Iranian Journal of Pathology

Abstract Background & Objective: The coronavirus disease brought worldwide uncertainty, and Iran was affected by it as well as many other countries in the world. Halting face-to-face education due to social distancing and resident re-employment in clinical wards leads to defective education. The aim of this survey was to evaluate the advantages and disadvantages of modifications made in pathology residency education in Iran.
Methods: This online survey was conducted on all pathology residents in Iran. An online 30-item questionnaire was developed and used in this study.
Results: Sixty residents (88.3% female) participated in this survey. The majority (70%) of the residents were over 30 years old. Fifty percent of the responders reported that their personal life was influenced by the pandemic. Skyroom and Adobe Connect were the most common platforms for online education with overall satisfaction of 65%. The webinars were considered suitable by 51.7% of the responders. Concerns at work were reported by 48.3% of the residents, while 78.3% reported being exposed to the disease and 55% reported being infected. Concerns about transmission of the disease to family members were reported by 90% of the responders.
Conclusion: This study showed that the pathology residency modifications were successful in providing education. However, their social and educational life characteristics might affect their satisfaction with online education.

Abstract Background & Objective: FFA usually has a gradual subtle course and might be overlooked by physicians or misdiagnosed with other types of hair loss including androgenetic alopecia, traction alopecia, and other types of patterned alopecia. In this study, we described clinicopathological features of patients with FFA referring for skin biopsy. Methods: This is a retrospective cross-sectional study on 26 patients with a diagnosis of FFA based on clinicopathological features. Firstly, the demographic and clinical features of patients were extracted from an electronic database. Then, skin biopsy specimens were reviewed regarding the presence or absence of hair follicles, site and severity of infiltrations, and presence of fibrosis. Results: Most of the patients were over fifty years of age (57.7%) with a mean age of 50.73 ± 10.03 years. Frontal region involvement was observed in all of the cases. Eyebrow hair loss was observed in 38.5% of cases. The most frequent clinical findings were the absence of vellus hairs in frontotemporal regions (96.2%) and perifollicular erythema (92.3%). The most common pathological features were involvement of the vellus hairs (84.6%), replacement of follicular epithelium with fibrous sheath (80.8%), and destruction of sebaceous glands (69.2%). Peri-infundibular and peri-bulbar interface changes were observed in 50% and 61.5% of skin biopsies, respectively. Perifollicular fibrosis was demonstrated in half of the skin biopsies. Conclusion: FFA is most commonly observed in females after the 5^th decade of life. The absence of vellus hairs and the replacement of follicular epithelium with fibrous sheath are the most common clinical and pathological features of the disease, respectively.

Abstract Background & Objective: Hospital-acquired infections (HAIs) are a major healthcare problem in hospitalized patients, especially in developing countries, where they affect millions of patients and cause high mortality rates. This study aimed to investigate multidrug-resistant bacterial strains in NIs at Imam Khomeini University Hospital in Urmia, Iran.
Methods: This cross-sectional study was conducted using a convenience sampling method. The study population comprised all positive clinical samples from HAIs registered in the laboratory of Imam Khomeini Hospital, Urmia, Iran, in 2019. Bacteria were identified by culturing the samples on blood agar and MacConkey agar, followed by performing standard biochemical tests. Antibiotic susceptibility testing was carried out using the disk diffusion method, in accordance with CLSI guidelines.
Results: Of the 607 positive samples, the most common microorganisms isolated were Escherichia coli (27.5%), Acinetobacter baumannii (18.5%), and Klebsiella pneumoniae (15.2%). The distribution of resistance to the number of antibiotics in bacterial isolates from the samples showed that 19.8% of them were resistant to one antibiotic and 13.2% were resistant to three antibiotics. 40.5% of the samples showed no resistance to antibiotics.
Conclusion: This study highlights the critical issue of HAIs and the prevalence of multidrug-resistant bacteria in Urmia, Iran. Urgent measures, including improved hygiene, accurate diagnostics, appropriate antibiotic use, and stakeholder education, are essential. Establishing a robust HAI surveillance system is also recommended. Future efforts should aim at understanding and mitigating the spread of these pathogens.

Abstract Background & Objective: Mast cells play a role in the immune responses to fatty liver disease. The present study aimed to investigate the diagnostic value of hepatic mast cell concentration (MCC) in NAFLD and NASH severity and fibrosis grade.
Methods: The present cross-sectional unremarkable hepatic histology, NAFLD, or NASH cases were enrolled. Demographic variables, BMI, hepatic stiffness assessed using fibroscan, portal inflammation, hepatic disease grade assessed using the NAFLD Activity Score (NAS), and hepatic fibrosis severity assessed using the NASH fibrosis stage, hepatic necrosis severity, and hepatic steatosis severity of the patients were collected. The hepatic specimens underwent immunohistochemical (IHC) staining.
Results: Of a total of 92 patients with a mean age of 38.7±13.3 years, 56 (60.9%) were males. There were significant relationships between the NAS score of the patients and hepatic steatosis. Moreover, the NASH fibrosis stage had significant relationships with the variables of hepatic necrosis, steatosis, and stiffness. There were significant positive correlations between the mast cell concentration (MCC) in all zones of the hepatic tissue (zone 1, zone 2, zone 3, portal area, and total) and the variables of age, BMI, and hepatic necrosis, steatosis, and stiffness. The patients with a higher NASH fibrosis stage showed a significantly higher MCC in all zones of the hepatic tissue.
Conclusion: Hepatic mast cell number may have a significant impact on the grade and fibrosis in NAFLD. However, it is recommended to perform further studies with larger sample sizes on patients with various etiologies for hepatic injury to confirm the present study results.

Abstract Background & Objective:  Placenta provides nutrition and protection from various infections and toxins to the baby while they are in the mother’s womb. The present study was done to see the effects of coronavirus infection on the placenta of infected mothers and the final pregnancy outcome.
Methods: A total of 50 antenatal women (25 infected with coronavirus and 25 uninfected women) were enrolled and their placentae were examined for any significant histopathological changes. These changes were then correlated with the final pregnancy outcome.
Results: A significant number of placentae from infected mothers demonstrated features of maternal (54%) and fetal malperfusion (76%). However, no significant adverse pregnancy outcome was noted.
Conclusion: Increased rates of maternal malperfusion, and fetal malperfusion may be seen in placentae from infected women. However, these changes may not progress to any adverse fetal outcomes.

Abstract Background & Objective: CD24 is a small, highly glycosylated membrane protein whose expression is associated with tumorigenesis and the progression of several types of cancer. Prostate adenocarcinoma is one of the most common cancers in men, and microscopic Gleason grading is an important factor affecting prognosis. This study aims to investigate the relationship between immunohistochemical expression of CD24 and its relationship with benign prostatic hyperplasia (BPH) and Gleason grade in prostate adenocarcinoma.
Methods: This cross-sectional study was conducted on 163 patients, with an average age of 70.63±9.05 years, including 78 (47.9%) patients with prostate adenocarcinoma and 85 (52.1%) patients with benign prostatic hyperplasia., referred to Mostafa Khomeini Hospital in Tehran between 2018 and 2021, who underwent open prostatectomy or Trans Urethral Resection of Prostate (TURP). Immunohistochemical staining was used to evaluate CD24 expression, and Gleason grade was determined in the case of prostate adenocarcinoma. Data were analyzed with SPSS 22 and a P-value<0.05 was considered statistically significant.
Results: The percentage and intensity of CD24 staining in prostate adenocarcinoma patients was significantly higher than in BPH patients (P<0.05). Gleason score strongly correlated with the percentage and intensity of CD24 staining (P<0.05). The immunoreactive score, obtained by multiplying the CD24 expression percentage with staining intensity, was also significantly related to the Gleason score (P<0.05).
Conclusion: CD24 expression can be considered as a factor in differentiating cases of prostate adenocarcinoma from benign prostatic hyperplasia. Also, a high level of this marker can indicate the progress of prostate cancer.

Abstract Background & Objective: Diabetic patients often develop lesions called non-diabetic renal diseases (NDRD), whose prognostic and therapeutic implications vary from diabetic nephropathy (DN). Since early identification of NDRD is associated with a better prognosis, we aimed to understand its spectrum.
Methods: One hundred and thirty-four patients were included in a cross-sectional study. Their clinical, and laboratory data and indications for biopsy were recorded. Two cores of renal tissue were studied under light microscopy and immunofluorescence; patients were classified into NDRD, NDRD+DN, and DN groups.
Results: Of all the patients studied, five were diagnosed with type 1 diabetes mellitus (DM1), and the rest were type 2 diabetes mellitus (DM2). Overall, the male-to-female ratio was 3:1. The Mean age of NDRD patients was the greatest, and males were predominant in all three groups. CKD was the most common presentation. Except for significantly greater proteinuria and hematuria in the DN and NDRD groups respectively, others were not different. Infection-related glomerulonephritis was the most common lesion among the NDRD+DN group, whereas IgA nephropathy and acute tubulointerstitial nephritis were frequent in the NDRD group.
Conclusion: Based on our findings, renal biopsy should be considered in all those diabetic patients with lesser onset duration presenting with hematuria, no/minimal retinopathy, and minimal proteinuria. A precise diagnosis helps in providing timely therapy for NDRD and prolonging renal and patient survival.

Abstract Background & Objective: Breast cancer is thought to arise from non-invasive breast lesions, such as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). DCIS is considered a direct precursor of invasive carcinoma. The morphological features alone do not reflect the biological truth of this disease. Therefore, we investigated features of carcinoma in situ and the invasive components in women diagnosed with breast cancer.
Methods: This study was a cross-sectional study. The corresponding IHC slides were selected from the pathology archive and examined by the pathologist. Fifty-one samples which showed both in situ and invasive components confirmed immunohistochemically, were included in the study.
Results: In 70.6% of the cases a high grade of in situ and invasive carcinoma was observed. In 45.1% of the studied cases, a solid structure was observed in in-situ carcinoma, and no otherwise specified structure was observed in invasive carcinoma. In 74.5% of both in situ and invasive carcinoma types, ER.PR had a positive value. In 45.5% of the cases, both in situ and invasive carcinoma components show low Ki67. In 42.2%, both in situ and invasive carcinomas were Her2 negative. There was no significant difference between the grade (P=0.687), Her2 type (P=0.532), and structure (P=0.532). ER.PR (P=1.00) and Ki67 (P=0.180) of in situ and invasive carcinoma in this study.
Conclusion: Our study showed differences between in situ and invasive biomarker expression. According to our findings, owing to heterogeneity, in situ components can't be representative of invasive components for treatment choices.

Abstract Background & Objective: Subclinical hypothyroidism (SCH), is defined as an asymptomatic state characterized by a normal serum concentration of free thyroxine and elevated serum concentration of TSH. This study aims to investigate the complex interplay between hyperinsulinism, insulin resistance, beta cell function, and low-grade chronic inflammation in Iranian women with SCH. Methods: Eighty women with SCH and 80 healthy women as controls matched to the patient group for sex, age, and body mass index (BMI), were enrolled in this prospective cross-sectional study. TSH, free T3, free T4, highly sensitive C-reactive protein (hs-CRP), fasting insulin, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, HOMA-IR index, Beta cell function (HOMA-B index) and insulin sensitivity were determined. Results: Hs-CRP was not statistically different between the SCH patients and the control group (3.7±3.2 Vs 3.6±4.0, P>0.05). Total cholesterol and LDL-cholesterol were significantly higher; however, triglyceride and HDL-cholesterol were not statistically different in patients with SCH as compared with the control group. Fasting insulin levels and HOMA-IR and Beta cell function (HOMA-B) were significantly higher in SCH women compared to the control group. A positive correlation between HOMA-IR and HOMA-B with TSH levels was found (r=0.324, r=0.191, P<0.05 respectively). A positive correlation between insulin levels and hs-CRP (r=0.22, P<0.05), also between insulin levels and TSH (r=0.312, P<0.05) and LDL- LDL-cholesterol was obtained (r=0.27, P<0.05). Conclusion:  Iranian women with SCH may exhibit elevated atherogenic parameters (hyperinsulinemia, LDL-cholesterol, and total cholesterol), HOMA-IR, and HOMA-B.

Abstract Background & Objective: Hypervascularity is a characteristic feature of renal cell carcinoma (RCC) and microvessel density (MVD) predicts tumor metastasis. Nestin is a stem cell marker that is expressed in proliferating endothelial cells and newly formed vessels and Fms-related tyrosine kinase 1 (FLT1) is a proangiogenic factor. This study aimed to evaluate the expression of Nestin and FLT1 in RCC and their prognostic impact. Methods: This retrospective study included sixty cases of RCC after obtaining ethical approval. Sections were immunohistochemically stained by Nestin and FLT1 then their expressions were compared to different clinicopathological parameters. MVD was evaluated using Nestin and CD34 and compared to the different parameters. Results: Nestin was expressed mainly in endothelial cells of small vessels in 65% of cases while FLT1 was expressed in tumor and endothelial cells in 73.3% of cases. Their expressions were significantly associated with aggressive tumor parameters including larger tumors, high-grade tumors, wider tumor extension, and advanced stage. Moreover, Nestin expression was significantly associated with metastasis. MVD evaluated by Nestin showed more associations with larger tumors, high-grade tumors, wider tumor extension, advanced stage, and metastasis than MVD measured by CD34. Nestin and FLT1 positivity and high MVD measured by Nestin were significantly associated with short overall survival. Conclusion: Nestin and FLT1 expressions in RCC may be associated with aggressive tumor features and short patients’ overall survival. MVD evaluated by Nestin may be correlated with tumor progression and metastasis. Nestin and FLT1 may be used as prognostic biomarkers in RCC.

Abstract Background & Objective: Cerebrospinal fluid (CSF) analysis is helpful in the diagnosis of infections of the central nervous system (CNS), especially after neurosurgical procedures. This study aimed to evaluate the diagnostic value of CSF markers for diagnosis of post-neurosurgical meningitis (PNM). Methods: Patients with neurosurgical procedures whose CSF was obtained for any reason (meningitis and non-meningitis) during 2020 and 2022, at Imam Khomeini Hospital Complex, Tehran, Iran, were included. Serum and CSF lactate dehydrogenase (LDH), glucose, protein, white blood cells (WBC), red blood cells (RBC), and CSF/serum glucose and LDH ratio were compared between the patients who were diagnosed with PNM and those without meningitis. Results: A total of 115 patients were included, of whom 23 patients were diagnosed with PNM and 92 with non-meningitis. No significant differences were observed in patients’ age, gender, and underlying diseases between the two groups. Findings showed a significantly (P=0.029) lower level of the mean CSF glucose (59.5 mg/dL ±33.9) in patients with meningitis than in patients without meningitis (76.8 mg/dL ± 37.5). The mean CSF/serum glucose ratio was 43.7% in the meningitis group and 56.3% in the non-meningitis group (P=0.008). The mean WBC count and neutrophil dominance were significantly higher in the meningitis group. No significant differences were observed in CSF LDH, Protein, and RBC between the two groups. Conclusion: A CSF glucose level of less than 60 mg/dL, a CSF/serum glucose ratio of less than 0.44, and a higher CSF WBC and neutrophil count can help diagnose PNM.

Abstract Background & Objective: Antibiotic resistance in urinary tract infection (UTI) is increasing nowadays, therefore, the aim of this study was to evaluate the resistance patterns of many pathogens toward several antibiotics that are in common use in our hospitals.
Methods: Subculture and identification of pathogenic bacteria were performed on 1148 hospitals' bacterial primary cultures which were considered positive for UTI. An antibiotic sensitivity test was performed by using the disc diffusion method. The rates of resistance were statistically analyzed and correlated with the types of antibiotics and bacteria.
Results: It was found that 1148 out of 2087 urine samples were UTI positive, the majority of cases (76%) were from females (P<0.0001). Escherichia coli and Klebsiella were the most isolated Gram-negative bacteria, while Staphylococcus spp. was the most isolated Gram-positive pathogen. E. coli showed the highest resistance rate among all bacteria, while Streptococcus spp. was the most sensitive. The highest resistance was noticed to be against gentamicin and ampicillin, while the most effective drugs were imipenem and amikacin. There was a significant difference in resistance rates among the different bacterial categories (P<0.0001), while no significant difference was noticed in resistance rates among antibiotics categories (P>0.05).
Conclusion: Elevated rates of antibiotic resistance were noticed in this study in UTI-causing bacteria; therefore, it is highly important at least to every general hospital to investigate the antibiotic resistance rates occasionally to determine the proper antimicrobial treatment as well as re-evaluate antibiotics which were considered as empirical.

Abstract We report a 4.5-year-old girl with recurrent episodes of bilateral lower limb weakness following periods of upper respiratory tract infection since the age of 1.5 years. Nerve conduction velocity and electromyography studies suggested distal motor neuropathy. The whole exome sequencing analysis revealed a homozygous variant, c.955G>A (p.Gly319Ser), of the mitochondrial trifunctional protein α-subunit (HADHA) gene. This variant has already been reported as pathogenic in an Iranian consanguineous family with a probable diagnosis of Charcot-Marie-Tooth disease. In addition, this variant, in compound heterozygosity with another likely pathogenic variant, has been known to be linked with mitochondrial trifunctional protein deficiency.

Abstract Primary periocular histiocytoid carcinoma is a very rare malignant tumor. Until now, less than 50 cases have been reported in the English literature. It is characterized by resistant epiphora, limitation in extraocular motility, and ptosis. The definitive diagnosis of this lesion is made based on detecting histological histiocytoid features along with tracing positivity of specific biomarkers using immunohistochemistry. However, pathologists may be faced with two major obstacles in the diagnosis of this tumor including distinguishing it from metastatic histiocytoid lesions and also from benign mimics such as reactive inflammatory lesions. Here, we describe a case of primary periocular histiocytoid carcinoma located on the eyelid as well as review the literature to clarify the histopathological and diagnostic features of this tumor. 

Abstract Dear Editor, I found the recent publication by Andrianto et al. (1) in the Iranian Journal of Pathology, titled "α-Smooth Muscle Actin as Predictors of Early Recurrence in Early-Stage Ductal Type Breast Cancer After Mastectomy and Chemotherapy," intriguing. This study, employing a cross-sectional immunohistochemical approach, investigates the significance of α-smooth muscle actin (α-SMA) as a potential biomarker for early recurrence in invasive ductal adenocarcinoma (IDC) of the breast. In the current era of precision medicine, it is apt to be on the look for novel biomarkers in predictive oncology, especially in breast cancer which remains one of the leading causes of cancer-related mortality in women despite scientific advancements. However, it's crucial to thoroughly understand the scientific methodology to fully grasp the paper's findings and utilize the same in clinical practice or research settings.