Keywords: Periapical Diseases;Cyst;Granuloma;Abscess;Actinomycosis;Cemento-osseous Dysplasia;Histopathology;Infections.

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International Journal of Oral & Maxillofacial Pathology. 2012;3(3):02-07 ISSN 2231 2250 Available online at http://www.journalgateway.com or www.ijomp.org Original Research Histopathological insight into periapical lesions: An institutional study from Punjab Bhullar Ramanpreet, Sandhu V Simarpreet, Bhandari Rajat, Bhullar Amandeep, Gupta Shruti Abstract Background: Periapical lesions are the lesions pertaining to the tissues around the apex of a tooth root, including the periodontal membrane and the alveolar bone. A variety of lesions can mimic the pulpo-periapical lesions radiographically for example keratocystic odontogenic tumor, periapical cement-osseous dysplasia, benign tumors and locally aggressive or malignant neoplasias. Aims and Objectives: The purposes of this retrospective study were to determine the incidence of different lesions in specimens diagnosed in our department as well as to compare our findings with other studies from different geographical locations of the world. Material and Methods: Departmental retrospective archival retrieval from 2008 to 2011 reviewed 173 cases of periapical lesions. Lesions were analyzed for location of lesion, age and gender of the patient and diagnosis reported by oral pathologists. Results: Pulpo-periapical lesions were the most prevalent clinical diagnosis followed by odontogenic tumors. Apart from them, other diagnosis observed were odontogenic cysts other than radicular cyst, infections, focal cementosseous dysplasia & central giant cell granuloma. Mean age for overall periapical lesions was 37.17 years with male to female ratio of 1.62:1. Lesions were most common in the anterior maxilla followed by mandibular posteriors. Conclusion: The clinico radiological diagnosed pulpoperiapical lesions can present a spectrum of different pathosis hence histopathology is mandatory for diagnosis of periapical lesions. Keywords: Periapical Diseases;Cyst;Granuloma;Abscess;Actinomycosis;Cemento-osseous Dysplasia;Histopathology;Infections. Bhullar Ramanpreet, Sandhu V Simarpreet, Bhandari Rajat, Bhullar Amandeep, Gupta Shruti. Histopathological insight into periapical lesions: An institutional study from Punjab. International Journal of Oral & Maxillofacial Pathology; 2012:3(3):02-07. International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved. Received on: 03/03/2012 Accepted on: 03/08/2012 Introduction Diagnosis of periapical lesions has long been controversial. Periapical lesions vary from innocent anatomic variations to benign conditions and oral manifestations of systemic diseases that may become the responsibility of the dentist to recognize and bring to the attention of the patient s physician. 1 Various studies have emphasized on the periapical lesions of pulpal origin and there are sporadic studies on the unusual pathologies that masquerade periapical lesions. 2,3 Small incipient lesions may be mistaken for a common periapical granuloma or cyst and the tooth may be treated endodontically or extracted with the lesion going undiagnosed or inadequately treated. So a differential diagnostic work up prior to definitive treatment is mandatory and necessitates a biopsy in order to execute a more aggressive treatment in contrast to a conservative one. 4 Extensive search in the indexed English literature showed a dearth of statistical based studies. Surprisingly there is no study on periapical lesion in North India particularly from Punjab. The aim of this work was to carry out a pathological study on periapical lesions and to analyze variables such as age, gender, site, and histological type, as well as to compare our findings with other studies from regional and global variations. Materials and Methods A retrospective study consisted of 173 periapical lesions obtained from the department of oral and maxillofacial pathology over a period of four years. The specimens were submitted by endodontists, oral surgeons, periodontists and general dentists from the year 2008 to 2011. The following pertinent data was recorded: (a) source of biopsy specimen, (b) sex of the patient, (c) age of the patient, (d) location of tooth associated with lesion, (e) diagnosis reported by oral pathologists. Categorization of all lesions was done as pulpo-periapical lesions (periapical granuloma, periapical cyst, periapical abscess, and periapical scar), odontogenic cysts other than radicular 2012 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved

ISSN 2231 2250 Histopathological insight into periapical lesions... 3 cyst, odontogenic tumors, infectious lesions, focal cement-osseous dysplasia (FOCD) and central giant cell granuloma (CGCG). The Microsoft Excel TM software was used for data analysis and construction of graphs. Results During a period of four years, a total of 173 specimens were received from various departments of the Institute. Periapical Granuloma was most commonly diagnosed lesion while there was lowest incidence of FOCD. Overall periapical lesions were diagnosed more frequently in males 61.85%, with male to female ratio of 1.62:1 (Graph 1). The mean age for overall periapical lesions was 37.17 years (Graph 2). The lesions obtained were maximum in the age range of 31-40 years (32.95%). The lesions were minimum (5.2%) in the age range of 61-70 years (Graph 3). The youngest affected patient was 16 years and the oldest was 65 years. In relation to site, maxilla accounted for maximum (63.01%) number of cases (Graph 4). The site wise distribution revealed that lesions were most common in the anterior maxilla followed by mandibular posteriors. Among all periapical lesions, the largest diagnosed group was pulpo-periapical lesions, which accounted for 153 (88.44%) cases (Graph 5). The second largest group was odontogenic tumors, which accounted for 6 (3.45%) cases. The entities other than pulpo-periapical comprises of 13.29% of total lesions. The diagnosis observed were odontogenic tumors, odontogenic cysts other than radicular cyst, infections, FOCD and CGCG (Table 1). Graph 3: Age and sex wise distribution of lesions. Graph 1: Sex wise distribution of lesions. Graph 4: Distribution of periapical lesions according to site. Graph 2: Age distribution of different lesions (PG-Periapical Granuloma, PC-Periapical Cyst, PA-Periapical Abscess, OT- Odontogenic Tumor, OC-Odontogenic cyst other than PC, Inf-Infections, FCOD-Focal Cemento-ossous Dysplasia, CGCG-Central Giant Cell Granuloma, PS-Periapical Scar). Graph 5: Distribution of lesion into various categories. Discussion Clinical and radiographic evaluation of periapical lesions are subject to diagnostic confusion. The incidence of odontogenic lesions often leads clinicians to ignore other

4 Bhullar RamanPreet, et al. ISSN 2231-2250 possibilities within the differential diagnosis. 5 Some cases of benign and malignant lesions mimicking periapical lesions such as keratocystic odontogenic tumor (KCOT), cysts of nasopalatine canal, PCOD, benign tumors and locally aggressive or malignant neoplasias have been described in the literature. Therefore, histopathological study of periapical lesions is mandatory in order to confirm the diagnosis and distinguish it from non-inflammatory lesions. 6 Lesions No. Percentage Periapical granuloma 85 49.13 Periapical cyst 43 24.86 Periapical abscess 22 12.72 Odontogenic tumors 6 3.47 Odontogenic cysts other than PC 3 1.73 Infections 5 2.89 FCOD 2 1.16 CGCG 4 2.31 Periapical scar 3 1.73 Table 1: The lesion-wise distribution of subjects. Most of the periapical lesions (70% and 95%) are complications resulting from pulpal necrosis and the majority of these lesions respond to conservative root canal treatment. There have been anecdotal reports on the pathological entities associated with root apices e.g Ameloblastoma, 6-8 CGCG, 9-13 Actinomycosis, 14-20 KCOT, 21-25 FCOD, 26-28 Hemangioma 29 and glandular tissue 30 (Table 2). A comparison of previous findings with results of present study is presented in Table 3. Variation in relative numbers of cysts and granulomas in these studies is thought to be due to two main factors: sample selection and histological criteria for distinguishing cysts from granulomas. When reviewing the various histological criteria for each of the cited studies, differences exist between the various methods of histological diagnosis. Standard histological criteria must be used to accurately compare the results of studies, and without this standardization comparison is of little value. In 1973, Hirsch et al. 31 devised a classification for histological diagnosis of surgically excised periapical tissue that is widely accepted today and would serve as a good standard for comparison in future studies. The specimens in this study came from a variety of contributors and the surgeries were performed for a variety of reasons. Baumann and Rossman (1956) selected teeth that had undergone root resection or periapical curettage and Wais (1958) biopsied only anterior teeth with periapical lesions. 32,33 Some authors biopsied endodontic failures for the most part. 1-3,34,35 Lalonde and Luebke (1968) 36 studied specimens submitted by oral surgeons following extraction of the involved tooth, 6% of which had endodontic therapy. Variability would exist when comparing results from these cited studies since a portion of the tissue was biopsied before endodontic therapy, another portion after endodontic therapy, and a third portion combined the two. Therefore, in our opinion, the variability in these studies can be accounted for by the varying histological criteria and different methods of sample selection in each study. 1 Pathosis Reference with Year Navarro C et al 2004, Ameloblastoma 6-8 Cunha EM et al 2005, Dos Santos et al 2010 Glickman GN 1998, Dahlkemper P et al 2000, CGCG 9-13 Nary Filho H et al 2004, Lombardi T et al 2006, Actinomycosis 14-20 KCOT 21-25 Selden HS 2008 Sakellariou et al 1966, Borssen E et al. 1981, Weir JC et al.1982, Nair PNR et al 1984, Happonen RP et al 1986, Kalfas S et al.2001, Hirshberg A et al 2003 Stajcic Z et al 1987, Nohl F et al 1996, Garlock J et al 1998, Ali M et al 2003, Kavita R et al 2011 FCOD 26-28 Drazic R et al 1999, Galgano C et al 2003, Bhandari R et al 2012 Hemangioma 29 Orsini G et al 2000 Glandular tissue 30 Childers E et al 1990 Table 2: Histological diversity of periapical pathosis. The present retrospective study found that odontogenic tumors have a larger potential for endodontic misdiagnosis. The most commonly diagnosed tumor was ameloblastoma followed by Adenomatoid odontogenic tumour (AOT), and

ISSN 2231 2250 Histopathological insight into periapical lesions... 5 ameloblastic fibroma. Epidemiological studies have also found ameloblastoma to be third commonly diagnosed odontogenic lesion. The diagnosis of ameloblastoma is important because of its locally aggressive nature and greater tendency for recurrence. 6,7 Year Authors % Cyst % Granu loma % Othe rs Sam ples 1954 Priebe et al 54.5 45.5-101 1956 Bauman n & Rossma 26 74-121 n 1956 Sommer et al 6.4 84 9.2 170 1958 Wais 26 64 10 100 1964 Patterso n et al 14 84 2 501 1966 Bhaskar 42 48 10 2308 1968 Lalonde & 43 45 12 800 Luebke 1976 Block et al 6.1 93.9-230 1988 Stockdal e and Chandle 16.8 77.3 5.9 1108 r 1989 Spatafor e et al 42.0 52.0 6.0 1659 2006 Ricucci et al 8.7 61.4 28.7 57 2006 2011 Diegues et al 53 42 5 255 2011 Omoregi e et al 1.5 16.9 15.3 136 2011 Our 11.5 24.86 49.13 Study 6* 173 Table 3: Comparative distribution of periapical lesions in chronological order. *Without including periapical abscess. There have been reports of CGCG in the periapical area which were treated by conventional root canal treatment. So it is important to follow up the healing process of endodontically treated periapical radiolucency and biopsy is mandatory for diagnosis and sequential treatment. 9-13 Five case of actinomycosis were found in this study. Periapical actinomycosis is thought to be rare and only few case reports have been reported. Actinomycotic infection in periapical lesions could be more prevalent than reported. The increased incidence of periapical actinomycosis in our study could be contributed to the fact that ours is a secondary referral center and primarily deals with rural farmer community. 37 Most of periapical actinomycosis does not differ clinically from other periapical lesions. Cases of periapical actinomycosis have a favourable outcome after conservative surgical curettage along with short- term conservative antibiotic treatment. The exact contribution of Actinomyces to the perpetuation of the periapical lesion should be further investigated. 14--20 Periapical cyst was the most commonly diagnosed odontogenic cyst followed by KCOT. This finding was supported by Stajcic and Paljm (1987) who studied 565 specimens of periapical radiolucencies and found that KCOT represented 0.7% of the clinically and radiographically diagnosed radicular cysts. 21 Almost 20% of the maxillary KCOT occurred in periapical region. The diagnosis of KCOT is important because of its frequent recurrence and aggressive behavior. 23 Moreover it could have an association with nevoid basal cell carcinoma syndrome. In the present study, two cases of FCOD were diagnosed in the periapical area. FCOD s occurs mostly in posterior mandible. These are asymptomatic and are detected on routine radiographic examination. Radiographically, the lesion in osteolytic stage resembles pulpo-periapical lesion. The lesion tends to well defined, but the borders are slightly irregular. Lesions occur in dentulous and edentulous areas, with many examples noted in extraction sites. 26,28 In present study, the incidence of other diagnostic entities is quite substantial and these need to be treated accordingly as the consequences of these pathosis could be severe and mutilating to the patient. Periapical radiolucencies that do not heal after conventional root canal treatment or with an incomplete history or some unusual radiographic image should receive surgical treatment and mandatory biopsy. Thus, the histopathology remains a gold standard in diagnosis of periapical infections. Conclusion The clinico-radiological diagnosed periapical lesions can present as a spectrum of different pathosis. Hence histopathology is mandatory for diagnosis of periapical lesions. Author Affiliations 1. Dr.Bhullar Ramanpreet K, Senior Lecturer, 2. Dr.Sandhu V Simarpreet, Professor and Head, 3. Dr.Bhandari Rajat, Senior Lecturer, Department of Oral and Maxillofacial Pathology, 4. Dr.Bhullar

6 Bhullar RamanPreet, et al. ISSN 2231-2250 Amandeep, Senior Lecturer, Department of Prosthodontics, 5. Dr. Gupta Shruti, PG Student, Department of Oral and Maxillofacial Pathology, Genesis Institute of Dental Sciences and Research, Ferozepur, India. Acknowledgement We would like to thank all the staff members in the Department of Oral Pathology for their support and cooperation. References 1. Spatafore CM, Griffin JA, Keyes GG, Wearden S, Skidmore AE. Periapical biopsy report: An analysis over l0-year period. J Endod 1990;16(5):239-41. 2. Bhaskar SN. Periapical lesions, types, incidence and clinical features. Oral Surg 1966;21:657-71. 3. Stockdale CR, Chandler NP. The nature of a periapical lesion, a review of 1108 cases. J Dent 1988;16:123-9. 4. Kuc I, Peters E, Pan J. Comparison of clinical and histologic diagnoses in periapical lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89(3):333-7. 5. Ortega A, Farina V, Gallardo A, Espinoza I, Acosta S. Non-endodontic periapical lesions: A retrospective study in Chile. Int Endod J 2007;40:386 90. 6. Navarro C, Principi S, Massucato E, Sposto M. Maxillary unicystic ameloblastoma. Dento Maxillofac Radiol 2004;33:60 2. 7. Cunha EM, Fernandes AV, Versiani MA, Loyola AM. Unicystic ameloblastoma: a possible pitfall in periapical diagnosis. Int Endod J 2005;38:334 40. 8. Dos Santos EP, Araújo FEN, Valido DP, Lima SO, De Albuquerque-Júnior RLC, Soares AF. Desmoplastic ameloblastoma mimicking a periapical lesion. Rev Odonto Cienc 2010;25(3):306-9. 9. Glickman GN. Central giant cell granuloma associated with a non-vital tooth: A case report. Int Endod J1998;21:224 30. 10. Dahlkemper P, Wolcott JF, Pringle GA, Hicks ML. Periapical central giant cell granuloma: A potential endodontic misdiagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:739 45. 11. Nary Filho H, Matsumoto MA, Fraga SC, Goncales ES, Servulo F. Periapical radiolucency mimicking an odontogenic cyst. Int Endod J 2004;37:337 44. 12. Lombardi T, Bischof M, Nedir R, Vergain D, Galgano C, Samson J, et al. Periapical giant cell granuloma misdiagnosed as odontogenic cyst. Int Endod J 2006;39:510 5. 13. Selden HS. Central giant cell granuloma: A troublesome lesion. J Endod 2006;26:371 3. 14. Sakellariou PL. Periapical actinomycosis: report of a case and review of the literature. Endod Dent Traumatol 1966;12(3):151-4. 15. Borssen E, Sundqvist G. Actinomyces of infected dental root canals. J Oral Surg 1981;51(6):643-8. 16. Weir JC, Buck WH. Periapical actinomycosis. Report of a case and review of the literature. Oral Surg Oral Med Oral Pathol 1982;54:336-40. 17. Nair PNR, Schroeder HE. Periapical actinomycosis. J Endod 1984;10:567-7. 18. Happonen RP. Periapical actinomycosis: A follow-up study of 16 surgically treated cases. Endod Dent Traumatol 1986;2:205-9. 19. Kalfas S, Figdor D, Sundqvist G. A new bacterial species associated with failed endodontic treatment: identification and description of Actinomyces radicidentis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:208-14. 20. Hirshberg A, Tsesis I, Metzger Z, Kaplan I, Aviv T. Periapical actinomycosis: A clinicopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:614-20. 21. 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(5):593-5. 22. Nohl F, Gulabivala K. Odontogenic keratocyst as periradicular radiolucency in the anterior mandible: Two case reports. Oral Surg, Oral Med Oral Pathol Oral Radiol Endod 1996;81:103 9. 23. Garlock J, Pringle A, Hicks L. The odontogenic keratocyst: a potential endodontic misdiagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:452 6. 24. Ali M, Baughman R. Maxillary odontogenic keratocyst: A common and serious clinical misdiagnosis. J Am Dent Assoc 2003;134:877 83. 25. Rao K, Smitha, Umadevi HS, Priya NS. Clinicopathologic study of 100 odontogenic cysts reported at VS Dental College-a retrospective study. J Adv Dent Res 2011;2(1):51-9. 26. Drazic R, Minic AJ. Focal cementoosseous dysplasia in the maxilla

ISSN 2231 2250 Histopathological insight into periapical lesions... 7 mimicking periapical granuloma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88(1):87-9. 27. Galgano C, Samson J, Küffer R, Lombardi T. Focal cemento-osseous dysplasia involving a mandibular lateral incisor. Int Endod J 2003;36(12):907-11. 28. Bhandari R, Sandhu SV, Bansal H, Behl R, Bhullar RK. Focal cemento-osseous dysplasia masquerading as a residual cyst. Cont Clin Dent 2012;3(1):S60-2. 29. Orsini G, Fioroni M, Rubini C, Piattelli A. Hemangioma of the mandible presenting as a periapical radiolucency. J Endod 2000;26:621 2. 30. Childers E, Johnson J, Warnock G, Kratochvil F. Asymptomatic periapical radiolucent lesion found in an area of previous trauma. J Am Dent Assoc 1990;121:759 60. 31. Hirsch J, Ahlstrom U, Hendkson P. Periapical surgery. Int J Oral Surg 1979;8:173-85. 32. Baumann L, Rossman SR. Clinical, roentgenologic and histopathological findings in teeth with apical radiolucent areas. Oral Surg 1956;9:1330-6. 33. Wais FF. Significance of findings following biopsy and histologic study of periapical lesions. Oral Surg 1958;11:650-3. 34. Block RM, Bushell A, Roddgues H, Langetand K. A histopathologic, histobacteriologic and radiographic study of periapical endodontic surgical specimens. Oral Surg 1976;42:656-78. 35. Patterson SS, Shafer WG, Healey HJ. Periapical lesions associated with endodontically treated teeth. J Am Dent Assee 1964;68:191-4. 36. Lalonde ER, Luebke RG. The frequency and distribution of periapical cysts and granulomas: An evaluation of 800 specimens. Oral Surg Oral Med Oral Pathol 1968;25(6):861-8. 37. Jeffe Davis MI. Analysis of forty-six cases of actinomycosis with special reference to its etiology. Am J Surg 1941;52(3):447-54. Corresponding Author Dr.Sandhu V Simarpreet, Professor and Head, Department of Oral & Maxillofacial Pathology, Genesis Institute of Dental Sciences & Research, Ferozepur, India. Ph: +91-9888887438 Email: s_vrk@yahoo.com Source of Support: Nil, Conflict of Interest: None Declared.