Periapical lesions are one of the common pathological conditions seen in dental practice and typically occur with pulpal infection and necrosis.[1] These lesions occur as a result of microbial invasion of the root canal system and an inflammatory response in the periapical tissues.[2] The most frequent periapical inflammatory pathologies are periapical granulomas and radicular (periapical) cysts.[3] Both lesions can develop secondary to chronic apical periodontitis, but have different biological behavior, histopathological features, treatment response, and prognosis. This differentiation is critical for proper treatment planning and successful endodontic treatment.[4]

Inflammation of the epithelium and the surrounding tissue, forming a mass at the apex of a non-vital tooth, is called a periapical granuloma.[5] Histologically, it is characterized by the infiltration of chronic inflammatory cells, fibroblasts, and capillaries, and granulation tissue.[6] A radicular cyst is an epithelium-lined pathological cavity, typically developing from chronic inflammation, as a result of proliferation of the epithelial cell rests of Malassez.[7] The radicular cysts are considered the most prevalent inflammatory odontogenic cysts and can grow larger and larger as a result of the osmotic pressure and the growth of the epithelial structure.[8]

Periapical lesions make up a significant percentage of oral pathological specimens received for biopsy worldwide.[9] According to studies, periapical granulomas make up around 45-60% of chronic periapical lesions, while radicular cysts make up almost 15-35% of cases.[10] These lesions are especially common in people who do not have good oral hygiene, have untreated dental caries, and have low access to dental care.[11] Radiographically, both lesions are often well-defined periapical radiolucencies related to a non-vital tooth.[12] The use of advanced diagnostic modalities such as cone beam computed tomography (CBCT), aspiration techniques, and histopathological analysis has contributed to an overall increased accuracy of diagnosis; however, there are still difficulties with differentiation.[13]

In recent years, there has been more and more focus on the correlation of radiographic and histopathological features to enhance the non-invasive diagnostic methods. But there is some controversy about the accuracy of the radiographic criteria for differentiating between periapical granulomas and cysts. Several lesions that were originally thought to be cysts have been subsequently proven histologically to be granulomas, which reflects the diagnostic challenges that confront the clinician.[14, 15] Therefore, comparative studies with emphasis on the diagnostic and morphological features of these lesions are needed to define more precisely the diagnostic criteria and the prognosis for their treatment.

The reason for the present study is the clinical difficulty of making a correct diagnosis between periapical granuloma and radicular cyst by conventional methods. Both lesions generally have similar clinical and radiologic features, but have different histopathologic architecture and therapeutic considerations, and a detailed comparative evaluation is necessary. Based on the diagnostic and morphological aspects of these lesions, this study is designed to make a contribution towards an increased diagnostic accuracy, to a more suitable treatment planning and to a deeper knowledge of the biological behavior of chronic periapical lesions. This study was designed to compare the clinical, radiographic and histopathologic features of periapical granuloma and radicular cysts

The present work was a comparative a cross-sectional study. The period of study was 6 months from June to December, 2025. Clinical examination and radiographs were used to assess patients with periapical lesions around non-vital teeth and biopsy specimens were taken during extraction, endodontic surgery or cyst enucleation, and then subjected to histopathological examination for diagnosis and comparison of the morphology of periapical granulomas and radicular cysts. The sample size was determined with the OpenEpi sample size calculator, using a previous prevalence of periapical granulomas is 53.7%, and 95% confidence level with 8% margin of error; the calculated sample size was 150 patients.[16] A non-probability consecutive sampling technique was used for patient recruitment. The inclusion criteria were patients of both sexes who were at least 18 years old and who had an apicoectomy, surgical enucleation, or extraction of teeth with periapical lesions that were suggestive of periapical granuloma or radicular cyst, and had submitted tissue for histopathological examination. Patients who had recurrent lesions, had previously treated periapical lesions, had odontogenic tumors, had systemic inflammatory diseases involving the oral tissues, had inadequate biopsy specimens and had incomplete clinical and radiographic records were excluded from the study. Patients with inclusion criteria who gave informed written consent were enrolled in the study after obtaining approval from the institutional ethical review committee. A structured proforma was used to document detailed demographic and clinical data such as age, gender, presenting symptoms, tooth involved, and duration of symptoms and the vitality status of the affected tooth. Clinical examination and radiographic evaluation with periapical radiographs and/or orthopantomograms were used to assess the size, location, border characteristics and radiographic appearance of the lesions. Samples were obtained in the Department of Oral and Maxillofacial Surgery, following the collection of tissues from patients undergoing the procedures of tooth extraction, apicoectomy, curettage, or cyst enucleation under sterile conditions. The excised specimens were fixed in 10% buffered formalin and forwarded to the Department of Oral Pathology for histopathology. These tissues were routinely processed, embedded in paraffin wax, cut, and stained with hematoxylin and eosin. The histopathological examination was carried out by an experienced oral pathologist who distinguished the periapical granuloma from the radicular cyst, based on various morphological features such as the epithelial lining, inflammatory cell infiltration, vascularity, collagen distribution and cystic cavity formation. The results were recorded in a systematic and organized manner for comparative analysis. Data collected were entered and analyzed in IBM SPSS version 26. Normality for continuous variables such as age and lesion size was determined using the Shapiro–Wilk test and was determined to be normally distributed (p > 0.05). Quantitative variables were expressed as mean ± standard deviation values, and categorical variables like gender, type of lesion, clinical symptoms, tooth involvement, radiographic characteristics and histopathological features were presented in frequencies and percentages. An independent sample t-test was used for inferential analysis to compare the continuous variables (age and lesion size) between the periapical granuloma and radicular cyst groups. The Chi-square test or Fisher’s exact test, as appropriate, was used to assess associations between categorical variables and lesion type. A p-value of ≤0.05 was considered to be statistically significant.

A total of 150 patients with periapical lesions were included in the study whose mean age was 34.8 ± 11.2 years. There was a slight male predominance with the majority of the participants in the 31-45 age group compared to females. The periapical granuloma was the predominant periapical lesion in the sample, as its prevalence in the histopathological examination was 61.3% as compared to 38.7% for the presence of any radicular cyst. The most common presenting symptom was pain, followed by swelling, sinus tract formation and asymptomatic cases. The most frequently affected area was the maxillary anterior teeth and all the cases were related to non-vital teeth, indicating the close association between pulpal necrosis and periapical pathosis. Radiographically, the majority ranged from 1-2 cm, with most lesions seen as well-defined unilocular radiolucencies and ill-defined borders and a multilocular pattern being less common. The results indicated the typical radiographic features of chronic periapical lesions (Table 1).

The histopathology of the different kinds of lesions was compared and statistically significant differences were observed between the different kinds of lesions. Epithelial lining and cystic cavity formation were consistently found in radicular cysts and vascularity and inflammatory infiltrate were seen more in granulomas. In addition, the presence of collagen density and cholesterol clefts was more prominent in the cystic lesions, suggesting structural differences between the two entities (Table 2).

Radiographically, larger lesion size and well-defined borders were significantly associated with radicular cysts, while ill-defined borders were more common with granulomas. In both lesion types however, the overall radiographic appearance of a unilocular radiolucency was present (Table 3). The analysis of clinical symptoms revealed that pain was more closely related to granulomas and swelling, and asymptomatic presentation was more closely related to radicular cysts. There was no statistically significant difference in sinus tract formation between the two groups, suggesting that there were no distinct clinical differences between the two lesions (Table 4).

Table 1: Demographic, Clinical, and Radiographic Characteristics of Study Participants (n = 150)

Table 2: Histopathological Characteristics of Periapical Granulomas and Radicular Cysts

Table 3: Comparison of Radiographic Findings Between Periapical Granulomas and Radicular Cysts

Table 4: Association of Clinical Symptoms with Lesion Type

In the present study, the diagnostic and morphological features were compared between periapical granulomas and radicular cysts, based on clinical, radiographical and histopathological parameters. Periapical granuloma formed 61.3% and radicular cysts 38.7% of the lesions in the present study. The results were similar to the study by Danuchit Banomyong et al. in 2023, where periapical granulomas were more common (81.9%) than cysts (18.1%).[3] Likewise, Myciński Paweł et al. detected the presence of granulomas in 65.4% of patients and radicular cysts in 34.6% of lesions.[17]

The mean age of patients in the present study was 34.8 ± 11.2 years, with most patients belonging to the 31–45 years age group. Radicular cysts were more frequent among older patients compared to granulomas. The mean age of occurrence of radicular cysts was also slightly higher than that of granulomas in the South Indian cohort study.[3] Male predominance was also noted in the current study and this was corroborated by previous investigations which showed that chronic periapical lesions were more prevalent in males. [18]

The pattern of distribution of lesions in the present study was that the anterior teeth of the maxillae were affected more frequently than the other teeth in both types of lesions. The results of the present study were in agreement with previous reports indicating maxillary incisors as the most commonly involved teeth because of their increased susceptibility to trauma and pulpal necrosis. A higher incidence of lesions in the anterior maxillary area was also reported in the clinicopathological studies.[3, 19]

The most frequent presenting symptom in granulomas was pain, and in radicular cysts, it was swelling. This could be due to the size and gradual growth of cysts. Similar observations were noted in the clinical study involving chronic inflammatory periapical lesions, with radicular cysts frequently causing swelling and cortical expansion, and granulomas being more likely to be symptomatic and cause pain and tenderness.[19]

The present study revealed that there was a significant relationship between radiographically well-defined, corticated borders and lesions greater than 2 cm in dimension in the presence of a radicular cyst. Granulomas, in contrast, were more likely to have poorly defined margins. The results were similar to the 2024 population study of the Tamils which showed that well-defined corticated radiolucencies were common in cases of radicular cysts, while most of the granulomas had poorly demarcated margins.[18] Likewise, in the 2025 retrospective observational study, periapical cysts had larger diameters on radiographs compared to granulomas.[20]

The histopathological results of the present study showed that the presence of epithelial lining and cystic cavity formation had a significant relationship with the presence of radicular cysts, whereas increased vascularity and granulation tissue predominated in cases of periapical granuloma. Cholesterol clefts and dense collagen fibers were more commonly found in cysts. These findings were consistent with classical descriptions of radicular cysts as reported in a previous study which stated that epithelial lining and cystic cavity formation were characteristics of radicular cysts.[3]

One key finding in the present study is that there was a remarkable difference between the appearance on radiograph and definitive diagnosis by histopathology. A few lesions that had a radiographic appearance of cysts proved to be granulomas on histopathology. There are several previous studies that have pointed out the lack of correlation between clinical/radiographic and histological diagnosis. In my previous report by Myciński Paweł et al., only partial agreement was found between radiological and histopathological diagnosis, and another big study with 317 biopsy specimens showed only fair agreement between clinical and histological diagnosis (k = 0.059).[17]

The current results thus support the idea that histopathologic analysis continues to be the definitive diagnosis of chronic periapical lesions. Improved diagnostics by using advanced imaging techniques is possible; however, radiographic features are not enough for accurate differentiation between granulomas and cysts. The studies of Kizil Z and Energin K showed that only 66.6% of the cases were diagnosed radiographically in accordance with histopathologic diagnosis.[16]

The present study showed that there was a significant overlap between the clinical and radiologic features of the periapical lesions, and a significant number of clinical and radiographic features that appeared suggestive of granuloma were observed in radicular cysts as well. Histopathology, therefore, remains a key factor in the correct diagnosis and treatment planning. The results of this study provide important comparative information about the morphological and diagnostic features of chronic inflammatory periapical lesions and add to the increasing evidence that underscores the importance of making a diagnosis based on microscopic examination.

The results of the present study emphasize the importance of diagnosing periapical granulomas and radicular cysts based on clinical and radiographic appearance. Both lesions often have similar symptoms and radiolucent appearances and can be confused for one another, resulting in poor diagnosis or treatment planning. The study confirms the importance of performing a histopathology examination as the gold standard for the definitive diagnosis which should be routinely considered, particularly for lesions with persistent radiolucency, larger size or atypical radiographic features. Early and accurate identification of a radicular cyst is especially crucial as it may need surgical intervention, e.g. enucleation, while a granuloma may be possible to treat with regular endodontic treatment. Thus, using biopsy and histopathological examination as routine clinical practice can enhance prognosis, minimize recurrence, and adequately manage cases in endodontic and oral surgical practice.

There were some limitations in the present study. It was performed in one tertiary care hospital and may not be applicable to other populations. The number of samples was sufficient for analysis, but was still relatively small and may not reflect the entire range of periapical lesions in the general population. Radiographic evaluation was undertaken mainly based on conventional imaging which may not be as sensitive in the evaluation of lesion extent and characteristics when compared with other more sophisticated imaging modalities like cone beam computed tomography (CBCT). Furthermore, the diagnosis of categorisation could have been affected by inter-observer variation of the histopathological interpretation, which was minimised by the expert evaluation. Finally, because the study was cross-sectional, the progression of the lesions and long-term treatment outcomes were not evaluated,

Periapical granulomas and radicular cysts involve marked similarities in clinical and radiographic characteristics, which makes it difficult to make a definitive diagnosis before the surgery. However, there were marked differences at the histopathological level in terms of epithelial lining, formation of cystic cavities and inflammatory tissue characteristics. Well-defined and larger radiolucencies were more likely to be associated with radicular cysts, whereas granulomas were more likely to have smaller and more ill-defined radiolucencies. The results highlight the importance of histopathological examination in accurate diagnosis and suitable treatment planning. Diagnostic accuracy and best management of patients for periapical pathologies requires a combined clinical, radiographic, and microscopic approachhe

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