The Status of Spermatogenesis in Germ Cell Tumor Bearing Testis and Its Association with Metastatic Disease.

INTRODUCTION: We aimed to evaluate the status of spermatogenesis detected by histological examination of non-tumoral testicular tissues in tumor bearing testis and its association with advanced stage disease. PATIENTS AND METHODS: We retrospectively reviewed patients with testicular germ cell tumors (TGCTs) that undergone radical orchiectomy. All non-tumoral areas of the orchiectomy specimens were examined for the status of spermatogenesis. Patients were divided into two groups as localized (stage I) and metastatic (stage II-III) disease and analyzed separately for seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT). RESULTS: Four hundred fifty-four patients were included in our final analysis. Of those, 195 patients had SGCT, and 259 patients had NSGCT. Three hundred and six patients had localized disease at the time of diagnosis. Median (Q1-Q3) age was 31 (26 - 38) years and 102 (22.5%) patients had normal spermatogenesis, 177 (39.0%) patients had hypospermatogenesis and 175 (38.5%) patients had no mature spermatozoa. On multivariate logistic regression analysis, embryonal carcinoma >50% (1.944, 95 %CI 1.054-3.585, P = .033) and spermatogenesis status (2.796 95% CI 1.251-6.250, P = .012 for hypospermatogenesis, and 3.907, 95% CI 1.692-9.021, P = .001 for absence of mature spermatozoa) were independently associated with metastatic NSGCT. However, there was not any variables significantly associated with metastatic SGCT on multivariate logistic regression analysis. CONCLUSION: Our study demonstrated that only 22.5% of patients with TGCTs had normal spermatogenesis in tumor bearing testis. Impaired spermatogenesis (hypospermatogenesis or no mature spermatozoa) and predominant embryonal carcinoma are associated with advanced stage NSGCT.

A Rare Case of Xanthomatous Meningioma.

Xanthomatous meningioma is an extremely rare subtype of metaplastic meningiomas with few cases reported in the literature. Histopathologically, it is composed of oval-shaped cells that have central nuclei and cytoplasm with lipid-filled vacuoles, resembling macrophages. Here, the authors present a case of xanthomatous meningioma and discuss the hypotheses related to its origin and the differential diagnosis. A 40-year-old woman presented with an increased headache complaint over the past month. A computed tomography scan revealed a heterogeneous mass on the right parietal lobe, following which a right craniotomy was done. Microscopic examination showed neoplastic meningothelial cells with whorl formation and areas of xanthomatous changes. Both meningothelial and xanthomatous cells were positive with vimentin, progesterone, and epithelial membrane antigen. CD68 and lysozyme were expressed only in the xanthomatous component, and there was no expression with periodic acid-Schiff (PAS) stain and PAS-diastase. As the diagnostic criteria of atypical meningioma were not observed, a diagnosis of xanthomatous meningioma, WHO grade I, was made. Owing to the characteristic xanthomatous changes, its differential diagnosis includes grade II clear cell meningioma, Rosai-Dorfman disease, and hemangioblastoma. To avoid misidentifying these cells as macrophages, a high degree of awareness of this unique subtype of meningioma is required.

Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes

Abstract Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.

Splenic infarction is not rare in granulomatosis with polyangiitis.

Splenic involvement is rarely reported in patients with ANCA-associated vasculitides (AAVs), particularly in those with granulomatosis with polyangiitis (GPA) and is in fact considered to be underestimated. We aimed to investigate the frequency of splenic lesions-mainly infarction-and related factors in patients with AAVs. Patients with AAV whose abdominal or thoracic computed tomographies (CTs) were performed at or after diagnosis were included in the study. CT images were examined for splenic lesions. Overall, 69 patients (median age at diagnosis 54 [IQR 24] years; 55% with GPA, 29% with microscopic polyangiitis, and 16% with renal-limited disease) were included in the analysis. Splenic pathologies were detected in 19 (28%) patients; 12/19 (63%) splenomegaly and 7/19 (37%) splenic infarction. All patients with splenic infarction exhibited GPA with PR3-ANCA-positive serology. Three of these seven patients had autosplenectomy. Patients with splenic infarction were younger at diagnosis (p = 0.018) with also significantly higher ear-nose-throat (ENT) (%100 vs 37; p = 0.002) and eye involvement (%50 vs %12; p = 0.044) than patients without splenic infarction. Splenic pathologies are not rare in AAVs. Furthermore, infarction can help separate GPA from MPA. In young patients with GPA, particularly those with ENT and eye involvements, physicians should consider splenic infarction.Key Points• Splenic infarction is more common than previously thought in ANCA-associated vasculitides, particularly in granulomatosis with polyangiitis.• Detecting splenic infarction can help differentiate granulomatosis with polyangiitis from other subgroups.

Unusual intraconal localization of orbital giant cell angiofibroma.

Giant cell angiofibroma (GCA) is a recently reported rare soft-tissue tumor that can develop in various sites including orbit. Orbital GCAs were mainly located in the eyelid or extraconal regions such as lacrimal gland and conjunctiva. We report an atypical case of a GCA arising in the intraconal area of the orbit in a 65-year-old male patient. The tumor was excised in total by lateral orbitotomy. Histological and immunohistochemical features were consistent with the diagnosis of GCA. No recurrence was observed during the follow-up of over 2 years. GCA is a rare tumor that should be considered in the differential diagnosis of intraconal orbital tumors. Complete surgical removal is the current optimal treatment option.

Unusual locations of hydatid disease: A 10-year experience from a tertiary reference center in Western Turkey.

INTRODUCTION: Hydatid disease is an endemic parasitic infection caused by Echinococcus granulosus mostly seen in the Mediterranean countries. The most affected organ is the liver, however hydatidosis can be found anywhere in the human body. METHODS: The records of patients who were diagnosed with hydatid disease in our hospital from December 2005 to February 2016 were analyzed retrospectively. The cases were evaluated and recorded depending on their gender, age and the localization of the cysts. RESULTS: A total of 329 patients diagnosed over a 10-year period were included in our study. There were 202 females (61.4%) and 127 males (38.6%). The hydatid cysts were located in the liver in 257 (78.1%) patients and in unusual locations in 72 (21.9%) patients. The most common unusual site for hydatid cysts was the spleen followed by bones, central nervous system, soft tissue, the kidney and the gall bladder. Amongst these 72 patients who had hydatid cysts in unusual locations; 33 patients had concomitant liver hydatidosis, whereas 39 patients had primary involvement of unusual sites. Two patients with malignancies also had hydatid cysts in different locations. CONCLUSION: Hydatid disease affects many organs in the body and therefore it can pose a major diagnostic dilemma and it may mimic other entities. In endemic areas, a differential diagnosis of hydatid disease should be considered for cystic masses in any anatomical location.

Extra-Gastrointestinal Stromal Tumor of Prostate.

BACKGROUND: Extra-gastrointestinal stromal tumor is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract. Prostatic extra-gastrointestinal stromal tumor has rarely been noted. CASE REPORT: A 56 year-old man presented with pain in the anal region. A digital rectal examination revealed that the prostate was markedly enlarged with a smooth, bulging surface. Computerized tomography images showed a 6 cm heterogeneous, infiltrative tumor within the prostate gland extending to the trigon of the bladder, left seminal vesicle and rectum. The tru-cut biopsy of the prostate was reported as leiomyoma. It was decided to perform surgery and the masses were easily and completely removed from the adjacent structures. The case was reported as extra-gastrointestinal stromal tumor within the intermediate- risk category with free surgical margins. Four years after the surgery, a locoregional failure was observed and treated with imatinib. CONCLUSION: Stromal tumor, although rare, should be considered in the differential diagnosis in patients with an enlarged prostate.

DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease.

BACKGROUND: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. RESULTS: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium BeadArrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. CONCLUSIONS: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. CpG methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.

Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model.

BACKGROUND: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. METHODS: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. RESULTS: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. CONCLUSION: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.

[Evaluation of clinical and laboratory findings of adult visceral leishmaniasis cases]. / Eriskin viseral leysmanyaz olgularinin klinik ve laboratuvar bulgularinin degerlendirilmesi.

Visceral leishmaniasis (VL, kala-azar) is a zoonotic infection caused by Leishmania species which are transmitted to humans by the bites of infected female phlebotomine sandflies. Leishmania infantum is the responsible species of VL in Aegean, Mediterranean, and Central Anatolia regions of Turkey mainly observed sporadically in pediatric age groups. The aim of this study was to evaluate the clinical and laboratory findings of adult patients with VL who were admitted to our hospital. A total of 10 patients (3 female, 7 male; age range: 18-67 years, mean age: 39.3 ± 16.51) followed in the infectious diseases clinic of the hospital between 2000 and 2013 were evaluated retrospectively. The diagnosis of VL was based on the presence of appropriate clinical and physical examination, as well as biochemical findings, positive serological test results (indirect fluorescent antibody test, and rK39 rapid antigen test) and/or detection of amastigote forms of parasite in the bone marrow aspiration samples. Of the cases three were diagnosed with both bone marrow and serology positivity, five with bone marrow positivity and one of each only with liver biopsy and positive serology result. Time interval from onset of the symptoms until the establishment of the specific clinical diagnosis was ranged from 2 to 12 weeks. The most frequent initial symptoms were fever, fatigue and abdominal distension. None of the patients had immunosupressive conditions such as HIV infection, corticosteroid use, immunosupressive treatment, or transplantation. All the patients were from Aegean region and six were living in rural areas. In all cases, hepatosplenomegaly, increased erythrocyte sedimentation rate, albumin/globulin ratio inversion, anemia, leukopenia and among nine cases trombocytopenia were detected. In one case acute renal failure has been developed before treatment and the patient was admitted to dialysis program. Bacterial superinfection occurred in two cases. Patients were treated with either meglumine antimonate (Glucantime(®), 20 mg/kg/day, intramuscularly for 28 days) or liposomal amphotericin B (3 mg/kg/day, intravenously for the first 5 days, then on 14(th) and 21(st) days) according to the availability of drugs. During one year follow-up period all of the patients improved and no recurrence was seen in any patient. In conclusion, among adult patients with fever uncontrolled within 2-week course of ampiric antibiotic treatment without any infectious focus or malignancy, VL should also be considered.

Comparison between Radiological and Invasive Diagnostic Modalities in Diagnosis of Breast Cancer.

BACKGROUND: Breast cancer is the most common cause of deaths of cancer in women. Nowadays, following completion of imaging methods, mainly fine needle aspiration biopsy (FNAB) and core biopsy methods have been used for establishing cytopathological diagnosis although discussions regarding superiority continue. MATERIALS AND METHODS: Those with a complaint of "mass in breast" along with those diagnosed to have a mass as a result of routine physical examination among all patients applying to our clinic between 01.01.2009 and 31.12.2011 were retrospectively assessed. Totals of 146 and 64 patients with complete radiological observation who had undergone FNAB and core biopsies, respectively, were evaluated. Postoperative pathological results of patients of both groups receiving surgery were also taken into consideration. All results were compared in terms of false positivity/negativity, sensitivity/specifity, surgery types and distribution of postoperative results with regard to diagnoses along with those of malignant/benign masses with regard to quadrants determined. RESULTS: Diagnostic malignancy power of mammographic BIRADS classification was 87.3%. However, the value was 75% in the core biopsy group. Sensitivity and specifity following comparison of FNAB and postoperative pathology results of those receiving surgery were 85.4% and 92.9% while they were 93.5% and 100% in the core biopsy group. Diagnostic malignancy power, calculated by determining AUC in ROC analysis, of FNAB was 89.1% while that of core biopsy was 96.7%. CONCLUSIONS: It was shown that core biopsy is superior to FNAB in terms of sensitivity, specificity and accurate histopathological classification. However; quick, cheap and basic diagnosis by means of FNAB should not be ignored. Sensitivity of FNAB is rather high in experienced hands and furthermore it would be expected to be lower than with core biopsy.

Cytopathological features of matrix-producing carcinoma of the breast.

Matrix producing carcinoma (MPC) of the breast is a very rare subtype of metaplastic carcinoma with heterelogous elements, which comprises <0.1% of invasive breast carcinomas. There are very few reports describing the cytological features of MPC. In this article, we aimed to discuss cytological, histopathological and immunohistochemical features of this rare entity in a 59-year-old woman.

Significance of IMP3, nucleophosmin, and Ki-67 expression in papillary thyroid carcinoma.

The purpose of our study was to investigate the diagnostic value of expression of IMP3, nucleophosmin, and correlation of these markers with Ki-67 proliferation index in papillary thyroid carcinoma and benign neoplasms of thyroid gland. The aim was also to investigate whether there is a difference between papillary and micropapillary carcinomas with regard to clinicopathologic parameters beside IMP3, nucleophosmin, and Ki-67 proliferation index. It was concluded that IMP3 and nucleophosmin cannot be a routine diagnostic marker for discrimination of papillary carcinomas and benign lesions. IMP3 positive staining was quite scarce in IMP3 positive papillary carcinomas although specifity of IMP3 is 100%. A statistically significant correlation was not detected between nucleophosmin, IMP-3, and Ki-67 proliferation index. A statistically significant correlation was found between tumor size, lymphovascular embolism, and Ki-67 proliferation index. There was also significant correlation between tumor size and lymphovascular embolism.

Hormone receptor, HER2/NEU and EGFR expression in ovarian carcinoma--is here a prognostic phenotype?

PURPOSE: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. MATERIALS AND METHODS: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. RESULTS: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. CONCLUSIONS: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

The prevalence of IgG4-positive plasma cell infiltrates in inflammatory bowel disease patients without autoimmune pancreatitis.

BACKGROUND/AIMS: IgG4-related autoimmune disease can exist in other organs even when there is no evidence of autoimmune pancreatitis. The aim of our study was to determine the prevalence of IgG4-positive plasma cells in the histopathological evaluations of colon biopsy specimens in IBD patients. MATERIALS AND METHODS: The number of IgG4-positive plasma cells with strong cytoplasmic immunoreactivity was counted in each colon biopsy from inflammatory bowel disease patients who had no evidence of autoimmune pancreatitis. Five high power fields (HPFs) in the highest density plasma cell infiltration area were counted and were then averaged. An average >10 cells/HPF was considered significant for IgG4-related disease. RESULTS: We detected IgG4-positive plasma cell staining in the colon of 21 of 119 patients (17.6%). Of these 21 patients, 5 had elevated serum IgG4 levels (>140 mg/dL). Of the total, 4.2% (5/119) had both IgG4-immunstaining and elevated IgG4 serum levels. The demographic features, disease type and activity, and response to treatment (especially to steroid treatment) were similar between the IgG4-negative and IgG4-positive groups. CONCLUSION: In our study, 4.2% of patients with the diagnosis of IBD had elevated IgG4 serum levels and significant IGg4 immunostaining. Together, these two parameters indicate the possible diagnosis of an IgG4-related systemic disease.

Lack of correlations among histopathological parameters, Ki-67 proliferation index and prognosis in pheochromocytoma patients.

BACKGROUND: In this study prognostic correlations of histopathologic parameters and the Ki-67 proliferation index and as well as the diagnostic value of immunohistochemical markers in pheochromocytomas were evaluated. MATERIALS AND METHODS: A total of 22 patients diagnosed with a pheochromocytoma between 2000-2010 in Izmir Katip Celebi University Ataturk Training and Research Hospital were included. Diagnostic value of the PASS scoring system, and prognostic correlations of histopathologic parameters and Ki-67 proliferation index were investigated. SPSS for Windows 17.0 software was used for statistical analysis. RESULTS: There was no statistically significant correlation between recurrence and clinicopathologic parameters or the PASS score (PASS>4). In addition, there were no statistically significant correlations between PASS score and clinicopathologic parameters, such as diameter (5 cm), weight (>100g), gender (female/male ratio) and age (25-45/45-55/>55). Besides, there were no significant correlation between diameter and clinicopathological parameters and also recurrence. However, there was a statistically significant correlation between Ki-67 proliferation index and capsule invasion (p=0.047). CONCLUSIONS: Some but not most of the findings in our study were concordant with the literature. To clarify relationships, investigations with standard scoring systems which are not affected by subjective factors and feature appropriate histopathological criteria should be made on larger study groups.