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A Survey of Oral and Maxillofacial Biopsies Over a 23-year Period in the Southeast of Iran

Statement of the Problem: The prevalence of oral and maxillofacial lesions differs in various populations and is an important concern for health care providers. Purpose: The present study aimed to evaluate the relative frequency and distribution of oral and maxillofacial lesions in patients referred to the Department of Oral and Maxillofacial Pathology, Kerman Faculty of Dentistry in southeast Iran Materials and Method: In the present retrospective study, the collected data consisted of age, gender, lesion location, and the clinical and histopathological diagnoses of all the biopsy samples diagnosed in 23 years (1997–2020). The data were analyzed with SPSS 22, using the chi-squared test and ANOVA (p< 0.05). Results: From 2092 lesions with a definite diagnosis, 1202 (57.5%) and 890 (42.5%) cases belonged to female and male patients, respectively. The mean age of the subjects was 39.06±17.71 years, and the most frequent location of the lesions was the buccal mucosa (25.2%). The frequencies and number of non-neoplastic lesions, neoplasms, and premalignant lesions were 84% (n=1758), 13.3% (n=278), and 2.7% (n=56), respectively. Reactive lesions were the most common cases, with 34.6% (n=724), and lichen planus was the most frequent lesion with 18.1% (n=379). Squamous cell carcinoma was the most frequent lesion in patients >70 years of age (27.6 %). Conclusion: The present study provided useful data on the frequency and distribution of oral lesions over 23 years and made it possible to compare its results with those of studies carried out in other countries. Non-neoplastic lesions were the most common category, and lichen planus, pyogenic granuloma, and irritation fibroma were the most frequent lesions in descending order.


Introduction
The oral and maxillofacial areas can be affected by a wide variety of lesions with different origins and characteristics [1]. Although it is sometimes possible to reach a clinical diagnosis based on clinical examinations, in the majority of cases, it is necessary to carry out further evaluations, including biopsies. Histopathological evaluation is the gold standard to reach a definitive diagnosis and render proper treatment to patients [2][3][4]. Given the wide range of oral and maxillofacial lesions, it is necessary for the oral healthcare specialists, including general dental practitioners, to have adequate knowledge on the clinical and demographic characteristics of these lesions because some of the benign lesions in this area might exhibit similar clinical or radiographic manifestations and might even resemble malignant lesions [5][6][7]. Unlike dental and periodontal lesions about which dentists have adequate knowledge, the diagnosis of some oral and maxillofacial lesions might pose a challenge. Therefore, collecting the data on biopsied lesions not only can increase knowledge about the prevalence and distribution of these lesions in the Iranian population but also can emphasize the lesions that oral healthcare specialists might encounter in their routine practice at a higher frequency [8][9][10].
Several studies have reported the relative prevalence of biopsied lesions of the oral and maxillofacial regions in different parts of the world. However, the majorities of these reports have been confined to a specific age group or a specific group of lesions, or have been based on clinical examinations without histopathological evaluations. Limited studies on histopathological diagnosis that included a full complement of oral lesions and patients in all age groups have been carried out on oral and maxillofacial lesions all over the world [11][12][13][14][15][16][17][18][19][20][21][22].

Materials and Method
The present retrospective study was carried out on the biopsies taken from July 1997 to July 2020 from the patients referred to the Department of Oral and Maxillofacial Pathology, which had undergone histopathological evaluations. The Ethics Committee of Kerman University of Medical Sciences approved the protocol of the study under the code K.97.285.
The demographic data of the patients were collected from the database of the Department, which included age, gender, and other data on the location of the lesions, the clinical and histopathological diagnosis. The samples related to the repetition of the biopsies, which had already been diagnosed (e.g. for the excisional biopsy of a lesion that had already been diagnosed by using an incisional biopsy) were excluded. In addition, samples with descriptive and non-definitive diagnoses and normal tissues were excluded.
Based on the histopathological diagnosis, the lesions were categorized into three main groups of non-neoplas-tic, neoplastic, and premalignant lesions. Then the nonneoplastic lesions were divided into eight subgroups including reactive lesions, infectious and non-specific inflammatory lesions, cystic lesions (odontogenic or non-odontogenic), pigmented lesions, osseous lesions, salivary glands lesions, tooth-related and periodontiumrelated lesions, and immune system-related lesions. The neoplastic lesions were divided into two subgroups including benign (odontogenic and non-odontogenic) and malignant. The data were analyzed with SPSS 22, using the chi-squared test, ANOVA, and post hoc tests at a significance level of p< 0.05. In terms of the classification of the histopathological diagnosis, 1758 cases (84%) were non-neoplastic lesions, 278 cases (13.3%) were neoplastic lesions, and 56 cases (2.7%) were premalignant lesions. The nonneoplastic lesions were more common in female subjects compared to neoplastic and premalignant lesions, and the difference was significant (p= 0.026). The mean age of the patients with premalignant lesions was higher than that of patients with neoplastic and non-neoplastic lesions; neoplastic lesions were detected in patients with a higher mean age compared to non-neoplastic lesions (p< 0.001).

Of
The most common areas affected were the buccal mucosa (n=529), the mandible (n=265), and the maxillary gingiva (n=215). The other areas were the mandibular gingiva (n=206), the tongue (n=199), the maxilla (n=196), the labial mucosa (n=147), the vestibule (n=96), the palate (n=87), the alveolar ridge (n=69), the floor of the mouth (n=20), the alveolar socket (n=14), the skin (n=12), and the salivary glands (n=8). In 29 cases, the data were missing about the location of the lesion. The buccal mucosa was the most common area of involvement for the non-neoplastic and premalignant lesions; however, the tongue was affected by the neoplastic lesions at a significantly higher rate (p<0.05). Table 1 presents the distribution of the lesions in the three main groups in terms of gender, age, and the most common location of involvement.

Non-neoplastic lesions
The most prevalent subgroups of non-neoplastic lesions were reactive lesions (n=724)  Table 2 presents the 5 most prevalent lesions in each subgroup of non-neoplastic lesions in terms of gender, age, and the most common area(s) affected.
There were no significant differences in the distribution of benign and malignant neoplasms between the male and female patients (p= 0.6). However, benign odontogenic neoplasms were significantly more prevalent in female patients compared to male patients (p= 0.05).
The majority of benign neoplasms (n=138) were non-odontogenic, and a minority of them (n=28) were odontogenic. Of all the non-odontogenic benign tumors, squamous papilloma (n=42) and acquired melanocytic nevus (n=17) were the most frequent lesions; of all the benign odontogenic tumors, ameloblastoma (n=11) and odontoma (n=9) were the most common ones.
Of 112 malignant neoplasms evaluated in the present study, squamous cell carcinoma (SCC) was the most prevalent one with 82 cases, and odontogenic carcinosarcoma, olfactory neuroblastoma, and plasmacytoma were the least frequent ones with one case each.  Table 4).

Discussion
Studies on the frequency of oral and maxillofacial lesions are an essential aspect of oral healthcare programs and provide epidemiologic data on the distribution of these lesions in different populations [23][24]. In the present retrospective study, 2092 oral and maxillofacial biopsies were evaluated. Evaluation of the data showed a higher frequency of these lesions in female subjects  [13] and Jordan [7]. In the present study, reactive lesions were reported as the most prevalent subgroup (31.1%), in line with the majority of previous studies [7,10,12,14]. Since the oral cavity is subject to various traumatic and irritating agents, such a finding is expect- ed [25][26]. In this group, pyogenic granuloma was the most common lesion (9.1% of all the lesions). Although some studies have reported a similar finding [19,14], the majority of studies have reported irritation fibroma as the most common reactive lesion [6][7][11][12]. In addition, pyogenic granuloma had the highest prevalence in female patients and the maxillary gingiva, in agreement with the results of previous studies [10,14].
Immune system-related lesions were the second most prevalent subgroup in the present study (18.6%).
Lichen planus was the most common lesion in this subgroup and the most common lesion of all the lesions. In line with the results of studies in the United Kingdom [6] and Kuwait [11], lichen planus was more common in female patients and the buccal mucosa. Evaluation of similar articles shows significant variations in the arrangement of common subgroups.
In a study by Monterio et al. [12], cystic lesions constituted the second most common subgroup of lesions; in studies by Ali et al. [11] and in a study by Alkhateeb et al. [7], inflammatory lesions, and in a study by Jones and Franklin [6], tooth-related lesions were the second most common subgroups. It appears that one of the reasons for these differences is the use of different classification systems in different studies. A search in the literature did not show any two studies that have used a similar classification system for lesions. In addition, ethnic and geographical variations, differences in sample sizes, and the mechanism of referrals of the patients might cause these differences [27].
In the present study, lichen planus was the most frequent lesion; however, none of the similar studies has reported such a finding. Pyogenic granuloma [10,14], irritation fibroma [6][7][11][12], and radicular cyst [28] have   Cystic lesions were the third most common subgroup (12.2%) in the present study. In accord with the majority of previous studies, radicular and dentigerous cysts were the most frequent cystic lesions, in descending order, with a higher frequency in the mandible [6,10,12,27]. Of all the non-odontogenic cysts, the nasopalatine duct cyst exhibited a higher frequency, consistent with the results of studies in Jordan [7] and Portugal [12].
In the present study, neoplastic lesions (11.9%) were less frequent than the non-neoplastic lesions. The prevalence of these lesions has been reported in other studies at 9.5% [12] and 27.6% [27] in Brazil, and 14.7% in Kuwait [11]. In the present study, benign neoplasms were more frequent than the malignant lesions, compatible with the results of other studies [10,14,[26][27].
Squamous papilloma (1.8% of all the lesions) was the most frequent benign neoplasms in the present study.
Jones and Franklin [6] and Ali et al. [11] reported similar results; however, Alkhateeb et al. [7] and Monterio et al. [12] reported that squamous papilloma was the second most common benign neoplasm after pleomorphic adenoma. Benign odontogenic tumors comprised 1.1% of all the samples in the present study. The prevalence of these lesions was 2.3% in Kuwait [11] and 3.4% in Lybia [10], which confirms a low prevalen-  and Hatem et al. [10], ameloblastoma was the most prevalent odontogenic tumor, with a higher prevalence in the mandible.
In the present study, malignant neoplasms com-  [12]. In studies carried out in Lybia [10], Brazil [12], and Spain [28], similar to the present study, epithelial dysplastic lesions related to leukoplakia or erythroplakia were reported as the most prevalent premalignant lesions, with a higher frequency in male subjects compared to female subjects. In addition, a higher prevalence of SCC, compared to dysplas-  [12,27].

Conclusion
Generally, the majority of the lesions in the present study were non-neoplastic, and lichen planus was the most common lesion among all the lesions. Malignant neoplasms comprised 4.8% of all the lesions, and SCC was the most frequent malignancy (73.2%). The present study not only did provide useful information about the frequency and distribution of oral lesions and assistance for the proper differential diagnosis of these lesions but also carried out a comparison of this prevalence with the data available from other countries.