Classification and prognostic evaluation of ameloblastoma using multiplanar CT imaging: a retrospective analysis
Ameloblastoma is the most common benign odontogenic tumor, which develops from the odontogenic epithelium . It is locally aggressive and destructive, with a high propensity for recurrence . Therefore, detailed examination and accurate diagnosis are essential for correctly selecting the surgical technique and obtaining optimal outcomes. Most ameloblastoma patients experience jaw swelling with or without pain . However, these clinical symptoms are insufficient to differentiate ameloblastoma from other jaw tumors and cysts. Imaging-based diagnosis is crucial for diagnosing ameloblastoma. Hence, several imaging characteristics have been identified the differential diagnosis of jaw lesions. Ameloblastomas are typically classified into three different types: (1) conventional; (2) unicystic; and (3) peripheral ameloblastoma . This classification is indicative of the behavior and prognosis of ameloblastoma, as well as the histopathologic type. Since imaging studies are routinely performed before biopsy, diagnosing ameloblastoma type using imaging modalities is highly helpful in prognostication. The diagnosis of ameloblastoma using panoramic radiographs has been refined for a long time, as they are typically used as the primary examination in dental clinics. In recent decades, there has been a significant accumulation of data regarding radiographic signs in three-dimensional imaging modalities such as computed tomography (CT), as their use in ameloblastoma diagnosis has increased . Conventionally, the morphology of lesions on two-dimensional (2D) radiographs was classified as either unilocular or multilocular, and multilocular lesions were described as having a honeycomb or soap bubble appearance. However, differences between a 2D radiograph and a CT in terms of locularity have been documented, and incomplete septal lesions may appear as multilocular lesions with septal compartments on panoramic radiography . Furthermore, because 2D radiographs cannot depict the internal nature of ameloblastoma , the necessity to analyze the 3D imaging features, including locularity, effect on adjacent structures, and internal characteristics, has increased. This study aimed to perform a multi-planar evaluation of ameloblastoma using CT images, reclassify the lesions in terms of locularity, and correlate the locularity with imaging features and recurrence.   Case selection and clinical data This study was approved by the Seoul National University Dental Hospital Institutional Review Board (IRB050/03–19). This retrospective study included all histopathologically confirmed ameloblastoma cases identified from the database of Seoul National University Dental Hospital between 2003 and 2018. The exclusion criteria included: (1) patients who lacked both CT and panoramic images; (2) those with recurrent and peripheral ameloblastoma; (3) cases in which effects on the perilesional structures could not be evaluated, such as in edentulous area; and (4) cases in which the entire lesion was not excised or the patients were not followed up. The demographic and surgical records were examined from electronic dental records. In particular, the surgical methods were classified as enucleation, curettage, resection, and mandibulectomy. The period of total follow-up was recorded. If a recurrence occurred, the time frame from the time of surgery to the recurrence was specified. Imaging analysis Panoramic and CT images of 255 patients were analyzed. The classification and imaging characteristics were accessed jointly by two radiologists with over 15 and 20 years of experience. In cases of disagreement, the final results were reached through discussion and consensus. Conventional classification was employed to classify the lesions in accordance with their locularity: either unilocular or multilocular (Figs. a and a) after the panoramic radiographs of each case were analyzed. The lesions were classified into three groups based on the presence and completeness of septa on CT images: unilocular ameloblastoma, lesions with no internal septum (Fig. b and c); pseudo-multilocular ameloblastoma, a solitary locular lesion with an incomplete septum or septa, thus giving the illusion of a multilocular lesion (Fig. b and c); and multilocular ameloblastoma, lesions with a complete septum or septa (Fig. b and c). Subsequently, additional imaging features on CT images were analyzed: the presence of expansion, cortical thinning, cortical perforation (an abrupt discontinuity of the cortical lining), and root resorption. The average and maximum lengths of the lesions were also recorded, as well as the greatest length in each axial and coronal view, using PACS viewer software (G3 PACS, Infinitt Co., Seoul, Korea). Statistics analysis The type of locularity of the lesions on CT and panoramic images was compared. The incidence rates of local effects, including cortical perforation and external root resorption, were calculated and compared between the locularity groups. The independent t-test was used for continuous variables, and a chi-square test or Fisher’s exact test was employed for categorical variables. Multiple logistic regression analyses were performed to identify the factors that are associated with the recurrence. All the statistical analyses were performed using the IBM SPSS Statistics 25.0 software (SPSS, Chicago, IL, USA).   This study was approved by the Seoul National University Dental Hospital Institutional Review Board (IRB050/03–19). This retrospective study included all histopathologically confirmed ameloblastoma cases identified from the database of Seoul National University Dental Hospital between 2003 and 2018. The exclusion criteria included: (1) patients who lacked both CT and panoramic images; (2) those with recurrent and peripheral ameloblastoma; (3) cases in which effects on the perilesional structures could not be evaluated, such as in edentulous area; and (4) cases in which the entire lesion was not excised or the patients were not followed up. The demographic and surgical records were examined from electronic dental records. In particular, the surgical methods were classified as enucleation, curettage, resection, and mandibulectomy. The period of total follow-up was recorded. If a recurrence occurred, the time frame from the time of surgery to the recurrence was specified.   Panoramic and CT images of 255 patients were analyzed. The classification and imaging characteristics were accessed jointly by two radiologists with over 15 and 20 years of experience. In cases of disagreement, the final results were reached through discussion and consensus. Conventional classification was employed to classify the lesions in accordance with their locularity: either unilocular or multilocular (Figs. a and a) after the panoramic radiographs of each case were analyzed. The lesions were classified into three groups based on the presence and completeness of septa on CT images: unilocular ameloblastoma, lesions with no internal septum (Fig. b and c); pseudo-multilocular ameloblastoma, a solitary locular lesion with an incomplete septum or septa, thus giving the illusion of a multilocular lesion (Fig. b and c); and multilocular ameloblastoma, lesions with a complete septum or septa (Fig. b and c). Subsequently, additional imaging features on CT images were analyzed: the presence of expansion, cortical thinning, cortical perforation (an abrupt discontinuity of the cortical lining), and root resorption. The average and maximum lengths of the lesions were also recorded, as well as the greatest length in each axial and coronal view, using PACS viewer software (G3 PACS, Infinitt Co., Seoul, Korea).   The type of locularity of the lesions on CT and panoramic images was compared. The incidence rates of local effects, including cortical perforation and external root resorption, were calculated and compared between the locularity groups. The independent t-test was used for continuous variables, and a chi-square test or Fisher’s exact test was employed for categorical variables. Multiple logistic regression analyses were performed to identify the factors that are associated with the recurrence. All the statistical analyses were performed using the IBM SPSS Statistics 25.0 software (SPSS, Chicago, IL, USA).   On panoramic radiographs, most cases were classified as multilocular ameloblastoma (68.6%) and the rest 80 cases (31.4%) were classified as unilocular ameloblastoma. Based on CT images, pseudo-multilocular ameloblastoma was the most prevalent type (46.3%), followed by unilocular (29.4%), and multilocular (24.3%). On three-dimensional CT images, 64.6% of the lesions that appeared multilocular on two-dimensional panoramic radiographs were observed as pseudo-multilocular, making it the more commonly observed type compared to true multilocular lesions (Table ). Cortical perforation, root resorption, and size were significantly associated with the type of CT locality (Table & , p < 0.05). Cortical perforation was almost always present in multilocular lesions, and was least prevalent in the unilocular group. Root resorption was most observed in the pseudo-multilocular group, followed by the unilocular and multilocular groups. In panoramic images, there was no correlation between locality categories and 3D image features. In this study, the recurrence rate of ameloblastoma was 14.11% (36/255). A multiple logistic regression analysis was conducted to identify factors associated with the recurrence rate, and it was confirmed that mandibulectomy and size larger than the average were significant indicators (Fig. ). In comparison to small lesions, the risk of recurrence was 0.92 times lower for large-sized lesions on average ( p = 0.049). Furthermore, among surgical techniques, mandibulectomy reduced the risk of recurrence by 0.87 times compared to enucleation ( p = 0.042). There were no other significant variables related to recurrence.   In the present study, based on the ameloblastoma morphology, the groups were categorized as unilocular, pseudo-multilocular, and multilocular using CT images. Most ameloblastoma lesions were revealed to exhibit a pseudo-multilocular morphology. The pseudo-multilocular lesions were the largest among the different types of lesions that were observed on the CT scan. Contrary to the cortical perforation that is frequently observed in CT images of multilocular types, root resorption was the most significant imaging feature in pseudo-multilocular types. The recurrence was exclusively associated with the size and operation technique. Conventionally, the lesional morphology has been described simply as multilocular or unilocular using panoramic or intraoral radiographs, when CT scans were not performed routinely. Multilocularity, which has been documented to be characterized with “soap-bubble” or “honeycomb” appearance, was one of the characteristic imaging features. While CT has been extensively used for diagnosis for some time, it continues to employ a straightforward classification into unilocular and multilocular. There has been no published work that has attempted to redefine locularity . The new types we defined classify lesions into distinct categories based on their septal characteristics. A multilocular type lesion consists of multiple locules, each forming distinct spaces separated by complete septa. In contrast, the pseudo-multilocular type has incomplete septa, which, when viewed three-dimensionally, reveal interconnected areas. This distinction allows clear differentiation between the two types. Using 3D CT imaging, this study revealed that the multilocular appearance resulted from the projection effect of the pseudo-multilocular appearance of the lesion. The true multilocular ameloblastoma was diagnosed only in 24.3% cases in the present study, which was consistent with the findings of other studies that reported septation in unilocular lesions . It implies that the incomplete septa in the lesion was not completely dividing the lesion, resulting in the lesion being continuous despite the presence of a septa. In one report, the macroscopic and microscopic appearances were correlated with conventional 2D radiographs. However, 2D radiographs were inadequate for demonstrating the internal appearance of ameloblastoma . Therefore, CT imaging is essential to accurately identifying the lesion characteristics. When we divided the groups based on lesion morphology as unilocular, pseudo-multilocular, and multilocular, there were no significant differences in CT imaging characteristics in terms of expansion and cortical thinning. However, cortical perforation was detected more commonly in multilocular lesions, and root resorption was observed more frequently in pseudo-multilocular lesions. It is challenging to compare these image characteristics with previous reports because almost all papers classify lesional morphology exclusively as unilocular and multilocular. These papers report expansion, perforation, and root resorption in multilocular ameloblastoma lesions . The pseudo-multilocular type lesions exhibited the greatest lesion size. Unilocular ameloblastoma has been believed to be unicystic ameloblastoma in imaging analysis for a long time . Consequently, it is reasonable to infer that the multilocular lesion expands and the locules merge to form a pseudo-multilocular type with incomplete septa, with the exception of the unilocular type, which is believed to possess distinct characteristics. Thus, we can hypothesize that expansion and cortical thinning are image characteristics that result from the increasing size of the lesion, whereas perforation is independent of the lesion size and is particularly prevalent in multilocular ameloblastoma. A recurrence rate analysis found that larger lesions and more extensive surgical excision (as in mandibulectomy) were associated with lower recurrence rates. This can be interpreted as a comparable outcome to other studies that advocate for a wide resection margin . While analyzing imaging characteristics and recurrence factors, it was hypothesized that the novel CT-based classification of locularity type employed in this study and imaging characteristics that reflect aggressiveness such as perforation (discontinuity) and root resorption would be related to recurrence. However, these were determined to be unrelated to the recurrence rate. This implies that the recurrence rate cannot be accounted for by a single or a few factors. This is because the wide resection and large lesion may only be partially related to the aggressive characteristics of the lesion. Since larger lesions are more likely to lead to the selection of mandibulectomy, these two factors associated with recurrence may not be independent but rather interrelated. It may also be because the cases included in this analysis were associated with a small number of recurrences, making it difficult to derive sufficiently meaningful results through statistical analysis. Consequently, regulated prospective experiments with numerous samples are required to investigate the correlation between the recurrence rate and the factors that indicate tumor aggressiveness in imaging studies. Recently, a significant amount of information has been established regarding the key mutated genes associated with ameloblastoma’s etiology and pathology. Additionally, several studies have demonstrated the genetic factors that are specific to subtypes of ameloblastoma . This rapid development is also causing significant modifications in the treatment of ameloblastoma, which has impacted the quality of life through repeated surgery and recurrences. Results with favorable prognosis have been reported using molecular targeted therapy . Nevertheless, imaging is the primary diagnostic examination in the clinic before histopathologic or genetic analysis when making treatment strategies. Consequently, it would be of the utmost importance to make an accurate diagnosis with more accurate 3D information using multiplanar images. This study provides novel and basic insights for the classification of ameloblastoma using 3D CT images, though there are additional areas that require further investigation using three-dimensional imaging especially behavior or prognosis of the lesion. The present study has certain limitations. First, the histopathologic subtype of the ameloblastoma lesions was not examined. This is a critical limitation of this research; however, it is a retrospective observational study, and the histopathologic reports were insufficient to accurately represent the precise subtype. In addition to the new CT-based classification of ameloblastoma locularity, the lesional behavioral differences based on histopathologic subtypes should be considered in a subsequent study. Additionally, the correlation between histopathologic type and additional imaging features from contrast-enhanced CT/MR is necessary to provide a more detailed explanation of the tumor behavior. Utilizing the contrast enhancement information, tumor characteristics such as cystic and solid portions of the lesions can be differentiated. The other limitation was that we depended on the retrospective records. The records pertaining to surgical methods and specifics may vary depending on the surgeon, and the patient’s clinical features may differ from those that were recorded; however, reflection on this aspect was not feasible due to the retrospective nature of the study. In the future, a prospective and controlled study with a large sample size, utilizing a standard imaging modality and surgical approach, should be conducted to ensure a more precise analysis.   The retrospective study utilized CT imaging to reclassify ameloblastoma into more precise locularity types, thereby providing insights into the true three-dimensional structure. Many ameloblastomas, traditionally classified as multilocular in 2D radiological images, is actually a pseudo-multilocular lesion caused by lobulation or incomplete septa when evaluated with 3D images. No direct correlation was found between the newly defined locularity types and recurrence rates. Future research should focus on controlled prospective studies to investigate the relationships between the tumor’s imaging characteristics, surgical outcomes, and recurrence rates in a larger cohort.   