IGM continues to be an important problem for both surgeons and patients due to the difficulty in the diagnosis and treatment of the disease, as well as acute and chronic exacerbations and long-term effects on quality of life. The prognosis of IGM is not as clear as its treatment. IGM may be misdiagnosed as breast cancer.
BC is still a worldwide public health dilemma. It is the most common female malignancy in the world and the primary cause of mortality due to cancer in women. Early diagnosis provides the best survival rate; thus, novel diagnostic markers are essential for reducing mortality and morbidity. Inflammatory factors such as the preoperative CRP, interleukin (IL)-6 and − 8, and tumor necrosis factor-α is associated with BC prognosis [25–27]. The NLR, which is a new indicator of systemic inflammation, plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear.
In our study, there was a statistically significant difference between the IGM and the BC with respect to fibrinogen, Fib/Alb, CRP, WBC, neutrophil, NLR, PLR, and monocyte values. Some of these variables are components of IGM (WBC and CRP) and are therefore not surprising. More importantly, there was a negative relationship between CRP and albumin and a positive relationship between CRP and WBC, NLR, PLR, and ESR
Systemic inflammation and infection can promote thrombosis by increasing the serum levels of fibrinogen, leukocytes, coagulation factors, and cytokines, and by altering the metabolism and function of certain cells, monocytes, macrophages (28). Although there have been many studies [29, 30, 31, 32] on cancers and inflammatory diseases with inflammatory cytokines, fibrinogen, CRP, albumin, and hematological indexes as inflammatory markers, these parameters are limited in the differential diagnosis of IGM and early onset BC. ESR is an important indicator of acute phase response. The proteins involved in ESR include fibrinogen, alpha and beta globulin, and albumin . Among these, fibrinogen has the asymmetric molecular structure that makes the most contribution . The major finding of the present study was the highest levels of fibrinogen and Fib/Alb in the IGM group. Levels of albumin, a negative acute phase reactant, were also found to be significantly lower in the IGM group than in the control group. ESR was found to be significantly increased in the IGM at both the first and second hours compared to the control. Moreover, it increased significantly in the second hour compared to BC. While the negative correlation was found between CRP and 1-h ESR with albumin, a positive correlation was found between CRP and 1-h ESR and 2-h ESR in IGM. Zheng et al.  found f FIB/ALB ratio was associated with BC prognosis and claimed that the preoperative FIB/ALB ratio in particular could be related to BC survival and prognosis. Destek et al.  found increased plasma fibrinogen levels (460 mg/dL) in 37-year-old and 14-week-old pregnant IGM patients. β-fibrinogen-455 G > A pathological gene polymorphisms were also observed in the IGM group. As described in their case, fibrinogen gene polymorphisms and induced inflammatory and autoimmune disorders may play a role in unknown IGM etiology. Yigitbasi et al.  found that significant differences were not observed between the IGM, BC, and control groups with regard to total protein, albumin, and CA15-3 levels. Low-grade infections reflected by increased/decreased levels of acute phase proteins, such as fibrinogen, albumin, and Fib/Alb ratio, may be partly responsible for the inflammatory processes observed in breast lesions.
CRP, a member of the pentraxin family and a marker of inflammation, constitutes the prototype of acute phase proteins. CRP is a major acute phase reactant in humans, with an acute and rapid rise in response to infection and tissue damage. In response to all types of tissue damage and infection, the human body activates various mechanisms to correct this damage. The most important of these mechanisms is the acute phase response. In addition to radiological data and breast biopsy, circulating CRP levels may be non-invasive biomarkers that can help differentiate IGM from BC. CRP levels were found to be highest in the IGM group in the current study. A positive correlation was also found between 1-h ESR, 2-h ESR, WBC NLR, and PLR and CRP in IGM. ROC analysis results in the IGM group showed that cut-off values, the best sensitivity, and specificity for CRP were > 3.625 (94.55% and 70% respectively). This is consistent with the results of our other study  and Jacquin-Porretaz et al. . Contrary to these results, Yigitbasi et al.  demonstrated that the CRP levels of the BC group were significantly higher than those of the IGM and control groups. Akalın et al.  found that CRP values were significantly higher in breast abscess and IGM groups compared with the control group. Furthermore, there was no significant difference in CRP between the breast abscess and IGM groups. Their ROC analysis revealed cut-off values; the best sensitivity and specificity for CRP were 1.5 (61–76%) in the IGM group, suggesting that CRP cannot be a useful tool for the differential diagnosis of BC and IGM. These differences in study results may be due to the limitation of the small number of patients in all these studies. Another reason could be the sustained increase in the concentrations of acute phase proteins as the inflammation progresses. This difference may also be due to the different inflammation statuses of cancer patients.
Chronic inflammation is thought to be a predisposing factor for cancer formation by initiating the carcinogenesis process . Changes in some complete blood count parameters affected by inflammation and other causes can be used to predict cancer prognosis and survival . Clinicians generally use a complete blood count (CBC) in their daily practice, especially in inflammatory diseases and treatment follow-up. Recently, the use of hematological indexes, such as NLR, monocyte-tolymphocyte ratio (MLR), and PLR, as simple and inexpensive biomarkers for the demonstration of systemic inflammation has been increasing. Çetinkaya et al.  investigated 41 IGM patients with a mean follow-up time of 28.4 months. These results demonstrated that an increased NLR was predictive of poor outcomes in patients with IGM. In our study, the highest levels of WBC, neutrophil, NLR, and monocytes were found in the IGM group. Moreover, a positive correlation was found between CRP and WBC, NLR, and PLR in IGM. There are positive correlations between NLR, WBC, and neutrophil in IGM. These parameters are increasingly being used as prognostic markers for predicting the prognosis of cancers [15, 16, 18]. Kargin et al.  claimed that pre-treatment NLR may be a predictive factor for long-term recurrence after treatment in patients with granulomatous mastitis. They also compared NLR in patients with (n = 7) and without (n = 52) recurrence and found that NLR was significantly higher in patients with a recurrence, but they did not perform a ROC analysis to support their observations. In our study, according to the ROC analysis for BC and IGM groups., the sensitivity (65%) and specificity (74%) of the NLR were found to be low. According to the results of the ROC analysis, NLR might not be a good biomarker for differentiating BC and IGM. The reason for the low sensitivity and specificity may be due to the different inflammation statuses of cancer patients. The routine collection of the CBC in clinical practice is simple and cost-effective to the patient, making the NLR a highly promising indicator for monitoring the systemic inflammatory status of IGM.
Surgical treatment of IGM is controversial due to delays in wound healing, high local recurrence rates, and poor cosmetic results. In a study by Yau et al. , surgical treatment was applied to 11 patients diagnosed with IGM. The last surgical intervention needs of the patients occurred between 1 and 5 months. More than one surgical intervention was performed due to the recurrence of 8 patients . In the current study, the recurrence rate of IGM was 20% at 2 years of follow-up . The relationship between the number of biochemical laboratory findings and hematological indexes and recurrence was evaluated. In patients with recurrent IGM, fibrinogen, Fib/Alb ratio, CRP, neutrophil, NLR, and 2-h ESR increased, while lymphocyte levels decreased compared to non-recurrent patients. NLR and CRP predicted recurrence with a sensitivity of 81.2% and 100% and specificity of 61.36% and 47.73%, respectively, while Fib/Alb ratio and fibrinogen predicted recurrence with a sensitivity of 54.55% and 72.73%, and specificity of 95.45% and 95.45%, respectively, in patients with IGM. Our results showed that these parameters have a significant effect on the recurrence of the disease. Similar to our results, Çetinkaya et al.  demonstrated that increased preoperative NLR (cut-off value of 5.02) was indicated as a recurrence predictor in patients with IGM recurrence. Kargin et al.  reported recurrence in four (20%) patients who received steroid treatment, while recurrence was observed in three (7.9%) patients who received surgical treatment. In the study, there was no significant difference in the pre-treatment NLR and recurrence between the surgical and medical groups . However, regardless of the treatment performed, the NLR of patients with relapse was higher than that of patients without relapse. Thus, the authors reported that the pre-treatment NLR value in IGM patients may predict recurrence in the long term . Therefore, there is a need for large studies on the effectiveness of treatment methods applied and their effects on recurrence, based on the characteristics of patients.