Evaluation of inflammatory response using hemogram index parameters in phyllo des tumors: acase-control study

Authors

Abstract

AimPhyllodes tumors are rare fibroepithelial breast tumors accounting for less than 1% of all breast neoplasms. They are classified as benign, borderline, or malignant. Although diagnosis is mainly established by imaging and core needle biopsy, histopathological evaluation may occasionally be insufficient for accurate subtype differentiation. This study aimed to investigate the potential diagnostic value of hemogram index parameters in patients with phyllodes tumors.
MethodsThis retrospective study included 26 patients diagnosed, treated, or followed up for phyllodes tumors at Akdeniz University Faculty of Medicine and 26 control subjects who presented for unrelated conditions. Hemogram parameters analyzed were white blood cell count (WBC), neutrophil, lymphocyte, monocyte, and platelet counts, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and red blood cell distribution width (RDW).
ResultsWBC, neutrophil count, and NLR were significantly higher in the patient group compared with controls, whereas MPV was higher in controls. When benign cases were compared with borderline/malignant cases, only platelet count was significantly higher in the borderline/malignant group. In the three-group comparison, neutrophil count, NLR, and MPV were significantly elevated only in the borderline/malignant group compared with controls. No other significant differences were observed.
ConclusionHemogram-derived inflammatory markers may support the diagnostic evaluation and subtype differentiation of phyllodes tumors. As an inexpensive and widely available test, hemogram parameters could serve as adjunctive biomarkers. Larger prospective studies are needed to confirm these findings.

Keywords

Introduction

Phyllodes tumors are a rare type of fibroepithelial tumor of the breast, accounting for less than 1% of all breast neoplasms, with an estimated incidence of approximately 2.1 per 1,000,000 individuals. Although they can occur at any age, they are uncommon in adolescents and the elderly, with a peak incidence between the ages of 45 and 49.¹

Phyllodes tumors are classified into three groups: benign, borderline, and malignant. This classification is based on the histopathological characteristics of the tumor. The primary approach to treatment is surgical, and when negative surgical margins can be achieved, breast-conserving surgery (lumpectomy or partial mastectomy) should be the preferred method to prevent local recurrence. In cases where negative margins cannot be obtained, mastectomy may be necessary.² Since phyllodes tumors metastasize hematogenously, axillary metastasis is rare, and axillary surgery is therefore not routinely performed .³

Phyllodes tumor diagnosis can be made through ultrasound, mammography, and magnetic resonance imaging (MRI), while a definitive diagnosis requires core needle biopsy. Histopathological examination is essential for distinguishing between benign, borderline, and malignant subtypes. Positron emission tomography (PET) is also recommended in the diagnosis of malignant phyllodes tumors.⁴ The treatment and follow-up plan vary depending on the histopathological subtype, with core biopsy being the first-line method to determine this subtype.⁵ In cases where a core biopsy is inconclusive, and excisional biopsy is recommended.⁴ According to the latest guidelines published by the National Comprehensive Cancer Network (NCCN), negative surgical margins are sufficient for benign phyllodes tumors, whereas for borderline and malignant tumors, a margin of at least 1 cm is recommended.⁶ Malignant tumors have a 10–20% risk of distant metastasis.⁷ Determining the histopathological subtype in the preoperative period is critical not only for guiding the surgical approach but also for evaluating the potential for distant metastasis and planning additional preoperative investigations accordingly.

It is well-established that inflammatory processes play a role in cancer development. A complete blood count (CBC) is a simple and widely available test in all healthcare settings, and hemogram index parameters derived from it are useful for assessing systemic inflammation.⁸ Due to their ease of interpretation and the significant role of inflammation in cancer development and prognosis, numerous recent studies have investigated the relationship between hemogram index parameters and precancerous or cancerous lesions. These studies can provide valuable insights to guide diagnosis and treatment planning.

In this study, we investigated the values of hemogram index parameters across different histopathological subtypes of phyllodes tumors. The aim was to evaluate the potential utility of hemogram index parameters as an alternative diagnostic tool in the differential diagnosis of phyllodes tumor subtypes.

Materials and Methods

This study included 26 patients diagnosed with phyllodes tumors who underwent surgery and were diagnosed, treated, or followed up at Akdeniz University Faculty of Medicine Hospital. Hemogram results obtained during the preoperative period, when no acute pathological conditions were present, were evaluated. These patients constituted the patient group.
The control group consisted of age-matched individuals who were scheduled for elective surgeries, such as umbilical or inguinal hernia repair, at our institution and had hemogram testing performed during a preoperative period in which no acute pathological conditions were present.
The hemogram index parameters of the patient and control groups were compared in the study.
Inclusion criteria for the patient group were: being over 18 years of age, having a diagnosis of phyllodes tumor confirmed by core needle biopsy, and being scheduled for surgery based on this diagnosis.
Patients under the age of 18 and those who had any acute pathological conditions that could elevate inflammatory markers at the time of hemogram testing were excluded from both groups.
Conditions that could potentially increase inflammatory parameters, such as the presence of secondary tumors, metastatic phyllodes tumors, hypertension, diabetes mellitus, autoimmune diseases, urinary tract infections, upper or lower respiratory tract infections, and benign or malignant hematological disorders, were taken into account for both the patient and control groups. Patients with any of these conditions were excluded from the study (Supplementary Figure 1).
The patient group was divided into two subgroups based on histopathological subtypes, considering the presence of precancerous and cancerous lesions and the associated inflammatory processes: a benign group and a borderline+malignant group. These two subgroups were evaluated separately and in comparison with the control group for statistical analysis.
The hemogram index parameters assessed in the study included: white blood cell count (WBC), neutrophil count, lymphocyte count, monocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and red blood cell distribution width (RDW).



Ethical ApprovalThis study was approved by the Ethics Committee of Akdeniz University, Faculty of Medicine (Date: 2024-01-25, No: TABEK-24).

Statistical AnalysisDescriptive statistics were presented using frequency, percentage, mean, standard deviation, median, minimum, maximum, and 25th–75th percentiles (Q1–Q3). The assumption of normality was assessed using the Shapiro-Wilk test. For comparisons of numerical data between two groups, the Independent Samples t-test was used when the data followed a normal distribution; otherwise, the Mann-Whitney U test was applied. For comparisons among three groups, the Kruskal-Wallis H test was used when the distribution was not normal, and the Bonferroni-Dunn post hoc procedure was applied for pairwise comparisons if significant results were found. When the numerical values of all groups followed a normal distribution, one-way ANOVA was used, and in cases where Levene's test indicated non-homogeneity of variances, the Welch test was applied. A p-value of less than .05 was considered statistically significant.

Reporting GuidelinesThis study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Results

The patient group included 26 individuals: 15 diagnosed with benign phyllodes tumors and 11 with borderline or malignant phyllodes tumors. Similarly, 26 individuals were evaluated in the control group. The mean age of the patient group was 48, and the control group consisted of individuals from a similar age range, with a mean age of 48.23. There was no statistically significant difference in age between the groups.
A comparison of the hemogram parameters between the patient and control groups is presented in Supplementary Table 1. The mean WBC count in the patient group was 7.99 (SD: 1.93), significantly higher than that of the control group at 6.95 (SD: 1.47) (p = 0.033). The median neutrophil count was 5.23 (Q1: 3.67–Q3: 6.16) in the patient group and 3.69 (Q1: 3.06–Q3: 4.65) in the control group, also significantly higher in the patient group (p = 0.009).
The median NLR was 2.4 (Q1: 1.69–Q3: 2.86) in the patient group, higher than that of the control group at 1.57 (Q1: 1.29–Q3: 2.09) (p = 0.007). The median MPV was 9.45 (Q1: 8.8–Q3: 10.6) in the patient group, which was significantly lower than the control group's value of 10.55 (Q1: 10.2–Q3: 10.8) (p = 0.011). No statistically significant differences were found between the two groups for the other parameters (p > 0.05) (Supplementary Table 1).

When the index parameters of the two subgroups within the patient cohort were compared, a statistically significant difference was observed only in platelet levels. Patients diagnosed with benign phyllodes tumors had lower platelet counts compared to the malignant + borderline group, and this difference was statistically significant (p = 0.043). No significant differences were found between the two groups in terms of the other parameters (p > 0.05).
In the comparison among the three groups, neutrophil count (p = 0.027),NLR (p = 0.024), and MPV (p = 0.036) showed at least one group with a statistically significant difference. The median neutrophil count in the malignant+borderline group was 5.34 (Q1: 4.21–Q3: 6.08), which was higher than that of the control group (3.69 [Q1: 3.06–Q3: 4.65]) (p = 0.027). The median NLR value in the malignant + borderline group was 2.5 (Q1: 1.81–Q3: 2.82), which was higher than that of the control group (1.567 [Q1: 1.294–Q3: 2.089]) (p = 0.024). In contrast, the median MPV value in the malignant + borderline group was 8.9 (Q1: 8.8–Q3: 10.4), which was lower than that of the control group (10.55 [Q1: 10.2–Q3: 10.8]) (p = 0.036). However, no statistically significant differences were found between the two histopathological subtypes within the patient group. (Supplementary Table 2)

Discussion

In our study, when comparing the patient group with the healthy control group, WBC count, neutrophil count, and NLR were found to be higher in the patient group. This finding is thought to be primarily associated with the inflammatory processes present in the patient group, suggesting that hemogram index parameters may have diagnostic value. Conversely, MPV was lower in the patient group compared to the control group.

To date, there are no studies in the literature directly evaluating the relationship between phyllodes tumors and hemogram index parameters. However, there are several recent studies focusing on breast cancer.

In a study by Sun et al., NLR, MPV, and RDW levels were observed to be higher in the patient group compared to the control group. Consistent with our findings, NLR was elevated in the patient group, although WBC and neutrophil counts were not significantly different between groups in their study.⁹

In a large population-based study by Tian et al., LMR, NLR, and PLR values were found to be above normal in patients with breast cancer presenting with bone metastases.¹⁰

Divsalar et al. compared 160 breast cancer patients with 160 healthy controls and found significant differences in hemoglobin, hematocrit, MCV, and RDW levels. Moreover, when comparing NLR, PLR, WBC, and erythrocyte counts between the two groups, minor yet statistically significant differences were observed (p < 0.05). Similarly, in our study, WBC and NLR values were elevated in the patient group.¹¹

In contrast, Dal et al. found no statistically significant differences in hemogram parameters when comparing male breast cancer patients with healthy controls, which differs from most other findings in the literatüre.¹²

In our study, no significant differences were found between the benign and borderline+malignant subgroups, except for platelet count.

Similarly, in a study by Elyasinia et al. investigating the association between breast cancer stage and hemogram parameters, a significant increase in platelet count was observed with advancing cancer stage.¹³

In contrast to our findings, Liu et al., in a study involving 200 patients, found that NLR was significantly higher in patients with malignant breast masses compared to those with benign lesions.¹⁴

A meta-analysis by Yang et al., evaluating 37 studies and over 7,000 breast cancer patients versus more than 7,000 controls (either healthy individuals or those with benign breast conditions), showed that NLR values were significantly higher in breast cancer patients compared to both control groups. In contrast, our study showed that among the three groups compared, NLR was significantly higher only in the malignant + borderline group compared to the control group, with no significant difference between the benign phyllodes group and either the malignant + borderline or control groups.¹⁵

The same meta-analysis also found that PLR values were higher in breast cancer patients compared to healthy controls, but not significantly different from those with benign breast disease. Additionally, LMR values were lower in breast cancer patients compared to both the control and benign disease groups.¹⁵

Most studies support the finding that NLR is elevated in diseased groups, in line with our results. However, Li et al. reported no significant difference in NLR between breast cancer patients and controls, although PLR and LMR were significantly higher in the breast cancer group (p<0.05).¹⁶

Limitations

This study has several limitations. First, the retrospective design and relatively small sample size may limit the generalizability of the findings. Second, the study was conducted at a single center, which may introduce selection bias. Third, hemogram parameters were evaluated at a single preoperative time point, and dynamic changes over time were not assessed. Finally, although inflammatory conditions were carefully excluded, subclinical inflammation could not be completely ruled out.

Conclusion

Although there are studies with varying results, it is evident that hemogram index parameters tend to increase in breast cancer and many other cancer types due to inflammation. However, with further research, standardized assessments for specific cancer subtypes across different organs are expected to become clearer over time. As indicators of systemic inflammation, hemogram index parameters may serve as useful tools in the identification of borderline and malignant tumors.

As the number of studies and investigations on this topic increases, the reliability and diagnostic power of these parameters will be better defined. In light of data provided by future studies, hemogram index parameters may represent a practical and accessible alternative tool to assist in preoperative diagnosis, due to their simplicity, cost-effectiveness, and ease of application.

Declarations

Abbreviations

CBC, complete blood count;
LMR, lymphocyte-to-monocyte ratio;
MPV, mean platelet volume;
MRI, magnetic resonance imaging;
NCCN, National Comprehensive Cancer Network;
NLR, neutrophil-to-lymphocyte ratio;
NMR, neutrophil-to-monocyte ratio;
PET, positron emission tomography;
PLR, platelet-to-lymphocyte ratio;
Q, quarter;
RDW, red blood cell distribution width;
SD, standard deviation;
STROBE, Strengthening the Reporting of Observational Studies in Epidemiology;
WBC, white blood cell count.

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About This Article

Received:

February 16, 2026

Accepted:

April 24, 2026

Published Online:

May 1, 2026