The results of this study are noteworthy for several reasons. The patients in the DC group were older than usually reported (see below) – most were diagnosed in the age range of 40 to 69. Some studies reported a peak in the second to the fourth decade [33–35]. Other studies reported the peak in the 5th and 6th decades [36–38], but in the 7th decade, a decrease was expected based on those results. In our population, however, the opposite results were found – in the 7th decade, the incidence did not decrease; it was even, albeit negligibly, higher than in the previous ones.
Further observations like the male-to-female ratio and the relation to the particular impacted teeth were in line with previous studies [1]. In our study sample, however, the proportion of patients with multiple DCs (6.6%) was higher than what is usually reported in the literature (Table 1). The only two studies reporting higher numbers of patients with multiple DCs are those by Noujem and Nasr (2021) [35] and Fickling (1968) [39], with an exceptionaly high rate of 22.9% and 20.9% respectively. Where the proportion of the total number of multiple cysts is concerned, it was 13.3% in our cohort. Again, two studies reported a higher proportion of multiple cysts [35, 40]. However, it has to be emphasized that the number of patients with multiple cysts is probably a better indicator of their prevalence as the number of DOCs can vary among patients (some may have two, some three and some even more DCs).
Table 1
Prevalence of multiple dentigerous cysts (DCs) in different countries
Region | Total number of | Reference |
patients with a DC | patients with multiple DCs | DCs | multiple DCs |
UK | N/A | 7 | 67 | 14 (20.9%) | Fickling 1965 [39] |
Chile | N/A | N/A | 546 | 61 (11.0%) | Ochsenius et al. 2007 [33] |
British Columbia, Canada | 2029 | 51 (2.5%) | 2082 | N/A | Zhang et al. 2010 [34] |
Taiwan | 332 | 6 (1.8%) | 338 | 12 (3.6%) | Lin et al. 2013 [54] |
Turkey | N/A | 3 | 114 | N/A | Karabas et al. 2020 [38] |
Lebanon | 109 | 25 (22.9%) | 137 | 53 (38.7%) | Noujeim and Nasr 2021 [35] |
Massachusetts, USA | 198 | N/A | 218 | 37 (17.0%) | Caruso et al. 2022 [40] |
Czech Republic | 286 | 19 (6.6%) | 308 | 41 (13.3%) | Current study |
N/A – non-applicable/specified, or unknown |
It should be noted that the practice and timing of extracting the impacted wisdom teeth will certainly affect the prevalence of DCs, including multiple ones. In countries where people are more encouraged to get their impacted teeth extracted at a younger age, the prevalence of both solitary and multiple DCs will be lower [34]. This might cause the false impression that multiple DCs are not very common in such countries.
Bilateral or multiple DCs are usually reported to occur predominantly in patients with syndromes associated with impacted teeth or supernumerary teeth [1, 3–5, 14]. While this seems to be true for MPS [7–10], we have not found any literature on the prevalence of multiple DCs in the other syndromes associated with these cysts, such as cleidocranial dysplasia, or Gardner syndrome. A radiographic study of 40 patients with cleidocranial dysplasia did not describe this feature on panoramic X-rays [41].
Where MPS patients are concerned, given the very low incidence of MPS [42], it seems plausible that non-syndromic multiple DCs are much more prevalent in the population than the syndromic ones. In other words, there is a higher chance of the occurrence of multiple DCs in MPS patients, but considering the low numbers of MPS patients in the general population, non-syndromic DCs probably constitute a majority of multiple DCs in the population. This is also supported by the numerous case reports of multiple non-syndromic DCs available in the literature (Supplement 1). Most cases of multiple DCs were symetrically bilaterally located in the mandible (Fig. 2). It should be, however, emphasized that multiple DCs have to be carefully distinguished from multiple hyperplastic calcifying dental follicles [43]. The cause of the occurrence of multiple and bilateral DCs in otherwise healthy patients is unknown. In one patient with bilateral DCs, a polymorphism of the 1qh + chromosome was described [44]. However, no other case report or study investigated this polymorphism so we are unable to draw any conclusions on whether this might be the reason for multiple non-syndromic DC occurrence.
Besides the well-known mutation in the Patched (PTCH) gene, molecular pathways associated with primary cilia might also play a role in DC development [45]. Moreover, age-related events in dental follicles are poorly explored and crucial molecular changes leading to cystic transformation may have a higher probability of occurring in older patients with impacted teeth [46].
Regarding the OKC group, the demographic data are consistent with the results of previous studies – the majority of patients were male and most of the patients were in the second, third and fourth decades of their lives [1]. The location of occurrence (mostly the lower jaw in the distal area) was also in line with previous studies. Papers on multiple OKCs report their occurrence to vary from 4.3–15.2% of all patients with OKCs; the result detected in our study, 10.5% (Table 2), is consistent with these findings. However, the proportion of OKC patients with NBCCS was relatively higher (7%) than usually reported. Only three studies reported higher rates of NBCCS patients (Table 2).
Table 2
Prevalence of multiple odontogenic keratocysts (OKCs) in different countries
Region | Total number of patients with | Reference |
an OKC | multiple OKCs | non-NBCCS multiple OKCs | NBCCS multiple OKCs |
Georgia, USA | 87 | 6 (6.9%) | 5 (5.7%) | 1 (1.1%) | Payne 1972 [55] |
Indiana, USA | 283 | 20 (7.0%) | 10 (3.5%) | 10 (3.5%) | Brannon 1976 [56] |
Mexico | 57 | 3 (5.3%) | 1 (1.8%) | 2 (3.5%) | Ledesma-Montes et al. 2000 [57] |
Singapore | 70 | 3 (4.3%) | 2 (2.8%), both male | 1 (1.4%), male | Chow 1998 [58] |
South Korea | 256 | 39 (15.2%) | 11 (4.3%) | 28 (11.0%) | Myoung et al. 2001 [59] |
Iran | 74 | 6 (8.1%) | 0 | 6 (8.1%) | Habibi et al. 2007 [60] |
South Korea | 181 | 7 (3.9%) | 3 (1.7%) | 4 (2.2%) | Yang et al. 2011 [61] |
India | 186 | 20 (10.8%) | 14 (7.5%) | 6 (3.2%) | Singh et al. 2013 [62] |
Saudi Arabia | 75 | 10 (13.3%) | 7 (9.3%) | 3 (4.0%) | Bello 2016 [63] |
China | 455 | 50 (11.0%) | 31 (6.8%) | 19 (4.2%) | Fidele et al. 2019 [64] |
Italy | 113 | 23 (19.2%) | 0 | 23 (19.2%) | Favia et al. 2022 [65] |
Turkey | 43 | 3 (6.9%) | 1 (2.3%) | 2 (4.7%) | Yilmaz et al. 2022 [66] |
India | 32 | 2 (6.3%) | 1 (3.1%) | 1 (3.1%) | Ac et al. 2023 [67] |
Czech Republic | 85 | 9 (10.5%) | 3 (3.5%) | 6 (7.0%) | Current study |
NBCCS – Naevoid Basal Cell Carcinoma Syndrome |
Only 3.5% of non-syndromic OKC patients in our cohort developed multiple OKCs. This is about half of that reported by González-Alva (2008), who identified multiple lesions in 24 cases (13.1%) in their group of 183 patients with OKCs [47]. Of those 24 patients, 11 (6%) were associated with NBCCS and the remaining 13 (7.1%) were non-syndromic.
NBCCS is caused by a mutation in the PTCH gene, but non-syndromic multiple OKCs are regarded as an incomplete variant of NBCCS [48]. Hence, just as NBCCS, non-syndromic OKCs might also have a familial occurrence [2, 49–51]. Also, many cases of non-syndromic OKCs have been reported in the literature (Supplement 2). Still, a multitude of retrospective studies suggest that NBCCS-associated multiple OKCs are more prevalent than non-syndromic ones (Table 2).
In our study, only 4 cases of OOCs were retrieved, all in the mandible and without recurrence after enucleation. One of the patients had bilateral synchronous cysts in the posterior area of the mandible. This seemingly high absolute proportion (25%) is, however, probably just a chance finding caused by the very low number of OOCs in our cohort as multiple OOCs generally to occur very rarely. Oh et al. (2022) summarized ten reported multiple OOCs in a literature review [25]; later the same year, Ono et al. (2022) published a study on more cases [26], making up a total of only thirteen cases so far. Most of them had two OOCs, two patients had three OOCs and in one case described by Cheng et al. (2014), the patient had four OOCs [52]. None of the patients were known to have a syndrome or systemic condition. The genetic background of OOCs is still unclear - while Wang et al. (2022) suggested that OOCs don’t harbor the PTCH mutation and, therefore, arise due to different reasons than OKCs [53], Ono et al. (2022) reported PTCH mutations in all three studied patients with multiple OOCs [26].