Accuracy for diagnosis of periapical cystic lesions

Clinical differentiation between cystic lesions of endodontic and non-endodontic origin is of importance because correct diagnosis may affect treatment decision making. Most radicular cysts are treated with conservative approaches and, therefore, are not surgically removed. The objective of this study was to determine the accuracy of clinical diagnosis of periapical lesions as compared to the histological findings, and to evaluate various associated factors. All biopsy specimens submitted for histological evaluation from 2002 to 2009 were assessed. Only cases of periapical lesions with complete patient data and clinical diagnosis were included. Sensitivity, specificity and accuracy of the clinical diagnosis were calculated and various patient-related factors were evaluated. Of the 4,908 cases, 183 met inclusion criteria. Histologically, there were 171 lesions of radicular cysts and 12 cases of non-endodontic cysts, including OKC and Incisive Canal Cyst. The diagnostic accuracy for clinical diagnosis for radicular cysts was 91.84% and 91.84% for non-endodontic cysts. There was a high accuracy of clinical differentiation between cystic lesions of endodontic and non-endodontic origin. However, some non-endodontic lesions may be incorrectly diagnosed clinically as lesions of endodontic origin. Histological evaluation may be necessary for the correct diagnosis. Further clinical studies are needed to evaluate clinical examination and histological diagnosis of periapical lesions.


Materials and methods
All biopsy specimens submitted to the oral pathology department between the years 2002 and 2009 were reviewed. The study was approved by Tel Aviv University the ethics committee (IRB reference number 1810.10). Informed consent was obtained from all subjects. All methods were carried out in accordance with relevant guidelines and regulations. Only cases of biopsy of periapical area adjacent to endodontically treated teeth were included. The collected specimens included biopsies following teeth extraction, apical surgery and cyst enucleation. Only cases with detailed clinical information including age, gender, clinical diagnosis, location of lesion, size of lesion were included. Cases without a clinical diagnosis or radiographic evaluation and cases that were not diagnosed histologically as radicular cyst (RC) or non-endodontic cysts (NEC) were excluded from the study. The biopsy tissue samples were fixed in 10% buffered formalin and embedded in paraffin. For each case, random 5-µm sections were cut and stained with hematoxylin and eosin, periodic acid-Schiff, and Gram stain. 3 random sections were analyzed per sample. The radiographic cystic lesion size was measured and the mean height by width was obtained in millimeters. The cystic lesions were classified according to size as following: • small (< 10 mm) • large (> 10 mm) We classified small lesion from large lesion based on the threshold used in previous researches 22,23 . The results were evaluated statistically as following. The association between the clinical diagnoses and histological diagnoses, gender, lesion size and lesion location were analyzed using chi-squared test analysis.
Association between the age of the patient and clinical and histological diagnoses was analyzed using t tests for descriptive numeric data.
Sensitivity, specificity and accuracy of the clinical diagnosis were calculated. Sensitivity was defined as proportion of people who test positive for the disease among those who have the disease. Specificity was defined as the proportion of healthy patients known not to have the disease, who will test negative for it.
In the present study the sensitivity was defined as radicular cyst and the specificity was defined as nonendodontic cysts.
Accuracy was defined as the proportion of both true positives and true negatives cases among the total number of cases examined.
The p-value was set at 0.05.

Results
Of the 4,908 cases examined, 183 cases met the criteria for inclusion (Fig. 1). Mean patient age was 40.16 years, with a 54.6% male predilection. No association was found between age and gender and between clinical and histological diagnoses. Of the 183 cases, 89 (48.9%) were located in the mandible and 94 (51.1%) were located in the maxilla.
Of the 183 cases, 159 (86.5%) were classified as large, 24 (13.5%) were classified as small. For large lesions there was a significantly higher prevalence of both radicular cysts and NEC (p < 0.05), Sensitivity, specificity and accuracy for clinical diagnosis are presented in Table 2 and ROC charts are presented in Fig. 2.

Discussion
In the present study, the association between the clinical and histological diagnoses was evaluated in 184 cases.
However, the biopsy specimens used in the present study were curetted and thus fragmented in several cases, making histological differentiation inaccurate. Periapical granulomas were diagnosed when there was no clear epithelial-lined lumen, and were not included in the present study. Moreover, it was not possible to evaluate with certainty the communication between the biopsy specimens and the root canal, due to the fact that the specimens did not contain root tips.
Kontogiannis et al. 24 found that NEC constituted 3.42% of the total cases of periapical lesions. These findings correspond with the findings in the present study, in which 6.6% of the cases were NEC.
Jones et al. 13 , evaluated the demographics of odontogenic cysts diagnosed in a UK population over a 30-year period, and found that out of 7,121 specimens that were diagnosed as odontogenic cysts, 3,724 (52.3%) were  www.nature.com/scientificreports/ radicular cysts. These findings correspond with the present study, in which 58.3% (7 cases out of 12) of NEC were histologically diagnosed as radicular cysts. The present study indicates that the diagnostic accuracy for clinical diagnosis for radicular cysts was 91.84%. Other studies of periapical biopsy specimens have suggested that in 0.7-5% of the cases there were differences between clinical and histological diagnoses 1,3,4,25 . However, these studies have not calculated the accuracy or the sensitivity of the diagnosis.
The present study refers to the clinical diagnostic accuracy for radicular cysts as opposed to NEC whereas. Stockdale et al. 25 calculated the difference in accuracy between radicular cysts and periapical granuloma. They found that the clinical diagnostic accuracy for radicular cysts was 41% and that the clinical diagnostic accuracy for periapical granuloma was 81.4%, which they consider to be a relatively high. We can conclude that the current clinical and radiological processes for distinguishing between periapical granuloma and radicular cysts is not accurate enough.
The present study indicates that for large lesions there was a significantly higher prevalence of both radicular cysts (83%) and NEC. Mortensen et al. 22 indicated that lesions larger than 15-20 mm, can be safely classified as cysts. However, various studies have indicated that basing diagnoses on radiographic analysis is not enough. Matsuda et al. 26 concluded that only through clinical and radiographic examination it is not possible to confirm the diagnosis of lesions.
Clinical differentiation between cystic lesions of endodontic and non-endodontic origin is of importance because correct diagnosis may affect treatment decision making. Most radicular cysts are treated with conservative approaches (endodontic treatment) and, therefore, are not surgically removed 19 . Furthermore, radicular cysts, are related to preventable causes (such as infections) and actions to promote oral health may help to reduce the prevalence of these lesions 27 .
This paper calculated the accuracy, sensitivity and specificity for differentiating between cystic lesions of endodontic and non-endodontic origin. We can conclude from our findings that while the current accuracy of clinical and radiological processes for distinguishing between the various periapical pathoses is high, the gold standard for diagnosis and identification of periapical lesions is histological examination.

conclusions
There was a high accuracy of clinical differentiation between cystic lesions of endodontic and non-endodontic origin. However, some non-endodontic lesions may be incorrectly diagnosed clinically as lesions of endodontic origin. Histological evaluation may be necessary for the correct diagnosis.
Further clinical studies are needed to evaluate clinical examination and histological diagnosis of periapical lesions.