CD47 expression in urothelial carcinoma and its correlation with histopathological findings.

BACKGROUND: The incidence of bladder cancers (BCs) is increasing day by day in both males and females with increased smoking. New treatment protocols are required due to the long follow-up times and high recurrence rates. CD47 (integrin-associated protein) is a membrane receptor that is effective in normal and pathophysiological events such as apoptosis, proliferation, adhesion, and immunity. Phagocytosis of both normal and tumor cells is prevented, by binding to the ligand signal regulatory protein-1 (SIRP-1)α on macrophages. Anti-CD47 antibodies can eliminate the binding and may be effective in treatment. METHODS: The study included 194 cases with urothelial carcinoma (UC) who underwent transurethral resection (TUR) of the bladder and had been followed up for one year. Cytoplasmic and membranous staining was preferred for CD47-positive staining. Staining results were compared with tumor grades, pathologic tumor stage, recurrence, and metastasis grade. RESULTS: The prevalence and intensity of CD47 staining in BCs were evaluated in this study. High-grade tumors were stained more pronouncedly compared with low-grade tumors and normal epithelium. The prevalence of CD47 staining was significant in pT2 (Pathological tumor stage 2, invades of muscularis propria) tumors, and its correlation with pTa (Pathological tumor stage a, noninvasive papillary carcinoma) tumors was significant ( P < 0.001). In the intensity evaluation, there was a significant difference between pTa and pT2 and between pT1 (Pathological tumor stage 1, invades lamina propria) and pT2 ( P = 0.003). CONCLUSION: CD47 is expressed strongly in high-grade tumors. The prevalence and intensity of CD47 staining are high in pathologic tumor stage, recurrence, and distant metastases and are considered poor prognostic markers. We believe that anti-CD47 antibodies can be used as an alternative to the current treatment or in combination with other medications, and the systemic side effects that may occur with intravesical treatment can be prevented.

Analysis of SMARCA4 and SMARCA2 Loss in Lung Sarcomatoid Carcinomas.

OBJECTIVE: Sarcomatoid carcinomas of the lung are a group of aggressive tumors. It has been reported that losses of SMARCA4 and SMARCA2, which play a role in the repair and remodeling of chromatin, contribute to the initiation, progression, and differentiation of neoplasms. The aim of our study was to examine SMARCA4 and SMARCA2 profiles in sarcomatoid carcinomas of the lung. MATERIAL AND METHOD: We screened pleomorphic carcinomas (PCs), carcinosarcomas (CSs), and pulmonary blastomas (PBs). The loss of SMARCA4 and SMARCA2 expression in the tumors was evaluated using immunohistochemical methods. The tumors were also examined to determine immunophenotype, histological tumor diagnosis, surgical resection, tumor histological component, largest tumor diameter, and lymph node metastasis status. RESULTS: Sixty-nine cases were screened, of which 84% were PCs, 13% were CSs, and 2.8% were PBs. In PCs components, 84.4% were biphasic and 15.5% were monophasic. The PCs showed the most frequent loss of SMARCA4 (25.8%) and SMARCA2 (44.8%). A loss of SMARCA4 and SMARCA2, respectively, was detected in 14.2% and 24.4% in both components of biphasic PCs; 12.2% and 14.2% in the sarcoma component of biphasic PCs; 0% and 8.1% in the carcinoma component of biphasic PCs; 22.2% and 33.3% in monophasic PCs; 0% and 22.2% in both components of CSs; and 0% and 22.2% in the sarcoma component of CSs. CONCLUSION: These findings demonstrate a loss of expression of SMARCA4 and SMARCA2 in pulmonary sarcomatoid carcinomas. Loss of the SMARCA complex may be caused by the heterogeneous morphological profile of sarcomatoid carcinomas, independent of tumor histopathological parameters.

Significance of CD47 expression in endometrial carcinoma.

Objectives: CD47 is a membrane protein that belongs to the immunoglobulin superfamily and regulates macrophage phagocytosis negatively. As CD47 expression at the cancer cell membrane would inhibit the phagocytic activity of immune cells, it is connected to an unfavorable prognosis in leukemia and malignancies of various solid organs. Materials and. Methods: In this study, retrospectively evaluated 72 patients who had been diagnosed with endometrial carcinoma at Pathology Department and had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO) and/or lymphadenectomy. CD47 expression was evaluated in tumorous and nontumor areas in all patients considering cytoplasmic and membranous brown staining in cells. The proportion of expression was evaluated as well as the intensity and an "h score" was obtained. This score was compared with known prognostic parameters. Results: CD47 expressions showed a statistically significant correlation with tumor grade (P < 0.05); however, no significant relationship was observed with myometrial invasion depth and lymph vascular invasion status (P = 0.923 and P = 0.754, respectively). Conclusions: As with other tumors, anti-CD47 antibody may be an alternative treatment option in patients with high-grade endometrial carcinoma.

Association of CDH1 -160 C → A and -347 G→ GA polymorphisms and expression of E-cadherin and gastric cancer: A case-control study.

OBJECTIVES: The loss of function of the E-cadherin (CDH1) gene with -160 C→A and -347 G→GA polymorphisms is regarded as a critical step for gastric cancer. It was aimed to investigate possible association of these polymorphisms and immunoexpression of E-cadherin with gastric cancer. MATERIAL AND METHODS: Gastric adenocarcinoma patients and individuals with benign gastric pathologies were included in this case-control study. Demographic data and pathological findings were recorded. Immunohistochemical staining of E-cadherin expression and analysis of -160 C→A and -347 G→GA polymorphisms were done. Differences between allele frequencies of -160 C→A and -347 G→GA polymorphisms and expression of E-cadherin were the primary outcomes. RESULTS: There were 78 gastric cancer patients (Group A) and 113 individuals with benign gastric pathologies (Group B). The number of male patients and mean age were higher in Group A (p <0.001). -160 C→A and 347 G→GA polymorphisms and their allelic distributions showed no difference between the groups (p> 0.05 for all). There was a significant association between -160 C→A polymorphism and grade of E-cadherin expression (p= 0.013). There were no significant differences between survival rates with -160 C→A, 347 G→GA and intensity of E-cadherin expression (p> 0.05 for all). There was no significant association between -160 C→A and -347 G→GA polymorphisms and gastric cancer. CONCLUSION: There was no impact of E-cadherin expression on tumoral features and survival in gastric cancer. -160 C→A polymorphism may influence the expression of E-cadherin in gastric cancer.

Mucin Expression in Mucinous Pancreatic Cysts: Can String Sign Test Predict Mucin Types? A Single Center Pilot Study.

BACKGROUND: Mucinous pancreatic cystic lesions (PCLs) express different mucin (MUC) types according to their histomorphologic types. High cystic fluid viscosity may help in the detection of mucinous PCLs. We hypothesized that high cystic fluid viscosity may be suggestive of a certain MUC type in mucinous PCLs. METHODS: Prespecified MUC types (MUC1, MUC2, MUC4, MUC5AC, and MUC6) were evaluated in 18 definitively diagnosed mucinous PCLs with sufficient tissue material and prediagnostic cyst fluid viscosity evaluation-string sign (SS)-test. We evaluated the agreement of MUC expression with positive SS test results. Later, we compared cystic fluid carcinoembryonic antigen (CEA) between the prespecified MUC expressing and nonexpressing cyst types. RESULTS: A total of 18 mucinous PCL patients, 11 females, with mean age ± SD (59.7 ± 13.3) were included. Almost all malignant mucinous PCLs expressed MUC1 (71.4%) (P = .023). We found no significant agreement between the prespecified MUC types and positive SS, except MUC4 which had mild agreement. Also, no significant relation was found between cystic fluid CEA levels and MUC expression (P = .584). CONCLUSION: We did not detect a significantly moderate or good agreement between the prespecified MUC types and SS test. MUC1 was highly expressed in malignant mucinous cysts; however, it was incompatible with the SS test. MUC4 expression showed mild agreement with the SS test in a small number of patients.

Cyst Fluid Carcinoembryonic Antigen Level Difference between Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms.

BACKGROUND/AIMS: The role of cyst fluid carcinoembryonic antigen (CEA) level in differentiating mucinous pancreatic cystic lesions (PCLs) is controversial. We investigated the role of cyst fluid CEA in differentiating low-risk (LR)-intraductal papillary mucinous neoplasms (IPMNs) from high-risk (HR)-IPMNs and LR-mucinous cystic neoplasms (MCNs). METHODS: This was a retrospective study of 466 patients with PCLs who underwent endoscopic ultrasound-guided fine-needleaspiration over a 7-year period. On histology, low-grade dysplasia and intermediate-grade dysplasia were considered LR, whereas high-grade dysplasia and invasive carcinoma were considered HR. RESULTS: Data on cyst fluid CEA levels were available for 50/102 mucinous PCLs with definitive diagnoses. The median CEA (range) levels were significantly higher in HR cysts than in LR cysts (2,624 [0.5-266,510] ng/mL vs. 100 [16.8-53,445]ng/mL, p=0.0012). The area under the receiver operating characteristic curve (AUROC) was 0.930 (95% confidence interval [CI], 0.5-0.8; p<0.001) for differentiating LR-IPMNs from LR-MCNs. The AUROC was 0.921 (95% CI, 0.823-1.000; p<0.001) for differentiating LR-IPMNs from HR-IPMNs. Both had a CEA cutoff level of >100ng/mL, with a negative predictive value (NPV) of 100%. CONCLUSION: Cyst fluid CEA levels significantly vary between LR-IPMNs, LR-MCNs, and HR-IPMNs. A CEA cutoff level of >100ng/mL had a 100% NPV in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

Benign Solitary Pulmonary Necrotic Nodules: How Effectively Does Pathological Examination Explain the Cause?

Aims: We investigated the histopathological features of solitary pulmonary necrotic nodules (NNs) of undetermined cause. We combined our findings with those obtained using other methods to determine how well the etiological factors were explained. Methods: We screened patients who underwent surgery to treat solitary pulmonary granulomatous and nongranulomatous NNs of undetermined cause. The NN sizes and features of both the NNs and adjacent parenchyma were evaluated. Histochemical analyses included Ehrlich-Ziehl-Neelsen (EZN), Grocott, and Gram staining. Polymerase chain reaction (PCR) was used to detect tuberculous and nontuberculous mycobacteria, panfungal DNA, Nocardia, Francisella tularensis types A and B, and actinomycetes. Results: The NNs were granulomatous in 78.9% and nongranulomatous in 21% of the 114 patients included. EZN staining or PCR was positive for Mycobacterium in 53.5% of all NNs: 62.2% of granulomatous and 20.8% of nongranulomatous NNs. We found a weak but significant correlation between granulomatous NNs and Bacillus positivity and a significant correlation between granulomas surrounding the NNs and the presence of multiple necroses. The NN etiology was determined via histopathological, histochemical, and PCR analyses in 57% of patients but remained undetermined in 42.9%. Conclusion: The causes of both granulomatous and nongranulomatous NNs can be determined by pathological examination. Granulomatous necrosis and granulomas in the adjacent parenchyma are important for differential diagnosis. When both features are present, they strongly support a diagnosis of tuberculosis, even in the absence of bacilli.

Unusual Histopathological Findings in Appendectomy Specimens: A Retrospective Analysis of 2047 Cases.

BACKGROUND: In this study, we retrospectively evaluated cases of patients who had undergone appendectomy in our hospital and aimed to present the efficiency of diagnostic tests and demographic data of cases. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis. In addition, the demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and reanalysis of archived resected appendix specimens was carried out. METHODS: Files of 2047 patients (1329 males, 718 females, sex ratio: 1.85, age range: 1-87 years, mean age: 26, 50 years), who had been operated with a diagnosis of acute appendicitis in the emergency department of Bezmialem Vakif University Medical Faculty from November 2011 to June 2014, were retrospectively evaluated. RESULTS: Cases were separated into 2 groups. Cases with histopathologic examination reported as acute appendicitis constituted group 1 (n = 2013, 98.34%), and cases with pathologic findings other than acute appendicitis constituted group 2 (n = 34, 1.66%). The second group consisted of 8 low-grade mucinous neoplasms, 7 mucoceles, 6 carcinoid, 5 granulomatous inflammation, 4 intraluminal Enterobius vermicularis, 1 endometriosis externa, 1 adenocarcinoma infiltrated to serosa, 1 mesenteric cyst, and 1 low-grade adenocarcinoma formed in mucinous cystic neoplasm background. CONCLUSION: Acute appendicitis is the most common emergency surgical condition. Although most of the resected appendectomy specimens showed typical histopathologic findings, some (1.66%) showed unusual histopathologic findings. Even if the macroscopic appearance of the specimen is normal or acute appendicitis, we suggest routine histopathological examination.

Analysis of Appendiceal Neoplasms on 3544 Appendectomy Specimens for Acute Appendicitis: Retrospective Cohort Study of a Single Institution.

BACKGROUND Appendiceal neoplasms are rare and generally determined in appendectomy specimens for acute appendicitis. Depending on a tumor's histopathology and size, appendectomy or right hemicolectomy are the surgical treatment options. Adenocarcinomas, mucinous neoplasms, goblet cell carcinoids and neuroendocrine tumors are the types of the primary appendiceal neoplasm histopathology. In this study, we aimed to determine the incidence of appendiceal neoplasms in an acute appendicitis cohort. Also, histopathological distributions, demographic data, preoperative radiological diagnosis, and intraoperative findings were revealed for analysis, retrospectively. MATERIAL AND METHODS Between October 2011 and September 2017, 3554 appendectomies were performed for acute appendicitis in Bezmialem University Hospital, Istanbul Turkey. The medical records of these consecutive 3554 patients were evaluated retrospectively. After the histopathological analysis of the appendectomy specimens, a total of 28 patients were detected as having appendiceal neoplasm including appendiceal adenocarcinoma, low grade mucinous neoplasia, and appendiceal neuroendocrine tumors. RESULTS Appendiceal neoplasms were determined in 28 out of 3554 acute appendicitis patients with an incidence of 0.78%. According to the histopathological types, 3 of the cases (10.7%) were appendiceal adenocarcinoma, 8 of the cases (28.5%) were low grade mucinous neoplasia, and 17 of the cases (60.8%) were neuroendocrine tumors. The overall incidence of the appendiceal neuroendocrine tumors was 0.48%. CONCLUSIONS The information obtained from our study suggests that pathological examination of the specimen may not be necessary if there is no doubt according to preoperative radiological diagnosis and/or intraoperative findings of the surgeon.

Spinal cord ischemia after endoscopic ultrasound guided celiac plexus neurolysis: case report and review of the literature.

INTRODUCTION: Endosonography guided celiac plexus neurolysis is efficacious in the management of severe pain due to advanced pancreatic cancer. Although endoscopic ultrasound (EUS) guided celiac neurolysis (CN) is mostly a safer procedure than the percutaneous posterior approach, severe complications such as paraplegia have been reported. CASE REPORT: We describe a patient with advanced adenocarcinoma of the pancreas and severe pain who developed irreversible paraplegia after EUS guided CN. CONCLUSIONS: Endosonography guided celiac plexus neurolysis also might be complicated with paraplegia as already observed with percutaneous approach. The underlying mechanism could not be explained clearly until now. We detected concomitant embolic occlusion of Adamkiewicz and anterior radicularis magna arteries in magnetic resonance angiography. So, this procedure must be considered only for malignancy patients.

EUS-guided FNA of a portal vein thrombus in hepatocellular carcinoma.

Portal vein thrombosis is a relatively rare but well-known complication of cirrhosis that has a prevalence of between 1% and 5.7%. On the contrary, in case of hepatocellular carcinoma (HCC), it is a much more frequent complication. In this paper, we presented three cases that had liver cirrhosis, mass and portal vein thrombosis in liver. We were not able to diagnose the cases through imaging methods, laboratory results or histopathologically, however, they were diagnosed with endoscopic ultrasonography- fine needle aspiration EUS-FNA from portal vein thrombus.

Co-existence of acute appendicitis and inflammatory myofibroblastic tumor of the small intestine: A case report.

INTRODUCTION: Inflammatory myofibroblastic tumor as a rare neoplastic lesion is seen most commonly in the pulmonary system. Beside the presence of limited number of inflammatory myofibroblastic tumors of the gastrointestinal tract in the literature, co-existence with acute appendicitis has not been reported before. PRESENTATION OF CASE: A 27-year-old woman admitted to emergency department with acute abdominal pain at the right lower quadrant. The initial diagnosis was as acute appendicitis. Intraoperatively, a mass with a diameter of almost 5 cm originated from the distal ileal segments neighboring the appendix was seen. The patient was managed by segmental resection of the small intestine including the mass with appendectomy. Histologically, there were bundles of spindle cells accompanied by lymphoplasmocytic infiltration. The immunohistochemical studies showed that tumor cells were positive for smooth muscle actin, vimentin, perinuclear activity for anaplastic lymphoma kinase and CD 68. The final pathologic diagnosis was inflammatory myofibroblastic tumor. DISCUSSION: Concomitant resection of tumoral lesions detected in the neighbor intestinal segments during appendectomy should be considered to diagnose and treat. For the diagnosis of inflammatory myofibroblastic tumor, immunohistochemistry pattern including positivity for actin, vimentin, CD 68 and anaplastic lymphoma kinase plays a crucial role. Therefore, detailed immunohistochemistry analysis should be performed in suspicious cases. CONCLUSION: Coexistence of inflammatory myofibroblastic tumor located in the gastrointestinal system with acute appendicitis is a rare event. Complete surgical excision should be regarded as the mainstay of the treatment. Long-term follow up with serial imaging techniques is recommended.

The importance of upper gastrointestinal endoscopy in morbidly obese patients.

BACKGROUND/AIMS: Obesity is an epidemic and its prevalence and number of patients underwent bariatric surgery continue to increase worldwide. This study aimed to evaluate endoscopic findings and co-morbidities, to investigate the prevalence of Helicobacter pylori (H. pylori) infection and the relationship between body mass index (BMI) and gastroesophageal sphincter incompetency in obese patients. MATERIALS AND METHODS: An upper gastrointestinal system endoscopy and mucosal sampling were performed in all patients hospitalized for bariatric surgery. Age, gender, BMI, co-morbidities and endoscopic findings were recorded. Gastroesophageal sphincter incompetency was classified according to Hill classification. The patients were divided into two groups: group I, endoscopically normal and group II, endoscopically abnormal. RESULTS: Total 127 patients were enrolled into prospective study. Of these, 93 (%73.2) were female and the mean age was 38.9±12.5 years (range: 16-68). Abnormal endoscopic findings and H. pylori were detected in 80.4% and 44.9% of patients, respectively. In group II, patients were older, BMI higher and H. pylori more prevalent (all statistically significant). Diabetes mellitus, hypertension and dyslipidemia were the most frequent common co-morbidities. Rate of multiple co-morbidities were more common in group II. Gastroesophageal sphincter incompetency in total group was observed in a rate of 46.5% and was weakly correlated with BMI. CONCLUSION: Four-fifths of obese patients have at least one endoscopic abnormal finding, three fourth at least one co-morbidity and half H. pylori positivity. Upper gastrointestinal system endoscopy should be performed routinely in all patients to predict and prevent complications following bariatric surgery.

Endotracheal ectopic parathyroid adenoma mimicking asthma.

Primary benign tumors of the trachea are uncommon. These tumors may cause tracheal occlusion and lead to a misdiagnosis of asthma. Ectopic parathyroid adenoma (EPA) can be seen anywhere between the mandibular angle and the mediastinum. The distal part of the trachea is a rare location for EPA, and EPA obstructing the endotracheal lumen has not been reported in the literature. We herein describe a 52-year-old female with a several-year history of asthma treatment who presented with progressive dyspnea. Computed tomography revealed a mass that was obstructing the tracheal lumen. Total mass excision was performed via endobronchial treatment, and pathologic examination revealed EPA.

Thoracic primitive neuroectodermal tumor: an unusual case and literature review.

We describe herein a rare case of a primary primitive neuroectodermal tumor (PNET) in the mediastinum of a 75-year-old man. Grossly, the tumor was located in the left upper anterior mediastinum. Transcutaneous fine-needle biopsy (TCNB) revealed small round-cell proliferation. The expression immunohistochemical analysis was confirmed the diagnosis of PNET. He was successfully treated with chemotherapy and is alive with no sign of recurrence for 17 months after the diagnosis.

Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors.

PURPOSE: The diagnosis of benign and malignant uterine smooth muscle tumors depends on morphologic criteria such as nuclear atypia, coagulative tumor cell necrosis and mitotic activity. Most of these tumors are readily classifiable into benign or malignant categories using these criteria. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. Hence, it would be useful to have additional markers which could help to distinguish these tumors. The aim of the study was to evaluate p16 and p21 expressions in uterine smooth muscle tumors and determine whether p16 and p21 have a potential value in the differential diagnosis of problematic cases. In addition, we evaluated whether the differential expression of p16 and p21 in uterine leiomyosarcomas correlated with tumor recurrence and patient survival. METHODS: p16 and p21 expressions were investigated by immunohistochemistry from paraffin-embedded tissues in 53 cases of uterine smooth muscle tumors consisting of 15 cases of leiomyoma, 14 cases of atypical leiomyoma (leiomyoma with bizarre nuclei), 3 cases of smooth muscle tumor of uncertain malignant potential (STUMP) and 21 cases of leiomyosarcoma. Cases were evaluated with respect to both staining percentage and intensity. RESULTS: There was a statistically significant difference in p16 and p21 staining percentage and intensity between leiomyosarcomas and the other groups. There was no difference in p16 and p21 expressions between leiomyomas, atypical leiomyomas (leiomyoma with bizarre nuclei) and STUMPs. Multivariate analysis showed that the tumor stage was the only independent significant prognostic factor for overall survival in leiomyosarcomas. Neither p16 nor p21 was correlated with disease-free or overall survival. CONCLUSIONS: Our findings suggested that p16 and p21 may be of value as an adjunct to conventional morphologic criteria in the assessment of problematic uterine smooth muscle tumors.