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.

Correlation of REG1A, Claudin 7 and Ki67 expressions with tumor recurrence and prognostic factors in superficial urothelial urinary bladder carcinomas.

Aim: Superficial urothelial urinary bladder tumors are neoplasms that frequently recur and have a potential for invasion and metastasis. REG gene family is composed of various acute phase reactants, lectins, antiapoptotic factors, and growth factors that are effective on pancreatic island cells, neural cells, and epithelial cells. REG1A and REG1B are two forms of the human REG1 gene. It is reported that they are expressed in several cancers and are correlated with the prognosis of the patient. Claudins are integral transmembrane proteins that interconnect cells. However, their role in human tumorigenesis is extremely controversial. The aim of this study is to evaluate the relationship of REG1A, claudin 7 protein expressions, and Ki67 proliferation index in superficial urothelial urinary bladder tumors with well-known parameters of prognosis and tumor recurrence, and also to clarify whether these parameters are independent prognostic factors or not. Materials and Methods: A hundred and eleven patients diagnosed with superficial urothelial carcinoma between 2011 and 2016 years in our hospital and followed up in our urology clinic were included in this study. The slides prepared from paraffin blocks were immunohistochemically stained with REG1A, claudin 7, and Ki67 antibodies. Results: REG1A showed positive staining in 37 (33%) and negative staining in 74 (67%) of urothelial tumors. Claudin 7 was positive in 24 (22%) and negative in 87 (78%) cases. REG1A expression showed a positive correlation with tumor stage and tumor recurrence; a high Ki67 proliferation index was positively correlated with tumor stage and grade. The loss of claudin 7 expression was related to tumor recurrence. Besides, tumors with REG1A expression and claudin 7 loss had a shorter survival independent of recurrence. Conclusion: In urothelial tumors, REG1A expression and loss of claudin 7 might be significant markers of prognosis that predict tumor recurrence.

Clinicopathological Evaluation of 15 Ectopic Adrenal Tissues.

BACKGROUND: Ectopic adrenal tissue is a rare condition associated with embryological development defects seen in many different areas in the abdomen and pelvis. Here, we aimed to discuss the clinicopathological features of ectopic adrenal tissues diagnosed in our clinic, in light of the literature. METHODS: We included cases of ectopic adrenal tissues incidentally detected in the specimens from patients undergoing operation for various diagnoses during 2012- March 2020. The cases were examined according to gender, age, location and accompanying pathological diagnoses. During this period, 15 cases of ectopic adrenal tissues (6 paratubal, 3 paraovarian, 2 paratesticular, 1 spermatic cord, 1 paraaortic, 1 liver capsule, 1 omentum) were detected accompanied by two endometrial carcinomas, two serous cystadenomas, one seminoma, one mixed germ cell tumor, one bilateral ovarian serous carcinoma and hepatic high-grade colon adenocarcinoma metastasis. RESULTS: In this report, the fifth ectopic adrenal tissue accompanying a malignant testicular tumor, the fifth and sixth ectopic adrenal tissues occurring with ovarian serous cystadenoma, the first case observed with serous cystadenocarcinoma and the first case detected with hepatic adenocarcinoma metastasis are presented. Our cases are mostly women and adult men. CONCLUSION: Ectopic adrenal tissues can lead to hormonal problems and also to adrenal cortex and medulla neoplasms. Microscopically, they may be confused with clear cell gynecological and germ cell tumors. If the ectopic focus is misdiagnosed as an implant, a benign entity may be incorrectly reported as malignant. Also, it is important to prevent mis-staging in malignancies. For precise diagnosis, an immunopanel such as inhibin, melan A, and calretinin can be performed.

Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) Immunohistochemistry in Pheochromocytoma, Head and Neck Paraganglioma, Thoraco-Abdomino-Pelvic Paragangliomas: Is It a Good Idea to Use in Routine Work?

BACKGROUND: In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups. METHODS: A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant. RESULTS: SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001). CONCLUSION: To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.

Extramedullary myeloma in ectopic parathyroid adenoma: A case report.

Extramedullary myeloma, a subgroup of multiple myeloma, is a rare condition characterised by extra-skeletal infiltration of clonal plasma cells. Although parathyroid adenoma's co-morbidity with multiple myeloma is common, extramedullary myeloma, an ectopic parathyroid adenoma has not been reported in the literature. This is the first study in literature that presents extramedullary myeloma that infiltrated ectopic parathyroid adenoma in the mediastinum after multiple myeloma treatment. In its course of relapse, the extramedullary myeloma created mass effect and no laboratory findings were present due to its non-secretory nature.

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.

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.

Extranodal Marginal Zone Lymphoma of the Parotid Gland.

Non Hodgkin lymphomas correspond to 25 % of all head and neck cancers. These rare tumors only include less than 5 % of malign tumors in parotid region. Differential diagnosis of these tumors cover many malign and benign tumors of the parotid gland. Definite diagnosis depends on sufficient tissue material of parotidectomy specimen. Treatment modality is surgical removal of the lesion with or without additional radiation and chemotherapy depending on the stage of the tumor. Prognosis is better than other forms of the B-cell lymphoma. We present a 54 year old woman who suffered from progressively and slowly growing mass on parotid region, without any inflammatory disease or chronic infection, diagnosed with mucosa associated lymphoid tissue lymphoma of the parotid gland. Parotid gland was totally excised by superficial parotidectomy and there is no recurrence after 5 years postoperative period.

Primary Dural Spinal Lymphoma Presentation of a Rare Spinal Tumor Case.

Background. Primary spinal dural lymphomas (PSDL) are tumors with characteristic histopathology of a lymphoma, which are completely in the spinal epidural space without any other systemic involvement. Extranodal primary lymphoma involving nervous system prefers thalamus/basal ganglia, periventricular region, cerebellum, eyes, meninges/dura, and cranial nerves or spinal cord. Rare spinal localization with acute spinal cord compression is worth attention. Case Presentation. A 48-year-old male presented with a several-month-long history of upper back pain. Lately, he had numbness and weakness at both lower extremities and was unable to walk for one week. A spinal MRI showed a thoracic lesion with cord compression at T2-T4 levels. The patient underwent surgical decompression, with his final histopathology showing diffuse large B-cell lymphoma. Systemic work-up was negative for nodal disease. Following surgery, he received radiotherapy combined with chemotherapy. He experienced a good outcome after four years. Conclusion. The upper thoracic cord is a rare location for primary spinal lesions/metastases, both of which prefer the lower thoracic and upper lumbar regions. In cases of progressive paraparesis, there should be immediate surgical intervention in the case of denovo disease, followed by combined radiotherapy and chemotherapy procedures.

Clinical importance of phosphatase of regenerating liver-3 expression in breast cancer.

BACKGROUND: Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors. METHODS: PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by χ² test. Kaplan-Meier test and log rank method were used to define prognostic importance of PRL-3 expression. RESULTS: Of 122 breast cancer tumor samples, 46 (37.7 %) were negative while 76 (62.3 %) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P = 0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P = 0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P > 0.05). CONCLUSION: Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group.

The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast.

Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P≥0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.

The relationship of COX-2 expression with estrogen receptor, progesterone receptor and prognostic parameters in endometrial carcinomas.

AIM: Endometrial cancer (EC), which is the most common gynecologic cancer, develops as a result of disruption of the delicate balance between cell proliferation and cell loss, or apoptosis through activation of oncogenesis, or loss of tumor suppressor genes. Among the biochemical factors proposed to give a more detailed characterization of EC biology, estrogen receptors (ER) and progesterone receptors (PR) play a major role. Most of the studies in the literature have shown increased expression of cyclooxygenase-2 (COX-2) in EC. Recent experiments suggest that COX-2 antagonizes cell apoptosis, increases the invasiveness of malignant cells and promotes angiogenesis. The aim of this study was to investigate the expression of COX-2 in EC, to study its correlation to established menstrual status, grade, myometrial invasion, lymph node status, stage and ER and PR status. MATERIAL & METHODS: The study was performed on 72 ECs. Immunohistochemically was analyzed for ER, PR, and COX-2. RESULTS: COX-2 positivity was found in 91.7% of the cases. In 61 cases (84.7%) there was ER positive staining, and in 59 cases (81.9%) PR positive staining was observed. We have not found a statistically significant relation between COX-2 and prognostic factors, ER and PR. CONCLUSIONS: A high expression rate still suggests a probable relation with endometrial carcinogenesis. If such a relation exists, new therapeutic options might be available in the future.

The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas.

BACKGROUND: Endometrial carcinoma (EC) is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2) gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Immunohistochemical (IHC) analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. RESULTS: We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. CONCLUSIONS: Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

Myasthenia gravis and autoimmune Addison disease in a patient with thymoma.

The association of thymoma with myasthenia gravis has been well documented. However, the relationship between these two syndromes and Addison disease are very rarely encountered in clinical practice. We report on a 32-year-old man who underwent a resection for thymoma 48 months ago. The diagnosis of Addison disease was made followed by a diagnosis of myasthenia gravis on the basis of a high titer of acetylcholine receptor levels. The treatment of oral prednisolone 7.5 mg/day and oral prostigmine 180 mg/day was initiated. His symptoms and physical signs were improved after this treatment. To our knowledge, this is the fourth reported case of thymoma synchronously associated with myasthenia gravis and Addison disease.

[The comparison of the expansion of polyps according to the Ki-67 and computed tomography scores]. / Polip yayginliginin Ki-67 ve bilgisayarli tomografi skorlarina göre karsilastirilmasi.

OBJECTIVES: The disease extention in nasal polyps was compared by using the mitotic activity rates and the computed tomography scores. PATIENTS AND METHODS: This study was conducted on 19 nasal polyposis patients (8 males, 11 females; mean age 40.0+/-13.7 years; range 20 to 63 years). The preoperative computed tomography records of the patients were evaluated according to the Lund-Mackay grading system. The polyp tissues of the same patients were stained with the Ki-67 antigen for immunohistochemical evaluation. The correlation between the radiologic results and the Ki-67 values was compared by means of the Spearman's correlation test. RESULTS: The mean computed tomography score was observed as 14.3+/-4.7 (range 7-24). The mean Ki-67 score resulting from the immunohistochemical staining was calculated as 24.3+/-18.5 (range 3.3-73.5%). A significant correlation was determined between the Ki-67 values and the computed tomography scores. ("Spearman's" correlation factor: 0.677; p<0.001). CONCLUSION: As the mitotic activity rate of nasal polyps increases, both the volume of the polyps and the computed tomography scores increase as a result of the blockage of the sinus ostiums by the increased polyp volume.

A case of testicular rhabdomyosarcoma.

Pure testicular rhabdomyosarcoma is a very rare tumor and 7 cases have been reported in literature. A 20-year-old male patient presented with a painless right testicular swelling who underwent inguinal orchiectomy with suspicion of testicular malignancy. The case was regarded as an embryonal rhabdomyosarcoma according to histopathologic and immunohistochemical findings. The case is presented and the relevant literature is reviewed and discussed.