Infantile fibrosarcoma with an EGFR kinase domain duplication: Underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum

Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of...

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Published in:	Annals of diagnostic pathology Vol. 57; p. 151885
Main Authors:	van Spronsen, R., Kester, L.A., Knops, R.R.G., van de Sande, M.A.J., van Leenders, G.J.L.H., de Laat, P.C.J., Stortelder, E., Korpershoek, E., van Noesel, M.M., Meister, M.T., Koerkamp, M.J.A. Groot, de Graaf, N., Giovannoni, I., Tops, B.B.J., de Krijger, R.R., ter Horst, S.A.J., Flucke, U., Alaggio, R., Hiemcke-Jiwa, L.S.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-04-2022
Subjects:	Congenital mesoblastic nephroma EGFR kinase domain duplication Infantile fibrosarcoma RNA sequencing RNA sequencing EGFR kinase domain duplication Congenital mesoblastic nephroma Infantile fibrosarcoma
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Summary:	Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of EGFR, based on an EGFR kinase domain duplication (KDD), occurs in a subset of CMNs lacking an NTRK3 rearrangement, especially in the classic and mixed type. So far no EGFR-KDDs have been detected in IFS. We describe four pediatric tumors at the extremities (leg, n = 2; foot and arm n = 1) with histological features of IFS/CMN. Two cases showed classic IFS morphology while two were similar to classic/mixed type CMN. In all cases, an EGFR-KDD was identified without detection of a fusion gene. There were no abnormalities of the kidneys in any of the patients. This is the first description of IFS with an EGFR-KDD as driver mutation, supporting that IFS and CMN are similar lesions with the same morphological and genetic spectrum. Pathologists should be aware of the more fibrous variant of IFS, similar to classic/mixed type CMN. Molecular analyses are crucial to treat these lesions adequately, especially with regard to the administration of tyrosine kinase inhibitors. •Infantile fibrosarcoma (IFS) without a fusion gene may carry an EGFR kinase domain duplication.•This leads to activation of the EGFR-related pathways.•IFS is morphologically similar to congenital mesoblastic nephroma (CMN).•Therefore, IFS and CMN represent the same tumor at different locations.•They belong to the receptor protein kinase – soft tissue tumor family.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1092-9134 1532-8198
DOI:	10.1016/j.anndiagpath.2021.151885