| Title: |
Recurrent MDM2 Amplification in the Spectrum of HMGA2-Altered Pleomorphic Adenoma, Atypical Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma |
| Authors: |
Burghout,Kimberly S T; Breimer, G E; Koppes, S; Hazelbag,H M; Ooft, M L; Raicu,G M; Cleton-Jansen,A M; van Wezel,T; van Eijk, R; Terlouw,D; van Egmond, S L; Smit,V T H B M; Rupp,N J; Cohen,D; Pathologie Pathologen staf; Pathologie Opleiding; Pathologie Groep Van Diest; Projectafdeling ALS; Brain; MS KNO |
| Publication Year: |
2025 |
| Subject Terms: |
Journal Article |
| Description: |
INTRODUCTION: Pleomorphic adenoma is the most common neoplasm of the salivary glands. While the overall risk of malignancy is relatively low, a distinct molecular sub-group harboring HMGA2 alterations seems to show an increased risk of malignant progression to carcinoma ex pleomorphic adenoma. PURPOSE: This study investigates MDM2 amplification in HMGA2-altered pleomorphic adenoma, atypical pleomorphic adenoma, and carcinoma ex pleomorphic adenoma. METHODS: In this multicenter, retrospective case series analysis, we examined 37 cases of HMGA2-altered pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and pleomorphic adenoma with atypical features. A total of 18 cases were included from our institutional archives, with 19 additional cases derived from published literature. The cases from our institutes were analyzed for MDM2 amplification using a stepped approach by immunohistochemistry and FISH. RESULTS: Collectively, an MDM2 amplification was present in 27% of pleomorphic adenoma (4 of 15), compared to 78% of carcinoma ex pleomorphic adenoma (14 of 18) (p-value = 0.003). In the group of pleomorphic adenomas with atypical features, an MDM2 amplification was present in 50% of cases (2 of 4). These findings indicate an association between MDM2 amplification and malignancy. Strikingly, a mixed control group of 12 benign and malignant PLAG1-altered neoplasms showed no immunohistochemical staining for MDM2. CONCLUSION: Immunohistochemical MDM2 expression, including MDM2 amplification, is enriched in the group of HMGA2-altered pleomorphic adenoma, and potentially plays role in malignant progression. This study highlights the importance of recognizing the molecular sub-group of HMGA2-altered pleomorphic adenomas and integrate MDM2 analysis into routine diagnostics to corroborate the cytonuclear atypia in these challenging cases. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1936-055X |
| Relation: |
https://dspace.library.uu.nl/handle/1874/466038 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/466038 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.B6941DEF |
| Database: |
BASE |