Universität zu Köln

Fischer, Anne Kristin ORCID: 0000-0003-0665-9693, Heydt, Carina ORCID: 0000-0003-3184-9579, Siemanowski-Hrach, Janna ORCID: 0009-0000-8453-5229, Alibegovic, Vedat, Hauptmann, Kathrin, Vokuhl, Christian, Büttner, Reinhard ORCID: 0000-0001-8806-4786 and Fischer, Hans-Peter ORCID: 0000-0003-2584-4958 (2025). GNAQ-/GNA14-mutated hepatic vascular malformation with capillary proliferation in adults and children. Human Pathology, 165. pp. 1-10. Elsevier. ISSN 0046-8177

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Abstract

[Artikel-Nr.: 105934] Aims: Congenital hepatic vascular malformation with capillary proliferation (HVMCP) is a rare pseudo- tumourous liver lesion, to date only known in children. Diagnostic pitfalls in infant and, for the first time, in adult cases are histomorphologically characterised and molecularly analysed on driver mutations playing a role in angiogenesis and angioproliferation. Methods and results: We histomorphologically characterised 4 early childhood and 2 adult cases, which showed malformed venous, cavernous and dissecting CD34-positive, GLUT1-negative capillary formations, followed by trabecular disarrangement of the involved liver parenchyma. As shown exemplarily, infant cases can lead to misdiagnosis as Glypican 3-positive hepatoblastoma. In adults, broadened capillarized liver trabecules might imitate hepatocellular carcinoma and dense capillary formations can resemble endothelial tumours, particularly hepatic small vessel neoplasia. In all cases, vascular malformation was the diagnostic key feature. Custom hybrid- capture-based sequencing assays were conducted, covering a broad range of genes active in angiogenesis and angioproliferation. Of the cases, 3, including 1 adult case, showed pathogenic activating driver mutations in GNAQ/GNA14. One adult lesion proved to be wild-type. Two wedge biopsies did not allow for molecular analysis. Conclusions: HVMCP has to be differentiated from true vascular neoplasms, particularly from hepatic congenital haemangioma, hepatic infantile haemangioma and hepatic small vessel neoplasia but also from solid malignant hepatocellular tumours. Recognition of the underlying vascular malformation might disclose the pseudotu- mourous nature even in biopsies. Detection of driver mutations in the Gqα-protein-coding gene family with activation of the downstream MAPK/ERK pathway may open up a future treatment option for non-resectable lesions with MAPK/ERK inhibitors. Clinical trial number: Ethic Votum BioMaSota No.13-091.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Fischer, Anne Kristin UNSPECIFIED https://orcid.org/0000-0003-0665-9693 UNSPECIFIED Heydt, Carina UNSPECIFIED https://orcid.org/0000-0003-3184-9579 UNSPECIFIED Siemanowski-Hrach, Janna UNSPECIFIED https://orcid.org/0009-0000-8453-5229 UNSPECIFIED Alibegovic, Vedat UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauptmann, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Vokuhl, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Büttner, Reinhard UNSPECIFIED https://orcid.org/0000-0001-8806-4786 UNSPECIFIED Fischer, Hans-Peter UNSPECIFIED https://orcid.org/0000-0003-2584-4958 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-810077
Identification Number:	10.1016/j.humpath.2025.105934
Journal or Publication Title:	Human Pathology
Volume:	165
Page Range:	pp. 1-10
Number of Pages:	10
Date:	November 2025
Publisher:	Elsevier
ISSN:	0046-8177
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Congenital hepatic vascular malformation ; associated with capillary proliferation ; GLUT1 negativity ; GNAQ/GNA14 mutation ; Vascular malformation English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81007