فهرست مطالب

Pathology - Volume:16 Issue: 1, Winter 2021

Iranian Journal Of Pathology
Volume:16 Issue: 1, Winter 2021

  • تاریخ انتشار: 1399/09/20
  • تعداد عناوین: 14
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  • Maryam Anvari, Atoosa Gharib, Maryam Abolhasani, Aileen Azari-Yaam, Farzaneh Gharalari, Moeinadin Safavi, Ali Zare-Mirzaie, Mohammad Vasei * Pages 1-19

    Molecular assays for detection of nucleic acids in biologic specimens are valuable diagnostic tools supporting clinical diagnoses and therapeutic decisions. Pre-analytical errors, which occur before or during processing of nucleic acid extraction, contribute a significant role in common errors which take place in molecular laboratories. Certain practices in specimen collection, transportation, and storage can affect the integrity of nucleic acids before analysis. Applying best practices in these steps, helps to minimize those errors and leads to better decisions in patient diagnosis and treatment. Widely acceptable recommendations, which are for optimal molecular assays associated with pre-analytic variables, are limited. In this article, we have reviewed most of the important issues in sample handling from bed to bench before starting molecular tests, which can be used in diagnostic as well as research laboratories. We have addressed the most important pre-analytical points in performing molecular analysis in fixed and unfixed solid tissues, whole blood, serum, plasma, as well as most of the body fluids including urine, fecal and bronchial samples, as well as prenatal diagnosis samples.

    Keywords: Body Fluids, Formaldehyde, Nucleic Acids, Pre-Analytical Phase
  • Mitra Rezaei, Mahboobeh Karimi-Galougahi, Azin Kheradmand *, Mihan Pourabdollah Toutkaboni, Hassan Mir Mohammad Sadeghi, Alireza Abdollahi, Amirnader Emami Razavi, Ali Safavi Naini, Farahnaz Bidari- Zerehpoosh Pages 20-26
    Background & Objective

    Human papillomavirus (HPV) has been associated with prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Similar to the global studies, different prevalence rates of this viral infection have been reported in Iran. Therefore, we aimed to report the prevalence of this virus and its significance in HNSCC patients.

    Methods

    Patients who were referred to the five hospitals of Tehran city from May 2018 to May 2019 were enrolled in this study. All patients were diagnosed with HNSCC based on pathologic study. The pathologic disease staging was defined, and DNAs were extracted from the fresh tissue samples via kits. After polymerase chain reaction (PCR), HPV positive samples were evaluated for determining genotypes and data analysis.

    Results

    Of the 46 patients, three patients (6.5%) had positive HPV with the following subtypes: 18 (in two patients), 52 (in three patients), 61 (in two patients), 67, and 73. Comparison of variables between the groups with and without HPV showed a significant difference based on the tumor’s lymphatic invasion (p =0.041), peripheral lymph node involvement (p =0.008), and histologic grade (p =0.011), but there was no statistically significant difference in terms of other variables such as age, primary tumor site, size, pathologic stage, vascular or perineural invasion, metastasis, smoking, and alcohol consumption.

    Conclusion

    HPV positivity is an important factor in the lymphatic invasion, peripheral lymph node involvement, and histologic grade of cases with HNSCC and should be further investigated for its effect on prognosis.

    Keywords: Human papillomavirus, Squamous cell carcinoma, Iran
  • Armin Borhan *, Zohreh Nozarian, Alireza Abdollahi, Reza Shahsiah, Hadiseh Mohammadpour, Arash Borhan Pages 27-32
    Background & Objective

    Nowadays, actin-binding proteins such as Villin and Gelsolin have been considered to be associated with aggressive tumors. This study mainly aims to determine the relationship between Gelsolin and Villin genes expression and metastasis of axillary lymph nodes in patients with breast cancer.

    Methods

    The included population consisted of 40 confirmed cases of female breast cancer (including 20 patients with breast cancer along with axillary lymph node metastasis and 20 patients without axillary lymph node metastasis). Expression of Villin and Gelsolin genes was evaluated using Real-time PCR and pre-designed primers.

    Results

    The mean expression level of Villin in groups with and without axillary lymph node metastasis was 3.33±1.35 and 0.87±0.88, respectively (p <0.001). The mean Gelsolin expression levels in both groups (with and without axillary lymph node metastasis) were 4.13±2.40 and 1.00±0.35, respectively (p <0.001). The significant relationships were independent of individuals’ age.

    Conclusion

     Patients with axillary lymph node metastasis may express significant higher level of Villin and Gelsolin gens.

    Keywords: Breast cancer, Gelsolin, Metastasis, Villin
  • Reza Gheitasi, Esmaeil Sadeghi, Mohammad Jafari * Pages 33-39
    Background & Objective

    Prostate adenocarcinoma is the most common malignancy in males, and the urothelial bladder carcinoma is also prevalent. The histological characteristic of these two tumors is very similar in high-grade cases, and their differentiation is difficult. This study was performed to compare the immunohistochemistry panel of high-grade prostate adenocarcinomas and high-grade urothelial bladder carcinomas.

    Methods

    In this cross-sectional study, 36 cases of prostate adenocarcinoma and 36 urothelial bladder carcinoma samples were collected from the pathology department of Shahid Beheshti Hospital in Hamedan. For each sample, expression of Cytokeratin 7, high-molecular-weight cytokeratin and Prostate-specific antigen markers was evaluated by immunohistochemistry. Comparison of expression of these markers in high-grade bladder tumors and prostate tumors was made by SPSS 25 using Chi-square test.

    Results

    In this study, the Cytokeratin 7 positivity was seen in 88.9% of bladder cancer versus 27.8% of prostate cancer samples. High-molecular-weight cytokeratin positive immunoreactivity was noted in 55.6% of bladder cancer and 5.6% of prostate cancer samples. Prostate-specific antigen marker showed positive results in 94.4% of prostate cancer samples, but no positivity was evident in those of bladder cancer.

    Conclusion

    A panel of immunohistochemical stains can be used to differentiate high-grade prostate adenocarcinoma from urothelial bladder carcinoma in those cases which are  challenging to diagnose.

    Keywords: Prostate adenocarcinoma, Cytokeratin 7, high-molecular-weight cytokeratin, Prostate-specific antigen Urothelial Bladder Carcinoma
  • Maryam Rezaee, Elmira Gheytanchi, Zahra Madjd, Mitra Mehrazma * Pages 40-50
    Background & Objective

    Colorectal cancer (CRC) is the third most common cancer worldwide with a high mortality rate. The main causes of death in patients are recurrence and metastasis which are mainly attributed to the small subpopulation of cells within tumors called cancer stem cells (CSCs). This study aimed to evaluate the correlation between the expression of AHDL1 and CD133 as CSC associated markers and clinicopathological characteristics in CRC.

    Methods

    In this cross-sectional study, a total of 483 CRC tumor samples were immunohistochemically stained for detection of CD133 and ALDH1 markers. Correlations of marker expression with clinicopathological factors were also evaluated.

    Results

    There was a significant correlation between the luminal intensity of CD133 and neural invasion (p =0.05) and between the cytoplasmic intensity of CD133 and metastasis (p =0.05). In terms of H-score, a positive significant relation was observed between cytoplasmic expression of CD133 and lymph node (p =0.02), neural (p =0.04) and vascular invasion (p =0.02). The ALDH1 cytoplasmic expression showed a significant correlation with tumor size (p =0.001).

    Conclusion

    Our findings showed that increased expression of CD133 and ALDH1 is associated with tumor progression and worse outcomes in CRC patients. These markers can be good candidates for localized targeting of CSCs using antibodies. Future researches need to be improved approaches for early detection of CRC, and treatment monitoring for CRC and other cancers.

    Keywords: ALDH1, Cancer Stem Cells, CD133, Colorectal cancer
  • Maryam Nasimi *, Alireza Ghanadan, Kambiz Kamyab, Vahidesadat Azhari, Tahereh Yousefi Pages 51-56
    Background & Objective

    Predicting the transformation of dysplastic or congenital nevi into malignant lesions results in a significant increase in the survival of patients. Some specific gene mutations have been reported to be very helpful in this regard. Therefore, this study aimed to evaluate the prevalence of BRAF V600E mutation in dysplastic and congenital nevi.

    Methods

    This cross-sectional study was conducted on patients with congenital (n=30) or dysplastic (n=30) nevi. For genomic analysis, the BRAF gene mutation (V600E) was evaluated using the real-time polymerase chain reaction.

    Results

    The prevalence of BRAF gene (V600E) mutation was found as 1 case (3.3%) in congenital and 8 cases (26.7%) in dysplastic nevi indicating the higher prevalence of this mutation in patients with dysplastic nevi (p =0.026). Moreover, in the dysplastic nevi group, the presence of BRAF gene mutation (V600E) showed  a significant relationship with the severity of dysplasia as the mutation rate was 25% in mild cases, in comparison with 54.5% in moderate dysplasia cases (p =0.009).

    Conclusion

    According to the results, 3.3% of the patients with congenital nevi and 26.7% of the subjects with dysplastic nevi were positive for BRAF V600E mutation. Furthermore, the severity of dysplasia could have a positive relationship with the presence of the mutation.

    Keywords: BRAF mutation, Congenital nevi, Dysplastic nevi
  • Narjes Soltani, Farzaneh Mirzaei, Hossein Ayatollahi * Pages 57-61
    Background & Objective

    Primary amenorrhea refers to the absence of menstruation in females of reproductive by age 16 when the development of secondary sexual characteristics is evident (breast development, pubic hair) or by age 14 when there are no secondary sexual characteristics are present. Primary amenorrhea can occur in several quite different reasons. Common hormonal causes of primary amenorrhea include constitutional delay, hypothalamic or pituitary disorders, chronic systemic disease, and primary ovarian insufficiency, some endocrine gland disorders, and other causes. Previous studies suggested that chromosomal abnormality is the second most common cause of amenorrhea. This report aims to measure the prevalence of the chromosomal abnormality in primary amenorrhea (PA) patients in the northeast of Iran.

    Methods

    Chromosomal study was carried out on 200 patients with clinical features. The standard method for culturing peripheral venous blood lymphocyte was to prepare metaphase chromosomes and perform routine GTG band analysis.

    Results

    The results revealed that 71% of PA had normal female karyotype (46,XX) and 29% showed different chromosomal abnormalities. The chromosomal abnormalities can be categorized into seven primary groups with or without mosaicism. 1- The most common karyotype was X chromosome aneuploidy (10.5%, n=21), 2- Male karyotype with or without structural abnormality of Y chromosome (5.5 %, n=11), 3- Mosaicism of turner karyotype and structural anomalies of X chromosome (4%, n=8), 4- Structural anomalies of the X chromosome (3.5%, n=7), 5- Mosaicism of turner karyotype and normal karyotype (3%, n=6), 6- Mosaicism of turner karyotype and male karyotype (1.5%, n=3) and 7- Super female karyotype (1%, n=2).

    Conclusion

    The present study has emphasized that early cytogenetic and timely investigation can be necessary for the evaluation of primary amenorrhea.

    Keywords: Chromosomal Abnormalities, cytogenetic study, Iran, Karyotyping, Primary Amenorrhea
  • Zohreh Rahimi *, Maryam Bozorgi Zarini Bozorgi Zarini, Ziba Rahimi, Ebrahim Shakiba, Asad Vaisi-Raygani, Mohammad Taher Moradi, Kheirolah Yari Pages 62-68
    Background & Objective

    Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC.

    Methods

    The present case-control study consisted of 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively.

    Results

    The 3R allele of TYMS enhanced the risk of BC by 2.84-fold (p <0.001). In the presence of TYMS 3R/3R, compared to TYMS 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, p =0.055). The frequencies of MTR c.2756A>G and MTRR c.66A>G variants were not significantly different among patients and controls.

    Conclusion

    We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele tends to increase the BC metastasis.

    Keywords: Breast cancer, Thymidylate synthase, Methionine synthase, Methionine synthase reductase, Polymorphism, Metastasis
  • Maryam Khayamzadeh, Fereshte Aliakbari, Zahra Zolghadr, Majid Emadeddin, Mahsa Ahadi, Mohammadesmaeil Akbari, Amir Reza Abedi *, Shahrzad Nematollahi, Seyed Jalil Hosseini Pages 69-74
    Background & Objective

    Bladder cancer is the fourth most common cancer in men and the most common cancer in women, comprising 8% of all males and 3% of female tumors. The present study aimed to estimate the five-year survival rates of bladder cancer in Iran.

    Methods

    Information on3,337 registered cases of bladder cancer was obtained from the Office of National Cancer Registry in the Ministry of Health and Medical Education (MOH & ME). A telephone survey was conducted to gather additional information, such as survival status, demographic, and clinical profile. Kaplan–Meier estimates of five-year survival rates were calculated according to the age of diagnosis, gender, pathological type, and provincial pole. Results and

    Conclusion

    Overall five-year survival rate was 77%. According to the pathologic type, five-year survival rates were 81%, 66%, 81%, 42%, 77%, and 82% in low-grade urothelial carcinoma, high-grade urothelial carcinoma, adenocarcinoma, undifferentiated carcinomas, Squamous Cell Carcinomas (SCCs), and other tumors, respectively. Additionally, those tumors  were 93%, 88%, 81%, 64%, and 44% among patients whose average ages at diagnosis were < 50, 50–59, 60–59, 70–79, and > 80 years old, respectively. Our study revealed that age and histological type were the major prognostic factors for survival in patients with bladder cancer. Therefore, given the histologic features of the tumor and patients with advanced age, a continuous screening would be highly warranted.

    Keywords: Urinary bladder neoplasm, Survival analysis, Iran, Disease registry
  • Alireza Abdollahi, Ali Labbaf, Mahboobeh Mafinejad, Maryam Sotoodeh-Anvari *, Farid Azmoodeh-Ardalan Pages 75-78
    Background & Objective

    The world is facing COVID-19 pandemic, and medical education system and consequently the evaluation of students at different levels have been overshadowed. Residency students are among those affected. In the present study, we aim to share our experiences regarding holding exams for pathology residents before and during the pandemic.

    Methods

    This cross-sectional study was carried out in Tehran University of Medical Sciences. The online exam, which consisted of 30 multiple-choice questions, was designed and held in April 2020 to evaluate pathology residents. To assess the quality of the exam, indices such as the number of questions, highest and lowest scores, the average score, the standard deviation, the variance, Cronbach’s alpha reliability coefficient, standard error of measurement, discrimination index, difficulty index, number/percentage of questions on three difficulty levels of easy, normal, hard were reviewed and analyzed.

    Results and Discussion

    The average score of the participants in the January exam which was held in the university’s exam center was 16.23 (±5.03), while the average score in the online exam which was held after the onset of the pandemic was 20.86 (±5.18). The average discrimination indices in the first and second exams were 0.36 and 0.38, respectively, and the average difficulty indices in the first and second exams were 0.54 and 0.70, respectively. We found the administration of this online examination would be a positive experience. By sharing it, we hope to pave the way for similar ventures in the other departments.

    Keywords: Coronavirus, COVID-19, Electronic exams, pathology
  • Fatmagul Kusku *, Damlanur Sakiz Pages 79-83

    Coronavirus is a single-stranded RNA virus that causes acute respiratory syndrome and various skin lesions. In addition, ischemic acral lesions have been reported in patients with severe coronavirus disease 2019 (COVID-19) due to coagulation disorders. We here present a case with ischemic acral lesions caused by COVID-19. The patient was 51-year old male who was hospitalized with COVID-19 pneumonia. After 28 days in the Intensive Care Unit, patient developed acroischemic lesions in the fingers and toes. In the histopathologic examination, vasculitis was observed as the infiltration of mixed-type inflammatory cells in the mid-sized muscular arteries wall. Moreover, microthrombosis was detected in small capillaries. It is clear that thrombotic lesions have occurred as a result of COVID-19 or administered treatment. Further studies are required to confirm and better characterize the skin reactions in COVID-19.

    Keywords: Acroischemia, COVID 19, Microthrombosis, Necrosis, Vasculitis
  • Elham Jafari, Shiva Didehban *, Shahriar Dabiri, Behshad Mofid Pages 84-89

    A heterogeneous group of CNS tumors are characterized by mixed neuroepithelial and mesenchymal features. Glial tumors manifesting this phenomenon are referred to as gliosarcoma. These tumors are usually mistaken for cerebral metastases or meningioma at operation. Their histological studies have revealed an admixture of gliomatous and sarcomatous tissues, which leads to a biphasic pattern. The mesenchymal component can present in different forms such as fibrosarcoma, undifferentiated pleomorphic sarcoma, chondro-osteogenic, and myogenic differentiation, as well as angiosarcomatous and liposarcomatous types. Squamous differentiation, adenoid formations and glandular structures may also be displayed. Herein, we report a rare case who was admitted to the emergency room with decreased consciousness resembling methadone poisoning. Clinical work-up showed a temporoparietal mass on radiological investigation. Histopathological evaluation of the brain mass revealed a gliosarcoma with adenoid formations and a mesenchymal component, which manifested as chondrosarcomatous differentiation. Immunohistochemical studies confirmed the histologic diagnosis through positivity for EMA, GFAP, S100, and vimentin expression in different components.

    Keywords: Adenoid Differentiation, Chondrosarcomatous Differentiation, Gliosarcoma
  • Atieh Zandnejadi, Arezoo Eftekhar-Javadi *, HEDIEH MORADI TABRIZ Pages 90-94

    Glioblastoma (WHO grade IV) is the most common malignant tumor of neural tissues in adults as a primary tumor. Because of blood brain barrier and short median survival of patients with glioblastoma, metastasis of this tumor is very rare. A 46-year-old man was admitted to Sina hospital with chief complaint of headache and visual impairment. After neuro-radiologic evaluation the patient underwent surgery. Pathologic examination of the tumor confirmed the diagnosis of glioblastoma multiforme. Cytogenetic study of the tumor cells confirmed GBM IDH1 wild type with TERT mutation and EGFR amplification. Two months after surgical resection, the tumor recurred with involvement of the dura matter. After the second operation, metastasis to the pelvic cavity and cervical lymph node was found. Almost all cases of glioblastoma metastasis had undergone surgery or any manipulation; this fact suggests that iatrogenic intra-vascular seeding of tumor cells at the time of resection and disruption of blood brain barrier could cause extra-neural metastasis.

    Keywords: Brain tumor, Glioblastoma, Metastasis, Pelvic Cavity
  • Payam Behzadi * Pages 95-96