Evidence map›Paper›PMID 40338436›Full record

ArticleHead and neck pathology2025

Recurrent MDM2 Amplification in the Spectrum of HMGA2-Altered Pleomorphic Adenoma, Atypical Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma.

Kimberly S T Burghout, G E Breimer, S Koppes, H M Hazelbag, M L Ooft, G M Raicu, A M Cleton-Jansen, T van Wezel, R van Eijk, D Terlouw and 4 more

Abstract readMulticenter Study
In one paragraph

Article in Head and neck pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kimberly S T BurghoutDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands. k.s.t.burghout@lumc.nl.
G E BreimerDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
S KoppesDepartment of Pathology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
H M HazelbagDepartment of Pathology, Haaglanden Medical Center, The Hague, The Netherlands.
M L OoftDepartment of Pathology, Pathology-DNA, location Rijnstate Hospital, Arnhem, The Netherlands.
G M RaicuDepartment of Pathology, St. Antonius Hospital, Utrecht, 3543 AZ, The Netherlands.
A M Cleton-JansenDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
T van WezelDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
R van EijkDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
D TerlouwDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
S L van EgmondDepartment of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands.
V T H B M SmitDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.
N J RuppDepartment of Pathology and Molecular Pathology, University Hospital, Zürich, Switzerland.
D CohenDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, ZA 2333, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPleomorphic 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.

methodsIn 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.

resultsCollectively, 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.

conclusionImmunohistochemical 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.

Indexed as

Adenoma, PleomorphicHMGA2 ProteinProto-Oncogene Proteins c-mdm2Salivary Gland NeoplasmsAdultAgedAged, 80 and overBiomarkers, TumorFemaleGene AmplificationHumansMaleMiddle AgedRetrospective StudiesBiomarkers, TumorHMGA2 ProteinHMGA2 protein, humanMDM2 protein, humanProto-Oncogene Proteins c-mdm2Malignant transformationMolecular analysisPleomorphic adenomaSalivary gland neoplasm

Identifiers

PMID40338436
PMCPMC12061814

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.