Stromal cells maintain tissue homeostasis through control over cell size, function, and response. Changes in the stromal microenvironment result in the presence of cellular components capable of modifying the extracellular matrix in pathological conditions [20, 24, 25]. OKC has specific histopathological characteristics, presenting aggressive behavior and a tendency to relapse compared to other types of cysts [26–28]. In a study in the literature by Tsukamoto et al. [23] differences in age, area and peripheral shape of OKC associated and not associated with a lower third molar were evaluated, showing that the mean age of patients in the associated group was lower than that of the non-associated group, while mean area of the cysts in the group associated OKC was higher than in the non-associated group, suggesting that an impacted tooth and its dental follicles may affect the occurrence and proliferation of an OKC. In another study evaluating DC and OKC associated with a lower third molar, the mean age of patients in the OKC group was lower than that of the DC group and the mean area of the OKC group was greater than DC, with no correlations reflected between the ages and areas in the DC and OKC groups. These findings suggest that both cysts do not develop gradually during the period when follicles are formed but appear at various random times during a patient's life [29]. In the present study, the mean age of patients in all groups was evaluated, finding a statistical difference between the iDC and nDC, OKC-A and OKC-N groups (p < 0.05). These findings demonstrate an association with existing studies in the literature.
MFs are differentiated fibroblasts that express α-SMA and have intermediate characteristics between conventional fibroblasts and smooth muscle cells [30] being able to remodel and degrade the extracellular matrix by secreting matrix metalloproteinases, driving the invasive growth of lesions odontogenic cyst [31]. The few studies that investigated the presence of MFs in odontogenic lesions suggest that the increase in the number of these cells contributes to the progression of the lesion and more aggressive biological behavior [13, 17, 21, 24, 25, 32, 33]. Anusai et al. [10] reported that epithelial and stromal cell interactions are fundamental in controlling the growth and clinical behavior of odontogenic cystic lesions and that MFs are seen in greater numbers in OKC than in DC. These immunohistochemical findings are also observed in other studies in the literature [13, 17, 20–22] and corroborate the results of this present study, in which we found statistical differences between the groups of DC (iDC and nDC) and OKC (OKC -A and OKC-N) (p < 0.05), agreeing that growth and aggressive biological behavior is greater in OKC compared to DC.
The first authors to investigate the presence of MFs in odontogenic lesions were Lombardi and Morgan [7]. These authors evaluated the expression of α-SMA and vimentin in odontogenic cystic lesions and in control groups, including PF, in which there was no significant expression of α-SMA. However, the study by Oliveira Ramos et al., [34] found high expression of MFs using the α-SMA in cases of PF, associating it with the probability of bone remodeling that occurs during tooth formation and eruption. De Souza-Neto et al. [6] also evaluated the expression of α-SMA in PF and found the myofibroblast phenotype in all cases used. In the current study, however, no expression of MFs was found in cases of PF, only marking of vascular smooth muscle cells. The lack of myofibroblast differentiation in PF appears to be consistent with the nature and function of this structure.
Gratzinger et al. [19] mention calponin as a primary actin-bound protein of tissues containing smooth muscles and present some studies in which it exhibits characteristics like α-SMA. Furthermore, these authors did not find positive cases of calponin for DC and OKC. In our study, only 1 case of DC and 3 cases of OKC were positive for MF using calponin, considering that calponin does not seem to be a reliable marker for myofibroblasts in these cases. No further studies were found that evaluated calponin expression in PF, DC, or OKC. Likewise, no studies were found with the expression of h-caldesmon in these cystic lesions.
Vimentin is a class II intermediate filament expressed primarily in mesenchymal tissue [35]. To date, only two studies provide data on vimentin in odontogenic cystic lesions [7, 35]. In this study, it was observed that all groups presented positive staining for vimentin, with the iDC group having the highest amount of expression, followed by nDC, OKC-A, OKC-N and PF. This can be explained by the presence of the inflammatory infiltrate, increasing the number of these cells. However, statistically, there is no difference between all groups compared (p > 0.05). In the study by Loreto et al., [14] in which the presence of fibroblasts in OKC variants was also evaluated, it is suggested that the different biological behavior of these lesions is not due to differences in the number of these cells, but to different metabolic activity. Thus, this study concludes that the lack of myofibroblastic differentiation appears to be consistent with the nature and function of the PF. OKC and DC show α-SMA expression, since in OKC (still, OKC-A greater than OKC-N) there is greater expression of the myofibroblastic phenotype than in DC. This may help to explain its distinctive growth potentials and aggressiveness.