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.

Comparison of preoperative penile elastographic ultrasound findings and pathological tissue results of patients implemented with penile prosthesis.

OBJECTIVE: Histopathological analysis of the relationship between penile elastography and erectile dysfunction. MATERIAL AND METHOD: 12 patients who applied to our clinic for erectile dysfunction in the last 1 year and accepted this study were included. Preoperative two-dimensional shear wave elastography imaging was performed in 12 patients and recorded in the Pascal (kPa) unit. Approximately 0.5 × 0.5 × 0.5 cm tissue samples were taken from the right and left cavernous tissue during penile prosthesis implantation operation. Tissue samples were sent to the pathology department. The percentage of the area covered by muscle fibers and elastic fibers in the corpus cavernosum was noted semi-quantitatively (ratio of muscle fibers and cavernous body elastic fiber score). All data obtained were compared with each other. RESULTS: Cavernous body elastic fiber score data(Grouped Score 1, 2 and 3) and percentage of cavernous body muscle fibers data (Grouped %10, %20, %30… %100) were compared with Shear wave elastography data (kPa). The results were not statistically significant according to the Kruskal Wallis Test. Cavernous body elastic fiber score and the percentage of cavernous body muscle fibers were also compared, it was not statistically significant according to the Kruskal Wallis test and Spearman's correlation test. CONCLUSIONS: Penile shear wave elastography can be used clinically to quantitatively assess the amount of smooth muscle cells and elastic fibers in the penis, but it deserves to be studied with a larger number of patients and a more specific interpretation of the pathology preparation.

Could increased expression of aquaporin-1 be an etiological cause in childhood noncommunicating hydroceles that do not regress spontaneously?

BACKGROUND: Aquaporins are membrane water channel proteins that are expressed in the epithelium and endothelium. Their primary function is to control the flow of water in the membranes of the cells. OBJECTIVE: In this study, we investigated whether there is increased expression of aquaporin-1 in the tunica vaginalis of hydrocele patients in childhood that do not regress spontaneously an whether it has an effect on the etiology of hydrocele. STUDY DESIGN: Boys who were diagnosed with hydrocele and scheduled for surgery were included and formed the hydrocele group. Boys in the same age range who underwent surgery for inguinal hernia or undescended testicles were included as a control group. Aquaporin-1 expression was evaluated by immunohistochemical examination of capillaries in tissue samples taken from the tunica vaginalis during the operation. Aquaporin-1-positive vessels were counted by selecting 5 unrelated areas with the highest vascular density, and the average number of vessels was calculated for each case. RESULTS: A total of 48 male patients were included in the study. Of these, 27 constituted the hydrocele group (mean age 3.51 ± 2.59 years), and 21 constituted the control group (inguinal hernia, n = 17; undescended testicle, n = 4) (mean age 3.95 ± 3.80 years). The mean ages of both groups were statistically similar (p = 0.32). The mean numbers of aquaporin-1-positive vessels at the capillaries in the tunica vaginalis of the patients were 20.74 ± 7.10 in hydrocele group and 17.23 ± 4.07 in the control group. The expression of aquaporin-1 in the hydrocele group was significantly higher (p = 0.037). DISCUSSION: It was shown that aquaporin-1 expression was higher in adult cases with hydrocele. Also an increase in aquaporin-1 expression was detected in tunica vaginalis of children with hydrocele in our study. CONCLUSION: It was thought that aquaporin-1 overexpression may play a role in non-communicating hydroceles in children.

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.

Xanthogranulomatous pyelonephritis due to calculi in a 5-year-old girl.

BACKGROUND: Xanthogranulomatous pyelonephritis is characterized by the inflammatory destruction of the renal parenchyma and intensive renal fibrosis. It is named because of its pathological appearance; that of its granulomatous inflammatory process with lipid-laden macrophages, which appear yellow, hence `xantho` which is Greek for yellow. Xanthogranulomatous pyelonephritis is predominantly a disease of adults. In children it is diagnosed sporadically and is extremely rare in infants. The age of onset varies (21 days to 16 years), although 60-75% of cases have been diagnosed before 5 years of age. Recurrent urinary tract infections, obstructive nephropathy caused by renal calculus, malnutrition, abnormal lipid metabolism, altered immunologic response, lymphatic blockage, congenital urinary anomalies have been implicated in the etiology of xanthogranulomatous pyelonephritis in children. CASE: We report an unusual case of xanthogranulomatous pyelonephritis in a 5-year-old girl and discuss its clinical features, histopathological findings and treatment. In this article, we also emphasized the importance of diagnostic imaging in urinary tract infections which enabled us not to miss the underlying kidney stone disease. CONCLUSION: Nephrolithiasis may lead to very serious conditions such as xanthogranulomatous pyelonephritis. This condition can be easily diagnosed by ultrasound, but if not detected, it can lead to complete loss of renal function as in the case.

Focal Xanthogranulomatous Pyelonephritis in Brachydactyly Mental Retardation Syndrome (2q37 Deletion Syndrome).

Xanthogranulomatous pyelonephritis (XGP) is characterized by destruction of the renal parenchyma and granulomatous inflammation with lipid-laden foamy macrophages as well as inflammatory infiltration and intensive renal fibrosis. It generally occurs in adults, especially those in the fifth and sixth decades of life, but is occasionally seen in children as well. Brachydactyly mental retardation (BDMR) syndrome (OMIM 600430) is caused by a small deletion of chromosome 2q37 and is a rare condition, with roughly 100 cases reported worldwide. Here, we describe the case of a patient with deletion of chromosome 2q37, which is known as the BDMR syndrome, and XGP.

Association between neutrophil-lymphocyte & platelet lymphocyte ratios with prognosis & mortality in rapidly progressive glomerulonephritis.

Background & objectives: Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by features of nephritic syndrome and progressive loss of renal function over a short time. The objective of this study was to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic factors and pathological findings of renal biopsy in RPGN. Methods: Consecutive newly diagnosed RPGN patients who had follow up for at least six months were retrospectively analyzed. The estimated glomerular filtration rate (eGFR) was calculated. Albumin, C-reactive protein (CRP) levels and CRP/albumin ratio were also calculated. Results: Fifty four patients were included in the study. The mean age was 48.92±20.12 years. Clinicopathological diagnosis was pauci-immune glomerulonephritis (GN) in 40 while two had postinfectious GN, six systemic lupus erythematosus, three IgA nephropathy, two Henoch-Schönlein purpura and one membranoproliferative GN. The mean NLR was 7.02±6.34 and mean PLR was 273.90±39.15. Positive correlations between NLR and CRP levels (P=0.009, r=0.511) and CRP/albumin ratios (P=0.005, r=0.542) were observed. PLR and CRP/albumin ratios (P=0.041, r=0.412) were correlated positively. The per cent of fibrocellular crescents was negatively correlated with NLR (P=0.019, r=-0.291), and positively correlated with the lymphocyte count (P=0.05, r=0.256). In secondary crescentic subgroup, the per cent of fibrinoid necrosis had a positive correlation with PLR (P=0.013, r=0.642). Both NLR (P=0.036) and PLR (P=0.051) detected at the first month of the treatment period, were observed to be significantly correlated with mortality. Interpretation & conclusions: This study showed that NLR could predict mortality in patients with RPGN; correlated with systemic inflammation; showed a negative correlation with the per cent of fibrocellular crescents and could be regarded as a measure of glomerular inflammatory state. Moreover, PLR may be considered to be an indicator of disease severity in acute phase of crescentic GN.

Squamous cell carcinoma of the penis: a clinicopathological study from a population with late circumcision.

Squamous cell carcinoma (SCC) of the penis has been subject to only a few studies in populations where late childhood circumcision is performed. To asses clinicopathological features and human papillomavirus (HPV) status of penile SCC in men with late circumcision, eight institutions in the country volunteered to collaborate and 15 cases of penile SCC were collected from their pathology archives. The presence and genotype of HPV were determined in addition to clinicopathological features of the tumors. Findings were correlated with disease outcome. The mean age of the patients evaluated was 66.5 years. Histological subtypes were usual SCC (6∕15), papillary (2∕15), mixed (2∕15), basaloid (2∕15), acantholytic (1∕15), pseudohyperplastic (1∕15), and warty-basaloid (1∕15) carcinomas. HPV was identified in 33.3% of samples; HPV16 was detected in 60% of positive cases and was associated with basaloid and/or warty morphology. Cause-specific 1-year and 2-year survivals were 76.9% and 54.5%, respectively. The usual subtype and nodal metastasis were associated with worse outcome (p=0.045 and p=0.047, respectively). As a conclusion, our results suggest an inclination for penile SCC to develop at a later age in a population with late circumcision than the patients from the regions of high penile cancer incidence. These men seem to have less frequent HPV association and their outcome appears poorer than other populations, although reaching substantial provision is not possible due to our limited case number.

Diagnostic value of perinatal autopsies: analysis of 486 cases.

AIM: Autopsy is a beneficial procedure to determine the cause of death and the frequency of anomalies in perinatal losses. Even in the event of an autopsy not providing any additional information, completion of the procedure confirming the clinical diagnoses gives reassurance to both clinicians and parents. Here we present a 15-year archival study based on findings of perinatal autopsies. DESIGN AND METHODS: Four hundred and eighty-six cases from our archive were reviewed and according to the findings they were divided into three subcategories; (1) miscarriages (MCF); (2) fetuses terminated (FTA) for vital anomalies detected by prenatal ultrasonography; (3) premature or term newborns died within first month of life (neonates: NN). Autopsies were documented and classified according to week/age of cases, anomalies and causes of abortion or death. RESULTS: Two hundred and twenty-six of 486 cases (46.5%) were in MCF group while 227 (46.7%) and 33 (6.8%) were of them in FTA and NN groups, respectively. In FTA group, the most frequent anomaly detected was neural tube defects. In NN group, prematurity related complications were the most common cause of death. The autopsy process was found valuable in 39.7% of all cases. CONCLUSIONS: We suggest that autopsy procedure is diagnostically valuable even in situations when there is USG findings that are confirming FTAs or there is no important major fetal or placental anomaly detected in MCFs.

Pure Yolk sac presenting with inferior vena cava thrombus extending from bilateral external iliac veins to hepatic vein

ABSTRACT Introduction: Vena cava thrombus is an extremely rare complication of testicular tumors. We report on an unusual case of testicular tumor presenting with inferior vena cava thrombus extending from the left spermatic and bilateral external iliac veins to the hepatic vein. Case report: A-35-year old man presented with a 6-month history of left scrotal mass and a 1-day history of bilateral lower extremity edema. Computed tomography (CT) revealed the presence of thrombus extending from the left spermatic vein and bilateral external iliac veins to the hepatic vein, and multiple lymph node and lung metastases. 3 cycles of chemotherapy were given after the left high inguinal orchiectomy. Pathological examination demonstrated a pure yolk sac carcinoma with lymphovascular invasion and direct tumor extension into the left spermatic cord. CT and positron emission tompgraphy-CT obtained no findings of metastasis or recurrence at 3 months after the chemotherapy. Conclusion: We review this seldom case and discuss the literature with regard to its diagnosis and treatment.

Pure Yolk sac presenting with inferior vena cava thrombus extending from bilateral external iliac veins to hepatic vein.

INTRODUCTION: Vena cava thrombus is an extremely rare complication of testicular tumors. We report on an unusual case of testicular tumor presenting with inferior vena cava thrombus extending from the left spermatic and bilateral external iliac veins to the hepatic vein. CASE REPORT: A-35-year old man presented with a 6-month history of left scrotal mass and a 1-day history of bilateral lower extremity edema. Computed tomography (CT) revealed the presence of thrombus extending from the left spermatic vein and bilateral external iliac veins to the hepatic vein, and multiple lymph node and lung metastases. 3 cycles of chemotherapy were given after the left high inguinal orchiectomy. Pathological examination demonstrated a pure yolk sac carcinoma with lymphovascular invasion and direct tumor extension into the left spermatic cord. CT and positron emission tompgraphy-CT obtained no findings of metastasis or recurrence at 3 months after the chemotherapy. CONCLUSION: We review this seldom case and discuss the literature with regard to its diagnosis and treatment.

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.

Small Cell Carcinomas of the Bladder Highly Express Somatostatin Receptor Type 2A: Impact on Prognosis and Treatment--A Multicenter Study of Urooncology Society, Turkey.

Small cell carcinoma (SmCC) is a rare and aggressive neuroendocrine carcinoma of the bladder. Neuroendocrine carcinomas expressing somatostatin receptors (SSTR) in other viscera such as lung, pancreas, and gastrointestinal system respond to therapy with somatostatin analogs. In the present study, expressions of SSTRs 1 to 5 including type 2A are investigated by immunohistochemistry (IHC) and their relationship with clinicopathologic factors was evaluated. Hundred primary bladder SmCC cases were collected from 12 centers in Turkey. Forty-three cases were pure SmCC. Other cases had mostly papillary urothelial carcinoma as a second component. The percentage of the SmCC component ranged from 5% to 100%. SSTR-2A expression was membranous, whereas the other receptors showed cytoplasmic staining. The percentages of positive cases for SSTR-1, SSTR-2A, SSTR-3, SSTR-4, and SSTR-5 were 4% (3/75), 61.4% (54/88), 2.4% (2/84), 24.4% (20/82), and 6.25% (5/80), respectively. The percentage of SmCC component was positively correlated with the percentage of SSTR-2A expression (P=0.003) while negatively correlated with patient age (P=0.032). SSTR-2A expression was correlated with survival as a bad prognostic factor (P=0.018). SSTR-1, SSTR-3, SSTR-4, and SSTR-5 expressions did not show any statistical significance with any parameter. In conclusion, although the limited number of cases with adequate term follow-up, SSTR-2A expression could be a prognostic factor and somatostatin analogs therapeutic candidate for SmCCs of the bladder as these tumors show high percentage of SSTR-2A expression.

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.

Determination-of apoptosis and cell cycle modulators (p16, p21, p27, p53, BCL-2, Bax, BCL-xL, and cyclin D1) in thyroid follicular carcinoma, follicular adenoma, and adenomatous nodules via a tissue microarray method.

BACKGROUND/AIM: To identify the role of gene products associated with apoptosis and cell cycle in the pathogenesis of thyroid follicular neoplasm. MATERIALS AND METHODS: Thirty follicular adenomas (FAs), 16 follicular carcinomas (FCs), and 20 adenomatous nodules (ANs) were investigated with immunohistochemical staining of p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, and cyclin D1 via a tissue microarray method. RESULTS: Bcl-2 showed a significant difference between the benign groups (AN and FA) and the malignant group (FC). Bax was significantly higher in the FC group. p53 was lowest in the AN group and highest in the FC group with significant differences between the groups. p16 was significantly higher in the FC group than in the other groups. There was a significant difference between the AN group and neoplastic lesions in terms of p21 staining. The number of cases with positive p27 was lower in the AN group than the neoplastic groups. There was no significant difference in terms of Bcl-xL and cyclin D1. CONCLUSION: Cell cycle modulators, led by the Bcl-2 family, played an important role in the pathogenesis of thyroid follicular neoplasm, and p53, p16, and p21 in particular played a role in the carcinogenesis of FC.

Selenium, nickel, and calcium levels in cancerous and non-cancerous prostate tissue samples and their relation with some parameters.

In the present study, tissue samples of patients with cancerous and non-cancerous prostate were analyzed for their Se, Ni, and Ca contents. Possible relationship between Se, Ni, and Ca concentrations and some parameters including preoperative prostate-specific antigen (PSA) levels, histopathological neurovascular invasion, extra-capsular extension, seminal vesicle invasion, positive surgical margins, PSA relapse after radical prostatectomy, and total Gleason scores were obtained. Inductively coupled plasma (ICP) optical emission spectrometry and ICP-mass spectrometry instruments were used for the determination of analytes interested. All the system parameters in digestion and measurement steps were optimized to obtain efficient digestion and sensitive measurements. There was no statistically meaningful difference observed in the concentration of selenium in cancerous and benign prostatic tissues (p = 0.347) while nickel levels in cancerous tissues were observed as significantly lower than benign tissues (p < 0.001). In addition, calcium concentration in cancerous tissue samples were found to be statistically lower than those in benign tissues (p < 0.001) with mean values of 657 and 1,431 mg/kg, respectively.

A rare cause of glans penis masses in childhood: Fibroepithelial polyp.

Fibroepithelial polyps of glans penis are very rarely seen in childhood. A 6-month-old male admitted to our institution with a slowly enlarging glans penis mass on the ventral side of the glans penis. The mass was totally excised, and hystopathological diagnosis was a fibroepithelial polyp. All of the reported cases published previously, except one, are of adult age and all of them have been associated with the history of long-term condom catheter use. The presence of the case in childhood; however, suggests that the pathology might be congenital. This is the second pediatric case presented in the English literature.