The Difference Platelet Lymphocyte Ratio and Thrombocyte Volume between Benign Compared to Carcinoma Thyroid Gland

Fine Needle Aspiration (FNA) is an early diagnostic tool in thyroid cancer screening and helps to avoid unnecessary surgery. FNA has good sensitivity and specificity for thyroid cancer, with 84% 93% for sensitivity and 75% 99% for specificity. There are around 15% -30% of FNA results that are uncertain. Since a biopsy cannot be performed on the thyroid nodule to determine a malignancy, another modality of examination is needed [3].


Introduction
Among adults, thyroid nodules occur in 19-67%, while the incidence is higher in women and the elderly, but only 5-15% are in the form of thyroid cancer [1]. Thyroid nodules are a common condition and their clinical importance is to distinguish malignancy (4.0-6.5% of all thyroid nodules), evaluate the functional status of the nodule and whether it creates suppression symptoms [2].
Fine Needle Aspiration (FNA) is an early diagnostic tool in thyroid cancer screening and helps to avoid unnecessary surgery.
FNA has good sensitivity and specificity for thyroid cancer, with 84% -93% for sensitivity and 75% -99% for specificity. There are around 15% -30% of FNA results that are uncertain. Since a biopsy cannot be performed on the thyroid nodule to determine a malignancy, another modality of examination is needed [3].

Various inflammatory cell mediators and effectors are important
constituents of the local tumor environment. An oncogenic change will create an inflammatory microenvironment which will then stimulate further tumor formation. The inflammation works in the process of proliferation and survival of malignant cells, trigger the occurrence of angiogenesis and metastasis, damaging the adaptive immune response, and changing the response to various hormones and chemotherapeutic agents [4].
The inflammatory response is triggered by circulating cytokines and chemokines, which are released by malignant cells.
As a result, systemic changes such as neutrophilia, thrombocytosis and lymphocytopenia occur. Several investigations have shown that platelets not only support the occurrence of primary tumor cell growth via angiogenesis but also are associated with tumor metastasis through an immune system avoidance mechanism and inhibition of the lysis of tumor cells by natural killer cells [5].
Systemic inflammation due to cancer causes the expression of several inhibiting mediators, especially Interluekin-10 (IL- 10) and Transforming Growth Factor-β (TGF-β). This response results in immunosuppressive effects which then cause lymphopenia and lymphocyte dysfunction [6].
Average Platelet Volume (APV) is the initial indicator of platelet activation, which shows the average platelet size that reflects average platelet production. Relatively large and new platelets are more reactive and produce more thrombogenic factors [7,8].
The Platelet-Lymphocyte Ratio (PLR) and APV in thyroid nodules is expected to help predict the risk of malignancy, which can aid in the selection of cases for surgery or the decision to treat only conservatively. Currently, biocellular markers can be used to help determine whether thyroid nodules are benign or malignant and thus affect subsequent management [1,9]. Cell proliferation alone cannot cause cancer, but continuous cell proliferation in an environment rich in inflammatory cells, growth factors, activated stroma, and agents that cause damage to Deoxyribonucleic Acid (DNA), will obviously strengthen and/or trigger the risk of malignant neoplasms. Proliferative cells that maintain conditions of DNA damage and/or mutagenic damage (for example, cells capable of initiating themselves) will continue to multiply in a microenvironment rich in inflammatory cells and growth factors that support their growth [10].
However, this examination modality is not available in all hospitals, so researchers identified other modalities that could be used to predict the risk of malignancy in thyroid nodules, namely PLR and PV examinations. In addition, PLR and PV can also confirm benign FNA results in thyroid tests that have false negative values from 2% to 10% [3]. This study aimed to determine the difference in mean Platelet-Lymphocyte Ratio (PLR) and mean Platelet Volume (PV) between malignant thyroid tumors compared to benign thyroid nodules.

Methods
This study used a case-control design. The study was conducted   This difference was statistically significant (p = 0.032).

Discussion
In this study thyroid nodules were more common in women (87.5%) than in men (12.5%). The youngest age in this study was 16 years and the oldest 78 years out of 72 cases of thyroid nodules (Table 1). These results are consistent with previous studies that found thyroid nodules are more common in women and their frequency increases with age, lack of iodine consumption and radiation exposure [11]. Another study showed that the incidence of thyroid cancer is around 3-4 times higher in women [12].
Estrogen is thought to be associated with an increased incidence of thyroid nodules and thyroid cancer. Thyroid tissue expresses es-  This result is in accordance with the incidence of malignancy cases which increases with age. Most of these tumors occur in the 3rd to 6th decades of life (Katoh, 2015). This pattern is presumably possible because of changes in normal thyroid tissue and a decrease in the immune system that is in line with increasing age [14].
Thyroid cancer mainly originates from follicular cells with 3 main types: namely, papillary thyroid carcinoma, follicular thyroid carcinoma and anaplastic thyroid carcinoma. Papillary thyroid carcinoma is the most common type with 85-90% of all cases of thyroid malignancy followed by follicular thyroid carcinoma in 5-10% of cases [12]. Thyroid nodules can be caused by a variety Another study reported that there was statistically significant difference of neutrophil/lymphocyte ratio and platelet-lymphocyte ratio between benign and malignant thyroid especially in multifocal tumours [15][16][17]. Others study found that platelets contribute to tumor growth, invasion and angiogenesis. Platelets protect tumor cells from destruction by NK cells, thereby facilitating metastasis [18,19]. Another study reported that there is no significant relationship between papillary thyroid cancer and inflammatory hematological parameters including the eutrophil/ lymphocyte (N/L) ratio and Mean Platelet Volume (MPV) [20], but the other study obtained that the Neutrophil/Lymphocyte Ratio (NLR) is a simple index of systemic inflammatory response and has been shown to be a prognostic indicator in some types of cancer [21]. On the contrary, there is plenty of evidence to suggest that endothelial tumors and cell are influenced by VEGF, growth factors, secretion of interleukins secreted by platelets. Platelets play an important role in the metabolism of cancer pathogenesis with its angiogenic, metastatic and proteolytic activities [22].

Conclusion
Based on the results of this study, it can be concluded that there are statistically significant differences in the mean ratio of platelet lymphocytes and mean platelet volume between benign thyroid nodules compare to malignant thyroid nodules.