Periapical lesions are not always a sequelae of pulpal necrosis: a retrospective study of 1521 biopsies

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Periapical lesions are not always a sequelae of pulpal necrosis: a retrospective study of 1521 biopsies

T. G. Kontogiannis¹, K. I. Tosios², N. P. Kerezoudis¹, S. Krithinakis¹, P. Christopoulos³&

A. Sklavounou²

1Department of Endodontics, Dental School, University of Athens, Athens;²Department of Oral Pathology and Medicine, Dental School, University of Athens, Athens; and³Department of Oral and Maxillofacial Surgery, Dental School, University of Athens, Athens, Greece

Abstract

Kontogiannis TG, Tosios KI, Kerezoudis NP,

Krithinakis S, Christopoulos P, Sklavounou A.

Periapical lesions are not always a sequelae of pulpal necrosis: a retrospective study of 1521 biopsies. International Endodontic Journal, 48, 68–73, 2015.

Aim To record the incidence of lesions that were not the sequelae of pulpal necrosis (non-SPN) amongst 1521 biopsies of periapical lesions submitted with a clinical diagnosis of a sequelae of pulpal necrosis (SPN).

Methodology A retrospective study of 1521 biopsy request forms of specimens submitted for histopathological examination with a clinical diagnosis ‘periapical inflammation’, ‘periapical abscess’, ‘periapical granuloma’ or ‘periapical cyst’ during an arbitrarily selected 14-year period was undertaken. Gender and age of the patient, site and maximum diameter of the lesion, symptoms, inclusion of the final diagnosis in the differential diagnosis and specialty of the clinician submitting the biopsy material were recorded in each case. The final diagnosis for each case was extracted from the pathology report, and two groups were formed, SPN and non- SPN lesions. Differences between the respective features

of SPN and non-SPN cases were analysed with Yate’s chi-square test and t-test (significance level P< 0.05) Results In 52 of the 1521 cases examined (3.42%), the histological diagnosis was not consistent with a SPN. In most non-SPN cases, the histopathological diagnosis was not included in the differential diagnosis. The keratocystic odontogenic tumour [odontogenic keratocyst (OKC)] was the most frequent non-SPN lesion (34.62%). Other, yet less frequent, non-SPN lesions included glandular odontogenic cysts, lateral periodontal cysts, central ossifying fibro- mas as well as malignancies (metastatic carcinomas and Langerhans cell histiocytosis).

Conclusions Non-SPN lesions appeared in the periapical region mimicking a SPN, although rarely. Most of them were developmental cysts, in particular OKCs, but odontogenic tumours, such as ameloblastoma, or malignant lesions were also diagnosed. Histological examination of tissue harvested from periapical lesions should be performed, in particular when those lesions are large.

Keywords: malignant neoplasm, nonodontogenic cyst, odontogenic tumour, periapical disease, periapical granuloma, radicular cyst.

Received 15 November 2013; accepted 25 February 2014

Introduction

Pulp necrosis secondary to inflammation may be followed by the development of a periapical lesion, that is, periapical abscess, periapical granuloma or periapical cyst, collectively termed sequelae of pulpal necrosis (SPN) (Garlock et al. 1998, Kuc et al. 2000, Correspondence: Taxiarchis G. Kontogiannis, Department of

Endodontics, Dental School, University of Athens, 2 Thivon Street, 115 27 Athens, Greece (Tel.: +0030 6946355003;

fax: +0030 2106138485; e-mail: tkontogiannis@hotmail.

com).

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Vier & Figueiredo 2002). Diagnosis of a SPN is based on clinical and radiographic examination of the involved tooth, and root canal treatment usually results in satisfactory healing (Nary Filho et al.

2004). Failure of root canal treatment is an indication for endodontic surgery that may be followed by histopathological examination when an adequate amount of tissue or foreign material is removed (Peters & Lau 2003, European Society of Endodontology 2006).

It has been suggested that careful clinical diagnosis will differentiate an endodontic from a nonendodontic lesion, thus histopathological examination is considered not beneficial to the patient and adds to costs (Weisman 1975, Walton 1998, Omoregie et al. 2009).

A major argument in favour of this view is the rare recurrence of cases where histopathological examination of tissue harvested through endodontic surgery provided useful diagnostic information (Walton 1998).

However, this view has been challenged (Baughman 1999, Ellis 1999, Newton 1999, Ramer 1999, Sum- merlin 1999, Becconsall-Ryan et al. 2010).

A review of the literature reveals that a wide variety of lesions may mimic a SPN, when they develop in a periapical location. These lesions may be noninflam- matory developmental odontogenic cysts, such as odontogenic keratocyst (OKC) (August et al. 2000, Chapelle et al. 2004, Cunha et al. 2005), nasopalatine duct cyst, lateral periodontal cyst and traumatic bone cyst (Garlock et al. 1998, Kuc et al. 2000, Peters &

Lau 2003, Silva et al. 2003); infectious diseases, such as histoplasmosis, aspergillosis, actinomycosis and viral diseases (Hirshberg et al. 2003, Peters & Lau 2003, Slots et al. 2003); benign fibro-osseous lesions (Peters & Lau 2003, Sanchis et al. 2003, Perez-Garcıa et al. 2004); central giant-cell granuloma (CGCG) (Dahlkemper et al. 2000, Peters & Lau 2003, Lom- bardi et al. 2006); and odontogenic tumours, such as ameloblastoma (Chapelle et al. 2004, Cunha et al.

2005). There are also rare reports of malignancies in a periapical location, such as metastatic neoplasms, ade- nocarcinomas, lymphomas and odontogenic carcinoma (Peters & Lau 2003, Silva et al. 2003, Lee et al.

2007, Gbolahan et al. 2008, Becconsall-Ryan et al.

2010, Yamada et al. 2010). In a review of the literature, the incidence of non-SPN lesions in periapical location ranged from 0.7% to 5% (Peters & Lau 2003).

The aim of the present study was to record the incidence of non-SPN lesions amongst 1521 biopsies of periapical lesions submitted with a clinical diagnosis of a SPN.

Materials and methods

This is a retrospective study of 1521 biopsy request forms of specimens submitted for histopathological examination to the Department of Oral Pathology and Medicine, Dental School, University of Athens, with a clinical diagnosis ‘periapical inflammation’, ‘periapical abscess’, ‘periapical granuloma’ or ‘periapical cyst’.

The study was limited to an arbitrarily selected 14- year period (January 1990 to December 2004). The exact type of surgical procedure used to retrieve the specimen (tooth extraction, periapical curettage or apicectomy) was not stated. Cases submitted as ‘periapical lesion’, ‘cyst’ or ‘odontogenic cyst’ were excluded from the study, as those clinical diagnoses could describe non-SPN lesions.

Gender and age of the patient, site and maximum diameter of the lesion, symptoms, inclusion of the final diagnosis in the differential diagnosis and specialty of the clinician submitting the biopsy material [oral surgeon or oral and maxillofacial surgeon (OMFS), general dental practitioner (GP) or endodon- tist] were recorded in each case. The final diagnosis for each case was extracted from the pathology report, and two groups were formed, SPN and non- SPN lesions. For non-SPN lesions, the diagnoses were verified by reviewing the original slides, according to standard diagnostic criteria (Neville et al. 2009).

Differences between the respective features of SPN and non-SPN cases were analysed with Yate’s chi- square test and t-test (significance level P< 0.05), using SPSS Statistics 17.0 software (SPSS, Inc., Chi- cago, IL, USA).

Results

The final diagnoses were periapical abscess in five cases (0.32%), periapical granulomas in 476 cases (31.28%), radicular cyst in 988 cases (64.91%) and various non-SPN lesions in 52 cases (3.42%). Table 1 shows the main clinical features of the SPN and non- SPN cases studied. Significant differences were found between SPN and non-SPN lesion in the average age of the patients (P< 0.01), the average maximum diameter of the lesion (P< 0.01) and the presence of symptoms (P< 0.01), but the exact nature of those symptoms were not stated.

The final diagnoses of non-SPN lesions are shown in Table 2 and included developmental cysts (75.01%), odontogenic tumours (3.84%) and other lesions (21.15%), amongst them one case each of a

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metastatic malignant neoplasm of unknown primary and Langerhans cell histiocytosis. There was, also, an unusual case of a dental follicle excised from the periapical area of a first pre-molar in a patient that had been previously undergone extraction of an impacted second pre-molar. OKC was the final diagnosis in 18 of 52 non-SPN cases (34.62%). In 50 of 52 non-SPN cases, the differential diagnosis list did not include the final diagnosis.

The distribution of cases diagnosed per specialty of the submitting clinician is shown in Table 3. Most SPN cases (80.41%) and almost all non-SPN cases were submitted by OMFS.

Discussion

Overall, the main clinical features of SPN cases included in the present study are comparable to those of previous reports as it considers the gender and age of the patients and the location of the lesions (Lalonde

& Luebke 1968, Spatafore et al. 1990, Becconsall- Ryan et al. 2010). Granuloma is the most common periapical lesion, but the proportion of granulomas to cysts varies amongst different studies, possibly due to differences in the histopathological diagnostic criteria, as well as the type of procedure utilized for the exci- sion of the lesion (Love & Firth 2009, Becconsall- Ryan et al. 2010). In particular, in studies limited to lesions removed through endodontic surgery or tooth extraction, periapical granulomas pre-dominate (Stockdale & Chandler 1988, Spatafore et al. 1990, Nobuhara & del Rio 1993, Gbolahan et al. 2008, Omoregie et al. 2009, Love & Firth 2009), but when all periapical lesions are included, regardless of the type of procedure, the proportion of cysts increases (Bhaskar 1966, Lalonde & Luebke 1968). In the present study, this information was not available, thus all lesions were included. In addition, there was a pre- ponderance of large lesions, as is shown by the average maximum diameter (1.92 1.27 cm) and by the over-representation of cases submitted by OMFS (80.41%), that are more likely to be cysts (Bhaskar 1966).

Non-SPN lesions constituted 3.42% of the cases, and the contributing clinicians did not include them in their differential diagnosis. Other similar studies have reported an incidence of non-SPN lesions between 0.3% and 4% (Table 4). Studies on biopsy Table 1 Main clinical features of SPN and non-SPN cases

SPN Non-SPN P

Gender

Males 830 30

Females 636 22 0.89

Ratio 1.3 : 1 1.3 : 1

Average age (years)

41.34 15.03 47.29 18.78 0.0043 Region

Maxilla 917 28

Mandible 505 22 0.20

Ratio 1.82 : 1 1.22 : 1

Average maximum diameter (cm)

1.92 1.27 2.55 1.69 0.00005 Symptoms

Yes 922 31

No 219 21 0.00055

SPN, sequelae of pulpal necrosis.

P-values of statistically significant differences are in bold.

Table 2 Final diagnosis in 52 cases of nonsequelae of pulpal necrosis lesions

Final diagnosis

Number

of cases %

Developmental odontogenic cysts

Odontogenic keratocyst 18 34.62

Glandular odontogenic cyst 10 19.23

Lateral periodontal cyst or botryoid odontogenic cyst

6 11.54

Calcifying odontogenic cyst 3 5.77

Dentigerous cyst 2 3.85

Odontogenic tumours

Ameloblastoma 1 1.92

Ameloblastic odontoma 1 1.92

Other lesions

Fibro-osseous lesion–central ossifying fibroma

4 7.69

Foreign body reaction 2 3.85

Actinomycosis 1 1.92

Focal osteoporotic marrow defect 1 1.92

Metastatic carcinoma 1 1.92

Langerhans cell histiocytosis 1 1.92

Dental follicle 1 1.92

Total 52 100

Table 3 Total number of cases and non-SPN cases by specialty of the submitting clinician

Total number

of cases %

Non-SPN

cases %

OMFS 1223 80.41 51 4.17

GPs 275 18.08 1 0.36

Endodontists 24 1.58 0 0

Total 1521 100 52 3.42

OMFS, oral/oral and maxillofacial surgeons; GPs, general practitioners; SPN, sequelae of pulpal necrosis.

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material, however, do not accurately estimate the incidence of various periapical lesions, as many clinicians do not submit tissue in cases where they have

‘no doubt’ on their diagnosis or the tissue recovered is considered ‘limited’ (Kuc et al. 2000, Peters & Lau 2003). In addition, the results of those studies are not fully comparable as the inclusion criteria vary, whilst the endodontic status of each tooth and the individual indication for endodontic surgery are not stated. How- ever, non-SPN cases were found in two studies where all periapical lesions collected through endodontic surgery performed according to certain indications were biopsied (Stockdale & Chandler 1988, Nobuhara

& del Rio 1993). It is assumed that in those cases, careful clinical and radiographic evaluation of the teeth, considered ‘diagnostic’ of a SPN (Walton 1998), had been carried out. It should, also, be noticed that occasionally a nonendodontic periapical lesion may cause pulp necrosis, confounding evaluation (Baughman 1999).

Odontogenic keratocyst is the lesion most com- monly mimicking a SPN (Garlock et al. 1998, Peters

& Lau 2003, Cunha et al. 2005, Ortega et al. 2007, Omoregie et al. 2009, Becconsall-Ryan et al. 2010), as 0.7% (Peters & Lau 2003, Omoregie et al. 2009) to 9% (Garlock et al. 1998) of OKCs may present in a periapical region. In the present study, OKC accounted for 34.62% of all non-SPN cases. OKC has an aggres- sive biological behaviour, with local infiltrative growth and a high tendency for recurrence (Neville et al.

2009). Thus, its diagnosis that may be rendered only through histopathological examination would be cer- tainly beneficial to the patient. OKCs and calcifying odontogenic cysts are classified as odontogenic

tumours in the most recent WHO classification, referred to as keratocystic odontogenic tumour and calcifying epithelial odontogenic tumour, respectively (Barnes et al. 2005), a view not unanimously accepted (Neville et al. 2009). A high frequency of recurrence has, also, been reported for lateral periodontal cyst/botryoid odontogenic cyst, as well as glandular odontogenic cyst, both of them found to be common mimickers of a SPN in our study.

Fibro-osseous lesions were the second most common group of non-SPN lesions in the present study, and as in previous reports, most of them were consistent with periapical osseous dysplasias (Bhaskar 1966, Sanchis et al. 2003, Perez-Garcıa et al. 2004).

Those lesions do not affect pulp health, thus proper clinical evaluation should be diagnostic and prevent unnecessary damage to the involved tooth caused by periapical surgery (Sanchis et al. 2003, Perez-Garcıa et al. 2004).

Periapical ameloblastomas are unusual and Chap- elle et al. (2004) found 19 such cases in 21 years, accounting for approximately 0.7% of the periapical lesions they studied. CGCG usually represents approximately 5% of non-SPN cases, and at least one case of a CGCG clinically diagnosed as a SPN lesion may be found in many studies (Spatafore et al. 1990, Dahlk- emper et al. 2000, Kuc et al. 2000, Peters & Lau 2003, Lombardi et al. 2006); however, no case was found in the present series.

Metastatic carcinomas may imitate a SPN, although rarely (Spatafore et al. 1990, Peters & Lau 2003), but failure to diagnose them may result in serious delay in management and worsen prognosis for the patient (Lee et al. 2007). McClure et al.

(2013) found 26 cases (2.1%) of metastatic malignancies in a periapical location amongst 1221 patients and Shen et al. (2009) 20 cases (0.21%) amongst 9239 patients. Lung and breast were the most common primary sites, and there was a pre- dilection for the posterior mandible. In the present study, one case of metastatic malignancy was found. Information retrieved by the biopsy request form as well as the histopathological report indi- cated that its primary origin was unknown and manifested as a periapical lesion related to a right maxillary canine.

Langerhans cell histiocytosis encompasses a group of rare disorders of the reticuloendothelial system characterized by abnormal proliferation of Langerhans cells (Neville et al. 2009). Cases masquerading as SPNs have been reported rarely, and most of them Table 4Incidence of non-SPN lesions in previous studies

and the present one

Reference

Total number of cases

% non-SPN cases

Bhaskar (1966) 2308 1.3

Seltzer et al. (1967) 87 1.15

Stockdale & Chandler (1988) 1108 0.3

Spatafore et al. (1990) 1659 4

Nobuhara & del Rio (1993) 150 2

Kuc et al. (2000) 805 1

Ortega et al. (2007) 4006 0.65

Becconsall-Ryan et al. (2010) 2419^a 2

Present study 1521 3.42

SPN, sequelae of pulpal necrosis.

aIncludes 1570 cases with a provisional diagnosis of periapical granulomas and 849 cases with a provisional diagnosis of periapical cyst.

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are localized eosinophilic granulomas (Madrigal- Martınez-Pereda et al. 2009) that behave in a benign manner. As an oral lesion may occasionally be the primary manifestation of Langerhans cell histiocytosis, early diagnosis is of outmost importance for the patient.

Most periapical biopsies and non-SPN cases were submitted by OMFS, followed by GPs and endodontists. The percentage of periapical biopsies submitted by GPs (18.08%) is comparable to that reported from Northern Ireland (12%) (Cowan et al. 1995), New Zealand (16%) (Becconsall-Ryan et al. 2010), the Uni- ted Kingdom (21%) (Warnakulasuriya & Johnson 1999) and Spain (24.5%) (Franklin & Jones 2006).

As GPs do not usually perform endodontic surgery and refer patients to OMFS or endodontists, it is possible that those cases represent tissue curetted from the tooth socket after an extraction. The most possible explanation for the limited number of cases submitted by endodontists is that they feel confident in their provisional diagnosis, as they routinely perform all proper diagnostic procedures (Garlock et al. 1998, Cunha et al. 2005, Omoregie et al. 2009). On the other hand, OMFS are trained to consider submission of any tissue removed from the oral and maxillofacial region for pathologic examination. The percentage of non-SPN lesions to the total number of biopsies submitted by GPs was 0.36% and OMFS 4.17%, com- pared to 6.6% and 6.4%, respectively, in the study of Kuc et al. (2000). This may be partly attributed to the finding of the present study that non-SPN cases, considered as a group, were larger that SPN lesions and large lesions are usually referred for management to OMFs. Although the significant differences found in the present study between SPN and non-SPN lesions should be considered with caution, as non-SPN lesions constitute a variable group of lesions with different clinical features, large size should be taken into account when clinicians consider whether to submit a lesion for histopathological examination.

Conclusion

Non-SPN lesions may appear in periapical regions mimicking a SPN, although rarely. Most of them are developmental cysts, in particular OKCs, but odontogenic tumours, such as ameloblastoma or malignant lesions may also be found. Thus, histopathological examination of tissue harvested from periapical lesions should be performed, in particular when those lesions are large.

Acknowledgements

There is no conflict of interest related to this study.

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