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Purpose The aim of this study was to evaluate the use of monopolar radiosurgery (MRS) assisted strabismus surgery and to compare its histologic and immunohistochemical wound healing outcomes with conventional surgery. Methods Superior rectus muscle resection was performed on 30 white rabbits with three different surgical muscle cutting techniques: monopolar radiosurgery (MRS group), conventional scissors preceded by bipolar electrocautery (BEC group), and conventional scissors with no cauterization (control group). Degree of tissue injury, bleeding, inflammation, and fibrosis, as well as wound healing rate (CD68+ cell number), were evaluated. Results In CS group, hemorrhage scores were significantly higher than those in the other groups (MRS group: Z = 5.182; p < 0.001 and BEC group: Z = 4.463; p < 0.001) and MRS group had lower scores than BEC group; however, the difference was not significant (Z = 1.423; p = 0.211). The tissue injury score in BEC group was higher when compared with MRS, and the difference was statistically significant (p = 0.028). Median inflammation scores at days 1 and 21 were lowest in MRS group, but the difference was not statistically significant among groups (day 1; p = 0.115, day 21; p = 0.095). The median fibrosis score was higher in the control group, when compared with MRS, and the difference was statistically significant (muscle-sclera; p = 0.011 and muscle-conjunctiva: p = 0.003). The macrophage score (number of CD68+ cells) was lowest in CS group; however, the difference was not significant (p = 0.657). Conclusions Monopolar radiosurgery is a novel method for strabismus surgery and provides equivalent hemostasis effects and wound healing properties, compared with conventional methods, and enhances surgeon comfort, as muscle incisions are made in one step with clean surgical area.

Epstein Barr virus (EBV) related lymphoproliferative diseases may occur in immunocompromised patients or patients with a history of drug use causing immunodeficiency. EBV positive mucocutaneous ulceration in the new classification of lymphoproliferative diseases in 2016 is very rare in children. Involvement occurs in the skin, oral mucosa, and gastrointestinal system. Gastric involvement is very rare in the literature. There is no case of gastric involvement in children. There are no specified modalities in the treatment of EBV positive mucocutaneous ulceration. We presented our pediatric patient with ataxia telangiectasia who presented with abdominal pain and difficulty swallowing and diagnosed with EBV positive mucocutaneous ulceration in the stomach. We started brentuximab vedotin during the treatment process, and complete remission was achieved after 6 cures of treatment. Our patient is the first case of EBV positive mucocutaneous ulceration in the pediatric case series.

© 2022 Elsevier LtdPoor graft function (PGF) and secondary failure of platelet recovery (SFPR) are significant causes of transplant related morbidity and mortality. Although thrombopoietin receptor agonists (TPO-RA), particularly Eltrombopag (EPAG), have been reported to be efficacious in the treatment of prolonged thrombocytopenia, potential long term adverse effects remain to be elucidated. This retrospective study was performed to determine the efficacy and toxicity profile of TPO-RAs in allogeneic hematopoietic stem cell transplant (alloHCT) recipients. Medical records of 27 patients [median age: 55(21−73) years; male/female: 15/12] who received posttransplant EPAG for SFPR or PGF were analysed. Eltrombopag was started on day 110(33−670) after transplant. Median initial dose was 25(25−50) mg/day which was properly escalated to a maximum dose of 75(50−100) mg/day. Duration of the treatment was median 120(31−377) days. Overall response rate (ORR) was 59.3% in the study population. Time-to-treatment response was 42(3−170) days. Mild-to-moderate bone marrow fibrosis was detected in the posttreatment biopsies of 12/22 patients (54.5%), 9 of whom did not represent any grade of myelofibrosis in their inital biopsies. The grade of posttreatment fibrosis was significantly increased when time-to-treatment response was longer (p = 0.008). Long term use of TPO-RAs may be considered as a potential cause of myelofibrosis in alloHCT recipients.

Inflammatory myofibroblastic tumors (IMTs) are mesenchymal solid tumors, in which anaplastic lymphoma kinase (ALK) gene rearrangement might be detected. A 48-year-old female presented with IMT of lung, treated with surgery. After a 39-month disease-free survival metastatic recurrence was occurred involving soft tissues both infra- and supradiaphragmatic regions. The biopsies obtained from metastatic regions confirmed the recurrence with ALK rearrangement in immunohistochemistry. Initial partial response observed early in treatment course remained as a stable disease with crizotinib treatment. Although an excellent outcome with overall survival of 57 months was observed in our case, there is not enough information about survivals with crizotinib and the treatment options beyond progression. Therefore, every individual case has a unique value paving the way for more effective treatment.

Aim: To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. Methods: PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. Results: PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (p = 0.008). No difference in survival was found between PD-L1-positive and negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. Conclusions: This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giantcell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.

Background: Sepsis is one of the leading causes of death in intensive care units. Dexmedetomidine is a sedative agent with anti-inflammatory properties. This study is designed to differentiate the impact of two different doses of dexmedetomidine on lung injury induced by sepsis. Methods: Adult male Wistar rats were randomly divided into four groups: sham (n = 6), control (n = 12), 5DEX (n = 12), and 10DEX (n = 12). Cecal ligation puncture (CLP) was applied for sepsis initiation. The 5DEX group received 5 & micro;g.kg-1.h-1 and the 10DEX group received 10 & micro;g.kg-1.h-1 dexmedetomidine intravenous infusions for a 1-hour period. Six hours after CLP, tumor necrosis factor-a (TNF-a), interleukin-113 (IL-113), and intercellular adhesion molecule-1 (ICAM-1) levels were analyzed in blood samples. Twenty-four hours after CLP, lung samples from the remaining rats were collected for the measurement of myeloperoxidase (MPO) activity, histological examination, and TdT- (terminal deoxynucleotidyl transferase) mediated fluorescent-dUTP labeling staining for apoptosis detection. Results: Serum cytokine release, MPO activity, and apoptosis in the lung were significantly increased in the CLP group compared with the sham and dexmedetomidine groups (p < 0.05). TNF-a, ICAM-1, and MPO were significantly lower in the 10DEX group compared with both 5DEX and control groups, while IL-113, total injury score, and apoptotic cell count had significantly lower values in both 10DEX and 5DEX groups compared with the control group (p < 0.05). Conclusion: Dexmedetomidine administration played a protective role against CLP-induced lung injury. High-dose dexmedetomidine was needed for suppressing the leukocyte-mediated lung injury and apoptosis of lung tissue. (c) 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Objective: patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor I (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. Material and method: in this study, we analyzed the EML4-ALK mutation using the FISH and IHC techniques in 251 lung adenocarcinoma (203 primary resections, 48 metastasectomies) cases. Correlative analyses were performed between the EML4-ALK mutation, the IGFR1, TTF1, and NapsinA expression, and the clinicopathologic factors in lung adenocarcinomas. Results: the EML4-ALK mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size. IGFR1 expression was identified in 49% of the cases and most of the ALK-mutated cases were also expressing the IGFR1 protein (66%). IGFR1 expression frequency was increased in metastasectomy specimens. Conclusion: a solid signet-ring cell pattern or mutinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor prognostic marker in patients with lung adenocarcinoma., Gazi University Scientific Research Projects

Purpose: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. Patients and Methods: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if >= 5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. Results: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). Conclusion: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

Ependymomas are tumors located in the central nervous system, mostly in the brain and spinal cord. This tumor is rarely seen as a primary mediastinal location. The aim of this study is to discuss this rare pathology in the clinical course of an unusual case. A 47-year-old female patient was referred to our clinic with the complaint of back and shoulder pain, via VATS posterior mediastinum located paravertebral mass excision was performed. The pathology reported as ependymoma. Two years later, CT scans of the routine control showed the well-defined mass in anterior mediastinum. The SUVmax of the lesion was measured as 9.3 at PET-CT. The lesion in the anterior mediastinum was excised by partial sternotomy. The pathology result was the same as the prior operation: Ependymoma. As our case, in these kinds of tumors meticulous follow-up of the patients is important for the detection and treatment of recurrent localization and distant metastases.

Solitary bone plasmacytoma is a rare disease in the skull. We present a 70-year-old patient who presented with a skull deformity due to the left parietooccipital tumor. Neurological examination found no deficit. The systemic scanning revealed no additional lesion. The surgery was planned, and the tumor was removed totally with the marginal bone around it. Histopathological examination confirmed solitary bone plasmacytoma. The patient is being followed-up without recurrence or progression to multiple myeloma. As the calvarial solitary bone plasmacytomas can be easily misdiagnosed preoperatively, the detailed examination of the CT features may be helpful for the planning and course of the surgery.

Purpose Anaplastic lymphoma kinase (ALK) gene rearrangement exists in approximately 3-7% of non-small cell lung cancer (NSCLC) and more than 15% split or isolated red signals among 50 tumor nuclei scored in the FISH analysis defines as ALK-positive. The previous studies showed that the high EGFR mutational load related to better outcomes in EGFR mutant NSCLC. Therefore, we aimed to investigate the effect of the ALK break-apart ratio on treatment outcome in metastatic ALK-positive NSCLC. Methods The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled. The 30%, 40%, 50%, 60%, and 70% break-apart ratios were determined as a threshold value, and each of these was evaluated separately. Based on the results of these analyses, we detected the optimal threshold value and also performed further investigations. Results A total of 70 patients were enrolled in the study. The most significant decrease in the risk of the progression or death was detected at the 50% threshold value and it was accepted as the optimal threshold. The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004). The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) Discussion In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.

Background: Programmed death-ligand 1 (PD-L1) has been determined as a reliable prognostic factor for various malignancies. In this study, we aimed to determine the prognostic effect of PD-L1 expression in tumor-infiltrating immune cells (TIICs) of nasopharyngeal carcinoma (NPC) patients.Methods: Seventy patients diagnosed with non-metastatic NPC were included in the study. PD-L1 expression on immune cells was analyzed by immunohistochemical method. Patients were categorized into two groups according to the PD-L1 expression level in TIICs (level of PD-L1 staining ≥5% positive vs

Malignant pleural effusion (MPE) confers dismal prognosis and has limited treatment options. While immune-checkpoint inhibition (ICI) proved clinical efficacy in a variety of malignancies, data on the prognostic role of PD-L1 in MPE is scarce. We retrospectively studied PD-L1 tumour proportion score and Ki-67 index in pleural biopsies or cytologies from 123 patients (69 lung cancer, 25 mesothelioma, and 29 extrathoracic primary malignancies). Additionally, the impact of C-reactive protein (CRP) and platelet count was also analysed. Median overall survival (OS) after MPE diagnosis was 9 months. Patients with PD-L1 positive tumours (≥1%) had significantly shorter OS than patients with negative PD-L1 status (p = 0.031). CRP and Ki-67 index were also prognostic and remained independent prognosticators after multivariate analysis. Interestingly, Ki-67 index and CRP influenced the prognostic power of PD-L1. Finally, patients receiving ICI tended to have a longer median OS and CRP - but not PD-L1 - was a significant prognosticator in this subgroup. In summary, histological and circulating biomarkers should also be taken into account as potential biomarkers in ICI therapy and they may have an impact on the prognostic power of PD-L1. Our findings might help personalizing immune-checkpoint inhibition for patients with MPE and warrant further prospective validation.

Objectives Organizing pneumonia is an important disease that is associated with non-specific clinical findings and radiographic appearance. Our aim was to examine the clinical and radiological features, laboratory findings, diagnostic approach, and response to therapy in subjects with cryptogenic (COP) and secondary organizing pneumonia (SOP). Materials and methods Patients' medical records were retrospectively reviewed between 2010 and 2016 in our hospital. We analyzed the symptoms, radiological features, pulmonary function tests, laboratory data, bronchoalveolar lavage findings, treatment, and prognosis. Results Thirty-seven patients were diagnosed with COP and 19 patients with SOP. The most common causes of SOP were determined as rheumatologic diseases. The most common symptoms were cough (71.4%) and dyspnea (66.1%). Bilateral symmetrical consolidations were the most prominent radiological appearance in both COP and SOP. The general radiographic findings were not different in COP and SOP. However, pulmonary lesions were located rather in the central (p=0.023) and middle (p=0.001) zones in patients with SOP. Corticosteroid (CS) therapy was administered to 34 (60.7%) patients. Two patients showed deterioration despite CS therapy. Conclusion The clinical and radiographic findings, treatment response, prognosis were similar in patients with COP and SOP.

Introduction Programmed death ligand 1 (PD-L1) is a marker that widely used for prediction of response to immunotherapy. Dynamic alteration of PD-L1 expression are the major problems for reflection of the actual status of the PD-L1. So, we aimed to investigate the factors that may be associated with PD-L1 expression in lung cancer. Materials and Methods The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The patients were stratified according to PD-L1 expression level as ≥ 50% and < 50%. Result Totally, 217 patients were enrolled. The clinicopathologic features were similar between two groups, except the amount of cigarette consumption. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammmotry index were found significantly lower in PD-L1 ≥ 50% (p< 0.001, p= 0.006 and p= 0.003, respectively) and also negatively correlated with PD-L1 level (rho= -0.255, p< 0.001; rho= -0.17, p= 0.013; rho= - 0.185, p= 0.006, respectively). Conclusions According to the results of our study, peripheral blood parameters can be used to the prediction of the high PD-L1 expression and can be used for reflection of current PD-L1 expression.

Peripheral T-cell lymphomas expressing follicular helper T-cell (T-FH) markers have recently been identified. Although this type of lymphomas consist of malignant proliferation of T-cells, they may also exhibit B-cell clonality. We report a case of a 72-year-old woman with multiple erythematous to violaceous nonscaling plaques and tumors on her trunk. Histopathological analysis revealed a dense infiltration of medium-to-large-sized atypical cells throughout the entire dermis. The result of immunohistochemical analysis showed that the infiltrating T-cells expressed programmed death-1 (PD-1), CD10, Bcl-6, CD3, CD4, CD2, and CD5. The infiltrate also contained scattered atypical large B-cells. Based on the clinical appearance and the histopathological findings, we diagnosed the patient with secondary cutaneous dissemination of peripheral T-cell lymphoma with expression of a T-follicular helper phenotype.

Objective Convex probe endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is a minimally invasive technique with high sensitivity in the mediastinal staging of non-small cell carcinoma (NSCLC). In recent years, molecular testing has been developed to study genetic mutations in NSCLC. There are studies revealing improved survival in advanced NSCLC using targeted therapy as the first-line treatment in these patients. The aim of this study was to evaluate the adequacy of EBUS-TBNA in providing adequate size specimens for EGFR, ALK and ROS1 genetic mutation analysis in patients with adenocarcinoma or not otherwise specified (NOS) lung cancer. Materials and methods Charts of patients diagnosed with lung adenocarcinoma or NOS via EBUS-TBNA were retrospectively reviewed. Information on patient demographics, number of lymph nodes sampled, their size and location, targeted gene mutations and the adequacy of the material sampled for the molecular testing was recorded. Results A total of 114 patients were included in the study, adenocarcinoma 86 (75%) and NOS 28 (25%). EGFR gene mutation was studied in all of the patients included in the study while ALK in 113 and ROS1 in 98. The material adequacy ratios for EGFR gene mutation, ALK and ROS1 rearrangements were found to be 88.6%, 93.8% and 91.8%, respectively. EGFR gene mutation, ALK and ROS1 rearrangements were found positive in 13 (11.4%), 9 (8%) and 1 (1%) patients, respectively. Conclusion The study demonstrated that EBUS-TBNA provides adequate material for mutation analysis in patients with newly diagnosed adenocarcinoma or NOS lung cancer.

Objective: Few data are available on the clinical significance of 18-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) results in patients with leukemia. We investigated the utility of FDG-PET/CT at the time of relapsed/refractory disease in pediatric patients with leukemia. Methods: Medical records of 28 children with suspected leukemia progression or recurrence during/after chemotherapy or allogeneic stem cell transplantation (allo-SCT) were retrospectively reviewed to determine the utility of FDG-PET/CT. Results: Twenty-two of the 28 patients have documented abnormal imaging findings during clinical follow-up, while six had were interpreted as not demonstrating signal consistent with active leukemia. Of the 22 patients with abnormal FDG-PET/CT studies 14 were found to have FDG-PET/CT reported as consistent with active leukemia and increased leukemia blasts on bone marrow biopsy. Regarding the eight patients without positive FDG-PET/CT and proven leukemia relapse, four had discordant findings on FDG-PET/CT and biopsy, and four had FDG-PET/CT reported as infection. Mean maximum standardized uptake values (SUVmax) were significantly higher among patients whose FDG-PET/CT findings were positive for leukemia as opposed to infectious disease (p < .05). Mean SUVmax was also significantly higher among patients with multifocal lesions on FDG-PET/CT than among those with diffuse lesions (p < .05). Conclusions: The findings suggest that FDG-PET/CT may be a complementary imaging modality that could be combined with bone marrow examination to improve detection of subtle leukemic infiltration in children with suspected leukemia progression or recurrence after chemotherapy or allo-SCT.

Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy.Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically.Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (pp

Aim of the study: Our study was designed to evaluate the acute effects of malathion on rat liver tissues. Material and methods: The animals were divided into 4 groups of 6 animals/each. Group 1 (control group) received corn oil, while groups 2, 3, and 4 were given malathion dissolved in corn oil at a dose of 100, 200 and 400 mg/kg, respectively. 24 hours after malathion administration, animals were sacrificed and liver tissues were collected. The liver tissues were then analysed biochemically and histopathologically. Results: Butyrylcholinesterase levels in groups 2, 3 and 4 were significantly lower than that of group 1. Total oxidant status and tumour necrosis factor alpha level were significantly increased in group 4 compared to group 1. Catalase activities of groups 3 and 4 were significantly higher than that of group 1. Arylesterase activity was significantly decreased in groups 3 and 4 compared to group 1. In groups 3 and 4, some vacuoles in hepatocytes were revealed and hydropic degeneration was observed in group 4. Conclusions: Acute administrations of malathion results in hepatotoxicity in a dose-dependent manner. © 2019 Termedia Publishing House Ltd.. All rights reserved., Firat University Scientific Research Projects Management Unit: 01/2015-01, This study was conducted at Gazi University Medical Biochemistry Research Laboratories, Ankara, Turkey and was supported by Gazi University Scientific Research Projects under project code 01/2015-01. None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.

Malignant mesothelioma (MM) is an aggressive cancer with a poor prognosis. The most common genetic alteration in MM is the deletion of the INK4a/ARF locus, which encodes the p16 protein and is located on the short arm of chromosome 9 (9p21). Recently, it has been shown that homozygous deletion of 9p21 has both diagnostic and prognostic significance in MM. It is a known fact that, to interpret fluorescence in situ hybridization (FISH) signals, a cut-off value for each probe should be determined for a correct diagnosis. To our knowledge, there is no consensus or confirmed protocol for cut-off values to evaluate FISH signals in MMs. Therefore, the aim of our research was to address 9p21 deletion status and p16 expression profiles of MM by determining our own cut-off values and the effectiveness of using p16 negativity and 9p21 deletion as markers for differentiating MMs from benign mesothelial proliferations in 114 cases. We established a cut-off value for the detection of 9p21 deletion by using 13 benign reactive cases (6 reactive mesothelial hyperplasias and 7 chronic fibrinous pleuritis cases) and found between 0-7%. According to our calculations, homozygous deletion was defined by loss of both p16 gene signals in at least 13.3% of the nuclei that showed at least 1 signal for the CEP 9 probe. Our FISH results showed homozygous 9p21 deletion in 82 of the 114 cases of MM (71.9%), and p16 expression was negative in 75 of the 114 cases (65.8%). The correlation between loss of p16 protein expression and 9p21 deletion was statistically significant. Among the p16-negative cases, 86.7% also had the 9p21 deletion. The combined examination of the 9p21 deletion and loss of p16 expression is helpful for diagnostic purposes, but because the FISH method is an expensive technique and loss of p16 expression is not specific for mesotheliomas, p16 negativity can guide practitioners to eliminate cases that require further investigation by FISH. The variability in the significance of 9p21 homozygous deletion results from inconsistencies among different institutes, suggesting that each institute should establish its own cut-off value using reactive mesothelial proliferations. Alternatively, global studies are needed to assess cut-off values.

e20532Background: Prognostic significance of PD-1/PD-L1 axis expression in non-small cell lung cancer (NSCLC) remains uncertain despite being a predictive biomarker for novel immunotherapeutics. In...

Primary myelofibrosis (PMF) is a clonal stem cell disease, characterized by bone marrow fibrosis. Ruxolitinib is a selective inhibitor of JAK-1 and JAK-2 used to treat PMF. Its mechanism of action is based on the reduction of signal transduction and cytokine levels; including IL-6 and tumor necrosis factor alpha. Increased infection risk related to Ruxolutinib is rarely reported. Here we describe a case of tuberculosis infection ractivation in a female patient treated with Ruxolitinib. During the treatment, she complained of night sweats, weight loss and enlarged mass in the neck. Excisional mass biopsy revealed a necrotizing granulomatous lymphadenitis. QuantiFERON-TB and PPD tests were not able to diagnose the tuberculosis infection. Therapy with Ruxolitinib was interrupted due to possible immunsuppressive effects and the patient was treated with the standard antituberculosis regimen. After six months, the patient’s symptoms had resolved and there was no lymphoadenopathy. In conclusion, it is important to assess the risk of tuberculosis activation before Ruxolitinib treatment. In addition, the diagnosis of tuberculosis using QuantiFERON-TB and PPD may be misleading in patients treated with Ruxolutinib.

Richter9s transformation (RT) refers to the development of aggressive lymphoma during the course of CLL. Clinically, patients with RT present with an aggressive disease course with rapidly enlarging lymph nodes, hepatosplenomegaly, and elevated serum lactate dehydrogenase levels. But rarely it presents with extra nodal organ involvement at the beginning.We are reporting this case as our patient presented with RT in the lung involvement diagnosed while research of cavitary lesion etiology.An 80-year-old female patient was accepted to our clinic with complaints of malaise, fatigue, loss of appetite, weight loss of 10 kg within the last three months, and cough, sputum production, fever, and deterioration in her state of consciousness within the last month. The patient had been followed up with the diagnosis of CLL for two years without any medication.On thorax CT, a cavitary lesion measuring 2.9X3.5X3.1 cm was detected in the superior segment of the right lower lobe, diffuse multiple nodular lesions were detected in both lungs, and multiple mediastinal and bilateral hilar lymphadenopathies, the largest measuring 1.5 cm in diameter, were detected. Diagnostic bronchoscopy was performed.In the pathological examination of the transbronchial biopsy from cavitary lesion wall revealed T cell rich, large B cell lymphoma.It should be kept in mind that cavitary nodular lesions in the lungs could be observed when RT develops in patients with CLL.

Aim: The aim of the study was to evaluate angiogenesis-related parameters including vascular endothelial growth factor (VEGF), p300 expression, and microvessel density (MVD) in plasma cell myeloma (PCM). Material and Method: p300, VEGF, and Factor related antigen (for measurement of MVD) were applied to the para n-embedded bone marrow sections of 45 patients with PCM, immunohistochemically. Histomorphologic factors, clinical and laboratory findings, and overall survival (OS) were correlated with p300 and VEGF expression, and MVD. Results: VEGF overexpression (>= 50) was significantly associated with diffuse infiltration pattern and high percentage of plasma cell infiltration (p=0.014, p=0.002, respectively). Higher MVD was directly correlated with diffuse infiltration pattern and increased CRP levels (p=0.026, p=0.015, respectively). No significant difference was noted in percentage of survivors and OS with respect to p300, VEGF, and MVD. No significant correlation was noted between p300 expression, VEGF expression, and MVD. Discussion: Our findings revealed significant association of bone marrow infiltration pattern and quantity of neoplastic cells with MVD and VEGF expression. Although no association of p300 was shown with histomorphologic prognostic parameters, MVD, VEGF expression, or OS, this is the first study investigating the potential prognostic role of p300 expression in PCM, to the best of our knowledge. In conclusion, more-comprehensive studies are needed to further elucidate the interaction between angiogenesis and myeloma cells as well as the prognostic role of increased bone marrow angiogenesis in PCM.

Thymus gland involvement in Langerhans cell histiocytosis (LCH) is usually part of multi-system disease and may be more common than previously recognized. However, thymic involvement causing an anterior mediastinal mass is an extremely rare presentation of multisystem LCH. Here we report a 2-month-old-boy admitted to hospital with a giant anterior mediastinal mass with multisystem LCH involving the thymus, lungs, liver and skin. The differential diagnosis of mediastinal mass in children should also include LCH, especially multisystem disease. LCH should also be kept in mind in the differential diagnosis of skin lesions in infants, even if spontaneous regression occurs.