Blood and tissue levels of persistent organic pollutants and genetic susceptibility in patients with breast cancer.

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR. However, the GSTT1 null polymorphism represented a significant risk for breast cancer when OR adjusted for age and smoking status. CYP1A1 polymorphism was a significant risk factor for breast cancer, regardless of whether the OR was adjusted. These results suggest that exposure to certain POPs, GSTT1 and CYP1A1 polymorphisms, age, and smoking status are risk factors for breast cancer. In addition, the blood concentrations of some POPs represent surrogates for breast tissue concentrations.

PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

OBJECTIVE: Our primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. STUDY DESIGN: Records of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: The median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72-124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). CONCLUSION: This retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

Prognosis-related novel immunostaining pattern for programmed cell death ligand 1 and prognostic value of tumour-infiltrating lymphocytes in triple-negative breast cancer.

This study aims to determine the prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) in triple- negative breast cancer (TNBC). PD-L1 expression and TIL percentage were determined in TNBCs that did not receive neoadjuvant therapy. The relationship between PD-L1 expression and the percentage of TILs with survival was investigated. The presence of intratumoural PD-L1-positive tumour-infiltrating immune cells (TIICs) in tumours with ≥ 1% PD-L1 expression was identified as a new PD-L1 evaluation parameter. The presence of intratumoural PD-L1-positive TIICs as a new parameter in PD-L1-positive cases increased overall survival. The percentage of TILs increased in both overall and distant metastasis-free survival (p = 0.040 and p = 0.006, respectively). As a result, it was found that the risk of death was increased 5.18-fold (p = 0.013) in patients without intratumoural PD-L1-positive TIICs. This risk of death was calculated to be 5.40-fold higher in patients with TIL percentage ≤ 10% than in those with > 40% (p = 0.024), and the risk of distant metastasis was calculated to be 11.95 times higher. In our study, we discovered that the percentage of TILs made a statistically significant difference in TNBC survival. The presence of intratumoural PD-L1-positive TIICs in PD-L1-positive cases significantly increased survival.

Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system.

BACKGROUND: In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. METHODS: A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. RESULTS: At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. CONCLUSIONS: The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.

The usefulness of p16 and COX-2 expression on the prediction of progression to endometrial cancer.

OBJECTIVES: Endometrial cancer (EC) is the most commonly diagnosed gynecological cancer. Endometrial hyperplasia (EH) is a more common diagnosis than EC. Endometrial hyperplasia is found in approximately 1.5% of all women presenting with abnormal bleeding. Endometrial hyperplasia progresses to EC, and especially, cancer risk increases in cases with atypical hyperplasia. p16, one of the tumor suppressor proteins involved in the cell cycle, and COX-2, one of the key enzymes of prostaglandin synthesis, are important markers for the diagnosis of both EH and EC. There is lack of consensus in the classification, diagnosis and treatment of EH. The subject of changes in the cell cycle in the progression of endometrial pathologies may help to identify and prevent these affected pathways in the treatment stage. The aim of this study is to investigate the expression of p16 and COX-2 during the development of EC from EH. MATERIAL AND METHODS: We investigated COX-2 and P16 expressions in patients with proliferative endometrium, complex/simple endometrial hyperplasia and endometrioid adenocarcinoma. RESULTS: p16 expression increased in EH and EC (p<0.001). COX-2 expression was increased in endometrial cancer compared to other groups, but this increase was not found to be statistically significant. Although p16 and COX-2 expression were increased in patients with advanced grade/stage, lymphovascular invasion, and >50% of myometrial invasion, this increase was not statistically significant. CONCLUSIONS: More detailed studies are needed to investigate the prognostic significance of the COX-2 molecule. COX-2 might be a potential biomarker for the prognosis of endometrial cancer and a potential therapeutic target for EC treatment. Also, it might be used to prevent the progression of precursor lesions to invasive EC.

Is the presence of deep infiltrative endometriosis underestimated in the surgical management of endometriosis?

OBJECTIVES: The aim of the study was to determine the presence of deep infiltrative endometriosis (DIE) in the surgical management of endometriosis. MATERIAL AND METHODS: Operation notes and histopathological reports of women with endometriosis were retrospectively analyzed in the Ege University Hospital between 2008 and 2018. A total of 191 women with suspicious of endometriosis but without clinical signs of DIE were enrolled in the study. Laparoscopic diagnosis of DIE was compared with histopathological reports. There was no histopathology before surgery. Endometriosis was suspected only based on symptoms. RESULTS: A total of 213 lesions that were thought to be DIE were removed from 191 women with endometriosis. Among these 213 lesions, 179 specimens were reported as endometriosis and 34 lesions as fibro-adipose tissue. Forty-nine right uterosacral ligaments were excised, and endometriosis was detected in 44 out of 49 specimens. Histopathological examination of 45 left uterosacral ligaments revealed endometriosis in 35 specimens. Finally, 25 endometriotic nodules were removed from the recto-vaginal space, and 22 of these were verified as endometriosis by a pathologist. The positive predictive value of laparoscopic visualization for DIE in the group suspected of endometriosis but without any clinical findings of DIE was 84%. CONCLUSIONS: Women with the suspicious of endometriosis, qualified to surgery, because of infertility or pain, should be prudently investigated to confirm or to exclude coexistence of DIE even if no preoperative sign of DIE was observed to provide complete resection. Otherwise, DIE continues to grow, causes pain postoperatively, and complicates subsequent surgery.

A deep-learning model for transforming the style of tissue images from cryosectioned to formalin-fixed and paraffin-embedded.

Histological artefacts in cryosectioned tissue can hinder rapid diagnostic assessments during surgery. Formalin-fixed and paraffin-embedded (FFPE) tissue provides higher quality slides, but the process for obtaining them is laborious (typically lasting 12-48 h) and hence unsuitable for intra-operative use. Here we report the development and performance of a deep-learning model that improves the quality of cryosectioned whole-slide images by transforming them into the style of whole-slide FFPE tissue within minutes. The model consists of a generative adversarial network incorporating an attention mechanism that rectifies cryosection artefacts and a self-regularization constraint between the cryosectioned and FFPE images for the preservation of clinically relevant features. Transformed FFPE-style images of gliomas and of non-small-cell lung cancers from a dataset independent from that used to train the model improved the rates of accurate tumour subtyping by pathologists.

Breast Hemangioma Evaluation with Magnetic Resonance Imaging: A Rare Case Report.

Vascular tumors are rare in the breasts, and the most common forms include hemangiomas and angiosarcomas. Hemangiomas are rare benign vascular tumors. Most of them are asymptomatic and nonpalpable clinically, and the vast majority of such lesions are detected incidentally by mammography. Breast hemangiomas are difficult to diagnose using conventional imaging modalities since their imaging findings are variable. The following is a case presentation of an asymptomatic forty-five-year old female patient who was diagnosed with a rare hemangioma. Physical examination, ultrasonography (US) and mammographic examination were normal. Dynamic contrast enhanced magnetic resonance imaging (MRI) showed a non-mass pathological enhancement. After a short-term follow up, a comparative MRI was obtained and biopsy was planned, due to the heterogeneous non-mass enhancement on MRI. Needle core biopsy with US guidance was performed, resulting in benign findings. However, because of the discordance between imaging and histopathology, an MRI-guided wire localization followed by open surgical biopsy was performed. Histopathologic evaluation reported capillary hemangioma.The imaging findings, including US, mammography and MRI, of hemangioma are reviewed and described in this case report.

[A rare carcinoma metastasizing to the lung: Sertoli-leydig cell tumor]. / Akcigere metastaz yapan nadir bir karsinom: Sertoli-leydig hücreli tümör.

The lung is the most common site of metastasis for many malignancies. Especially the gastrointestinal system, gynecological malignancies and osteosarcomas frequently metastasize to the lung. It accounts for less than 0.5% of all ovarian neoplasms. The frequency of recurrence and metastasis is less than 5%. In most cases, they are stage I tumors, limited to the ovary and carry a good prognosis. Here, while investigating the nodules in the lung that were detected incidentally at the age of 64, the rare Sertoli-Leydig cell tumor of the lung is discussed clinically, radiologically and pathologically in the presence of a 64-year-old patient who was found to have undergone ovarian surgery 9 years ago. Since imaging methods and tumor markers did not yield significant results in terms of primary malignancy, wedge resection was performed from the left lung nodules. The histology of the lung nodule was the same as the poorly differentiated foci of the ovarian tumor. The immunohistochemical profiles of the two tumors were also similar. As a result of the evaluation of the patient's old materials belonging to the ovary and the samples taken from the lung together; The diagnosis was reached by obtaining similar results with the primary tumor in the immunohistochemical examination performed for the metastatic focus. Sex cord stromal tumors of the ovary, which rarely cause lung metastasis and have a tendency to recur and metastasis in a very long time after the first diagnosis, should also be kept in mind in the elderly woman and the patient with a gynecological history.

Primary ovarian rhabdomyosarcoma coexisting with Pseudo-Meigs' syndrome in a young patient: a case report and brief literature review.

Primary rhabdomyosarcoma is one of the malignant soft tissue sarcomas of childhood originating from embryonic mesenchyme. The tumor can occur in the head, neck region, and limbs, and genitourinary system. Primary ovarian rhabdomyosarcoma is an extremely rare malignancy with a few documented pediatric patients in the literature. Pseudo-Meigs' syndrome is a type of Meigs' syndrome that is usually associated with other benign ovarian tumors or any other type of malignant tumors. It is a rare condition characterized by ascites, pleural effusion, benign ovarian tumors or fibroma-like tumors, and resolution of ascites and pleural effusion after the removal of the tumor. A patient of Asian origin came to our clinic with symptoms of mild dyspnea, and gradually increasing abdominal swelling. Magnetic resonance imaging scans indicated masses with solid cystic components on both ovaries with a suspicion of malignancy, showing bilateral pleural effusion and massive ascites. This is the first reported case of a pure primary ovarian rhabdomyosarcoma associated with a Pseudo-Meigs syndrome in a young girl.

Comparison of HER2 status determination methods in HER2 (2+) patients: Manual fluorescent in situ hybridization (FISH) vs. dual silver enhanced in situ hybridization (SISH).

HER2 amplification has been demonstrated in 15-25% of invasive breast carcinomas and can be assessed using immunohistochemical and in situ hybridization methods. Here, we compared the accuracy of dual SISH to manual FISH in HER2 (2+) breast carcinoma and evaluated the feasibility of dual SISH method in routine practice. Sixty HER2 (2+) consecutive tumor samples diagnosed between January 2009 and February 2013 were selected. Demographic, histological and immunohistochemical features and FISH results were recruited from patient records and compared to dual SISH results. Nine (15%) of the 60 tumor samples were excluded from statistical analysis due to lack of interpretable SISH signals. HER2 staining percentages by immunohistochemistry differed between 20 and 80%. HER2 amplification was shown in 7 (13.7%) and 8 (15.7%) patients by FISH and SISH, respectively. Very good agreement was observed between FISH and SISH methods (kappa value: 0.92). Significant correlation was found between HER2 staining percentage and FISH positivity, in contrast to SISH positivity (p=0.012 vs. p=0.069). Our results are consistent with previously reported literature, indicating SISH can be used to determine HER2 status. However, preanalytical and analytical problems may cause inadequate or uncountable signals, making interpretation impossible for the pathologist and highlighting the importance of standardization and quality control programs.

Primary Ovarian Fibrosarcoma-An Unusual Tumor in an Adolescent: Case Report and Review of the Pediatric Literature.

BACKGROUND: Primary ovarian fibrosarcomas are rare and usually observed in perimenopausal and postmenopausal women. To our knowledge, to date, there are only 3 reports of ovarian fibrosarcoma in childhood and adolescence in the English-language literature. In this report, we aimed to present to our knowledge, the first pediatric case with advanced stage primary ovarian fibrosarcoma and to compare with previous cases. CASE: A 14-year-old teenage girl was admitted because of a giant abdominal mass. Imaging techniques revealed a giant heterogeneous and vascular ovarian mass. Salpingo-oophorectomy along with staging procedures were performed. Pathologic examination confirmed grade III ovarian fibrosarcoma with severe nuclear atypia and high mitotic count. Because of pulmonary metastasis, she received 4 courses of adjuvant combination chemotherapy (Ewing protocol). The patient withstood the treatment well and is disease-free at 2 years of follow-up. CONCLUSION: Fibrosarcoma of the ovary is an uncommon neoplasm with poor prognosis. To our knowledge, the presented patient is the first pediatric case with advanced staged primary ovarian fibrosarcoma to be treated with surgery and adjuvant chemotherapy.

The Importance of Minor Salivary Gland Biopsy in Sjögren Syndrome Diagnosis and the Clinicopathological Correlation.

OBJECTIVE: Minor salivary gland biopsy is one of the objective tests used in the diagnosis of Sjögren syndrome. The aim of our study was to compare the clinical and laboratory data of primary and secondary Sjögren syndrome cases with a lymphocyte score 3 and 4 in the minor salivary gland biopsy. MATERIAL AND METHOD: Data from a total of 2346 consecutive minor salivary gland biopsies were retrospectively evaluated in this study. Clinical and autoantibody characteristics of 367 cases with lymphocyte score 3 or 4 and diagnosed with primary or secondary Sjögren syndrome were compared. RESULTS: There was no difference between lymphocyte score 3 and 4 primary Sjögren syndrome patients in terms of dry mouth, dry eye symptoms and Schirmer test results but Anti-Ro and Antinuclear Antibody positivity was statistically significantly higher in cases with lymphocyte score 4 (p= 0.025, p= 0.001). Anti-Ro test results were also found to be statistically significantly higher in secondary Sjögren syndrome patients with lymphocyte score 4 (p= 0.048). CONCLUSION: In this study, the high proportion of cases with negative autoantibody but positive lymphocyte score is significant in terms of showing the contribution of minor salivary gland biopsy to Sjögren syndrome diagnosis. Lymphocyte score 3 and 4 cases were found to have similar clinical findings but a difference regarding antibody positivity in primary Sjögren syndrome. We believe that cases with lymphocyte score 4 may be Sjögren syndrome cases whose clinical manifestations are relatively established and higher autoantibody levels are therefore found.

Colonic malignant melanoma, primary or metastatic? Case report.

Gastrointestinal malignant melanomas, either primary or metastatic, are rare and overlooked tumors. There is also controversy regarding the actual existence of primary melanoma in the gastrointestinal tract apart from the esophagus and anorectal regions, where melanocytes normally exist. A case of malignant melanoma in the cecum is presented. The patient was a 30- year-old male who presented to the hospital for abdominal pain and diarrhea. The tumor was located mainly in the submucosa and measured 14x11x4.5 cm. The cut surface was solid, gray-white and fleshy. Histologically, tumor cells were arranged in compact nests or wide cords surrounded by fibrous stroma. The tumor cells had pleomorphic nuclei and quite rich cytoplasm; multinucleated, giant tumor cells were intermingled. Although no tumor cells contained apparent brown pigment, most were found to be positive for S-100 protein, HMB-45, Melan-A, and vimentin. The possibility of a metastatic lesion was considered. While the patient had a history of a pathologically examined dorsal nevus excision two years before, there was no evidence of either cutaneous or ocular primary melanoma at the time of diagnosis. Moreover, a thorough postoperative investigation did not reveal any other lesion in any other site favoring a metastatic spread. There was also no evidence of recurrent disease or metastasis one year after the surgery. This case is presented in view of its rare occurrence in the cecum. The difficulties in the diagnostic course are discussed, together with a literature review on distinguishing a primary mucosal melanoma from a metastatic one from an unknown or regressed cutaneous primary tumor.

Benign fibroblastic polyp of the colon: a case report.

There are a fair number of polyps in the gastrointestinal tract, which cannot be classified under a certain category. We report herein a 50-year-old man with a 6-mm sigmoidal polyp; he had been operated previously for rectal carcinoma. The polyp was characterized by benign-appearing spindle cells in the lamina propria leading to a wide separation and disorganization of the colonic crypts, accompanied by focal erosion and restricted areas suspicious for inflammatory fibroid polyp. The histologic features were found consistent with the disease spectrum of 'benign fibroblastic polyp of the colon' defined by Eslami-Varzaneh et al. The case is presented with a review of the literature and differential diagnostic considerations.