Yonsei Med J.  2017 Mar;58(2):388-394. 10.3349/ymj.2017.58.2.388.

Preoperative Lymphocyte-Monocyte Ratio Ameliorates the Accuracy of Differential Diagnosis in Non-Metastatic Infiltrative Renal Masses

• Han JH
• Yoon YE
• Kim SY
• Cho YI
• Rha KH
• Choi YD
• Han WK

• KMID: 2427128
• DOI: http://doi.org/10.3349/ymj.2017.58.2.388

Abstract

PURPOSE
Distinguishing infiltrative renal cell carcinoma (RCC) from transitional cell carcinoma (TCC) is a challenging issue due to their radiologic similarities. We evaluated systemic inflammatory biomarkers as parameters for distinguishing tumor types.
MATERIALS AND METHODS
A computerized search of medical records from November 2005 to October 2015 identified 116 patients with infiltrative renal masses who were difficult to diagnose confirmatively in radiological study. We investigated the diagnostic efficacy among these patients with their preoperative absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), absolute monocyte counts (AMC), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR).
RESULTS
The infiltrative RCC group demonstrated significantly lower ALC {1449/µL (1140-1896), median [interquartile range (IQR)]} than the TCC group [1860/µL (1433-2342), p=0.016]. LMR [median (IQR)] also was lower in the infiltrative RCC group [2.98 (2.32-4.14) vs. TCC group 4.10 (2.86-6.09); p=0.011]. In subgroup analysis, non-metastatic infiltrative RCC showed lower ALC and LMR and higher NLR than non-metastatic TCC. Within non-metastatic infiltrative renal masses, multivariate logistic regression analysis revealed that younger patient age and lower LMR were associated with infiltrative RCC [odds ratios (OR) 0.874, p=0.024 and OR 0.461, p=0.048, respectively]. Receiver operating characteristic curve analysis showed that younger age and lower LMR were highly predictive of non-metastatic RCC (area under the curve=0.919, p<0.001).
CONCLUSION
Age and LMR were significantly different between patients with infiltrative renal mass. These are potential markers for distinguishing between infiltrative RCC and TCC without metastasis.

Keyword

Infiltration; renal cell carcinoma; transitional cell carcinoma; lymphocyte; monocyte

MeSH Terms

Adult
Age Factors
Aged
Biomarkers, Tumor/*blood
Carcinoma, Renal Cell/*diagnosis/pathology/secondary
Carcinoma, Transitional Cell/*diagnosis/pathology/secondary
Diagnosis, Differential
Female
Humans
Kidney Neoplasms/*diagnosis/pathology
Leukocyte Count
Lymphocyte Count
*Lymphocytes
Male
Middle Aged
*Monocytes
Neutrophils
Prognosis
ROC Curve
Retrospective Studies
Biomarkers, Tumor

Figure

• 

  Fig. 1 (A and B) Pathologically proven infiltrative renal cell carcinoma and transitional cell carcinoma in preoperative multi-detector computed tomography. (C and D) Cross sections of the pathologic specimens of each tumor after surgical resection.

Reference

1. Pickhardt PJ, Lonergan GJ, Davis CJ Jr, Kashitani N, Wagner BJ. From the archives of the AFIP. Infiltrative renal lesions: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographics. 2000; 20:215–243.

2. Raza SA, Sohaib SA, Sahdev A, Bharwani N, Heenan S, Verma H, et al. Centrally infiltrating renal masses on CT: differentiating intrarenal transitional cell carcinoma from centrally located renal cell carcinoma. AJR Am J Roentgenol. 2012; 198:846–853.

3. Bata P, Tarnoki DL, Tarnoki AD, Novak PK, Gyebnar J, Kekesi D, et al. Transitional cell and clear cell renal carcinoma: differentiation of distinct histological types with multiphase CT. Acta Radiol. 2014; 55:1112–1119.

4. Sheir KZ, El-Azab M, Mosbah A, El-Baz M, Shaaban AA. Differentiation of renal cell carcinoma subtypes by multislice computerized tomography. J Urol. 2005; 174:451–455.

5. Li Y, Ding YU, Chen D, Yu Z, Gui Y, Yang S, et al. Renal cell carcinoma growing into the renal pelvis and mimicking transitional cell carcinoma: a case report and literature review. Oncol Lett. 2015; 9:1869–1872.

6. Saroha S, Uzzo RG, Plimack ER, Ruth K, Al-Saleem T. Lymphopenia is an independent predictor of inferior outcome in clear cell renal carcinoma. J Urol. 2013; 189:454–461.

7. Donskov F, Hokland M, Marcussen N, Torp Madsen HH, von der Maase H. Monocytes and neutrophils as ‘bad guys’ for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial. Br J Cancer. 2006; 94:218–226.

8. Mehrazin R, Uzzo RG, Kutikov A, Ruth K, Tomaszewski JJ, Dulaimi E, et al. Lymphopenia is an independent predictor of inferior outcome in papillary renal cell carcinoma. Urol Oncol. 2015; 33:388.e19–388.e25.

9. Hutterer GC, Stoeckigt C, Stojakovic T, Jesche J, Eberhard K, Pummer K, et al. Low preoperative lymphocyte-monocyte ratio (LMR) represents a potentially poor prognostic factor in nonmetastatic clear cell renal cell carcinoma. Urol Oncol. 2014; 32:1041–1048.

10. Park YH, Ku JH, Kwak C, Kim HH. Post-treatment neutrophil-to-lymphocyte ratio in predicting prognosis in patients with metastatic clear cell renal cell carcinoma receiving sunitinib as first line therapy. Springerplus. 2014; 3:243.

11. Keskin S, Keskin Z, Taskapu HH, Kalkan H, Kaynar M, Poyraz N, et al. Prognostic value of preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and multiphasic renal tomography findings in histological subtypes of renal cell carcinoma. BMC Urol. 2014; 14:95.

12. Hu K, Lou L, Ye J, Zhang S. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open. 2015; 5:e006404.

13. Wen RM, Zhang YJ, Ma S, Xu YL, Chen YS, Li HL, et al. Preoperative neutrophil to lymphocyte ratio as a prognostic factor in patients with non-metastatic renal cell carcinoma. Asian Pac J Cancer Prev. 2015; 16:3703–3708.

14. Pichler M, Hutterer GC, Stoeckigt C, Chromecki TF, Stojakovic T, Golbeck S, et al. Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer. 2013; 108:901–907.

15. Santoni M, De Giorgi U, Iacovelli R, Conti A, Burattini L, Rossi L, et al. Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma. Br J Cancer. 2013; 109:1755–1759.

16. Ohno Y, Nakashima J, Ohori M, Hatano T, Tachibana M. Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of recurrence in patients with nonmetastatic renal cell carcinoma. J Urol. 2010; 184:873–878.

17. Ohno Y, Nakashima J, Ohori M, Gondo T, Hatano T, Tachibana M. Followup of neutrophil-to-lymphocyte ratio and recurrence of clear cell renal cell carcinoma. J Urol. 2012; 187:411–417.

18. de Martino M, Pantuck AJ, Hofbauer S, Waldert M, Shariat SF, Belldegrun AS, et al. Prognostic impact of preoperative neutrophil-to-lymphocyte ratio in localized nonclear cell renal cell carcinoma. J Urol. 2013; 190:1999–2004.

19. Viers BR, Houston Thompson R, Boorjian SA, Lohse CM, Leibovich BC, Tollefson MK. Preoperative neutrophil-lymphocyte ratio predicts death among patients with localized clear cell renal carcinoma undergoing nephrectomy. Urol Oncol. 2014; 32:1277–1284.

20. Riemann D, Hase S, Fischer K, Seliger B. Granulocyte-to-dendritic cell-ratio as marker for the immune monitoring in patients with renal cell carcinoma. Clin Transl Med. 2014; 3:13.

21. Fox P, Hudson M, Brown C, Lord S, Gebski V, De Souza P, et al. Markers of systemic inflammation predict survival in patients with advanced renal cell cancer. Br J Cancer. 2013; 109:147–153.

22. Lucca I, de Martino M, Hofbauer SL, Zamani N, Shariat SF, Klatte T. Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma. World J Urol. 2015; 33:2045–2052.

23. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454:436–444.

24. Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006; 25:315–322.

25. Frankenberger B, Noessner E, Schendel DJ. Immune suppression in renal cell carcinoma. Semin Cancer Biol. 2007; 17:330–343.

26. Chang Y, An H, Xu L, Zhu Y, Yang Y, Lin Z, et al. Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma. Br J Cancer. 2015; 113:626–633.

27. Chang Y, Fu Q, Xu L, Zhou L, Liu Z, Yang Y, et al. Prognostic value of preoperative lymphocyte to monocyte ratio in patients with nonmetastatic clear cell renal cell carcinoma. Tumour Biol. 2016; 37:4613–4620.

28. Gu L, Ma X, Wang L, Li H, Chen L, Li X, et al. Prognostic value of a systemic inflammatory response index in metastatic renal cell carcinoma and construction of a predictive model. Oncotarget. 2016; 07. 16. [Epub]. DOI: 10.18632/oncotarget.10626.

29. Xia WK, Wu X, Yu TH, Wu Y, Yao XJ, Hu H. Prognostic significance of lymphocyte-to-monocyte ratio and CRP in patients with nonmetastatic clear cell renal cell carcinoma: a retrospective multicenter analysis. Onco Targets Ther. 2016; 9:2759–2767.

30. Hutterer GC, Sobolev N, Ehrlich GC, Gutschi T, Stojakovic T, Mannweiler S, et al. Pretreatment lymphocyte-monocyte ratio as a potential prognostic factor in a cohort of patients with upper tract urothelial carcinoma. J Clin Pathol. 2015; 68:351–355.

31. Luo HL, Chen YT, Chuang YC, Cheng YT, Lee WC, Kang CH, et al. Subclassification of upper urinary tract urothelial carcinoma by the neutrophil-to-lymphocyte ratio (NLR) improves prediction of oncological outcome. BJU Int. 2014; 113:E144–E149.

32. Dalpiaz O, Ehrlich GC, Mannweiler S, Hernández JM, Gerger A, Stojakovic T, et al. Validation of pretreatment neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma. BJU Int. 2014; 114:334–339.

33. Dalpiaz O, Pichler M, Mannweiler S, Martín Hernández JM, Stojakovic T, Pummer K, et al. Validation of the pretreatment derived neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma. Br J Cancer. 2014; 110:2531–2536.

34. Teng JJ, Zhang J, Zhang TY, Zhang S, Li BS. Prognostic value of peripheral blood lymphocyte-to-monocyte ratio in patients with solid tumors: a meta-analysis. Onco Targets Ther. 2016; 9:37–47.