Iranian Journal Of Pathology
Volume:17 Issue: 2, Spring 2022

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until  December 31st 2018. Data sources included  PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.

Glioblastoma is a type of brain cancer with aggressive and invasive nature. Such features result from increased proliferation and migration and also poor apoptosis of glioma cells leading to resistance to current treatments such as chemotherapy and radiotherapy. In recent studies, micro RNAs have been introduced as a novel target for treating glioblastoma via regulation of apoptotic signaling pathway, remarkably PI3K/AKT, which affect cellular functions and blockage or progression of the tumor. In this review, we focus on PI3K/AKT signaling pathway and other related apoptotic processes contributing to glioblastoma and investigate the role of micro RNAs interfering in apoptosis, invasion and proliferation of glioma through such apoptotic processes pathways. Databases NCBI, PubMed, and Web of Science were searched for published English articles using keywords such as 'miRNA OR microRNA', 'Glioblastoma', 'apoptotic pathways', 'PI3K and AKT', 'Caspase signaling Pathway' and 'Notch pathway'. Most articles were published from 7 May 2015 to 16 June 2020. This study focused on PI3K/AKT signaling pathway affecting glioma cells in separated subparts. Also, other related apoptotic pathways as the Caspase cycle and Notch have been also investigated. Nearly 40 miRNAs were found as tumor suppressors or onco-miRNA, and their targets, which regulated subcomponents participating in proliferation, invasion, and apoptosis of the tumoral cells. Our review reveals that miRNAs affect key molecules in signaling apoptotic pathways, partly PI3K/AKT, making them potential therapeutic targets to overcome the tumor. However, their utility as a novel treatment for glioblastoma requires further examination and investigation.

Eosinophils are normally found in different parts of the gastrointestinal tract and with less prevalence in the esophagus. Eosinophilic infiltration is increased as part of inflammatory reactions in various diseases. The aim of this study was to determine the count and distribution of eosinophils in esophageal specimens obtained for different causes.

Endoscopy and pathology reports of esophageal specimens in Shahid Beheshti University related hospitals, Tehran, Iran, were extracted from 2016 to 2019. The prevalence of gastroesophageal reflux disease (GERD), malignancy, eosinophilic esophagitis, and asymptomatic patients were determined as the percentages of total resection and biopsy specimens. Each group was calculated and randomly selected according to the inclusion criteria. All data were analyzed statistically using SPSS software.

A total of 258 biopsy and resection specimens were evaluated in this study. Fourty three cases (16.7%) diagnosed as normal esophageal mucosa , 42 cases (16.3%) as non-specific esophagitis, 155 cases (60.1%) diagnosed as gastroesophageal reflux disease, 4 cases (1.6%) showed malignancy and other diagnoses were recorded for 14 cases (5.4%). The numbers of eosinophils in the epithelium and lamina propria in the normal group were 0.1±0.5 and 2.08±2.33, respectively. The eosinophil count in different groups and its relation to different histopathologic findings were diverse.

The number of eosinophils within the lamina propria was significantly higher than those found within other layers. . The highest mean eosinophil count was observed in the epithelium and the lamina propria of cases diagnosed as GERD.

Gastric cancer (GC) persists to be a major health issue globally, and the need to investigate new molecular markers for improving the survival of patients continues. CDX2 is a homeobox caudal protein family member encoded by the CDX2 gene and is probably playing a role in intestinal epithelial differentiation and proliferation. This study aimed to assess the expression of this protein in gastric cancer cells in addition to its correlation with multiple clinicopathological parameters.

This observational retrospective study was carried out on 80 gastric cancer cases in Erbil, Iraq. CDX2 protein immunoexpression in tumor cells, as well as its correlation with several clinicopathological criteria, were investigated.

CDX2 was detected in 38.75% of GC patients. We found a significant correlation between CDX2 expression and the age of patients (P=0.02). Even though the protein was more expressed in tumors with negative lymphovascular invasion and intestinal GC, there was no significant correlation between the expression of this protein and invasion. In addition, CDX2 expression was not significantly correlated with patient gender, tumor grade, nodal status, and tumor stage.

CDX2 expression was observed to be downregulated in younger patients. It could be due to the higher frequency of diffuse GC, in which CDX2 is expressed less than the intestinal type, in younger individuals.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located at chromosome 10. PTEN is a regulator of the PI3K/AKT signaling pathway that inhibits cell proliferation and promotes apoptosis. PTEN loss of function occurs in a spectrum of cancers, including colorectal adenocarcinoma. This study aimed to investigate the probable correlation of negative PTEN expression with clinicopathological features and colorectal adenocarcinoma (CRC) patients'''' survival.

In this cross-sectional study using Immunohistochemistry stainingPTEN expression status on 151 CRC tissues was evaluated. Then the results of IHC staining was compared to those of clinicopathological features. The relationship between PTEN and KRAS mutation status was also investigated.

Of 151 CRC samples, 89 (58.9%) were negative for PTEN expression. Loss of PTEN expression was associated with KRAS mutation (P

Various studies showed the use of epidermal growth factor receptors (EGFRs) gene mutations in the therapeutic plan of patients with advanced lung cancer. This study aimed to investigate the frequency and types of EGFR gene mutations among Iranian patients with lung adenocarcinoma referred to a specialized lung diseases hospital from 2014 to 2019.

The data of all patients with lung adenocarcinoma referred to the Molecular Department of Masih Daneshvari Hospital Laboratory (National Research Institute of Tuberculosis and Lung Diseases) from 2014 to 2019 for EGFR mutation tests were collected. Patients' characteristics data and information on the frequency and types of EGFR gene mutations were obtained from the hospital information system (HIS). The collected data were analyzed using SPSS 25.

A total of 570 individuals (Mean age of 58.74, 51.6% Male) were included in the study; 113 out of 570 patients (19.8%) were diagnosed with gene mutation. In terms of the type of mutation, 65 participants (57%) showed deletion, 48 patients (42.1%) were diagnosed with replacement, and one (0.9%) case demonstrated both. Notably, the mutation rate detected among the female patients was significantly higher than the male ones (P=0.001); in particular, deletion type of mutation was found more among women, although both genders were the same in terms of the replacement frequency. However, the age had no effect on the mutation in this study (P=0.05).

Among Iranian patients with lung adenocarcinoma, 19.8% harbored EGFR gene mutation. This mutation was found in association with lung cancer and could affect the patient's therapeutic plan.

The existence of eosinophils in the gastric mucosal epithelium is unusual, while the term "eosinophilic gastritis" has become overused due to the increased numbers of eosinophils found in gastric specimens. Thus, we aimed to assess the number and distribution of eosinophils in gastric specimens in Shahid Beheshti University of Medical Sciences hospitals.

This study was performed on 318 patients with gastric diseases who had undergone endoscopic biopsy or gastrectomy in the hospitals affiliated with Shahid Beheshti University from 2016 to 2018. By referring to the archives of pathology departments, patients' demographic and clinical information, endoscopic and histopathological findings were collected. The data was then statistically analyzed using SPSS software version 24 with a significance level of P-value< 0.05 in all tests.

The participants were 157 men and 161 women, with an average age of 51.21 years. There was no significant correlation between eosinophil distribution and age, gender, or primary gastric locations. However, there was a strong correlation between the count of eosinophils in the lamina propria and intestinal metaplasia. Mean eosinophil count per high power field (HPF) was 12, 23, and 14 in mild, moderate, and severe degrees of intestinal metaplasia, respectively. An increase in eosinophil count was seen along with lymphoplasma cells infiltration up to 8/HPF in mild cases, 13/HPF in moderate cases, and 14/HPF in severe cases.

Eosinophil counts in the lamina propria layer show a significant positive relationship with the eosinophil sheet, presence of Heliobacter pylori microorganism, intestinal metaplasia, and lymphoplasma cells infiltration.

Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma.

The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated.

A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis.

The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.

Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells.

A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis.

Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis.

Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.

This study examines the extent of scientific publications and patents in pathology and forensic medicine globally and the citation relationship between them from 2011 to 2020, indexed in the Scopus database.

In this scientometric study, data were extracted from the SciVal citation database. Search feature and library study method and annual growth rate, relative growth rate, and linear model were used to retrieve and analyze the data. The scientometric indicators included the number of publications and patents of the university in collaboration with industry, the number of articles cited by patents, the number of patents cited by articles, the average number of patents cited by articles, and the number of articles cited.

The results showed a poor collaboration between academia and industry in pathology and forensic Medicine, and North America is the busiest region in this field. The average growth of patents based on articles, the number of articles mentioned in patents, citations to patents, and the average number of patents of an institute in the articles of that institute have a positive exponential relationship. Based on the linear model, the relationship between articles and citations equals R2 = 0.982, which is inverse and negative. The data set of articles and citations was suitable for polynomial (R2 = .994), linear (R2= .982) and exponential (R2 = .887) models.

The research process of pathology and forensic medicine is inappropriate, and the citation relationships between articles and patents in this field are weak. Strengthening the link between academia and industry in pathology and forensic medicine can strengthen research in this field.

Ovarian cancer is associated with the highest mortality rate among gynecologic malignancies. Despite new therapeutic strategies, ovarian cancer still has a high risk of metastasis and mortality. Endocan is a newly identified endothelial cell activation marker, which is responsible for angiogenesis, tumor invasion, and aggressive behavior of tumors. The aim of this study was to assess Endocan expression in different types of ovarian tumors and to identify its relationship with clinicopathologic characteristics of ovarian tumors.

This cross-sectional study was conducted on 183 tissue samples, including benign, borderline, and malignant ovarian tumors collected from the University Kebangsaan Malaysia Medical Center archive of Pathology during 2005-2015. Mouse monoclonal anti-human Endocan/ESM-1 Clone MEP08 was used at a dilution of 1:400 for immunohistochemical (IHC) staining. All the information was collected by a checklist, and the association between clinicopathological features and high or low levels of Endocan -MVD was evaluated using Pearson chi-square, Fischer's exact, or Monte Carlo tests.

The prevalence of Endocan positivity was significantly higher in malignant compared to borderline and benign ovarian tumors (P<0.001). There was also a significant association between type of tumor and Endocan status in malignant ovarian tumors (P=0.02), indicating that Endocan positivity was more likely in serous malignant ovarian tumors compared to other ovarian tumor types. However, the tumor stage was not significantly associated with Endocan status (P=0.31).

This study showed that Endocan positivity may show the highest prevalence among malignant tumors suggesting that high Endocan expression would be negatively associated with ovarian tumor behavior.

CCL4 (C-C chemokine ligand4) is a chemoattractant involved in tumors' development, progression, and metastasis. The relationship between the ccl4 gene polymorphisms and the risk of OSCC has not been studied in Iran. This study aimed to identify the effect of ccl4 gene polymorphism on OSCC susceptibility in the population of Southeastern Iran.

In this case-control study, a total of 100 participants, 50 patients with OSCC who were referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran, and 50 healthy people were included. The DNA was extracted from the tissue blocks of OSCC patients. The rs10491121 and rs1634507 in the ccl4 gene were evaluated by the tetra-ARMS (Amplification Refractory Mutation System)- PCR technique. Data were analyzed in SPSS (version 21) using the Chi-square and logistic regression test.

CCL4 genotyping showed that AA+AG genotype in rs10491121 and AA+CA genotype in rs1634507 were slightly higher in control than in the case. Still, the risk of OSCC in both polymorphisms was not significantly different. The minor allele (A) in the rs10491121 and rs1634507 polymorphisms were more common in OSCC compared to the control group (OR = 1.2, 95% CI: 0.66 – 2.22, P=0.54) (OR = 1.6, 95% CI: 0.85-3.07, P=0.15). There was no association between OSCC histopathological grades and CCL4 genotypes at these two sites.

Our results showed no association between ccl4 gene polymorphism and the risk of oral cancer in the population of Southeastern Iran.

Triple-Negative Breast Carcinoma (TNBC) is characterized by an absence of estrogen receptor, progesterone receptor and HER2 neu expression, with distinct molecular, histological and clinical features, aggressive clinical course and a poor prognosis. The objective was to evaluate the expression of Cytokeratin5/6 (CK 5/6), Epidermal Growth Factor Receptor 1 (EGFR 1), E-cadherin and Androgen receptor in tissue sections of TNBC.

All modified radical mastectomy samples received negative for the three markers were subjected to further studies with CK5/6, EGFR 1, E- cadherin and Androgen receptor staining. The clinical and pathological data were tabulated and statistically analysed using the Chi-square test, and cross-tabulation was done to assess the correlation between these markers.

Of 94 samples classified as TNBC, 31 (33%) were positive for CK 5/6, 47 (50%) for EGFR, 32 (34%) for E Cadherin and Androgen receptor, respectively. We had one positive patient for all four markers, 13 patients were negative for all four. Thirty-five cases were positive for only one marker, 32 were positive for two markers, and 13 were positive for three markers. Analysis revealed certain interesting patterns, namely - E cadherin was the most common isolated marker expressed in our cohort of TNBC with 15 of 35 positives.

This study highlights the presence of a unique subtype of TNBC, which are negative for all the four markers studied here, with unique histomorphology of absent tumour necrosis and stromal lymphocytic infiltration being unique.

Papillary thyroid carcinoma (PTC) is considered as a relatively common type of malignancy showing a wide morphologic spectrum. Different variants of this tumor have been reported. Among PTC variants, PTC with nodular fasciitis-like stroma (PTC‑FLS) is rare. This variant consists of stromal components rich in spindle cells and accounts for 60-80% of tumors. In addition, there are small foci of epithelial components in PTC‑FLS though its features are similar to conventional PTC. In this case study, we present a new case with PTC‑FLS. The case is a 28-year-old female who was referred to the ENT clinic due to a painless mass on the anterior part of her neck. The mass showed a gradual increase in size over the 6 months prior to her referral. Thyroid test results were normal. Ultrasound imaging demonstrated an 84 × 36 mm heterogeneous nodule in the right thyroid lobe without calcifications but increased vascularity. There were also some reactive lymph nodes in both sub-mandibular areas. An ultrasound-guided fine-needle aspiration (FNA) biopsy of the right thyroid lobe nodule revealed a benign thyroid adenomatoid nodule. Following right thyroid lobectomy, final pathologic studies confirmed a diagnosis of PTC with exuberant fibromatosis-like stroma. In the 20-day post-surgery visit, the patient was found asymptomatic. Re-evaluation of the left thyroid lobe and follow-up were recommended. In this study, a diagnosis of a rare variant of PTC, i.e., PTC-FLS, was made through a combination of ultrasonography, fine needle aspiration cytology, and histological examination.

Uterine leiomyoma with hepatic vasculopathy, specifically non-cirrhotic portal fibrosis (NCPF), has hitherto been undescribed. NCPF is characterized by elevated portal pressure sans cirrhosis and has previously not been described in association with a gynecological pathology. We report the case of a female under evaluation for a heterogeneously enhancing intrauterine mass with multiple hepatic lesions with increased uptake of fluorodeoxyglucose on positron emission analysis. Fibroscan values were increased. Histopathologic evaluations revealed a leiomyoma with liver tissue showing tubercular granulomas, thin wispy fibrotic strands, and rounded portal tracts pointed to NCPF. No evidence of malignancy was seen. Metabolic imaging may be unreliable to distinguish between benign and malignant uterine pathology and granulomatous and malignant hepatic lesions. Elastography may also be ineffective in diagnosing the etiology of liver fibrosis. Histopathological analysis hence remains essential despite noninvasive tests. Further research is required on females afflicted with NCPF to exclude a hormonal link.

Nevus comedonicus (NC) is a rare developmental anomaly of the folliculosebaceous apparatus, which appears as numerous dilated papules containing firm, darkly pigmented, horny plugs. It appears shortly after birth and mostly before the age of 10; however, late-onset cases have been reported. There is no gender or racial predilection. Moreover, NC can be a component of nevus comedonicus syndrome, a neurocutaneous disorder with skeletal, ocular, and central nervous system abnormalities. EHK properties in NC are not a common finding and are rarely seen in association with each other. This paper reports a healthy, 27-year-old young woman who has been developing numbers of asymptomatic unilateral linear skin lesions on her chest, waist, right thigh, and popliteal fossa in a unilateral linear pattern over ten years. Skin biopsy revealed dilated follicular ostia with orthokeratotic hyperkeratosis, columns of parakeratosis, cornoid flagellation, epidermolytic hyperkeratosis, and mild acanthosis on its wall.