Iranian Journal Of Pathology
Volume:14 Issue: 3, Summer 2019

Clinical databases have been developed in recent years especially during the course of all medical concerns including laboratory results. The information produced by the diagnostic laboratories have great impact on health care system with various secondary uses. These uses are sometimes as publishing new extracted information of laboratory reports which have been widely applied in the scientific journals. Nowadays, some large scale or national databases are also formed from the integration of these data from smaller centers in the field of human health in many countries. These databases are beneficial for different stakeholders who may need these information. Unfortunately, reviewing some of these uses has indicated lots of errors in quality control, test validity, uniformity and so on. More importantly, some of the diagnostic procedures have been applied in the clinical diagnostic laboratories without even preliminary clinical evaluation studies. Therefore, any taken conclusion from these analyzed data may not be reliable.  This use requires checking the several specifications that have been notified in this study. Current review also intends to show how the correct information should be to extract for the scientific reports, or integrated in large scale databases.

Basal cell carcinoma (BCC) is classified into BCC1 or low risk (nodular, superficial type) and BCC2 or high risk (micronodular, morpheaform, infiltrative, and basosquamous types) based on clinical behavior. This study attempts to evaluate immunohistochemical (IHC) findings and clinical features associated with local aggressiveness and recurrence in BCC lesions. This is a cross-sectional descriptive study conducted on 42 paraffin blocks (22 BCC1, 20 in BCC2) at Pathology Department of Afzalipour Teaching Hospital. First, demographic features of the patients were recorded and pathology blocks were classified by two dermatopathologists based on histopathological types of BCC1 and BCC2. Then, primary monoclonal antibodies including CD10, CD1a, SMA, Ki67, CD34, and P53 were utilized for IHC study. We compared BCC1 and BCC2 according to IHC markers, demographic features of patients, and tumoral features. The mean number of Langerhans cells (LCs) within epidermis above tumor mass was 14+1.92 and 4.7±1.23 in BCC1 and BCC2, respectively; these results show a significant difference between the two groups (P=0.001). P53 was positive in 41.13±6.39% and 74.5 ±6.26% of the tumor cells in BCC1 and BCC2 groups, which was statistically significant (P=0.001). Also, the mean number of blood vessels was 14.40±1.30 and 21.40±1.97 in BCC1 and BCC2, that was statistically significant (P=0.005).  Higher numbers of angiogenesis (SMA positive) and positive P53 were observed in BCC2 than BCC1. Also, more active positive CD1a cells were observed in BCC1 compared to BCC2.

Human papillomavirus (HPV) is the main cause of genital warts and some anogenital cancers in male and female subjects which is commonly transmitted by sexual contacts. The objective of this cross-sectional study was to examine the prevalence of HPV genotypes in 10,266 Iranian male and female population, according to their age. Samples were collected from the penile and anal sites of male subjects and the vagina and cervix of female subjects in a time period between 2011 and 2016. HPV DNA was detected in PCR using the MY09 and MY11 primers, and the INNO-LiPA assay was applied for HPV genotyping. To investigate the relevance of HPV infection and age, the samples were classified into 4 age groups (13-29, 30-44, 45-59, and 60-74). Totally, the most common low risk HPV genotypes detected in the studied male and female subjects were HPV-6 (77.7% and 43.3%) and HPV-11 (13.7% and 11.4%), and more frequent high risk HPV genotypes were HPV-16 (5.5% and 16.6%) and HPV-52 (3.2% and 9.6%), respectively. High burden of the HPV infection was observed at ranges of 30 and 44 years (51.8%) with a peak at ranges between 30 and 32 years. No considerable statistically significant correlation was found between HPV infection and age (P=1). This study gave an epidemiological overview of circulating HPV genotypes in Iranian population to develop future vaccination policies, though the findings of prevalent HPV genotypes in female subjects were inconsistent with the previous studies reported in Iran.

Brucellosis is one of the most prevalent bacterial zoonotic diseases which afflicts both humans and animals. Genetic factors play an important role in susceptibility to brucellosis. One of these factors is interferon-gamma (IFN-g), which is vital in the defense mechanism against infectious diseases such as brucellosis. The purpose of this study was to evaluate the relationship between two single nucleotide polymorphisms (SNPs) at positions -611 and -56 within the promoter region of interferon-gamma receptor-1 gene (IFN-g R1) and brucellosis. In this research,thegenomic DNA was collected from 60 peripheral blood samples infected with brucellosis and 68 healthy volunteers. DNA was extracted by salting out method. Then, DNA genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). The results showed that there is a significant difference in -611 SNP frequencies between control and patient groups. At position -611, CC genotype was related to patient group (P=0.024) and TT genotype was related to the control group. According to the results, males had a higher frequency of Brucella infection. The presence of C allele in position -611 in IFNγ R1 gene promoter was related to a higher risk of disease and susceptibility to brucellosis. Moreover, the presence of T allele in position -611 in IFN-g R1 gene promoter was related to a lower risk of disease.

To study the immunophenotype of prostate cancer (PC) with the presence and absence of intraluminal inclusions (IIn), depending on the grade score. A total of 30 PC samples with IIn (group E) and 30 PC samples without them (group C) were studied. These groups were divided into 2 subgroups, depending on the grade of malignancy, which was determined according to the Gleason score as moderate and high-grade tumors. Macroscopic analysis, hematoxylin-eosin staining, immunohistochemistry (androgen receptors, p53 and Bax proteins, Hsp70 and Hsp90, CD68, VEGF, OSN, MMP-1) were used. The expression level of VEGF was higher in the more differentiated tumors of the control group (P<0.01). Increased expression of prognostic-adverse markers p53 (in the presence of IIn, P<0.01) and MMP-1 (P<0.05) was observed. Also, a higher level of OSN expression was found in PC tissue with IIn (P<0.01) due to its participation in the processes of biomineralization. The expression level of CD68 and Bax protein was higher in the PC group with IIn (both P<0.01). Furthermore, Hsp90 had a significantly lower expression level in the PC of group E (P<0.05). the presence of IIn in the PC samples of group E promotes tissue remodeling with mechanical trauma, chronic inflammation, and fibrosis development. The presence of IIn in PC leads to the increase of OSN, CD68 and Bax expression and decrease of Hsp90 and VEGF expression. High expression of p53 and MMP-1 and low expression of OSN and VEGF was identified as a characteristic of high-grade tumors.

Recent studies from gene profiling have revealed some genes that are overexpressed in the epithelial-mesenchymal transition (EMT) process and are responsible for its initiation and activation resulting in tumor progression and metastasis. The present study aimed to assess the role of genes involved in the EMT process and the association of these genes with axillary lymph node and vascular invasion in breast cancer (BC) patients. In this case-control study, the tumor samples were initially extracted from 33 BC patients. The samples of 15 BC tissues without vascular and axillary invasion were also prepared from the biobank as a control group. RNAs from both tumor and control samples were extracted and stabilized. For assessing overexpression in tumor tissues of selected 18 genes, the real time technique was employed.   There was a significant increase in MMP-2 gene fold expression in tumor cells with vascular invasion regardless of axillary involvement compared to the control group (P=0.0008) and also in the comparison of the control group with those with vascular invasion and not axillary lymph node involvement (P=0.003). In addition, gene fold expression of tissue inhibitors of metalloproteinase-1(TIMP-1) was decreased in axillary involving tumor cells compared to control group (P=0.045), and also in comparison with all samples that did not present any axillary lymph node involvements including the control group and the group with isolated vascular invasion (P=0.012). Overexpression of MMP-2 and under-expression of TIMP-1 were associated with more invasive behavior in breast tumor cells.

In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors. In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented. The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression. The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.

Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic inflammatory immune response. Current therapies mostly rely on glucocorticoids which are accompanied by side-effects and mostly fail to achieve a favorable remission. Th17 subpopulation of T cells is increased in exacerbated SLE as IL-17 cytokine is overexpressed. However, IL-17 is reported to be resistant to glucocorticoids in various disorders. Here, we evaluated the plasma level of IL-17 among newly diagnosed and under-treatment SLE patients to understand the effect of glucocorticoids on Th17 response.  A total of 40 female SLE patients and 20 age- and sex- matched normal subjects were enrolled. IL-17 plasma level was evaluated using ELISA cytokine assay and analyzed with previously obtained IL-10, IFN-γ, and GILZ levels. Our findings revealed that IL-17 was overexpressed among under-treatment SLE patients. There was a significant correlation between IL-17 and IFN-γ and significant reverse correlations between IL-17, IL-10, and GILZ levels. IL-17 was not significantly correlated with the disease activity. According to the role of IL-17 in tissue injury and the fact that glucocorticoids are not successful in preventing organ damages in SLE, the overexpressed IL-17 in response to therapies could be introduced as an underlying reason.

Liver biopsy is the main method for grading and staging liver disorders, but the effects of clinical information and optimal biopsy specimen size on interpretation remain contentious. The aim of the study was to evaluate the impact of clinical information and quality of liver specimen on inter-observer agreement for liver disease. A total of 289 consecutive biopsy specimens from 2010 to 2017 were re-evaluated by five pathologists using the modified Ishak and non-alcoholic fatty liver diseases (NAFLD) activity score (NAS) systems. Detailed clinical information was extracted from medical records of patients and the size of all liver biopsy samples was recorded. Full agreement between primary diagnosis and final diagnosis was obtained in 214 cases (74%). The remaining cases, namely 22 (7.6%) and 53 (18.3%) biopsies had minor and major diagnostic discrepancies, respectively. The results showed that the overall agreement was significantly higher in cases with complete clinical information than patients without any clinical information and even with partial clinical information (P<0.001). Interestingly, no significant difference in inter-observer agreement was achieved with a length over 20 mm (P=0.181). However, the inter-observer variation significantly decreased when the number of portal tract was more than 10 (P=0.001). This study identified the impact of clinical information and the number of portal tracts as the key factors to diagnosis. Therefore, request forms for liver biopsies should always be accompanied with the clinical history. Moreover, adequacy of biopsy specimens is very useful for accurate evaluation of samples by pathologists.

Glioblastoma-multiforme is the high grade form of astrocytic tumors with a short survival time, which are the most common type of brain tumors. Therefore, finding new therapeutic options is essential. Cyclin D1 is expressed in some human malignancies and can be a potential target for therapeutic intervention. The aim of the present study was to determine this relationship. This is a cross-sectional study conducted in the pathology department of Al-Zahra Hospital in Isfahan, Iran. In this study, 100 samples diagnosed with astrocytic tumors between 2011 and 2015 that met the study’s requirements were studied and immunohistochemical staining for cyclin D1 was performed for each specimen. At the end, the relationship between the expression of cyclin D1 and various variables including tumor grades, tumor subtypes and patient demographic features were examined using appropriate statistical tests.   Of the 100 samples, cyclin D1 was positive in 60 samples and negative in 40 samples. Moreover, in 26 samples, the amount of the marker was low, while in 34 samples it was high. Following the results of the study, there was a significant difference (P =0.038) in the expression of the cyclin D1 marker among the four different grades of astrocytic tumors. The results showed that the expression of cyclin D1 was associated with different tumor grades, especially the high level of expression in grade 4, and the amount of cyclin D1 increased as the level of grade glioma increased.

Malakoplakia is a rare granulomatous disease of the genitourinary system. Gastrointestinal tract is the second most common site of involvement. It usually mimics a malignancy but its association with adenocarcinoma has been rarely reported.  A 59-year-old male patient with the history of weight loss and rectal bleeding for two months prior to administration was referred to our hospital. Pre-operative CT scan revealed a large sigmoid colon mass with the extension and invasion to the serosal surface as well as multiple regional metastatic lymph nodes. The patient underwent sigmoidectomy with the primary pathologic diagnosis of adenocarcinoma. Pathologic examination revealed a moderately differentiated adenocarcinoma invading peri-colic adipose tissue and inflammatory reaction compatible with malakoplakia at the invasive borders of the tumor with the extension to the serosal surface. In the patients with gastrointestinal malakoplakia, the presence of possible adjacent malignancy should be screened. The possibility of over-staging should also be considered for adenocarcinoma cases in association with malakoplakia.

Synovial sarcomas are soft tissue neoplasms mostly located in the lower extremities of young adults. A case of synovial sarcoma of the thigh in a 35-year-old male with the predominant epithelial component is reported. Microscopically the tumor showed variable-sized well-differentiated glands lined by the cuboidal cells with small foci of spindle cell component between glandular structures. Immunohistochemically glandular components showed positivity for the pan CK and EMA while CD99 and TLE1 were positive in both glandular and spindle cell components. This type of synovial sarcoma could be indistinguishable from metastatic adenocarcinoma and malignant adnexal tumor, thus, immunohistochemistry and molecular studies play an essential role in the exact diagnosis of this type of tumor.

Mast Cell Leukemia (MCL), a rare subtype of systemic mastocytosis is defined by bone marrow involvement as atypical and aleukemic mast cells, if more than 20% and less than 10% of peripheral WBCs are mast cells, respectively. We met a case of aleukemic MCL presenting with anemia and ascites for 2 years, referred for BM evaluation, suspicious of leukemia. Our findings included BM involvement by diffused aggregates of oval- and spindle-shaped atypical mast cells, lacking mature mast cells and other hematopoietic cells. The mast cells were absent in peripheral blood smear. Further assessments showed positive reaction of mast cells metachromatic granules with Tryptase, Giemsa and Toluidine blue stains, the expression of CD117/KIT and CD45 by immunohistochemistery, and elevated level of serum Tryptase. Radiologic investigations revealed generalized lymphadenopathy, and massive hepatosplenomegaly, followed by the cervical lymphadenectomy, and liver wedge biopsy. Suspicious peritoneal lesions were identified and underwent excisional biopsy. Microscopic evaluations showed lymph nodes and liver involvement by cancer cells and the same features in peritoneal seeding. Multiple organs damage progressed in few months and the patient died despite surgery and chemotherapy. In conclusion, we report an extremely rarecase of aleukemic MCL with multiple organs damage such as liver, peritoneum, spleen, gastrointestinal tract and BM, presenting by ascites. According to this case and previous parallel studies, we suggest some clinicopathologic features in favor of poor prognosis, including the presence of multiple organs damage, hepatomegaly, ascites, peritoneal seeding, the absence of mature mast cells and other hematopoietic cells in the BM, and elevated serum Tryptase level.