Hepatic epithelioid hemangioendothelioma: Clinical characteristics, diagnosis, treatment, and prognosis

Table 1 General features of patients with hepatic epithelioid hemangioendothelioma

General feature	No. of patients	%
Presence of symptoms, n = 254
Asymptomatic	69	27.2
Symptomatic	185	72.8
Epigastric pain	99	39.0
Hepatosplenomegaly	39	15.4
Inappetence	34	13.4
Abdominal distension	31	12.2
Weight loss	27	10.6
Fatigue	26	10.2
Epigastric discomfort	25	9.8
Hydrothorax and ascite	18	7.1
Fever	12	4.7
Jaundice	24	9.4
Thoracalgia and humeral back pain	20	7.9
Nausea and vomiting	10	3.9
Edema	8	3.1
Cough and expectoration	9	3.5
Abdominal mass	2	0.8
Hematemesis and melena	2	0.8
Intrahepatic involvement type, n = 197
Multinodular type (including diffuse type)	168	85.3
Mononodular type	29	14.7
Type of involvement, n = 197
Intrahepatic involvement	129	65.5
Extrahepatic involvement	68	34.5
Lung	44	22.3
Lymph node	11	5.6
Bone	13	6.6
Peritoneum	7	3.6
Spleen	10	5.1
Pleura	4	2.0
Omentum	2	1.0
Liver function, n = 157
Normal	89	56.7
Abnormal	68	43.3
Elevated ALT in U/L	40	25.5
Elevated AST in U/L	40	25.5
Elevated TBIL in μmol/L	24	15.3
Elevated ALP in U/L	43	27.4
Elevated GGT in U/L	32	20.4
Tumor markers
Elevated AFP in ng/mL	8/171	4.7
Elevated CEA in ng/mL	7/130	5.4
Elevated CA19-9 in U/mL	13/135	9.6
Elevated CA125 in U/mL	14/53	26.4
Plain CT scan, n = 198
Low density lesions	195/198	98.6
High density or uneven density lesions	3/198	1.4
Calcification	30/198	15.2
Capsular retraction	34/198	17.2
Confluent masses	42/198	21.2
Contrast-enhanced CT, n = 163
Tumor edge enhancement	138/163	84.7
Tumor edge without enhancement	25/163	15.3
Target sign	33/163	20.2
Lollipop sign	19/163	11.7
Immunohistopathological markers
FVIII-RAg	117/118	99.2
CD34	215/218	98.6
CD31	171/173	98.8
Vimentin	94/95	98.9
SMA	12/27	44.4
Desmin	0/13	NA
Hepatocyte	8/58	13.8
CK	38/81	46.9
EMA	6/34	17.6
AFP	0/34	NA
CEA	0/11	NA
S-100	1/33	9.1
D2-40	7/11	63.6
Genetics
YAP1-TFE3	3/4	75.0
WWTR1-CAMTA1	3/5	60.0

HEHE: Hepatic epithelioid hemangioendothelioma; CT: Computed tomography; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; CK: Cytokeratin; GGT: Gamma-glutamyl transferase; SMA: Smooth muscle actin; EMA: Epithelial membrane antigen; FVIII-RAg: Factor VIII-related antigen; YAP-1: Yes-associated protein 1; TFE3: Transcription factor E3; WWTR1: WW domain-containing transcription regulator 1; CAMTA1: Calmodulin-binding transcription activator 1.

Table 2 Treatments and prognosis of patients with hepatic epithelioid hemangioendothelioma

Treatment and outcome, n = 118	n (%)	Mean survival time in months, mean ± SD
LR	35 (29.7)	158.6 ± 20.5
LT	19 (16.1)	147.3 ± 13.8
Palliative treatment	15 (12.7)	4.2 ± 0.8
TACE	12 (10.2)	90.8 ± 13.4
Chemotherapy	13 (11.0)	71.4 ± 23.5
Other treatments	6 (5.1)	55.0 ± 17.0
Antiangiogenic therapy	18 (15.3)	83.1 ± 9.7

LR: Liver resection; LT: Liver transplantation; TACE: Transhepatic arterial chemotherapy and embolization.

Table 3 Results of univariable and multivariate analysis

Parameter	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Sex, male/female	1.175 (0.549-2.513)	0.678
Age, > 45 yr/≤ 45 yr	0.952 (0.447-2.027)	0.898
Symptoms, symptomatic/asymptomatic	3.047 (0.911-10.185)	0.070
AFP, elevated/normal	1.261 (0.555-2.863)	0.579
Liver function, abnormal/normal	2.720 (1.236-5.988)	0.013	2.258 (1.017-5.009)	0.045
Maximum diameter of tumor, ≥ 5 cm/< 5 cm	2.430 (0.856-6.901)	0.096
Intrahepatic metastasis, yes/no	3.553 (1.228-10.277)	0.019	3.930 (1.152-13.404)	0.029
Extrahepatic metastasis, yes/no	2.328 (1.065-5.089)	0.034		0.558
Treatments, nonsurgical treatment/surgical treatment	2.831 (1.195-6.704)	0.018	2.591 (1.022-6.565)	0.045

HR: Hazard ratio; CI: Confidence interval; AFP: Alpha fetoprotein.