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

Table 1 Main clinical-pathological aspects of malignant vascular hepatic tumors in adults

Tumor type	HEHE	HAS	HPC	HPEComas-NOS	KS	HSVNs
Epidemiology	Very rare, 30-40 yr, F: M ratio 3:2	2% of primary hepatic neoplasms, 50-60 yr, M:F ratio 3-4:1	Very rare, 40-50 yr, M:F ratio 1:1	Extremely rare, mostly female	8.3%-34% of AIDS-related tumors	Rare, mean age 54 yr, male predominance
Etiology	-	Thorotrast, vinyl chloride monomers and arsenical compounds exposure, radiation	-	-	HHV-8, HIV infection	-
Gross pathology	Multiple ill-defined firm, tan- to white-colored nodules	Multicentric infiltrative sponge-like hemorrhagic nodules	Well-circumscribed solitary lesion, with hemorrhage and cystic degeneration on sectioning	Pale tan, friable soft tumor	Multiple irregulat red-brown masses	Poorly circumscribed, single nonencapsulated hemorrhagic tumor
Histology	Epithelioid/spindle cells surrounded by myxoid stroma, presence of cytoplasmic vacuoles, intravascular tumor growth	Spindle-shaped/epithelioid tumor cells with ill-defined borders, frequent mitotic figures	Hypervascular tumor, spindle-shaped cells	Large epithelioid tumor cells surrounding small vessels	Spindle tumor cells, separated by slit-like vascular channels	Thin-walled small vascular spaces , delineated by hobnail-like endothelial cells, no mitotic figures
Immunohistochemical markers	CAMTA 1 expression, Ki-67 expression > 10%	ERG, VEGFR2	Vimentin, S-100, muscle-specific actin, smooth muscle actin, CD 34	gp 100 protein, HMSA-1, SMA, vimentin	HHV8-LANA 1	CD34, CD31, FLI1, Ki-67 index < 10%
Molecular features	WWTR1-CAMTA1 and YAP1-TFE3 fusion genes	TP53, KRAS-2 mutations	12q13-15 alterations in some cases	Genetic changes of the TSC genes	HHV8- DNA detection	Hotspot GNAQ, PIK3CA mutation
Clinical features	Oligosymptomatic → portal hypertension, venooclusive disease	Abdominal pain, weight loss, malaise, portal hypertension, hemoperitoneum	Asymptomatic → hemoperitoneum→ paraneoplastic syndromes (hypoglycemia)	Mostly asymptomatic → hemoperitoneum	Asymtomatic/oligosymptomatic	Mostly asymptomatic
Imaging US/CEUS	Hypoechoic heterogeneous mass/nodules	Heterogeneous echogenicity; CEUS: Central nonenhancement, irregular enhancement of the tumor periphery in arterial and portal phase, complete wash-out in the late phase	Hypoechoic, hypervascular tumors	Heterogeneous hypoechoic lesion	Heterogeneous cystic lesion, solid areas and hyperechoic strands surrounding peripheral portal branches	Hypoechoic and heterogenous tumor. ceus: Intense early and homogeneous enhancement in the arterial phase, continuing in the portal phase, isoechoic in delayed phase
Native CT scan	Extent of the tumor assessment, focal atrophy, retraction of the liver capsule	Hypoattenuating pattern of the tumor	Hypodense/ isodense tumor	Low-density mass	Inhomogeneous liver structure, multiple hypodense scattered small-sized nodules, mostly located in periportal regions	Nonspecific
Contrast-enhanced CT scan	Multiple hepatic bilobar hypoattenuating lesions; larger tumors: halo or target-type pattern of contrast enhancement (typically)	Hypodense lesions, various patterns of contrast enhancement; isodense after contrast administration; large tumors: heterogeneous structure, various patterns of early contrast enhancement ± focal irregular areas/ peripheral rim enhancement; arterioportal shunting	Lobulated tumor: Solid zones with contrast enhancement, cystic areas, with speckled calcifications	Heterogeneous and intense enhancement on arterial phase, slightly hypodense aspect on portal phase and enhancing rim on delayed phase	Nonspecific	Nonspecific
CT angiography	Nonspecific	Multiple/solitary hypervascular masses, heterogeneous early and progressive contrast enhancement	Highly vascular tumor	Nonspecific	Nonspecific	Nonspecific
MRI T1-weighted	Hypo-intense lesions	Heterogeneous hiperintense pattern	Hypo-intense lesion	Nonspecific	Hypointense on T1-weighted in-phase scanning and hyperintense on T1-weighted out-of-phase scanning	Nonspecific
MRI T2-weighted	Hyper-intense heterogeneous pattern		Hyper-intense heterogeneous pattern		Nonspecific
MRI DW	Variable		Not known
Extracellular contrast MRI	Larger tumors: peripheral halo or target-type of enhancement, ± peripheral hypo-intense rim of avascular tissue	Mild enhancement in the early phase, progressive homogeneous enhancement, with complete tumor wash-out in delayed and parenchymal phase	Heterogeneous contrast enhancement
FDG PET	Variable uptake	Increased uptake	Increased uptake	Controversial results	Nonspecific	Nonspecific
Prognosis	75% 5-yr survival rate following surgery	Very poor, 2-yr survival rate under treatment < 3%	50% 5-yr disease free survival after Ro surgery	Not very clearly defined	Reserved	Benign/low-grade neoplasia – currently, prognosis not well defined
Treatment	Liver resection Liver transplantation; TACE; Chemotherapy, antiangiogenic agents	Tumor/hepatic resection; Liver transplantation contraindicated; Adjuvant/palliative chemotherapy, antiangiogenic agents, immunotherapy	Aggressive surgery; Radiotherapy, chemotherapy, antiangiogenic treatment	Follow-up; Surgical resection Chemo-, radiotherapy, mTOR inhibitors, immunotherapy; SRBT, TAE, RFA	ARV HIV treatment; Systemic chemotherapy; Novel targeted treatments under study; HHV-8 replication inhibitors	Resection and long-term follow-up

SRBT: Stereotactic body radiation; TAE: Transarterial embolization; FLI1: Friend leukemia integration 1; HEHE: Hepatic epithelioid hemangioendotheliomas; HAS: Hepatic angiosarcoma; HPC: Hepatic hemangiopericytoma; HPEComas-NOS: Hepatic perivascular epithelioid cell tumors-not otherwise specified; HSVNs: Hepatic small vessel neoplasms; KS: Kaposi sarcoma; AIDS: Acquired immune deficiency syndrome; HHV-8: Human herpesvirus-8; VEGFR2: Vascular endothelial growth factor receptor 2; TSC: Tuberous sclerosis complex; US: Ultrasound; CT: Computed tomography; MRI: Magnetic resonance imaging; PET: Positron emission tomography; FDG: Fluorodeoxyglucose; ARV: Antiretroviral; TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation.