## 4 Discussion
Pathologic analysis of the DFs included the evaluation of the same histological variables considered by [PERSON] et al. in their series of patients [4]. Overall, our histological data indicate that tissue variations and changes may also occur in the DFs from impacted asymptomatic third molars when they appear normal through CBCT. However, of the considered histological variables, only odontogenic remnants and mild mesenchymal degeneration were appreciable in more than half of the samples. Of note, squamous metaplasia, the presence of which has been considered by some authors but not by others to be indicative of the development of a dentigerous cyst, was observed in 5 out of the 13 DFs (38.46%) [5; 6; 13; 37; 38; 40]. Obviously, the evidence of odontogenic remnants, mesenchymal degeneration and squamous metaplasia has no prospective value per se, but their appropriate evaluation has important clinicopathologic implications for the correct assessment of a DF as normal. This is mandatory to avoid histological misinterpretation and, consequently, histological misdiagnosis that can be related to the lack of familiarity and experience with these tissue specimens [4]. The presence of odontogenic remnants within the connective tissue of DFs is a well-known phenomenon [4]. It is generally thought that odontogenic remnants are inactive and do not have clinical significance. Thus, their evidence is not synonymous of a pathologic DF per se. However, they represent the source of odontogenic lesions including cysts and tumors [38]. In addition, their frequency and number have been reported to decrease with the increase in patient age [45; 49]. In the present series, odontogenic remnants were detected in 69.23% (9/13) of the samples. This value is remarkably like that previously reported by [PERSON] and [PERSON] in their study on 847 DFs [4]. Features of ameloblastic differentiation including tall columnar cells with nuclear polarization and stellate reticulum type tissue, as well as nuclear and cytoplasmic pleomorphism and/or mitotic activity, amyloid deposition and Liesegang-ring-type calcifications have to be searched carefully to avoid misdiagnosis. Indeed, the absence of these features is the mainstay to differentiate normal DFs from diverse odontogenic tumors including ameloblastomas, ameloblastic fibromas and calcifying epithelial odontogenic tumor (Pindborg tumor). In the present study, these features were not detected in any of the DFs in which odontogenic remnants were found. Myxoid changes were detected in 61.53% (8/13) of the samples included in this study. This value is also substantially like that previously reported by [PERSON] and [PERSON] in their study [4]. To be aware of this change is important, because an absence of appropriate radiographic correlation may lead to the misinterpretation of a normal DF with myxoma [4]. Indeed, DFs appear radiographically as well-demarcated, thin, semicircular and usually symmetric radiolucencies around unerupted teeth; are virtually always less than mm 3 mm thick; and are never destructive. In contrast, myxomas appear as larger and typically poorly circumscribed, and are often expansile, destructive radiolucent lesions. When radiographic data are not available, the evidence of an epithelial lining, as in our samples, makes the recognition of DF possible because it always lacks in myxomas. Squamous metaplasia has been considered a histopathologic feature indicative of the development of a dentigerous cyst in some studies [5; 6; 13; 40]. Consequently, it is not a surprise that the diagnosis of dentigerous cyst is the most common misdiagnosis of DFs [4]. Of note, the evidence of squamous metaplasia (and the risk of dentigerous cyst development) is known to increase with age [5; 6]. For example, the frequency of squamous epithelium was reported by [PERSON] et al. to be 16.7% in patients 13 to 21 years old and 73.9% in patients 22 to 69 years old [45].