Differentiating malignant and benign focal liver lesions in children using CEUS LI-RADS combined with serum alpha-fetoprotein

Table 1 The clinical characteristics of enrolled 60 patients

Characteristics	All Patients (n = 60)	Patients with malignant lesions (n = 20)	Patients with benign lesions (n = 40)	P value2
Age, yr; mean ± SD, (range)	11.0 ± 5.2 (0-18)	9.7 ± 5.4 (0-18)	11.7 ± 5.1 (0-18)	0.98
Gender, n (%)				0.54
Male	26 (43.3)	10 (50.0)	16 (40.0)
Female	34 (56.7)	10 (50.0)	24 (60.0)
AFP level (ng/mL), n (%)				< 0.05
AFP > 20	14 (23.3)	12 (60.0)	2 (5.0)
AFP < 20	46 (76.7)	8 (40.0)	38 (95.0)
High-risk factors1				0.24
High risk for HCC1	14 (23.3)	7 (35.0)	7 (17.5)
No high risk for HCC1	46 (76.7)	13 (75.0)	33 (82.5)

¹High risk for hepatocellular carcinoma (HCC) in focal liver lesions in contrast-enhanced ultrasound liver imaging reporting and data system included cirrhosis, chronic hepatitis B viral infection, and current or prior HCC.

²P values showed whether there were significant differences in age, gender, alpha-fetoprotein level or high-risk factors between the benign and malignant groups.

Note-data are numbers of patients with percentages in parentheses. AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma.

Table 2 Number of included fills with each diagnosis, stratified by reference standard

Diagnosis	All flls (n = 63)	Flls from Patients > 5 yr (n = 53)
Pathologic analysis	2	42
Malignant liver lesions	22	17
HCC	10	10
HB	6	2
Undifferentiated sarcoma	2	1
Non-Hodgkin’s lymphoma	1	1
Neuroendocrine carcinoma	1	1
Desmoplastic small round cell tumor	1	1
Perivascular epithelioid cell tumor	1	1
Benign liver lesions	30	25
FNH	14	12
RN/DN	3	3
Area of granulomatous inflammation	3	3
Adenomatoid hyperplasia	3	3
Infantile hemangioendothelioma	2	0
Liver abscess	1	0
Other benign tumors	3	3
Follow-up < 50% size increase in 12 mo	11	11
Hemangioma	3	3
FNH	3	1
RN/DN	2	2
Other benign tumors	3	3

FLLs: Focal liver lesions; HCC: Hepatocellular carcinoma; HB: Hepatoblastoma; FNH: Focal nodular hyperplasia; DN: Dysplastic nodule; RN: Regenerative nodule.

Table 3 All focal liver lesions in contrast-enhanced ultrasound liver imaging reporting and data system categorization and distribution of elevated alpha-fetoprotein

CEUS LI-RADS	No. of nodules (n = 63)	No. of malignant lesions (n = 22)	No. of benign lesions (n = 41)	AFP > 20 ng/mL (n = 16)
LR-1	4	0	4	0
LR-2	0	0	0	0
LR-3	8	0	8	0
LR-4	23	0	23	2
LR-5	22	18	4	13
LR-M	6	4	2	1

FLLs: Focal liver lesions; CEUS LI-RADS: Focal liver lesions in contrast-enhanced ultrasound liver imaging reporting and data system; AFP: Alpha-fetoprotein.

Table 4 Imaging characteristics of different types of focal liver lesions

Image features	Malignant lesions			Benign lesions
	HCC (n = 10)	HB (n = 6)	Other malignant lesions (n = 6)	FNH (n = 17)	RN/DN (n = 5)	Other benign tumors (n = 18)
Gray-scale echogenicity
Hyperechoic	3	4	5	4	2	9
Hypoechoic	7	2	1	13	3	9
Arterial phase, hyperenhancement
Homogeneous	4	2		9	1	4
Inhomogenous	6	4	5	8		5
Rim			1			2
Peripheral nodular						3
Isoenhancement					2	2
Hypoenhancement					2	2
Late phase
Hyperenhancement				10		5
Isoenhancement				5	5	8
Hypoenhancement	10	6	6	2		5
Washout
< 60 s		1	3			1
Marked, ≤ 120 s			1

Data are numbers of nodules. FLLs: Focal liver lesions; HCC: Hepatocellular carcinoma; HB: Hepatoblastoma; FNH: Focal nodular hyperplasia; DN: Dysplastic nodule; RN: Regenerative nodule.

Table 5 Performance of various diagnostic criteria for differentiating benign and malignant focal liver lesions

Diagnostic criteria	Sensitivity (%)	Specificity (%)	Accuracy (%)	AUC
Criterion I	100.0 (84.6-100.0)	29.3 (16.1-45.5)	54.0 (40.9-66.6)	0.646 (0.516-0.763)
Criterion II	63.6 (40.7-82.8)	95.1 (83.5-99.4)	84.1 (72.7-92.1)	0.794 (0.673-0.885)
Criterion III	100.0 (84.6-100.0)	80.5 (65.1-91.2)	87.3 (76.5-94.4)	0.902 (0.801-0.963)

Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated alpha-fetoprotein (AFP, ≥ 20 ng/mL) as malignancies; criterion III took LR-4 lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. AUC: Area under the curve.

Table 6 Comparison of different criteria on indicators of diagnostic performance

P value	Sensitivity	Specificity	Accuracy	AUC
Criterion I vs criterion II	< 0.017	< 0.0001	< 0.017	> 0.017
Criterion I vs criterion III	-	< 0.0001	< 0.0001	< 0.0001
Criterion II vs criterion III	< 0.017	> 0.017	> 0.05	> 0.05

Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated alpha-fetoprotein (AFP, ≥ 20 ng/mL) as malignancies; criterion III took LR-4 lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. AUC: Area under the curve.