Analysis of intrahepatic sarcomatoid cholangiocarcinoma: Experience from 11 cases within 17 years

Table 1 Clinical findings of the patients with intrahepatic sarcomatoid cholangiocarcinoma

Case	Sex	Age	Chief complaint	Stone	CS	Chronic hepatitis	LC	HCC	Tumor size (cm)	Number of mass	Metastasis	Stage (TNM)
1	M	45	RUQ pain	-	-	CHB	+	+	7.5	7	LN, IH	IVB
2	M	67	Lt. flank pain	-	-	CHC	+	-	2.5	1	Bone, LN	IVB
3	M	55	RUQ pain, fever	CST	+	-	-	-	6.5	2	LN	IVA
4	M	66	RUQ pain, fever	GB stone	-	-	-	-	10.0	1	Lung, LN	IVB
5	M	56	RUQ pain, Fatigue	-	-	CHB	+	-	8.0	1	Thymus, LN	IVB
6	F	66	RUQ pain	CST	-	-	-	-	7.5	1	LN	IVB
7	M	68	Wt. loss, Fatigue	CST	-	-	+	-	6.0	1	Lung, Bone, LN	IVB
8	F	55	RUQ pain, fever	-	-	-	-	-	8.5	3	LN	IVA
9	M	49	LUQ pain, fever	-	-	CHB	+	-	9.5	3	LN	IVA
10	M	65	RUQ pain	-	-		-	-	9.5	15	LN, IH	IVA
11	M	61	RUQ pain	-	-		-	-	5.0	1	Diaphragm, LN	IVB

CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; CS: Clonorchis sinensis; CST: Cholecystectomy; GB: Gallbladder; HCC: Hepatocellular carcinoma; IH: Intrahepatic; LC: Liver cirrhosis; LN: Lymph node; LUQ: Left upper quadrant; RUQ: Right upper quadrant.

Table 2 Baseline clinical characteristics of the patients of intrahepatic bile duct adenocarcinoma and sarcomatoid cholangiocarcinoma n (%)

		Adenocarcinoma	Sarcomatoid	P value
Gender	Male	155 (71.8)	9 (81.8)	0.732
	Female	61 (28.2)	2 (18.2)
Age	< 60	73 (33.8)	5 (45.5)	0.518
	≥ 60	143(66.2)	6 (54.5)
Abdominal pain	No	106 (49.1)	1 (9.1)	0.011
	Pain	110 (50.9)	10 (90.9)
Fever	No	195 (90.3)	7 (63.6)	0.022
	Fever	21 (9.7)	4 (36.4)
Jaundice	No	199 (92.1)	11 (100.0)	1.000
	Jaundice	17 (7.9)	0 (0.0)
Weight loss	No	201 (93.1)	10 (90.9)	0.561
	Weight loss	15 (6.9)	1 (9.1)
GB stone	No	164 (75.9)	8 (72.7)	0.730
	GB stone	52 (24.1)	3 (27.3)
Hepatitis	No	190 (88.0)	7 (63.6)	0.063
	CHB	21 (9.7)	3 (27.3)
	CHC	5 (2.3)	1 (9.1)
LC	No	183 (84.7)	6 (54.5)	0.022
	LC	33 (15.3)	5 (45.5)
Serum CEA	< 5 ng/mL	123 (56.9)	10 (90.9)	0.029
	≥ 5 ng/mL	93 (43.1)	1 (9.1)
Serum CA19-9	< 37 U/mL	64 (29.6)	6 (54.5)	0.098
	≥ 37 U/mL	152 (70.4)	5 (45.5)
Main mass	Single	145 (67.1)	6 (54.5)	0.513
	Multiple	71 (32.9)	5 (45.5)
Mass size	< 5 cm	90 (41.7)	1 (9.1)	0.054
	≥ 5 cm	126 (58.3)	10 (90.9)
LN metastasis	No	84 (38.9)	1 (9.1)	0.057
	LN meta.	132 (61.1)	10 (90.9)
Distant metastasis	No	140 (64.8)	4 (36.4)	0.104
	Distant meta.	76 (35.2)	7 (63.6)
TNM stage	I or II	76 (35.2)	0 (0.0)	0.018
	III or IV	140 (64.8)	11 (100.0)

CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; LC: Liver cirrhosis; LN: Lymph node.

Table 3 Laboratory findings of the patients with intrahepatic sarcomatoid cholangiocarcinoma

Case	CEA (ng/mL)	CA19-9 (U/mL)	AFP (ng/mL)	PIVKA-II (mAU/mL)	AST (U/L)	ALT (U/L)	TB (mg/dL)	DB (mg/dL)	ALP (U/L)	GGT (U/L)
1	0.74	> 1200.00	131.67	69	25	19	1.0	0.4	387	115
2	1.45	3.38	66.45	16	31	10	0.7	0.2	252	32
3	0.10	3.00	2.54	35	54	96	0.4	0.2	892	137
4	2.35	1809.57	1.73	N/A	42	30	0.9	0.6	1385	N/A
5	1.81	2.33	2.31	20	43	57	1.0	0.6	1520	203
6	12.70	710.38	3.92	N/A	23	39	0.7	0.3	1133	253
7	1.18	12.59	2.70	20	23	16	0.6	0.4	638	224
8	3.15	> 1200.00	1.71	N/A	30	31	1.1	0.6	757	323
9	1.08	< 2.00	1.52	N/A	80	30	0.7	0.5	476	98
10	3.56	599.14	1.02	N/A	37	47	1.1	0.8	804	N/A
11	1.81	5.77	3.02	14	34	36	0.3	0.1	369	35

AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; DB: Direct bilirubin; GGT: Gamma-glutamyl transferase; N/A: Not applicable; PIVKA-II: Protein-induced by vitamin K antagonist-II; TB: Total bilirubin.

Table 4 Imaging findings of the patients with intrahepatic sarcomatoid cholangiocarcinoma

Case	US	CT Non-E	CT arterial	CT portal	CT delayed	Initial radiologic impression
1	Lobulated, heterogeneously hyperechoic	N/A	Thin rim enhancement	Gradual centripetal enhancement	Gradual centripetal enhancement	HCC
2	Lobulated hypoechoic	Ill-defined hypodense	Minimal to mild heterogeneous enhancement	Progressive heterogeneous enhancement	Progressive heterogeneous enhancement	HCC
3	Lobulated, heterogeneously hypoechoic internal hyperechoic	N/A	Non to minimal rim enhancement	Mild irregular rim enhancement	N/A	IHCC
4	Ill-defined hypoechoic	heterogeneously hypodense	Irregular rim enhancement	Gradual centripetal enhancement	N/A	Hepatic abscess
5	Lobulated, heterogenoeusly hypo- and hyper-echoic	N/A	Peripheral enhancement	Gradual centripetal enhancement	Gradual centripetal enhancement	HCC
6	Lobulated hyperechoic	N/A	Irregular rim enhancement	Irregular rim enhancement	N/A	IHCC
7	Lobulated, heterogeneously hypoechoic internal hyperechoic	Ill-defined hypodense	Irregular peripheral enhancement	Gradual centripetal enhancement	Gradual centripetal enhancement	HCC
8	Ill-defined heterogenoeusly hypo- and hyper-echoic	Ill-defined hypodense	Irregular peripheral enhancement	Gradual centripetal enhancement	N/A	IHCC
9	Lobulated, heterogenoeusly hypo- and hyper-echoic	N/A	Irregular peripheral enhancement	Gradual centripetal enhancement	N/A	Lymphoma
10	Lobulated, heterogeneously hyperecmoic	N/A	Minimal rim enhancement	Rim enhancement	N/A	IHCC
11	Well-defined, heterogeneously hypoechoic	Lobulated hypodense	Irregular peripheral enhancement	Irregular peripheral enhancement	N/A	IHCC

CT: Computed tomography; HCC: Hepatocellular carcinoma; IHCC: Intrahepatic cholangiocarcinoma; N/A: Not applicable; Non-E: non-enhanced; US: Ultrasonography.

Table 5 Immunohistochemistry of the patients with intrahepatic sarcomatoid cholangiocarcinoma

Case	Specimen	Positive IHC results	Negative IHC results
1	Needle biopsy	CK19, vimentin	HSA, CD10
2	Needle biopsy	CK, vimentin, CEA, AFP	CK7, CK19, HSA, c-kit, CD117
3	Needle biopsy	CK, CK19, vimentin	CK8, Desmin, EMA, CEA, c-kit, S-100
4	Needle biopsy	CK, CK8, CK19, vimentin, CEA, EMA	HSA, AFP, TTF-1
5	Needle biopsy	CK, CK8, CK19, vimentin, SMA	HSA, CD5, CD68, HMW-CK
6	Needle biopsy	CK7, CK8, CK19, vimentin, CEA	HSA
7	Needle biopsy	CK7, CK8, CK19, vimentin, CD34	HSA, CEA, HMW-CK
8	Needle biopsy	CK19, vimentin, CEA, p53	CD31, CD34
9	Needle biopsy	CK19, vimentin, CEA	CK7, Desmin, HSA, SMA, c-kit, S-100
10	Needle biopsy	CK, CK19, vimentin, CEA	HSA, CD31
11	Needle biopsy	CK7, CK19, vimentin, MUC1	HSA, CD10

AFP: Alpha-fetoprotein; CD: Cluster of differentiation; CEA: Carcinoembryonic antigen; CK: Cytokeratin; EMA: Epithelial membrane antigen; HMW-CK: High molecular weight cytokeratin; HSA: Hepatocyte specific antigen; IHC: Immunohistochemistry; MUC1: Human mucin-1; SMA: Smooth muscle actin; TTF-1: Thyroid transcription factor-1.

Table 6 Treatment and outcome of the patients with intrahepatic sarcomatoid cholangiocarcinoma

Case	Sex	Age	Tumor size (cm)	Number of mass	Stage (TNM)	Treatment	Outcome	F/U duration (d)
1	M	45	7.5	7	IVB	Chemotherapy	Died	47
2	M	67	2.5	1	IVB	Chemotherapy	Died	148
3	M	55	6.5	2	IVA	Chemotherapy	Died	129
4	M	66	10.0	1	IVB	Supportive	Died	20
5	M	56	8.0	1	IVB	Chemotherapy	Died	72
6	F	66	7.5	1	IVB	Chemotherapy	Died	125
7	M	68	6.0	1	IVB	Supportive	Died	19
8	F	55	8.5	3	IVA	Chemotherapy	Died	31
9	M	49	9.5	3	IVA	Chemotherapy	F/U loss	43
10	M	65	9.5	15	IVA	Supportive	Died	14
11	M	61	5.0	1	IVB	viscum album	Survived	379

F/U: Follow-up.