Quarterly Journal of Anatomical and Clinical Pathology
The IRANIAN JOURNAL OF PATHOLOGY (IJP is an Open Access journal and publishes original research papers, reviews, case reports, short communications, and letters to the editor with priority for high-quality original papers on mechanisms of disease and clinical trials. We accept manuscripts that report important findings on disease pathogenesis and basic biological mechanisms related to disease, without preference for a specific analytical method. High priority is given to studies on human diseases and relevant experimental models that use cellular, molecular, biochemical & immunological approaches in conjunction with morphology, and to manuscripts that report new diagnostic methods or analytical systems and their application in studies of disease pathogenesis and diagnosis.
Abstract Laboratories must go beyond delivering accurate results; they must embody the principles of ethical care and human dignity. By prioritizing respect, empathy, and patient-centeredness, they enhance both the technical and human quality of healthcare. Ethical practices establish a foundation of trust and professionalism, ultimately benefiting patients, staff, and the healthcare system as a whole. Organizations are more successful when they tap into their customers' emotions by communicating effectively and empathetically. Ultimately, honoring human dignity in laboratories is not merely a moral ideal; it is a practical imperative that yields emotional, professional, and institutional rewards.
Abstract Background & Objective: Epidermal growth factor receptor (EGFR) mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC). The L858R mutation in exon 21 of the EGFR gene is associated with responsiveness to targeted therapies in NSCLC patients. This study aimed to evaluate the frequency of L858R mutation and its correlation with clinicopathological characteristics in NSCLC patients. Methods: In this cross-sectional study, Allele-specific Polymerase Chain Reaction (ASPCR) was used to detect L858R mutation in genomic DNA obtained from 336 patients diagnosed with NSCLC. Patients were categorized into mutation-positive groups and mutation-negative subgroups. Associations between the L858R mutation, clinicopathological features, and overall survival were analyzed using appropriate statistical methods. Results: The L858R mutation was identified in 6% of patients (20 out of 336) and showed no significant association with clinicopathological features such as age, gender, tumor grade, histology subtypes, or metastasis (all P > 0.05). Survival analysis indicated an overall mortality rate of 81.8%, with no statistically significant difference in median survival between mutation-negative (11 months) and mutation-positive groups (8 months, P=0.246). Cox regression analysis identified Tumor Grade I as a b significant prognostic factor in both Univariate (HR=0.46, P=0.031) and multivariate (HR=0.46, P=0.040) models. Conclusion: The frequency of the L858R mutation in this Iranian cohort with NSCLC was lower than that reported in global studies. However, its association with metastasis and mortality indicates the potential clinical relevance of this mutation in treatment planning.
Abstract Background & Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by dysregulated autoantibody production and diverse clinical manifestations. Despite advances in research, the diagnosis and management of SLE remain challenging. This study evaluated plasma levels of interleukin-1β (IL-1β) and microRNA-146a (miR-146a) in patients with SLE and explored their potential as diagnostic and prognostic biomarkers. Methods: Blood samples were collected from 100 patients with SLE and 100 healthy controls. Patients with SLE were further classified into newly diagnosed (ND; n=50) and under treatment (UT; n=50) subgroups. Plasma IL-1β levels were quantified using ELISA, and circulating miR-146a expression was assessed by quantitative reverse transcription PCR. Results: Patients with SLE exhibited significantly higher plasma levels of IL-1β and miR-146a compared with healthy controls. ND patients demonstrated the highest concentrations of both biomarkers. Among patients with SLE, those with lupus nephritis (LN) showed markedly elevated IL-1β levels compared with those without LN. Longitudinal analysis during a 24-week follow-up indicated that higher baseline IL-1β levels were associated with an increased risk of LN development, supporting its potential prognostic relevance. Conclusion: IL-1β and miR-146a are elevated in patients with SLE, with IL-1β levels correlating with new-onset disease and LN development. These findings suggest that IL-1β and miR-146a may serve as useful biomarkers for diagnosing, monitoring, and predicting disease progression in SLE, although further validation is warranted.
Abstract Background & Objective: Fine-needle aspiration cytology (FNAC) is a minimally invasive, rapid, and relatively safe diagnostic method for the initial evaluation of lymphadenopathy of unknown origin. In May 2020, the Sydney System was proposed to provide recommendations for diagnostic categorization, FNAC of lymphadenopathy, pathology reporting, and related practices. This study aimed to analyze the applicability of the Sydney System in lymph node FNAC and to evaluate diagnostic accuracy and risk of malignancy (ROM) for each diagnostic category. Methods: A 2-year retrospective diagnostic study was conducted from January 2019 through December 2020. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy (DA), and ROM were calculated using histopathology as the gold standard. Results: A total of 632 lymph node FNAC cases were included, with histopathological follow-up available in 45 cases. The median age of patients was 26 years, with a male-to-female ratio of 1.2:1. Cervical lymph nodes were most frequently involved (367 cases, 58.1%). Overall sensitivity, specificity, and diagnostic accuracy were 66.7%, 85.0%, and 76.3%, respectively. ROM by diagnostic category was: nondiagnostic (25%), benign (5.2%), atypia of undetermined significance (AUS) (50%), suspicious (80%), and malignant (88.8%). Conclusion: FNAC demonstrated high diagnostic efficacy when applied using the proposed Sydney System, supporting the utility of this standardized reporting scheme for lymph node cytology.
Seyed Alireza Mirsharifi, Shirzad Nasiri, Seyed Mohammad Tavangar, Mohammadamin Parsaei
Abstract Background & Objective: Adrenal tumors present a notable prevalence of 4-7% in individuals above 40 years old. Current guidelines recommend adrenalectomy for hormone-secreting, potentially malignant, or large (>4 cm) lesions. However, the outcomes of adrenalectomy and their clinical-pathological associations remain poorly defined. This study assessed adrenalectomy outcomes and explored its clinical, demographic, and pathologic correlates. Methods: In this retrospective cohort study, the medical records of all patients who underwent adrenalectomy from March 2016 to March 2021 at a referral center in Tehran were reviewed. Also, a clinical follow-up via telephone was conducted. The chi-square test, independent t-test, and analysis of variance were utilized for statistical analysis. Results: Data from a total of 75 patients (55 females) were reviewed. The mean age of the participants was 42.67 years. Of them, 60%, 22.7%, 14.7%, and 1.3% had pheochromocytoma, Cushing's syndrome, Conn's syndrome, and insulinoma, respectively. Malignancy was associated with greater tumor size (p<0.000) and mitotic rate (p=0.046), and the presence of necrosis (p=0.001), and capsular and vascular invasion (p<0.000). Clinical follow-up visits of 45 patients indicated 84.4% showed a complete response to the treatment (surgical ± medical). Treatment response was significantly influenced by approach (laparoscopic favored; p=0.001), surgery duration (<150 minutes better; p=0.017), mass pathology (adenoma favored; p=0.034), and capsular invasion (absence better; p=0.012). Conclusion: Adrenalectomy outcomes were significantly affected by surgical approach and tumor pathology, notably capsular invasion. Larger studies are needed to determine the predictive values of clinical and pathologic variables in adrenalectomy for adrenal tumors.
Abstract Background & Objective: Iron deficiency anemia is the most prevalent form of anemia worldwide and can cause complications in children and adolescents. This study investigates the correlation between serum and urinary ferritin and evaluates the feasibility of using urinary ferritin to diagnose iron deficiency. Methods: In this case-control study, 45 patients with iron deficiency anemia were included in the case group and 45 healthy children in the control group. From each participant, 1.5 mL of blood and 5 mL of urine were collected, and serum and urinary ferritin levels were measured using the chemiluminescent immunoassay (CLIA) method with Mindray kits. The results were analyzed and compared using SPSS software, version 16 (IBM Corp). Results: The mean age of patients was 7.95 years, and that of controls was 7.26 years. Female patients constituted 62.2% of the case group, and female controls represented 46.7% of the control group. In patients, the mean serum ferritin level was 13.39 ng/mL (SD = 6.37), and the mean urinary ferritin level was 3.50 ng/mL (SD = 2.65). In controls, the mean serum ferritin level was 63.7 ng/mL (SD = 41.8), and the mean urinary ferritin level was 3.98 ng/mL (SD = 2.89). Urinary ferritin demonstrated lower diagnostic accuracy for iron deficiency anemia compared with serum ferritin. The Spearman correlation coefficient between serum and urinary ferritin was 0.155, indicating a weak positive correlation. Conclusion: The findings of this study demonstrate an insignificant relationship between urine and serum ferritin levels. These findings indicate that urinary ferritin is not a reliable non-invasive alternative for diagnosing iron deficiency.
Abstract Background & Objective: There are limited findings regarding histopathological changes in sleeve gastrectomy samples and their relationship with preoperative clinical and histopathological characteristics. The present study aims to assess histopathological findings in sleeve gastrectomy samples and identify the main determinants of these changes. Methods: This cross-sectional study retrospectively reviewed demographic, preoperative clinical, histological, and endoscopic findings of 258 patients who underwent laparoscopic sleeve gastrectomy surgery. Postoperative pathological findings were also evaluated. Results: Microscopic examination revealed pathological findings in 212 samples (82.2%). The most common histopathological finding reported in patients was chronic gastritis, present in approximately 67.1% of cases, followed by active gastritis in 13.6%. Additionally, 19.0% of patients tested positive for helicobacter pylori infection. A significant association was found between the history of hyperlipidemia and helicobacter pylori positivity (p = 0.039). Before surgery, 80 patients (41.7%) had normal endoscopic results, while at least one significant abnormal finding was observed in 58.3% of cases. However, there was no significant relationship between preoperative endoscopic findings and histopathological changes after surgery in almost all examined patients. Conclusion: Histopathological examination of sleeve gastrectomy samples reveals a high prevalence of abnormal findings, including active gastritis, Helicobacter pylori infection, intestinal metaplasia, and dysplasia requiring therapeutic management. However, tracking these changes in biopsy samples obtained from endoscopy before surgery may not be sufficient to predict the histopathological findings after sleeve gastrectomy.
Abstract Background & Objective: Gastric cancer (GC) is a lethal disease with poor prognosis. Long non-coding RNAs (lncRNAs) involved in the development of cancer through changes in their expression levels. In present study, we aimed to evaluate HOXA10-AS gene expression and its potential as a biomarker in GC. Methods: In this study 60 subjects (30 gastric carcinoma tissues and 30 adjacent non-carcinoma tissues) were examined. The expression level of the HOXA10-AS gene was evaluated using quantitative PCR. Furthermore, clinicopathological characteristicswere taken into consideration. Diagnostic value of the HOXA10-AS was examined by ROC curve analysis. Bioinformatics analysis was performed using different databases. Results: Expression of HOXA10-AS was significantly upregulated in GC tumoral tissues. Roc curve analysis revealed that the diagnostic power of HOXA10-AS was high (AUC = 0.64) in the tumor compared to the normal GC tissues. Conclusion: Our findings show that HOXA10-AS expression level is higher in the GC tumor compared to the adjacent non-carcinoma tissues and can act as a strong diagnostic biomarker in GC patients.
Abstract Background & Objective: Real-time PCR is widely used to detect SARS-CoV-2, the virus responsible for COVID-19, but false-negative results can occur even with internal controls. This study aimed to investigate the impact of using alternative internal control materials on the accuracy of SARS-CoV-2 detection kits. Methods: Between December 2021 and January 2022, 162 respiratory tract samples were collected from patients with suspected COVID-19 at Ghaem Hospital in Mashhad, IR Iran. Samples were initially tested with the Pishtaz Teb kit, which uses DNA internal control, and then negative samples were retested with the Geneova kit, which uses a RNA internal control. Positive and negative controls were consistently used to validate the results. Results: After retesting with the Geneova kit, only one patient out of 162 negative samples was positive for SARS-CoV-2. The Pishtaz Teb and Geneova controls consistently produced the expected results, but the Geneova internal control matched the Pishtaz Teb control in only 44% of cases. The higher threshold cycle value for Geneova internal control suggested RNA degradation during the experimental period. Conclusion: Proper quality control measures are crucial for accurate SARS-CoV-2 detection. The study highlights the importance of selecting reliable diagnostic kits with high sensitivity and specificity to reduce false-negative results, particularly in cases with a low viral load or early stages of the disease. The internal RNA control can detect RNA degradation and help identify false-negative diagnoses, leading to better disease control and management. Further research is needed to improve the accuracy of COVID-19 diagnostic tests.
Abstract Background & Objective: Spermatogenesis is a temperature-dependent process, and testicular heat stress can cause spermatogenic failure by inducing cell apoptosis and oxidative stress, ultimately leading to male infertility. Adipose-derived mesenchymal stem cells (AMSCs) have been considered an effective therapy for various tissue degenerations, demonstrating the ability to stimulate testicular regeneration and restore spermatogenesis. The current study focuses on the therapeutic potential of AMSCs on semen quality, testicular morphological changes, and oxidative stress parameters in rats exposed to heat stress. Methods: In this experimental study, 35 adult male rats were randomly assigned to five groups: Group I (control), Group II (vehicle), Group III (heat stress group, temperature-humidity index: 43 °C for 20 minutes), and Groups IV and V (treatment groups receiving 0.5×10⁶ and 1×10⁶ AMSCs, respectively, on the second and fifteenth days after heat stress induction). Sixty days after heat stress exposure, the animals were euthanized; serum testosterone levels and oxidative stress biomarkers were analyzed, and the testes and epididymis were collected for histological and sperm evaluation. Results: Scrotal heat stress caused deleterious effects on testicular histological structure and function. Testosterone levels and total antioxidant capacity were significantly reduced in the heat stress group. The 1×10⁶ AMSCs-treated group showed moderately preserved testicular tissue morphology. Apoptotic spermatogonia and primary spermatocytes decreased significantly in the AMSCs treatment groups in a dose-dependent manner. Malondialdehyde levels and total antioxidant capacity were also improved. Progressive sperm motility, sperm count, and viability were notably enhanced in the AMSCs-treated groups. Conclusion: A single dose-dependent injection of AMSCs demonstrated regenerative properties that improved with increasing cell number. Overall, administration of 1×10⁶ AMSCs can alleviate testicular damage and promote the spermatogenesis process in testicular hyperthermia.
Hawar Nasr mohammad, Arman Ahmadi, Mehrdad Payandeh, Mahsa Dabir, Mahdi Taghadosi, Fakhredin Saba
Abstract Background & Objective: Graft-versus-host disease (GVHD) is a major complication following allogeneic bone marrow transplant (BMT), often limiting therapeutic success in leukemia patients. Chemokine receptors, such as those encoded by Duffy (FY) and Kidd (JK) blood group genes, may influence GVHD development by modulating immune cell trafficking. To evaluate the association between donor and recipient Duffy and Kidd genotypes and GVHD incidence in leukemia patients undergoing HLA-identical sibling BMT. Methods: This retrospective cross-sectional study analyzed 100 DNA samples from 50 donor-recipient pairs (20 with GVHD, 30 without). Genotyping for FY and JK antigens was conducted using PCR-RFLP. Statistical analysis was performed using chi-square and logistic regression tests in SPSS v19, with significance set at P < 0.05. Results: Kidd and Duffy genotype distributions differed between BMT recipients who developed GVHD and those who did not. However, when gender was included as an additional variable, these associations in recipients were no longer statistically significant for either genotype. In donors, neither the Kidd nor the Duffy genotypes showed a significant association with GVHD status overall. Interestingly, when stratified by gender, a significant difference was observed only for the Kidd genotype in donors of GVHD-positive recipients, but not in donors of GVHD-negative recipients. However, multivariate logistic regression did not confirm any independent association between Kidd or Duffy genotypes and GVHD in recipients (OR = 2.94, 95% CI: 0.494–17.49, P = 0.236) or donors (OR = 2.273, P = 0.323). Conclusion: Kidd and Duffy blood group phenotypes may influence susceptibility to GVHD. Understanding this relationship can support better donor-recipient matching in BMT.
Erta Rajabi, Kousha Farhadi, Malihe Hassannezhad, Mahsa Azadbakhsh, Alireza Abdollahi, Seyed Hadi Kalantar, Sara Ghaderkhani
Abstract Background & Objective: Septic arthritis is an emergent condition caused by an infection of the joint synovial fluid. If left untreated, it can lead to irreversible damage to the affected joint. Our study focused on providing a concise profile of the Iranian population and the diagnostic roles of synovial pan-PCR and culture. Methods: In an observational study, we evaluated the characteristics of all patients diagnosed with septic arthritis and admitted to a teaching center hospital complex. We extracted and analyzed the study of population's demographics and laboratory values. Results: This study included 50 patients diagnosed with septic arthritis. 56% of our study population were male, and the mean age was 50.48. There were significant associations between synovial WBC counts and positive synovial culture results. Further comparison of the two diagnostic methods revealed higher pan-PCR accuracy than synovial culture. Conclusion: Pan-PCR may have higher diagnostic accuracy than synovial culture in hospitalized patients with septic arthritis.
Mais Mohammed Salim Mohammed Hasan, Iftikhar Kudair Abbas, Ibtihal Chiad Abbas, Kaswer Musa Jaafar, Rana Talib Fakher
Abstract Background & Objective: Cervical carcinoma is the fourth most common malignancy among women worldwide, with a disproportionately high incidence and mortality in developing countries, including Iraq, where 320 new cases and 62 deaths were reported in 2023. Although the Papanicolaou (Pap) smear remains the cornerstone of screening, findings across Arab populations have been inconsistent, underscoring the need for region-specific data. This study aimed to determine the prevalence and patterns of cervical epithelial cell abnormalities and assess the diagnostic accuracy of Pap smears in Najaf, Iraq. Methods: This retrospective, cross-sectional study was conducted over ten years (December 2014–December 2024) and included 3522 cervical Pap smears from women aged 16 to 80 years (mean, 36.97 ± 10.62 years) obtained at a private medical laboratory. Samples were classified according to the 2014 Bethesda System. Results: Of 3522 samples, epithelial cell abnormalities were identified in 192 (5.45%). Atypical squamous cells of undetermined significance (ASC-US) were the most frequent abnormality (3.78%). The highest prevalence was observed among women aged 40 to 60 years. A strong cytohistopathologic correlation was noted. The Pap test demonstrated a sensitivity of 76.19%, specificity of 80.30%, and overall diagnostic accuracy of 79.31%. Conclusion: The 5.45% prevalence of epithelial abnormalities, predominantly ASC-US, highlights the ongoing need for active cervical cancer screening programs. The significant concordance between cytologic and histopathologic findings confirms the diagnostic reliability of the Pap smear. Further studies are warranted to characterize local cytologic patterns and identify prevalent HPV genotypes to inform HPV vaccination and targeted prevention strategies.
Bahram Memar, Ali Moradi, Shohreh Khatami, Hassan Vosoughinia, Mitra Ahadi
Abstract Background & Objective: Inflammatory bowel diseases (IBD) is described by increased coagulability and prothrombotic state and can be associated with coagulopathies. Although many causes of increased coagulability and thrombosis have been reported in IBD, there is no definitive evidence for most of them. This study aimed to define the changes in Blood Coagulation Factors in patients with IBD compared to healthy controls. Methods: In this case-control study, serum levels of protein C, protein S, antithrombin III, fibrinogen, and Homocysteine were evaluated in 59 patients with a confirmed IBD, (23 with Crohn disease and 36 with ulcerative colitis) (case group) and 29 healthy individuals (control group) matched for age and gender. Results & Conclusion: Significant differences were found in all five studied markers between IBD and non-IBD patients (protein C (P=0.033), protein S (P=0.006), antithrombin III (P<0.001), fibrinogen (P=0.016) and Homocysteine (P<0.001)), however, multivariate analysis showed a significant role for only Homocysteine (OR=0.957, 95%CI: 0.93-0.986, P=0.003) in predicting IBD. Regarding the results, it can be alleged that despite the significant difference in the level of Blood Coagulation Factors between the IBD and non-IBD patients, only the serum level of Homocysteine has a predictive role for IBD.
Abstract Background & Objective: Hepatic porphyria is an autosomal dominant disorder characterized by a deficiency in enzymes involved in hepatic porphyrin metabolism. Disruptions in this metabolic pathway can be precipitated by various factors, including physical exertion, psychological stress, fasting, infections, and drug withdrawal. Clinically, the condition manifests as episodic lower abdominal colic and a range of neuropsychiatric symptoms. Case Presentation: A 74-year-old male farmer presented with a four-month history of intermittent abdominal pain, abdominal distension, generalized weakness, and anorexia. The diagnosis of hepatic porphyria was established through a combination of imaging studies, laboratory investigations, liver biopsy, and genetic testing, which revealed a pathogenic c.587G>T (p.C196F) mutation in the FECH gene. The patient exhibited mild cutaneous lesions along with significant abdominal pain, abdominal distension, accompanied by constipation, nausea, and vomiting. Conclusion: This case highlights the diagnostic challenges and poor prognosis of hepatic porphyria when specific therapies are unavailable. Early recognition and genetic confirmation are vital for guiding management, and clinicians should suspect porphyria in patients with unexplained abdominal pain and liver dysfunction.
Abstract Background & Objective: Plasmacytoma is a rare plasma cell dyscrasia marked by localized monoclonal plasma cell proliferation, distinct from multiple myeloma by its lack of systemic symptoms. Extramedullary plasmacytoma (EMP), the rarest form, typically occurs in the upper respiratory tract. Cervical involvement is rare. Chronic inflammation may play a role in the development of cervical plasmacytoma, though this remains unproven for cervical cases. Case Presentation: We present a unique case of a 74-year-old woman who presented with vaginal bleeding linked to a neglected pessary inserted 15 years earlier. Upon examination, we discovered overgrown tissue with active bleeding. The biopsy revealed a monomorphic plasma cell infiltration, and immunohistochemistry confirmed CD138-positive, BCL2-negative cervical plasmacytoma, a rare occurrence in the cervix. Conclusion: This case highlights the importance of considering cervical EMP in atypical cytology and suggests a possible link to chronic pessary-induced inflammation. Early diagnosis through histopathology and immunohistochemistry is essential.
Abstract Background & Objective: Mucopolysaccharidosis (MPS) type III, or Sanfilippo syndrome, is an autosomal recessive lysosomal storage disorder caused by mutations in genes encoding enzymes responsible for glycosaminoglycan (GAG) degradation. This case report describes two siblings with MPS type IIIB who exhibit a rare compound heterozygous mutation in the NAGLU gene. Case Presentation: A 7-year-old girl and her 4-year-old brother were referred for evaluation due to learning disabilities, aggressiveness, and coarse facial features. Enzyme assay using tandem mass spectrometry on dried blood spots in both siblings revealed absent N-acetyl-α-glucosaminidase activity. Conclusion: Targeted sequencing confirmed the diagnosis, identifying two heterozygous mutations, an in-frame insertion and a missense mutation, in exon 3 of the NAGLU gene: c.214_237dup (p.Ala72_Gly79dup) and c.625A>C (p.Thr209Pro). This rare genetic finding in two siblings with Sanfilippo syndrome type B underscores the importance of precise mutation identification. Accurate characterization of defective gene variants may provide insights into potential targets for gene therapy in monogenic disorders.
Abstract Background & Objective: COVID-19 infection is known to affect the kidneys, potentially resulting in Acute Kidney Injury (AKI). In some patients, however, renal failure may necessitate hemodialysis following a COVID-19 infection. Pneumothorax, hemothorax, cardiac arrhythmias, and endocarditis are some complications associated with Permcath insertion, a type of vascular access used in hemodialysis. Case Presentation: In this report, we present a 29-year-old man who suffered from endocarditis following hemodialysis treatments through a Permcath because of acute renal failure following COVID-19. Removing the large masses (3×3 cm) inside the right atrium (RA) and taking out the Permcath was completed surgically. Conclusion: A suitable Permcath and its accurate insertion are recommended to provide prompt AKI treatment and prevent further complications, such as endocarditis and thrombosis.
Abstract Tumor-infiltrating lymphocytes (TILs) form a pivotal part of the immune system’s defense against cancer, and their density, composition, and spatial distribution reflect both tumor biology and the degree of host immune activation. Across multiple carcinoma types—including breast, lung, colorectal, ovarian, and head and neck cancers—recent clinical studies and meta-analyses have shown that high levels of TILs, especially CD8⁺ cytotoxic T cells, are consistently linked with improved prognosis and enhanced responsiveness to chemotherapy and immune checkpoint inhibitors. Standardized assessment tools, such as the Immunoscore in colorectal carcinoma and stromal TIL evaluation guidelines in breast cancer, have improved reproducibility and clinical relevance. TILs not only act as prognostic and predictive biomarkers but are also being harnessed as therapeutic agents in emerging immunotherapy strategies, including adoptive cell therapy. Despite these advances, variability in evaluation methods and the functional heterogeneity of TIL subsets remain challenges. Standardization of assessment protocols and deeper characterization of TIL phenotypes will be essential to fully integrate these immune markers into routine oncology practice and optimize their potential in precision medicine.
Abstract In placental histopathology, the Langhans' fibrinoid layer holds a unique but often overlooked position. Although it was described over a hundred years ago and featured in classic medical texts, it has gradually faded from modern research. Langhans' fibrinoid is one of the most underappreciated and inconsistently described parts of placental structure. In this article, we revisit its historical roots, anatomical ambiguity, and potential clinical significance, aiming to give it a clear and updated definition in current placental studies and diagnostics.
Abstract Pathology is one of the most important and complex fields of medicine, focusing on the study and diagnosis of diseases through the analysis of tissues and cells. Recent advancements in artificial intelligence (AI) have brought significant transformations to many areas of medicine, including pathology. With its ability to process large datasets, perform deep learning, and analyze images, AI has improved the accuracy, speed, and efficiency of disease diagnosis. This article explores the role of artificial intelligence in the future of pathology and its impact on diagnostic, therapeutic, and educational processes within this field.
Abstract Background & Objective: Acute Myeloid Leukemia (AML) is a biologically diverse malignancy influenced by genetic abnormalities, with TP53 mutations playing a key role. Found in 5–10% of de novo AML and more common in therapy-related and secondary AML, TP53 mutations correlate with poor prognosis, chemoresistance, and reduced survival due to defective apoptosis and increased leukemic proliferation. These mutations often coexist with complex karyotypes and are more frequent in older patients, highlighting the need for improved prognostic tools and targeted therapies. This systematic review assessed the prognostic impact of TP53 mutations on overall survival (OS) and relapse-free survival (RFS) in adult AML. Methods: Following PRISMA guidelines, PubMed, Scopus, and Web of Science were searched through January 2025 for studies reporting OS and/or RFS by TP53 mutation status in adult AML. Data on study design, patient demographics, mutation frequency, and outcomes were extracted. Pooled hazard ratios (HRs) for OS and RFS were calculated using a random-effects model. Results: A total of 65 studies comprising over 6,000 adult AML patients were included in this systematic review and meta-analysis. The pooled HR for OS in TP53-mutated patients was 2.22 (95% CI: 2.08–2.37), indicating significantly worse survival than wild-type patients. For RFS, the pooled HR was 2.25 (95% CI: 1.98–2.56), reflecting a higher relapse risk. Heterogeneity was moderate for OS (I²=71%, p<0.01) and low for RFS (I²=0%, p=0.58). Conclusion: TP53 mutations strongly predict poorer overall and relapse-free survival in adult AML, supporting their integration into clinical risk models and emphasizing the need for novel therapeutic approaches in this high-risk subgroup.
Abstract Background & Objective: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, which can progress to fibrosis and cirrhosis. Serum ferritin has been proposed as a biomarker for liver disease, but its relationship with fibrosis severity in NAFLD remains unclear. This study explored the relationship between serum ferritin levels and liver fibrosis severity in NAFLD patients. Methods: In this cross-sectional study, 204 NAFLD patients were enrolled, including 139 with mild fibrosis and 65 with severe fibrosis. Baseline and demographic characteristics were compared between groups. Serum ferritin and other biochemical parameters were measured. Logistic regression analyses assessed the predictive value of serum ferritin levels for liver fibrosis severity, and a receiver operating characteristic (ROC) curve determined the optimal ferritin cutoff for identifying sever fibrosis. Results: Patients with severe fibrosis had significantly higher serum ferritin levels than those with mild fibrosis (197.70 ± 79.40 vs 95.70 ± 73.20, P<0.001). Logistic regression analysis confirmed a significant association between ferritin levels and fibrosis severity (OR = 1.015, 95% CI = 1.009–1.02, P<0.001). ROC analysis showed that ferritin distinguished severe from mild fibrosis with 80% sensitivity and 80% specificity at a cutoff of 129 ng/ml (AUC = 0.86). Conclusion: Elevated serum ferritin levels are associated with more severe liver fibrosis in NAFLD patients, supporting ferritin’s potential as a non-invasive biomarker for fibrosis severity. Further studies are needed to validate these findings and explore ferritin’s diagnostic and prognostic utility in diverse populations.
Amgad Ahmed Ezzat Othman, Mohamed S Hemeda, Khaled Mohamed Hassanein Mohamed, Mohammed Saad Ahmed, Ayman S Yassin, Mohamed Nabil Mohamed, Abd Elmoaty Arafat Abd Elmoaty, Mahmoud M. Khafagi, Mohammed Mostafa Mohammed Abdo Mostafa Mohammed Abdo, Mohamed Abdel Basit Ibrahim Mohamed
Abstract Background & Objective:Hepatitis B Virus (HBV) infection has highly negative consequences for the global population, with chronic hepatitis B (CHB) infection and the resulting hepatocellular carcinoma (HCC) representing one of the most concerning long-term outcomes. This study focuses on the use of several biomarkers (miRNA-122, HBcrAg, and M2BPGi) in liquid biopsies to evaluate their efficacy in detecting early-stage HCC and assessing risk in patients with CHB.Methods:This study included 90 participants. Of these participants, 30 had chronic hepatitis B (CHB), 30 had hepatocellular carcinoma with HBV (HCC), and 30 were healthy controls. Serum miRNA-122 was quantified with real-time PCR, and HBcrAg and M2BPGi were measured using ELISA.Results: MiRNA-122 had an AUC of 0.801 and a sensitivity of 85.2%, indicating the highest diagnostic performance among the studies evaluated. M2BPGi demonstrated strong performance, with an AUC of 0.84. By contrast, HBcrAg had a very weak discriminative value. These previously stated biomarkers can improve the peripheral non-invasive screening.Conclusion: In this initial cohort study, circulating miRNA-122 and M2BPGi demonstrate an unsuspected capacity to predict HCC differentiation in CHB patients. However, these are preliminary and have yet to be tested for robustness across multicenter studies with appropriately estimated sample sizes.
Abstract Background & Objective: Tumor necrosis factor-alpha (TNF-α) inhibitors are widely used in rheumatologic diseases but may increase the risk of primary tuberculosis (TB) infection or reactivation. Purified protein derivative (PPD) conversion is an important indicator of latent TB in immunosuppressed patients. This study aimed to determine the rate of PPD conversion and associated factors in patients receiving anti-TNF therapy. Methods: This prospective study included adults with rheumatologic diseases who initiated anti-TNF therapy between March 2021 and September 2023. Patients with prior TB, previous anti-TNF exposure, or a positive baseline PPD were excluded. A PPD test was performed before treatment and repeated one year later. An induration ≥5 mm at follow-up was considered conversion. Results: Sixty patients completed the study (mean age 44.29 ± 14.70 years; 56.7% male). Six patients (10.0%) demonstrated PPD conversion after one year of anti-TNF therapy. Most conversions occurred in individuals with psoriatic arthritis (66.6%). No cases of active TB were detected clinically or radiologically. Statistical analysis showed no significant association between PPD conversion and age, sex, disease duration, anti-TNF type, methotrexate or corticosteroid use, diabetes mellitus, or hypertension. Psoriatic arthritis was the only factor significantly associated with conversion (P = 0.03). Conclusion: Ten percent of patients receiving anti-TNF therapy developed PPD conversion, indicating new latent TB infection. Psoriatic arthritis was significantly associated with conversion, while medication type and other clinical factors were not. These findings support routine annual TB screening in anti-TNF recipients, particularly in regions with moderate or high TB prevalence.
Abstract Background & Objective: Enhanced glucose uptake creates a hyperglycaemic environment that contributes to the oral carcinogenetic cascade but has received less attention and has not been fully elucidated. This study aimed to assess the levels of free and bound carbohydrates in saliva and serum among healthy individuals, subjects with potentially malignant disorders, and oral cancer/oral squamous cell carcinoma (OSCC) patients. Methods: A cross-sectional comparative study was conducted among 90 subjects randomly selected based on clinical and histological criteria and allocated into three groups: Group 1, healthy individuals (n = 30); Group 2, potentially malignant disorders (n = 30); and Group 3, OSCC cases (n = 30). Saliva and serum samples were collected and subjected to biochemical analysis for carbohydrate level estimation. Descriptive statistics and the Mann–Whitney test were applied to assess differences between independent groups. Results: Mean salivary-bound total carbohydrate levels were 12.06 mg/dL, 37.67 mg/dL, and 65.45 mg/dL for Groups 1, 2, and 3, respectively. Mean serum-bound total carbohydrate levels were 30.39 mg/dL, 68.28 mg/dL, and 88.33 mg/dL for Groups 1, 2, and 3, respectively. Mean salivary-free total carbohydrate levels were 25.58 mg/dL (Group 1), 24.28 mg/dL (Group 2), and 53.13 mg/dL (Group 3), while mean serum-free total carbohydrate levels were 62.39 mg/dL, 74.01 mg/dL, and 193.68 mg/dL for Groups 1, 2, and 3, respectively. A highly significant increase was observed (P < 0.001). Conclusion: A substantial increase in serum and salivary total carbohydrate levels, particularly in bound forms, was observed across the three groups, highlighting the potential utility of carbohydrate levels as biomarkers for disease progression in oral cancer.
Nora Tawhid Abdelfattah El-Zohery, Sara Mohamad Abou-Fandoud, Asmaa Mohamed Saad Zaghloul Attaalla, Abeer Mohammed Amal Mohammed
Abstract Background & Objective: Laryngeal carcinoma is a common head and neck cancer with high morbidity and mortality. This study evaluates IDH1 immunohistochemical expression in pre-invasive and invasive laryngeal squamous cell lesions, its correlation with clinicopathological features, and its prognostic and therapeutic potential. Methods: A retrospective analysis of 65 laryngeal squamous cell lesion cases was conducted using IDH1 immunohistochemistry. Results: IDH1 expression significantly correlated with invasion status (intensity and H-score; p = 0.026, 0.025) and histopathological progression and grade (p = 0.033, 0.036). Two-year DFS and OS were 81.5% and 69%, respectively, with no significant association between survival outcomes and IDH1 H-score (p = 0.851, 0.225). Conclusion: According to our findings, increased IDH1 expression may be associated with features of aggressive tumor behavior and could hold clinical significance in laryngeal squamous cell lesions, potentially serving as a future therapeutic target.
Abstract Background & Objective: Pancreatic cancer is among the deadliest malignancies, with an increasing incidence and a 5-year survival rate below 10%. Due to the lack of sensitive and specific diagnostic markers, its identification remains challenging. Endoscopic ultrasound (EUS) has become an invaluable staging tool, particularly when CT scans fail to reveal masses. When combined with fine needle aspiration (FNA) or fine needle biopsy (FNB), EUS facilitates diagnostic confirmation. Methods: This cross-sectional study was conducted in 2023 at Shahid Sadoughi University of Yazd and involved 110 patients. Data on age, gender, pathology diagnosis, and findings from EUS, FNA, and FNB were retrospectively collected and analyzed using SPSS version 22. Results: Of the 110 patients, 74 (67%) were male and 36 (33%) were female, with a mean age of 61.5 years. Adenocarcinoma was the predominant diagnosis, accounting for 70% of cases. The most common clinical presentations were abdominal pain (observed in 75% of patients), jaundice, and weight loss. There was 85% agreement between EUS and pathological results. A malignant mass was identified in 69% of FNA cases, with the pancreatic head most frequently involved. Notably, diagnostic concordance between FNA and FNB reached complete agreement (100%) in lesions located in the pancreatic tail. Conclusion: The robust correlation between EUS and cytopathological findings and the outstanding agreement between FNA and FNB underscore the pivotal role of integrating these techniques for accurate pancreatic mass diagnosis. These findings validate the current diagnostic practices and provide new insights that can potentially improve patient outcomes.
Muskaan Arora, Saraswathy Sreeram, Adarsh Sugathan, Hema Kini, Pooja Suresh, Jyoti Kini
Abstract Background & Objective: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment and may hold prognostic significance in gastric cancer (GC). Limited data are available from the Indian population. Methods: In this retrospective study, CD68 immunohistochemistry was performed on 60 surgically resected gastric adenocarcinomas. TAM density was quantified as the average number of positive cells per high-power field and categorised into low and high groups using a cutoff of 50 cells/HPF. Associations with clinicopathological features were analysed using chi-square and logistic regression. Results: High TAM density was observed in 70% of cases and was significantly associated with larger tumor size (p = 0.05), increased tumor-infiltrating lymphocytes (p = 0.021), advanced pT stage (p = 0.007), lymph node metastasis (p < 0.001), and advanced clinical stage (p = 0.009). On multivariate analysis, lymph node metastasis remained an independent predictor of high TAM density (adjusted OR = 2.5; 95% CI: 1.02–6.2; p = 0.04). Conclusion: CD68+ TAM density correlates with adverse pathological features in GC and may serve as a useful prognostic marker for patient risk stratification.
Abstract Background & Objective: Breast cancer is a major global health concern, with HER2/neu overexpression observed in 15%-20% of cases, often indicating a more aggressive disease. It is important to accurately assess HER2 status using IHC and confirm it with FISH testing to guide targeted therapy decisions. The goal of this study was to improve HER2/neu detection in equivocal breast cancer cases, determine the rate of amplification in score +2 cases using FISH, and evaluate the correlation between FISH results and patient demographics such as age. Methods: This retrospective study analyzed 336 archived breast cancer cases with equivocal HER2/neu IHC scores (+2) from 2018 to 2024. IHC initially assessed HER2 expression, and ZytoLight® SPEC ERBB2/CEN 17 probes were used for FISH confirmation. Cases were classified into 5 ASCO-CAP 2023-defined groups based on HER2/CEP17 ratio and HER2 copy number. Final HER2 status guided clinical decision-making regarding eligibility for targeted therapy. Results: The majority of patients were female (91.1%) and aged 40-49 years (29.2%). HER2-negative status was most prevalent (71.1%), while 24.4% were HER2-positive. A significant association was found between gender and HER2 status (P = 0.002), with males showing higher HER2 positivity. A HER2/CEP17 ratio ≥2.0 was strongly associated with HER2 amplification (P = 0.0001). Conclusion: A significant association was observed between ERBB2 expression and gender, particularly with the HER2/CEP17 ratio, highlighting the importance of molecular profiling. Most patients (71.1%) belonged to Group 5, indicating HER2 negativity. These findings emphasize the clinical importance of precise HER2 testing, particularly in equivocal and male cases.
Maryam Lotfi, Mina Majdi, Parin Tanzifi, Tahereh Yousefi, Elham Nazar, Aysan Nozheh
Abstract Background & Objective: Squamous cell carcinoma (SCC) is characterized by infiltration of CD4+ and CD8+ T lymphocytes, which represent an early host immune response against malignant cells. This immune response may inhibit tumor progression and suppress malignancy. This study aimed to evaluate the density of CD4+ and CD8+ lymphocytes and their ratio within tumor nests and surrounding stroma in conventional laryngeal SCC. It also examined associations with prognostic factors such as regional lymph node metastasis, tumor histologic differentiation, vascular invasion, and perineural invasion. Methods: This retrospective study analyzed 54 laryngeal SCC samples from patients who underwent total laryngectomy and cervical lymph node dissection without prior neoadjuvant chemoradiation therapy. Immunohistochemistry was used to assess CD4+ and CD8+ T lymphocytes in tumor nests and surrounding stroma. Statistical analyses evaluated correlations between lymphocyte infiltration and prognostic factors, including lymph node metastasis, histologic differentiation, vascular invasion, and perineural invasion. Results: A significant association was found between high intratumoral CD8+ T lymphocyte density and a lower incidence of vascular and perineural invasion (mean, 10.9 cells/HPF vs 4.5 cells/HPF; p = 0.03). No significant correlations were observed between lymphocyte density and lymph node metastasis or tumor histologic differentiation. Conclusion: High intratumoral CD8+ T-cell infiltration correlates with reduced vascular and perineural invasion in laryngeal SCC, suggesting a protective role in limiting tumor invasiveness. These findings highlight the prognostic significance of CD8+ T lymphocytes and warrant further research into immune mechanisms affecting SCC progression and patient outcomes.
Mayada S Farrag, Mohamed S Hemeda, Ziad Emarah, Khaled El Naghy, Khaled Abdelwahab, Nesrine S Farrag, Afaf T Ibrahiem
Abstract Background & Objective: One of the most lethal as well as prevalent malignancies across the globe is colorectal cancer (CRC). MMP1, a certain type of matrix metalloproteinase, as well as EZH2, a histone methyltransferase, are gaining attention for their part in metastasis and tumor progression. This research analyses the expression of immunohistochemistry EZH2 and MMP1 in relation to colorectal carcinoma, and how these two proteins correlate with other clinicopathological features. Methods: An analysis was done retrospectively on 38 cases of colorectal cancer, which were formalin-fixed and paraffin-embedded. MMP1 and EZH2 staining were assessed immunohistochemically and correlated with the tumor’s stage, lymph nodes, clinical stage, and prognosis. Statistical analysis was conducted with SPSS version16.0 and a level of significance of p <0.05. Results: Markedly increased expression of EZH2 and MMP1 had a notable correlation with advanced T stage (p =0.01 and0.03) along with metastasis to the regional lymph nodes (p =0.027) and clinical stages III or IV (p =0.04 for EZH2 and p =0.023 for MMP1). Although both markers demonstrated a trend for decreased disease-free survival (DFS), neither achieved statistical significance for DFS or overall survival (OS). Conclusion: EZH2 and MMP1 overexpression were associated with aggressive clinicopathologic features (higher T stage, nodal involvement, and advanced clinical stage). However, neither marker showed a statistically significant association with overall survival (OS) or disease-free survival (DFS) in this cohort. Larger, adequately powered studies are required to clarify any potential prognostic value.
Abstract Background & Objective: Central nervous system (CNS) tumors display significant diversity in clinical behavior and morphology. Timely intraoperative diagnosis is critical for surgical decision-making. Squash cytology is a rapid, cost-effective tool for evaluating CNS lesions intraoperatively, especially where frozen section has limitations. This study aimed to assess the utility and diagnostic accuracy of squash cytology in the intraoperative diagnosis of intracranial and spinal cord space-occupying lesions, with correlation to histopathology. Methods: This prospective study included 57 patients undergoing surgery for CNS lesions at Government Medical College from January 2019 to June 2020. Intraoperative squash smears were prepared and stained with rapid hematoxylin and eosin. The cytological diagnosis was compared with paraffin-embedded histopathology. Statistical analysis was performed to evaluate sensitivity, specificity, diagnostic accuracy, and concordance in tumor grading. Results: Among the 57 cases, 91% were neoplastic and 9% were non-neoplastic. Meningioma (33.3%) and diffuse astrocytic/oligodendroglial tumors (28.1%) were the most common neoplasms. The diagnostic accuracy of squash cytology was 94.73%, with high sensitivity and specificity. Cytological grading matched histopathological grading in the majority of cases. Diagnostic errors were mainly observed in tumors with poor smearability, high cohesiveness, or crush artifacts. Conclusion: Intraoperative squash cytology is a valuable diagnostic adjunct in CNS surgeries. It offers high accuracy and rapid turnaround and is particularly useful in resource-limited settings. While histopathology remains the gold standard, squash cytology significantly aids intraoperative decision-making.
Abstract Background & Objective: Neonatal cholestasis (NC) is a significant clinical condition involving hepatobiliary dysfunction, often accompanied by immunological alterations regardless of etiology. Human leukocyte antigens (HLA) molecules, particularly classes I and II, play roles in autoimmune liver diseases. Previous studies showed inconsistent results regarding their expression in hepatocytes and cholangiocytes under normal and pathological conditions. This study aimed to evaluate immunohistochemical expression of HLA I and II in NC. Methods: A retrospective analysis included 45 pediatric NC cases: 27 with biliary atresia (BA), 13 with progressive familial intrahepatic cholestasis (PFIC), and 5 with idiopathic neonatal hepatitis (INH). Twenty normal liver samples from adult transplant donors served as controls. Immunohistochemistry was used to evaluate HLA I and II expression in hepatocytes and cholangiocytes. Results: Control livers lacked detectable HLA I and II expression. In NC cases, HLA I was expressed in hepatocytes (84.4%) and all cholangiocytes, while HLA II was expressed in both cell types across all cases. BA cases showed significantly higher cholangiocyte expression of HLA I (p = 0.001) and II (p < 0.001) compared to PFIC and INH. HLA I expression was linked to cholangiocyte proliferation (p = 0.005) and inversely with lobular inflammation (p = 0.027). Strong HLA II expression in hepatocytes correlated with severe portal inflammation (p = 0.048), while in cholangiocytes, to proliferation, neutrophilic cholangitis (p = 0.05), and mild lobular inflammation (p = 0.043). Conclusion: HLA I and II are upregulated in NC, especially in BA, which correlates with disease severity, suggesting a role in pathogenesis.
Abstract Background & Objective: CD155 is an immune checkpoint molecule that interacts with various activating and inhibitory receptors on T- lymphocytes and natural killer (NK) cells in the tumor microenvironment (TME). NK cells and tumor associated macrophages (TAMs) are major components of the immune TME. Methods: 85 cases of invasive breast carcinoma (IBC) were evaluated for immunohistochemical expression of CD155, CD56, and CD163. Results: CD155 was positive in 52.9% of cases, and was significantly associated with larger sized, higher grade, advanced stage tumors, positive lymphovascular invasion (LVI), and aggressive molecular subtypes of IBC. High density of CD56 stained tumor infiltrating NK cells was detected in 30.6% of cases, which was significantly related to larger sized, higher-grade tumors, and aggressive molecular subtypes. High density of stromal TAMs was detected in 55.3% of cases, and was significantly associated with large tumor sizes, higher grade, advanced stage, positive LVI, and aggressive molecular subtypes. CD155 expression was significantly correlated with the densities of NK cells and TAMs in TME. Conclusion: CD155 expression, high density of tumor infiltrating NK cells, and high density of stromal TAMs contribute to the progression of IBC. CD155 can play an important immunoregulatory role in the TME.
Supriya NovelTony, Shilpa M Bhimalli, Ganga S Pilli, Hemalatha K R, Prajna K Shetty
Abstract Background & Objective: Delayed Villous Maturation (DVM) is a histological hallmark in Gestational Diabetes Mellitus (GDM) pregnancies commonly observed after 36 weeks of gestation. It is associated with perinatal morbidity and mortality. Our study aims to assess DVM in the term placentas of GDM pregnancies and its association with its perinatal outcomes compared to normal pregnancies. Methods: A total of 120 term placentae from GDM and normal pregnancies were collected from the Obstetrics and Gynaecology Department for one year and subjected to histopathological examination to evaluate DVM and its association with placental morphology and perinatal outcomes. Results: The current study found statistically significant increased presence of DVM in GDM placentas and its association with placental weight, diameter, maternal weight, glycated haemoglobin and foetal weight. The present study also observed presence of DVM with chorangiosis in a GDM placenta. Conclusion: The present study has found a statistically significant association of DVM in GDM pregnancies with its perinatal outcomes compared to normal pregnancies. There is no antenatal ultrasound marker to detect placental DVM and adverse foetal outcomes caused due to it. Since there is risk of reoccurrence of DVM and type 2 diabetes in future pregnancies, identification of DVM in GDM pregnancies and its clinical association with foetal outcomes should be considered clinically important. This may explain the cause of intrauterine foetal deaths and adverse neonatal outcomes in the current pregnancy and indicating a need for comprehensive maternal care in future pregnancies to prevent perinatal outcomes by implementing Rescue by birth.
Abstract Background & Objective: Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disorder characterized by high spiking fevers, evanescent rash, arthritis, and systemic inflammation. Its diagnosis is challenging due to the lack of specific biomarkers and clinical overlap with infections, malignancies, and autoimmune diseases. Case Report: We present the case of a 20-year-old female with a two-year history of recurrent fever, polyarthritis, and erythematous rash, accompanied by generalized lymphadenopathy and splenomegaly. Initial workup revealed severe anemia, leukocytosis, markedly elevated serum ferritin, and abnormal liver function tests. Infectious and malignant etiologies were excluded. Lymph node biopsies initially suggested dermatopathic lymphadenitis, but subsequent histology showed paracortical hyperplasia with features mimicking peripheral T-cell lymphoma. Immunohistochemistry revealed a polyclonal T-cell population and hemophagocytosis, leading to a revised diagnosis of reactive lymphadenopathy associated with AOSD. The patient fulfilled criteria for secondary hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome. High-dose corticosteroid therapy resulted in significant clinical and biochemical improvement. Conclusion: This case highlights the diagnostic complexities of AOSD with secondary HLH, particularly when lymph node histology mimics malignancy. Awareness of the varied lymph node patterns in AOSD and integration of clinical, laboratory, and immunohistochemical data are crucial for accurate diagnosis and timely management, preventing unnecessary interventions and improving outcomes.
Abstract Signet ring cell carcinoma (SRCC) of the breast is an exceptionally rare subtype accounting for only 0.04% to 2.7% of all breast cancers. Pure SRCC is characterized by the presence of >90% signet ring cells and exhibits an aggressive clinical profile often associated with higher histologic grade, lympho-vascular invasion, hormone receptor positivity, and low HER2 expression. Differentiating primary mammary SRCC from metastases from gastrointestinal primary, especially in elderly patients with bilateral presentations, is of prime importance. Immunohistochemistry plays a crucial role in this regard, with primary breast SRCCs displaying ER, GATA3, and CK7 positivity and CK20 and CDX2 negativity. We report a case of bilateral signet ring cell carcinoma of the breast in an 82-year-old female. This case highlights the significance of recognising SRCC breast as a distinct pathological entity and thorough evaluation in case of bilateral presentation, as it is exceptionally uncommon and poses diagnostic and therapeutic challenges.
Mahdi Abdorrashidi, Mohammad Hossein Peypar, Amirmohammad Tohidinia, Fatemeh Zali, Sobhan Eisazadeh, Mohammad Ali Abyazi, Mohammad Heiat
Abstract Background & Objective: Nonalcoholic fatty liver disease, recently recognized as metabolic dysfunction-associated steatotic liver disease (MASLD), is a key factor in the development of chronic liver disease and the progression of liver fibrosis. It plays a significant role in increasing the risk of cirrhosis and hepatocellular carcinoma. Given the rapid developments in this field, keeping information up-to-date is essential to prevent misconceptions and ineffective decision-making. This study employs a scientometric approach to review scientific literature and analyze recent findings, offering a comprehensive overview of the current state of research in this field. Methods: In this approach, we explored data related to publication metrics, public perceptions, scientific conference, mobile apps, AI tools, and new medications. This was done using a set of keywords, including "Non-alcoholic fatty liver disease," "Metabolic dysfunction-associated steatotic liver disease," "Mobile application," and "Artificial intelligence." Results and Conclusion: This research highlights significant scientific advances in the field of MASLD, including major scientific meetings, highly cited publications, and the latest FDA-approved therapies. In addition, it examines emerging digital tools and public search frameworks, providing a structured picture of recent developments. These findings provide a comprehensive view of the dynamic MASLD research landscape and emphasize the roles of AI, mobile apps, and emerging therapies in its management.
Abstract Background & Objective: Atypical squamous cells (ASC) are the most common epithelial abnormalities found in cervical cytology reports. The clinical significance of ASC and atypical glandular cells (AGC) varies, making clinical management and follow-up challenges. Methods: All women diagnosed with ASC or AGC in the past 4 years and referred to a tertiary hospital were included. The study evaluated regression, persistence, or progression to significant abnormalities over a two-year follow-up period. Results: Out of 22,386 cervical cytology smears, 208 (4.8%) patients were diagnosed with ASC (ASC-US: 3%, ASC-H: 1.8%) or AGC (0.25%). Among ASC-US patients with documented follow-up, 11 (46%) showed significant abnormalities, while 13 (54%) showed insignificant abnormalities. In the ASC-H group, with available follow-up, 20 (72%) showed significant abnormalities, and 8 (28%) showed insignificant abnormalities. When considering ASC-US and cervical intraepithelial neoplasia 1 (CIN 1) as low-grade lesions, 19 (31%) patients with ASC-H had low-grade, and 13 (69%) had high-grade abnormalities. In the ASC-US group, 10 (99%) patients had low-grade lesions, while only 1 (1%) had high-grade lesions. Among AGC, not otherwise specified (NOS) patients with follow-up, 17 (65%) had significant lesions, and 9 (35%) had insignificant lesions. All 13 patients with AGC, favor neoplastic (FN)/adenocarcinoma in situ (AIS), showed significant lesions. Conclusion: While patients diagnosed with ASC-H and AGC are at a higher risk for significant lesions, ASC-US patients may also develop significant lesions. Thus, ASC-US is clinically significant, and these patients should be closely monitored.
Sadegh Masjoodi, Mohammad Hossein Anbardar, Mansoureh Shokripour, Navid Omidifar
Abstract Background & Objective: Whole Slide Imaging (WSI) has emerged as a transformative technology in the fields of clinical diagnostics, medical education, and pathology research. By digitizing entire glass slides into high-resolution images, WSI enables advanced remote collaboration, the integration of artificial intelligence (AI) into diagnostic workflows, and facilitates large-scale data sharing for multi-center research. Methods: This paper explores the growing applications of WSI, focusing on its impact on diagnostics through telepathology, AI-powered diagnoses and precision medicine, and educational advancements. In this report, we will highlight the profound impact of WSI and address the challenges that must be overcome to enable its broader adoption. Results & Conclusion: Despite its many advantages, challenges such as infrastructure limitations and regulatory issues need to be addressed for broader adoption. The future of WSI lies in its ability to integrate with cloud-based platforms and big data analytics, continuing to drive the digital transformation of pathology.
Abstract Extracellular vesicles (EVs) are cell-derived vesicles that play a critical role in host-pathogen interactions, facilitating intercellular communication and transporting both pathogen- and host-derived molecules during infection spread. To regulate their environment, for instance, by modulating innate and adaptive inflammatory immune responses, pathogens may alter the composition of EVs produced by infected cells. Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and Helicobacter pylori infection is considered a significant risk factor for its development. This cancer is characterized by significant inflammation mediated by EVs generated from infected host cells. H. pylori contributes substantially to inflammation, promoting disease progression. Moreover, H. pylori produces and releases vesicles known as outer membrane vesicles (H. pylori-OMVs), which contribute to the shrinkage and cellular transformation of the gastric epithelium. Although the vacuolating cytotoxin A (VacA) plays a critical role in pathogenesis, its association with EVs in H. pylori has not been previously addressed. Understanding the roles of extracellular vesicles and VacA during H. pylori infection—whether they benefit the host or the pathogen—could pave the way for new treatment approaches. This review briefly discusses the role of VacA and extracellular vesicles in the growth and pathogenesis of H. pylori.
Abstract Background & Objective: Subtyping non–small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is crucial for selecting appropriate molecular tests, as driver mutations are often subtype-specific. This study aimed to evaluate the utility of TTF-1, Napsin A, p40, and p63 immunohistochemical (IHC) markers in subtyping NSCLC on small biopsies, with the goal of identifying a minimal marker panel. Methods: This retrospective, cross-sectional study was conducted at Kasturba Medical College, Mangalore, from January 2014 to December 2020. All NSCLC cases diagnosed during the study period were included. Immunohistochemical expressions of TTF-1, Napsin A, p40, and p63 was evaluated and correlated with morphological findings. Results: Ninety-five NSCLC cases were included: adenocarcinoma (n = 35), squamous cell carcinoma (n = 57), and NSCLC-not otherwise specified (NOS) (n = 2). IHC reclassification based on marker expression resulted in six ADC cases retyped as SCC and eight SCC cases retyped as ADC. TTF-1 and Napsin A expression were significantly associated with adenocarcinoma (p < 0.001), while p40 and p63 expression were significantly associated with SCC (p < 0.001). Conclusion: IHC is essential in overcoming the diagnostic limitations of small biopsy specimens, especially in morphologically heterogeneous tumors. A minimal panel comprising TTF-1 and p40 is sufficient for accurate subtyping of NSCLC and can help preserve tissue for downstream molecular testing.
