Preferentially expressed antigen in melanoma (PRAME) expression has been described in Merkel cell carcinoma (MCC), but its clinicopathologic and biological significance remains incompletely characterized. We investigated PRAME expression in MCC and its relationship with Merkel cell polyomavirus (MCPyV) status, PD-L1 expression, tumor-infiltrating lymphocytes (TILs), clinicopathologic features, and clinical outcome. Thirty-five MCC cases from 3 centers were retrospectively reviewed. Histopathologic features and immunohistochemical expression of PRAME, PD-L1, MCPyV, and p53 were reassessed. PRAME positivity was defined as staining extent scores of 3+ or 4+ combined with at least moderate staining intensity. TILs were evaluated on hematoxylin and eosin sections. Clinicopathologic correlations were assessed statistically, and overall survival and distant metastasis-free survival were analyzed using Kaplan-Meier and Cox regression methods. PRAME expression was identified in 10 of 33 evaluable tumors (30.3%). Most positive cases showed diffuse nuclear staining, although one tumor demonstrated heterogeneous PRAME expression. MCPyV positivity was seen in 51.4% of cases, and PRAME expression was more frequent in MCPyV-positive tumors ( P =0.057). Combined PRAME/PD-L1 positivity was associated with higher TIL density ( P =0.018). PRAME expression was not associated with clinicopathologic parameters or survival. Lower PD-L1 expression (CPS <1) was independently associated with shorter overall survival. PRAME was expressed in approximately one-third of MCCs. PRAME expression was not independently associated with survival outcomes. Higher expression rates in MCPyV-positive tumors and associations with selected immune-related parameters warrant further investigation.

The purpose of this study was to evaluate the clinical features and symptoms of IgG4-related orbital disease (IgG4-ROD) cases from two ophthalmology clinics. The medical records of 20 patients with histopathologically proven IgG4-ROD diagnosed at 2 tertiary referral university hospitals in Turkey were retrospectively reviewed. The demographic profiles, clinical findings, and ocular symptoms of the patients were analyzed. The mean patient age was 40.9 ± 20.1 (5-67) years (65% female, 35% male). IgG4-ROD involvement was bilateral in 25% of cases. The involvement sites were lacrimal gland (84.2%), orbital soft tissues (52.6%), conjunctiva (15.8%). Multiple ophthalmic sites of involvement were detected in seven patients. Lacrimal gland involvement was the most frequent ophthalmic manifestation of IgG4-ROD. The most common complaints of the patients were swelling and redness of the eyelids. All patients responded to glucocorticoid treatment. However, one patient (5.3%) relapsed and required long-term corticosteroid and immunosupressive agent use. IgG4-ROD can present with overlapping features of clinical history, physical examination, and imaging findings. Therefore, in any orbital involvement - especially with eyelid swelling and redness, it is important to suspect IgG4-ROD and to perform biopsy to achieve the accurate diagnose.

Tr en Amaç: İmmünohistokimyasal yöntemler ve transmisyon elektron mikroskopisi (TEM) kullanılarak primer vezikoüreteral reflülü (VUR) ve dekstranomer / hyaluronik asit (Dx/HA) ile başarısız enjeksiyon tedavisi sonrası primer VUR'lu çocukların üreterovezikal bileşkesinde sitokin profillerinin ve ultrayapısal değişikliklerinin karşılaştırılması. Materyal ve Method: Aralık 2011 ve Ağustos 2014 tarihleri arasında, Uluslararası Reflü Çalışmasına göre grade I-V VUR olarak değerlendirilen 41 çocuğa üreteroneosistostomi uygulandı. Dx / HA ile başarısız enjeksiyon tedavisinin ardından 18 çocuğa primer VUR için üreteroneosistostomi uygulandı. Histopatolojik ve ultrayapısal değerlendirmeler için ameliyat sırasında altmış yedi distal intravezikal üreter elde edildi. Üreter duvarı düz kas organizasyonu ve transforme edici büyüme faktörü-β1 (TGF-β1), vasküler endotelyal büyüme faktörü (VEGF) ve CD34 immünohistokimyasal olarak değerlendirildi. Ultrayapısal değerlendirmeler ve morfolojik tanımlar yarı kantitatif olarak yapıldı. Bulgular: Hastaların 10'u (% 24,3) erkek, 31'i (% 75,7) kadındı. 28 üreterde başarısız Dx/HA enjeksiyon öyküsü mevcuttu. Histopatolojisi; Dx/HA ile başarısız enjeksiyon tedavisini takiben primer VUR hastalarında ve primer VUR hastalarında TGF-β1 ve VEGF ve CD34 düzeyleri aynıydı ancak kontrol grubu ile karşılaştırıldığında farklı idi (sırasıyla p=0.001,p<0.001 ve p<0.001). Ancak farklar reflü derecesi ile ilişkili değildi (sırasıyla p = 0.42, p = 0.26 ve p = 0.94). Tüm VUR örneklerinde kas hücrelerinde ultrayapısal değişiklikler gözlendi. Sonuç: Çalışmamız, tüm VUR örneklerinde kas hücrelerinin ultra apısal değişikliklerinin gözlendiğini göstermiştir. Primer VUR ve başarısız Dx/HA tedavisi olan primer VUR hastalar arasında sitokin miktarında anlamlı bir fark yoktu. VEGF, CD34 ve TGF-21 düzeyleri her iki primer VUR grubunda da karşılaştırılabilirdi. Purpose: To compare the cytokine profiles and ultrastructural changes in the ureterovesical junctions of children with primary vesicoureteral reflux(VUR) and children with primary VUR following failed injection therapy with dextranomer/hyaluronic-acid (Dx/HA) using immunohistochemical methods and transmission electron microscopy (TEM). Materials and Methods: 41 children underwent ureteroneocystostomy for VUR and 18 children underwent ureteroneocystostomy for primary VUR following failed injection therapy with Dx/HA. Sixty-seven distal intravesical ureters were obtained during surgery for histopathological and ultrastructural evaluations. The ureteral wall smooth-muscle organization and transforming growth factor-β1(TGF-β1), vascular endothelial growth factor(VEGF), and CD34 were evaluated immunohistochemically. The ultrastructural evaluations and morphological descriptions were performed semi-quantitatively. Results: Of the patients, 10(24,3%) were male and 31(75,7%) were female. 28 ureter had a history of failed Dx/HA injections. Histopathology; the amount of TGF-β1, and the VEGF and CD34 levels were same in the patients with primary VUR and patients with primary VUR following failed injection therapy with Dx/HA but different compared with the control group(p=0.001,p<0.001, and p<0.001, respectively), but the differences were not correlated with the grade of reflux(p=0.42, p=0.26 and p=0.94 respectively). Ultrastructural changes in the muscle cells were observed in all the VUR specimens. Conclusions: Our study demonstrated that ultra-structural changes in the muscle cells were observed in all VUR specimens. There was no significant difference in the quantification of cytokine assays between the patients with primary VUR and primary VUR with failed Dx/HA therapy. The quantification of VEGF, CD34, and, TGF-β1 levels was comparable in both primary VUR groups.