Frequency of Odontogenic Tumors: A Single Center Study of 1089 Cases in Japan and Literature Review

Abstract

Several attempts have been made to classify odontogenic tumors; however, the need for a uniform international classification system led the World Health Organization (WHO) to present a classification of odontogenic tumors in 1971. We aimed to evaluate the number and types of odontogenic tumors examined at the Tokyo Dental College Hospital in Japan to determine the frequency and types of odontogenic tumors, based on the 2017 WHO classification system, as this information has not been reported previously in Japan. We also compared the results of our evaluation with those reported in previous studies. We conducted a clinicopathological evaluation of odontogenic tumors examined at the Tokyo Dental College Hospital between 1975 and 2020. This included an analysis of 1089 cases (malignant, n = 10, 0.9%; benign, n = 1079, 99.1%) based on the 2017 World Health Organization Classification of Head and Neck Tumors. We identified 483 (44.3%), 487 (44.7%), and 109 (10.0%) benign epithelial odontogenic, mixed odontogenic, and mesenchymal tumors, respectively. The most common tumor types were odontoma (42.5%) and ameloblastoma (41.9%). Of the 1089 cases, 585 (53.7%) and 504 (46.3%) were male and female patients, respectively. Ameloblastoma and ameloblastic fibroma occurred more commonly in male patients, whereas odontogenic fibroma and cemento-ossifying fibroma affected female patients primarily. The age at diagnosis ranged from three to 87 (mean, 29.05) years. In 319 (29.3%) patients, the age at diagnosis ranged from 10 to 19 years. Ameloblastoma and odontoma were the most common tumor types among patients in their 20s and those aged 10–19 years, respectively. In 737 (67.7%) and 726 (66.7%) patients, the tumors were located in the mandible and posterior region, respectively. Ameloblastoma was particularly prevalent in the posterior mandible. Odontogenic tumors are rare lesions and appear to show a definite geographic variation.

Introduction

Odontogenic tumors originate in the tissues involved in tooth formation and most often develop in the jaw. While odontogenic tumors can be either benign or malignant, most of the reported tumors are benign [1, 2]. Histologically, these tumors can be divided into epithelial, mesenchymal, and mixed tumors. Regarding the frequency of odontogenic tumor occurrence, a multicenter study reported that ameloblastoma and odontoma were the most frequently occurring tumor types [3]. Several attempts have been made to classify odontogenic tumors; however, the need for a uniform international classification system led the World Health Organization (WHO) to present a classification of odontogenic tumors in 1971 [4]. This classification system formed part of the WHO International Histological Classification of Tumors series, which was then revised in 1992 [5] and 2005 [6]. Due to rapid advances in molecular pathology, this classification system was further revised in 2017 to include the consideration of genetic and immunohistological findings [7]. Currently, this system is widely used for odontogenic tumor classification. Although the incidence of odontogenic tumors has been reported to range from 1 to 9%, studies that were conducted in Asia [8–23], Europe [24–32], North America [33–36], South America [37–42], and Africa [43–53] have indicated regional differences in the occurrence of odontogenic tumors in different populations, which may have been the result of genetic and cultural differences among people from different geographical regions.

This study aimed to evaluate the number and types of odontogenic tumors examined at the Tokyo Dental College Hospital in Japan to determine the frequency and types of odontogenic tumors, based on the 2017 WHO classification system, as this information has not been reported previously in Japan. We also compared the results of our evaluation with those reported in previous studies.

Materials and Methods

According to the clinical record data that included the patients' age, sex, and anatomical location of the tumor, 1089 odontogenic tumors were examined at the Tokyo Dental College Hospital between 1975 and 2020. We divided the jaw into anterior and posterior regions to analyze the tumor-site distribution. The tumor site was determined according to the clinical data and by referring to the associated radiology, where available. All the cases were reviewed, and, if necessary, with respect to their histopathological classification, the tumors were reclassified according to the 2017 WHO classification system for benign and malignant odontogenic tumors. The independent opinions of two experienced oral pathologists were compared to reach the final diagnosis. In cases of doubt, we consulted a third expert oral pathologist to obtain a diagnosis by consensus.

Results

Frequency of Tumor Types

Among the 59,137 patients who underwent oral biopsies at Tokyo Dental College Hospital between 1975 and 2020, 1089 (1.8%) patients had been diagnosed as having odontogenic tumors. Of these patients, 99.1% of patients (n = 1079) had benign odontogenic tumors, whereas 0.9% of the patients (n = 10) had malignant odontogenic tumors (Table 1). Benign mixed odontogenic tumors were the most frequently identified tumors (n = 487), comprising 44.7% of the total number of tumors identified. Epithelial odontogenic tumors were identified in 483 patients, comprising 44.3% of all tumors identified. Mesenchymal odontogenic tumors were identified in 109 (10.0%) patients. Table 1 shows the frequency and percentage of each tumor type. The two most commonly occurring tumor types were odontoma (n = 463, 42.5%) and ameloblastoma (n = 456, 41.9%).

Table 1.

Frequency of odontogenic tumors

Type of tumor	Number	Percentage
Benign odontogenic tumors; 1079 cases (99.1%)
Epithelial origin; 483 cases (44.3%)
Ameloblastoma	456	41.9
Squamous odontogenic tumor	2	0.2
Calcifying epithelial odontogenic tumor	8	0.7
Adenomatoid odontogenic tumor	17	1.6
Mixed (epithelial-mesenchyme) origin; 487 cases (44.7%)
Ameloblastic fibroma	17	1.6
Primordial odontogenic tumor	0	0.0
Odontoma	463	42.5
Dentinogenic ghost cell tumor	7	0.6
Mesenchymal origin; 109 cases (10%)
Odontogenic fibroma	22	2.0
Odontogenic myxoma/myxofibroma	41	3.8
Cementoblastoma	8	0.7
Cemento-ossifying fibroma	38	3.5
Malignant odontogenic tumors; 10 cases (0.9%)
Ameloblastic carcinoma	1	0.1
Primary intraosseous carcinoma	8	0.7
Sclerosing odontogenic carcinoma	0	0.0
Clear cell odontogenic carcinoma	0	0.0
Ghost cell odontogenic carcinoma	0	0.0
Odontogenic carcinosarcoma	0	0.0
Odontogenic sarcomas	1	0.1
Total	1089	100.0

Frequency According to Sex

Table 2 shows the number of tumors according to sex (males, 53.7%). Ameloblastoma and ameloblastic fibroma occurred more frequently in male patients, whereas odontogenic fibroma and cemento-ossifying fibroma occurred more frequently in female patients.

Table 2.

Frequency of odontogenic tumors according to sex

Type of tumor	Male	Female	M:F ratio
Benign odontogenic tumors
Epithelial origin
Ameloblastoma	270	186	1.5:1
Squamous odontogenic tumor	1	1	1:1
Calcifying epithelial odontogenic tumor	3	5	1:1.7
Adenomatoid odontogenic tumor	8	9	1:1.3
Mixed (epithelial-mesenchyme) origin
Ameloblastic fibroma	13	4	3.3:1
Primordial odontogenic tumor	0	0	–
Odontoma	242	221	1.1:1
Dentinogenic ghost cell tumor	5	2	2.5:1
Mesenchymal origin
Odontogenic fibroma	6	16	1:2.7
Odontogenic myxoma/myxofibroma	20	21	1:1.1
Cementoblastoma	4	4	1:1
Cemento-ossifying fibroma	8	30	1:3.8
Malignant odontogenic tumors
Ameloblastic carcinoma	0	1	–
Primary intraosseous carcinoma	5	3	1.6:1
Sclerosing odontogenic carcinoma	0	0	–
Clear cell odontogenic carcinoma	0	0	–
Ghost cell odontogenic carcinoma	0	0	–
Odontogenic carcinosarcoma	0	0	–
Odontogenic sarcomas	0	1	–
Total	585	504	1.2:1
Percentage	53.7	46.3

M male; F female

Frequency According to Age

The mean patient age at the time of the odontogenic tumor diagnosis was 29.05 years (standard deviation [SD], ± 18.65; age range, 3–87 years). In terms of frequency according to age, the age at diagnosis ranged from 10 to 19 years in 319 (29.3%) patients. In 121 (11.1%), 210 (19.3%), 136 (12.5%), and 118 (10.8%) patients, the age at diagnosis ranged from 0 to 9 years, 20 to 29 years, 30 to 39 years, and 40 to 49 years, respectively (Table 3). A high incidence was observed among young patients, with 650 patients aged ≤ 29 years, comprising 59.7% of all patients. Ameloblastoma was the most common tumor type at diagnosis among patients in their 20 s. Odontoma was the most commonly occurring tumor at diagnosis in patients aged 10–19 years. Most of the patients with ameloblastic fibroma at diagnosis were aged 0–9 years (11/17).

Table 3.

Frequency of odontogenic tumors according to age

Type of tumor	Age group (years)									Total
	0–9	10–19	20–29	30–39	40–49	50–59	60–69	70–79	80–89
Benign odontogenic tumors
Epithelial origin
Ameloblastoma	8	71	106	76	77	54	41	19	4	456
Squamous odontogenic tumor	0	0	0	0	1	0	1	0	0	2
Calcifying epithelial odontogenic tumor	0	3	2	3	0	0	0	0	0	8
Adenomatoid odontogenic tumor	1	5	6	2	2	0	0	0	1	17
Mixed (epithelial-mesenchyme) origin
Ameloblastic fibroma	11	5	0	0	1	0	0	0	0	17
Primordial odontogenic tumor	0	0	0	0	0	0	0	0	0	0
Odontoma	94	215	70	33	19	15	11	6	0	463
Dentinogenic ghost cell tumor	0	3	1	0	0	0	3	0	0	7
Mesenchymal origin
Odontogenic fibroma	5	5	4	4	2	0	2	0	0	22
Odontogenic myxoma/myxofibroma	2	5	10	6	6	8	3	1	0	41
Cementoblastoma	0	4	4	0	0	0	0	0	0	8
Cemento-ossifying fibroma	0	2	7	12	8	6	2	1	0	38
Malignant odontogenic tumors
Ameloblastic carcinoma	0	0	0	0	1	0	0	0	0	1
Primary intraosseous carcinoma	0	0	0	0	1	6	1	0	0	8
Sclerosing odontogenic carcinoma	0	0	0	0	0	0	0	0	0	0
Clear cell odontogenic carcinoma	0	0	0	0	0	0	0	0	0	0
Ghost cell odontogenic carcinoma	0	0	0	0	0	0	0	0	0	0
Odontogenic carcinosarcoma	0	0	0	0	0	0	0	0	0	0
Odontogenic sarcomas	0	1	0	0	0	0	0	0	0	1
Total	121	319	210	136	118	89	64	27	5	1089
Percentage	11.1	29.3	19.3	12.5	10.8	8.2	5.9	2.5	0.5	100.0

Frequency in the Regions of the Jaw

In terms of the tumor site in the jaw, 355 (32.6%) tumors occurred in the anterior region and 726 (66.7%) tumors occurred in the posterior region (Table 4). Among the tumors located in the upper or lower jaw, 344 (31.6%) were maxillary tumors and 737 (67.7%) were mandibular tumors. Generally, the posterior mandibular region was the most affected, followed by the anterior maxillary and mandibular regions. Ameloblastoma showed a particular prevalence in the posterior mandibular region.

Table 4.

Frequency of odontogenic tumors according to the jaw region

Type of tumor	Maxilla		Mandible		Others	Total
	Anterior	Posterior	Anterior	Posterior
Benign odontogenic tumors
Epithelial origin
Ameloblastoma	14	30	35	369	8	456
Squamous odontogenic tumor	0	0	0	2	0	2
Calcifying epithelial odontogenic tumor	1	3	0	4	0	8
Adenomatoid odontogenic tumor	4	0	4	9	0	17
Mixed (epithelial-mesenchyme) origin
Ameloblastic fibroma	3	2	3	9	0	17
Primordial odontogenic tumor	0	0	0	0	0	0
Odontoma	172	70	99	122	0	463
Dentinogenic ghost cell tumor	5	1	1	0	0	7
Mesenchymal origin
Odontogenic fibroma	3	9	1	9	0	22
Odontogenic myxoma/myxofibroma	4	12	2	23	0	41
Cementoblastoma	1	2	1	4	0	8
Cemento-ossifying fibroma	0	6	2	30	0	38
Malignant odontogenic tumors
Ameloblastic carcinoma	0	0	0	1	0	1
Primary intraosseous carcinoma	0	2	0	6	0	8
Sclerosing odontogenic carcinoma	0	0	0	0	0	0
Clear cell odontogenic carcinoma	0	0	0	0	0	0
Ghost cell odontogenic carcinoma	0	0	0	0	0	0
Odontogenic carcinosarcoma	0	0	0	0	0	0
Odontogenic sarcomas	0	0	0	1	0	1
Total	207	137	148	589	8	1089
Percentage	19.0	12.6	13.6	54.1	0.7	100.0

Discussion

There have been several previous attempts to classify odontogenic tumors [4–7]. The WHO’s classification system for these tumors underwent a third revision in 2017 [7], and this system is now used widely internationally. In the 2017 WHO classification, clinical dynamics have been emphasized, and malignant tumors have been listed first, followed by benign tumors. Malignant tumors are classified into odontogenic carcinomas, odontogenic carcinosarcoma, and odontogenic sarcomas. Benign tumors are classified into epithelial odontogenic tumors, mixed epithelial and mesenchymal odontogenic tumors, and mesenchymal odontogenic tumors. Additionally, the classification of cysts was revised in 2017, with both keratocystic odontogenic tumor and calcifying cystic odontogenic tumor, which were classified as tumors in 2005, being reclassified as odontogenic keratocyst and calcifying odontogenic cyst, respectively. In this study, we classified all odontogenic tumors according to the 2017 WHO classification system and conducted a statistical analysis of the clinical data.

Frequency of Tumors

Odontogenic tumors represent a relatively small proportion of oral and maxillofacial lesions. In this study, we found that odontogenic tumors comprised only 1.8% of the cases in which oral biopsies had been performed. The reported incidence and prevalence rates of odontogenic tumors varied among countries. In studies conducted in South America, North America, and Europe, 2–5% of all the oral lesions were found to be odontogenic tumors [29, 33, 38]. However, a higher proportion was reported in studies conducted in Africa and Asia, with as much as 8.9% of all the oral tumors being odontogenic tumors [13, 18, 21, 44]. Along with the region in which a study was conducted, the classification system used to classify and diagnose odontogenic tumors may have affected the reported incidence and prevalence profiles of these tumors.

In our study that included 1089 odontogenic tumors, we found that benign tumors were overwhelmingly common (benign, 99.1%; malignant, 0.9%). Among the benign tumors, odontoma and ameloblastoma were the most common tumor types, comprising 84.4% of all tumors. There was a low incidence of other types of benign tumors, with odontogenic myxoma, cemento-ossifying fibroma, and odontogenic fibroma comprising 2.5–3.8% of all tumors, and adenomatoid odontogenic tumor and ameloblastic fibroma comprising 1.6% of all tumors. Cases involving these tumors have been reported previously; however, the reported incidences were relatively low [11, 21, 24]. A comparison of the prevalence of the tumors that were of the odontoma and ameloblastoma types revealed a marked difference between different countries. In China [18, 21, 23] and Nigeria [43], the proportion of odontogenic tumors that were reported to be ameloblastoma was found to be overwhelmingly high, whereas in Greece [29], Canada [36], and the United States [34], the proportion of odontogenic tumors that were identified as odontoma was found to be high. In contrast, the prevalence of ameloblastoma and odontoma was found to be almost equally common in Japan [20] and Turkey [24]. These differences may not only have been due to ethnicity, but also variations in the survey methods and sample sizes. Additionally, odontoma is associated mainly with few clinical symptoms and is often observed incidentally during clinical and radiographic examinations. Odontoma excision often involves a minor surgical procedure, and the resected tissue may not always be sent for histopathological examination; therefore, the incidence of odontoma may be underestimated in certain circumstances.

Malignant odontogenic tumors are very rare, and only 10 (0.9%) patients with these tumors were identified in this study. The ratio of benign to malignant tumors in our study was similar to that reported in previous studies [13, 38, 44]. However, in some studies, the proportion of malignant odontogenic tumors was reported to be > 5% [18, 28]. Primary intraosseous carcinoma was the most common malignant tumor type observed in our study (0.7%), in agreement with the proportions reported in studies conducted in the United Kingdom [25], China [18], Egypt [45], and Sri Lanka [13].

Frequency According to Sex

In this study, the overall male-to-female ratio among patients with odontogenic tumors was approximately 1.2:1. Equal proportions of male and female patients with odontogenic tumors have been observed in some studies [11, 20, 29] while in other studies that compared the prevalence of such tumors between male and female patients, the prevalence in male patients was higher [26, 29]. However, some studies reported a higher prevalence of odontogenic tumors among female patients [37, 39]. In our study, the male-to-female ratio among patients with ameloblastoma was 1.5:1, with a male predominance. This finding with regard to the predominance of male patients with ameloblastoma was consistent with the findings of previous studies [3, 21, 25, 26, 43]; however, studies conducted in Turkey [24] and Brazil [37] have reported a slight predominance of female patients. In our study, the male-to-female ratio among patients with ameloblastic fibroma was 3.3:1, showing a male predominance. The occurrence of ameloblastic fibroma in male patients was found to be more frequent than the occurrence in female patients. While this was consistent with the findings of some previous studies [21, 24, 25], other studies have reported the occurrence of ameloblastic fibroma more commonly among female patients [3, 37]. In patients with odontogenic fibroma, we found a male-to-female ratio of 1:2.7, showing a female predominance, which was also consistent with the findings of previous studies [43, 44]. However, equal prevalence rates [3] or a male predominance have also been reported [24, 25]. We observed a male-to-female ratio of 1:3.8 among patients with cemento-ossifying fibroma, showing a female predominance. This finding was consistent with that of previous studies [24, 52].

Frequency According to Age

The mean patient age at diagnosis was 29.05 years (SD, ± 18.65 years), which was similar to the mean age reported in other studies (range, 22.0–49.7 years) [3, 21, 24, 26, 37, 43]. Odontogenic tumors have been shown to affect young patients more commonly than older patients, and many studies have reported that the average age at first diagnosis in both male and female patients ranged from 20 to 29 years of age [11, 21, 38, 43]. In our study, the age at diagnosis in 29.3% of patients was 10–19 years of age and that in 19.3% of patients was 20–29 years, with 59.8% of all cases involved patients aged ≤ 29 years at the time of diagnosis. These findings were consistent with those of a previous study conducted in Japan [20]. The preferential occurrence of such tumors in young patients may have been due to odontogenic tumors arising from tissues involved in tooth formation and the development of such tumors coinciding with the period of tooth formation. However, since these tumors are asymptomatic in the absence of infection and are characterized by slow growth, some cases involving older patients were also observed in this study.

In our study, ameloblastoma was the most commonly occurring tumor type among patients aged 20–29 years and 30–39 years. Furthermore, the number of patients with adenomatoid odontogenic tumor aged 10–19 years and 20–29 years at the time of diagnosis (5/17 and 6/17, respectively) were found to be greater than those with adenomatoid odontogenic tumor in the other age groups. It was also found that, compared with other patient age groups, patients aged 0–9 years and 10–19 years had more commonly developed ameloblastic fibroma and odontoma, respectively. Compared with the number of patients with ameloblastic fibroma aged < 10 years at the time of diagnosis that was observed in previous studies [21, 38, 43], we observed a greater number of patients in this study (11/17), indicating that ameloblastic fibroma occurred more commonly in children aged < 10 years than in older patients. In Japan, ameloblastic fibroma is known to occur relatively commonly among children aged < 10 years [11]. In our study, we found that odontogenic myxoma occurred in patients in their 20 s and 50 s more commonly than in other age groups, and that cemento-ossifying fibroma occurred in patients in their 30 s more commonly than in other age groups. Furthermore, we found that primary intraosseous carcinoma occurred more commonly among patients in their 50 s. Generally, these results were consistent with those of previous studies [11, 21].

Frequency in Regions of the Jaw

Overall, the occurrence of tumors in the mandible was more frequent (ratio, 2.14:1) than those occurring in the maxilla, which was similar to previously reported ratios [8, 11, 18, 20, 21, 24, 25, 33, 37, 38, 43]. In studies conducted in Africa [15, 44, 45], the observed mandible-to-maxilla ratios were higher than those observed in studies conducted elsewhere. In our study, the posterior mandibular region was found to be the most common site of tumor occurrence, with 54.1% of tumors occurring in this region (Fig. 1A). The anterior maxillary and anterior mandibular regions were the sites of tumor occurrence in 19% and 13.6% of cases, respectively. These results were similar to those reported by Ismail et al. [9] and Shibahara et al. [20] Nalabolu et al. [12] and Soluk-Tekkesin et al. [24] who reported that the third most common site of tumor occurrence was the anterior maxillary region. The jaw-specific genetic mechanisms that control the evolution and development of maxillary and mandibular dentition differ, which may explain partially the difference in the incidence of odontogenic tumors in the mandible and maxilla [53].

Fig. 1.

Topographical distribution. A all odontogenic tumors, B ameloblastoma, C ameloblastic fibroma, D adenomatoid odontogenic tumor, E odontoma, F odontogenic myxoma, G cemento-ossifying fibroma. The figures represent numbers and percentages

Certain findings in our study regarding the sites of tumor occurrence showed a significant difference from those of previous studies. Similar to previous study findings [8, 11, 21, 25, 33, 37, 38], we found that ameloblastoma occurred predominantly in the mandibular region and rarely in the maxillary region, with the posterior mandibular region being the most common site of tumor occurrences in the mandible (Fig. 1B). Additionally, we observed that ameloblastic fibroma occurred predominantly in the posterior mandibular region (Fig. 1C). Some studies have reported that > 50% of adenomatoid odontogenic tumor occurred in the maxillary region [24, 37, 44]; however, our findings indicated that they occurred more frequently in the mandibular region, and > 50% of tumors occurred in the posterior mandibular region (Fig. 1D). It has also been previously reported that no difference was found between the upper and lower jaws with respect to the frequency of occurrence of adenomatoid odontogenic tumor [21, 38]; however, one study reported that these tumors occurred relatively more commonly in the mandibular region [3]. We found that odontoma occurred predominantly in the anterior maxillary and posterior mandibular regions (Fig. 1E). In previous studies, odontoma has been reported to occur relatively more frequently in the anterior maxillary region with complex odontoma occurring more frequently in the posterior mandibular region [21, 24]. In our study, benign mesenchymal odontogenic tumors occurred relatively more commonly in the posterior region. We also found that odontogenic myxoma and cemento-ossifying fibroma occurred commonly in the posterior mandibular region (Fig. 1F, G), which was consistent with previous reports [21, 24, 52].

Conclusion

In this study, we presented epidemiological data with respect to the occurrence of odontogenic tumors in a Japanese population. Geographic variations in the incidence of odontogenic tumors were found, and the prevalence of mixed odontogenic tumors in this Japanese population was higher than the occurrence in other populations. Our findings indicated a slight male predominance, with a significant proportion of odontogenic tumors occurring in the mandibular region. Odontoma and ameloblastoma were the most commonly occurring odontogenic tumors in this population, with malignant tumors originating from odontogenic tissues being observed rarely. Our study was the first retrospective analysis to determine the epidemiology of odontogenic tumors within a Japanese population based on the 2017 WHO classification system, which aids our understanding of such lesions, significantly.

Author Contributions

KK conceived the research project, collected and analyzed data, and contributed to the drafting of the manuscript. KM contributed to the drafting of the manuscript. KY, KN, YA, TC, MT, and AK collected and analyzed data and reviewed the manuscript. All the authors approved the final version of the manuscript.

Funding

Not applicable.

Data Availability

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Code Availability

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Declarations

Conflict of interest

All authors declare that they have no conflicts of interest.

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