Vascular tumours of the liver: a particular story

Abstract

Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term diseasefree survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed.

Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management

“…HAS is rarely encountered in children; it develops most commonly in the sixth and seventh decades of life and in men, with a male-to-female ratio of 3-4:1[1].…”

“…The most commonly involved areas are the abdominal and retroperitoneal spaces, lower limbs, head and neck, spine and cranium, while liver involvement is rarely encountered (< 1%). Hepatic HPC can be primary or metastatic, with primary hepatic tumor being seldom reported[1].…”

“…Some studies have suggested an association of HPC with prolonged steroid intake, trauma or hypertension[1].…”

“…PET scan is a reliable investigation modality to diagnose HPC and for follow-up (if the tumor uptakes the tracer). The imaging features may be suggestive of HPC, but they cannot confirm the diagnosis, which needs histological and immunohistochemical testing[1,20,69].…”

“…Due to their rarity, late diagnosis because of the lack/nonspecific symptoms, and diagnostic difficulties, to date, these primary mesenchymal (endothelial) hepatic tumors in adults represent a group of tumors that does not yet have well-established therapeutic guidelines. Challenges in their management are due to their wide range of tumor behavior, from definite benign tumors such as hepatic hemangiomas, benign/low-grade malignancies such as hepatic small vessel neoplasias (HSVNs), tumors with high malignant potential such as hepatic perivascular epithelioid cell tumors (PEComas), and hepatic hemangiopericytomas (HPCs), other tumors with intermediate degrees of malignancy such as hepatic epithelioid hemangioendotheliomas (HEHEs), up to malignancies developed more often in the context of immunodeficiency syndrome–Kaposi sarcomas (KSs), and high-grade malignancies with a poor outcome such as hepatic angiosarcomas (HASs)[1,2].…”