not clearly evident on the lining surface. Despite this, there are other histologic features that may be useful to distinguish each other. One aspect is the position of the nuclei from the basal stratum, normally orientated away from the basement membrane in KCOT, but not in OOCs or RCs (14, 19). This is particularly significant because oral pathologists have used this method to differentiate KCOT from OOC and keratinized RCs. In addition to this fact, it has been postulated that cystic lesions showing either orthokeratin or an epithelium similar to that seen in parakeratotic oral mucosa, as well as other pathologic conditions with scanty parakeratin areas, should not be diagnosed as KCOTs or even as OOCs (19–24). Although there are many articles reporting the immunohistochemistry cytokeratin profile expression for RC and KCOT, this information is not useful for OOC and keratinized RC. To this end, more studies should be done to clarify the possibility of discovering new biomarkers that will help clinicians and pathologists to clearly differentiate between the various cysts arising in jaws. Our review identified 7 cases of OOC mimicking periapical lesions (9, 10, 24–26), which are presented in Table 1. Our case is unusual for several reasons. First, it was reported in a 40-year-old woman who JOE — Volume 40, Number 3, March 2014
No Enucleation 27 19 9
No Enucleation
Conclusion Through the experience gained in the present case, we reinforce the importance of histopathologic examination of all excised periapical lesions because the clinical diagnosis may fail, and a misdiagnosis may be made. In addition, it is important to keep in mind that all keratinized cysts developing in the radicular region should be warily evaluated to rule out the presence of KCOT or even OOC, which in turn behaves more aggressively than RCs.
Acknowledgments The authors thank Fundac¸~ao Estadual de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq) for their financial support. The authors deny any conflicts of interest related to this study.
F
Maxilla, #8
References
ND, no data; NSR, no sign of recurrence.
40 Servato et al, 2012 (present) 8
39 Onuki et al, 2009 (25) 7
M
Mandible, #18
Swelling, pain, and fistula Swelling and pain
ND
No Enucleation 50 30 ND Mandible, #17 M 40 Li et al, 1998 (9) 6
JOE — Volume 40, Number 3, March 2014
developed a lesion in the anterior maxilla, an uncommon location for OOC (11, 19). Second, the lesion represents a significant issue for clinicians and pathologists, especially because OOC does not present a specific therapeutic strategy to be applied in all cases, and the prognosis is yet to be determined. Third, our case reinforces the importance of new studies focusing on the differentiation of these lesions through the establishment of reliable criteria for correct diagnosis (5–11, 19, 24–27). The treatments of OOCs and RCs are different in many aspects. It may be suitable to treat both lesions with surgical excision, and relapses are not expected (5–11, 19, 24–26). However, it has been suggested that the vast majority of RCs may be resolved following conservative endodontic therapy, with 85%–90% of apical lesions disappearing or becoming markedly reduced in size after conservative endodontic procedures, whereas the same outcome is not expected for OOCs (19, 27).
NSR, 2 y
NSR, 7 mo
NSR, 8 y
ND NSR, 9 y ND No ND ND 25 25 20 Enucleation 21 27 Stajcic et al, 1987 (24) Stajcic et al, 1987 (24) Vuhahula et al, 1993 (10) Li et al, 1998 (9) 2 3 4 5
M F
Maxilla, #8–#4 ND Maxilla, #14–#15 ND
10
ND ND
Treatment
Enucleation
Size (mm)
Asymptomatic
Radiolucency Site
Maxilla, #6 M 41
Age (y) Gender Author, year
Hancock et al, 1986 (26) 1
Case
TABLE 1. Cases of OOC That Resemble Radicular Cysts in the International Literature
Symptomatology
Unilocular/well-defined radiolucency associated with apical areas of #6 No data could be retrieved No data could be retrieved ND Unilocular radiolucency associated with apical areas of #14–#15 Unilocular radiolucency associated with apical area of #17 Unilocular radiolucency associated with apical area of #18 Unilocular/well-defined radiolucency associated with apical area of #8
Recurrence Follow-up
Case Report/Clinical Techniques
1. Koivisto T, Bowles WR, Rohrer M. Frequency and distribution of radiolucent jaw lesions: a retrospective analysis of 9,723 cases. J Endod 2012;38:729–32. 2. Aggarwal V, Logani A, Shah N. The evaluation of computed tomography scans and ultrasounds in the differential diagnosis of periapical lesions. J Endod 2008;34: 1312–5. 3. Tatlidil R, G€oz€ub€uy€uk MM. Mucinous adenocarcinoma of lung presenting as oral metastases: a case report and literature review. J Endod 2001;37:110–3. 4. Bueno MR, De Carvalhosa AA, Castro PH, et al. Mesenchymal chondrosarcoma mimicking apical periodontitis. J Endod 2008;34:1415–9. 5. Payne TF. An analysis of the clinical and histopathologic parameters of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol 1972;33:538–46. 6. Wright JM. The odontogenic keratocyst: orthokeratinized variant. Oral Surg Oral Med Oral Pathol 1981;51:609–18. 7. MacDonald-Jankowski DS, Li TK. Orthokeratinized odontogenic cyst in a Hong Kong community: the clinical and radiological features. Dentomaxillofac Radiol 2010;39: 240–5. 8. Dong Q, Pan S, Sun LS, Li TJ. Orthokeratinized odontogenic cyst: a clinicopathologic study of 61 cases. Arch Pathol Lab Med 2010;134:271–5. 9. Li TJ, Kitano M, Chen XM, et al. Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15 cases. Histopathology 1998;32: 242–51. 10. Vuhahula E, Nikai H, Ijuhin N, et al. Jaw cysts with orthokeratinization: analysis of 12 cases. J Oral Pathol Med 1993;22:35–40. 11. Macdonald-Jankowski DS. Orthokeratinized odontogenic cyst: a systematic review. Dentomaxillofac Radiol 2010;39:455–67. 12. Pindborg JJ, Kramer IRH, Torloni H. Histological Typing of Odontogenic Tumours, Jaw Cysts, and Allied Lesions, 1st ed. Geneva: World Health Organization/Springer-Verlag; 1971. 13. Kramer IRH, Pindborg JJ, Shear M. Histological Typing of Odontogenic Tumors. 2nd ed. Berlin: Springer-Verlag; 1992. 14. Philipsen HP. Odontogenic keratocystic tumor. In: Barnes L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon, France: IARC Press; 2005: 306–7.
Periapical Orthokeratinized Odontogenic Cyst
457
Case Report/Clinical Techniques 15. Nadalin MR, Fregnani ER, Silva-Sousa YT, da Cruz Perez DE. Presence of myofibroblasts and matrix metalloproteinase 2 in radicular cysts, dentigerous cysts, and keratocystic odontogenic tumors: a comparative immunohistochemical study. J Endod 2012;38:1363–7. 16. Johann AC, Caldeira PC, Caliari MV, et al. Metallothionein in the radicular, dentigerous, orthokeratinized odontogenic cysts and in keratocystic odontogenic tumor. J Oral Pathol Med 2011;40:270–6. 17. Aragaki T, Michi Y, Katsube K, et al. Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst. Hum Pathol 2010;41:1718–25. 18. Diniz MG, Galv~ao CF, Macedo PS, et al. Evidence of loss of heterozygosity of the PTCH gene in orthokeratinized odontogenic cyst. J Oral Pathol Med 2011;40:277–80. 19. Shear M, Speight P. Radicular cyst. In: Shear M, Speight P, eds. Cysts of the Oral and Maxillofacial Regions, 4th ed. Oxford, UK: Blackwell Munksgaard; 2008:123–42. 20. Pindborg JJ, Hansen J. Studies on odontogenic cyst epithelium: 2—clinical and roentgenologic aspects of odontogenic keratocyst. Acta Pathol Microbiol Scand (A) 1963;58:283–94.
458
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21. Antoh M, Hasegawa H, Kawakami T, et al. Hyperkeratosis and atypical proliferation appearing in the lining epithelium of a radicular cyst: report of a case. J Craniomaxillofac Surg 1993;21:210–3. 22. Browne RM. Metaplasia and degeneration in odontogenic cysts in man. J Oral Pathol 1972;1:145–58. 23. Browne RM. The odontogenic keratocyst: histological features and their correlation with clinical behaviour. Br Dent J 1971;131:249–59. 24. Stajcic Z, Paljm A. Keratinization of radicular cyst epithelial lining or occurrence of odontogenic keratocyst in the periapical region? Int J Oral Maxillofac Surg 1987;16: 593–5. 25. Onuki M, Saito A, Hosokawa S, et al. A case of orthokeratinized odontogenic cyst suspected to be a radicular cyst. Bull Tokyo Dent Coll 2009;50:31–5. 26. Hancock MA, Brown CE Jr, Hartman KS. Orthokeratinized odontogenic cyst presenting as a periapical lesion. J Endod 1986;12:539–41. 27. Lin LM, Ricucci D, Lin J, Rosenberg PA. Nonsurgical root canal therapy of large cystlike inflammatory periapical lesions and inflammatory apical cysts. J Endod 2009; 35:607–15.
JOE — Volume 40, Number 3, March 2014
Orthokeratinized Odontogenic Cysts Presenting as a Periapical Lesion: Report of a Case and Literature Review Jo~ ao Paulo Silva Servato, MS,* Sergio Vitorino Cardoso, PhD,* Marcelo Caetano Parreira da Silva, MS,† Mirna Scalon Cordeiro, PhD,† Paulo Rogerio de Faria, PhD,‡ and Adriano Mota Loyola, PhD* Abstract Introduction: Inflammatory cysts, granulomas, abscesses, and fibrous scars represent most periapical radiolucencies. However, other less common lesions, such as orthokeratinized odontogenic cysts (OOCs), can be found at this region, and they deserve to be discussed because the prognosis for an OOC is different from that expected for the ordinary inflammatory periapical diseases. Methods: An interesting case of OOC associated with a nonvital tooth in a 40-year-old woman is described. After a previous clinical diagnosis of a radicular cyst, the tooth was extracted, and the lesion was enucleated and submitted to microscopy examination. Results: Because of the detection of an orthokeratinized epithelium lining, a diagnosis of OOC was concluded. After 2 years of periodic follow-up, no signs of recurrence were detected. Conclusions: The presence of keratin in radicular lesions must be carefully evaluated to eliminate the diagnosis of lesions with more aggressive behavior, such as an OOC or even a keratocystic odontogenic tumor. Hence, histopathologic examination is mandatory to confirm the type of lesion and to differentiate other pathologic conditions, therefore establishing patients’ prognoses precisely. (J Endod 2014;40:455–458)
Key Words Differential diagnosis, odontogenic cysts, orthokeratinized odontogenic cyst, radicular cyst
From the *Oral and Maxillofacial Pathology Area, School of Dentistry, Federal University of Uberl^andia, Uberl^andia; † Department of Oral Surgery, UNITRI–Centro Universitario do Tri^angulo, Uberl^andia; and ‡Department of Morphology, Biomedical Science Institute, Federal University of Uberl^andia, Uberl^andia, Minas Gerais, Brazil. Address requests for reprints to Prof Dr Adriano Mota Loyola, Universidade Federal de Uberl^andia, Faculdade de Odonto logia–Area de Patologia, Av. Para, 1720 Campus Umuarama, CEP 38400-902 Uberl^andia, MG, Brazil. E-mail address: [email protected] 0099-2399/$ - see front matter Copyright ª 2014 American Association of Endodontists. http://dx.doi.org/10.1016/j.joen.2013.09.044
JOE — Volume 40, Number 3, March 2014
T
he diagnosis of apical radiolucencies associated with devitalized teeth poses a great challenge for both clinicians and pathologists. Although the most prevalent diagnosis in these cases is either radicular cyst (RC) or granuloma, other entities with much more aggressive behavior, including orthokeratinized odontogenic cyst (OOC) and keratocystic odontogenic tumor (KCOT), may develop in the same region, therefore requiring the attention of oral pathologists during the examination of the specimens to avoid an improper diagnosis (1–4). Thus, differentiation from an indolent to a life-threatening disease growing in the periapical region, although uncommon, is potentially real (3, 4). Hence, the faster the diagnosis, the better the prognosis will be, especially for those patients affected by tumors (3, 4). Whatever the lesion may be, microscopic examination remains the gold standard tool for making the correct diagnosis of such lesions and should be used for any soft tissues removed during surgical procedures. In this article, we describe a rare case of OOC mimicking a radicular cyst and present a pertinent review of the literature discussing different aspects of this odontogenic lesion, including its clinicopathologic and biological behavior, histopathologic features, and the prognosis and treatment of the affected patient.
Case Report A 40-year-old woman was referred to the Oral Medicine Department of Centro Universitario do Tri^angulo (UNITRI); she was complaining about spontaneous pain and swelling in the oral cavity. Her medical history was noncontributory. The patient’s dental history showed no previous buccal or facial pain, traumatic dental injury, or other abnormalities at the periodontal region. Clinical examination revealed a swelling in the region of tooth #8. It presented a large dental restoration and complete absence of vitality, as demonstrated by using tetrafluoroethane spray. No tooth mobility was detected. On palpation, both buccal and palatal structures surrounding the tooth were painless. Periapical radiography was taken and exhibited a unilocular, well-circumscribed, round-shaped radiolucent lesion measuring about 25 mm that was closely associated with the root of the right upper central incisor. The lesion appeared to slightly displace the adjacent tooth’s root, without provoking root resorption (Fig. 1A and B). On the basis of the dimension of the radiographic image and the close association with nonvital teeth, a hypothesis of radicular cyst was raised, and endodontic treatment was indicated. Because of finances and the poor prognosis for periodontal status, the patient refused to submit to this conservative treatment and preferred to remove all periodontally compromised teeth in conjunction with the lesion to further use a total dental prosthesis. After surgery, the lesion was immediately submerged in 10% neutral buffered formalin and sent to the laboratory to be examined microscopically. At the oral pathology laboratory, a brownish cystic lesion measuring 27 19 9 mm was cut into small pieces, processed according to standardized histotechnical methods, and then embedded in paraffin. Sections 5-mm-thick were obtained from the paraffin block and stained with hematoxylin-eosin. Microscopically, a keratinized, stratified epithelium was observed lining the lesion. In some areas of this epithelium, a predominance of orthokeratin intermixing with a small area of parakeratin could be noted (Fig. 1C). In general, the lining was composed of layers 4–7 cells in thickness, but other regions were thicker than this, especially in
Periapical Orthokeratinized Odontogenic Cyst
455
Case Report/Clinical Techniques
Figure 1. (A) Periapical radiography exhibited a unilocular, well-circumscribed, radiolucent cyst, measuring about 25 mm, associated with the root of the right upper central incisor (distal view). (B) Periapical radiography exhibited a unilocular, well-circumscribed, radiolucent cyst (mesial view). (C) Hematoxylin-eosin stain; original magnification, 40. Cystic lesion showing orthokeratinized stratified squamous epithelium, with 7–10 cell layers thick. The capsule was composed of a fibrous connective tissue wall that contained severe chronic inflammatory cells. (D) Hematoxylin-eosin stain; original magnification, 400. Cystic stratified epithelium exhibiting orthokeratinization; the basal cells are hyperchromatic and show little tendency to palisade or polarize.
those areas intensively infiltrated by inflammatory cells. In general, a well-defined, non-palisaded basal layer was seen in the whole extension of the epithelium, and the correspondent cells usually exhibited basophilic nuclei (Fig. 1D). Likewise, parts of the epithelium showed stratification as well as a slight or even complete absence of keratin on the surface, notably when associated with the underlying inflammatory foci in the cystic wall, resembling a typical radicular cyst. Moreover, the cystic wall was composed of fibrous connective tissue exhibiting a multifocal, intense, chronic inflammatory infiltrate, and odontogenic epithelial rests without forming satellite cysts were seen as well. The final diagnosis was OOC. After 2 years of follow-up, complete bone formation was observed, and there was no recurrence of the lesion.
Discussion In the present study, we described a rare case of OOC developing close to the radicular root of tooth #8, mimicking a radicular cyst. In contrast to radicular cysts that are primarily associated with the inflammatory process, OOCs are admitted to have a developmental origin as a result of PTCH gene mutation. They represent 10% of all cases previously diagnosed as odontogenic keratocyst (OK) (5–11). Payne (5) first described OOC in 1972, followed by Wright (6), who classified the lesion as a variant of the OK because of the presence of an orthokeratinized layer on the epithelium surface and less tendency of recurrence. For a long time, OOC has been recognized by the World Health Organization as an entity derived from OK (12, 13). However, in its last edition launched in 2005, the World Health Organization reclassified OK as KCOT, and OOC was recognized as a distinct entity different from KCOT (14). Taking into consideration and evaluating the pertinent literature, there have been few published series reporting clinical, histologic, and immunohistochemical profiles of OOC (5–11, 15–17). Clinically, OOC presents as a painless solitary lesion, occurring predominantly at the posterior region of the mandible in young males (10). Radiographically, 90% of OOCs are unilocular and exhibit a welldefined limit, buccolingual expansion, and complete absence of root resorption (11). However, in some circumstances, this lesion may develop to show different aspects and epicenters, including its rare association with Gorlin syndrome (11). In contrast to a radicular cyst, an OOC is a cystic lesion with great growth potential, and in some cases huge dimensions have been reported (5–11, 18). In the present reported case, the occurrence in the periapical region in close association with a nonvital tooth, the small dimension, and the absence of any kind of symptoms made it difficult to promptly recognize the precise nature of the lesion. Because of this, histologic 456
Silva Servato et al.
examination was crucial to conclude the diagnosis. Microscopically, OOC is characterized by the presence of medium-thickness orthokeratinized epithelium with non-palisaded cells in the basal layer. Sometimes parakeratinization and hyperplasia can be focally observed. Skin appendages (ie, hair follicles, sebaceous and sweat glands) and satellite cysts have not been described for these lesions (8, 10, 11). In radicular cysts, keratinizing epithelium has been observed in less than 2% of cases (orthokeratinization is predominant), representing a metaplastic process, and usually it is a focal phenomenon (19–22). In addition, Browne (22, 23) showed that the presence of keratin in RC was significantly associated with the age of patients, with higher incidence between the second and third decades of life (mean, 32.1 years), lower than that seen in non-keratinized radicular cysts (mean of 40.2 years and incidence peak above the third decade) (22, 23). Similar ages are described for OOCs. Even when these microscopic characteristics are actually considered as gold standard parameters to ultimately establish a differential diagnosis between OOC and keratinized RC, this is not an easy task. In fact, there are no specific criteria to distinguish keratinized RCs from OOCs and KCOTs. Although it might be made histologically, there are some instances in which a complete examination of the lining is mandatory to confirm the presence of orthokeratin covering the OOC’s epithelium completely (5–11, 19). On the other hand, as pointed out elsewhere (9, 23), a differential diagnosis among them may be difficult, particularly when there is a secondary infection and keratin is not clearly evident on the lining surface. Despite this, there are other histologic features that may be useful to distinguish each other. One aspect is the position of the nuclei from the basal stratum, normally orientated away from the basement membrane in KCOT, but not in OOCs or RCs (14, 19). This is particularly significant because oral pathologists have used this method to differentiate KCOT from OOC and keratinized RCs. In addition to this fact, it has been postulated that cystic lesions showing either orthokeratin or an epithelium similar to that seen in parakeratotic oral mucosa, as well as other pathologic conditions with scanty parakeratin areas, should not be diagnosed as KCOTs or even as OOCs (19–24). Although there are many articles reporting the immunohistochemistry cytokeratin profile expression for RC and KCOT, this information is not useful for OOC and keratinized RC. To this end, more studies should be done to clarify the possibility of discovering new biomarkers that will help clinicians and pathologists to clearly differentiate between the various cysts arising in jaws. Our review identified 7 cases of OOC mimicking periapical lesions (9, 10, 24–26), which are presented in Table 1. Our case is unusual for several reasons. First, it was reported in a 40-year-old woman who JOE — Volume 40, Number 3, March 2014
No Enucleation 27 19 9
No Enucleation
Conclusion Through the experience gained in the present case, we reinforce the importance of histopathologic examination of all excised periapical lesions because the clinical diagnosis may fail, and a misdiagnosis may be made. In addition, it is important to keep in mind that all keratinized cysts developing in the radicular region should be warily evaluated to rule out the presence of KCOT or even OOC, which in turn behaves more aggressively than RCs.
Acknowledgments The authors thank Fundac¸~ao Estadual de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq) for their financial support. The authors deny any conflicts of interest related to this study.
F
Maxilla, #8
References
ND, no data; NSR, no sign of recurrence.
40 Servato et al, 2012 (present) 8
39 Onuki et al, 2009 (25) 7
M
Mandible, #18
Swelling, pain, and fistula Swelling and pain
ND
No Enucleation 50 30 ND Mandible, #17 M 40 Li et al, 1998 (9) 6
JOE — Volume 40, Number 3, March 2014
developed a lesion in the anterior maxilla, an uncommon location for OOC (11, 19). Second, the lesion represents a significant issue for clinicians and pathologists, especially because OOC does not present a specific therapeutic strategy to be applied in all cases, and the prognosis is yet to be determined. Third, our case reinforces the importance of new studies focusing on the differentiation of these lesions through the establishment of reliable criteria for correct diagnosis (5–11, 19, 24–27). The treatments of OOCs and RCs are different in many aspects. It may be suitable to treat both lesions with surgical excision, and relapses are not expected (5–11, 19, 24–26). However, it has been suggested that the vast majority of RCs may be resolved following conservative endodontic therapy, with 85%–90% of apical lesions disappearing or becoming markedly reduced in size after conservative endodontic procedures, whereas the same outcome is not expected for OOCs (19, 27).
NSR, 2 y
NSR, 7 mo
NSR, 8 y
ND NSR, 9 y ND No ND ND 25 25 20 Enucleation 21 27 Stajcic et al, 1987 (24) Stajcic et al, 1987 (24) Vuhahula et al, 1993 (10) Li et al, 1998 (9) 2 3 4 5
M F
Maxilla, #8–#4 ND Maxilla, #14–#15 ND
10
ND ND
Treatment
Enucleation
Size (mm)
Asymptomatic
Radiolucency Site
Maxilla, #6 M 41
Age (y) Gender Author, year
Hancock et al, 1986 (26) 1
Case
TABLE 1. Cases of OOC That Resemble Radicular Cysts in the International Literature
Symptomatology
Unilocular/well-defined radiolucency associated with apical areas of #6 No data could be retrieved No data could be retrieved ND Unilocular radiolucency associated with apical areas of #14–#15 Unilocular radiolucency associated with apical area of #17 Unilocular radiolucency associated with apical area of #18 Unilocular/well-defined radiolucency associated with apical area of #8
Recurrence Follow-up
Case Report/Clinical Techniques
1. Koivisto T, Bowles WR, Rohrer M. Frequency and distribution of radiolucent jaw lesions: a retrospective analysis of 9,723 cases. J Endod 2012;38:729–32. 2. Aggarwal V, Logani A, Shah N. The evaluation of computed tomography scans and ultrasounds in the differential diagnosis of periapical lesions. J Endod 2008;34: 1312–5. 3. Tatlidil R, G€oz€ub€uy€uk MM. Mucinous adenocarcinoma of lung presenting as oral metastases: a case report and literature review. J Endod 2001;37:110–3. 4. Bueno MR, De Carvalhosa AA, Castro PH, et al. Mesenchymal chondrosarcoma mimicking apical periodontitis. J Endod 2008;34:1415–9. 5. Payne TF. An analysis of the clinical and histopathologic parameters of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol 1972;33:538–46. 6. Wright JM. The odontogenic keratocyst: orthokeratinized variant. Oral Surg Oral Med Oral Pathol 1981;51:609–18. 7. MacDonald-Jankowski DS, Li TK. Orthokeratinized odontogenic cyst in a Hong Kong community: the clinical and radiological features. Dentomaxillofac Radiol 2010;39: 240–5. 8. Dong Q, Pan S, Sun LS, Li TJ. Orthokeratinized odontogenic cyst: a clinicopathologic study of 61 cases. Arch Pathol Lab Med 2010;134:271–5. 9. Li TJ, Kitano M, Chen XM, et al. Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15 cases. Histopathology 1998;32: 242–51. 10. Vuhahula E, Nikai H, Ijuhin N, et al. Jaw cysts with orthokeratinization: analysis of 12 cases. J Oral Pathol Med 1993;22:35–40. 11. Macdonald-Jankowski DS. Orthokeratinized odontogenic cyst: a systematic review. Dentomaxillofac Radiol 2010;39:455–67. 12. Pindborg JJ, Kramer IRH, Torloni H. Histological Typing of Odontogenic Tumours, Jaw Cysts, and Allied Lesions, 1st ed. Geneva: World Health Organization/Springer-Verlag; 1971. 13. Kramer IRH, Pindborg JJ, Shear M. Histological Typing of Odontogenic Tumors. 2nd ed. Berlin: Springer-Verlag; 1992. 14. Philipsen HP. Odontogenic keratocystic tumor. In: Barnes L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon, France: IARC Press; 2005: 306–7.
Periapical Orthokeratinized Odontogenic Cyst
457
Case Report/Clinical Techniques 15. Nadalin MR, Fregnani ER, Silva-Sousa YT, da Cruz Perez DE. Presence of myofibroblasts and matrix metalloproteinase 2 in radicular cysts, dentigerous cysts, and keratocystic odontogenic tumors: a comparative immunohistochemical study. J Endod 2012;38:1363–7. 16. Johann AC, Caldeira PC, Caliari MV, et al. Metallothionein in the radicular, dentigerous, orthokeratinized odontogenic cysts and in keratocystic odontogenic tumor. J Oral Pathol Med 2011;40:270–6. 17. Aragaki T, Michi Y, Katsube K, et al. Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst. Hum Pathol 2010;41:1718–25. 18. Diniz MG, Galv~ao CF, Macedo PS, et al. Evidence of loss of heterozygosity of the PTCH gene in orthokeratinized odontogenic cyst. J Oral Pathol Med 2011;40:277–80. 19. Shear M, Speight P. Radicular cyst. In: Shear M, Speight P, eds. Cysts of the Oral and Maxillofacial Regions, 4th ed. Oxford, UK: Blackwell Munksgaard; 2008:123–42. 20. Pindborg JJ, Hansen J. Studies on odontogenic cyst epithelium: 2—clinical and roentgenologic aspects of odontogenic keratocyst. Acta Pathol Microbiol Scand (A) 1963;58:283–94.
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21. Antoh M, Hasegawa H, Kawakami T, et al. Hyperkeratosis and atypical proliferation appearing in the lining epithelium of a radicular cyst: report of a case. J Craniomaxillofac Surg 1993;21:210–3. 22. Browne RM. Metaplasia and degeneration in odontogenic cysts in man. J Oral Pathol 1972;1:145–58. 23. Browne RM. The odontogenic keratocyst: histological features and their correlation with clinical behaviour. Br Dent J 1971;131:249–59. 24. Stajcic Z, Paljm A. Keratinization of radicular cyst epithelial lining or occurrence of odontogenic keratocyst in the periapical region? Int J Oral Maxillofac Surg 1987;16: 593–5. 25. Onuki M, Saito A, Hosokawa S, et al. A case of orthokeratinized odontogenic cyst suspected to be a radicular cyst. Bull Tokyo Dent Coll 2009;50:31–5. 26. Hancock MA, Brown CE Jr, Hartman KS. Orthokeratinized odontogenic cyst presenting as a periapical lesion. J Endod 1986;12:539–41. 27. Lin LM, Ricucci D, Lin J, Rosenberg PA. Nonsurgical root canal therapy of large cystlike inflammatory periapical lesions and inflammatory apical cysts. J Endod 2009; 35:607–15.
JOE — Volume 40, Number 3, March 2014
