Human pathology · 2025
GNAQ-/GNA14-mutated hepatic vascular malformation with capillary proliferation in adults and children.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Fischer Anne Kristin, Heydt Carina, Siemanowski-Hrach Janna, Alibegovic Vedat, Hauptmann Kathrin, Vokuhl Christian, Büttner Reinhard, Fischer Hans-Peter
Аннотация
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 pseudotumourous 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.
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 pseudotumourous 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.