Showing papers in "iranian journal of pathology in 2020"

The novel coronavirus sars-cov-2 vulnerability association with abo/rh blood types

Abstract: Background & ObjectiveCoronavirus disease 2019 (COVID-19) is the most recent emerging viral disease. Defining the epidemiological aspects and factors influencing the susceptibility of the patients to COVID-19 has been an ongoing struggle. In the present study, we have investigated the connection between ABO histo-blood group phenotypes and the COVID-19.MethodsThis study was conducted on 397 patients with confirmed diagnoses of COVID-19 admitted to our center. Also, 500 individuals were selected to form the controls, all of whom had been disclosed to the same medical center in June 2019, before the onset of the outbreak.ResultsOur results demonstrated ABO histo-blood phenotypes are correlated with patients’ susceptibility to the infection. A higher rate of infection was observed among patients with the AB histo-blood group, while patients with the O histo-blood group have shown a lower rate of infection. The Rh blood group phenotype was not statistically significant in determining a patient’s vulnerability.ConclusionSimilar to several previous studies about other viral diseases’ association with ABO histo-blood groups, we have concluded that an individual’s ABO histo-blood group phenotype and his/her susceptibility to COVID-19 are indeed connected. So far, only one research has been conducted about this association. Interestingly, while we observed a decreased vulnerability to the disease among patients with an O histo-blood group, we have reached discordant results regarding the increased susceptibility among individuals with an AB histo-blood group, unlike A histo-blood group in the previous study.

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study.

Abstract: Background & objective Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association with neoadjuvant treatments. Methods This research was performed on newly diagnosed breast cancer patients referred to Omid Radiotherapy Center and radiotherapy and oncology departments of Emam Reza and Ghaem hospitals, in Mashhad, Iran. Serum levels of M30 and M65 fragments of Cytokeratin 18 were measured before and 24 hours after the first course of neoadjuvant chemotherapy. Changes in serum levels of Cytokeratin 18 and its fragments and their correlation with pathologic response were analyzed. Results Pre- and post-chemotherapy levels of M30 were respectively 223.9±18.94 and 250.7±23.92 U/L (P=0.24). For M65, these levels were respectively 301.5±313.9 and 330.2±352.2 U/L (P=0.1). Changes in M30 level during chemotherapy in patients with and without pathologic complete response were -20±92.69 and 43.1±106.5, respectively (P=0.1). For M65, these changes were respectively -247±55 and 76±240 (P=0.1). Baseline levels of M30 and M65 had no relation with menopausal status, tumor grade, hormone receptor status, Ki67 expression, molecular subtype, and stage. Conclusion Our findings showed statistically insignificant changes in the level of Caspase-cleaved- (M30) and uncleaved- (M65) cytokeratin 18 fragments (apoptotic and necrotic indicators, respectively) during neoadjuvant chemotherapy in patients with breast cancer. There was no notable relationship between tumor-related factors and either baseline levels or serum changes of CK18 fragments. Also, there was no correlation between M30/M65 level and pathologic response to neoadjuvant chemotherapy.

Hypocalcemia in Covid-19: A Prognostic Marker for Severe Disease.

Abstract: Background & Objective: Previous studies have addressed the electrolyte abnormalitiessuch as hypocalcemiain COVID-19 patients. We aimed to compare the laboratory findings especially the electrolyte levels amongCOVID-19 patients and healthy controls and evaluate their prognostic values. Materials and Methods: This case-control study included 91 COVID-19 patients and 169 healthy individuals. Their laboratory parameters including electrolytes, albumin, liver enzymes, complete blood count, vitamin D, and parathyroid hormone (PTH) were compared. We also analyzed the association between these markers and the major outcomes including severity, mortality and hospitalization. Results: Among patients with COVID-19, 59.3% of the patients had hypocalcemia on admission while in control group only 32.5% had low calcium level (OR=3.02, 95% CI: 1.79-5.13, p <0.001). The rates of death and ICU admission were significantly higher among the patients in hypocalcemic group than those of eucalcemic group (85.7% vs 14.3% and 33.3% Vs 9.1%, respectively). However, there was no significant difference in the mean PTH and vitamin D levels between the two groups. In terms of the severity of the infection, 74.1% of patients in hypocalcemic group had a severe infection while 24.3% of the patients in eucalcemic group were diagnosed with severe infection (OR=8.89, 95% CI: 3.38-23.37, p <0.001). Conclusion: Patients with COVID-19 had considerable laboratory abnormalities including hypocalcemia. The hypocalcemia was also associated with worse major clinical outcomes and higher mortality risk.

Persister cells formation and expression of type II Toxin-Antitoxin system genes in Brucella melitensis (16M) and Brucella abortus (B19).

Abstract: Background & objective Persister cells are defined as a subpopulation of bacteria that are capable of reducing their metabolism and switching to dormancy in stress conditions. Persister cells formation has been attributed to numerous mechanisms, including stringent response and Toxin-Antitoxin (TA) systems. This study aimed to investigate the hypothetical role of TA systems in persister cells formation of Brucella strains by evaluating toxins of type II TA systems (RelE, Fic, Brn T, cogT) expression. Methods Brucella strains treated with a lethal dose of gentamicin and ampicillin and to determine the number of surviving cells, bacterial colonies were counted at different time intervals. The role of TA systems in persister cell formation was then determined by toxin expression levels using qRT- PCR method. Results Our results showed the viability of persister cells after 7 h. The results of relative qRT- PCR showed higher levels of toxin gene expression due to stress conditions, suggesting the possible role of TA systems in persister cells formation and antibiotics tolerance. Conclusion The results of this study showed that considering the importance of persistence and the tolerance to antibiotics, further studies on persister cells formation and related genes such as the TA system genes in Brucella strains might help us to identify the precise mechanisms leading to persister cells formation.

Micronucleus Assay of Buccal Mucosa Cells in Waterpipe (Hookah) Smokers: A Cytologic Study

Abstract: Background & Objective: Micronucleus assay of buccal mucosa cells is a simple bio- monitoring method for diagnosing the genetic damages of toxic agents. The aim was to study the genotoxic effect of waterpipe smoking on buccal mucosa cells using micronucleus assay. Methods: This was a case control. A total of 30 male waterpipe smokers and 30 non-smokers were included in the study. The exfoliated buccal mucosa cells were scrapped using wooden spatula and were spread over glass slides. The mean number of micronuclei was determined using Feulgen-stained slides. The number of micronuclei per 1000 cells was calculated and compared between the two groups of smokers and non-smokers. Result: The mean number of micronuclei in waterpipe smokers and non-smokers was 1.94±0.39 and 1.68±0.35, respectively. The micronuclei count in waterpipe smokers was significantly higher than non-smokers (P=0). The difference between the number of waterpipe smoking and micronuclei count was significantly different (P=0). Conclusion: The mean number of micronuclei in buccal mucosa cells of waterpipe smokers was significantly higher than non-smokers. The genotoxicity effect of waterpipe was dose-dependent.

Evaluation of Phenotypic and Genotypic Characteristics of Carbapnemases-producing Enterobacteriaceae and Its Prevalence in a Referral Hospital in Tehran City.

Abstract: Background & objective Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide including Iran. The emergence of this pathogen is worrying as carbapenem is one of the 'last-line' antibiotics for treatment of infections caused by multi drug resistant gram- negative bacteria. The main objective of this study was to determine the prevalence of carbapenem-resistant Enterobacteriaceae in a referral hospital in Tehran, Iran. Methods In this study, all positive isolates of Enterobacteriaceae recorded in blood, urine, and other body fluids were studied during April 2017 to April 2018 in a referral hospital in Tehran. All cases of resistance to carbapenems were first tested by modified Hodge test. All cases with positive or negative test, after gene extraction, were examined genotypically based on the primers designed for the three Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and OXA-48 genes by conventional PCR method. Results 108 isolates (13.6%) were resistant to all cephalosporins as well as to imipenem and meropenem. In a genotypic study, including 45 isolates, 13 isolates were positive for OXA-48 gene, 11 isolates for OXA-48 and NDM genes, 11 isolates for OXA-48, NDM and KPC genes, 4 isolates for OXA-48 genes and KPC, 3 isolates for NDM, one isolate for KPC. On the other hand, two isolates were negative for all three genes examined. Conclusion OXA-48 gene was one of the most common genes resistant to carbapenems in Iran. According to studies, the prevalence of antibiotic resistance in Iran is rising dramatically, which reduces the choice of antibiotics to treat severe infections in the future.

Clinical Validation of Eleven Formulas for Calculating LDL-C in Iran.

Abstract: Background & objective Concentration of low-density lipoprotein (LDL) is a known risk factor for cardiovascular disease which is routinely measured or calculated as LDL-C in clinical laboratories. In order to decrease the cost, instead of its measuring, it is recommended to calculate it using multiple formulas that have been introduced up to now. The aim of this study was to assess the results of various formulas and comparison of these results with those of measuring method and to clarify the best formula for the Iranian population. Methods Concentrations of total cholesterol (TC), triglyceride (TG), cholesterol of high-density lipoprotein (HDL-C) and LDL-C in serums of 471 overnight fasting individuals were measured and also LDL-Cs of these samples were calculated by eleven different formulas according to their TC, TG, and HDL-C concentrations. Subsequently, results of measured and calculated LDL-C were analyzed statistically by paired t-test, correlation coefficient, and Passing-Bablok regression. In addition, for clinical evaluation, the differences between calculated and measured mean results were calculated and compared with an allowable total error. Results Paired t-test unraveled a significant difference between the results of measured and calculated LDL-C by various formulas. But for some formulas, these differences were not clinically significant. The best clinical and statistical agreement (correlation coefficient) was obtained by the Friedewald equation. Conclusion By using validated methods which have correct calibration and control system for measuring TC, TG, and HDL-C, we can use the Friedewald formula for calculating LDL-C in serum samples with TG up to 400 mg/dL.

Comparison of patient-collected and lab technician-collected nasopharyngeal and oropharyngeal swabs for detection of COVID-19 by RT-PCR

Abstract: Background & Objective: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR). Methods: Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed. Results: Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (p =0.001). Conclusion: Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.

Association of Human Papilloma Virus and Epstein-Barr Virus with Ovarian Cancer in Shiraz, Southwestern Iran.

Abstract: Background & Objective: Ovarian cancer is one of the most common cancers amongst women. The association of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) with ovarian cancer is inconclusive; therefore, the aims of this study were to evaluate the frequency of HPV and EBV in malignant, borderline, benign and normal ovarian tissues. Methods: In this case-control study, 205 Paraffin-embedded ovarian tissue specimens including 68 malignant, 27 borderline, 65 benign, and 45 normal tissues were included from December 2014 to January 2018 and subjected to DNA extraction. The β-globin gene was amplified using PCR to confirm the quality of the extracted DNA. The genomes of HPV (genotypes 16 and 18) and EBV were identified, using specific primers by PCR. Results: The mean age of participants was 43.42 ± 15.4 years. The frequency of HPV was statistically significant between malignant versus benign (p =0.02) and control groups (p =0.002), but not with borderline tumor group (p =0.78). Amongst HPV infected samples, 1 (4.5%) and 14 (63.6%) samples were infected with types 16 and 18, respectively. Also 4 (18.2 %) samples were infected with both genotypes. Eleven samples including 7(10.3%) malignant, 1 (3.7%) borderline, 3 (4.6%) benign and none (0%) of normal control groups were infected with EBV, which was statistically different between malignant and the normal control group (p =0.03). Conclusion: The results of our study showed the possible role of high risk HPVs as well as EBV in pathogenesis of ovarian cancer, and further studies are recommended to confirm these findings.

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients.

Abstract: Background & Objective: FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment. Methods: We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study. Results: FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, p =0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, p =0.003 and MFI 74.51 vs 57.15 p =0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, p =0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (p =0.61). Conclusion: A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

Serology testing for sars-cov-2: Benefits and challenges

Abstract: As COVID-19 was declared as a pandemic by the World Health Organization (WHO) in March 2020, it is an emerging need to discuss different aspects of this pandemic. In any pandemic, valid and rapid laboratory diagnostic tests are critically important for early diagnosis, which will increase the rate of successful treatment and more importantly prevent the spread of the disease.

Interobserver Agreement in Assessing Dysplasia in Colorectal Adenomatous Polyps: A Multicentric Iranian Study.

Abstract: Background & objective Most colorectal cancers (CRCs) arise from adenomatous polyps, and clinical management of this type of polyp is highly dependent on the reliability and validity of the pathological diagnosis. The aim of this study was to examine the interobserver agreement of five pathologists in assessing dysplasia in adenomatous polyps. Methods In this study, a total of 146 adenomatous polyps of patients undergoing colonoscopy were selected from hospitals of Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2017 and 2018. Five pathologists independently classified adenomatous polyps according to histologic type, nuclear pseudostratification, mitotic activity, nuclear polarity, nuclear pleomorphism, nuclear shape, nucleolus, chromatin pattern, cytology grade, architectural features, dysplasia, and final diagnosis. The overall kappa statistic (k) was used to assess agreement among pathologists. Results The mean age of the patients was 62.06 ± 13.06 (mean ± SD) with a male-to-female ratio of 2.2:1. The most common site of resection was the sigmoid colon (28.1%). The highest agreement was found for dysplasia grade (k=0.415) and histologic type (k=0.401), whereas the lowest agreement was found for mitotic activity (k=0.185), nuclear shape (k=0.187), and nucleolus (k=0.196). Conclusion Our findings indicate that agreement among pathologists in assessing dysplasia in adenomatous polyps is within fair to moderate levels of agreement. Therefore, there is a vital need to better clarify the current diagnostic criteria.

Characterization of Immunophenotypic Aberrancies in Adult and Childhood Acute Lymphoblastic Leukemia: Lessons from Regional Variation.

Abstract: Background & objective Although the antigen expression patterns of acute lymphoblastic leukemia (ALL) are well known, this study attempted to evaluate commonly used immune markers for immunophenotyping of acute leukemia to set the minimum of necessary diagnostic panels by flow cytometry. Methods This study evaluated 89 patients referred from all over the country to the Iranian Blood Transfusion Organization (IBTO) in Tehran from 2013 to 2015. We compared the immunophenotype patterns of childhood and adult ALLs including 69(77.5%) B-cell lymphoblastic lymphoma (B-LBL), 2(2.2%) Burkitt's lymphoma (BL), and 18(20.2%) T-cell lymphoblastic lymphoma (T-LBL) cases using flowcytometry with broad antibody panel. Results CD19 and CD79a were the most frequent markers for B-LBL while CD7 was the most sensitive marker in T-LBL; the frequency of CD7, CD3, and CD5 antigens were 100%, 38.9%, and 88.9%, respectively. TdT+/CD34+ was significantly higher in adult B-LBLs than children, which indicates blast cells are more immature in adults. In addition, CD10 and cCD79a were significantly higher in children with B-LBL like as CD5 and CD8 in children with T-LBL. Aberrant phenotypes including CD13, CD33, CD7, and CD117 were found in 7(10.1%) cases of B-LBL. These phenotypes were CD117, HLA-DR, and CD33 in 7(38/9%) cases of T-LBL. Expression of CD117 aberrant myeloid antigen was significantly more associated with T-LBL than with B-lineage ALL. Conclusion Significant differences were observed in antigen-expression patterns between adult and childhood ALLs. Further studies are needed to correlate specific markers with recurrent cytogenetic abnormalities and prognosis with therapeutic response.

Matrix metalloproteinase-9 (MMP-9) Expression in Non-Small Cell Lung Carcinoma and Its Association with Clinicopathologic Factors.

Abstract: Background & Objective: Matrix metalloproteinases-9 (MMP-9) is one of the most important enzymes to breakdown extracellular matrix which plays a major role in tumor invasion and metastasis. This study aimed to determine tumor MMP-9 expression in non-small-cell lung carcinoma (NSCLC) and whether it is associated with histopathologic factors and has prognostic value to affect overall survival (OS). Methods: The specimens of 92 patients with NSCLC diagnosis were included. Tumor sections were stained by immunohistochemistry method. Using scores for the percentage of cells positively stained and the intensity of staining, MMP-9 expression total score was classified as low-score (scores of 0 to 2), moderate-score (scores of 3 to 5), or high-score (scores of 6 or 7). OS was defined as the time interval since the diagnosis of NSCLC to the status at the last follow-up (dead or alive). The follow up period was up to 70 months. Results: About 74% of undifferentiated specimens (grade III tumors) showed high scores for MMP-9 expression which was significantly higher than moderately differentiated tumors (25% had high scores for MMP-9 expression) and well differentiated ones which did not have high scores (p <0.001). A total of 74 patients (80.4%) died during the follow-up period. Of this, 36% had high scores for MMP-9 expression. In contrast, none of the patients who were alive at the last follow-up had high scores for MMP-9 expression (p <0.001). Median OS was significantly lower in high score group (6 months) compared to moderate score (9 months) and high score group (15 months) (p <0.001). Conclusion: MMP-9 expression may serve as a significant prognostic factor for mortality and overall survival in NSCLC. Undifferentiated tumors significantly express higher MMP-9 immunohistochemically.

Investigation of HER-2 expression and its Correlation with clinicopathological parameters and overall survival of esophageal squamous cell carcinoma patients

Abstract: Background & objective Human epidermal growth factor receptor 2 (HER-2) exhibits a vast range of expression in esophageal squamous cell carcinoma (ESCC) patients as a biomarker. This paper aimed to investigate HER-2 expression and clinicopathological parameters of esophageal SCC. Methods HER-2 expression was assessed in 102 ESCC patients by immunohistochemistry. The HER-2 staining intensity , according to the Gastric HER2 Biomarker1.0.0.1 version of the college of American pathologists (CAP) protocol for gastric and gastroesophageal junction cancers, was graded as 0 (no reactivity in any of the cancer cells' membranes); 1+ (pale or hardly noticeable reactivity in the membrane of cancer cells' cluster [≥ 5 neoplastic cells] regardless of the positive cancer cells' percentage); 2+ (weak-to-moderate complete, basolateral, or lateral membranous reactivity regardless of the positive cancer cells' percentage); and 3+ ( strong complete, basolateral, or lateral reactivity in the membrane of the cancer cell cluster regardless of the positive cancer cells' percentage).In this regard, 3+ scored samples were considered as positive. If HER-2 expression was scored 2+, an additional fluorescence in situ hybridization (FISH) was performed. Fisher's exact test was employed for investigating the correlation of HER-2 expression status with patients' clinicopathological characteristics (including age, gender, tumor location, stage, grade, infiltration level, venous invasion, lymphatic invasion, and tumor recurrence). Kaplan-Meier analysis was done for the patients' survival assessments. Results Five patients (~5%) were HER-2 positive and no significant association was observed between HER-2 expression and clinicopathological properties. In addition, HER-2 expression status exhibited no significant association with the patients' overall survival (P=0.9299). Conclusion HER-2 is not a suitable prognostic biomarker for Iranian ESCC patients.

Different Immune Responses in Dangerous O Blood Donors.

Abstract: Background & Objective Dangerous O is very important to transfusion medicine and there has been reports by Food and Drug Administration (FDA) regarding some death relating incidences. As high iso-antibody production is closely associated with different immune reactions, a survey on the different immune response of dangerous O donors can lead to understanding their immune response profile. Objectives were to assess different immune responses in dangerous O cases. Methods Two groups of donors were selected after performing titration as a high titer (>512) and non-high titer (<128). Then CBC, CD markers, total immunoglobulin, complement assay, anti-VZV, -CMV, -EBV, -HSV, -Rubella, -Toxoplasma gondii, -HBV, -ASO, total protein and albumin, protein electrophoresis, lymphocyte proliferation, and gene expression of INF-gamma, IL2/4/10 were evaluated on both study groups. Results & Conclusion Total IgG, IgM, and IgA was higher in high titer group. Moreover, after using PHA and LPS, gamma globulins and lymphocyte proliferation were significantly higher in high titer cases. Real-time PCR also showed higher IL-2 production in high titer group. Identification of high responder's characteristics can be efficient in many complications. Moreover, high titer donors are dangerous for transfusion medicine. This pilot study showed differences in immune responses between HR and LR O blood donors for the first time. So, other aspects of the immune system such as genetic differences can be surveyed.

Assessment of Ki67 in Breast Cancer: A Comparison Between the Eye-10 Method, Stepwise Counting Strategy, and International System of Ki67 Evaluation.

Abstract: Background & objective Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, such as the Eye-10 method and stepwise counting strategy, are proposed to facilitate measurement. Methods Immunohistochemical staining of Ki67 was performed on 100 hormone-receptor-positive invasive ductal carcinoma specimens. Ki67LI was evaluated for each case, and then results were dichotomized by a cut-off point of 20%. Next, for each sample, an expert pathologist visually assessed percentages of Ki67-positive cells in 10% intervals at a glance (Eye-10 method). Finally, by using a dynamic process with rejection regions, Ki67 was defined so if the estimate belonged to the upper or lower rejection region, the Ki67 status had been determined and if the rejection region could not be reached after counting the maximum number of 400 tumor cells, the specimen was regarded as equivocal (stepwise counting strategy). Results The comparison between Eye-10 and Ki67LI revealed almost perfect agreement (kappa coefficient =0.889), and the concordance between the stepwise counting strategy and Ki67LI was substantial (kappa coefficient =0.639). Conclusion Both two methods left some results in the gray/intermediate zone, which is unavoidable. Both methods are much faster and simpler than evaluation of Ki67LI and are also reliable. Regarding the gray zone in both methods, further improvements in the methodology, as well as more analytical studies, are needed.

Desmoplastic Fibroma of the Jaws: A Case Series and Review of Literature.

Abstract: Desmoplastic fibroma (DF) is a benign, locally aggressive neoplasm that rarely occurs in the facial skeleton. It usually presents during the first three decades of life. Due to its aggressiveness and high recurrence rate, early diagnosis is imperative, and complete surgical removal of the lesion is the treatment of choice. Herein, we present three cases of DF namely a 2 year-old girl with a mandibular DF, a 9 year-old boy with a maxillary lesion and a 1.5-year old boy with a mandibular DF. Complete clinicopathological information, treatment plan and long-term follow-up of patients are discussed. Histopathologic features of 3 cases revealed non-capsulated spindle cell tumor with fascicular or swirling patterns in incisional biopsy. Immunohistochemical staining was performed to make a definitive diagnosis. Strongly positive nuclear immunoreactivity for β-catenin confirmed the diagnosis of desmoplastic fibroma in 3 cases. Segmental mandibulectomy, partial maxillectomy and hemimandibulectomy were done for the cases. There was no recurrence in our reported cases after 8 and 11 months and 3 years follow up, respectively. It is noteworthy that despite the aggressive nature of DF, young patients often respond well to wide resection treatment.

Solitary Fibrous Tumor of the Prostate: A Diagnostic Challenge: A Case Report.

Abstract: Solitary fibrous tumor (SFT) of prostate is an unusual type of mesenchymal neoplasm that can elicit a benign or malignant phenotype. It represents a diagnostic challenge as it can simulate poorly differentiated adenocarcinoma and various mesenchymal neoplasms of prostate. We report a case of prostate SFT in a 54-year-old patient, which was clinically misdiagnosed as nodular hyperplasia of prostate with cystitis. However, on follow-up, he was not relieved by the designated treatment. Furthermore, he complained of exacerbation of symptoms and consequently, had to undergo open prostatectomy. Based on histopathological and immunohistochemical (IHC) assessment, a diagnosis of SFT of the prostate was rendered. Additionally, we have discussed the histological mimics of SFT and the diagnostic and prognostic importance of IHC while evaluating such lesions.

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with Acne Vulgaris.

Abstract: Background & Objective To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV). Methods In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively. Results The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (P=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (P<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele. Conclusion We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.

Comparison of Diagnostic Methods in Detection of Squamous Cell Abnormalities in Iranian Women with Abnormal Pap's Smear Test and Associated Demographic and Issues.

Abstract: Background & objective Premalignant lesions of cervix have increased dramatically in recent years. Early diagnosis and management of abnormalities have an effective role in preventing the invasion of the disease and also in timely treatment. This study aimed to compare diagnostic methods in the detection of squamous cell abnormalities with abnormal Pap smear test. Methods This cross-sectional study was performed on 1000 women with abnormal Pap smears in 2007-2018. Sampling was performed with simple method. All samples were subjected to an immediate assessment of colposcopy and histopathology if suspected. The checklist included demographic information as well as symptoms, cytopathology, colposcopy and histopathology findings. Data analysis was performed using descriptive and statistical analysis (P Results A significant relationship between histopathology and Pap smear findings was found (P=0.009), also there was a significant correlation between histopathology and colposcopy findings (P=0.001). However, there was no significant relationship between clinical symptoms and histopathology findings (p=0.8). Sensitivity , specificity , positive and negative predictive value of Pap smear were 43%, 65.9%, 75.4%, 32.2% and of colposcopy were 74.7%, 39.5%, 75%, 39.1%, and of clinical symptoms were 72.6%, 28.1%, 71.1%, 29.7%, respectively. Conclusion Pap smear findings have the appropriate diagnostic accuracy in comparison with colposcopy and histopathology findings for screening and diagnosis of squamous intra-epithelial lesions. Also, there was higher sensitivity of colposcopy compared with Pap smear to detect cervical lesions. Therefore, it is advisable to use these methods simultaneously.

Mature Cystic Teratoma of Spinal Cord in a 16-Year-Old Male: A Case Report.

Abstract: Teratoma is a type of multipotential cell tumor, which includes a mixture of two or three germinal layers of ectodermis, endodermis, and mesodermis. Although neonatal sacrococcygeal teratoma has been frequently reported, its occurrence in older age is not common. In this study, we report a rare case of spinal intradural mature cystic teratoma in a 16-year-old male, emphasizing on considering this unusual condition in differential diagnosis of spinal cord cystic tumors.

Intravascular Large B-cell Lymphoma: A Report of Two Cases

Abstract: One of the rare variants of extranodal large B-cell lymphoma is intravascular large B-cell lymphoma (IVLBCL). Characteristics of IVLBCL include intraluminal selective proliferation of atypical lymphoid cells in small to medium-sized vessels. The etiologic of IVLBCL is unknown, but due to the growth pattern of this tumor, it is speculated that IVLBCL is caused by a defect in homing receptor of tumor cells. IVLBCL can involve any organ but central nervous system, lungs, and skin are the most involved sites. IVLBCL does not usually involve lymph nodes. IVLBCL mainly occurs in the middle aged to elderly population with a slight male predominance. Generally, IVLBCL is aggressive and rapidly fatal if left untreated. We here reported two cases of IVLBCL who succumbed to the disease at initial phase of treatment to emphasize the difficulty in diagnosis of IVLBCL due to its exclusive intravascular growth pattern and fulminant clinical course.

Assessment of p16 and Ki67 Immunohistochemistry Expression in Squamous Intraepithelial Lesion with Cytohistomorphological Correlation.

Abstract: Background & objective Cervical cancer is the most common cancer in women worldwide with high mortality, necessitating quicker diagnostic methods. We wish to enhance the existing cervical biopsies of Squamous Intraepithelial Lesions (SIL) using p16 and Ki67 as surrogate markers to assess correlation between its positivity and histological grade of the lesion. Methods Analysis of p16 and Ki67 expression was done on 31 histopathologically diagnosed cases of SILs. Positive expression of p16 was assessed based on a scoring system and compared with histology and cytology. Ki67 expression was studied and the correlation was observed with degree of dysplasia. Twenty cases of chronic cervicitis was assigned to the control group for comparison. Results Cases of HSIL showed greater expression of p16 as compared to LSIL. Sensitivity of p16 for HSIL was higher than that for LSIL. The specificity for HSIL and LSIL was 100%. Ki67 expression correlated well with the degree and level of dysplasia with a significant P-value of 0.002. Conclusion p16 and Ki67 positivity of SILs should point towards further evaluation. The expressions of p16 and Ki67 are useful markers for confirmation of SILs and in predicting HPV infection which can be further confirmed by HPV DNA testing.

Concurrence of Primary Cutaneous Extra Mammary Paget's Disease and Squamous Cell Carcinoma in situ of Vulva: A Case Report

Abstract: Extramammary Paget's disease and vulvar intraepithelial neoplasia are common lesions of vulve, but synchronous occurrence is rare in a same location. Herein we describe a concurrence of primary cutaneous extra mammary Paget's disease and squamous cell carcinoma in situ of vulva in an Iranian women. A 59 year old woman, initially presented to Kosar teaching hospital gynecology clinic April 2017 with a single, well defined, scaly, white ulcerated mass, 2 cm in diameter on right minor labia, but other examinations were normal. She had no urinary or gastrointestinal symptoms. Incisional biopsies from the mass represented concurrence extramammary Paget's disease and VIN3. She underwent radical vulvectomy .No evidence of disease recurrence was noted after 16 months follow up. Participant consent was obtained before patient was enrolled in this study. There are lot of diseases that involve genitalia and lead to vulvar lesions. But in this rare case, we diagnosed concurrence of extramammary Paget's disease and vulvar intraepithelial neoplasia in a same location. Additionally, the clinical presentation as a vulvar mass was found unusual. Therefore, we report the case to sensitize gynecologists and pathologists for uncommon pathologies and their manifestations in vulva.

Napsin-A Expression, a Reliable Immunohistochemical Marker for Diagnosis of Ovarian and Endometrial Clear Cell Carcinomas.

Abstract: Background & objective Clear cell carcinomas (CCC) differ from other types of ovarian and endometrial carcinomas in biology, behavior and response to chemotherapy. Histopathologic diagnosis may be challenging in some situations which necessitates immunohistochemistary (IHC) assessment. In this study we investigated the diagnostic utility of Napsin-A in diagnosis of ovarian and endometrial CCCs. Methods Ovarian and endometrial CCC samples from 2013 to 2018 in 3 general and women's hospital in Tehran were re-evaluated by 2 expert pathologists. Forty-two samples were included as case and 42 non-clear cell carcinomas (Non-CCC) of ovary and endometrium were selected as control group. Based on IHC study tumors with sum intensity and percentage score ≥2 (at least 1+ staining in more than 1% of tumor cells) were considered positive. Results The prevalence of endometrial and ovarian CCC in the case group were 15 and 27 respectively. The tumors in the control group included 22 cases of endometrioid, 2 high grade papillary serous carcinoma (HGSC) of endometrium, 6 endometrioid and 12 HGSC of ovary. Napsin-A positivity was observed in 35 (83%) of CCCs while 7 (17%) samples including 3 out of 15 endometrial and 4 out of 27 ovarian CCCs were Napsin-A negative. No positive reaction was seen in control group. The overall accuracy, specifity and sensitivity of Napsin-A for diagnosis of ovarian and endometrial CCCs were 83%, 100% and 83%, respectively. Sensitivity for ovarian and endometrial CCCs were 85% and 80%, orderly. Conclusion Napsin-A is an accurate and reliable marker for distinction of CCCs from non-CCCs in ovary and endometrium. A panel of antibodies may yield the highest diagnostic accuracy.

Sarcomatoid Chromophobe Renal Cell Carcinoma with Heterologous Component.

Abstract: Clear cell renal cell carcinoma (RCC) is the most common malignant renal tumor in adults, while chromophobe RCC (CRCC) is the third most common. Any subtypes of RCC can undergo sarcomatoid differentiation, but heterologous differentiation in sarcomatoid area is very rare in RCC. Here a 61-year male is presented with hematuria and palpable mass. Clinicoradiologically, RCC was considered and left radical nephrectomy was performed. A well-circumscribed renal mass located in the upper pole of the left kidney with variegation and extensive areas of bony hard calcification noted, was reported as CRCC with sarcomatoid differentiation containing heterologous component. CRCC subtype has good prognosis but show dismal prognosis when associated with sarcomatous differentiation. We found 11 cases of sarcomatoid CRCC containing heterologous elements reported in indexed English literature. CRCC must be differentiated from Conventional RCC and Oncocytoma. The extensive sampling of the tumor is needed. We report a very rare case of CRCC with sarcomatoid differentiation containing heterologous elements.

Cyclin D1 Expression in Patients with Laryngeal Squamous Cell Carcinoma

Abstract: Background & Objective: Laryngeal squamous cell carcinoma (LSCC) is considered to be one of the most common cancers of the head and neck, accounting for roughly 90% of all malignant tumors of the larynx. To have a timely diagnosis for a better and practical therapy, molecular markers have to be investigated. The aim of this study was to determine the expression of Cyclin D1 (CD1) in patients with laryngeal squamous cell carcinoma. Methods: In this study the demographic data of 82 patients with laryngeal squamous cell carcinoma, including age, gender and geographical region history of smoking and drug abuse, paraclinical findings, surgical description, and pathologic reports were extracted from their medical records. The stage and grade of the disease and tumor location were determined using their medical records. An appropriate tissue sample was selected. Then, the selected cancerous tissue samples stored as formalin-fixed paraffin-embedded tissue then were (Immunohistochemistry) IHC stained and analyzed in terms of the expression of CD1. Result & Conclusion : According to the results, 75 out of 82 (91.5%) investigated samples were positive for CD1 expression. There was a significant relationship between stage of the disease (P=0.041) and CD1 expression in patients with laryngeal squamous cell carcinoma. There was no significant relationship between gender (P=0.055), age (P=0.256), history of smoking and drug abuse (P=0.192), location of the tumor (P=0.90), grade of the disease (P=0.515) and geographical region (P=0.466) and CD1 expression in patients with laryngeal squamous cell carcinoma. The results of the present study showed that CD1 expression was higher (91.5%) in patients with laryngeal squamous cell carcinoma in comparison to the other studies. According to the results we can conclude that stage of the disease can significantly affect CD1 expression in patients with squamous cell carcinoma.

Assessment of Susceptibility to Five Common Antibiotics and Their Resistance Pattern in Clinical Enterococcus Isolates

Abstract: Background & objective Enterococcus Species are the common cause of nosocomial infections, which are highly resistant to different antibiotics. Therefore, determination of their antibiotic susceptibility patterns and simultaneous resistance to antibiotics is important for better treatment strategies. Methods 400 clinical Enterococcus isolates were collected from different hospitals in Tehran, Iran. Standard phenotypic-biochemical tests and PCR were used to identify the Enterococcus species. The antimicrobial susceptibility patterns and simultaneous resistance to selected antibiotics were determined by disk diffusion method according to the CLSI guidelines. All data analysis was performed using Python packages Scipy and Stats models. Results According to the biochemical and PCR analyses, among 400 Enterococcus species, 72% of samples were Enterococcus faecalis, 10.75% Enterococcus faecium, and 17.25% other Enterococcus species. The results determined antimicrobial resistances of these strains against gentamicin, vancomycin, fosfomycin trometamol, teicoplanin, and quinupristin/dalfopristin. Results confirmed a significant correlation between resistance to vancomycin and resistance to teicoplanin. This correlation remains significant when including only E. faecium or E. faecalis species. We also found a negative correlation between resistance to teicoplanin and quinupristin/dalfopristin. Additionally, Quinupristin/dalfopristin was the least effective antibiotic while vancomycin and teicoplanin were the most effective ones. Conclusion Based on the results and association between simultaneous resistance to some antibiotics such as vancomycin and teicoplanin, in the case of antibiotic resistance, the choice of a second antibiotic can be very important which can lead to good or bad effects.

Cytogenetics and Revised International Staging System (R-ISS): Risk Stratification in Multiple myeloma - A Retrospective Study in Indian Population.

Abstract: Background & objective Cytogenetic abnormalities in Multiple myeloma (MM) has emerged as the most important factor that determine the prognosis and survival. Fluorescence in situ hybridization (FISH) can detect a greater number of cytogenetic abnormalities as compared to conventional karyotyping and hence has become the standard test in determining genetic abnormalities in MM. The present study was planned as there is an unmet need to find out various cytogenetic abnormalities and to implement them in prognostic stratification by Revised International Staging System (R-ISS) among Indian population. Methods A single institution retrospective study was conducted among a total of 117 patients newly diagnosed as Multiple Myeloma. They were analyzed for various cytogenetic abnormalities by using interphase FISH (iFISH) and were staged according to Revised International Staging System (R- ISS). Results Out of the 117 patients studied, deletion 17p13 (p53) was present in 16 patients (13.67%). Thirty patients (25.64%) showed deletion 13q14.3. Three patients (2.56%) were detected to have t(4:14).Two patients (1.7%) had t(11:14) and t(14:16), respectively. Total of 19 patients (16.23%) in our study exhibited high risk cytogenetics and two among them had more than one high risk cytogenetic abnormalities. There was a 66.4% moderate correlation between ISS-III and high-risk cytogenetics which was statistically insignificant. Of the total 117 patients, 37 (31.62%) were staged R-ISS III. Conclusion High risk cytogenetics was found in 16.23 % of our study population and del 17p13 was the most common high-risk cytogenetic abnormality. Of the studied subjects, 31.62% had R-ISS III, which is significantly higher compared to western population.