Iranian Journal of Pathology最新文献

Background & objective: Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection.

Methods: To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed.

Results: The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways.

Conclusion: IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.

Background & objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-13 (IL13), which forms a complex with IL13 receptor α2 (IL13Rα2) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals.

Methods: We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL13, SEB-L-IL13, IL13-SEB, and IL13-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL13Rα2, MHCII, and TCR receptors through the HADDOCK 2.4 server. The candidate fusion protein was subjected to molecular dynamics simulation.

Results: There were differences among the designed fusion proteins. The model with the N-terminal domain of IL13 and containing an inter-domain linker (IL13-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL13-L-SEB fusion protein had a higher binding affinity to the IL13Rα2, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL13-L-SEB docked complexes.

Conclusion: The results suggest IL13-L-SEB is a promising novel fusion protein for cancer therapeutic application.

Background & objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance.

Methods: This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters.

Results: There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, the H-score of SOX4 expression showed a significant inverse relation with ERG expression (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05).

Conclusion: SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.

Background & objective: Endometrial Carcinoma (EC) is the most common gynecological cancer with a global incidence of 23.2 per 1 lakh population. Histological subclassification of EC is extremely crucial for the diagnosis, proper management strategies, and prognosis. This study was conducted in a tertiary care institute to analyze the expression pattern of a minimum panel of 4 markers (ER, p53, CEA, Napsin A) with emphasis on their utility in the routine histological subtyping, aberrant expression, and correlation with various clinicopathological parameters.

Methods: A time-bound cross-sectional observational and analytical study was conducted, which includes cases diagnosed in our laboratory from January 2016 to April 2021.

Results: Sixty cases diagnosed as EC during the study period formed the sample cases. The ER was expressed in 85% (53/60) of cases in the current study. Among them, 94% (50/53) were endometrioid endometrial carcinomas (EECs). A negative correlation was found between ER intensity and age (r= -1.48). Of 60 EC cases, 10 (16%) cases expressed p53. The tumors positive for p53 with higher intensity were negative for ER and vice versa. The expression pattern of ER and p53 was statistically significant (P=-0.021). On IHC, 84.6% (11/13) of CEA-positive cases expressed both ER and CEA, suggesting mucinous differentiation. Napsin A was expressed in two cases of EEC, FIGO grade I, and one case of serous carcinoma.

Conclusion: An inverse association was found between ER and p53 expression. The CEA is valuable in identifying EEC with mucinous differentiation.

Background & objective: FFA usually has a gradual subtle course and might be overlooked by physicians or misdiagnosed with other types of hair loss including androgenetic alopecia, traction alopecia, and other types of patterned alopecia. In this study, we described clinicopathological features of patients with FFA referring for skin biopsy.

Methods: This is a retrospective cross-sectional study on 26 patients with a diagnosis of FFA based on clinicopathological features. Firstly, the demographic and clinical features of patients were extracted from an electronic database. Then, skin biopsy specimens were reviewed regarding the presence or absence of hair follicles, site and severity of infiltrations, and presence of fibrosis.

Results: Most of the patients were over fifty years of age (57.7%) with a mean age of 50.73 ± 10.03 years. Frontal region involvement was observed in all of the cases. Eyebrow hair loss was observed in 38.5% of cases. The most frequent clinical findings were the absence of vellus hairs in frontotemporal regions (96.2%) and perifollicular erythema (92.3%). The most common pathological features were involvement of the vellus hairs (84.6%), replacement of follicular epithelium with fibrous sheath (80.8%), and destruction of sebaceous glands (69.2%). Peri-infundibular and peri-bulbar interface changes were observed in 50% and 61.5% of skin biopsies, respectively. Perifollicular fibrosis was demonstrated in half of the skin biopsies.

Conclusion: FFA is most commonly observed in females after the 5th decade of life. The absence of vellus hairs and the replacement of follicular epithelium with fibrous sheath are the most common clinical and pathological features of the disease, respectively.

Background & objective: Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been linked to some malignancies in humans. The aim of this study is to analyze the clinicopathological data of patients while investigating FGFR2 and FGFR3 immunohistochemical expression in invasive urothelial bladder carcinoma.

Methods: This retrospective cross-sectional study included 60 invasive urothelial carcinoma (UC) cases in the Pathology department, Faculty of Medicine, Menoufia University, from 2009 to 2020. All biopsies were stained for FGFR2 and FGFR3 antibodies. Complete clinical data were available for 44 patients treated and followed in clinical oncology and nuclear medicine departments.

Results: Advanced stage and high grade are significantly correlated with FGFR2 positivity (P=0.048 and 0.044, respectively). Cases presented with Perineural invasion showed a higher percentage of FGFR2 (P=0.023). There is a significant indirect linear correlation between FGFR3 expression and lymph node positivity (r= -0.265, P=0.041).

Conclusion: A high FGFR2 expression could be associated with poor prognostic parameters, while high FGFR3 expression would be associated with good prognostic parameters. These findings might highlight the importance of FGFR-targeted therapy as a FGFR2 antagonist and FGFR3 agonist for the treatment of urothelial carcinoma patients.

There has been a rise in COVID-19-associated mucormycosis (CAM) cases, particularly in low-income countries. We describe a case of primary cutaneous mucormycosis after recovering from COVID-19 in a kidney transplant recipient who had a known case of diabetes mellitus. The patient developed cutaneous ulcers due to Rhizopus oryzae in the right hand. She did not recall any trauma or injury at the affected site. Based on the appearance of the wound we suspected that healthcare-associated mucormycosis could be the causative agent. Due to the initial misdiagnosis as a bacterial infection, the appropriate treatment was delayed, and the lesions progressed rapidly to necrotic ulcers with jagged margins that deteriorated during hospitalization. She underwent consecutive surgical interventions and received broad-spectrum antifungal therapy. Finally, the patient deceased after 32 days of hospital stay. We reviewed the previous case reports of cutaneous mucormycosis occurring in COVID-19 patients and described patient characteristics, predisposing factors, location of ulcers, clinical presentation, management, and outcome. This report and existing published literature indicate a poor outcome for cutaneous mucormycosis in COVID-19 patients and the importance of early diagnosis, aggressive multidisciplinary management, and regular follow-up as a life-saving measure, especially in immunocompromised patients.

Background & objective: Primary extranodal lymphoma (pENL) is a malignant lymphoid neoplasm that presents with the main bulk of disease at an extranodal site. The incidence of primary pENL has risen sharply in recent years due to the advent of better diagnostic modalities. Diagnosing pENL can be challenging due to its morphological overlap with other tumors native to the site of origin. This study aims to establish the anatomic distribution, clinical presentations, possible etiologic correlations, and histological subtypes of pENL in a tertiary care center located in South India.

Methods: This is a retrospective study of 109 patients with pENL (69 males, 40 females, M: F = 1.7:1) over 5 years (October 2012 to September 2017). The tumors were reclassified according to WHO classification of Haematolymphoid tumors, 5th edition, 2022.

Results: pENL constituted 109/481 cases (22.6%) of all NHL cases, with the highest incidence in 7th decade. The gastrointestinal tract (39%) was the predominant site involved, followed by head and neck (26%). Diffuse large B cell lymphoma (DLBCL) was the most common histomorphological variant followed by Follicular lymphoma (FL). The majority of the patients were immunocompetent (89%) and presented with stage IV disease (31.1%) at diagnosis.

Conclusion: This study presents an overview of the diverse distribution patterns of both common and rare pENL within a tertiary care center. The accurate diagnosis of pENL necessitates the elimination of secondary extranodal involvement. It is important to note that the accurate diagnosis of pENL requires careful evaluation and exclusion of other possible causes.

Background & objective: The coronavirus disease brought worldwide uncertainty, and Iran was affected by it as well as many other countries in the world. Halting face-to-face education due to social distancing and resident re-employment in clinical wards leads to defective education. The aim of this survey was to evaluate the advantages and disadvantages of modifications made in pathology residency education in Iran.

Methods: This online survey was conducted on all pathology residents in Iran. An online 30-item questionnaire was developed and used in this study.

Results: Sixty residents (88.3% female) participated in this survey. The majority (70%) of the residents were over 30 years old. Fifty percent of the responders reported that their personal life was influenced by the pandemic. Skyroom and Adobe Connect were the most common platforms for online education with overall satisfaction of 65%. The webinars were considered suitable by 51.7% of the responders. Concerns at work were reported by 48.3% of the residents, while 78.3% reported being exposed to the disease and 55% reported being infected. Concerns about transmission of the disease to family members were reported by 90% of the responders.

Conclusion: This study showed that the pathology residency modifications were successful in providing education. However, their social and educational life characteristics might affect their satisfaction with online education.

Background & objective: Subclinical hypothyroidism (SCH), is defined as an asymptomatic state characterized by a normal serum concentration of free thyroxine and elevated serum concentration of TSH. This study aims to investigate the complex interplay between hyperinsulinism, insulin resistance, beta cell function, and low-grade chronic inflammation in Iranian women with SCH.

Methods: Eighty women with SCH and 80 healthy women as controls matched to the patient group for sex, age, and body mass index (BMI), were enrolled in this prospective cross-sectional study. TSH, free T3, free T4, highly sensitive C-reactive protein (hs-CRP), fasting insulin, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, HOMA-IR index, Beta cell function (HOMA-B index) and insulin sensitivity were determined.

Results: Hs-CRP was not statistically different between the SCH patients and the control group (3.7±3.2 Vs 3.6±4.0, P>0.05). Total cholesterol and LDL-cholesterol were significantly higher; however, triglyceride and HDL-cholesterol were not statistically different in patients with SCH as compared with the control group. Fasting insulin levels and HOMA-IR and Beta cell function (HOMA-B) were significantly higher in SCH women compared to the control group. A positive correlation between HOMA-IR and HOMA-B with TSH levels was found (r=0.324, r=0.191, P<0.05 respectively). A positive correlation between insulin levels and hs-CRP (r=0.22, P<0.05), also between insulin levels and TSH (r=0.312, P<0.05) and LDL- LDL-cholesterol was obtained (r=0.27, P<0.05).

Conclusion: Iranian women with SCH may exhibit elevated atherogenic parameters (hyperinsulinemia, LDL-cholesterol, and total cholesterol), HOMA-IR, and HOMA-B.