The Prognostic Impact of Tumor Microenvironment and Checkpoint Blockade-Associated Molecules (PD-1, PD-L1, CD163 and CD14) in Nodal Diffuse Large B-cell Lymphoma, NOS.

It is aimed to determine expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), CD163 and CD14 in diffuse large B-cell lymphomas (DLBCL), and whether these markers may predict prognosis in DLBCL cases. A total of 52 nodal DLBCL, NOS cases with no known extranodal involvement at the time of diagnosis were evaluated. PD-1, PD-L1, CD163, and CD14 were studied by immunohistochemistry. The relationships between the results and clinical and laboratory prognostic markers were investigated. It was observed that patients with PD-1 expression < 5 positive cells/HPF had worse overall survival. No significant relationship was found between survival and PD-L1, CD163 and CD14 expressions. In addition, cases that are > 60 years of age, that have Eastern Cooperative Oncology Group (ECOG) performance score ≥ 2, stage IV disease, high International Prognostic Index score score (≥ 3), elevation of LDH, low albumin level, low hemoglobin level, low peripheral blood lymphocyte count, high peripheral blood neutrophil/lymphocyte ratio, high peripheral blood platelet/lymphocyte ratio were found to have worse overall survival. It was concluded that in patients with low number of PD-1 positive tumor-infiltrating lymphocytes have low survival rates and therefore PD-1 expression may be useful in indicating prognosis.

c-MET positivity and its relationship with histopathological findings in gastric carcinomas exhibiting HER2 gene expression.

Context: Co-expressions of receptor tyrosine kinases such as c-MET and HER2 were reported in many studies. The concomitant expression is associated with more aggressive clinical course. Aims: In this study, it was intended to investigate the correlation of the positivity of c-MET and HER2 with histopathologic findings and their impacts on prognosis. Subjects and Methods: After the decision of the ethics committee, a total of 64 cases, whose HER 2 status was studied by dual silver in situ hybridization/immunohistochemistry method, were included in the study. Immunohistochemical staining for c-MET was performed to all cases and the evaluation was performed similarly to the criteria for HER2 evaluation, but cytoplasmic staining was also considered significant. Statistical Analysis Used: The data were analyzed using SPSS 20 for Windows. Results: c-MET positivity which is considered by the score of 2+ and 3+ was found only in 34.4% of HER2 positive cases while it was 59.3% in HER2 negative cases (P = 0.045). The sole histopathological feature associated with c-MET positivity was distal gastric localization (P = 0.016). Conclusions: Even though higher rates of c-MET positivity in HER2 positive cases were stated in the literature, contrary results were obtained in this study. Comparing the HER2+/c-MET + co-expression group with the other groups, no difference was found about age, sex, macroscopic and microscopic characteristics. The presence of c-MET positivity in cases with HER2 expression suggests that c-MET expression might be associated with the resistance to Trastuzumab.

Relationship of Tumor-Associated Macrophage Population Detected by CD68 PG-M1, CD68 KP1, and CD163 with Latent EBV Infection and Prognosis in Classical Hodgkin Lymphoma.

OBJECTIVE: To evaluate the quantity of tumor-associated macrophages (TAMs) in cases of Hodgkin Lymphoma of classical type (cHL), and to reveal possible associations between TAM intensity and latent Epstein-Barr virus (EBV) infection, overall survival, progression-free survival, prognostic indices, and clinicopathological parameters. MATERIALS AND METHODS: A total 46 cases of cHL with complete clinical records were selected and re-evaluated histopathologically. Staining for CD68 (PG-M1; KP1 clones) and CD163 was evaluated and the cut-off values were defined. Also, all cases were evaluated using the chromogen in situ hybridization (CISH) method with EBER (Epstein-Barr virus-encoded RNA) probes for the presence of possible EBV infection. RESULTS: It was found that high expression levels of PG-M1 and high International Prognostic Scores (IPS) were associated with shortened overall survival (p=0.047, p=0.013). Cases with 2 or less areas of nodal region involvement were observed to have longer progression-free survival period (p=0.043). Higher expression levels of CD68 PG-M1, CD68 KP1, and CD163 were found to show significant associations with the presence of some clinical parameters such as the presence of B symptoms, spleen involvement, and the presence of EBV infection. CONCLUSIONS: Our findings suggest that increase of PG-M1+ TAM is associated with shortened overall survival, while higher expressions of all immunohistochemical markers are statistically significantly associated with the presence of EBV infection and clinical parameters mentioned above. These findings indicate that highlighting the TAM rate via macrophage markers in cases of cHL could be helpful in determining the prognostic risk groups and the relevant results should be mentioned in pathology reports.

Sonic hedgehog, TBX18, and TSHZ3 proteins involved in pyeloureteral motility development are overexpressed in ureteropelvic junction obstruction. An immunohistochemical, histopathological, and clinical comparative study.

OBJECTIVES: To compare pathological samples obtained from cases that underwent surgery for ureteropelvic junction (UPJ) obstruction with samples obtained during autopsies of subjects.  METHODS: Retrospectively, 42 patients who had undergone surgery due to UPJ obstruction (group 1) were included in the study. Histopathological and immunohistochemical features for sonic hedgehog (SHH), TBX18, and TSHZ3 of UPJ were evaluated and findings were compared with 20 autopsy cases (group 2).  RESULTS: In group 1, the scores were statistically significantly higher in terms of cytoplasmic SHH, nuclear TBX18, cytoplasmic and nuclear TSHZ3 staining. Statistically, no correlation was found between age and the staining scores belonging to these 3 antibodies in group 1 and group 2. Intense inflammation was found to be related with nuclear staining for TBX18.  CONCLUSION: Gene product expressions of SHH, TBX18 and TSHZ3 are statistically higher in patients with UPJ obstruction, when compared with control group. The explanation may be the reactivation of the processes, which had shown their effects in the embryological period, due to the chronic inflammation and long-term micro-trauma created by the disease.

Predictive value of cyclooxygenase-2 over expression for identifying prostate cancer from benign prostatic hyperplasia in prostate biopsy specimens.

BACKGROUND: We studied cyclooxygenase-2 (COX-2) immunohistochemical staining intensity both in prostatic biopsy and surgical samples of patients with prostate cancer to determine if it might provide prognostic information for the decision of re-biopsy indication. METHODS: Twenty-eight patients undergone radical prostatectomy whose final pathologic examination revealed prostatic adenocarcinoma were included in the study. Twelve patients with BPH in their pathological examination of both prostatic biopsy and open prostatectomy were considered as a control group. Intensity of COX-2 receptor was examined with immunohistochemical staining according to standard techniques. RESULTS: Positive COX-2 receptor staining was obtained 89.3% of biopsy samples and 93% of surgical samples in all cancer patients. The rate of agreement in COX-2 receptor staining of biopsy samples and radical prostatectomy samples was 76% in same patients (P=0.54). Similarly, the COX-2 receptor levels in biopsy specimens of patients with BPH open surgery compared with samples of the agreement still rate was 41% (P=0.41). Prostate cancer exchanging COX-2 receptor levels in patients with biopsy specimens in patients with BPH were found significantly more (P=0.008). CONCLUSIONS: In this study the feasibility of presence of COX-2 receptor staining in biopsy samples was shown. We have also demonstrated that COX-2 staining intensity was higher in prostatic biopsy samples of patients with prostatic cancer than patients with BPH. This leads a conclusion that, higher COX-2 expression levels in biopsy specimens may be used to decide re-biopsy in borderline preoperative PSA levels as well as in the cases with suspicious pathological findings for cancer.

The Role of Endobronchial Biopsy in the Diagnosis of Pulmonary Sarcoidosis.

OBJECTIVES: This study aimed to investigate the additional diagnostic value of endobronchial biopsy (EBB) in the diagnosis of pulmonary sarcoidosis. MATERIALS AND METHODS: This retrospective cross-sectional study included 59 patients with a preliminary diagnosis of sarcoidosis who were admitted to the Pulmonary Diseases Outpatient Clinic of a tertiary healthcare center between January 2005 and October 2012. The socio-demographic characteristics of the patients as well as clinical and radiological findings were recorded. All patients, irrespective of the presence of an endobronchial lesion (EBL), underwent fiberoptic bronchoscopy (FOB); two to four specimens were taken using EBB from the carina of the right middle lobe in the patients with EBL. RESULTS: Of the patients, 39 (66.1%) had normal bronchoscopic findings, while 5 had EBL. Diagnosis was based on EBB in 11 patients (18.6%). Six patients (15.3%) with normal bronchial mucosae were pathologically diagnosed by EBB. There was no statistically significant relationship between the diagnostic ratio of EBB and disease stage, extrapulmonary involvement, FOB findings, elevated lymphocyte rate in bronchoalveolar lavage (≥ 13%), a CD4/CD8 ratio of ≥ 3.5, and serum angiotensin-converting enzyme (ACE) level (p> 0.05). CONCLUSION: EBB not only offers the advantage of a high diagnostic ratio in patients with mucosal abnormalities but also contributes to pathological diagnosis in patients with normal mucosa. We recommend using EBB to support diagnosis with a low complication rate for patients undergoing FOB with a preliminary diagnosis of sarcoidosis in healthcare centers, where endobronchial ultrasound (EBUS) is unavailable.

[Sinonasal-type haemangiopericytoma: a case report]. / Sinonazal tip hemanjioperisitom: bir olgu sunumu

Sinonasal-type hemangiopericytomas, which comprise less than 0.5% of all sinonasal neoplasms, arise unilaterally in the nasal cavity as polypoid masses with a mean diameter of about 3 cm. A 34-year-old female patient was admitted due to nasal obstruction and epistaxis. A polypoid mass covered with intact mucosa that originated both from the right inferior concha and lateral nasal wall was detected by nasal endoscopy. The tumor, extending from the oropharynx to the nasopharynx, was measured as 3,5x3x2 cm. Although exhibiting characteristic histopathological features and typical clinical symptoms, this case with unexpected immunohistochemical findings can provide a viewpoint on the nature of this kind of tumors.

Chronic inflammation: a poor prognostic factor for endoscopic dacryocystorhinostomy.

Endoscopic endonasal dacryocystorhinostomy (En-DCR) success can be affected by many factors. In this study, we aimed to determine the effect of chronic inflammation on the surgical outcome of En-DCR. A series of 25 primary En-DCR cases and their lacrimal sac specimens were involved in the study. The surgical outcomes were assessed subjectively (satisfied and unsatisfied) and objectively (successful and unsuccessful). All the specimens were examined for the chronic inflammation related histopathological features (inflammatory cell infiltration, fibrosis and capillary proliferation) and graded according to their severity. Moreover, a "chronic inflammation score" was established to determine the intensity of chronic inflammation using the grade of histopathological features. A quantitative and statistical analysis of histopathological features and chronic inflammation were performed between patients with satisfactory and unsatisfactory outcome; and patients with successful and unsuccessful outcome. The overall success rate according to subjective and objective assessment was 60%. However, 9 of 10 patients with unsatisfactory and/or unsuccessful outcome (90%) had severe chronic inflammation of lacrimal sac. In subjective assessment, inflammatory cell infiltration (p = 0.050), fibrosis (p = 0.037), capillary proliferation (p = 0.007) and chronic inflammation (p = 0.003) had a statistically significant difference between patients with satisfactory and unsatisfactory outcome. In objective assessment, statistically significant differences were detected between patients with successful and unsuccessful outcome when they compared according to inflammatory cell infiltration (p = 0.027), capillary proliferation (p = 0.007) and chronic inflammation (p = 0.003). Chronic inflammation related histopathological features of variable degree may have a role on En-DCR outcome. Chronic inflammatory score can be used as an indicator of En-DCR success.

Isolated solitary intramedullary spinal cord metastasis presenting as the first manifestation of small-cell lung cancer: report of a rare case.

Background. Intramedullary spinal cord metastases presenting as the first manifestation of malignancies are extremely rare lesions. Case Description. The authors report a 74-year-old woman who presented with an isolated intramedullary spinal cord metastasis which presents as first manifestation of malignancy without central nervous system and/or other organ involvement. She went under surgery, and after histopathological evaluation, primary focus was determined in lung in positron emission tomography. She is still alive after 9 months since the first diagnosis of primary focus. Conclusion. In patients with solitary intramedullary lesion in the spinal magnetic resonance imaging, whole-body investigation might help for diagnosis of primary focus and approach to treatment.

Does asthma control as assessed by the asthma control test reflect airway inflammation?

BACKGROUND AND AIMS: The treatment of asthmatic patients is particularly focused on the control of symptoms as well as functional and inflammatory parameters. In our study, we investigated the relationship between the asthma control test (ACT) which evaluates symptoms and airway inflammation and functional parameters. MATERIALS AND METHODS: Stable asthmatic patients admitted to our pulmonary outpatient clinic were enrolled in the study consecutively and underwent the ACT, pulmonary function tests and methacholine bronchial provocation test (MBPT). Additionally, fractional exhaled nitric oxide level (FeNO) and induced sputum cell distribution were assessed. All these parameters were re-evaluated at the third month after adjusting medications of the patients according to baseline ACT scores. RESULTS: Of the 101 patients screened, we analyzed 83 who proceeded to the follow up visit. At the baseline visit, 8 were totally controlled, 36 partially controlled and 39 uncontrolled according to ACT. At the follow up visit, 10 were totally controlled, 39 partially controlled and 34 uncontrolled. Comparison of the two visits in terms of all parameters revealed significant reductions only in the percentages of patients with MBPT positivity (p = 0.029) and FeNO levels > 20 ppb (p = 0.025) at follow up. The percentages of patients with FeNO > 20 ppb, MBPT positivity, induced sputum eosinophilia or induced sputum neutrophilia did not show significant differences between totally controlled, partially controlled and uncontrolled groups at both baseline and follow up visits. CONCLUSION: Although the ACT scores did not show significant correlations with the airway inflammation parameters tested in this study, a marked reduction in the percentage of patients with MBPT positivity and FeNO > 20 ppb at follow up may suggest the importance of the control concept in the management of asthma.

Immunohistochemical analysis of Ki-67, p53 and Bcl-2 expression related to histological features in gastroesophageal reflux disease.

BACKGROUND/AIMS: The endoscopic and histologic findings of gastroesophageal reflux disease are usually indistinct. The current study was designed to define accurately the histology in gastroesophageal reflux disease and to develop a hypothesis that reflux produces immunohistochemical changes. METHODS: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 20 patients with evidence of reflux with 24-hour pH-meter monitoring and from 20 control subjects without clinical or endoscopic reflux. The pathogenesis of reflux esophagitis was discussed by comparing the histopathologic changes with determined Ki-67, p53 and Bcl-2 immunoreactivity. RESULTS: In this study, the presence of esophagitis was determined endoscopically in only 55% of the patients with gastroesophageal reflux disease, while microscopic esophagitis was detected in 60% of them. No correlation was found between presence of endoscopic esophagitis and microscopic esophagitis in the patients with gastroesophageal reflux disease. There was a significant difference between control cases and the patients according to histological parameters, which included basal activity (p=0.006), height of papillae (p=0.006), intraepithelial neutrophils (p=0.000), intraepithelial eosinophils (p=0.006), congestion (p=0.001), and dilated intercellular spaces (p=0.006). Immunohistochemically, there was a significant difference in the expression of p53 and Ki-67 between the three study groups (patients with/without microscopic esophagitis, controls) (p<0.05). However, there was no difference in Bcl-2 between the patients with reflux and control cases. CONCLUSIONS: In this study, we considered that microscopic esophagitis does not always accompany reflux, and the lack of reliable diagnostic histologic criteria is still a serious problem for pathologists. Immunohistochemically, an increase in cell proliferative activity and p53 protein accumulation to repair oxidative DNA damage related to reflux were observed. However, the close Bcl-2 immunoreactivity in all groups that was indicated by a weak positivity suggests that the inhibition of apoptosis may not be involved in reflux esophagitis.

Urachal urothelial carcinoma diagnosed at a radical prostatectomy operation: a case report.

BACKGROUND: Urachal carcinomas are rare tumors, and the majority of them are adenocarcinomas. Up to now, only 21 urachal urothelial carcinomas (UCas) have been reported. Here, we describe a case of high grade UCa arising from the urachal remnants. CASE: A 66-year-old man presented with voiding difficulties. Prostate specific antigen (PSA) was 5.46 ng/mL. Prostatic adenocarcinoma (PCa) (Gleason score 6) was diagnosed by needle biopsies. After the diagnosis of high grade, muscle invasive UCa with intact mucosa on frozen examination of the dome of bladder wall during the radical prostatectomy operation (RPO), partial cystectomy was performed. Microscopically, among the tumoral islands, cystic structures lined by cells with a benign appearance, which are considered urachal remnants, were noted. Cytokeratin 7 and high-molecular-weight cytokeratin were strongly positive, PSA and carcinoembryonic antigen were negative. Radiotherapy was given for both UCa and PCa. Six months after the diagnosis, an undifferentiated tumor was detected in a bladder transurethral resection specimen; thus, chemotherapy was given. After 1 course of chemotherapy, the patient was doing well. CONCLUSION: The origin of urachal carcinomas is usually obscured as it is a highly invasive carcinoma. The patient presented here was diagnosed incidentally during RPO. Although the stage was advanced, the tumor was detected before urachal remnants were destroyed. The treatment choice for urachal carcinomas is cystectomy. Adjuvant chemotherapy and radiotherapy are controversial.

Primary orbital neuroblastoma in a neonate.

Neuroblastoma is an undifferentiated malignant tumor of the primitive neuroblasts. Orbital neuroblastoma is typically a metastatic tumor. We describe a two-days-old girl, who presented with a large tumor in her left orbit. Magnetic resonance imaging revealed that the tumor originated from the retrobulbar area, extending into the upper and lateral orbit. She was operated on the fifth day of life. A histopathologic diagnosis of neuroblastoma was made. Medical evaluation including chest roentgenogram, ultrasonography of the abdomen, whole body computerized tomogram and bone scintigraphy showed no evidence of systemic involvement or metastasis. Neuroblastoma should be considered in the differential diagnosis of neonatal orbital tumors.

[A case of posttraumatic intracranial meningioma]. / Bir olguda travma sonrasinda intrakranyal meningiom olusumu.

Several etiologic factors have been proposed in the development of meningiomas, including trauma, radiation, oncogenic viruses, chromosomal abnormalities, and hormonal factors. We presented a 71-year-old female patient who had undergone an operation for a head trauma 27 years ago. Brain computed tomography scans showed a contrast-enhancing intracranial mass lesion, 5 x 4 x 4 cm in size, leading to diffuse edema in the left frontal region. At surgery, a tumoral mass was detected below the former craniotomy flap, with dural invasion, and a total excision was performed. Two silver clips were also noted in the previous surgical site. Histopathologic diagnosis was made as a transitional meningioma. No recurrences were detected within a year follow-up period.

Col IV and Fn distribution in prostatic adenocarcinoma and correlation of 67LR, MMP-9 and TIMP-1 expression with Gleason score.

OBJECTIVE: To assess the immunoreactivity of 5 proteins related to basement membrane (BM) and extracellular matrix in order to investigate whether any of them correlates with differentiation of prostatic adenocarcinoma (PAc). Two of these markers are collagen type IV (Col IV), the collagenous component of basement membrane, and fibronectin (Fn), an adhesion protein in extracellular matrix. Others are matrix metalloproteinase-9 (MMP-9), a type IV collagenase, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), which has a high affinity for MMP-9, and 67-kd laminin receptor (67LR), which belongs to the non-integrin laminin binding receptor family. STUDY DESIGN: Forty-three PAc cases with Gleason scores ranging between 5 and 10 and 10 benign prostatic hyperplasia (BPH) cases, the control group, were included in the study. Formalin-fixed and paraffin-embedded tissue slides from each case were immunostained with the avidin-biotin-peroxidase method. Immunoreactivity was determined by means of a scoring system similar to the Gleason scoring system. RESULTS: Overexpression of Col IV, Fn, 67LR and MMP-9 was detected in PAc as compared with BPH, whereas no difference was determined in TIMP-1 expression. Among these, only 67LR correlated statistically with Gleason score. CONCLUSION: Expression of 67LR in tumor cells was significantly increased in parallel to tumor grade. This may be useful in microscopic evaluation of PAc.

Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder.

OBJECTIVES: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. METHODS: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). RESULTS: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically ( P>0.05). Reproducibility was lower in low-grade tumors for both classifications. CONCLUSIONS: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.

The systemic cellular immune response in the Helicobacter pylori-associated duodenal ulcer and chronic antral gastritis.

BACKGROUND/AIMS: The exact pathogenesis of Helicobacter pylori infection is not fully understood. This study aims to evaluate the specific subset composition of peripheral blood lymphocytes in patients with H. pylori-positive duodenal ulcer n = 14), chronic antral gastritis n = 28), since reports so far have led to inconclusive and conflicting results. METHODOLOGY: 42 patients with dyspepsia and 50 controls underwent the following procedures: 1) gastroscopy and gastric biopsy (five specimens) 2) histology, 3) serologic test for anti-H. pylori antibodies IgG (Pyloriset EIA-G, Orion Diagnostica) and anticytotoxin associated gene A (cag A) IgG antibodies (VIVA Diagnositika by ELISA), 4) analysis of the peripheral blood lymphocytes using monoclonal antibodies reacting with lymphocyte cell surface antigens (anti-CD3, anti-CD19, anti-CD4, anti-CD8, anti-CD16 + CD56, anti-HLA DR) by flow-cytometry (Becton-Dickinson) to detect possible changes in the lymphocytes subpopulations in patients with duodenal ulcer and chronic antral gastritis. RESULTS: We found no alteration in total T and B lymphocytes and CD4+ T, CD8+ T lymphocytes and natural killer cells of both duodenal ulcer and chronic antral gastritis patients compared to normal persons. Although there was a slight increase in the proportion of active T lymphocytes in duodenal ulcer and chronic antral gastritis groups comparing to healthy subjects the difference was not statistically significant. CONCLUSIONS: These data indicate that there is no systemic alteration in the specific immune system in response to H. pylori in patients with duodenal ulcer and chronic antral gastritis.