Handan DEREBAŞINLIOĞLU, Hande DEMİR, Sanem NEMMEZİ KARACA

Cilt Kanserlerinin Ayırıcı Tanısında İnflamatuar Belirteçlerin Yeri

Amaç: Bu çalışmanın amacı, cilt kanserinin ayırıcı tanısında ve ilk tanı anında lenf nodu metastazının öngörülmesinde inflamatuar belirteçlerin rolünün belirlenmesidir. Gereç ve YÖntem: Bazal hücreli karsinom, skuamöz hücreli karsinom veya malign melanom nedeniyle ameliyat edilen hastalar retrospektif olarak tarandı. NLR, LMR, PLR, SII ve Plt×NLR hesaplandı. Tümör tipi, ilk tanıda lenf nodu metastazının varlığı, tümör lokalizasyonu ile inflamatuvar ve hematolojik parametreler arasındaki ilişkiler araştırıldı. Tümör lokasyonu, baş boyun ve diğerleri olarak sınıflandırıldı. Bulgular: Çalışmaya toplam 257 hasta dahil edildi. Tümör yerleşimine göre WBC, NLR, PLR, LMR, SII veya Plt×NLR'de istatistiksel olarak anlamlı farklılık saptanmadı. Skuamöz hücreli karsinomalı hastalarda NLR, PRL, SII ve Plt×NLR değerleri bazal hücreli karsinomalı hastalara göre daha yüksekti. PLR düzeyi 180,7 ve üzerinde olan hastalarda ilk tanı anında lenf nodu metastazı riski 10.3 kat daha yüksekti. Plt×NLR 747 ve üzeri olan hastalarda ilk tanıda saptanan lenf nodu metastazı riski 8,9 kat daha fazlaydı. SII 414 ve üzeri olan hastalarda ilk tanıda saptanan lenf nodu metastazı riski 7,1 kat daha yüksekti. Sonuç: İnflamatuvar belirteçler cilt kanserlerinin ayırıcı tanısında ve lenf nodu metastazı riskinin belirlenmesinde yardımcı olabilir. Ancak tümör lokalizasyonuna göre bir farklılık göstermemektedir.

Anahtar Kelimeler:

Bazal hücreli karsinom, skuamöz hücreli karsinom, malign melanom, nötrofil-lenfosit oranı (NLR), lenfosit-monosit oranı (LMR), Sistemik immün-enflamasyon indeksi (SII) trombosit/lenfosit oranı (PLR), Sistemik immün-enflamasyon indeksi (SII) trombosit/lenfosit oranı (PLR)

The Role of Inflammatory Markers in the Differential Diagnosis of Skin Cancers

Aim: The purpose of this study was to evaluate the role of WBC count, NLR, LMR, PLR, Systemic immune-inflammation index (SII) [(platelet count X neutrophil count) \ lymphocyte count] and platelet count (Plt)×NLR in the differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma and to determine the effect of tumor type, prediction of lymph node metastasis at initial diagnosis and location on these inflammatory markers. Material and Method: Patients who underwent surgery for basal cell carcinoma, squamous cell carcinoma, or malignant melanoma were retrospectively screened. NLR, LMR, PLR, SII and Plt×NLR were calculated. Relationships between tumor type, prediction of lymph node metastasis at initial diagnosis, tumor localization and the inflammatory and hematological parameters of interest were investigated. Tumor location was classified as head and neck and others. Results: A total of 257 patients were included in the study. No statistically significant differences in WBC, NLR, PLR, LMR, SII or Plt×NLR were detected according to tumor location. The patients with squamous cell carcinoma had higher NLR, PRL, SII and Plt×NLR values than those with basal cell carcinoma. The risk of lymph node metastasis at the time of initial diagnosis was 10.3 times higher in patients with PLR levels of 180.7 and higher. The risk of lymph node metastasis detected at initial diagnosis was 8.9 times higher in patients with Plt×NLR of 747 and higher. The risk of lymph node metastasis detected at initial diagnosis was 7.1 times higher in patients with SII of 414 and higher. Conclusion: Inflammatory markers seem to be useful in the differential diagnosis of skin cancers and determined the risk of lymph node metastasis. However, it does not differ according to tumor localization.

Keywords:

Basal cell carcinoma, squamous cell carcinoma, malignant melanoma, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), Systemic immune-inflammation index (SII), and platelet to lymphocyte ratio (PLR,

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Diakos CI, Charles KA, McMillan DC et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol 2014;15(11):e493-503.
Altan M, Haberal HB, Akdoğan B et al. Critical prognostic analysis of neutrophil–lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma. Int J Clin Oncol 2017;22:964–71.
Guthrie GJ, Charles KA, Roxburgh CS et al. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 2013;88(1):218-30.
Chen JH, Zhai ET, Yuan YJ et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol 2017;23(34):6261-72.
Petrillo A, Laterza MM, Tirino G et al. Systemic-inflammation-based score can predict prognosis in metastatic gastric cancer patients before first-line chemotherapy. Future Oncol 2018;14(24):2493-505.
Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States; incidence. J Am Acad Dermatol 1994;30(5 Pt 1):774-78.
Baykan H, Benderli CY, Ozyurt K. Roles of White Blood Cells and Subtypes as Inflammatory Markers in Skin Cancer. Asian Pac J Cancer Prev 2015;16(6):2303-6.
Douglas Hanahan D,Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011;4:144(5):646-74.
Diakos CI, Charles KA, McMillan DC, et al. Cancer-related inflammation and treatment effectiveness. Lancet Oncol 2014;15(11):e493-503.
Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol 2015;12:584-96.
Mantovani A, Allavena P, Sica A et al. Cancer-related inflammation. Nature 2008;454(7203):436–44.
Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9(3):162–74.
Ashcroft GS, Yang X, Glick AB et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1999;1(5):260–66.
Li AG, Lu SL, Zhang MX et al. Smad3 knockout mice exhibit a resistance to skin chemical carcinogenesis. Cancer Res 2004;64(21):7836–45.
Mueller MM. Inflammation in epithelial skin tumours: Old stories and new ideas. Eur J Cancer 2006;42(6):735-44.
Cataisson C, Joseloff E, Murillas R et al. Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways. J Immunol 1 2003;171(5):2703-13.
Clements B, Lewis H, McKinstrey S et al. A late, fatal complication of a high energy thermal injury to the scalp. Ann Plast Surg 1995;35(6):650–53.
Kaplan RP. Cancer complicating chronic ulcerative and scarifying mucocutaneous disorders. Adv Dermatol 1987;2:19–46.
Gur E, Neligan PC, Shafir R et al. Squamous cell carcinoma in perineal inflammatory disease. Ann Plast Surg 1997;38(6):653–57.
Yamada T, Suzuki M, Hiraga M et al. Squamous cell carcinoma arising on scars of epidermolysis bullosa acquisita. Br J Dermatol 2005;152(3):588–90.
Kowal-Vern A, Criswell BK. Burn scar neoplasms: a literature review and statistical analysis. Burns 2005;31(4):403–13.
Ozyazgan I, Kontas O. Previous injuries or scars as risk factors for the development of basal cell carcinoma. Scand J Plast Reconstr Surg Hand Surg 2004;38(1):11–15.
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12:253–68.
Gandini S, Ferrucci PF, Botteri E et al. Prognostic significance of hematological profiles in melanoma patients. Int J Cancer 2016;139(7):1618-25.
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer 2016;16:431–46.
Richards DM, Hettinger J, Feuerer M. Monocytes and macrophagesin cancer: development and functions. Cancer Microenviron 2013;6:179–91.
Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011;11:123–34.
Ray-Coquard I, Cropet C, Van Glabbeke M et al. Lymphopeni as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 2009;69:5383–91.
Wade RG, Robinson AV, Lo MCI et al. Ratios as Biomarkers of Survival in Cutaneous Melanoma: A Multicenter Cohort Study. Ann Surg Oncol 2018;25(11):3341-49.
Fang HY, Huang XY, Chien HT et al. Refining the Role of Preoperative C-Reactive Protein by Neutrophil/Lymphocyte Ratio in Oral Cavity Squamous Cell Carcinoma. Laryngoscope 2013;123(11):2690-9.
Cho MS, Bottsford-Miller J, Vasquez HG et al. Platelets increase the proliferation of ovarian cancer cells. Blood 2012;120(24):4869-72.
Khalid A, Wolfram J, Ferrari I et al. Recent advances in discovering the role of CCL5 in metastatic breast cancer. Mini Rev Med Chem 2015;15:1063–72.
Velez J, Enciso LJ, Suarez M et al. Platelets promote mitochondrial uncoupling and resistance to apoptosis in leukemia cells: a novel paradigm for the bone marrow microenvironment. Cancer Microenviron 2014;7:79–90.
Zhang F, Gong W. Prognostic Value of the Platelet-to-Lymphocyte Ratio in Patients With Melanoma: A Meta-Analysis. Front Oncol 2020;28(10):1116.
Kusumanto YH, Dam WA, Hospers GA et al. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003;6(4):283–87.
Azab B, Bhatt VR, Phookan J et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and longterm mortality in breast cancer patients. Ann Surg Oncol 2012;19(1):217–24.
Ding PR, An X, Zhang RX et al. Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer. Int J Colorectal Dis 2010;25(12):1427–33.
McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 2013;39(5):534–40.
Templeton AJ, McNamara MG, Seruga B et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. JNCI J Natl Cancer Inst 2014;106(6):1-11.
Templeton AJ, Ace O, McNamara MG et al. Prognostic role of platelet-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Prev Biomarkers 2014;23:1204–12.
Nishijima TF, Muss HB, Shachar SS et al. Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 2015;41:971–8.
Goto W, Kashiwagi S, Asano Y et al. Predictive value of lymphocyte-tomonocyte ratio in the preoperative setting for progression of patients with breast cancer. BMC Cancer 2018;18(1):1137.
Leontovich AA, Dronca RS, Nevala WK et al. Effect of the lymphocyte-to-monocyte ratio on the clinical outcome of chemotherapy administration in advanced melanoma patients. Melanoma Res 2017;27(1):32-42.
Hieken TJ, Glasgow AE, Enninga EAL et al. Sex-Based Differences in Melanoma Survival in a Contemporary Patient Cohort. J Womens Health (Larchmt) 2020;29(9):1160-7.
Nosrati A, Wei ML. Sex disparities in melanoma outcomes: the role of biology. Arch Biochem Biophys 2014;563:42-50.
Bulliard JL, De Weck D, Fisch T et al. Detailed site distribution of melanoma and sunlight exposure: aetiological patterns from a Swiss series. Ann Oncol 2007;18(4):789-94.
Netscher DT, Spira M. Basal cell carcinoma: an overview of tumor biology and treatment. Plast Reconstr Surg 2004;113:74e-94e.
Youl PH, Janda M, Aitken JF et al. Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice. Br J Dermatol 2011;165(1):35-43.
Larson DL, Larson JD. Head and neck melanoma. Clinics in Plastic Surgery 2010;37(1):73-77.
Garbe C, Büttner P, Bertz J et al. Primary Cutaneous Melanoma Prognostic Classification of Anatomic Location. Cancer 1995;75(10):2492-98.
Cherpelis BS, Marcusen C, Lang PG. Prognostic Factors for Metastasis in Squamous Cell Carcinoma of the Skin. Dermatol Surg 2002;28:268–73.
Schmults CD, Karia PS, Carter JB et al. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol 2013;149(5):541-7.
Scrivener Y, Grosshans E, Cribier B. Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. British Journal of Dermatology 2002;147:41–7.
Piva de Freitas P, Senna CG, Tabai M et al. Metastatic Basal Cell Carcinoma: A Rare Manifestation of a Common Disease. Case Rep Med 2017:8929745.
Brantsch KD, Meisner C, Schönfisch B et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. The Lancet Oncology 2008;9(8):713–20.
Joseph MG, Zulueta WP, Kennedy PJ. Squamous cell carcinoma of the skin of the trunk and limbs: the incidence of metastases and their outcome. ANZ Journal of Surgery 1992;62(9): 697–701.
Voiculescu VM, Lisievici CV, Lupu M et al. Mediators of Inflammation in Topical Therapy of Skin Cancers. Mediators Inflamm 2019;2019:8369690.
Essner R, Lee JH, Wanek LA et al. Contemporary surgical treatment of advanced-stage melanoma. Arch Surg 2004;139(9):961-6.
Ranieri JM, Wagner JD, Wenck S et al. The prognostic importance of sentinel lymph node biopsy in thin melanoma. Ann Surg Oncol 2006;13(7):927-32.
Kalady MF, White RR, Johnson JL et al. Thin Melanomas. Predictive Lethal Characteristics From a 30-Year Clinical Experience. Ann Surg 2003;238(4):528–37.
Sandru A, Voinea S, Panaitescu E et al. Survival rates of patients with metastatic malignant melanoma. J Med Life 2014;7(4):572-6.
Grivennikov SI, Greten FR, Karin M. Immunity, Inflammation, and Cancer. Cell 2010;140:883–99.
Fest J, Ruiter R, Mulder M et al. The systemic immune-inflammation index is associated with an increased risk of incident cancer—A population-based cohort study. Int J Cancer 2020;146(3):692-8.
Yang R, Chang Q, Meng X et al. Prognostic value of Systemic immune-inflammation index in cancer: A meta-analysis. J Cancer 2018;9(18):3295-302.
Hu B, Yang XR, Xu Y et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res 2014;20:6212–22.