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Case Reports
. 2025 Dec 22;13(1):255.
doi: 10.1186/s40478-025-02165-y.

YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier

Catherine Godfraind  1 , Nabil Djebbour  2 , Romain Appay  3 , Anne Pagnier  4 , Raia Doumit  5 , Julien Masliah-Planchon  6 , Fabien Forest  7 , Fanny Burel-Vandenbos  8 , Jean Boutonnat  9 , Berengere Dadone-Montaudié  10   11
Affiliations
Case Reports

YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier

Catherine Godfraind et al. Acta Neuropathol Commun. .

Abstract

Embryonal tumors with multilayered rosettes (ETMR) are rare embryonal tumors that usually affect children under two years old. They are characterized histologically by the presence of multilayered rosettes and by the immunohistochemical expression of LIN28A. Their genetic hallmarks include C19MC amplification, which is most common, followed by DICER1 mutation. Each of these alterations correlates with a specific methylation class in the Heidelberg central nervous system tumor classifier and the National Institutes of Health brain tumor classifier. Meanwhile, 2.5 percent of LIN28A-positive embryonal tumors lack the previously mentioned genetic alterations associated with ETMR. Here, we present and discuss a case of this type. A posterior fossa tumor was found in a five-month-old infant. Histologically, the lesion appeared as an embryonal tumor, lacking multilayered rosettes but showing focal positivity for LIN28A. It did not show C19MC amplification or DICER1 mutation, yet it clustered within the ETMR non-C19MC-altered methylation class of the Heidelberg classifier (V12.5) and the ETMR-DICER class of the NIH classifier. Additionally, a YAP1::MAML2 fusion was identified, a finding not yet associated with these methylation classes.

Keywords: DICER1 mutation; YAP1::MALM2 fusion; ETMR; ETMR DICER1-altered; ETMR non-C19MC methylation class.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The patient’s parents agree to introduce their child into the French RENOCLIP network, which is linked to a research agreement. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A–B: T2-weighted MRI showing a heterogeneous lesion with hyper- and hypo-intense regions. C: Methylscape UMAP for the proband. D: H&E stain revealing a poorly differentiated tumor lacking an architectural pattern. E: H&E stain showing a perivascular anucleated region. F: H&E stain with hyperchromatic nuclei demonstrating molding. G, J: IHC for LIN28A, GFAP showing partial positivity. H and I: IHC for IN1, BRG1 showing nuclear positivity. K: IHC for Ki67 indicating a heterogeneous proliferation index, with regions reaching 60%. L: IHC for YAP-C showing loss of nuclear expression in tumor cells
See this image and copyright information in PMC

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