An epithelial odontogenic tumor called adenoid ameloblastoma (AA) has recently been included in the new WHO classification. However, AA has considerable overlapping features with a preexisting entity, dentinogenic ghost cell tumor (DGCT). This study compared the clinical, histologic, and molecular characteristics of AA and DGCT. Eight cases of odontogenic tumors initially diagnosed as AA or DGCT were included in this study. Quantitative histologic analysis, b-catenin immunohisto-chemistry, and molecular profiling using next generation sequencing were performed. Additionally, accumulated clinical data of AA and DGCT were statistically analyzed. Nuclear b-catenin accumu-lation was detected in all cases in common, although the tumors studied histologically consisted of varying combinations of the AA-like phenotype, ghost cells, and dentinoid. However, CTNNB1 hot-spot mutations were not found in any case. Instead, loss-of-function mutations in tumor suppressor genes involved in the WNT pathway, including the APC, SMURF1, and NEDD4L genes, were found regardless of histologic type. In addition, KRT13 mutations were detected in 2 cases with a high proportion of ghost cells. Finally, a literature analysis revealed clinical similarities between the previously reported cases of AA and DGCT. These findings suggest that from a clinical and molecular point of view, AA and DGCT represent a histologic spectrum of WNT pathway-altered benign odontogenic tumors rather than 2 distinct tumors. Moreover, previously unidentified keratin mu-tations may be associated with ghost cell formation found in specific types of odontogenic lesions.(c) 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.
