Abstract
Hepatic small vessel neoplasm (HSVN) and anastomosing hemangioma (AH), are two capillary liver neoplasms that are challenging to differentiate in clinical practice. This study aimed to refine their classification through integrated histopathologic and molecular analyses. We conducted a bicentric retrospective study of 25 cases (15 resections and 10 biopsies). Four liver pathologists independently reviewed histologic and immunohistochemical features. Targeted DNA next generation sequencing and RNA sequencing were performed on 21 and 15 cases, respectively. Seven lesions (28%) were diagnosed as AH, presenting as well-demarcated tumors with fibrotic stroma, often associated with cirrhosis (5/7, 71%). The remaining 18 lesions (72%) were identified as HSVN, typically infiltrative and occurring predominantly in non-cirrhotic livers (78%). Microscopically, HSVN displayed two distinct patterns: (1) a classic pattern (8/18, 44%) composed of small, thin-walled vessels, and (2) a hepatocellular-reactive pattern (7/18, 39%) with small vessels interwoven with regenerative hepatocellular trabeculae. A mixed pattern appeared in 3/18 cases (17%). No cytologic atypia or mitoses were observed. Tumor cells consistently expressed ERG, CD31, and CD34, with Ki67 indices <10% in all cases. Mutations in GNA genes were found in 20 of 21 cases (95%), distributed between GNA14 (81% overall: 4 AH and 13 HSVN, p=0.544) and GNAQ (19% overall: 2 AH and 2 HSVN, p=0.544). Transcriptomic analysis revealed no differentially expressed genes between AH and HSVN. After a median follow-up of 18 months, no recurrence was observed in resected tumors. Tumor growth was noted in three non- or partially resected cases (two AH and one HSVN). In conclusion, despite subtle pathological differences, HSVN and AH exhibit overlapping clinical and molecular features, supporting their reclassification as a single benign entity, namely AH. Notably, some lesions exhibit a hepatocellular-reactive pattern that closely mimics hepatocellular adenoma, posing a significant diagnostic challenge, particularly in biopsy specimens.