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Published on: February 28, 2019
Adenoid Ameloblastoma and Dentinogenic Ghost Cell Tumor Share WNT Pathway Mutations, Challenging Current Diagnostic
Jiang Xue1, Wenyi Zhang2, Jiaying Bai3
1Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China; Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China; National Center of Stomatology, Beijing, China; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China.
Purpose:
This study aimed to investigate the molecular features of 2 morphologically overlapping rare odontogenic neoplasms, adenoid ameloblastoma (AA) and dentinogenic ghost cell tumor (DGCT).
Materials And Methods:
Thirteen World Health Organization--confirmed cases, including 7 AAs and 6 DGCTs, were analyzed. Central histologic review and β-catenin immunohistochemistry were performed on all specimens. Paired tumor-normal whole-exome sequencing was conducted to evaluate copy number alterations and tumor mutational burden. All critical genetic variants identified through bioinformatic analysis were independently validated using Sanger sequencing to ensure data accuracy.
Results:
AA and DGCT showed modest differences in anatomic distribution and clinical course (AA: median age 36 years, mandible predominant, median symptom duration 69 months, local recurrence 71%; DGCT: median age 33 years, maxilla predominant, median symptom duration 17 months, local recurrence 33%). Nuclear β-catenin labeling was present in all tumors. Canonical WNT drivers (CTNNB1 exon-3 hotspot substitutions or truncating APC lesions) occurred in both entities, and overall putative WNT axis involvement reached 4 of 7 AA and 4 of 6 DGCT (P > .9999) cases. Among the AA cases, 1 harbored concurrent CTNNB1 and APC2 mutations, whereas another showed concurrent APC and AXIN1 alterations. AA more frequently harbored chromosome 1 and chromosome 5 loss (including the APC locus) and demonstrated higher mean tumor mutational burden than DGCT. No canonical MAPK or SHH driver alterations were identified.
Conclusions:
Together, these findings support a shared WNT/β-catenin-driven molecular landscape underlying AA and DGCT, suggesting that they represent overlapping morphologic manifestations within a broader odontogenic tumor spectrum rather than strictly distinct entities. Whole-exome sequencing further expands previous observations of low CTNNB1 mutation frequencies by revealing additional WNT pathway alterations beyond canonical CTNNB1 mutations. Larger multicenter and functional studies are warranted to refine tumor classification and prognostic assessment.
