|Year : 2022 | Volume
| Issue : 2 | Page : 155-159
The role of neutrophil to lymphocyte and platelet to lymphocyte ratios in diagnosing thyroid nodule
Haider Salim Mihson, Ayad Khani Maikhan, Ali Rodan Shuwelif
Department of Surgery, Al-Kindy Teaching Hospital, Baghdad, Iraq
|Date of Submission||16-Sep-2022|
|Date of Decision||06-Oct-2022|
|Date of Acceptance||21-Oct-2022|
|Date of Web Publication||2-Jan-2023|
Dr. Ali Rodan Shuwelif
Al-Kindy Teaching Hospital, Palestine Street, Baghdad
Source of Support: None, Conflict of Interest: None
Background: Thyroid nodule is a common clinical finding and may be associated with a 5%–7% risk for malignancy. Methods for the detection of malignancy had their own drawbacks, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may give a promising result to solve this dilemma. The Aim of the Study: This study aims to evaluate NLR and PLR as predictors of malignancy in solitary thyroid nodules. Also, to estimate their effect on tumor size, lymph node metastasis, and extrathyroidal extension. Patient and Methods: Prospective cohort study conducted at Major Teaching Hospital over a period of 1 year. Patients with solitary thyroid nodules were included in the study and according to histopathological results divided into two groups (A: Malignant and B: Benign), blood samples were drawn from participants, and measurement of lymphocyte, neutrophil, platelet, NLR, and PLR was done. Results: Both NLR and PLR were higher in cases of malignancy with a cutoff point for NLR >2.9 associated with 84.8% sensitivity (SN) and 71.4% specificity (SP), while PLR >140.15 associated with 87.9% SN and 71.4% SP. High NLR is further associated with larger tumor size. Conclusion: Both NLR and PLR are good predictors of malignancy of thyroid nodules. NLR of more than 2.9 is associated with larger-size tumors.
Keywords: Benign thyroid nodules, malignant thyroid nodules, Neutrophil–to-lymphocyte ratio, platelet-to-lymphocyte ratio
|How to cite this article:|
Mihson HS, Maikhan AK, Shuwelif AR. The role of neutrophil to lymphocyte and platelet to lymphocyte ratios in diagnosing thyroid nodule. Mustansiriya Med J 2022;21:155-9
|How to cite this URL:|
Mihson HS, Maikhan AK, Shuwelif AR. The role of neutrophil to lymphocyte and platelet to lymphocyte ratios in diagnosing thyroid nodule. Mustansiriya Med J [serial online] 2022 [cited 2023 Jun 4];21:155-9. Available from: https://www.mmjonweb.org/text.asp?2022/21/2/155/366635
| Introduction|| |
Newly discovered solitary thyroid nodule was increasing in rate recently with detection rate may reach 65%. Yet only 5%–7% risk of being malignant, methods of detection of malignancy mostly invasive (fine-needle aspiration cytology [FNAC] or lobectomy), yet ultrasound had proved to be useful in some instances but also lacks specificity (SP). The result of FNAC is diagnostic in cases of papillary thyroid cancer but still class 3 Bethesda further workup (in the form of genetic testing or lobectomy) proved to be mandatory. The pathology behind thyroid malignancy may be linked to the inflammatory process as described by previous studies,, these results take attention to investigate the level of inflammatory markers to aid in diagnosing malignancy in thyroid nodules.,, The widely available easily performed complete blood count gives good predictors of malignancy in the form of mean platelet volume, and red blood cell distribution width. While, the new hematological parameters neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) proved to be of diagnostic value in many inflammatory and autoimmune conditions (inflammatory bowel disease and thyroiditis) and recently many malignancies such as breast cancer, lung cancer, gastric cancer, and many other diseases. Although NLR and PLR had been studied by previous researchers, no clear estimation for sensitivity (SN), and SP at a specified cutoff point was found.
The aim of the study
The aim of the study is to evaluate NLR and PLR as predictors of malignancy in a solitary thyroid nodule. Also, to estimate their relationship with tumor size, lymph node (LN) metastasis, and extrathyroidal extension.
| Patients and Methods|| |
A prospective cohort study was conducted at a major teaching hospital over a period extended over 1 year (March 1, 2021– March 1, 2022). The study included all euthyroid patients diagnosed to have solitary thyroid nodules and would be subject to lobectomy, or total thyroidectomy (cases were chosen for surgery if they have Bethesda class 3, 4, or 5). Patients with medical comorbidity or chronic drug users, and patients with thyroiditis, or abnormal thyroid function test were excluded from the study. All participants were informed about the nature of the study and informed consent was obtained. Data collected from participants include age, gender, previous history of malignancy, or chronic medical conditions for identification of exclusion criteria. Before induction of anesthesia, 1 ml of venous blood was drawn and kept in an EDTA tube for measuring hematological parameters (NLR and PLR) using ABX Micros ES 60 hematology analyzer (Horiba, France). All participants undergo ultrasound examination of the neck to assess for LN enlargement, and the size of thyroid nodule enlarged LN s undergoing FNAC. Patients were subjected to surgery (lobectomy or thyroidectomy) and the thyroid samples were sent for histopathological study (HP), the information gathered from the HP report were the type of nodule (benign or malignant), size, and extrathyroidal extension. According to the HP results, the patients have divided into two groups group A were HP showed malignancy, and group B were HP showed benign nodules.
The study proposal was reviewed and accepted by the scientific committee of the same hospital.
Data were entered into IBM– SPSS V26 (IBM Corporation, Armonk, NY, USA) for statistical analysis, and data were presented in the form of counts, percentages, mean, and standard deviation appropriate. Chi-square, Fisher's exact test, and student t-test were used as applicable. Predictive abilities were checked using the receiver operator characteristic curve (ROC).
| Results|| |
Total cases enrolled in the study was 82 cases, and according to the HP study, 33 cases (40.2%) were diagnosed as malignant thyroid nodule (Group A), and 49 cases (59.8%) were diagnosed as benign thyroid nodule (Group B). Group A included 3 cases (3.6%) of follicular thyroid cancer, 1 case (1.2%) had anaplastic thyroid cancer and 29 case (35.4%) with papillary thyroid cancer. The HP of thyroid specimen also showed that five cases had extrathyroidal extension, and ultrasound showed six cases to have enlarged LN (the FNAC of all cases showed metastatic papillary thyroid cancer).
Regarding age, gender, neutrophil count, and platelet counts there was no significant difference between the two groups.
Lymphocyte count was significantly lower in cases of malignancy than in benign cases. Higher NLR and PLR were found in cases of thyroid malignancy and these results were significantly different from benign thyroid nodules [Table 1].
|Table 1: The distribution of study variables according to the diagnostic groups|
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After the application of ROC curve analysis [Figure 1] and [Figure 2], predictive abilities of NLR and PLR were obtained as explained in [Table 2].
|Figure 1: ROC curve for NLR. ROC: Operator characteristic curve, NLR: Neutrophil-to-lymphocyte ratio|
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|Figure 2: ROC curve for PLR. ROC: Operator characteristic curve, PLR: Platelet-to-lymphocyte ratio|
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|Table 2: Predictive ability of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio|
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According to the cutoff pointes, comparison of the characteristic of tumor showed that NLR more than 2.9 was associated with mean tumor size 2.4 ± 0.71 cm. LN and extrathyroidal extension of the tumor involvement were not different regarding NLR. While all the three-tumor characteristic were not different regarding PLR. [Table 3] shows the tumor characteristics according to the cutoff points of both NLR and PLR.
|Table 3: Relationship between neutrophil-to-lymphocyte ratio and platelet-to -lymphocyte ratio with tumor size, lymph node status, and extrathyroidal extension|
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| Discussion|| |
The widely available use of thyroid FNAC fall into the trap of over-diagnosing thyroid malignancy with consequential increased rate of thyroid surgery., This concept raises a red flag to investigate another predictor of malignancy in addition to FNAC.
The current study showed no difference in regard to the age of presentation of the cases, similar result found by Ceylan et al. and Offi et al. Although some studies showed that old age patients would be more prone for the risk of malignant thyroid nodules and also increased risk for aggressive form of malignancy as suggested by Deng et al. These differences in the result may attributed to the small sample size used in the current study.
There was no difference between the two groups in regard to gender, similar results also found by Ceylan et al. and Offi et al., while Bessey et al. in their large study (n = 3730) found that thyroid disorders were more common in females but malignancy rate were higher in male. Du et al. also found that age-standardized incidence of thyroid cancer was higher in males than females. This difference in the results may attributed to the large sample size of these studies in comparison to the current study (only 15 males were included in this study), thus increase in the likelihood of type II error.
Lymphocyte count was lower in cases of thyroid malignancy than benign, similar result found by Offi et al. Neutrophil count was not different statistically similar result found by Offi et al., Liu et al. The mechanism by which malignancy associated with lymphopenia still under investigation, this lymphopenia was found of poor prognosis in many malignancies as found by Sawa et al. in their study that conducted on patients with breast cancer, and in the study conducted by Ray-Coquard et al. who included different types of carcinomas, sarcomas, and lymphomas and found that lymphopenia is a poor prognostic factor for these types of malignancies.
This study showed that neutrophil count was not different between the two groups. Similarly, Sit et al. found that no significant difference in the neutrophil count between benign and malignant thyroid nodules. This result highlights the unformal changes in the neutrophile count in thyroid nodules, but it is important to note that the high neutrophile count should be associated with lymphopenia for the increase the risk of malignancy, as neutrophil act as an escort for malignant cell and involved in the progression of cell cycle as found by Szczerba et al.
Platelet count was not different statistically in this study, Offi et al., and Martin et al. found similar result.
NLR was higher in cases of malignant thyroid nodule, with level of NLR more than 2.9 the SN for detecting malignancy was 84.8% and SP of 71.4%, with relative risk for the malignancy was 2.97 time those with NLR <2.9.
This result was supported by studies conducted by Ozmen et al., Ceylan et al. with an estimated cut-off point of 1.92 but they did not estimate the predictive ability in their studies, Gong et al. also found a significant difference with cut-off point of 2 again no estimation for predictive ability, Ozmen et al. applied ROC curve analysis but only estimated the area under the curve (AUC) to be 0.831, a result comparable to our result (in this study AUC was 0.885).
NLR highlights the effect of the proinflammatory nature of the thyroid malignancy, as it was found by Zhang et al. that malignant cells tend to activate neutrophil through multiple interleukins and tumor necrosis factors, this lead to the promotion of malignant cells and increased the ability of cell migration.
On the other hand Offi et al. found that NLR was not different between cases of benign and malignant thyroid nodules, this result may be explained by the type of nodule included in their study (only Bethesda class 3: Follicular lesion of undetermined significance, or atypia of undetermined significance), while in the current study class 3, 4, and 5 were included.
PLR was higher in cases of malignant thyroid nodule, with level of PLR more than 140.15 the SN for detecting malignancy was 87.9% and SP of 71.4%, with relative risk for the malignancy was 3.08 time those with PLR <140.15.
Offi et al. found a significant difference in the level of PLR in cases of Bethesda 3 between benign and malignant thyroid nodules, with cutoff point more than 121.665 were associated with 69.5% SN and 48.1% SP. This variation of SN and SP may be attributed to inclusion of cases of Bethesda 3, 4, and 5 in the current study that gives wider range for PLR measurement than in their study.
The malignant cells tend to activate both the inflammatory cells and platelets, the inflammatory cells additionally activate platelet by release of chemoattractant for platelets, that lead to serial conformational changes and activation of the platelets, the ratio between inflammatory cells to platelets reflect the abnormality that occurred in malignancy, as higher ratio in malignant than in benign nodule reflect the additional activation of platelet (mediated by tumor cells) rather than the usual activation by inflammatory cells alone.
Regarding tumor characteristics tumor size was larger in cases of NLR more than 2.9 this result was supported by the results found by Ceylan et al. who studied the relationship of NLR with tumor size and found that NLR higher than 1.92 was associated with mean tumor size of 2.79 ± 1.48 cm and this result may mark inflammatory process in the behavior of these tumors. Liu et al. also found significant correlation of the tumor size with NLR. Gong et al. found that mean tumor size was larger in cases of NLR more than 2. On the other hand, Kim et al. found no difference in regard to tumor size but they predefined the size into two groups <1 and more than 1 cm this result making room for information bias.
The PLR was not different regarding tumor size similar result found by Ceylan et al.
LN involvement was not different in regard to the levels of both NLR and PLR similar result found by Ceylan et al., and Kim et al.
Only five cases had extrathyroidal extension in the current study, no significant difference in regard both NLR and PLR was found. Kim et al. (n = 1066) also found no significant difference in their study. While Ceylan et al. (n = 201), found a significant difference in the level of NLR but no difference in PLR. This variation may be attributed to the samples size of these studies.
Limitation of the study was the small sample size, also the unavailability of genetic testing as all cases subjected for diagnostic lobectomy or thyroidectomy, that it could be avoided by such study. The other limitation was the difficulty in follow-up of the patients, as our center does not have a specialized oncologist, so we had to refer the patient to other hospitals, this lead to difficult follow-up and inability to estimate the effect of these parameters on survival of the patients.
| Conclusion|| |
Both NLR and PLR are good predictors of malignancy of thyroid nodule. NLR more than 2.9 is associated with larger-size tumors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]