Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: A literature review

Table 1 Clinical characteristics of patients with hepatoid adenocarcinoma in the literature review n (%)

	Number	Male (total), n	Female (total), n	Ratio M:F	Age (range), yr	Elevated serum AFP	Lymph node metastasis	Liver metastasis	Lung metastasis	Other metastasis	Operation	Chemotherapy	Median survival (range), mo
Total	217 (100)	135 (194)	59 (194)	2.3:1	63 (21–100)	78 (84.8)	122 (57.5)	94 (46.3)	7 (3.4)	16 (7.9)	138 (80.2)	49 (52.1)	12 (1.2-66)
Stomach	182 (83.9)	121 (159)	38 (159)	3.2:1	63.3 (28–100)	56 (87.5)	115 (63.9)	84 (48.8)	5 (2.9)	9 (5.2)	107 (77.5)	34 (50)	13 (1.2-66)
Gallbladder	8 (3.7)	2	6	1:03	66.1 (55–76)	3 (75)	2 (28.6)	3 (42.9)	0 (0)	1 (14.3)	7 (100)	2 (28.6)	12 (5-20)
Uterus	7 (3.2)	–	7	–	69.4 (61–86)	7 (100)	2 (28.6)	2 (28.6)	1 (14.3)	1 (14.3)	7 (100)	5 (71.4)	22 (12-36)
Lung	5 (2.3)	4	1	4:01	54.8 (49–68)	2 (60)	2 (40)	1 (20)	NA	2 (40)	5 (100)	2 (50)	15 (2-45)
Urinary bladder	4 (1.8)	4	–	–	70 (61–85)	4 (100)	NA	NA	NA	NA	4 (100)	NA	19 (12-26)
Esophagus	2 (0.9)	1	1	1:01	60 (44–76)	0 (0)	0 (0)	1 (50)	0 (0)	0 (0)	2 (100)	1 (50)	N/A
Peritoneum	2 (0.9)	1	1	1:01	46.5 (21–72)	1 (50)	1 (50)	1 (50)	0 (0)	0 (0)	1 (50)	2 (100)	6
Retroperitoneum	1 (< 0.5)	1	–	–	47	1 (100)	0 (0)	0 (0)	0 (0)	1 (100)	0 (0)	1 (100)	N/A
Testis	1 (< 0.5)	1	–	–	36	1 (100)	0 (0)	0 (0)	1 (100)	0 (0)	1 (100)	NA	28
Ovary	1 (< 0.5)	–	1	–	59	1 (100)	0 (0)	0 (0)	0 (0)	1 (100)	0 (0)	1 (100)	N/A
Jejunum	1 (< 0.5)	–	1	–	40	1 (100)	0 (0)	0 (0)	0 (0)	0 (0)	1 (100)	NA	N/A
Transverse colon	1 (< 0.5)	–	1	–	59	NA	0 (0)	1 (100)	0 (0)	0 (0)	1 (100)	1 (100)	N/A
Rectum	1 (< 0.5)	–	1	–	50	1 (100)	0 (0)	0 (0)	0 (0)	0 (0)	1 (100)	NA	N/A
Ureter	1 (< 0.5)	–	1	–	80	NA	0 (0)	1 (100)	0 (0)	1 (100)	1 (100)	0 (0)	N/A

AFP: α-fetoprotein; NA: Not available.

Table 2 Immunohistochemical staining characteristics of patients with hepatoid adenocarcinoma in the literature review n (%)

	Number	AFP	Hep Par1	CEA	CK18	CK19	CK20	CK7	AE1/AE3	α1-AT	CD10	GPC3
Total	217 (100)	177 (91.6)	24 (38.1)	37 (78.7)	22 (100)	27 (100)	6 (28.6)	4 (15.4)	12 (92.3)	10 (91)	5 (62.5)	10 (100)
Stomach	182 (83.9)	156 (90.6)	12 (26.7)	27 (75.0)	17 (100)	16 (100)	5 (38.5)	0 (0)	10 (100)	7 (87.5)	0 (0)	10 (100)
Gallbladder	8 (3.7)	5 (83.3)	4 (66.7)	3 (75)	1 (100)	6 (100)	0 (0)	2 (33.3)	1 (100)	1 (100)	3 (100)	NA
Uterus	7 (3.2)	6 (85.7)	NA	1 (100)	NA	NA	NA	NA	NA	NA	1 (100)	NA
Lung	5 (2.3)	4 (100)	0 (0)	1 (100)	1 (100)	1 (100)	1 (50)	2 (0)	NA	NA	1 (100)	NA
Urinary bladder	4 (1.8)	4 (100)	4 (100)	4 (100)	NA	NA	NA	NA	NA	NA	NA	NA
Esophagus	2 (0.9)	2 (100)	1 (50)	NA	NA	NA	NA	NA	NA	2 (100)	NA	NA
Peritoneum	2 (0.9)	1 (50)	1 (100)	NA	1 (100)	NA	0 (0)	NA	1 (50)	NA	NA	NA
Retroperitoneum	1 (< 0.5)	NA	NA	NA	NA	NA	NA	NA	0 (0)	NA	NA	NA
Testis	1 (< 0.5)	1 (100)	0 (0)	NA	NA	NA	NA	NA	NA	NA	NA	NA
Ovary	1 (< 0.5)	1 (100)	NA	1 (100)	NA	NA	NA	NA	NA	NA	NA	NA
Jejunum	1 (< 0.5)	1 (100)	1 (100)	NA	1 (100)	1 (100)	0 (0)	0 (0)	NA	NA	NA	NA
Transverse colon	1 (< 0.5)	NA	NA	NA	NA	1 (100)	NA	NA	NA	NA	NA	NA
Rectum	1 (< 0.5)	1 (100)	1 (100)	NA	1 (100)	1 (100)	0 (0)	0 (0)	NA	NA	NA	NA
Ureter	1 (< 0.5)	1 (100)	NA	NA	NA	1 (100)	0 (0)	NA	NA	NA	0 (0)	NA

CEA: Carcinoembryonic antigen; CK: Cytokeratin; AE1/AE3: Anti-pancytokeratin AE1/AE3; CD10: Cluster of differentiation 10; α1-AT: α1-Antitrypsin; GPC-3: Glypican 3; AFP: α-fetoprotein; NA: Not available.

Table 3 Comparison of positive rates of commonly-used key immunohistochemical stains in hepatocellular carcinoma, hepatoid adenocarcinoma, and common gastric adenocarcinoma

IHC stains	HCC1	HAC2	Common GAC34
AFP	8.2%-37%	92.1%	0%-0.8%
GPC-3	84%	100%	3.4%
Hep Par 1	73%-93%	38.1%	4%-47%
CK19	8.2%-15%	100%	83.6%-89.7%

IHC: Immunohistochemical; HCC: Hepatocellular carcinoma; HAC: Hepatoid adenocarcinoma; GAC: Gastric adenocarcinoma.

¹HCC: AFP stain in 218 cases[16,29,30], GPC-3 stain in 56 cases[30], Hep Par 1 stain in 308 cases[16,29-32] and CK19 stain in 233 cases[16,29,33];

²HAC data source: Data based on our review in Table 2;

³Common GAC data source: AFP stain in 122 cases[34,35], GPC-3 stain in 118 cases[35], Hep Par 1 stain in 108 cases[22,32], CK19 stain in 384 cases[33,36];

⁴Common GAC means GAC except HAC.