Revisiting Hepatic Small Vessel Neoplasms and Anastomosing Hemangiomas as a Unique Capillary Liver Neoplasm: A 25-Case Series With Pathomolecular Correlations

Abstract

Hepatic small vessel neoplasm (HSVN) and anastomosing hemangioma (AH) are 2 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 (A.B., A.L.B., V.P., C.G.) 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 noncirrhotic livers (78%). Microscopically, HSVN displayed 2 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 of 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 = .544) and GNAQ (19% overall: 2 AH and 2 HSVN, P = .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 3 nonresected or partially resected cases (2 AH and 1 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.