Histopathological diagnosis of microvascular invasion in hepatocellular carcinoma: Is it reliable?

Table 1 Baseline characteristics of the rabbit liver tumor model, n (%)

Variables	Results
Rabbit liver tumor model
Success	37 (92.5)
Failure	3 (7.5)
Rabbit weight (kg), mean ± SD
Before tumor transplanting	2.5 ± 0.4
After successfully modeling	2.8 ± 0.4
Time of tumor growth (day), mean ± SD	20.4 ± 4.0
Tumor location
Left lateral lobe of liver	32 (80.0)
Left medial lobe of liver	5 (12.5)
Mesentery	2 (5.0)
Subcutaneous	1 (2.5)
Intrahepatic tumor number
Single	37 (100.0)
Multiple	0 (0.0)
Intrahepatic tumor size (cm), mean ± SD	1.9 ± 0.5
Microvascular invasion
Positive	30 (81.1)
Negative	7 (18.9)
Concomitant > 1 mm satellite nodule
Yes	9 (30.0)
No	21 (70.0)

Table 2 Performance of protocols A, B, C, D, and three consecutive interval whole-mount slide images at the tumor center for detecting microvascular invasion in 37 specimens, using the overall microvascular invasion detection rate as the reference standard

Metrics	Protocol A	Protocol B	WSI3	Protocol C	Protocol D
Positive rate	0.27 (10/37)	0.43 (16/37)	0.59 (22/37)	0.62 (23/37)	0.68 (25/37)
Accuracy	0.46 (0.42-0.75)	0.62 (0.45-0.77)	0.78 (0.61-0.90)	0.81 (0.64-0.91)	0.86 (0.70-0.95)
Sensitivity	0.33 (0.18-0.53)	0.53 (0.35-0.71)	0.73 (0.54-0.87)	0.77 (0.57-0.89)	0.83 (0.65-0.94)
Specificity	1.00 (0.56-1.00)	1.00 (0.56-1.00)	1.00 (0.56-1.00)	1.00 (0.56-1.00)	1.00 (0.56-1.00)
Positive predictive value	1.00 (0.66-1.00)	1.00 (0.76-1.00)	1.00 (0.82-1.00)	1.00 (0.82-1.00)	1.00 (0.83-1.00)
Negative predictive value	0.26 (0.12-0.47)	0.33 (0.15-0.57)	0.47 (0.22-0.73)	0.50 (0.24-0.76)	0.58 (0.29-0.84)
False negative rate	0.67 (0.47-0.82)	0.47 (0.29-0.65)	0.27 (0.13-0.46)	0.23 (0.11-0.43)	0.17 (0.06-0.35)

WSI₃: Three consecutive interval whole-mount slide images at the tumor center.

Table 3 Performance of protocols A, B, C, D, and three consecutive interval whole-mount slide images at the tumor center for detecting microvascular invasion in 15 specimens, using protocol E as the reference standard

Metrics	Protocol A	Protocol B	WSI3/protocol C/protocol D
Positive rate	0.40 (6/15)	0.53 (8/15)	0.60 (9/15)
Accuracy	0.47 (0.22-0.73)	0.60 (0.33-0.83)	0.67 (0.39-0.87)
Sensitivity	0.43 (0.19-0.70)	0.57 (0.30-0.81)	0.64 (0.36-0.86)
Specificity	1.00 (0.05-1.00)	1.00 (0.05-1.00)	1.00 (0.05-1.00)
Positive predictive value	1.00 (0.52-1.00)	1.00 (0.60-1.00)	1.00 (0.63-1.00)
Negative predictive value	0.11 (0.01-0.49)	0.14 (0.01-0.58)	0.17 (0.01-0.64)
False negative rate	0.57 (0.30-0.81)	0.43 (0.19-0.70)	0.36 (0.14-0.64)

WSI₃: Three consecutive interval whole-mount slide images at the tumor center.

Table 4 Comparisons of the number of microvascular invasion in metastatic distance groups using various sampling protocols, n (%)

MVI metastatic distance groups	Sampling protocol
	A	P value1	B	P value2	C	P value3	D	P value4	E
≤ 1.0 mm	12 (80.0)	0.004	22 (61.1)	< 0.001	64 (59.8)	1.000	64 (51.2)	0.005	118 (29.9)
1.1-3.0 mm	2 (13.3)	0.066	9 (25.0)	0.014	20 (18.7)	0.083	23 (18.4)	0.005	86 (21.8)
3.1-5.0 mm	0 (0.0)	0.083	3 (8.3)	0.041	12 (11.2)	0.102	16 (12.8)	0.006	45 (11.4)
5.1-10.0 mm	1 (6.7)	0.317	2 (5.6)	0.039	10 (9.4)	0.102	14 (11.2)	0.014	74 (18.7)
> 10.0 mm	0 (0.0)	1.000	0 (0.0)	0.317	1 (0.9)	0.066	8 (6.4)	0.008	72 (18.2)

¹The Wilcoxon matched-pairs signed-rank sum test was used to compare A vs B.

²The Wilcoxon matched-pairs signed-rank sum test was used to B vs C.

³The Wilcoxon matched-pairs signed-rank sum test was used to C vs D.

⁴The Mann-Whitney U test was used to compare D vs E.

MVI: Microvascular invasion.