Iranian Journal of Pathology

Abstract Background & Objective: The spread of carbapenem-resistant Pseudomonas aeruginosa is a global concern. Metallo-beta-lactamase (MBL) enzymes cause extensive drug resistance among Gram-negative bacteria. The current study aimed at determining the prevalence of MBL-producing P. aeruginosa in Iran.
Methods: A total of 43 studies were found out of which 36 were adopted. Data were collected from Google, Google Scholar, Science Direct, PubMed, Scopus, Embase, and Sciverse. The terms “Pseudomonas aeruginosa”, “metallo-beta-lactamase”, “prevalence”, “carbapenems”, and “Iran” were searched. Data from the isolates not producing MBLs were excluded from the study. Data were analyzed with Graph Pad Prism 6, meta-analysis section.
Results: According to the results of the current study, 36 surveys indicated that 55% of the clinically isolated P. aeruginosa in Iran were resistant to imipenem and meropenem, among which 37.72% were the MBL producers. Among genes encoding MBLs, bla_VIM and bla_IMP were predominant with the prevalence of 12.91%±11.01% and 12.50%±23.56%, respectively. No report of harboring bla_NDM1 and bla_SPM1 by P. aeruginosa was found, similar to most of the other countries in Asia. The prevalence of bla_VIM and bla_IMP from burn settings were 11.50%±3.5% and 24.65%±23%, respectively. Furthermore, the prevalence of these genes was not significantly different among burn and non-burn isolates (P=0.942 and P=0.597, respectively). Moreover, no relationship was observed between the MBL production and patients’ age range.
Conclusion: Approximately half of P. aeruginosa isolates were carbapenem-resistant in Iran, and approximately half were the MBL producers. The bla_VIM and bla_IMP were the predominantMBLs among P. aeruginosa strains, while other genes were not found in P. aeruginosa. Moreover, there was no significant difference between bla_VIM and bla_IMPamong burn and non-burn isolates. Due to the multiple drug resistance conferred by MBLs, detection and control of their spread alongside proper therapeutic regimens in hospitals and community settings are essential to prevent infection acquisition.

Abstract Background & objective The immunoregulatory effects of transforming growth factor (TGF)-βand interleukin-12 (IL-12) and immunomodulatory actions of vitamin D (VD) were reported in several studies. This study aims to evaluate VD effects on IL-12 and TGF-β expression in experimental autoimmune encephalomyelitis (EAE).
Methods: EAE was induced in three groups of C57BL/6 mice by immunization with MOG and administered intra-peritoneally 200 ngVD, PBS or olive oil (OO) from day +3 to +30. One group was also considered as healthy control group. At day 31, cytokines expression in the spinal cord and their serum levels were determined using real time-PCR and ELISA, respectively.
Results: IL-12 gene expression and its serum levels in PBS-injected- or OO-administrated EAE groups were significantly higher than healthy group. IL-12 gene expression in EAE group treated with VD was significantly decreased compared to PBS-injected- or OO-administrated EAE groups (P Conclusion: VD modulates the expression of IL-12 and TGF-β in spinal cord and serum of EAE mice.

Abstract Background & Objective: The common epithelial ovarian tumors are classified into serous, mucinous, clear cell, endometrioid, the Brenner, mixed, and undifferentiated types. Cytoskeleton intermediate filament composition of ovarian tissues indicates that the cytokeratin and vimentin are observed in ovarian surface epithelium along with the common ovarian epithelial tumors. The current study aimed at investigating the cytokeratin and vimentin expression in epithelial ovarian tumors to establish a diagnostic relevance.
Methods: Sixty-six common epithelial ovarian tumors were studied using anti-cytokeratins (Monoclonal Mouse Anti-Human Cytokeratin Clones AE1/AE3; DAKO, Denmark,) and anti-vimentin (Monoclonal Mouse Anti-Vimentin, Clone V9; DAKO, Denmark,) to ascertain the intermediate filament profiles in formalin-fixed and paraffin-embedded surgical pathology materials.
Results: All ovarian epithelial tumors expressed cytokeratin in a uniform fashion. Vimentin was coexpressed with high intensity in 62.5% of serous carcinomas, mild intensity in 25% of mucinous adenocarcinoma, and moderate intensity in single case of endometrioid adenocarcinoma. Vimentin decoration in mucinous carcinoma had a focal involvement, whereas malignant endometrioid and serous decoration tended to involve larger areas. There was a significantly increased expression of vimentin in serous cystadenoma and serous carcinoma, compared with their mucinous counterparts. Also, vimentin expression and histologic grade of serous tumors showed a positive correlation. No association was found between vimentin expression and degree of differentiation in mucinous, endometrioid, and Brenner tumors.
Conclusion: The current investigation emphasized the efficiency of immunohistochemistry (IHC) typing as a tool for a more precise characterization of the origin and differentiation of human neoplasms.

Abstract Background and objective:Cytogenetic damage in exfoliated buccal epithelial cells due to environmental and occupational exposure is often monitored by micronucleus (MN) assay using liquid based cytology (LBC) preparations. This study was performed to evaluate MN in exfoliated buccal epithelial cells of building construction workers using LBC preparations.
Material and methods: LBC preparations of exfoliated buccal epithelial cells from 100 subjects [50 building construction workers (cases) and 50 administrative staffs (controls)] was evaluated by May-Grunwald Giemsa, Hematoxylin and Eosin and Papanicolaou stains. Student’s t test was used for statistical analysis and a P value of Results: The mean frequencies of MN for cases were significantly higher than controls regardless of staining methods used.There were statistically significant differences between smokers and non-smokers of the controls as well as duration of working exposure (5 years) and smokers and non-smokers of cases (P=0.001). However, there were meaningful differences regarding mean frequencies of MN between smokers, non-smokers, those with alcohol consumption or not in cases and controls using various stains (P=0.001).
Conclusion: There was an increased risk of cytogenetic damage in building construction workers. However, evaluation of MN of exfoliated buccal epithelial cells in building construction workers serve as a minimally invasive biomarker for cytogenetic damage. LBC preparations can be applied for MN assay as it improves the quality of smears and cell morphology, decreases the confounding factors and reduces false positive results.

Abstract Background and Objectives: Iran, as a developing country, is experiencing high burdens of Helicobacter pylori (Hp)-associated non-communicable diseases. Hp stool antigen test (HpSA) is widely used as an inexpensive and feasible noninvasive method to diagnose Hp infection, instead of invasive approaches. The current study aimed at evaluating the diagnostic and predictive values of HpSA test for Hp infection in Iranian patients with dyspepsia.
Materials and methods: The current cross sectional study was performed on 100 patients with dyspepsia. Gastric mucosal specimens were taken, processed, and examined according to the standard protocols. Simultaneously, stool samples were obtained and sent to laboratory for further analyses. Hp stool antigen titers were assessed using enzyme-linked immunosorbent assay (ELISA) technique.
Results:Stool antigen titers were not associated with gender (P-value=0.284), but correlated to age (r=0.213, P-value=0.034).Considering0.385 as a cutoff point, the HpSA test had 80.4% sensitivity and 85.7% specificity.
Conclusion: Based on cost-effectiveness of HpSA test, the current study findings corroborated the use of HpSA test to detect and follow-up patients with Hp infection, as an alternative method to detect Hp rather than invasive procedures.

Abstract Background & Objective Angiogenesis is an essential component of tumor growth. Expression of PSMA on the neo-vasculature of many solid tumors, including glioblastoma multi-form, has been determined. The pattern of expression suggests that PSMA may play a functional role in angiogenesis.
Methods: expression of PSMA in different grades of brain glioma was evaluated by the immunohistochemistry method to determine the probable usefulness of anti-PSMA antibody as complementary target therapy in different grades of glioma.
Results: Overall, 72 cases of low (grade I and II) and high (grade III and IV) grade gliomas were evaluated for expression of PSMA. Positive PSMA staining was observed in 12 (33.3%) of high grade and 3 (8.3%) of low grade gliomas. Although, high grade tumors more commonly had positive result for PSMA (P value=0.009), the intensity of staining was significantly stronger in low-grade tumors (P value=0.009).
Conclusion: Expression of PSMA in different grades of glioma might provide a basis for further investigations focusing on selective target therapy in combination with the current standard care in all glioma grades, to improve treatment efficacy.

Abstract Background and objective:Millions of people in developing countries lose their lives due to acute respiratory infections, such as Influenza A & B and Adeno viruses. Given the importance of rapid identification of the virus, in this study the researchers attempted to design a method that enables detection of influenza A, B, and adenoviruses, quickly and simultaneously. The Multiplex RT PCR method was the preferred method for the detection of influenza A, B, and adenoviruses in clinical specimens because it is rapid, sensitive, specific, and more cost-effective than alternative methods
Methods:After collecting samples from patients with respiratory disease, virus genome was extracted, then Monoplex PCR was used on positive samples and Multiplex RT-PCR on clinical specimens. Finally, by comparing the bands of these samples, the type of virus in the clinical samples was determined.
Results:Performing Multiplex RT-PCR on 50 samples of respiratory tract led to following results; flu A: 12.5%, fluB: 50%, adeno: 27.5%, negative: 7.5%, and 2.5% contamination.
Conclusion: Reverse transcription-multiplex Polymerase Chain Reaction (PCR) technique, a rapid diagnostic tool, has potential for high-throughput testing. This method has a significant advantage, which provides simultaneous amplification of numerous viruses in a single reaction. This study concentrates on multiplex molecular technologies and their clinical application for the detection and quantification of respiratory pathogens. The improvement in diagnostic testing for viral respiratory pathogens effects patient management, and leads to more cost-effective delivery of care.  It limits unnecessary antibiotic use and improves clinical management by use of suitable treatment.

Abstract Background and objective Aside from direct toxic effects, Sulfur Mustard (SM) induced serum hormone abnormalities may aggravate ocular complaints, including Ocular Surface Discomfort (OSD) (burning, itching, and redness), dry eye sensation, photophobia, blurred vision, foreign body sensation, and pain. The aim of the current study was to investigate the possible association of ocular complaints with serum hormone concentrations in chronic phase of Sulfur Mustard (SM) exposure.
Methods:As a part of Sardasht Iran Cohort Study (SICS), 372 SM-exposed patients and 128 non-exposed participants were enrolled. Ocular complaints and ocular surface biomicroscopic conditions and serum hormones were compared.
Results:The exposed with tearing group had significantly higher mean serum levels of testosterone and prolactin (ng/mL) than controls (5.75 vs. 4.75, P=0.031; 11.71 vs. 8.42, P=0.009). The exposed with OSD group had significantly higher mean serum levels of prolactin than controls (12.48 vs. 6.90, P=0.002). The exposed with photophobia group had significantly higher mean serum levels of testosterone than the matched exposed (6.25 vs. 5.65, P=0.013). The exposed with blurred vision group had significantly higher mean serum levels of Thyroglobulin (Tg) (ng/mL) than the matched exposed (65.73 vs. 32.6, P=0.003).
Conclusion: Higher mean serum levels of testosterone (in exposed with tearing and photophobia) and prolactin (in exposed with tearing and OSD) may play protective roles against SM effects. Higher mean serum levels of Tg may deteriorate the tear film integrity and optical surface, which causes blurred vision. In the chronic phase of SM toxicity, some ocular surface problems are associated with alterations in the serum concentrations of testosterone, prolactin, and Tg.

Abstract Background and objective:Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis.
Methods: This retrospective study was carried out on 55 consecutive patients with breast cancer referred to a Training Tertiary Healthcare Center in Kerman, Iran since 2009 to 2014. After diagnostic approval, the tissue samples of patients were examined for estrogen and progesterone receptors, ki67 and HER2-neu markers by using immunohistochemical staining. Then the patients were treated with 6 cycles of Neoadjuvant chemotherapy regimens by Doxorubicin and Taxans or 4 chemotherapy cycles, containing Anthracycline and Cyclophosphamide and 4 cycles of Paclitaxel. After mastectomy, their samples were reexamined for ki67 again and classified into three groups (low: ki67<15%), medium (Ki67 = 16-30%) and high (Ki67> 30%).
Results: Before chemotherapy, 54.5% of the patients had high expression of Ki67. But after chemotherapy, 52.7 of the patients had complete therapeutic response showing that the Ki67 level was reduced significantly (P=0.003).
Conclusion: Before and after Neoadjuvant chemotherapy, Ki67 measurements may be used as a predictive marker of therapeutic response.

Abstract Background & objective: Introduction: First detection of any solid tumour as metastatic deposits in bone marrow directs clinicians to start searching for the primary tumour. Detection of bone marrow metastasis determines the stage of the malignancy, prognosis, mode of treatment, chemotherapeutic response and follow-up in case of relapse. The aim of the current study was to analyse the clinico-haematological presentation and morphological pattern of infiltration of solid tumours detected first as metastatic deposits on bone marrow examination.
Methods:Three-year retrospective analysis of MGG-stained bone marrow aspiration smears and touch imprints of the bone marrow biopsy and Hematoxylin and Eosin (H&E) stained histopathological sections of biopsies was performed at the Department of Pathology at a tertiary care institute (January 2014 to December 2016). The morphological pattern of metastatic deposits and haematological profiles of the patients were analysed. Exclusion criterion was the presence of hematolymphoid malignancies.
Results: In 22 cases, bone marrow was the first site of detection of metastasis. The age of the patients ranged from 3 years and 10 months to 82 years, with equal gender predilection. Overall, 16 cases had cytopenias, 9 cases each had leucocytosis and leukoerythroblastic presentation. The metastasis was from Ewing’s sarcoma, prostate carcinoma, gastric adenocarcinoma invasive duct carcinoma breast, gallbladder carcinoma, lacrimal duct carcinoma and invasive papillary urothelial carcinoma.
Conclusions: Bone marrow examination is a cheap and reliable investigation to detect metastasis in an unsuspecting case. Bilateral trephine biopsies are recommended to increase the efficacy of detecting bone marrow metastasis.

Abstract Sinonasal teratocarcinosarcoma (STCS) is a rare, morphologically heterogeneous and highly aggressive tumour of ambiguous origin. It is characterized by the presence of benign and malignant epithelial, mesenchymal and neuroectodermal components. Because of their rarity and heterogeneity, these lesions are often misdiagnosed, leading to management difficulties. Adequate sampling with a high index of suspicion is needed to diagnose this rare tumour. We reported here a 48-year old man with right nasoethmoidal mass eroding the cribriform plate with intracranial extension. An initial incisional biopsy was performed and a diagnosis of craniopharyngioma was made. Subtotal endoscopic excision of the mass revealed features of STCS. Immunohistochemistry confirmed the same. The patient was subsequently treated with radiotherapy. The histogenesis, histopathological features, immunohistochemistry findings, clinical features and treatment were discussed here. Till date, there are less than 100 cases reported in English literature.

Abstract Sarcomatoid carcinoma is a high‑grade rare malignant tumor with both epithelial and mesenchymal components. Sarcomatoid carcinoma in the upper urinary tract is very rare. We reported here a case of sarcomatoid carcinoma of renal pelvis with osteosarcomatous differentiation, with involvement of the ureter and renal parenchyma in a 68-year-old female. Histologically, predominant pleomorphic spindle cell sarcoma component with osteoid production and urothelial carcinoma component with in situ areas were identified. Immunohistochemical analysis showed vimentin positivity in sarcomatous component and cytokeratin positivity in carcinomatous component.

Abstract ysgerminoma is one of the two most common types of ovarian germ cell tumors. Providing accurate pathologic diagnosis and treatment planning, the prognosis is good even in advanced stages. Pathologic diagnosis is generally straightforward. In microscopic examination, the usual known growth patterns in tumor cells are solid, trabecular, insular and rarely pseudoglandular.
In this paper, we reported an advanced ovarian dysgerminoma with different microscopic patterns of growth, including pseudopapillary and macrofollicular structures, in an 18-year-old woman. The patient underwent staging laparotomy and is currently receiving chemotherapy.

Abstract Ovarian small cell carcinoma is a rare and highly malignant tumor with poor prognosis. It usually presents in younger females with features of hypercalcemia. The exact histogenesis of the tumor is unclear and it may present as an undifferentiated tumor. In such cases, immunohistochemistry (IHC) plays an important role to confirm the diagnosis. Limited treatment options are available and mainly include radical surgery followed by adjuvant therapy in advanced stages. The current report was a rare case of small cell carcinoma of ovary presenting no symptoms of hypercalcemia diagnosed on histopathological examination and IHC findings.

Abstract An ectopic thyroid is a form of thyroid dysgenesis in which an entire or parts of the thyroid gland may be located in another part of the body than what is the usual place. The most frequent location is the base of tongue. Although most cases are asymptomatic, symptoms related to tumor size and its relationship with surrounding tissues, hormonal dysfunction and seldom malignancy may also occur. Any disease affecting the thyroid gland may involve the ectopic thyroid, including malignancy.

Abstract Among different staining methods used to demonstrate the nuclear abnormalities, Feulgen is one of the most reliable method. Feulgen staining is specific, sensitive method for evaluating the DNA damages.It has been shown that using non-DNA specific stains for monitoring the nuclear anomalies lead to false-positive or false-negative results. From self-experience, immersing the stained slides in hematoxylin for 3-5 minutes in final step after staining the slides with light green, provides a greater ground contrast and very better visualizing of nucleus. By this method, a clear distinction can be made between micronuclei and other structures suggestive of a micronucleus.