Iranian Journal Of Pathology
Volume:14 Issue: 2, Spring 2019

The primary goal of this study is to develop a rigorous understanding ofthe correlation between COX-2 expression and malignant melanoma prognostic factors. In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well.   The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme. We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.

S100A8/A9 is a heterodimer calcium-binding protein which is involved in tumor cell proliferation, adhesion and invasion, and is proposed as a biomarker for better diagnosis and prognosis in many cancers. The aim of this study was to evaluate the simultaneous serum-based level of S100A8/A9 and CA15-3 as well-illustrated cancer biomarkers, as well as their prognostic value in breast cancer patients and healthy matched controls. Thirty breast cancer patients at different stages of disease and healthy matched controls with no history of inflammatory, autoimmune diseases, or cancer, were enrolled in the study. The levels of S100A8/A9 and CA15-3 were assessed serologically using the Enzyme-linked immunosorbent assay (ELISA) method, and the relevance of these markers with patients’ clinicopathological features were subsequently assessed.   Based on our data, the serum levels of both S100A8/A9 and CA15-3 were significantly higher in patients compared to the healthy controls, and thus positively correlated with tumor size. Also, statistical analysis shows that the serum level of S100A8/A9 has 100% specificity and sensitivity (AUC = 1.00, 95% CI) for the diagnosis of breast cancer patients. According to our data as well as other observations, the S100A8/A9 heterodimer can be considered as a potential biomarker for the proper diagnosis and prognosis of breast cancer.

Anti-CK5/6 monoclonal antibodies have an established role in breast disease diagnosis. Anti-CK5 monoclonal antibodies have recently become commercially available. There has been growing interest in the staining characteristics of anti-CK5 and its potential diagnostic role in place of anti-CK5/6. We aim to compare and contrast the staining characteristics of anti-CK5/6 vs anti-CK5.   58 tissue blocks containing 122 different lesions were selected from tissue archives. Two specimens (groups) were taken from each lesion One (group) was stained with anti-CK5 and the other (group) with anti-CK5/6 monoclonal antibodies, using the Streptavidin-biotin immuno-peroxidase method. The two groups of slides were compared and contrasted for lesion staining pattern and for intensity, using light microscopy. Results showed that the diagnostic staining pattern was exactly the same in both anti-CK5 and anti-CK5/6 groups, and also showed that anti-CK5, stained most of the lesions more intensely than anti-CK5/6. Anti-CK5 performed at least as well (for lesion-pattern staining), and better (for lesion staining intensity) than did anti-CK5/6 in the diagnosis of a wide range of breast tissues and lesions. It may be justified to safely replace anti-CK5/6 with anti-CK5 in future routine clinical use, with resultant diagnostic and economic benefits.

Early diagnosis of malignant pleural mesothelioma (MPM) is the key point of its treatment. The main problem is the precise diagnosis of mesothelioma and its differentiation from metastatic lung adenocarcinoma. Mesothelioma exhibits complex immunohistochemical characteristics. The aim of this study was to study hybrid immunohistochemistry in the differential diagnosis of primary malignant pleural effusion from metastatic pulmonary cancers. Twenty tissue samples in paraffin blocks from the pathology department of Imam Reza Hospital in Tabriz whose pathology reports cited mesothelioma or metastatic lung adenocarcinomas, were included in the studies. These tissues were deemed appropriate for IHC in terms of tissue quality and quantity. They were studied and evaluated for pathological markers.   In patients with adenocarcinoma CK7 in 100% of patients (13 patients), TTF1 in 61.5% of patients (8 patients) and CEA in 53.8% of patients (7 patients) were positive, but HBME1 and Calretinin were negative for all patients. In patients with mesothelioma, HBME1 and Calretinin were positive in 100% of patients (7 patients) and TTF1, CEA and CK7 were negative. The results of this study showed that CEA, CK7, TTF1, Calretinin and HBME1 are suitable criteria for differentiating between metastatic lung adenocarcinoma and mesothelioma, and can differentiate the mesothelioma and adenocarcinoma with high accuracy.

This study was aimed to evaluate the collagen fibers qualitatively and its correlation with microvascular density in various grades of oral submucous fibrosis (OSMF).   The present study comprised of total 40 cases of oral submucous fibrosis. Picrosirius red staining was done on all the specimens’ sections. They were analyzed for the colour and orientation of collagen fibers. Morphometric measurements were done using image analysis on immunohistochemical stained sections for Factor VIII-related antigen and analyzed for microvascular density. Picrosirius red polarizing microscopy results revealed that there was a shift in the colour of collagen fibers from greenish yellow to orange red and red colour as the severity of the oral submucous fibrosis increased. The collagen fibers showed mixed orientation in early oral submucous fibrosis and parallel orientation in advanced oral submucous fibrosis. There was a significant decrease in microvascular density from early to advanced oral submucous fibrosis. The change in the colours and orientation of collagen fibers in early and advanced oral submucous fibrosis could be attributed to the fibre thickness, type of collagen, alignment and packing, cross-linking of the fibers and the section thickness. However, in advanced cases the vascularity is reduced which may predispose to epithelial atrophy and subsequent malignant changes.

Adenocarcinoma of the prostate is the second most common cause of cancer. The loss of CD10 is a common early event in human prostate cancer and is seen in lower Gleason Score malignancies while increased and altered expression is seen in high Gleason Score tumors, lymph nodes and bone metastasis. This was a prospective observational study conducted on 75 patients suspected to have prostate cancer. Immunohistochemical profile was assessed for PSA, AMACR and CD10 immunostaining. The intensity of CD10 expression and pattern of CD10 staining of tumor cells was evaluated.   The patients were in age group of 50-90 years with a mean age of 70.97 ± 9.51 years. As the Grade Group/Gleason Score increased, the number of cases showing negative expression decreased and the pattern of expression changed from membranous to cytoplasmic to both types of expression. As the serum PSA levels increased the intensity of expression changed from focally positive to diffusely positive. The pattern of expression also changed from membranous to cytoplasmic to both (membranous + cytoplasmic) types of expression with an increase in PSA levels. By immunohistochemical analysis we can identify CD10 positive tumors, which may warrant more aggressive initial therapy. A number of drugs against CD10 are available based on which potential targeted therapies could be formulated.

Infertility refers to the failure in achieving pregnancy of a couple after one year of regular sexual intercourse without using a protection method. The purpose of this research work was to evaluate the current status of the test and quality control performance in semen analysis in selected laboratories. The semen analysis was performed in the Laboratory of Andrology in terms of macroscopic examination which include volume, color, viscosity, pH and acidity, and in terms of microscopy: the rate of sperm movement, the exact number of sperms per ml of semen, the percentage of sperm viability and movement, the presence of germ cells and white blood cells. Several questions for each part of the test were selected and answered by the director of the laboratories or andrology section supervisor.   There was a wide range in the performance of selected medical laboratories in Tehran regarding the standards of semen analysis according to the World Health Organization (WHO) Laboratory Manual for the examination and processing of human semen, fifth edition in 2010. They followed the instructions related to the sample collection in about 70% of the evaluated parameters, initial macroscopic examination in about 87% of the selected subjects, and the microscopic evaluation of sperm in about 65% of the test parameters. some laboratories do not follow the instructions of the WHO in performing semen analysis, and most of them do not follow the suggested methods in all parts of the test.

This study was undertaken to analyze the immunohistochemical expression of fibroblast growth factor receptor (FGFR3) in urothelial carcinoma and correlate its expression with the pathological stage, recurrence and other clinicopathological parameters. A retrospective study was undertaken on paraffin blocks of 55consecutiveurothelial carcinoma specimens in 28 months received in Sri Ramachandra Medical College, Chennai, India. Blocks with the sections containing the tumor and adjacent normal epithelium were chosen for the immunohistochemical (IHC) study of FGFR3.   IHC expression of FGFR3 in high grade (HG) invasive urothelial carcinoma was positive in 18% cases, 66.7% of HG non-invasive urothelial and 82.6% of low grade (LG) non-invasive urothelial carcinomas. The FGFR3 expression was presented in 78.1% of non-invasive carcinoma. In case of invasive urothelial carcinoma, the FGFR3 positivity was observed in 18.2% of tumors (P<0.05). FGFR3 expression in LG tumors was positive in 82.6 % of the cases whereas 32.3% of HG cases were positive for FGFR3 (P<0.05). FGFR3 was expressed in 14.3 % of HG invasive tumors which recurred. HG non-invasive tumors were positive for FGFR3 in 80% of the cases. LG non-invasive tumors were positive for FGFR3 in 72.7% of cases (P<0.05). The expression of FGFR3 is higher in low grade, non-invasive tumors and recurrent non-invasive tumors. The targeted therapy for FGFR3 may be used as one of the modes of treatment for urothelial carcinoma. It can also be used as a marker to determine the grade in difficult cases and the risk of recurrence.

Lymphoepithelial - like carcinoma, is rarely recognized in the urinary bladder and less commonly occurs with papillary transitional cell carcinoma i.e. mixed pattern. Also, less uncommon is the occurrence of carcinoma in situ changes in the adjacent urothelium of these tumors. Here, a case of lymphoepithelial – like carcinoma and papillary transitional cell carcinoma associated with carcinoma in situ changes of urothelium of the urinary bladder has been reported the prognosis of this type of malignancy as well as its management will be discussed. Meanwhile, immunohistochemical stains have been carried out to differentiate it from lymphoma of the urinary bladder and the findings will be discussed.

The malignant transformation of conventional giant cell tumor of bone (GCTOB) is rare and usually occurs with irradiation. Here we report two neglected cases of conventional GCTOB with spontaneous malignant transformation at 11 and 16 years after initial diagnosis. In the former case, the patient refused to receive any treatment following the incisional biopsy, and in the latter, the first recurrence that occurred 5 years after initial treatment, was neglected. Although rare, the occurrence of sarcomatous changes in these cases indicates that secondary malignant transformation may be part of the natural course of this tumor. In addition, in both cases, immunohistochemistry showed diffuse and strong p53 expression in the malignant tumor but not in the primary lesion. It suggests that p53 overexpression may play a key role in the malignant transformation of GCTOB and that investigating for p53 expression in recurred lesions may help in predicting cases of giant cell tumor, prone to malignant transformation.

Renal hemangioma is a rare tumor which can be capillary or cavernous. There have been less than 30 renal capillary hemangioma cases reported in the English literature. Herein we will report a case of renal hemangioma which was detected in a 74-year-old man operated with the impression of urothelial carcinoma of hilum.

Heterotopic pancreas (HP) is generally asymptomatic and found incidentally. It can act very rarely as a leading point for intussusception. Thus, it should be considered as a differential diagnosis of the mass lesions leading to the intestinal intussusception. Herein, we report an unusual case of HP as a cause of ileocolic intussusception.

Dear Editor, Cigarette smoking has destructive effect on periodontal tissue. The rates of loss of periodontal attachment and recession of gingival are higher in smokers than non-smokers (1-2). Previous studies on the inflammatory immune responses in smokers’ periodontitis have mainly focused on the role of neutrophils. Tumor necrosis factor–α, prostaglandin E2 and matrix metalloproteinase-8 have been shown to rise in smokers with periodontitis (3-4). Different functions of mast cells and eosinophils in inflammatory immune responses make them distinctive cells in disease pathogenesis (5-6). In an investigation, our team examined the effect of smoking on mast cells density in chronic periodontitis. The study showed that the mean number of mast cells in smokers was significantly lower compared to the non-smokers. Based on the literature, no research was found regarding the effect of cigarette smoking on eosinophil cells in human periodontitis. Eosinophils and mast cells regulate the hypersensitivity reactions by affecting each other function (5). Thus, in the next study, we examined this issue on the same samples. The results revealed that the number of eosinophil count in smokers was significantly lower than non-smokers. Considering the findings of both studies on decreased number of mast cells and eosinophils in the same samples, it seems that cigarette smoke had an apoptotic function on extra-vascular immune inflammatory related cells in human periodontitis. According to our opinion, with the death of mast cells and eosinophils, a cascade of different events occurs in the microenvironment of gingiva which causes more tissue damage in the smokers. The apoptotic effect of cigarette smoke on gingival connective tissue must be studied in the enzymatic level.The Heme Oxygenase-1 (HO-1)/Carbon Monoxide (CO) system demand to explain the pathogenesis of diseases by using the basic metabolism and enzymatic activities. HO-1 has a regulatory action on inflammatory signaling programs. CO is an end-product of HO-1. CO affects the apoptosis and cellular inflammation by modulating the inflammatory related cytokines. Modulating the HO-1 and application of CO-releasing molecules are new therapeutic strategies in inflammatory diseases (7). Based on our previous findings, we suggest that further study on HO-1/CO can probably determine the effect of cigarette smoke on inflammatory immune cells in human chronic periodontitis. The system can be potentially considered as a therapeutic target in inflammatory disease of periodontium in cigarette smokers. Conflict of Interest The authors declared no conflict of interest regarding the publication of this article.

Dear Editor, Dengue is an important arbovirus infection. This infection can result in an acute febrile illness. The important hematological abnormalities included hemoconcentration and thrombocytopenia (1). Due to the decreased platelet count, the patient might develop petechiae and hemorrhagic complication. In endemic area, the presumptive diagnosis of dengue is usually derived by the clinical findings (1). Sometimes, the atypical clinical presentation of dengue can be seen. The dengue without thrombocytopenia is possible and might be difficult for diagnosis (2). Here, the authors present an interesting case of dengue with platelet count and no hemocon-centration.  The automated hematogram can help explain the aberrant complete blood count finding.  The patient was a 13 years old female patient. The chief complaint was high fever for 4 days and petechiae for 1 day. The tourniquet test was positive. The complete blood count was done and the hemoglobin level was 12.4 g/dL and platelet count was 276,000/mm3. In the present case, there was no thrombocytopenia and no hemo-concentration. However, the autoamted hematogram (Figure 1) showed flag that platelet interpretation was possible. From history taking, the patient was a known case of beta-thalassemia/hemoglobin E disorder. The additional dengue NS1 Ag test was positive. The patient was diagnosed to have dengue and received the standard fluid replacement therapy. She got full recovery within 1 week. In the present case, the unexpected normal platelet count despite overt petechiae might be explainable by the automated hematogram. The patient had the underlying hemoglobin disorder problem that results in anisopoikilocytosis and microcytic anemia. With the underlying abnormal hematological parameter, anemia, no hemoconcentration can be explained. Regarding the platelet count, the microcytosis, anisocytosis and poikilocytosis can interfere with the platelet count in autoamted hematology analytical process. Nevertheless, the automated hematogram and flag can help explain and assist the physician in charge for further use of definitive diagnosis test for dengue.