Iranian Journal Of Pathology
Volume:18 Issue: 3, Summer 2023

Recently, prevalence of hepatitis B virus (HBV), and hepatitis C virus (HCV) co-infection with Human immunodeficiency virus (HIV), has dramatically increased worldwide due to their shared routes of transmission. Compared to sporadic infection with HIV, HBV, and HCV, concurrent infection with these agents increases the effects and complications of these viruses. Furthermore, co-infection may also alter therapeutic strategies against HIV. Accordingly, choosing appropriate biomarkers to detect these co -infections is one of the main concerns in the field of diagnostic pathology. Up to now, several markers have been introduced for simultaneous diagnosis of HIV, HBV, and HCV. In this regard, serum adenosine deaminase activity (ADA), Fibro Tests, AST-to-Platelet Ratio Index (APRI), Fibrosis-4, Hyaluronic acid, and micro ribonucleic acids have been investigated as potential biomarkers for diagnosis of HIV-HCV/HBV co-infections. This work summarizes the diagnostic value of current and emerging biomarkers in HIV patients concurrently infected with HBV and HCV.

From the beginning of the COVID-19 epidemic, clinical laboratories around the world have been involved with tests for detection of SARS-CoV-2. Currently, RT-PCR (real-time reverse transcription polymerase chain reaction assay) is the gold standard for identifying the virus. Many factors are involved in achieving the highest accuracy in this test, including parameters related to the pre-analysis stage. Having instructions on the type of sample, how to take the sample, and its storage and transportation help control the interfering factors at this stage. Studies have shown that pre-analytical factors might be the cause of the high SARS-CoV-2 test false-negative rates. Also, the safety of personnel in molecular laboratories is of utmost importance, and it requires strict guidelines to ensure the safety of exposed individuals and prevent the virus from spreading. Since the onset of the outbreak, various instructions and guidelines have been developed in this field by the institutions and the Ministry of Health of each country; these guidelines are seriously in need of integration and operation. In this study, we try to collect all the information and research done from the beginning of this pandemic in December 2019- August 2022 concerning biosafety and protective measures, sample types, sampling methods, container and storage solutions, sampling equipment, and sample storage and transportation for molecular testing of SARS-CoV-2.

The progression and recurrence of urothelial carcinoma (UC) are correlated with carcinoma in situ and urothelial dysplasia. It is frequently challenging to distinguish dysplasia and carcinoma in situ from reactive atypia only based on histological characteristics. In daily practices, 2 of the adjunct immunohistochemistry markers (cytokeratin 20 (CK20) and p53) are used in addition to the histology to diagnose carcinoma in situ. This is accomplished by combining histological research results with immunohistochemistry. This systematic review summarizes the current findings on the diagnostic significance of p53 and CK20 as adjunct markers to urine cytology in the detection of UC. A systematic search of the relevant literature was conducted using PubMed, Wiley Online Library, and ScienceDirect databases. After screening for the eligibility criteria, a total of 14 selected articles were reviewed. Data extraction included a total number of samples, specimen samples, type of cells, and outcome parameters (mainly sensitivity and specificity). Urine cytology alone had a sensitivity of 75%-85% and specificity of 66%-95%. CK20 with urine cytology staining showed improved sensitivity and specificity in the range of 77%-94% and 71%-100%, respectively; p53 immunostaining with urine cytology showed a sensitivity of 52%-86% and specificity of 80%-98%. The dual staining in combination with urine cytology showed comparatively higher sensitivity and specificity in the range of 70%-90% and 74%-100%, respectively. This was more evident for high-grade UC (HGUC). Overall, single or dual staining combined with urine cytology was effective in this detection and can be applied as an adjunct marker in urine cytology.

To gain insight into the pathogenesis and clinical course of COVID-19 from a historical perspective, we reviewed paraclinical diagnostic tools of this disease and prioritized the patients with a more severe form of disease admitted to intensive care units (ICUs). The objective was to better predict the course and severity of the disease by collecting more paraclinical data, specifically by examining the relationship between hematological findings and cytological variation of blood neutrophils and monocytes. This retrospective study was conducted on 112 patients with confirmed COVID-19 admitted to Imam Hossein Hospital (Tehran, Iran) from August to September 2020. Peripheral blood smears of these patients were differentiated according to several cytological variations of neutrophils and monocytes, and the correlation to the severity of the disease was specified. The mean percentages of degenerated monocytes, degenerated granulocytes, and spiky biky neutrophils were significantly different among critical and non-critical patients (P<0.05). Degenerated monocytes and granulocytes were higher in critical patients as opposed to spiky biky neutrophils, which were higher among non-critical ones. Comparing the peripheral blood smears of COVID-19 patients (regarding pulmonary involvement in chest computed tomography [CT] scans [subtle, mild, moderate, and severe groups]), the twisted form of neutrophils was significantly higher in the subtle group than in the mild and moderate groups (P=0.003). Different cytological morphologies of neutrophils and monocytes, including degenerated monocytes, degenerated granulocytes, and spiky biky and twisted neutrophils, could help to predict the course and severity of the disease.

Brain tumors are the most frequent solid tumors in children. High-grade tumors are more challenging in diagnosis. Atypical teratoid rhabdoid tumor (ATRT) may be mistaken for other high-grade brain tumors. Molecular genetic analysis of ATRT has shown deletion and mutation in the hSNF5/INI1 gene in most of the cases. The INI1 protein expression can be helpful for the accurate diagnosis.

In this study, immunohistochemical staining  (IHC) using INI1 antibody was performed to determine the possibility of ATRT misdiagnosis. Totally, 147 tumors including 6 ATRTs, 81 medulloblastomas, and 60 other CNS tumors were examined in children between 0 and 17 years old.

No nuclear staining was found in the six ATRT cases, while most of other CNS tumors demonstrated nuclear staining. Five cases were previously diagnosed with medulloblastoma, primitive neuroectodermal tumor (PNET), and anaplastic oligodendroglioma, while the diagnoses were changed to ATRT based on the re-evaluation of the H&E slides and INI1 study. Additionally, two cases were recurrent tumors whose features were consistent with those of ATRT. The INI1 immunostaining was negative in these cases.

INI1 was very helpful in distinguishing ATRT from its mimickers in challenging cases. All known ATRT cases in this study were immunonegative for INI1. Thus, INI1 is recommended to be used in the initial IHC panel for the high-grade brain tumors, especially in children under the age of three years, so that they can benefit from intensified therapeutic regimens.

Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a worldwide pandemic. The first case of COVID‐19 was reported from Wuhan in the Hubei Province of China in December 2019; however, the disease's origin is still mysterious. Whole-genome sequence analysis is essential for monitoring the spread of infectious diseases as well as studying the pathogenesis and evolution of viruses. In this study, analysis of 198 fully sequenced genomes from Iran and West Asia was carried out to study mutations, phylogeny, amino acid changes, clades, and lineages of these genomes as well as comparison of these sequences with those of reference Wuhan genome of NC_045512.2.

In total, 198 completely sequenced genome data from Iran and West Asia were collected from GenBank. Mutation detection was carried out using a trial version of CLC Genomics Workbench v.21.0 (QIAGEN, Germany). Online tools such as GISAID Mutations App and Pangolin were used for further analysis of the results.

In this study, several unique mutation sites were identified in the Iranian genomes (n = 8); positions 1397 G>A and 29742 G>T were the most frequent changes in more than 85% of the Iranian genomes. Mutation rate, mutation per sequence, and transition versus transversion for the Iranian genomes included 4.73, 14.14, and 1.6, respectively. Generally, C>T alteration was the most common substitution in all the sequences.

The ORF1ab, N, and S were the genes with the most changes. The current data can help researchers predict future epidemics and establish better strategies to control viral pandemics.

Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal.

Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively.

A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086).

There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC.

p16 is a tumor suppressor gene, loss of which is usually associated with poor epithelial differentiation, resulting in tumor progression, which correlates with aggressive clinical behavior and poor prognosis. CDK 4/6 inhibitors can be used as a therapeutic target in p16 negative cases. Bladder cancer is one of the most prevalent cancers, prognosis of which depends not only upon the histopathological type, grade, and invasiveness but also on many other factors. The purpose of this study was to examine p16 expression in bladder urothelial carcinoma among the people who receive treatment at a tertiary care facility in Chattogram, Bangladesh.

At the Department of Pathology, Chittagong Medical College we did this cross-sectional study from July 2019 to September 2021. The study included fifty-one cases of primary urothelial bladder cancer for histopathological examinations. Immunostaining was done by using a primary antibody against p16.

Among the 51 cases, twenty-six cases (51%) showed positive p16 expression. The proportion of patients with high-grade (66.7%) and muscle-invasive (86.4%) tumors were more prone to show p16 negativity.

The result of this study shows the high grade and muscle-invasive urothelial bladder cancer is linked to reduction of p16 expression, which may provide additional prognostic information to stratify the high-risk patients and can also guide treatment plans, being a therapeutic target.

Talin-1 is a constituent of the multiprotein adhesion complexes that play  main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess  expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients.

The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Thereafter, immunohistochemical (IHC) staining was used to study the expression patterns of the talin-1 protein using 46 paraffin-embedded OSC tissue specimens, 25 benign tumors, and 20 normal tissues, which were assembled in tissue microarrays (TMAs). We also assessed the potential association between the expression of the talin-1 protein, various clinicopathological parameters, and survival outcomes.

Our IHC examination for talin-1 was significantly overexpressed in OSC tissues compared to benign tumors and normal tissues. The Kaplan-Meier survival analysis has also indicated statistically significant differences in terms of disease-specific survival (DSS) and progression-free survival (PFS) between the patients with high and low expression levels of talin-1, respectively.

The talin-1 protein was overexpressed in OSC tissues, and a high expression level of talin-1 was found to be significantly associated with tumor aggressiveness and poorer DSS or PFS. Therefore, talin-1 may serve as a molecular marker of cancer progression and a novel prognostic biomarker in these patients.

Some of the patients with myelodysplastic syndrome (MDS) are categorized as good prognosis based on the Revised International Prognostic Scoring System (IPSS-R). However, these patients may have poor clinical outcomes. It seems that the current diagnostic tools and IPSS-R cannot consider genetic factors for determining the prognosis of MDS patients.

This cross-sectional study included all adult MDS patients of both genders who were admitted from March 2015 to March 2020 to the Hematology wards of two educational tertiary hospitals in Iran (Namazi and Faghihi, affiliated with Shiraz University of Medical Sciences). Study data included relevant retrospective data from medical records and the results of immunohistochemical p53 staining on bone marrow biopsies.

Of the 84 patients, 65 (77.4%) showed p53 expression in bone marrow. They had shorter median survival than those without p53 expression. Considering both variables of P53 IHC results and IPSS-R score, the patients who died with low-risk IPSS-R score presented high p53 expression.

This study shows that the investigation of p53 expression by IHC at the time of diagnosis is a valuable indicator of survival rate in MDS patients. These data suggest that the immunohistochemical analysis of p53 can be a prognostic tool for MDS and should be used as an adjunct test to make decisions on the best therapeutic choice.

Invasive breast carcinoma (IBC) is the most commonly diagnosed cancer among women in India. The conventional visual method of evaluation of Tumor-Stroma Ratio (TSR) and Stromal Tumor-Infiltrating Lymphocytes (sTIL) appears to be subjective. The present study aims to evaluate the utility of the indigenously designed square grid method for the evaluation of tumor-stroma ratio and stromal tumor-infiltrating lymphocytes in invasive breast carcinoma by assessing the inter-observer variability.

This was a retrospective study conducted at a rural tertiary care referral institute from July 2018 to June 2020. In each case, microphotographs were taken from 10 representative fields in H&E-stained sections for evaluating TSR in low-power and sTIL in high-power. Both the parameters were evaluated employing an indigenously designed square grid applied onto microphotographs in the power-point slides by making use of principles of the Pythagorean theorem. Both parameters were separately evaluated by two pathologists. Cohen kappa statistics was the statistical tool used to analyze inter-observer variability.

Thirty cases were analyzed. Invasive breast carcinoma of no special type (IBC-NST) was the most common histopathological type (26 cases (86.67%)). For TRS evaluation, a Kappa value of 0.78 suggested substantial agreement with an agreement of 91.67%. For sTIL evaluation, a Kappa value of 0.51 suggested moderate agreement with an agreement of 88.33%. The P-values were statistically highly significant (P<0.001).

Square grid method is a novel technique for evaluating TSR and sTIL in invasive breast carcinoma. It can be considered an example of the application of Pythagoras’ theorem in Pathology.

Since December 2019 in Wuhan, China there is a new form of pneumonia and after expansion in other countries, World Health Organization (WHO) called it Coronavirus Disease 2019 (COVID-19). Since the clinical laboratory findings have played an important role in the progression of the disease, this study aimed to evaluate the laboratory findings in COVID-19 patients (before vaccination).

In this case-control study that was conducted from February to August 2020; the laboratory test status in 101 positive COVID-19 patients was evaluated and compared with 101 healthy individuals.

The results of our study showed that 21% of patients had low WBC, 24.75% low RBC, 37.62%, low Hb, 18.81% with low HCT, 29.7%, low Plt, 41.58% had High PT, 71.29% high CRP, 17.82% high urea, 11.88% high CR, 15.84% high LDH, 10.89% low sodium, 14.75% low potassium (K). The quantitative examination of blood factors showed that lymph%, mixed%, PLT, HCT, Hb, and RBC were higher in the control group than in the case group. While Neu%, WBC, PTT, CRP, UREA, LDH, K in the patient group were higher than in the control group.

According to the results of the study, it can be concluded that in the clinical treatment of COVID-19 patients, much attention should be paid to the laboratory indicators to identify and intervene early in critically ill patients.

Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes are among the most important causes of infection in human. Inventing rapid methods to identify these species can help in providing appropriate and effective treatment options. Therefore, the current study aimed to develop a multiplex touch-down PCR method to identify rapidly the aforementioned species patients' sputum samples, simultaneously.

A total of 50 sputum samples of patients with respiratory infections resistant to treatment were collected. After DNA extraction and primer design, the complete capsule (CAP) region II, capsular polysaccharide biosynthesis (cpsA) and the structural regulator of transcription (spy) genes were amplified for detecting H. influenzae, S. pneumoniae and S. pyogenes by multiplex touch-down PCR.

Among 50 samples prepared from patients with different diseases, 27 samples were positive for amplified genes. The frequency of presence of pathogens in the collected samples included 14% H. influenzae, 20% S. pneumoniae and 20% S. pyogenes. Also, in some patients, the simultaneous presence of two or three pathogens were observed.

In general, it can be concluded that the PCR touchdown method developed in the present study is an effective and fast method for the simultaneous identification of H. influenzae, S. pneumoniae and S. pyogenes pathogens in clinical samples of patients.

Prostatic adenocarcinoma (PAC) is one of the most common tumors worldwide. Immunohistochemical expression of cytokeratins has been evaluated in the diagnosis and prognosis of tumors. The aim of the present study is the evaluation of Cytokeratin-7 (Ck-7) and Cytokeratin-19 (Ck-19) expression and its relationship with Gleason score in patients with PAC.

In this cross-sectional study, 78 samples from 78 patients with PAC referred to Mostafa Khomeini Hospital were gathered. Samples were immunohistochemically stained by Ck-7 and Ck-19 markers. The percentage of each marker in tumor cells was determined, and its relationship with Gleason scores and Gleason grade groups was analysed by SPSS version 24.

The expression of Ck-7 and Ck-19 were seen in 37.2% and 82.1% of samples, respectively. The mean of Ck-7 expression in tumor cells was 4.98%±7.19 (ranged 0 to 26%), while the mean of Ck-19 expression was 41.02%±23.36 (ranged 0 to 78%). There was no relationship between Ck-7 expression with Gleason scores and Gleason grade groups. However, Ck-19 expression was increased in higher Gleason scores and Gleason grade groups (P<0.001). No relationship was found between age and Ck-7 (P=0.309) and Ck-19 (P=0.375).

The Ck-7 expression in PAC samples is weak and focal and had no relationship with the Gleason scores and Gleason grade groups. However, Ck-19 expression in PAC was high and was associated with tumor dedifferentiation of samples. There was no relationship between the expression of both markers with the patient's age.

Viral infections are associated with the pathogenesis and progression of human malignancies. Several studies have suggested the role of viral infections in papillary thyroid carcinoma (PTC). However, the results are still conflicting, and the potential role of viruses in PTC tumorigenesis remains to be elucidated. In the present study, we aimed to investigate the presence of parvovirus B19, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1/HSV-2), and human papillomavirus (HPV) types 16 and 18 in PTC.

In this cross-sectional study, paraffin-embedded tissue blocks of 40 patients with PTC were used. Tissue blocks were studied for the presence of the virus genome using real-time polymerase chain reaction (PCR).

Of the 40 patients with PTC, there was 1 positive case of HPV (2.5%), while 6 cases were positive for parvovirus B19. HSV and CMV DNAs were not detected in any cases.

Correlations among HSV, CMV, and PTC are unexpected in our patient population. But parvovirus B19 and, to a lesser extent, HPV DNA genomes were detected in PTC using real-time PCR.

Malignant melanoma of the sinonasal area is a rare tumor that arises from melanocytes in the nasal mucosa and is more aggressive than the cutaneous type with a poor prognosis.We report a 60-year-old female with the initial chief complaint of nasal cavity fullness, continuous epistaxis, and nasal bone deformity in the past two months.In a primary examination, a black mass was found, and in an excisional biopsy, the pathologist reported sinonasal malignant melanoma, which was confirmed after IHC staining.In spindle cell tumors of the head and neck area, we should be aware of mucosal malignant melanoma as a differential diagnosis.