Neoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2) positive BC, and in estrogen receptor-positive (ER+)/ HER2- BC with high-risk features. In ER+/HER2- breast cancer, pathological complet rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status. METHODS: Retrospective data analysis from Kartal Dr. Lütfi Kirdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. RESULTS: Of 203 patients, 11.8% achieved pCR. Ki67 (p<0.001) and ER percentage (p<0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p=0.003, HR: 1.02) and ER percentage (p=0.019, HR: 0.97) as independent predictors of pCR probability. CONCLUSION: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤ 24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.

The association of PD-L1 expression and CD8-positive T cell infiltration rate with the pathological complete response after neoadjuvant treatment in HER2-positive breast cancer.

PURPOSE: Achieving a pathological complete response (pCR) after neoadjuvant therapy in HER2-positive breast cancer patients is the most significant prognostic indicator, suggesting a low risk of recurrence and a survival advantage. This study aims to investigate clinicopathological parameters that can predict the response to neoadjuvant treatment in HER2 + breast cancers and to explore the roles of tumour-infiltrating lymphocytes (TILs), CD8 + T lymphocytes and PD-L1 expression. METHODS: This single-centre retrospective study was conducted with 85 HER2-positive breast cancer patients who underwent surgery after receiving neoadjuvant therapy between January 2017 and January 2020. Paraffin blocks from these patients were selected for immunohistochemical studies. RESULTS: A complete pathological response to neoadjuvant treatment was determined in 39 (45.9%) patients. High Ki-67 index (> 30%), moderate to high TIL infiltration, PD-L1 positivity and high CD8 cell count (≥ 25) were significantly associated with pCR in univariate analyses (p: 0.023, 0.025, 0.017 and 0.003, respectively). Multivariate regression analysis identified high Ki-67 index (> 30%) and CD8 cell infiltration as independent predictors for pCR in HER2-positive breast cancer. CONCLUSIONS: High Ki-67 index, and high CD8 cell count are strong predictors for pCR in HER2-positive breast cancer. Tumours with high Ki-67 index, high TILs and CD8 infiltration may represent a subgroup where standard therapies are adequate. Conversely, those with low TILs and CD8 infiltration may identify a subgroup where use of novel strategies, including those that increase CD8 infiltration could be applied.

Can BAP1 expression loss in mesothelial cells be an indicator of malignancy?

BACKGROUND: Malignant mesothelioma is a highly aggressive tumor that can be confused with a benign mesothelial lesion, especially cytomorphologic lesions. BRCA1-associated protein 1 (BAP1) acts as a tumor suppressor. In this study, we aim to investigate the value of BAP1 staining of malignant mesothelioma cases with expression loss and diagnosis in cell block and biopsy tissue. METHODS: Between January 2009 and March 2017, 64 mesotheliomas, 117 reactive mesothelial hyperplasias, and 20 fibrinous pleuritis/pericarditis were diagnosed with morphologic and immunohistochemical findings in our pathology clinic and were included in the study. Formalin-fixed, paraffin-embedded tissues were immunohistochemically examined for BAP1. Inflammatory and stromal cells were used as positive internal controls. BAP1 was assessed for nuclear staining in mesothelial cells. RESULTS: Examinations of the relationship between patient diagnosis and BAP1 biopsy status showed that the BAP1 loss rate (76.6%) was significantly higher in malignant mesothelioma cases than in other benign diseases (0%) (p<.001). Sensitivity and specificity were 76.56% and 100%, respectively, for biopsy tissue from malignant mesothelioma. Sensitivity and specificity were both 100% for BAP1 test on cell block tissue. Furthermore, the consistency between BAP1 cell block and biopsy results was excellent (ĸ=0.90) and the correlation was significant (p<.001). CONCLUSIONS: This study shows that BAP1 expression loss in both cytology and biopsy tissue in biopsy-confirmed malignant mesothelioma cases is an essential parameter for malignant mesothelioma diagnosis.

Effect of Preparation Technique on Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Sample Adequacy: 3 Years of Experience from a Single Center.

OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used to sample mediastinal lymph nodes and lesions. However, the methodological details of an optimal preparation technique for aspirated material have not yet been clearly determined. This study was an evaluation of the effect of 2 preparation techniques on the adequacy of aspirated specimens. MATERIAL AND METHOD: A retrospective analysis was performed of EBUS-TBNA samples obtained at the institution over a total of 36 months. Two periods were examined. Almost all of the aspirated material was smeared onto slides and fixed with 95% alcohol in the first period of the study. Subsequently, to improve diagnostic ability, a pair of slides was prepared from each needle pass: the first was air-dried, and the second was fixed in 95% alcohol. The remainder of the aspirate was kept for cell block analysis. RESULTS: In total, 462 samples were obtained from 260 patients. The overall sampling adequacy was 74% in the first and 81.1% in the second period (p < 0.05). Approximately 14% of the specimens included a sufficient number of cells for immunohistochemical cell block evaluation in the first period and 42% in the second period (p < 0.001). Histological subtyping of non-small cell lung carcinoma was determined in 18 (56.3%) and the primary origin of a tumor was determined based on morphological and immunohistochemical properties in 32 (84.2%) of the patients in the first and second periods, respectively. CONCLUSION: The access to a sufficient EBUS-TBNA sample and the ability to perform the appropriate preparation can impact the specific diagnosis and treatment of patient with a single procedure.

Endobronchial ultrasound-guided transbronchial fine needle aspiration: Determinants of adequacy.

BACKGROUND: This study aims to evaluate the factors influencing the adequacy of endobronchial ultrasound-guided transbronchial fine needle aspiration specimens. METHODS: A retrospective analysis of 1,700 endobronchial ultrasound-guided transbronchial fine needle aspiration samples obtained from 822 patients (500 males, 322 females; mean age 56±13 years; range 16 to 83 years) was performed between March 2011 and March 2014 at our center. Variables potentially associated with sampling adequacy, such as all cytological materials and procedure notes (lymph node and/or lesion size, localization, needle pass number, and slide number) were examined. RESULTS: The overall specimen adequacy was 79.8%. The specimen adequacy was associated with needle pass number (p≤0.001). Adequacy rate was 66.9% for one needle pass and 85.8% for three needle passes. According to the sampling regions, adequacy rates showed a difference [69.2%-85.8%; (p≤0.005)]. In the multivariate logistic regression analysis of subcarinal (7) lymph node station, patient age (odds ratio, 0.983; 95% confidence interval, 0.966-1.000; p=0.049) and number of slides (odds ratio, 1.240; 95% confidence interval, 1.062-1.448; p=0.006) were independent determining factors of specimen adequacy. While independent determinants of specimen adequacy for the right paratracheal (4R) region were lymph node size (odds ratio, 1.486; 95% confidence interval, 0.973-2.268; p=0.067) and number of slides (odds ratio, 1.418; 95% confidence interval, 1.146-1.756; p=0.001), they were lymph node size (odds ratio, 1.594; 95% confidence interval, 0.960-2.645; p=0.071) and number of needle passes (odds ratio, 2.277; 95% confidence interval, 1.360-3.811; p=0.002) for the right interlobar (11R) region. Independent determinant of specimen adequacy for the left paratracheal (4L) lymph node station was the number of needle passes (odds ratio, 1.656; 95% confidence interval, 0.955-2.869; p=0.072). CONCLUSION: During endobronchial ultrasound-guided transbronchial fine needle aspirations, particularly when rapid on site evaluation cannot be applied, consideration of factors affecting adequacy according to lymph node localizations may increase the chance for obtaining materials with suitable quality for cytologic evaluation.

Pericardial hydatid cyst and tuberculosis co-existence.

Tuberculosis and hydatid cyst are still major health problems in developing countries. Co-existence of these two infections is also seen commonly. In this article, we present a 15-year-old-girl patient who applied with cardiac tamponade accompanied by pleural and pericardial effusion and was diagnosed as pericardial hydatid cyst and pericardial tuberculosis. To the best of our knowledge, this is the first case with such feature reported in the literature.

Review of Hydatid Cyst with Focus on Cases with Unusual Locations.

OBJECTIVE: This study has been conducted so as to contribute to health statistics of hydatid cyst by the data obtained from our clinic, and to discuss hydatid cysts in unusual locations. MATERIAL AND METHOD: Cases diagnosed as hydatid cyst at Dr. Lutfi Kirdar Kartal Research and Education Hospital Pathology Clinic between 2007 and 2015 have been evaluated based on criteria such as age, sex and location. RESULTS: A total of 364 cases, 209 females and 155 males, have been included in the study. The subjects in the cases are aged between 4 and 81 (mean: 38.84). Regarding the sites, 254 (69.8℅) of the cases are located in liver, and 53 (14.6℅) in the lung. Fifty-seven cases (15.6℅) have been detected in unusual sites other than the lung or liver. The rate of isolated organ involvement, other than the lung and liver, has been found to be 10.3℅. CONCLUSION: Since hydatid cyst can be found in all the body sites, it should be taken into account in the differential diagnosis of all cystic lesions.

Histopathological and Immunohistochemical Evaluation of Pannus Tissue in Patients with Prosthetic Valve Dysfunction.

BACKGROUND: Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. METHODS: A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-ß) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. RESULTS: Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-ß, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. CONCLUSIONS: Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist of periannular tissue migration, myofibroblast and extracellular matrix proliferation with vascular components. It is a chronic active process in which mediators such as TGF-ß, VEGF and MMP-2 play roles in both matrix formation and degradation.

Epithelioid trophoblastic tumor.

OBJECTIVE: To describe a case of epithelioid trophoblastic tumor (ETT) in a postmenopausal woman, which had several peculiar features that differentiate it from previously reported ETTs. CASE REPORT: ETT of the uterus is a rare form of trophoblastic tumor with only 100 cases distinguished until now. Our case differs from the previously reported ones due to its several exceptional features. Our patient had no history of trophoblastic or gynecological disease; is postmenopausal; had endocervical extension from the beginning; recurrences and metastasis at follow up; and had a high Ki-67 index and a normal beta-human chorionic gonadotropin value. CONCLUSION: Because precise differential diagnosis will alter the therapeutic approach and prognosis, it is necessary for treating physicians to be aware of these unusual presentations.

Alternative causes of bioreaction to prosthetic heart valves: three cases with pannus formation.

Pannus formation is an infrequent but serious complication of prosthetic heart valve surgery. The cause of pannus is recognized as a bioreaction to the prostheses; histological investigations have shown that pannus comprises collagen and elastic tissues containing endothelial cells, chronic inflammatory cells, and myofibroblasts. However, the detailed mechanism of its formation has not been fully demonstrated. We aimed to evaluate the potential role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the pathogenesis of pannus formation in three patients with mechanical prosthetic heart valves. Pannus specimens removed from the prostheses were fixed in 10% neutral-buffered formalin for 24 hours after surgical removal and paraffin-embedded using standard procedures. Serial sections were cut at 4 µm for immunohistochemistry analysis. Hematoxylin and eosin (HE) was used in the histological analysis. VEGF and MMP-2 were studied in the immunohistochemistry analysis. Three patients with mechanical prosthetic obstruction due to pannus overgrowth underwent redo valve surgery. In the first and second patients, the mitral prosthesis was explanted along with the pannus overgrowth. The third patient had both aortic and mitral prostheses; the aortic prosthesis was explanted with obstructive pannus formation, whereas the mitral valve was spared with excision of the nonobstructive pannus. The immunohistochemical study demonstrated the expressions of MMP-2 and VEGF in all of the pannus specimens acquired from these cases. VEGF and MMP-2 may play a role in the mechanism of pannus formation as the elements of the chronic active inflammatory process.