Preoperative Blood Inflammatory Markers for the Differentiation of Uterine Leiomyosarcoma from Leiomyoma

Figures & data

Table 1 Clinical Features and Laboratory Values Between Uterine Leiomyosarcoma and Leiomyoma

Pre - & Postmenopause	LMS, Median (IQR) (n=79)	LM, Median (IQR) (n=257)	P-value
Age (years)	54	44	< 0.001
Postmenopause (%)	46 (58.2)	41 (16.0)	< 0.001
BMI (kg/m^2)	24.65	23.72	0.145
Overweight(≥23kg/m^2)	49 (62.0%)	142 (55.5%)	0.369
WBC (per µL)	6690.0	5805.0	< 0.001
ANC (per μL)	4314.1	3387.6	< 0.001
CRP (mg/dL)	1.00	0.04	< 0.001
LDH (U/L)	425.0	185.5	< 0.001
NLR	2.36	1.91	< 0.001
Premenopause	LMS, Median (IQR) (n=33)	LM, Median (IQR) (n=216)	P-value
BMI (kg/m^2)	23.98	23.53	0.438
Overweight(≥23kg/m^2)	20 (60.6)	116 (54.0)	0.598
WBC (per µL)	6230.0	5770.0	0.141
ANC (per μL)	3970.7	3388.9	0.092
CRP (mg/dL)	0.69	0.04	0.005
LDH (U/L)	387.5	175.0	<0.001
NLR	2.30	1.95	0.089

Note: P-values for comparisons of medians were obtained using the Mann–Whitney-U test.

Abbreviations: LMS, uterine leiomyosarcoma; LM, uterine leiomyoma; IQR, interquartile range; WBC, white blood cell; ANC, absolute neutrophil count; CRP, C-reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil-lymphocyte ratio.

Table 2 Clinical Features and Laboratory Values Between Uterine Leiomyosarcoma, Leiomyoma with Degeneration, and Leiomyoma Without Degeneration

	LMS, Median (IQR) (n=79)	LM, Median (IQR)		P-value
		With Degeneration (n=92)	Without Degeneration (n=165)
Age (years)	54^a	44^b	44^b	< 0.001
Postmenopause (%)	46 (58.2)^a	9 (9.9)^b	32 (19.4)^b	< 0.001
BMI (kg/m^2)	24.65	22.85	23.96	0.055
Overweight(≥23kg/m^2)	49 (62.0%)	44 (48.4%)	98 (59.4%)	0.144
WBC (per µL)	6690.0^a	6190.0^a	5620.0^b	< 0.001
ANC (per μL)	4314.1^a	3701.6^b	3283.5^b	< 0.001
CRP (mg/dL)	1.00^a	0.04^b	0.04^b	< 0.001
LDH (U/L)	425.0^a	196.5^b	166.0^b	< 0.001
NLR	2.36^a	2.00^b	1.90^b	< 0.001

Notes: ^a,bMedians with the same letter (superscript a, b) are not significantly different; P-values for comparisons of medians were obtained using the Kruskal–Wallis test; A post-hoc test (Bonferroni) was applied with pairwise comparison between medians.

Abbreviations: LMS, uterine leiomyosarcoma; LM, uterine leiomyoma; IQR, interquartile range; WBC, white blood cell; ANC, absolute neutrophil count; CRP, C-reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil-lymphocyte ratio.

Table 3 Univariate and Multivariate Analyses for the Discrimination of Variables That Predict Uterine Leiomyosarcoma

	Univariate		Multivariate
	OR (95% CI)	P value	OR (95% CI)	P value
Age (years) (<50 vs ≥50)	5.46 [3.18, 9.38]	<0.001	Adjusted	Adjusted
Menopause (%) (post vs pre)	7.31 [4.18, 12.77]	<0.001	3.40 [1.54, 7.49]	0.002
WBC (per µL) (≤5940 vs >5940)	2.72 [1.59, 4.67]	<0.001	2.09 [1.18, 3.73]	0.012
ANC (per μL) (≤3404 vs >3404)	3.74 [2.04, 6.85]	<0.001	3.17 [1.68, 6.02]	<0.001
CRP (mg/dL) (≤0.195 vs >0.195)	29.50 [8.05, 108.10]	<0.001	21.74 [5.59, 84.62]	<0.001
LDH (U/L) (≤339.5 vs >339.5)	10.27 [4.45, 23.70]	<0.001	10.77 [4.50, 25.76]	<0.001
NLR (≤2.157 vs >2.157)	2.81 [1.64, 4.80]	<0.001	2.58 [1.44, 4.60]	0.001

Note: Results of multiple logistic regression with variables show a P-value less than 0.05 in univariate regression; Multivariate model is adjusted for age.

Abbreviations: OR, odds ratio; CI, confidence interval; WBC, white blood cell; ANC, absolute neutrophil count; CRP, C-reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil–lymphocyte ratio.

Table 4 Predictive Efficacy of Clinical Characteristics and Laboratory Data

	AUC	95% CI	Sensitivity	Specificity	LR+	LR-	PPV	NPV	P-value
Age (years)	0.756	0.694–0.817	0,646	0.750	2.584	0.137	0.443	0.873	<0.001
WBC (per µL)	0.652	0.583–0.720	0.696	0.543	1.523	0.200	0.320	0.853	<0.001
ANC	0.669	0.601–0.737	0.784	0.508	1.593	0.136	0.315	0.890	<0.001
CRP	0.878	0.818–0.939	0.857	0.831	5.071	0.028	0.429	0.975	<0.001
LDH	0.846	0.746–0.945	0.667	0.900	6.670	0.050	0.818	0.800	<0.001
NLR	0.645	0.575–0.715	0.635	0.617	1.658	0.220	0.324	0.854	<0.001
NLR+LDH	0.863	0.746–0.945	0.667	0.900	6.670	0.050	0.818	0.800	0.049
NLR+LDH+Age	0.864	0.761–0.955	0.926	0.700	3.087	0.024	0.676	0.933	0.049

Abbreviations: AUC, area under curve; CI, confidence interval; WBC, white blood cell; ANC, absolute neutrophil count; CRP, C-reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil–lymphocyte ratio; LR+, Positive likelihood ratio; LR-, Negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value.

Table 5 Summary of Recent Studies Using NLR as a Preoperative Diagnostic Marker

Author (Year)	Type of Malignancy	Number of Subjects	Measurement	NLR Cut-off value	Comment
Non-Gynecologic
Zheng et al (2018)	Glioma	750	NLR, LMR	2.25	Glioma vs acoustic neuroma, menigioma
Çolak et al (2019)	Hodgkin lymphoma	26	NLR	5.8	Hodgkin lymphoma vs reactive lymphadenopathy
Adhyatma et al (2019)	Prostate cancer	172	NLR, PLR, PSA	3.08	Prostate cancer vs BPH
Yapar et al (2020)	Enchondroma and low-grade chondrosarcoma.	101	NLR, MLR	2.0	Cartilaginous tumors vs healthy control
Tezol et al (2020)	Lymphoma in children	190	NLR, MLR, PLR, and RDW	3.17	Lymphoma vs reactive lymphadenopathy
Gynecologic
Eo et al (2018)	EOC	229	NLR, LMR, PLR	2.64	Malignancy vs benign ovarian mass
Kim et al (2010)	Uterine sarcoma	34	NLR, CA-125	2.12	Uterine sarcoma vs leiomyoma
Cho et al (2016)	Uterine sarcoma	31	NLR	2.1	Uterine sarcoma vs leiomyoma
Zhang et al (2020)	LMS	45	NLR, LDH, PLT	2.8	Uterine leiomyosarcoma vs leiomyoma
Present study	LMS	79	NLR, CRP, LDH or combination	2.157	Uterine leiomyosarcoma vs leiomyoma

Abbreviations: EOC, epithelial ovarian cancer; NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio; RDW, red cell distribution width; PSA, prostate-specific antigen; CRP, C-reactive protein; LDH, lactate dehydrogenase; LMS, leiomyosarcoma; PLT, platelet.

Figure 1 Receiver operating characteristic (ROC) curves for (A) age at diagnosis, (B) WBC count, (C) absolute neutrophil count (ANC), (D) C-reactive protein (CRP), (E) lactate dehydrogenase (LDH), (F) neutrophil-to-lymphocyte ratio (NLR), (G) LDH+NLR, and (H) LDH+NLR+Age.