ARE THERE ANY VARIATION IN NEUTROPHIL LYMPHOCYTE RATIO , MEAN PLATELET VOLUME AND PLATELET COUNT BETWEEN PAPILLARY THYROID CANCER AND BENIGN NODULAR THYROID DISEASES

Objective: Neutrophil lymphocyte ratio (N/L) and mean platelet (Plt) volume (MPV), the markers of systemic inflammatory response, has been investigated in many cancers, but data for the head and neck cancers and thyroid carcinoma are limited. It had been purposed to study N/L, MPV, and Plt levels in papillary thyroid carcinoma (PTC) as a diagnostic marker. Material and Methods: A total of 104 patients, had undergone ultrasonography guided fine needle aspiration (FNA) and thyroidectomy, for the indicated cases, between April 2010 and August 2013, were enrolled in the study. The laboratory tests, regarding N/L, MPV, and Plt, of the cases had been collected retrospectively. Results: No difference was found between PTC and benign nodular thyroid diseases (BNTD) in terms of age, gender, size of the nodule, N/L, MPV, and Plt (p > 0.05). Conclusion: The preoperative inflammatory hematological parameters, in terms of N/L, MPV, and Plt, may not be useful as a predictive diagnostic marker of the thyroid malignancy, PTC.


INTRODUCTION
Thyroid cancer, the most common endocrine cancer, that has the dramatically increased incidence worldwide in terms of new diagnosis and mortality with the significant change in the papillary histotype (1)(2)(3)(4)(5).The shortage of the clically proven markers in the diag-nosis of thyroid cancers like the other head and neck cancers still sustains the adversity in absolute and definitive preoperative diagnosis in the field of Neck-Endocrine Surgery.Many studies established the augmentation of neutrophil lymphocyte ratio (N/L) and mean platelet (Plt) volume (MPV), the markers of systemic inflammatory response, being related with the progression and survival of the certain types of cancers (6,7).
In the present study, the laboratory tests of the patients that have thyroid nodules have been evaluated retrospectively and the relationship between papillary thyroid cancer (PTC) and the inflammatory hematological parameters including N/L, MPV, and Plt had been investigated.

MATERIAL AND METHODS
A retrospective analysis comprised of the patients that posses the nodular thyroid disease, who had undergone one-endocrine surgeon performed ultrasonography (US) guided fine needle aspiration (FNA) between April 2010 and August 2013.The documents were consisting the complete blood counts and US guided FNA (US-g-FNA) cytologies (FNACs) which had been reported according the guidance of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), a 6-diagnostic-category system which was constituted through multidisciplinary formulation, which was proposed at the National Cancer Institute (NCI) As a result, cases were divided into two groups, benign nodular thyroid diseases (BNTD), diagnosed by the current TBSRTC I Class II as Group 1and PTC whose diagnoses also had been verified histopathologically as Group 2. They were taken into account if the age, gender, size of the tumor had ben correlated to the inflammatory hematological parameters regarding N/L, MPV, and Plt.

The Criteria for Incorporation into the Study
The screening outcome revealed the 104 cases in conformity with the criteria for being incorporated into the study.95 cases with BNTD and 9 cases with PTC had been enrolled the present study between April 2010 and August 2013 by excluding the hematologic disorders, cardiac disorders, autoimmune diseases, inflammatory or infective diseases, endocrinologic diseases and diabetes, the patients with the elevated thyroid antibodies or impaired thyroid function tests, liver diseases, renal failure, recurrent disases, previous or accompanying other malignancies, as well as those who had medical records as to the usage of steroids, anticoagulants, and alcohol along with those with a medical history of hepatitis.

Statistical Analysis
The statistical analysis were performed by using SPSS 23.0 computer program.The Fisher Exact Test was applied for gender parameter.The Mann Whitney U-tests were applied for MPV, N/L and size parameters due to the samples not being obtained from normal population according to Kolmogorov-Simirnov and Shapiro Wilk Normality tests.The Independent sample t-tests were used to detect difference among two groups for age and Plt parameters and p value less than 0.05 was considered as statistically significant.

RESULTS
9 (8.65%) out of 104 cases possesing thyroid nodules (male/female: 15/89, 10.41%/61.8%) had PTC, while 95 (91.35%) had BNTD.It had not been detected any statistically significant difference between the cases with BNTD, Group 1 and cases with PTC, Group 2 in terms of age, gender, size of the nodule, N/L, MPV, and Plt (p > 0.05) (Figure 1a-f).Therefore, according to the statistical test results, there was no difference between PTC and benign thyroid nodules for all the parameters (Table 1

DISCUSSION
As a common clinical problem, the thyroid nodules, reveal the prevalance of approximately 5% in women and 1% in man living in iodine-sufficient areas of the world epidemiologically in palpation, whereas 19%-68% is the detection rate in high resolution US, with higher frequencies in women and elderly (9).The thyroid nodules are important clinically as long as eliminating the thyroid cancer comprising 7%-15% of the cases being based on age, sex, radiation exposure history to head and neck and thorax, particularly during first two decades, family history, and the other factors (15,16).
Differentiated thyroid cancer (DTC), consisting PTC, follicular thyroid carcinoma (FTC), and Hurthle cell carcinoma (HCC), constitutes vast majority, > 90%, of the thyroid cancers (17).In the United States, the yearly incidence of thyroid cancer has nearly tripled from 4.9 per 100,000 in 1975 to 14.3 per 100,000 in 2009 and virtually the entire change has been attributed to an increase in the incidence of papillary thyroid cancer (18,19).One study estimates PTC will being  (20).N/L, known as marker of systemic inflammatory response, have been associated with progression and survival in most kind of cancers (6,7).Chang et al (21) found N/L, Hb, and Plt count beneficial for predicting long-term mortality in cases with nasopharyngeal carcinoma.N/L estimated as a negative indicator for oral cancer (22), breast cancer (23), and pancreatic adenocarcinoma (24).Feng et al (25) reported in a pilot study the elevated levels of N/L in cases with papillary thyroid microcarcinoma (PTmC) and PTC.Hower, N/L was not statistically different the patients with BNTD and PTC, in the present study.Similiar to the present study, Liu et al (26) reported a metanalysis on December 2016 to be able to clarify the undecided association between N/L and DTC.They conducted a systematic meta-analysis based on 7 prospective cohort studies published between 2013 and 2015, to investigate a potential association between N/L and DTC comprising 7349 patients.It was not detected any significant difference in N/R between the patients with benign nodules and PTC aged < 45 years and those aged ³ 45 years, similar to our study.
Larger platelets are more metabolically and enzymatically active than the smaller ones.MPV reflects platelet activity indicating being an important biological variable (26).In a Turkish study, MPV was suggested as a possible biomarker in the diagnosis of PTC and estimator for therapeutic effectiveness in PTC in terms of its attenuated postoperative levels (27).However, we haven't detected significant difference between the groups, BNTD and PTC, in terms of MCV and Plt.

CONCLUSION
The present study lasted approximately three and a half years.However, a retrospective design, a relatively low sample count, not analyzing postoperative values of hematologic parameters and not comparing them with the preoperative ones were the limitations of the present study.

13 Figure 1b -
Figure 1b -The median MPV from PTC and Control group

2 1
Department of Pathology, Giresun University Faculty of Medicine, Giresun, Turkey 2 Division of Endocrine Surgery, Department of General Surgery, Giresun University Faculty of Medicine, Giresun, Turkey

DOI: 10.24125/sanamed.v13i1.209 UDK: 616.441-074:577.175.4
Thyroid Fine Needle Aspiration State of the Art and Science Conference held in Bethesda, Maryland, 2007.TBSRTC is at present the most used and accepted reporting system ).

Table 1 -
The comparison of demographic features and hematological paramaters between the patients with benign nodular thyroid disease and PTCFigure 1a: The median N/L from PTC and Control group