INTRODUCTION
With recent advancements in dentistry, there was an emanated necessity to create awarness about the oral manifestations and its treatment modalities among the dental professions. However, in most cases, dentists are the first people to notice the patient's oral lesions. Without doubt, accurate diagnosis would prevent the progression of many diseases and malignant lesions. Oral mucosa can be affected to a large number of diseases and lesions. Accordingly, systematic examination of the mouth is very important.[1] A detailed knowledge of oral and gingival pathological lesions is essential so as to differentiate them from normal variations of mouth.[23] Many systemic diseases have different gingival and oral mucosal manifestations. One of the manifestations is papules of various sizes and clinical appearances. A variety of developmental lesions such as Bohn nodules, Fordyce granules, papilloma and fibroma are common in the mouth and cause confusion in the diagnosis. Papules with white and yellow color in the gingival area can be seen. Despite advances in dentistry and medicine, details of the nature and epidemiology of them are not available.[4] Hence, a precise definition of lesions similar to that in previous investigations mentioned in the case reports is needed. Exostosis, gingival cyst,[5] hamartoma,[6] papilloma and fibroma,[7] According to previous observations, few lesions such as exostosis, gingival cyst, hamartoma, papiloma and fibroma have similar appearance mimicking gingival papules. Gingival papules are lesions that are created in the area of gingiva and their color is white or yellow. If the nature of these normal variations is detected, no specific treatment and patient follow-up are required.[4] Gingival papules (gingival fibrous nodules or gingival nodules) are all benign and in some ways similar to small fibromas. Of course, their clinical and histological features differentiate them from lesions such as secondary oral nodules of epidermolysis bullosa. These papules are single or multiple, somewhat rolled out and with bright color in the boundary between the area of adhesive gingiva and alveolar mucosa and their consistency is also firm. In the previous studies, the term “gingival fibrosis nodules” has been used for these lesions.[8] Due to the presence of these lesions in the mucogingival area, the term “mucogingival papules” is also used to describe these lesions.[3] Most of the documented research studies on gingival papules are case reports lacking original studies on evaluating gingival papules with normal variations in oral cavity. The purpose of this study was to investigate the clinical and histopathological manifestations of unclassified gingival papules in Urmia Dentistry School.
MATERIALS AND METHODS
This cross-sectional descriptive study on 500 patients admitted to the Department of Oral and Maxillofacial Pathology, Urmia School of Dentistry, Iran. The sample size (498) was determined by using SCC power software through pilot experiments on 100 patients and taking into account the following parameters (α = 0.05, standard deviation = 4.1, P = 0.68). Epidemiological data and the demographics of the patients, such as age, sex, skin disease, smoking, history of systemic disease (convulsions, anemia, high blood pressure, cardiovascular disease and diabetes), genetic diseases, mouth breathing, pregnancy, breastfeeding and contraceptive pills, along with histopathological findings were obtained.[9] The study had no exclusion criteria other than not wanting to participate in the study, and diagnosis was other well-known lesions. The patient was given a questionnaire with a consent form. The questionnaire was designed according to the researchers of the project ideas, and its validity was confirmed by professors of Urmia Faculty of Dentistry. The biopsy of two patients with gingival papules was prepared. The samples were fixed in formalin for 48 h and paraffin blocked. Five-micron sections were prepared using a microtome in the Pathology Laboratory of Urmia Faculty of Dentistry. The sections were deparaffinized in xylene and rehydrated in ethanol and water. The procedure was followed by H&E staining. Slides of the samples were analyzed in terms of collagen density, lymphocytes, blood vessels and regular or irregular collagen.[10]
Informed consents were obtained from all the patients including who were participated in biopsy procedure. No intervention was done, and actually, the purpose of clinical examinations was characterization of the gingival papules.
Statistical analysis
Statistical Package for the Social Sciences (SPSS) statistical software for data analysis was used. The frequency and percentage of patients with gingival papules in general and on the basis of variables were determined. The effects of variables in the prevalence of gingival papules were analyzed using Fisher's exact test. Type I error rate in this study was 0.05, and if the Type II error rate of less than or equal to the first type error was estimated, assuming significant correlation was obtained.
RESULTS
In this research, 500 patients referred to the dental school were evaluated. Of these, 340 patients (68%) had gingival lesions and 160 (32%) had no gingival lesions. 193 were male (38.6%) and 307 were female (61.4%). Of the 340 patients with gingival lesion, 139 (40.9%) were male and 201 (59.1%) were female. Out of 160 patients without gingival lesion, 54 (33.8%) were male and 106 (66.2%) were female. Fisher's exact test showed that there were no significant differences in the incidence of lesions in both groups of women and men (P = 0.389). In other words, gender factor has no clear effect on the incidence of gingival lesions in the examined patients. Of the 340 patients with gingival lesions, 127 (37.4%) were single and 213 (62.6%) were married. Of the 160 patients with no gingival lesion, 71 (44.4%) were singles and 89 (55.6%) were married. There was no significant difference in terms of being single or married. The average age of the participants in the research was 34.32 ± 13.96 years. The age of the patients involved with gingival lesions was between 20 and 40 years. Among the subjects studied, 130 were students (27.2%), 130 (26.2%) were homemakers, 101 (20.4%) were free-employed, carpenter and worker, 82 (16.5%) were employees, teacher and trainer, 18 (3.6%) were retired and unemployed, 13 (2.6%) were doctors, 7 (1.4%) were engineers, 6 (1.2%) were pediatrics under the age of 6 and 8 (1.6%) were military men. Jobs did not make any significant effect on the presence of gingival papules. Of the 340 patients with gingival lesion, 64 (18.8%), and of the 160 noncomplicated subjects, 20 (12.5%) were tobacco consumers. Although most people who used tobacco had gingival lesions, there was no significant difference in the frequency of smoking in the two groups of patients with lesion and no lesion [Table 1; Fisher's exact test; P = 0.09].
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Table 1: Distribution of patients in terms of smoking in two groups with lesion and no lesion
Of the 340 patients with gingival lesion, 293 (86.2%) had no mouth breathing and 47 (13.8%) had mouth breathing. Of the 160 patients without lesion, 135 (84.4%) were left with no mouth breathing and 25 (15.6%) had mouth breathing. Fisher's exact test did not show a significant difference in the frequency of gingival lesions in the presence or absence of mouth breathing. In other words, mouth breathing did not significantly affect the incidence of gingival lesions in the examined patients (P = 0.588). Of the patients under study, 490 had no skin disease and 10 had skin disease. In 340 patients with gingival lesion, 335 (98.5%) had no skin disease and 5 (1.5%) had skin diseases. Furthermore, in 160 patients with no gingival lesion, 155 (96.9%) had no skin disease and 5 (3.1%) had skin diseases. Due to Fisher's exact test, skin diseases do not significantly affect gingival lesions in patients (P = 0.303). Of the 340 patients with gingival lesion, 23 (6.8%) had already detected gingival lesions. Two patients (0.6%) noticed changes in the color and size of their gingival lesions. Six patients (1.8%) reported that they have a history of gingival lesions in their families. None of the lesions examined were painful. According to the results of the study, 340 patients with gingival lesions, 332 (97.6%) had papules in white color, 3 (0.9%) had pink lesion and 5 (1.5%) had melanotic lesions. Of the total 340 patients with gingival lesion, 186 (54.7%) people were involved in the anterior, 20 (5.9%) people in the posterior areas, while 134 (39.4%) people in the posterior and anterior regions. Of the total 340 patients with unclassified gingival papules, 337 (99.1%) cases had well-defined borders, and 3 (0.9%) of them had no well-defined borders. Of the 340 patients with gingival lesions, 31 (9.2%) patients were suffering from periodontitis and 95 (27.9%) were suffering from gingivitis. In 214 (62.9%) cases, no periodontal disease was reported. Among the total samples, 198 (58.4%) involoved maxilla, 39 (39.2 %) involoved mandible and 103 (30.4%) involoved both maxilla and mandible. There were no significant differences in the position of the right and left jaws. 133 (39.1%) individuals had single lesions and 207 (60.9%) had multiple lesions. Six people (1.8%) were diagnosed with genetic disease and 334 (98.2%) had no disease. 331 (97.3%) people were involved in the keratinized gingiva region, 1 (0.3%) in the nonkeratinized gingiva and 8 (2.4%) in the border between these two areas. The highest number of gingival lesions was found around the upper canine region and the lowest number in the second molars area of the mandible and maxilla. There was no lesion around the third molar teeth. In addition, among the patients, the medications did not affect the appearance of gingival papules. The average size of the papules in the patients with gingival lesion was 0.61 ± 0.36 mm (a range of 0.5–5 mm). Of the 201 women with gingival disease, only one (0.5%) was pregnant and 200 (99.5%) were not pregnant. Of the 106 women with no gingival disease, only one (0.9%) was pregnant and 105 (99.1%) were not pregnant. Fisher's exact test showed that there was no significant difference in the incidence of gingival lesions in terms of pregnancy or nonpregnancy (P = 0.27). Among women with gingival disease, 4 (2%) patients, and among women with no gingival disease, 5 (4.7%) patients had breastfeeding their baby. According to Fisher's exact test, women who were breastfeeding their baby were less likely to develop gingival papules (P < 0.004). Among women with gingival papules, 7 (3.5%) women and 5 (4.7%) women without gingival papules used contraceptive pills. Fisher's exact test showed that those who used contraceptives were less likely to develop gingival lesions (P < 0.02). In other words, the incidence of gingival lesions in consumers of contraceptive pills was lower than those without taking these pills.
First case
A 25 year old female patient visited the dental clinic with cheif complaint of tooth surface irreguarity on the labial surface of central incisor tooth. She took a dose of pantoprazole for about 6 months but did not take any medicine at the time of the examinations and had a history of smoking. During the examination, large, multiple, white and nonmoving papules were observed on maxillary and mandibular labial surfaces in the keratinized and nonkeratinized gingival region. These lesions were not painful and the patient did not feel pain at palpation. The patient was not aware of any lesions, and with permission from her, she was removed from the site of the lesion at a size of 3–3 mm from the lesion site, which had a size of 2–2 mm in the gingival margin of the labial keratinized gingiva of the canine region of the maxilla on the left.
Histopathological analysis
Healthy gingival characteristics
Gingival epithelium was 70% keratinized and 30% nonkeratinized. Under the epithelium was the lamina propria, which contains dense connective tissue, small blood vessels, nerves, fibroblasts, immune cells (lymphocytes, macrophages, neutrophils and plasma cells) and collagen bundles (regular and nonregular).
Gingival papule
The lesion has a tissue similar to healthy gingiva, except that, in these papules, collagens were irregular and dense in bundles, close to the surface and covered with parakeratinized squamous epithelium. In addition, a small number of lymphocytes were scattered under epithelium. A number of small blood vessels were observed in the tissue [Figure 1].
Figure 1: (a) Clinical view of papular lesion in the first patient (anterior maxilla). (b) Histological section of gingival papule in the first patient containing a healthy stratified squamous epithelium and dense collagenous fibers of connective tissue (H&E stain, ×40)
Second case
The second patient was a 21-year-old man who referred to the dental school for routine examinations. The patient did not have a special medical history but suffered from shortness of breath and had now improved. He did not take any special medications and did not have an allergy. He had a history of alcohol and cigarette smoking. When routine examinations were done, a number of white and pale-colored papules were observed that were painless and intact and did not feel pain at palpation. After obtaining consent from the patient, an excisional biopsy was performed on the labia surface of right mandibular incisors.
Histopathological analysis
Small and slightly dense papules in this sample contained dense collagenous tissue. The irregular collagen bundles were close to the surface of the papules and covered by parakeratinized stratifies squamous epithelium. Lymphocytes have been scattered in the connective tissue, and a number of small blood vessels have been detected in the tissue [Figure 2].
Figure 2: (a) Clinical view of papular lesion in the second patient (anterior mandible). (b) Histological section of gingival papule in the second patient containing a healthy stratified squamous epithelium and dense collagenous fibers of connective tissue (H&E stain, ×40)
DISCUSSION
Gingival papules are considered normal variations and similar to other normal variations caused by collagen in the mouth.[23] Their etiopathogenesis has not yet been conclusively identified, but they seem to be nothing but an anatomical variation and only have a different appearance.[3] There is no detailed information on the epidemiology of gingival papules, although it seems that lesions are more common in men and in the age range of 25–30 years. In the present study, the prevalence of papules in the gingival area was 68%, which was a significant rate. On the other hand, the prevalence of lesions was 40.9% in men and 59.1% in women, which contradicted the results of the previous study. The mean age of the patients with gingival lesions was 34.9 years, slightly more than the previous one.[4] In previous studies, lesions in the labial mucosa have been seen in both upper and lower jaw, but more lesions appear in the mandible and mucogingival location.[23] According to the results of this study, gingival lesions were detected in the maxilla (58.4%), maxilla and mandible (30.4%) and mandible (11.2%). It was also observed more in the anterior (54.7%), posterior and anterior regions (39.4%) and posterior regions (5. 9%). Most of the gingival papules (97.6%) were white in the study, and only 0.9% of them had pale pink color. In general, the gingival papules are white to pink and appear individually or multiple with soft surfaces, and their consistency is firm and their size is reported to be about 1–4 mm. Further, these lesions are well defined and nonmoving. Of the 340 patients with unclassified gingival papules in the present study, 99.1% were well defined. The papules are generally asymptomatic and are known to just a few patients. For this reason, these papules are usually present in the gingiva for a long time, and there is no bone resorption in radiography.[4] Some conditions such as gingival cysts,[5] exostoses, multiple hamartomas and gingival manifestations of nodular sclerosis,[6] focal epithelial hyperplasia and papillomas are very similar to gingival papules.[7] Exostoses are seen as firm nodules when touched, and the results of their clinical examinations may also be similar to gingival papules. Gingival nodules are differentiated from gingival cyst by the presence of fluid in the latter lesion. Cysts usually appear at the top of the mucogingival line, which contradicts the posture and position of the gingival papules.[2] Gingival fibroma is more coronal in comparison with gingival papules and occurs in most cases in the interdental papilla. Compared to gingival papules, they may develop over a shorter period of time. The focal epithelial hyperplasia caused by human papillomavirus can be multiple lesions in areas other than gingiva.[11] In the histological sections, the gingival papules demonstrate dense collagen tissue, covered by stratified squamous epithelium, and have no signs of inflammation that are consistent with the histological details of the present study.[23] Clinical examinations in the study of Srivathsa et al. demonstrate 1–4 mm papules, located in the mucogingival region, which are firm or multiple lesions. These papules appear slightly pink or white. All of the lesions were painless. Patients had no history of systemic disease and were unaware of the presence of lesions.[4] These findings are consistent with the results of this study. In the diagnosis of gingival lesions, a detailed history of existing lesions, along with a complete examination of body systems, especially skin changes, and questions about symptoms such as joint pain, muscle weakness, shortness of breath, double vision and chest pain, presents more information (due to the presence of oral symptoms in some systemic diseases).[8] The possibility of infection and malignancy should always be considered.[12] Giunta described Clinical and histological characteristics of gingival fibrosis nodules in five patients. They prepared biopsies from all five patients and identified lesions and their characteristics. These single or multiple nodules were firm in consistency. They appeared in the anterior part of the mandible and in the mucogingival area.[2] Shulman et al. examined the incidence of oral mucosal lesions in American adults. These lesions were different from the lesion studied in this research. Denture-related lesions, cigarette and nicotine-related lesions, amalgam-related lesions, buccal mucosa and lip bites and white abrasions were investigated.[13] AlDosari and Al-Mobeeriek investigated the prevalence of Fordyce granules, leukoplakia, traumatic and abrasive lesions in patients referred to a Saudi dental school.[14] Cebeci et al. examined the prevalence and distribution of oral mucosal lesions in the Turkish adult community. These lesions include anatomical variations, traumatic lesions, white lesions and benign and malignant lesions. They introduced the anatomical variations as the most common lesions.[15] Bernabé et al. reported the presence of white palatal papules as oral manifestations of Darier's disease. In this patient, skin lesions of papules were present in the neck and chest and forearm. This was unlike the studied lesions in our research, which did not include systemic disease.[16] Ali et al. reported the number and type of oral lesions in patients undergoing dental treatment at Kuwaiti University. They divided the oral soft tissue lesions into six groups: white, red, pigmented, ulcerated, miscellaneous and exophytic. White lesions, pigmentation and exophytic lesions were the most common lesions in oral mucosa.[1] In their study, smokers were more likely to have oral lesions. This is an acceptable issue because cigarette is a risk factor of many white and pigmented lesions.
In the present study, women who breastfeed their children or used contraceptives were involved with gingival papules with less frequency. However, the frequency of these individuals is much lower, and since the present study was descriptive cross-sectional, no causal relationship has been investigated, and more studies are needed to determine the effects of contraceptive pills and breastfeeding on gingival papules. It is suggested that more research is done in other dental schools to make the results universally acceptable.
CONCLUSION
There were no significant differences in the incidence of gingival papules by gender, smoking, mouth breathing, skin diseases and pregnancy, but breastfeeding women or contraceptive pills consumers are less likely to develop gingival papules. Gingival papules in the patients referred to Urmia Dentistry School were mostly white and well defined and in the anterior keratinized gingival part of the maxilla were formed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
We wish to express our deep appreciation to our colleagues and technical assistants.
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