Special AT-rich sequence binding protein 2 (SATB2), β-catenin, and CD10 immunohistochemistry provides insights into the histopathologic features and cellular differentiation of adenomatoid odontogenic tumor

Adenomatoid odontogenic tumor (AOT) is an odontogenic tumor histologically characterized by duct- and rosette-like structures. Although having distinct histologic features, AOT may show whorled cellular masses resembling morules seen in WNT pathway-altered odontogenic tumors (WNT-OTs). This study aimed to investigate the expression of morular markers in AOT. Twenty-four odontogenic tumors, consisting of 11 AOTs, 6 developing odontomas, and 7 WNT-OTs, were included. Special AT-rich sequence binding protein 2 (SATB2), β-catenin, CD10, and CDX2 immunohistochemistry was performed and evaluated for each histologic component by tumor type. Whole-exome sequencing was performed in 3 AOTs. In AOT, a nodular growth pattern was highlighted by CD10 positivity in circumferential cells, and aggregates of small duct-like structures composed of cuboidal cells were revealed by β-catenin immunohistochemistry. Duct- and rosette-like structures in AOT were both positive for SATB2 and β-catenin, showing similar immunohistochemical profiles to ameloblast-lineage cells in developing odontoma. Two immunohistochemically distinct cell types were identified in nodules in AOT, and both cell types showed different immunohistochemical profiles from morules in WNT-OTs. The fibrous capsule of AOT showed similar SATB2 and CD10 expression patterns to the dental follicle in developing odontoma. In AOTs associated with a large cyst, the change in SATB2 expression was found in the basal layer of the cystic lining connected to the tumor. All 3 AOTs studied harbored the KRAS G12V mutation without other pathogenic mutations. SATB2, β-catenin, and CD10 immunohistochemistry provides novel insights into the histopathologic patterns, cellular differentiation, and tumor development of AOT and may aid in its diagnosis.