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Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing. The possible association between TRPV1 in nerve fibers and neuropeptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP) in the recurrence of pterygium has not been examined before. The pterygia from 64 patients were used to determine changes in SP and VIP levels using 10 min acetic-acid extraction that yielded mainly neuronal peptides. There was a sufficient amount of pterygium tissues from the 35 patients for further immunohistochemical analysis of TRPV1 and S100, which is a glial marker to visualize nerve fibers. SP and VIP levels increased markedly in cases with primary and secondary recurrences, and there was a close correlation between SP and VIP levels. TRPV1 expression increased in the epithelium, while stromal expression decreased in recurrences. Nerve fibers were demonstrated mainly in the stroma, and serial sections confirmed the localization of TRPV1 with the nerve fibers. These results together with previous findings demonstrated that the increased epithelial expression of TRPV1 in recurrent pterygia might be involved in the pathogenesis, and the inhibition of epithelial TRPV1 activity may prevent recurrence.

Prostate cancer is one of the most common types of cancer with rapidly growing incidence rates in the world. The incidence and mortality rates of prostate cancer are widely variable in different populations. The prostate cancer includes multiple genetic modifications such as deletion in specific genome sequences of tumor-suppressor genes and alterations in specific chromosomal sites associated with oncogene activation. It is difficult to determine whether the hereditary changes leading to prostate cancer are associated with one or more specific genetic features. Prostate carcinogenesis is complex and has not been fully explained. If we can better understand prostate carcinogenesis, we can also find targeted therapy. Therefore, we talked about the major genetic and epigenetic changes involved in prostate carcinoma.

The aim of this research is toexamine self sufficiency of the students for piano courses in professional music education in terms of different variables. For this purpose, the differences between self sufficiencies of the students for piano courses in professional music education in grade 1, 2, 3 and 4 of faculty of education, state conservatory and faculty of fine arts has been determined in terms of different variables such as university, faculty, age, gender and graduated high schools. This is a descriptive research with scanning model. The population of this research consists of the students from grade 1, 2, 3 and 4 of the universities granting professional music education in Turkey; and the sample group of this research consists of 550 students, which have been selected with random sample method from grade 1, 2, 3 and 4 of Turkish universities giving professional music education during 2017-2018 academic year, such as Departments of Music Education of Niğde Ömer Halisdemir, Yüzüncü Yıl and Harran Universities, the Faculties of FineArts in Akdeniz, Atatürk and Nevşehir Hacı Bektaş Veli Universities, the State Conservatories of Afyon Kocatepe, Selçuk, Kafkas Universities. The data for this research has been collected with “Self Sufficiency Scale for Piano Course” which was developed by Kurtuldu and Bulut (2016). According to research findings, there is a significant difference between the self sufficiency scores of the students in music education and the self sufficiency scores undersub-dimension of the scale in terms of variables such as university, age, gender and graduated high schools; however there is no significant difference in terms of variables such as faculty, level of education grade.

BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs, including the colon. Accordingly, studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression. Although Numb, Itch, and seven in absentia homolog-1 (Siah-1) have been shown to contribute to the regulation of Notch signaling, their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date. AIM To evaluate Numb, Itch, and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior. METHODS Expression of Notch-1, Numb, Itch, and Siah-1 was investigated in 50 colorectal carcinomas, 30 adenomas, and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analyses. RESULTS In contrast to Notch-1, which is expressed at higher levels in tumor tissues and adenomas, expression of Numb, Itch, and Siah-1 was stronger and more frequent in normal mucosa (P < 0.01). There was a positive correlation between Notch-1 expression and high histological grade, the presence of lymph node metastasis, and advanced-stage tumors, whereas expression of Numb, Itch, and Siah-1 was absent or reduced in tumors with these clinicopathological parameters (P < 0.05). In survival analysis, expression of Notch was related to poor prognosis but that of Numb, Itch, and Siah-1 correlated with improved survival (P < 0.05). Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis (P < 0.05). CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma (CRC) progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.

Arastirma, Suriye'den Turkiye'ye goc eden genc bireylerin goc sonrasi kulturel uyum surecinde yasadiklari psikolojik yansimalar, uygulamada kullanilan yontemlerin hemsirelik ve tedavi boyutunu sistematik olarak arastirmak amaciyla planlanmistir. Calisma 2015-2019 tarihleri arasinda gerceklestirilmisti. Arastirma icin Yuksekogretim Kurulu (YOK) tez tarama merkezi, Google Scholar, PsychINFO- American Psychological Association, PubMED veri tabanlari kullanilmistir. Bu cercevede PICOS kriterlerine gore 40 calisma icerik analiziyle degerlendirilmistir. Calismada kulturel uyum surecinde goc olgusunun ruh sagligina etkisi, goc, savas gibi travma kaynakli olaylar ile hemsirelik ve tedavi yontemleri kapsaminda incelemenin faydali olacagi dusunulerek hareket edilmistir. Arastirmanin sonucuna gore goc olgusu bireylerde ruhsal sorunlar (travma sonrasi stres bozuklugu, anksiyete vb.) kulturlesme stresi ve yasam kosullarinda olumsuz riskler (korku, aitlik sorunu, yabancilik duygusu) ile karsilastiklari tespit edilmistir. Bu surecte hemsire olarak goc sonrasi sagligi gelistirme ve koruma boyutu ele alinmaktadir. Karsilasilan sorunlara karsi olusturulan tedavi sureci yontemlerinin (EMDR, telepsikiyatri) olumlu yonde gelistirilmeye calisildigi belirlenmistir.

Lichen planopilaris (LPP) is characterized by erythematous, keratotic follicular papules and cicatricial alopecia. LPP, the most common cause of cicatricial alopecia, is usually seen in women and causes significant psychosocial morbidity. We describe here a 42-year-old woman with a 6-month history of hair loss accompanied by itching on the scalp. Dermatological examination revealed patchy cicatricial alopecia in the vertex and band-like purple flat patches and plaques following the Blaschko lines on the right half of the body, together with post-inflammatory hyperpigmentation. Histopathological examination of the scalp biopsy was consistent with LPP, while thigh biopsy was consistent with lichen planus. With the histopathological and clinical evidence, our patient was evaluated as LPP associated with LP and successfully treated with topical corticosteroid. A few LPP and LP cases following the Blaschko lines have previously been reported separately. However, LPP, together with LP following Blaschko lines, have not been reported in the same patient.

Adult hypertrophic pyloric stenosis in the form of focal pyloric hypertrophy is an uncommon but a well-established lesion. In most cases, clinical findings suggest malignancy, and despite advances in imaging techniques, preoperative diagnosis is difficult. Herein, an example of focal pyloric hypertrophy is presented with a review of the literature to emphasize the clinicopathological characteristics of this lesion. In a 43-year-old man with abdominal discomfort, endoscopy showed a 1.5 cm nodular lesion near the pylorus that necessitated surgery to exclude malignancy. Pathological examination allowed the diagnosis of focal pyloric hypertrophy. The present case and the review revealed that focal pyloric hypertrophy is a male dominant lesion in middle-aged patients. The clinical diagnosis is problematic, and its initial diagnosis depends on a high clinical suspicion in patients with upper gastrointestinal system complaints irrespective of the duration of the symptoms. It is not known whether it is a separate entity from the diffuse form. Although both are similar in a clinical point of view, etiopathogenetic studies are required to clarify their differences completely. Moreover, the rare occurrence of focal pyloric hypertrophy and the lack of diagnostic clinical findings do not exclude its consideration in the differential diagnosis, especially in patients with gastric outlet obstruction.

Objectives: The aim of this study was to compare the smartphone-based gait analysis data of patients who underwent total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). Patients and methods: Between January 2016 and April 2019, a total of 51 patients (3 males, 48 females; mean age: 60.92 years; range, 51 to 70 years) who were operated with UKA or TKA in our clinic were retrospectively analyzed. The patients were divided into two groups according to the type of procedure as the UKA group (n=17) and unilateral TKA group (n=34). Gait analysis was made via a smartphone application (Gait Analyzer software version 0.9.95.0) with data acquired from the accelerometer of the smartphone. This analysis was performed using data collected from the Acceleration Sensor LSM6DSO into the Samsung Galaxy Note 10 Plus phone. Gait velocity, step time, step length, cadence, step time symmetry, step length symmetry, and vertical COM (vert-COM) parameters were measured. Results: There were no statistically significant differences between the groups in respect of age, sex, body mass index, operated side, and follow-up duration. Compared to the TKA group, the UKA patients showed a better gait pattern in gait velocity (p=0.03), step time symmetry (p=0.005), and step length symmetry (p=0.024). No significant difference was detected in step time (p=0.807), step length (p=0.302), cadence (p=0.727) and vert-COM parameters (p=0.608). Conclusion: The gait of UKA patients is closer to the physiological pattern with a better gait velocity, step time symmetry, and step length symmetry than TKA patients. The surgical treatment option of UKA for knee medial compartment osteoarthritis leads to a better gait pattern than TKA.

PURPOSE: This study aims to identify chest computed tomography (CT) characteristics of coronavirus disease 2019 (COVID-19), investigate the association between CT findings and laboratory or demographic findings, and compare the accuracy of chest CT with reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Overall, 120 of 159 consecutive cases isolated due to suspected COVID-19 at our hospital between 17 and 25 March 2020 were included in this retrospective study. All patients underwent both chest CT and RT-PCR at first admission. The patients were divided into two groups: laboratory-confirmed COVID-19 and clinically diagnosed COVID-19. Clinical findings, laboratory findings, radiologic features and CT severity index (CT-SI) of the patients were noted. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of chest CT were calculated for the diagnosis of COVID-19, using RT-PCR as reference. RESULTS: The laboratory-confirmed and clinically diagnosed COVID-19 groups consisted of 69 (M/F 43/26, mean age 50.9±14.0 years) and 51 patients (M/F 24/27, mean age 50.9±18.8 years), respectively. Dry cough (62.3% vs. 52.9%), fever (30.4% vs. 25.5%) and dyspnea (23.2% vs. 27.5%) were the most common admission symptoms in the laboratory-confirmed and clinically diagnosed COVID-19 groups, respectively. Bilateral multilobe involvement (83.1% vs. 57.5%), peripheral distribution (96.9% vs. 97.5%), patchy shape (75.4% vs. 70.0%), ground-glass opacities (GGO) (96.9% vs. 100.0%), vascular enlargement (56.9% vs. 50.0%), intralobular reticular density (40.0% vs. 40.0%) and bronchial wall thickening (27.7% vs. 45.0%) were the most common CT findings in the laboratory-confirmed and clinically diagnosed COVID-19 subgroups, respectively. Except for the bilateral involvement and white blood cell (WBC) count, no difference was found between the clinical, laboratory, and parenchymal findings of the two groups. Positive correlation was found between CT-SI and, lactate dehydrogenase (LDH) and C-reactive protein (CRP) values in the laboratory-confirmed COVID-19 subgroup. Chest CT and RT-PCR positivity rates among patients with suspected COVID-19 were 87.5% (105/120) and 57.5% (69/120), respectively. The sensitivity, specificity, PPV, NPV and accuracy rates of chest CT were determined as 94.2% (95% confidence interval [CI], 85.8-98.4), 21.57% (95% CI, 11.3-35.3), 61.90% (95% CI, 58.2-65.5), 73.3% (95% CI, 48.2-89.1) and 63.3% (95% CI, 54.1-71.9), respectively. CONCLUSION: Chest CT has high sensitivity and low specificity in the diagnosis of COVID-19. The clinical, laboratory, and CT findings of laboratory-confirmed and clinically diagnosed COVID-19 patients are similar.

Aim: Prostate cancer is one of the most common cancers in the world and its incidence is rapidly increasing. Currently, several new treatment strategies that target specific signaling pathways as well as immunotherapy are being explored for prostate cancer. In the current study, we aimed to investigate the frequency and clinicopathologic features associated with Notch1 gene expression using immunohistochemistry and real-time-polymerase chain reaction in patients with prostate cancer.Methods: This research was planned as a cohort study. Tissue samples of 60 patients with prostate cancer and 20 patients with benign prostatic hyperplasia were selected from the archives. Twenty patients with benign prostatic hyperplasia were used as the control group. The relative expression levels of Notch1 gene were determined by real-time-polymerase chain reaction while Notch1 protein expression was analyzed using immunohistochemistry.Results: We found Notch1 gene expression at a significant level in 17 (28.3%) of 60 patients with prostate carcinoma. We found a significant correlation between high Gleason scores (P=0.007), high ISUP (International Society of Urologic Pathologists) grade group scores (P=0.008) and high prostate-specific antigen levels (P=0.018) for Notch1 gene expression. Conclusions: We conclude that Notch1 is important in prostate carcinogenesis. Therefore, determining Notch1 will be an essential step in targeted therapies in patients with prostate carcinoma., Amaç: Prostat kanseri dünyada en yaygın görülen kanserlerden biridir ve sıklığı giderek artmaktadır. Şu anda, prostat karsinomu için etkin bir tedavi yöntemi olmamakla birlikte immünoterapiyi ve spesifik sinyal yolaklarını hedefleyen yeni tedavi stratejileri araştırılmaktadır. Biz bu çalışmada prostat kanseri hastalarında immünohistokimya ve Real-Time polimeraz zincir reaksiyonu ile Notch1 gen ekspresyonunu ve klinikopatolojik özellikler ile ilişkisini araştırmayı amaçladık.Yöntemler: Bu araştırma bir kohort çalışma olarak planlandı. Hastane arşivimizden 60 tane prostat kanseri ve 20 tane benign prostat hiperplazisi olan hastaların parafin blokları seçildi. Benign prostat hiperplazisi olan 20 hasta kontrol grubu olarak kullanıldı. Notchl gen ekspresyonu seviyeleri immünohistokimya ve Real-Time polimeraz zincir reaksiyonu kullanılarak analiz edildi.Bulgular: Çalışmamızda 60 prostat karsinomu tanılı hastamızın 17'sinde (%28,3) Notch1 gen ekspresyonunu anlamlı düzeyde yüksek bulduk. Ayrıca yüksek Gleason skoru (P=0,07), yüksek ISUP skoru (P=0,008) ve yüksek prostat spesifik antijen düzeyi (P=0,018) ile Notch1 ekspresyonu arasında anlamlı bir korelasyon bulduk.Sonuçlar: Prostat karsinogenezinde Notch1'in önemli olduğu sonucuna vardık. Bu nedenle, Notch1 prostat karsinomlu hastalarda hedefe yönelik tedavilerde önemli bir adım olacaktır.

Objective: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. Materials and Methods: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT. The capacity of sTILs and iTILs in predicting pCR to NACT in LABC analyzed using receiver operating characteristic (ROC) curve analysis. Results: According to ROC curve analysis, the optimum sTILs and iTILs cut-off points (the number of positive cells per square millimeter of tissue) for patients with LABC patients with pCR (+) were 19 (area under the curve (AUC): 0.668, 95% confidence interval [CI] [0.501–0.835],P = 0.064) and 4 (AUC: 0.786, 95%CI [0.666–0.907],P = 0.002), respectively. Of the 62 patients, 26 had sTILs >19 and 25 had iTILs >4. The patients were divided into two according to percent of sTILs (sTILs >19 and sTILs ≤19 groups) and iTILs (iTILs >4 and iTILs ≤4 groups). Both sTILs >19 and iTILs >4 patients were associated with development higher pCR. While pCR was significantly higher in iTILs >4 patients (P = 0.002), it was not significantly in sTILs >19 patients (P = 0.107). Conclusions: There is significantly an association between pCR and increased number of intratumoral TILs (>4 cells/mm 2 of tissue) in BC who received NACT.

Metastatic lobular carcinoma to stomach is seen as small round cells in linear cords within the normal tissue and it is not easily differentiated from signet cell adenocarcinoma of the stomach. Differentiating synchronous primary gastric carcinoma from metastatic involvement is vital in accurately planning treatment. Herein, we report a case of gastric metastatic invasive lobular breast carcinoma initially misdiagnosed as synchronous gastric and breast carcinoma and discuss the diagnostic and therapeutic challenges.

Endometrial carcinoma is the most commonly encountered gynecological cancer in women worldwide and is also one of the popular models of the hormone-dependent carcinomas. This study was aimed to evaluate and compare the concentrations of five paraben molecules (methylparaben, ethylparaben, N-propylparaben, benzylparaben, isobutylparaben + N-butylparaben) in the endometrial and myometrial tissue samples of patients diagnosed with endometrial carcinoma and benign gynecologic diseases. A total of 88 patients were included in the study and chemical analysis was performed on 176 tissue samples. The study group comprised of 33 patients with endometrial carcinoma and 6 patients with endometrial intraepithelial neoplasia. The control group comprised of 49 patients. One endometrial and one myometrial tissue samples were collected from each patient. The analyses were performed using ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). At least one type of paraben molecule was detected in 23.07% (9/39) of the patients in the study group, and in 2.04% (1/49) of the patients in the control group; this difference between the groups was statistically significant (p = .002). N-Propylparaben and isobutyl + N-butylparaben were the most frequently detected (in 7/10 of the samples) paraben molecules in the study. Tumor characteristics (tumor diameter, myometrial invasion, architectural grade, nuclear grade, lymphovascular space invasion, and tumor stage) were comparable between the two groups of endometrial carcinoma (paraben-detected and paraben-undetected groups). In conclusion, paraben molecules were more frequently detected in the endometrial carcinoma tissue samples than in the normal endometrium.

Sarcomas account for 0.1 to 0.2% of all prostatic malignancies. Rhabdomyosarcoma is a malignant tumor that shows skeletal muscle sarcomeric differentiation. About 35% of rhabdomyosarcomas occur in the head-neck, 40% on the limbs and other areas and 25% in the genitourinary system. Only 5% of them arise in the prostate or bladder. Primary prostatic rhabdomyosarcoma usually develops in infancy and childhood at around 10 years of age. A 20-year-old male presenting with a complaint of right-left side pain was diagnosed with bilateral hydronephrosis after a series of tests. His urethrography showed a severely narrowed, firm and fixed prostatic urethra, so a needle biopsy was performed. The microscopic examination detected an invasive tumor within fibromuscular stroma and prostate glands. The tumor consisted of oval to round tumor cells with hyperchromatic nuclei and irregular contours in places, as well as cells with occasional eosinophilic cytoplasm. Immunohistochemically, the tumor cells showed a positive immunoreaction for myogenin, desmin and c-kit. Based on these findings, the patient was diagnosed with embryonic rhabdomyosarcoma. The case has been presented for discussion, since prostatic embryonic rhabdomyosarcoma is a rare disease with diagnostic challenges in differentiating from other prostatic tumors, Sarkomlar tüm prostat malignensilerinin %0,1-0,2’sini oluşturur. Rabdomyosarkom, iskelet kası sarkomerik diferansiasyonu gösteren malign tümördür. %35 baş- boyun bölgesi, %40 ekstremite ve diğer alanlar, %25 genitoüriner sistemde izlenir. %5 oranında prostat ve mesanede görülür. Primer prostatik rabdomyosarkom genellikle infant ve çocukluk çağında ortalama 10 yaş civarında izlenir. 20 yaşında sağ-sol yan ağrısı yakınması ile hastanemize başvuran hastanın yapılan tetkikleri sonrası bilateral hidronefroz görüldü. Yapılan üretrografide prostatik üretranın çok daraldığı, sert ve fiske olduğu izlendi ve iğne biyopsi alındı. Mikroskobik incelemede prostat bez yapıları ve fibromüsküler stroması içinde invaziv tümör saptandı. Tümör, oval yuvarlak, yer yer düzensiz kontürlü hiperkromatik nukleusa sahip, arada eozinofilik sitoplâzmalı hücrelerden oluşmaktaydı. Tümör hücreleri immünhistokimyasal yöntemle uygulanan myogenin, desmin, c-kit ile pozitif immünreaksiyon gösterdi. Bu bulgularla olgu embriyonal rabdomyosarkom olarak tanı aldı. Olgu prostatik embriyonel rabdomyosarkomun nadir izlenmesi ve diğer prostatik tümörlerden ayrımı yönünden tartışıldı

Squamoid eccrine ductal carcinoma (SEDC) is a subtype of malignant tumours of skin appendices, showing eccrine and apocrine differentiation. It is a rare tumour and making a histopathological diagnosis is difficult. Our patient was a 79-year-old male, presenting to our hospital with the complaint of a long-term persistent wound in the scalp. An excisional biopsy was performed due to a preliminary diagnosis of a pyogenic granuloma. However, the patient was diagnosed with squamoid eccrine ductal carcinoma. Although an excisional biopsy was performed, the tumour was present on the surgical margins. Consequently, the patient underwent an extended re-excision but the tumour was detected at the surgical margins again. We aimed to present this case as SEDC is a rare tumour.

Current methods for diagnosis and staging of prostate adenocarcinoma are not sensitive enough to distinguish between patients with indolent disease and those that should receive radical treatment. Epithelial-mesenchymal transition (EMT) is a well-characterized process involved in tumor invasion and metastasis. The aim of this study is to analyze the expression of β-catenin, Snail, and E-cadherin in prostate cancer patients with prospective evaluation of their value in predicting disease-free survival (DFS). One-hundred-and-three consecutive prostate carcinoma patients who underwent radical prostatectomy and 35 patients with benign prostate hyperplasia (BPH) were enrolled. Age, initial PSA level, tumor size and clinical stage were documented for adenocarcinoma patients and they were enrolled in active surveillance with serum PSA levels. Recurrence was defined as PSA level of ≥ 0.2 ng/ml on at least 2 occasions over a 2-month period. Immunohistochemical staining intensity was scored as negative, weakly positive, moderately positive, and strongly positive. For Snail and β-catenin immunoreaction, the tumors were considered nuclear positive when more than 5 % of the nuclei of tumor cells were positively stained. Patients with prostate cancer had weaker β-catenin (p < 0.0001), Snail (p = 0.006), and E-cadherin (p = 0.02) staining when compared to BPH patients and the frequency of nuclear positivity for β-catenin and Snail were higher in adenocarcinoma group (p < 0.0001). Increased expression and nuclear positivity of β-catenin were associated with advanced stage (p = 0.012 and p = 0.003) and higher tumor volume (p = 0.013 and p = 0.002). Additionally, patients with increased Snail expression had higher Gleason scores and tumor volume at presentation (p = 0.008 and p = 0.004). However, there were no significant DFS differences in adenocarcinoma patients who did and did not have β-catenin, Snail, and E-cadherin expression as assessed with log-rank test. Expressions of β-catenin, Snail, and E-cadherin were significantly lower in prostate cancer patients compared to BPH patients and both β-catenin and Snail had nuclear staining pattern in patients with adenocarcinoma. However, none of these markers predicted DFS in 36-month follow up of our cohort.

A total of 81patients with an ampullary ectopic pregnancy undergoing salpingectomy were enrolled in the study. The ampullary pregnancies were classified according to the depth of trophoblastic infiltration into tubal wall as follows: Stage I, limited to mucosa; Stage II, extension to the tubal muscularis; Stage III, complete tubal wall infiltration up to the serosa. An association was observed between serum β-human chorionic gonadotropin (β-hCG) levels and the depth of trophoblastic infiltration. Significantly higher severe ischemic changes and rupture of tubal wall were observed in patients with stage III infiltration compared with the other groups. A significant association was found between the absolute depth of trophoblastic invasion and severe ischemic changes, and also rupture of serosa. In conclusion, serum β-hCG levels are associated with depth of trophoblastic invasion into the tubal wall, severe ischemic changes, and rupture of the tubal wall.

Sorafenib which is used in the treatment of renal, thyroid and hepatocellular cancers is a multi-targeted tyrosine kinase inhibitor. Though sorafenib is associated with some side effects, it is known that sorafenib is generally well tolerated compared to other tyrosine kinase inhibitors. In the present case, hepatocellular cancer was diagnosed seven months ago. The disease was in stage IIIB at the time of diagnosis. Sorafenib was initiated with a dose of 400 mg twice daily because of disease progression after two cycles of doxorubicin. The reactions on the skin of the arms and the body of the patient occurred in the eighth week of treatment. Skin biopsy was performed and urticaria was diagnosed after pathologic examination. No other disorders or drugs which may cause urticaria were detected in the patient. Skin reactions disappeared one week after sorafenib discontinuation without any further intervention.

The aim of this study was to evaluate hepatic polyunsaturated fatty acids (PUFAs) and inflammatory response in an animal and cell model of endoplasmic reticulum (ER) stress. Rats were divided into control, tunicamycin (TM)-treated, and TM + tauroursodeoxycholic acid (TUDCA)-treated groups. Hepatic ER stress was induced by TM and the ER stress inhibitor TUDCA was injected 30 min before induction of ER stress. Liver THLE-3 cells were treated with TM and TUDCA was administered in advance to decrease cytotoxic effects. Necroinflammation was evaluated in liver sections, while cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay kit. ER stress was confirmed by immunofluorescence and Western blot analysis of C/EBP-homologous protein and 78-kDa glucose-regulated protein. Arachidonic acid (C20:4n-6), dihomo-γ-linolenic acid (C20:3n-6), eicosapentaenoic acid (C20:5n-3), and docosahexaenoic acid (C22:6n-3) in liver tissue and THLE-3 cells were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Phospholipase A2 (PLA2), cyclooxygenase (COX), and prostaglandin E2 (PGE2) were measured in tissue and cell samples. Hepatic ER stress was accomplished by TM and was alleviated by TUDCA. TM treatment significantly decreased PUFAs in both liver and THLE-3 cells compared to controls. PLA2, COX, and PGE2 levels were significantly increased in TM-treated rats and THLE-3 cells compared to controls. TUDCA leads to a partial restoration of liver PUFA levels and decreased PLA2, COX, and PGE2. This study reports decreased PUFA levels in ER stress and supports the use of omega-3 fatty acids in liver diseases demonstrating ER stress.

Objectives Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey. Materials and methods The HLA genotypes of 841 consecutive recipients and 3071 family members were retrospectively reviewed. Results Matched related donors were identified for 368/841 recipients (44%). Extended family donor searches were performed for 111/181 pediatric recipients (61%), with nonsibling matched related donors found for 23 patients (21%). Matched related donors were found for a significantly higher proportion of pediatric patients (52%) than adult patients (41%) (odds ratio of 2.5; 95% confidence interval, 1.9-4.1; P = .02). The percentage of pediatric versus adult patients with 3 or more siblings was 13% versus 46% (odds ratio of 5.6; 95% confidence interval, 3.6-8.5; P = .001). The most frequent HLA class I antigens at each locus were HLA-A*02 (20.2%), HLA-B*35 (19.5%), and HLA-C*07 (19.8%). The most frequent HLA class II antigens at each locus were HLA-DRB1*11 (21.6%) and HLA-DQB1*03 (40.2%). The most common 3-locus haplotypes were HLA-A*24 B*35 DRB1*11 (F:0.020) and HLA-A*01 B*08 DRB1*03 (F:0.015). When adult and pediatric groups were combined, the most common locus haplotypes were found in 43/345 sibling donors (12%) and in 7/23 nonsibling pediatric donors (30%) (odds ratio of 2.7; 95% confidence interval, 1.2-6.4; P = .02). Conclusions The results indicate that, in Turkey, it can be beneficial to revise donor search algorithms to include an extended family donor search before an unrelated donor search. This type of search can be effective because of the HLA haplotype diversity in Turkey, the frequency of consanguinity, and the country's limited donor pool.

Breast carcinoma metastasis to the fallopian tube is extremely rare. Distinction between a primary fallopian tumor and metastasis of breast cancer is crucial since treatment and prognosis are different. However, it is difficult to confirm pathologically without surgery. Herein, we report a 46-year-old woman with a history of left modified radical mastectomy for breast cancer 13 years ago, presenting with a left adnexial mass. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pathology findings revealed cytokeratin (CK) 7, ER, and PR positive tumor cells. Mammoglobuline, P53, CK20, GCDFP-15 and, thrombomoduline were negative. HER2 was also 2+. Fluorescence in situ hybridization (FISH) for HER2 was negative. Based on the morphology and immunophenotype of the tumor, we established the diagnosis as metastasis of breast cancer to the fallopian tube.

Previous studies have revealed the activation of neutral sphingomyelinase (N-SMase)/ceramide pathway in hepatic tissue following warm liver ischemia reperfusion (IR) injury. Excessive ceramide accumulation is known to potentiate apoptotic stimuli and a link between apoptosis and endoplasmic reticulum (ER) stress has been established in hepatic IR injury. Thus, this study determined the role of selective N-SMase inhibition on ER stress and apoptotic markers in a rat model of liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reactions monitoring (MRM) method using ultrafast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared with controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78 kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NF-kB levels, hepatic TUNEL staining, cytosolic cytochrome c, and caspase-3, -8, and -9 activities which were significantly increased in IR injury. Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.

Prostate-specific membrane antigen (PSMA) is a typ. 2 transmembrane protein that is highly expressed in prostate cancer cells. Ga-PSMA PET/CT imaging is a modality used to determine the extent of prostate cancer. Various other neoplasias may also express PSMA, which appears as Ga-PSMA uptake in PET/CT imaging. A 71-year-old man with prostate cancer underwent Ga-PSMA PET/CT imaging for restaging after having an elevated prostate-specific antigen level. Subcutaneous lesions showing focal PSMA uptake were detected, one of which was excised. The histopathologic diagnosis was dermatofibroma.

Benign cystic mesothelioma (BCM) is a rare tumor arising from endothelial cells of the pelvic visceral or parietal peritoneum. It is a clinically and histopathologically benign disease. Etiology and pathogenesis of BCM remain unclear. Familial Mediterranean fever (FMF) is an inherited disorder characterized by episodes of fever, and abdominal, chest and/or joint inflammation. Association between malignant mesothelioma and FMF has been reported previously; however, co-existence of FMF and BCM is rare. Here, we report a case of BCM in a 43-year-old male patient with FMF.

The objective of this study is to determine and discuss the causes of a giant endometrial polyp in a postmenopausal woman without hormone/drug use and to submit interesting clinical presentation. Here we report a seventy-year-old female patient who was admitted to our hospital with lower back pain. There were no other complaints from her. Physical examination was normal. For further examination, computed tomography was performed and a heterogeneous mass, with a diameter of 10×9 centimeters, was detected in the uterine cavity. Hysterectomy because of suspected endometrial cancer was performed. Histopathological examination showed us a giant endometrial polyp with edematous and focal fibrotic stroma, large thick walled blood vessels between normal sized and cystically dilated endometrial glands. To the best of our knowledge, this is the first report of a giant endometrial polyp which is unrelated to use of drugs such as tamoxifen and raloxifene; however, based on the history of the patient it may be associated with long-term consumption of thyme, which is a kind of phytoestrogen.

Median raphe cysts present anywhere between the external urethral meatus and the anus. The cysts can occur at parameatus, glans penis, penile shaft, scrotum, or perineum. Perianal region is an extremely rare location for these lesions. Here we present a 50-year-old male patient who presented with a cystic, fluctuant lesion, located at 12 o’clock in perianal region. Microscopic examination revealed a cystic lesion with keratinized and nonkeratinized stratified squamous epithelium, pseudostratified ciliated epithelium, and scattered goblet cells. The final diagnosis of the lesion was median raphe cyst. Ciliated cells and perianal localization in median raphe cysts are extremely rare characteristics.

Background: The two basic methods that are currently accepted to identify the HER2 status are immunohistochemistry and flyorescence in situ hybridization (FISH) . The aim of this study was to perform the dual-color silver in situ hybridization (dc-SISH) technique as an alternative to FISH. Materials and Methods: A total of 40 invasive breast carcinoma cases were assessed for HER2 gene amplification by FISH and dualcolor SISH. Results: Significant correlation was found in the HER2 expression results obtained with the two approaches (p=0.001, p

Oxidative stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS)-2 have been shown in the pathogenesis of liver ischemia-reperfusion (IR) injury. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression therefore this study determined the role of selective N-SMase inhibition on nitrative and oxidative stress markers following liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Nitrative and oxidative stress markers were determined by evaluating NOS2 expression, protein nitration, nitrite/nitrate levels, 4-hydroxynonenal (HNE) formation, protein carbonyl levels and xanthine oxidase/xanthine dehydrogenase (XO/XDH) activity. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. NOS2 expression, nitrite/nitrate levels and protein nitration were significantly greater in IR injury and decreased with N-SMase inhibition. Treatment with a selective N-SMase inhibitor significantly decreased HNE formation, protein carbonyl levels and the hepatic conversion of XO. Data confirm the role of nitrative and oxidative injury in IR and highlight the protective effect of selective N-SMase inhibition. Future studies evaluating agents blocking N-SMase activity can facilitate the development of treatment strategies to alleviate oxidative injury in liver I/R injury.

In this study, we sought to evaluate the effect of endoplasmic reticulum (ER) stress on hepatic polyunsaturated fatty acids (PUFAs) and inflammatory response through cyclooxygenase (COX)-mediated pathway. Male Wistar rats which were allowed free access to standard rat chow were randomly divided into control, tunicamycin (TM) treated and TM + tauroursodeoxycholic acid (TUDCA) treated groups. Hepatic ER stress was induced by intraperitoneal injection of tunicamycin and the ER stress inhibitor TUDCA was injected 30 minutes before hepatic induction of ER stress. The presence of ER stress was confirmed by increased intracellular levels of C/EBP-homologous protein (CHOP) and 78-kDa glucose-regulated protein (GRP78). Necroinflammation was evaluated in liver sections stained with hematoxylin-eosin using the Ishak-modified hepatic activity index. Levels of arachidonic acid (AA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in liver tissue were determined by an optimized multiple reaction monitoring method using ultra fast-liquid chromatography coupled with tandem mass spectrometry. Phospholipase A2 (PLA2), COX and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in the inflammatory pathways. Tunicamycin treatment significantly decreased all measured PUFAs and increased AA/EPA ratio in liver tissue compared to controls. Tissue activity of PLA2, COX and PGE2 levels were significantly increased in liver tissue of TM treated rats compared to controls. Tauroursodeoxycholic acid lead to a partial restoration of liver PUFA levels and significantly decreased PLA2, COX and PGE2 levels compared to TM treated rats. The results of this study reveal the presence of a proinflammatory state in hepatic ER stress as shown by significantly increased AA/EPA ratio. To our best knowledge, this is the first study reporting altered PUFA levels in ER stress and supports the use of omega-3 fatty acids as adjuvant treatment in liver diseases demonstrating ER stress. Acknowledgement This study was supported by a grant from TUBITAK; # 214S223.

Here, we present the case of a 31-year-old woman patient who underwent distal pancreatectomy with the history of gastric bypass surgery for obesity. The final histopathological diagnosis of the lesion was nesidioblastosis. Nesidioblastosis is the most common cause of organic persistent hyperinsulinemic hypoglycemia in newborns; however, it is rare in adults. In adults, it is difficult to diagnose nesidioblastosis with only clinical findings. The definitive diagnosis of the disease depends on the histopathological examination of pancreatic tissue and the exclusion of insulinoma.

Objective Cutaneus leishmaniasis, a chronic self-limited disease of the skin, is usually caused by Leishmania Tropica. It is endemic in Southeastern Anatolia. The definitive diagnosis depends on demonstration of the parasites by smear and culture or its identification in tissue section. This study aimed to evaluate clinical and histopathological skin lesions in cutaneous leishmaniasis cases in Antalya, Turkey. Material and method Our study included 28 patients diagnosed with cutaneous leishmaniasis at the Pathology Department of Akdeniz University Medical Faculty. Histopathological sections were stained with Haematoxylin-Eosin, Giemsa or Leishman for visual examination of cellular components by two dermatopathologists. The epidermal (acanthosis, hyper-parakeratosis, atrophy, lymphocytic exocytosis) and dermal changes that may indicate lymphohistiocytic infiltration and granuloma formation were investigated. The parasitic load was classified according to the modified Ridley's parasitic index. Results Out of 28 cases, 11 had hyperparakeratosis, 17 had orthokeratosis, 20 had acanthosis, 4 had epidermal atrophy, and 7 had exocytosis. Typical epithelioid cell granulomas with giant cells and a rim of lymphocytes were present in 16 cases. Leishman-Donovan bodies were extremely rare in typical granulomatous lesions. The other 12 cases showed lymphohistiositic infiltration, giant cells and prominent plasma cells. There were numerous Leishman-Donovan bodies in these lesions. Conclusion We investigated the epidermal and dermal changes that would facilitate the histopathological diagnosis of cutaneous leishmaniasis in this study. We found that atrophy, acanthosis, and orthokeratosis were early stage indicators, while exocytosis, hyperparakeratosis, and atrophy were indicative of late stage disease.

Prostate Cancer (PCa) holds the second place in terms of cancer-related mortality rate among men. The Notch signalling pathway regulates the proliferation and differentiation in embryonic and adult tissues and determines the cell fate. The body of knowledge in the present literature is currently controversial about the effect of the Notch pathway on prostatic cancer. Therefore, the present study aimed to examine the immunolocalization and expression levels of Notch1-4, Jagged1-2, Delta, HES1 and HES5 from among the members of the Notch signalling pathway in tissues of normal, prostatic intraepithelial neoplasia (PIN) and malignant prostate. The current study included a sample of 20 patients with localised prostatic adenocarcinoma, 18 patients with high grade PIN (H-PIN) and 18 normal prostatic tissue. Immunolocalisations of Notch1, 2, 3, 4, Jagged1, 2, Delta, HES1 and HES5 were identified through the immunohistochemical method. The findings of the present study showed that all in-scope members of the Notch signalling pathway were localised in PIN structures to a greater extent than in other tissues and from amongst these members, specifically Notch1, Notch4, Jagged1 and HES1 were at more significant levels. Consequently, the findings of the present study may indicate that the Notch signalling pathway can play a role especially in the formation of PIN structures.

Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case.

This study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on endoplasmic reticulum (ER) stress and apoptotic markers in a rat model of liver ischemia reperfusion (IR) injury. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Sphingmyelin and ceramide levels in liver tissue were determined by tandem mass spectrometry. Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78 kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NF-kB levels, hepatic TUNEL staining, cytosolic cytochrome c and caspase-3, -8 and -9 activities which were significantly increased in IR injury. Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.

Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID) three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn’s disease (CD) due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and he died in the postoperative seventh day. Laboratory analysis was seronegative. CMV inclusion containing cells were detected in postmortem biopsies taken from liver, lungs, and lymph nodes.

Background: The diagnostic approach to thyroid nodules involves ultrasound-guided fine needle aspiration biopsy (US-FNAB).We especially aimed to evaluate the contribution and the place of US-FNAB in preoperative evaluation of the malignant cases and draw attention to discordant cases diagnosed with papillary thyroid microcarcinoma (PTMC). Materials and Methods: A total of 276 cases were retrospectively reviewed who were subsequently diagnosed with a malignancy and who underwent US-FNAB. Results: Some 45 were found to have previously undergone the US-FNAB procedure. Of the patients in whom the surgical specimen was diagnosed with a malignancy, 21 (46.7%) were diagnosed as malignant or suspicious for malignancy, and 24 (53.3%) were concluded as benign or insufficient for diagnosis. Patients with the diagnosis of PTMC outnumbering the others was a striking finding (11 cases, 24%). Conclusions: We suggest performing repeat aspiration biopsy considering sampling errors in cases where inconsistency exists between clinical findings and cytological results in thyroid nodules smaller than 10 mm in diameter and with suspicious findings on ultrasonography.

GDF-15 (Growth Differentiation Factor-15) is a member of the transforming growth factor β (TGF-β) superfamily. GDF-15 is not only involved in cancer development, progression, angiogenesis and metastasis, but also controls stress responses, bone formation, hematopoietic development, adipose tissue function and cardiovascular diseases. GDF-15, which is regulated by p53, has shown antitumorigenic and proapoptotic activities in vivo and in vitro. Also, GDF-15 is involved in skin biology and histamine-induced melanogenesis; it is overexpressed in melanoma cells and is associated with depth of tumor invasion and metastasis. GDF-15 level is increased in patients with systemic sclerosis and is related with the degree of skin sclerosis and intensity of pulmonary fibrosis. In the future, GDF-15 may be a potential target for therapy in benign disorders with skin fibrosis and malignant lesions of the skin.

Background.Development of neuroepithelial tumors from mature cystic teratoma is very rare. We present a case of oligodendroglioma developing inside mature cystic teratoma.Case.Eighteen-years-old female, right adnexal mass with solid and cystic areas was detected. Sections showed all three germ layers. Also, a tumoral lesion was observed in a glial fibrillary matrix. Tumor was composed of monotonous, uniform cells which have oval-round nucleus, perinuclear halo, and indistinct cytoplasm. GFAP, EGFR, P53 were positive.Conclusions.We diagnosed oligodendroglioma arising from mature cystic teratoma. There was no recurrence at the end of 13 months followup. The number of cases which have been reported in the literature is only a few.

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Introduction. In colorectal carcinoma, tumoral tissues infiltrate with various immune/inflammatory cells along their invasive margins and the increased S100A8/A9 expression in these immune cells infiltrating the tumor has recently been demonstrated. We examined S100A8/A9 as a potential therapeutic target in the treatment of colorectal carcinoma.Materials and Methods. The current study included a sample of 80 patients diagnosed with CRC (30 cases with distant metastasis, 30 cases with lymph node metastasis, and 20 cases with no metastasis). Peritumoral and intratumoral S100A8 and S100A9 expressing inflammatory cells were counted in primary tumors and their metastasis and correlated with clinicopathological parameters.Results. The peritumoral and intratumoral S100A8/A9 positive cells showed no correlation with age, gender, or depth of tumor invasion. However higher counts of peritumoral and intratumoral S100A8/A9 positive cells were associated with larger tumor size, higher grade, and the presence of metastasis(P<0.05).Conclusion. Our study also found significantly higher number of S100A8/A9 positive cells in the tumor microenvironment among patients with large tumor size, high grade, and metastatic disease. Moreover, in our study, we observed that the expression in the tumor metastasis appeared similar to that of primary tumor.

Objective TTF-1 is widely used as an immunohistochemical marker of lung and thyroid tumors. However, TTF-1 expression has been described in tumors from other sites. The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet. We characterized expression of two TTF-1 clones in primary brain tumors with relevance to tumor types and grades. Material and method We studied immunohistochemistry with tissue micro-array, using both clones (8G7G3/1 and SPT24) in 45 primary brain tumors of different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1 schwannoma and 1 medulloblastoma. Results We have found TTF-1 nuclear staining using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III). Focal and weak staining was seen in three cases and moderate-strong and diffuse staining was seen in one case. All the tumors were negative with clone 8G7G3/1. Clone SPT24 was more sensitive but less specific. Conclusion TTF-1 can also be expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1 expression was a rare finding in previous studies, however strong and diffuse staining was not observed until today. We think that TTF-1 nuclear expression in high-grade astrocytic tumors cannot rule out primaries even when diffuse and strong staining. Clinical and pathological parameters should be evaluated together.