Oral Reactive Hyperplastic Lesions: Prevalence in Egypt and Proposal of Novel Classification System

doi:10.21203/rs.3.rs-4302133/v1

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Oral Reactive Hyperplastic Lesions: Prevalence in Egypt and Proposal of Novel Classification System

https://doi.org/10.21203/rs.3.rs-4302133/v1

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Background

this study aimed to estimate the prevalence of oral reactive hyperplastic lesions (ORHLs) as well as their distribution in the oral cavity in the Egyptian population over the past 13 years. We also introduced a novel classification system for ORHLs that may help in standardized categorization and better understanding of the nature of these common oral lesions.

Methods

All the records of histopathologically diagnosed ORHLs over the past 13 years (2011 to 2023) were retrieved from the archives of Oral & Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University. The extracted quantitative data was presented as frequencies and percentages of ORHLs. The proposed classification system has used 2 letters and 1 digit to describe ORHLs considering both the clinical appearance of the lesions as well as their characteristic histopathological patterns.

Results

ORHLs represented 33% of the total number of diagnosed cases in the tested period (2256/6858 cases). Among the examined types of ORHLs, irritational fibroma was the most encountered type (40%) followed by pyogenic granuloma (25%). Regarding anatomic location, gingiva was the most common site for ORHLs, where more than half of the cases (52%) were reported in it.

Conclusion

The present study clearly demonstrated the high prevalence of ORHLs as one of the most frequently encountered categories of oral pathology. This highlights the importance of the proposed standardized categorization and consistent description of these common oral lesions based on their clinical appearances and characteristic histopathological findings. This classification enhances the overall knowledge and understanding of ORHLs nature allowing effective communication among healthcare providers as well as accurate diagnosis, treatment planning, and research work.

Oral

Reactive

Hyperplastic

Prevalence

Egypt

Oral Reactive Hyperplastic Lesions (ORHLs) are non-neoplastic hyperplasias that represent an escalated reparative response against low-grade long-standing local irritation (Gandhi et al., 2016). In many cases, these hyperplastic lesions may closely simulate neoplastic proliferations, placing a great challenge during the process of differential diagnosis (Lakkam et al., 2020). Being continuously exposed to a wide variety of stimuli, tissues of the oral cavity represent a common site for ORHLs, where dentists commonly face during routine examinations. Among these low-grade stimuli, dental plaque and calculus, sharp edges of carious or badly broken-down teeth, ill-fitting oral appliances, and faulty dental restorations are commonly reported (Gali, 2021).

Despite being the most frequently encountered category of oral mucosal lesions (Justyna et al., 2018), few epidemiological studies have evaluated the prevalence of reactive lesions worldwide. Assessing the incidence of these common lesions is important for increasing practitioner awareness as well as optimizing health care service allocation. Also, knowledge about the distribution of different ORHLs is essential for prompt diagnosis and early intervention. For the best of our knowledge, epidemiological studies on ORHLs in Egypt are scarce and limited (Aly et al., 2022).

In general, categorization of pathologies based on their common characteristics is of utmost importance in the healthcare field, as it advances medical knowledge and enhances accurate diagnosis, treatment planning, as well as research work. Concerning ORHLs, there is no consistent classification, however various confusing clinical and histopathological classifications have been equivocally described in literature. Another source of confusion in inspection of such lesions is the inconsistent terminology, where different names are applied to the same histological picture (Dutra et al., 2019). Accordingly, the current study was accomplished to fill this gap of knowledge, elucidate the frequency and distribution of ORHLs in Egypt, and to shed light on novel standardized classification system that may help in categorization and better understanding of the nature of these common oral lesions.

In the current study, cases were retrieved from the archives of Oral & Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University, where all the registered specimens belong to patients of Qasr El-Aini Dental Hospital. All the records of histopathologically diagnosed ORHLs over 13 years (2011 to 2023) were included, and all the sites of the lesions were determined from the clinical data. The cases were re-examined and classified according to the novel system for classification of ORHLs, which is proposed in the present study.

This system took into consideration the clinical appearance of the lesions in the oral cavity as well as their characteristic histopathological features. The clinical pictures comprised 4 groups, each of them was designated by a capital letter: (A) mucosal colored swellings, (B) red to purple swellings, (C) verrucous papillary swellings, and (D) ulcerative lesions. On the other hand, the histopathological features were based on the nature of the tissue showing the hyperplastic changes whether involving both epithelium and connective tissue, involving epithelium only or involving connective tissue only, these histopathological groups were designated as 1,2,3, respectively (Table 1).

Moreover, presence or absence of special diagnostic histological findings was also counted in the proposed classification, thus the histopathological groups were subclassified into subgroups (a) or (b), where the small letter “b” denoted presence of further special diagnostic histological findings. In conclusion, each reactive lesion would be described clinically and histopathologically by 2 letters (1 capital & 1 small) and 1 digit as shown in table (1), for example: irritational fibroma is described as “A1a”, where “capital A” denotes the clinical appearance as a mucosal coloured swelling, “1” denotes hyperplasia of epithelium and the connective tissue components and “small a” denotes absence of further diagnostic findings. Another examples pyogenic granuloma and peripheral giant cell granuloma share the same designation “B1b”; the “capital B” denotes the clinical appearance as a red swelling, “1” denotes hyperplasia of epithelium and the connective tissue components and “small b” denotes presence of further diagnostic findings which are numerous dilated blood vessels and multinucleated giant cells, respectively.

The second point of interest in the current study was to determine the prevalence of ORHLs and distribution of such lesions in the oral cavity as well as their most common sites. The quantitative data were presented as frequencies and percentages of ORHLs. Statistical analysis was achieved with IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.

Table (1): Classification of ORHLs according to clinical appearance and histopathological characteristics.

Groups	Subgroups	(A) Mucosal-colored swellings	(B) Red to purple swellings	(C) Verrucous papillary lesions	(D) Ulcerative lesions
(1) Epithelial and connective tissue components hyperplasia	(a) No further findings	• Irritational fibroma • Denture fissuratum	• Epulis granulomatosum	• Palatal papillomatosis	• None
	(b) with diagnostic findings	• Peripheral ossifying fibroma	• Pyogenic granuloma • Pregnancy tumour • Peripheral giant cell granuloma	• None	• Necrotizing sialometaplasia
(2) Epithelial hyperplasia only	(a) No further findings	• None	• None	• Verruca vulgaris • Condyloma acuminatum	• None
(2) Epithelial hyperplasia only	(b) with diagnostic findings	• None	• None	• Heck’s disease • Verruciform xanthoma	• None
(3) Connective tissue component hyperplasia	(a) No further findings	• None	• None	• None	• None
(3) Connective tissue component hyperplasia	(b) with diagnostic findings	• Traumatic neuroma	• None	• None	• Traumatic eosinophilic ulcer

Over the period of 13 years (2011 to 2023), 6858 oral and maxillofacial cases were registered in the archives. Out of them, 2256 cases of ORHLs were identified. The overall percentage of ORHLs was 33%, which accounted for third of the cases, with annual percentages ranging from about 48–22%. All the percentages of ORHLs throughout the experimental period were illustrated in table (2) and figure (1).

Concerning the groups of ORHLs, twelve different types of ORHLs (table 3, Fig. 2) were detected among the examined cases. Irritational fibroma was the most encountered type (40%) followed by pyogenic granuloma (25%), then peripheral giant cell granuloma (16.5%) and peripheral ossifying fibroma (11%). The vast majority of the identified ORHLs were mucosal coloured swellings (53%), followed by red to purple swellings (45%) (Fig. 3). Both clinical presentations (98%) showed hyperplastic changes involving epithelium and fibrovascular connective tissue components which include fibroblasts, collagen fibers, dilated blood vessels and chronic inflammatory cell infiltrate (Fig. 4). In other words, based on the proposed novel classification, most of the ORHLs within the experimental period belonged to 2 main groups A1a (42%) and B1b (43%) followed by the groups A1b (11%) and B1a (2%).

In addition to the basic hyperplastic changes, further special diagnostic histopathological findings were detected in 11% of the mucosal coloured swellings, namely peripheral ossifying fibroma, which is characterized by formation of mineralized product. The nature of this mineralized component is variable as it represents a combination of bone, cementum-like material, or dystrophic calcifications. On the other hand, 43% of the red to purple swellings comprising pyogenic granuloma, pregnancy tumor and peripheral giant cell granuloma showed numerous dilated blood vessels that are engorged with red blood cells. Furthermore, aggregations of multinucleated giant cells have made peripheral giant cell granuloma very distinctive histopathologically (Fig. 4).

Sites of most of the cases (83.6%) were determined from the clinical data, except for 16% of the cases, their sites were not specified. About 9 main sites were reported in the current study, namely: gingiva, tongue, lip/labial mucosa, cheek mucosa, palate, alveolar ridge in edentulous areas, vestibule, extraction socket and floor of mouth. Generally, gingiva was the most common site for ORHLs, where more than half of the cases (52%) were reported in it, followed by the cheek mucosa (15%) and tongue (4%). Contrarily, the least common site was the floor of mouth (0.04%) (table 3).

It is worth noting that some ORHLs showed exclusive localization such as peripheral giant cell granuloma and peripheral ossifying fibroma which were limited to the gingiva or the alveolar ridge, as well as few cases related to healing extraction sockets. Similarly, epulis granulomatosum was specifically seen in extraction sockets, except for 2 cases which were detected on the alveolar ridge after healing of the socket. Moreover, most of the traumatic neuroma cases occurred in relation to the mental foramen (table 3).

Table (2): The annual number of ORHLs cases relative to the total number of diagnosed cases as well as their percentages within the experimental period.

Year	2011	2012	2013	2014	2015	2016	2017	2018	2019	2020	2021	2022	2023	Total
ORHLs	131	160	158	179	187	190	207	206	181	99	136	230	192	2256
All cases	316	333	397	454	568	495	604	562	508	325	614	885	797	6858
Percentage	41%	48%	40%	39.5%	33%	38%	34%	36.6%	35.6%	30.5%	22%	26%	24%	33%

Figure (1)

Line chart representing overall prevalence of ORHLs (2011–2023).

Figure (2)

Pie chart showing the different types of ORHLs (2011–2023).

Table (3): Distribution of the detected ORHLs within the experimental period and their sites.

ORHLs per site	Gingiva	Tongue	Lip/ Labial Mucosa	Cheek mucosa	Palate	Alveolar ridge	vestibule	Floor of mouth	Extraction socket	NS	Total number of cases	Percentage
Irritational fibroma	278	49	42	267	24	16	2	0	0	231	909	40.3%
pyogenic granuloma	382	34	27	66	10	20	4	1	0	22	566	25%
Peripheral giant cell granuloma	260	0	0	0	0	26	0	0	8	78	372	16.5%
Peripheral ossifying fibroma	226	0	0	0	0	6	0	0	1	23	256	11%
Epulis granulomato-sum	0	0	0	0	0	2	0	0	48	0	50	2.2%
Denture (epulis) fissuratum	1	0	7	3	1	3	14	0	0	5	34	1.5%
Pregnancy tumor	24	1	0	1	0	0	0	0	1	4	31	1.4%
Eosinophilic ulcer	1	10	1	3	0	0	0	0	0	3	18	0.8%
Verruca vulgaris	0	2	4	1	2	0	0	0	0	0	9	0.4%
Traumatic neuroma	1	1	0	1	2	3	0	0	1	3	9	0.4%
Heck’s Disease	0	0	1	0	0	0	0	0	0	0	1	0.04%
Condyloma accuminatum	0	1	0	0	0	0	0	0	0	0	1	0.04%
Total	1173	98	82	342	39	76	20	1	59	366	2256
Percentage	52%	4%	3.6%	15%	2%	3.4%	0.9%	0.04%	2.6%	16%
*NS: not specified

Figure (3): Photos of the possible clinical presentations of ORHLs, (A): A case of irritational fibroma showing a mucosal-coloured swelling. (B): A case of pyogenic granuloma showing a red-coloured swelling. (C): A case of verruca vulgaris showing a white verrucous papillary lesion. (D): A case of traumatic eosinophilic ulcer showing a mucosal ulceration.

Figure (4): Photomicrographs showing the possible histopathological presentations of ORHLs, hyperplastic epithelium and connective tissue components with collagen fiber bundles are evident in cases (A-D). No further findings observed in irritational fibroma case (A), however characteristic histological features are observed such as dilated blood vessels in pyogenic granuloma case (B), giant cells in peripheral giant cell granuloma case (C) and bone trabeculae in peripheral ossifying fibroma case (D). Hyperplastic epithelium only is evident in cases: verruca vulgaris (E) and Heck’s disease (F). Case (G) shows hyperplastic neural tissue in traumatic neuroma and case (H) a traumatic eosinophilic ulcer showing connective tissue with intense chronic inflammatory cell infiltration.

The current prevalence or cross-sectional study is designed as a population-based one to estimate the frequency of ORHLs in Egypt over a 13-year-period of time. The present population sample is believed to be an appropriate representative for the Egyptian population, as the specimens were retrieved from the Oral and Maxillofacial Pathology laboratory of Qasr El-Aini Dental Hospital, which is one of the largest and most reputable dental hospitals in Egypt. It is worth noting that this hospital provides health services not only to the residents (over 22 million) of the metropolitan area “Greater Cairo” but also many Egyptians residing in rural regions and smaller cities with over 223,200 patients per year (Gamil et al., 2021).

In agreement with our results, recent epidemiologic studies have revealed that ORHLs represent the diagnostic category with the highest presentation (Baddireddy et al., 2022). Similar results were obtained in pediatric and adolescent patients by Aly et al. (2022) in Egypt, and Melo et al. (2023) in Brazil. In the same context, the current work has revealed that the percentage of ORHLs throughout the experimental period is 33%, this prevalence has exceeded almost all the results of previous studies. Babu and Hallikeri (2017) and Dutra et al., (2019) pointed out that ORHLs have constituted for 20.2% and 22.25%, respectively. On the other hand, Reddy et al. (2012), Kadeh et al. (2015), Vidyanath et al. (2015) and Baddireddy et al. (2022) observed about half this percentage which ranged from 10.7–13.18%.

Concerning irritational fibroma, many terms are used to describe such lesions in literature, including inflammatory fibrous hyperplasia, focal fibrous hyperplasia and traumatic fibroma. Regardless of the variable used terminologies, most of the previous studies have agreed with our finding that irritational fibroma is the most prevalent (40%). However, they reported different percentages 57.4% (Reddy et al., 2012), 69.3% (Vidyanath et al., 2015), 47% (Babu and Hallikeri, 2017), 37.4% (Sangle et al., 2018), 72.09% (Dutra et al., 2019) and 61% (Zhao et al., 2023). On the contrary, few research showed that pyogenic granuloma is the most common ORHL, followed by irritational fibroma (Kashyap et al., 2012 and Kadeh et al., 2015).

In line with our results, Naderi et al. (2012), Reddy et al., (2012), Babu and Hallikeri (2017) and Dutra et al. (2019) have shown that pyogenic granuloma is the second most common ORHL, with a percentage ranging from 18–27%. In the present work, the observed prevalence has lied within the same range (25%). It is worth noting that some authors have suggested presence of considerable overlap among some different histological entities of ORHLs including pyogenic granuloma, where its predominant vascular component may be replaced by fibrous tissue and subsequent calcification, hence, diagnosed as irritational fibroma or peripheral ossifying fibroma, respectively. For many years, it has been a point of debate whether these reactive proliferations are distinct entities or represent stages in the evolution of a single lesion. Some authors have postulated that these pathological entities represent one lesion at various histological developmental stages (Karuma et al., 2021).

Although ORHLS may occur in any oral site, gingiva was the most affected site (52%). Similar results were obtained by Naderi, et al. (2012) and Nair et al. (2019). Kadeh et al. (2015) and Hunasgi et al. (2017) attributed the frequent involvement of gingiva to its accessibility to different sources of irritation. Exclusive localization of peripheral giant cell granuloma and peripheral ossifying fibroma to the gingiva or alveolar mucosa may be attributed to the fact that they originate from the periosteum or periodontal ligament (Shadman et al., 2009 and Wu et al., 2022). This finding is consistent with Ghandi et al. (2016), Patil et al. (2014), Neville et al. (2016) and Fligelstone & Ashworth (2023).

From histopathological point of view, the microscopic findings of such lesions have largely reflected their possible causes. The main cause behind 98% of the detected cases in the experimental period is chronic low-grade trauma induced by various factors such as dental plaque and calculus, sharp edges of carious or badly broken-down teeth, ill-fitting oral appliances, and faulty dental restorations. This could explain why all these cases belonged to group (1) thus showed hyperplasia of both epithelium and connective tissue components.

On the other hand, almost all the ORHLs that belonged to group (2) are induced by human papilloma virus (HPV). Successful HPV infection begins by entry and replication in stratified squamous epithelial cells with their concomitant differentiation leading to some changes including epithelial hyperplasia (Shafti-Keramat et al., 2003 and Rautava & Syrjänen, 2012). In the current work, the HPV induced lesions (verruca vulgaris, Heck’s disease and condyloma acuminatum) constituted less than 1% of the detected cases, which may indicate limited spread of such infection in the Egyptian community.

Moreover, more than 54% of the detected cases showed the designation (b) due to presence of further special histopathological findings. These findings have aided in diagnosis of ORHLs such as mitosoid cells in Heck’s disease. Also, they may be responsible for special clinical picture such as the highly vascular proliferations in pyogenic granuloma and pregnancy tumor, or the abundant hemorrhage and deposits of hemosiderin pigment which make peripheral giant cell granuloma attains darker clinical presentation compared to that of pyogenic granuloma. Moreover, they may reflect the nature of the lesion as the observed proliferation of neural tissue and salivary ductal hyperplasia in traumatic neuroma and necrotizing sialometaplasia, respectively.

One of the obstacles in the current classification was the potential of some ORHLs to attain different clinical appearances such as peripheral ossifying fibroma which may appear as a mucosal coloured or reddish coloured swelling. Another example, necrotizing sialometaplasia which appears as a swelling before it undergoes ulceration. So, we modified the classification to allow flexible change of the designations (A, B, C or D) according to the clinical picture of each case.

For the best of our knowledge, the proposed novel classification system is the first classification of ORHLs that has taken into consideration the importance of both clinical inspection of oral lesions and the gold standard histopathological examination. These two pillars greatly enhance the overall knowledge and understanding of the nature of such lesions, their possible causes and appropriate treatment planning. This classification has depended on using 2 letters and 1 digit to describe ORHLs, this offers standardized categorization and consistent description of such lesions which promotes effective communication among healthcare providers. Furthermore, they allow consistent documentation of ORHLs, which facilitates data collection and analysis for research purposes.

ORHLs

oral reactive hyperplastic lesions

HPV

Human papillomavirus

Ethics approval and consent to participate: "This study was approved by the Research Ethical Committee at Faculty of Dentistry, Cairo University. Informed consent was waived by the ethics committee Research Ethical Committee at Faculty of Dentistry, Cairo University.".

Consent for publication: Not applicable.

Availability of data and materials: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests: There are no conflicts of interest.

Funding: This work was entirely self-funded; no grants were obtained for it.

Authors' contributions: Safa Fathy wrote the manuscript. The data entry and collecting were handled by Heba Khaled and Ahmed Metwally. The project was guided by Safa Fathy and Hatem Amer, who were also responsible for the of data curation and English language editing of the paper. The final manuscript was evaluated and approved by each author.

Acknowledgements: The authors express their sincere appreciation to Oral & Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt.

Authors' information (optional): Not applicable.

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No competing interests reported.

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Oral Reactive Hyperplastic Lesions: Prevalence in Egypt and Proposal of Novel Classification System

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