Iranian Journal of Pathology

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.

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.

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.

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.

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.

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.