MEAN PLATELET VOLUME: AN OVERLOOKED HERALD OF MALIGNANT THYROID NODULES.

Physicians and surgeons pay much attention to evaluating thyroid nodules due to the malignant potential of these growths. Inflammation has a crucial role in the development of cancer. Increase in the mean platelet volume (MPV) has been described in various inflammatory conditions. Since some of thyroid nodules are malignant, we aimed to compare MPV values between patients with malignant and benign thyroid nodules after precise pathologic diagnosis. We retrospectively analyzed hemograms of patients having undergone thyroid surgery for thyroid nodule between January 2013 and January 2015, and compared them to those recorded in healthy subjects. MPV was higher in the malignant thyroid nodule group than in the benign nodule group (9.1±1 fL vs. 7.8±0.8 fL). The difference was statistically significant (p<0.001). Increased MPV should be considered as an assistive diagnostic tool in differentiating malignant and benign thyroid nodules. However, further prospective studies are required to confirm its usefulness in this population.

Introduction

Physicians and surgeons pay much attention to evaluating thyroid nodules due to the malignant potential of these growths. Women are more likely to develop thyroid nodules, and in iodine deficient countries, its prevalence may reach 5% (). Advances in imaging modalities such as ultrasound scan have increased the rate of nodule detection in the gland. The prevalence of thyroid nodules on ultrasound may be as high as 67% (). Since an important proportion of thyroid nodules include malignant cells, clinicians should search for possible malignancy, especially in suspected nodules. Ultrasound scan and scintigraphy features help discriminate these nodules, especially in cases with a history of exposure to radiation.

Inflammation has a crucial role in the development of cancer (, ). Association between neoplasm and many inflammatory markers has been studied recently (). One of these markers is the hemogram derived mean platelet volume (MPV). It is an index of routine hemogram tests and reflects platelet size. Activation of platelets is associated with an increase in MPV value (). An increase in MPV has been described in various inflammatory conditions (-). Not only inflammatory diseases with a high inflammatory burden, but also neoplastic disorders have been associated with MPV. Elevated MPV is reported in gastric () and colon cancer (). Moreover, increased MPV has been proposed as a prognostic factor in critically ill patients ().

Since some of thyroid nodules are malignant, we aimed to compare MPV values in patients with malignant and benign thyroid nodules after precise pathologic diagnosis.

Materials and Methods

Patient selection

The subjects having undergone surgery for thyroid nodule at our surgery departments between January 2013 and January 2015 were included in the study. Based on pathologic examination of thyroid gland surgical specimens, these patients were divided into two groups of malignant nodules and benign nodules. The study was approved by the institutional Ethics Committee. Demographic and laboratory data were obtained from the hospital computerized database. Preoperative hemogram values of thyroid nodule patients, white blood cell count (WBC), hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), platelet count (PLT), thyroid stimulating hormone (TSH) and MPV were recorded.

Active infection, diabetes mellitus, thyroiditis, any other type of malignancy, inflammatory diseases were set as exclusion criteria. Patients on corticosteroid or aspirin treatment were also excluded.

The Beckman Coulter LH 780 autoanalyzer (Beckman Coulter Inc., Brea, CA, USA) was used to perform hemogram tests. Hemogram and other biochemical and pathological assays were conducted at laboratories of our university hospital.

Statistical analysis

Statistical analysis was conducted by use of SPSS software (SPSS15.0; SPSS Inc., Chicago, IL, USA). Data were expressed as mean ± SD or median (min-max). Student’s t-test or Mann-Whitney U test was used to compare variables between the study groups. The level of statistical significance was set at p<0.05.

Results

A total of 199 subjects, 101 patients with malignant and 98 patients with benign thyroid nodules, were included in the study. Median age of the malignant and benign thyroid nodule patients was 43 (25-77) and 45 (26-60) years, respectively. Age was not significantly different between malignant and benign thyroid nodule groups (p=0.79).

The malignant thyroid nodule group consisted of 77 women and 24 men, whereas the benign nodule group included 75 women and 23 men. Gender distribution was not significantly different between the groups (p=0.96).

White blood cell count, Hb, Htc, MCV, PLT and TSH levels were not different between the malignant thyroid nodule group and benign nodule group (p>0.05 all). General characteristics and laboratory data of the study groups are summarized in Table 1.

Table 1

General characteristics and laboratory data of study groups

		Group		p
		Malignant nodule	Benign nodule
Gender	Men (n)	24	23	0.96
	Women (n)	77	75
		Mean ± SD
WBC (K/mm3)		6.9±1.7	7.2±1.9	0.13
Hb (g/dL)		13.5±1.2	13.6±1.1	0.79
Htc (%)		40±3.5	40.5±3	0.33
MCV (fL)		86.8±3.7	87.3±4.2	0.34
PLT (K/mm3)		249±63	260±58	0.19
MPV (fL)		9.1±1	7.8±0.8	<0.001
		Median (min-max)
Age (years)		43 (25-77)	45 (26-60)	0.79
TSH (uIU/mL)		1.21 (0.01-5.7)	0.93 (0.01-4.4)	0.60

WBC = white blood cell count; Hb = hemoglobin; Htc = hematocrit; MCV = mean corpuscular volume; PLT = platelet count; MPV = mean platelet volume; TSH = thyroid stimulating hormone

The MPV was higher in the malignant thyroid nodule group as compared with the benign nodule group (9.1±1 fL vs. 7.8±0.8 fL), yielding a statistically significant difference (p<0.001).

The receiver operating characteristic curve (ROC) analysis was performed to define the sensitivity and specificity of MPV in detecting malignant nodules. The MPV cut-off value of 8.25 had 81% sensitivity and 66% specificity in determining malignant nodules (p<0.001; area under the curve (AUC) 0.84; lower bound 0.78; upper bound 0.89).

Discussion

The main finding of the present study was that elevated MPV might indicate malignancy in patients with thyroid nodules. MPV is considered to be associated with certain malignancies. Elevated MPV values have been reported in various types of cancer at the time of diagnosis (). Another study reports on increased MPV in patients with colon cancer, which was reduced after surgery (). Increased MPV has also been reported in gastric ()and epithelial ovarian tumors ().

We will discuss the rationale for MPV elevation in cancer at this point. Inflammation causes an increase in the levels of circulating cytokines. These cytokines, especially interleukin (IL)-6, may interfere with megakaryopoiesis in bone marrow and cause production of larger platelets. This may be the underlying reason for increased MPV in cancer patients. Cancer is also associated with chronic inflammation, thus such a causal relationship may be present.

Various diagnostic tools are available to differentiate malignant from benign thyroid nodules. Ultrasonography characteristics of malignant thyroid nodules, vertical rather than horizontal shape, spiculated borders, hypoechogenicity and microcalcifications all have about 40%-48% sensitivity in detecting malignancy (). Leenhardt et al. report on sonography sensitivity and specificity for thyroid nodule malignancy of 75% and 61%, respectively ().

Cold thyroid nodules on thyroid scintigraphy require further evaluation for suspicious malignancy. However, Kountakis et al. report that only 27.5% of hypofunctional (cold) thyroid nodules were malignant on scintigraphy (). Although hot nodules in scintigraphy are considered almost always benign (), malignancy was detected in 6% of hyper functioning hot nodules (). Diagnostic accuracy of a combination of sonography and scintigraphy is not excellent either. Only about 35% of sonographic solid and scintigraphically cold nodules were reported as malignant by fine needle aspiration cytology (FNAC) ().

In our study, the sensitivity and specificity of MPV at a threshold of 8.25 were better than by ultrasound and scintigraphy.

Fine needle aspiration cytology of thyroid nodule, which is considered as the most important method for detecting malignancy in thyroid nodules, has a sensitivity of 91% in selecting malignant nodules (). However, the rate of false-negative and false-positive results of FNAC can be as high as 11% and 7%, respectively (). Owing to higher sensitivity and specificity of MPV at 8.25 threshold, we think that it can be used in combination with sonography, scintigraphy and FNAC to establish the nature of thyroid nodules. Such a combination not only increases diagnostic accuracy, but also may improve the cost-effectiveness by reducing repeated expensive techniques (FNAC, etc.) in cases of non-diagnostic test results.

Not only thyroid disease but also metabolic alteration such as obesity, type 2 diabetes mellitus and diabetic nephropathy were associated with MPV levels in hemogram tests (, ).

There were several limitations to the present study. First, the retrospective design made our results difficult to interpret. Another limitation was the relatively small study population. Finally, we did not compare sonography, cytology and scintigraphy test results of the study population with MPV, which should be the subject of another study in the near future.

In conclusion, increased MPV should be considered as an assistive diagnostic tool in differentiating malignant and benign thyroid nodules. However, further prospective studies are required to confirm its usefulness in this population.