The effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes in patients with breast cancer.

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.

New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.

LONG-TERM SURVIVAL EFFECTS OF PREOPERATIVE BREAST MRI IN PATIENTS WITH BREAST-CONSERVING SURGERY.

The benefit of breast magnetic resonance imaging (MRI) in breast-conserving surgery (BCS) is unclear. Our study compared breast cancer patients with and without preoperative breast MRI and their long-term oncologic outcomes are reported. A total of 1378 BCS cases with early breast cancer between 1996 and 2017 were reviewed. Patients with carcinoma in situ or neoadjuvant treatment or having breast MRI after tumor excision were excluded. Of 1378 patients, 270 (19.5%) had preoperative MRI. There were no significant differences regarding T and N stage and molecular subtypes between the groups. Surgical margins were significantly wider in the breast MRI group. Five-year overall survival (OS) was 96.9% in the MRI group and 94.3% in the control group, and this difference was not significant (p=0.11). Five-year local-regional recurrence-free survival (LRFS) was not significantly different either (98.8% and 96.5%, respectively, p=0.41). When analyses were repeated only for patients with hormone receptor-negative or triple-negative breast cancer, there was still no significant difference in OS, LRFS, or disease-free survival. In conclusion, MRI does not seem necessary in all patients undergoing BCS. New prospective randomized controlled trials are needed to determine appropriate use of preoperative MRI and its effects on oncologic outcomes in early breast cancer patients.

Usefulness of imaging findings in predicting tumor-infiltrating lymphocytes in patients with breast cancer.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have been determined as a new prognostic indicator of immunotherapy response in breast cancer (BC). The aim of this study is to investigate the effectiveness of imaging features in predicting the TIL levels in invasive BC patients. METHODS: A total of 158 patients with invasive BC were included in our study. All lesions were evaluated based on the BIRADS lexicon. US was performed for all the patients and 89 of them underwent MRI. The histologic stromal TIL (sTIL) levels were assessed and associations between the sTIL levels and imaging features were evaluated. RESULTS: Tumors with high sTIL levels had more circumscribed margins, round shape, heterogeneous echogenicity, and larger size on ultrasonography (p < 0.005). There was a statistically significant positive correlation between the sTIL levels and ADC value (p < 0.001). Tumors with high sTIL levels had significantly more homogeneous enhancement than the tumors with low sTIL levels (p = 0.001). Logistic regression analysis showed that the ADC was the most statistically significant parameter in predicting the sTIL levels (the odds ratio was 90.952; p = 0.002). The optimal cutoff value for ADC in predicting low and high sTIL levels was found to be 0.87 × 10-3 mm2 s-1 (AUC = 0.726, 73% specificity, and 60% sensitivity). CONCLUSIONS: Imaging findings, especially the ADC, may play an important role as an adjunct tool in cases of uncertain situations and may improve the accuracy of biopsy results. The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis. KEY POINTS: • Preoperative assessment of TILs is an important biomarker of prognosis and treatment efficacy. • ADC value can be a useful tool in distinguishing high and low sTIL levels as a non-invasive method. • The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis and an optimal treatment for the BC patients.

Comparison of breast cancer patients who underwent partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (M + I) regarding quality of life (QOL), cosmetic outcome and survival rates.

PURPOSE: The latissimus dorsi muscle has long been used in breast cancer (BC) patients for reconstruction. This study aimed to compare early stage BC patients who had partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (MI) with respect to quality of life (QoL), cosmetic outcome (CO), and survival rates. PATIENTS AND METHODS: The data of patients who underwent PM + MLDF (Group 1) and M + I (Group 2) between January 2010 and January 2018 were evaluated. Both groups were compared in terms of demographics, clinical and pathological characteristics, surgical morbidity, survival, quality of life, and cosmetic results. The EORTC-QLQ C30 and EORTC-QLO BR23 questionnaires and the Japanese Breast Cancer Society (JBCS) Cosmetic Evaluation Scale were used to assess the quality of life and the cosmetic outcome, respectively. RESULTS: A total of 317 patients were included in the study, 242 (76.3%) of them in group 1 and 75 (23.6%) of them in group 2. Median follow-up time was 56 (14-116) months. There were no differences identified between the groups in terms of tumor histology, hormonal receptors and HER-2 positivity, surgical morbidity, and 5-year overall and disease-free survival. Group 2 patients were significantly younger than group 1 (p = 0.003). The multifocality/multicentricity rate was higher in group 2 (p ≤ 0.001), whereas tumor size (p = 0.009), body mass index (BMI, p = 0.006), histological grade (p ≤ 0.001), lymph node positivity (p = 0.002), axillary lymph node dissection (ALND) rate (p = 0.005), and presence of lympho-vascular invasion (LVI, p = 0.013) were significantly higher in group 1. When the quality of life was assessed by using the EORTC QLQ C30 and BR23 questionnaires, it was seen that the body image perception (p < 0.001) and nausea/vomiting score (p = 0.024) were significantly better in PM + MLDF group whereas physical function score was significantly better in M + I group (p = 0.012). When both groups were examined in terms of cosmesis with JBCS Cosmetic Evaluation Scale, good cosmetic evaluation score was significantly higher in patients in MLDF group (p = 0.01). DISCUSSION: The results of this study indicate that in comparison to M + I procedure, the PM + MLDF procedure provides significantly superior results in terms of body image and cosmetic result with similar morbidity and oncologic outcomes. In selected patients with small breasts and a high tumor/breast ratio, PM + MLDF may be an alternative to subcutaneous mastectomy and implant.

Synchronous presentation of muscle-invasive urothelial carcinoma of bladder and peritoneal malign mesothelioma.

INTRODUCTION: Cancer is one of the most important leading cause of death in man and woman in the world. The occurrence of new cancer has become more frequent in recent years due to strict screening protocols and occupational and environmental exposure to carcinogens. The incidence of secondary malignancies has also increased due to close medical follow-up and advanced age. Herein, we report a case and its management diagnosed as synchronous peritoneal malignant mesothelioma and muscleinvasive urothelial carcinoma.

Possible role of stress, coping strategies, and life style in the development of breast cancer.

Objective The aim of the present study was to investigate the possibility of the effect of life long stressful events, along with coping method used, perception of social support, and life style on the development of breast cancer. Methods In this hospital-based case control study, the study group comprised 250 women with breast cancer who were followed by Florence Nightingale Breast Study Group. Control group included 250 women, who had similar sociodemographic characteristics to the study group. Data were collected with semi-structured interview form, Healthy Life Style Behavior Scale, Coping Strategy Indicator, and Stress Evaluation Form developed by us. Results In multivariate analysis, family history of cancer (OR: 1.55, 95% CI: 2.29-1.05), inadequate social support (OR: 1.83, 95% CI: 1.23-2.73), and loss of father during childhood (OR: 2.68, 95% CI: 5.52-1.30) and serious stressor within the last five years (OR: 4.72, 95% CI: 7.03-3.18) were found to be risk factors increasing the risk of breast cancer. When family history of cancer was excluded from the model, the presence of psychiatric disorder history (OR: 1.95, 95% CI: 3.26-1.17) and major life events (OR: 2.24, 95% CI: 4.07-1.24) were added to the model as risk factors. Conclusion The present study indicates that especially the stressful events experienced within the last five years plays an undeniable role in the risk of breast cancer. Social support may be as important in the period before the diagnosis as in the period after diagnosis.

Synchronous and metachronous bilateral breast cancer: A long-term experience.

PURPOSE: The objective of this study was to assess the demographic, pathologic and survival characteristics of patients who were diagnosed as having bilateral breast cancer. METHODS: A review was conducted of the records pertaining to patients who presented to our clinic and were diagnosed as having breast cancer. Any second cancer diagnosed within 12 months of initial diagnosis was defined as synchronous bilateral breast cancer. Assessment included treatments administered to the patients and survival rates, as well as their demographic, reproductive and pathologic features. RESULTS: The total number of patients who were diagnosed as having bilateral breast cancer in the context of the present study was 99. Among the patients with synchronous breast cancer, the median age at the time of initial diagnosis was found as 57 years. The median age of the discovery of first tumor among the patients with metachronous tumor was 52 years and the median age of second tumor detection was 59 years. Family history in metachronous tumor was significantly greater (p=0.041). The median time of metachronous cancer incidence was 96 months. The length of disease-free period among the patients with synchronous tumor was 126.3 months, whereas it was 243.7 months in those with metachronous tumor (p=0.041). CONCLUSION: The incidence rate of synchronous breast tumors has been rising thanks to growing awareness and the leading-edge imaging methods. The fact that the second tumor developed after more than 5 years among the patients with metachronous cancer gave rise to the increased rate of survival.

Receptor discordance rate and its effects on survival in primary and recurrent breast cancer patients.

PURPOSE: The receptor status of breast cancer plays a critical role in clinical practice. During the metastatic process, a change in the biological characteristics of the tumor can be seen. This study aimed to investigate the hormone receptor and HER2 status changes between primary and recurrent breast cancers and their effect on survival. METHODS: Eighty-six breast cancer patients with biopsy- proven local recurrences or distant metastases during the follow-up period were included in the study. Patients with metastatic disease at the time of first diagnosis or with history of previous neoadjuvant chemotherapy were excluded. RESULTS: Forty-three of the 86 patients (50%) had changes in at least one of the estrogen receptor (ER), progesterone receptor (PR), or HER2. ER, PR and HER2 discordance rates were 12.7, 38.3, and 15.1%, respectively, and PR discordance was significantly higher (p=0.000). Among all molecular subtypes, the triple negative breast cancer (TNBC) subtype showed the least change. When the effect of chemotherapy on receptor change was analyzed, PR discordance was significantly higher in the group who received chemotherapy (p=0.029). Analysis of the hormonotherapy effects on receptor discordance revealed results similar to those of chemotherapy. Only the PR discordance was significantly greater in the group that received hormonotherapy (p=0.000). None of the three receptor discordances or loss of any receptor were related to survival. Primary tumor TNBC subtype and disease-free-interval (DFI) shorter than 5 years were found as independent prognostic factors that negatively affected overall survival (OS). CONCLUSION: This study showed that during recurrent disease there was 50% discordance in the expression of ER, PR, and HER2. The receptor showing the greatest discordance and influence from the systemic treatment was PR. A significant relationship between receptor discordance and survival could not be demonstrated in our study.

Tumoral melanosis in an adolescent after trauma: a clinicopathological dilemma.

Tumoral melanosis (TM) is a histologic term used to indicate a nodular accumulation of melanophages in the dermis clinically presenting as a pigmented lesion. It is usually associated with regression of melanoma and nonmelanoma melanocytic pigmented lesions. We present the case of a 16-year-old girl with a suspicious pigmented macule on her right knee that appeared after trauma. The lesion was completely excised and diagnosed as TM.

MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification.

Background: The minichromosome maintenance protein-2 (MCM-2) is a more sensitive proliferation marker than Ki-67. This study aimed to evaluate the relationship between MCM-2 and Oncotype DX recurrence score (ODX-RS) and determine an MCM-2 cutoff value in high-risk patients according to TAILORx risk categorization. Methods: Hormone receptor (HR) positive HER-2 negative early-stage breast cancer patients (pT1-2, pN0-N1, M0) who had ODX-RS were included in the study. According to the TAILORx trial, patients were divided into two groups with high (ODX-RS ≥26) and low risk (ODX-RS <26) in terms of ODX-RS. Formalin-fixed-paraffin-embedded tissues of patients were re-evaluated, and 3 µm sections were prepared for MCM-2 immuno-histochemical staining. The relationship between ODX-RS and the percentage of MCM-2 staining was evaluated in two groups. The ROC curve analysis was performed to determine the MCM-2 cut-off value for the TAILORx high-risk group (ODX-RS ≥26). Results: The mean MCM-2 value was significantly higher in the high-risk group [(60.2 ± 11.2 vs 34.4 ± 13.8, p < 0.001)]. In the multivariate analysis, MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003) and progesterone receptor (PR) levels ≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003) were found to be independent factors indicating a high-risk group. A one-unit increase in MCM-2 level increased the likelihood of being in the high-risk group by 1.27 times. In the ROC curve analysis, the optimal MCM-2 cut-off level was 50 (AUC: 0.921, sensitivity: 86.7%, specificity: 96.0%, p < 0.001). Conclusion: Our study is the first study in the literature to investigate the relationship between ODX-RS and MCM-2 levels in HR-positive HER-2 negative early breast-cancer patients. In this study, MCM-2 was an independent risk factor in identifying high-risk patients according to TAILORx risk classification. MCM 2 cut-off value (50) may help the decision on adjuvant chemotherapy in patients where the Oncotype DX test cannot be performed.

The effect of scrotal reconstruction with skin flaps and skin grafts on testicular function.

Due to its unique composition, the reconstruction of scrotal skin defects is a major clinical challenge. This study was designed to evaluate the effects of scrotal reconstruction, using skin grafts and skin flaps, on spermatogenesis. In Group 1, the rats did not undergo surgery and were used as controls. In Group 2, after removal of all of the scrotal skin to expose the testicles, the defect was repaired using a skin flap from the right groin region. In Group 3, the reconstruction was achieved using skin grafts. All the rats were killed at 2 months postoperatively and evaluated. The mean wet weights of the testicles in the control group were significantly higher compared with that of the graft group. The mean height of the germinal epithelium was significantly greater in the control and flap groups compared with that of the graft group. The Johnsen score for spermatogenesis in the control group was higher than that in the graft group. The use of flaps resulted in testicular function that was comparable to that of the control group, whereas the use of grafts resulted in diminished testicular function. Therefore, we suggest that flaps may be the first choice for scrotal reconstruction.

Sclerosing polycystic adenosis of the parotid gland presenting with a Warthin tumor.

Sclerosing polycystic adenosis (SPA) frequently presents as an isolated process, however it may involve adjacent benign salivary gland neoplasia. In this article, we present a 77-year-old female case with a 10-year history of a slow-growing mass of the left parotid gland of SPA presenting with a Warthin tumor. The patient underwent left superficial parotidectomy. The histopathological examination revealed SPA and multifocal Warthin tumor.

Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer.

Next-generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer-related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low-risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low-risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.

The effect of multifocal and multicentric tumours on local recurrence and survival outcomes in breast cancer.

PURPOSE: The purpose of this study was to compare the multifocal (MF)/multicentric (MC) breast cancers with unifocal (UF) breast cancers in terms of tumour characteristics, treatment methods, loco-regional recurrence and survival rates. METHODS: Patients who were treated with a diagnosis of early-stage breast cancer (stage I,II) and had regular follow-up were included in the study. MF tumours were defined as having more than one tumour focus in the same quadrant, whereas MC tumours refered to the presence of more than one tumour focus in different quadrants. RESULTS: In total, 1865 patients with invasive breast cancer were evaluated, 1493 (80.1%) of whom had UF cancer, 330 (17.7%) had MF cancer, and 42 (2.3%) had MC cancer. After comparing the groups with each other, it was seen that MF and MC breast cancers occurred more often at early ages and that lymph node invasion (LNI) was greater. No differences were seen between the 3 groups in terms of local recurrence-free survival (RFS) and overall survival (OS) rates . In multivariate analysis, it was found that MF and MC tumours had no impact on local recurrence and OS. In multivariate analysis, it was understood that HER2 positivity and triple-negative breast cancer (TNBC) had an impact on local recurrence, and age, lymphovascular invasion (LVI), T3 tumour, lymph node positivity and TNBC subtype had an impact on OS. CONCLUSION: Although MC and MF tumours show aggressive features such as high lymph node positivity and LVI, they have similar loco-regional recurrence and survival rates to UF tumours.

Chondroid syringoma: a case report.

BACKGROUND: Chondroid syringoma is a benign skin adnexal tumor. The reported incidence of chondroid syringoma among primary skin tumors is low and has been reported at 0.01-0.098%. CASE: A 57-year-old woman presented with a 10-year history of a slowly growing lump on her philtrum. Fine needle aspiration cytology was performed. The smears showed cohesive groups of round cells embedded in a chondromyxoid ground substance. A diagnosis of benign appendageal tumor of the skin was made. Surgical excision of tumor was done. Histopathologic examination was consistent with chondroid syringoma. CONCLUSION: Chondroid syringoma should be included in the differential diagnosis of a slowly growing nodule on the head or neck. The diagnosis can be confirmed by means of fine needle aspiration cytology. The treatment of choice is local excision.

Metastatic basal cell carcinoma presenting as a neck mass.

Neck masses are common in physicians' daily practice; however, there is a small possibility that the origin of the neck mass is a basal cell carcinoma (BCC). We present a BCC of the scalp that metastasizes to the neck without any lymphoid involvement. We also reviewed possible risk factors for metastasis of the BCC, which is a probable cause of neck mass.

Renal cytokine and histopathologic changes following acutely increased intra-abdominal pressure: an animal study.

BACKGROUND: The reason for acute renal failure (ARF) in abdominal compartment syndrome (ACS) is thought to be due to the increase in renal venous pressure. In this study, the changes in plasma and renal tissue cytokine levels and histopathologic changes in renal tubular and glomerular cells were evaluated and compared in a model of acute elevation in abdominal tension with different pressures. METHODS: Eighteen Sprague-Dawley rats were randomly assigned into three groups: Sham-operated rats and rats in Groups 1 and 2, in which 20 and 30 mmHg of intra-abdominal pressure (IAP) was applied for 60 minutes, respectively. Left kidneys of the animals and intracardiac blood samples were taken at the end of the procedures. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were investigated in plasma and renal tissue samples. Renal tissues were also evaluated for histopathologic changes. RESULTS: Renal tissue and plasma TNF-alpha and IL-6 levels were found to be significantly increased when the sham-operated group was compared to the study groups (p<0.05). Renal tissue changes showed that the total histopathologic scores were significantly increased in study groups compared to the sham-operated group (p<0.05); tubular changes were more prominent than glomerular changes. CONCLUSION: Abdominal tension linearly can cause renal tubular histopathologic changes. Cytokines may play a role in ARF due to ACS.

Oncocytic lipoadenoma of the parotid gland: a case report with fine needle aspiration cytology findings.

Oncocytic lipoadenoma of the salivary gland is a rarely encountered tumor. A 56-year-old man presented with a two-year history of a slow-growing mass of the left parotid gland. Computed tomography scan with contrast showed a 7x6.5x6 cm well-circumscribed solid parotid mass of the left superficial and deep lobe. Fine-needle aspiration yielded oncocytic cells exclusively, suggesting Warthin tumor or an oncocytoma. Left total parotidectomy was performed. A diagnosis of oncocytic lipoadenoma was made. At six-month follow-up no evidence of recurrence has been noted. Oncocytic lipoadenoma should be considered in the differential diagnosis of oncocytic proliferations and oncocytic tumors in the parotid gland.