TERT Promoter Mutation in Benign and Malignant Salivary Gland Tumors; A Cross-Sectional Study.

Background & Objective: Telomere-related tumorigenesis mechanisms in the salivary gland, including mutation in the promoter region of TERT, have been rarely investigated. Therefore, the present study aimed to investigate the mutation in the promoter region of TERT in benign and malignant salivary gland tumors. Methods: This was a descriptive-analytical cross-sectional study. Tissue samples of 54 patients with primary salivary gland tumors sent to the pathology department of Rasool-e-Akram Hospital from September 2017 to September 2021 were examined. Fifteen samples including two groups of the most common benign tumors (n=5; 3 pleomorphic adenomas and 2 Warthin tumors) and four groups of the most common malignant tumors (n=10; 3 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas, 2 acinic cell carcinoma, and 2 salivary duct carcinoma) were selected. The promoter region of TERT, including well-known hot spot regions, is sequenced using the Sanger sequencing method. Data were analyzed using statistical software R version 4.1.2. Results: Of 15 salivary gland tumor specimens, consisting of 5 benign tumors and 10 malignant tumors after DNA sequencing, TERT promoter region mutation was only seen in one of the adenoid cystic carcinoma samples, located at -146 bp upstream from ATG (chr5: 1,295,250 C>T). Conclusion: TERT promoter mutation was not different in malignant and benign salivary tumors. Nonetheless, there are a few studies that report TERT promoter mutation in adenoid cystic carcinoma of the salivary gland, necessitating the need for further investigations.

Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study.

Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.

Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma.

INTRODUCTION: Recent developments in genomic sequencing have led to the identification of somatic mutations in isocitrate dehydrogenase 1 (IDH1) in various malignancies. IDH1 R132H is the most common mutation of IDH1, which affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This study is designed to evaluate the association between the expression of IDH1 R132H and clinicopathological characteristics in laryngeal squamous cell carcinoma (LSCC). METHODS: The expression pattern and clinical significance of IDH1 R132H were investigated in tissue microarrays (TMAs) of 50 LSCC tumors as well as adjacent normal tissues using immunohistochemistry. Then the exons of the 12 tumor samples with negative/weak positive staining were sequenced by applying polymerase chain reaction (PCR). RESULTS: The results demonstrated that the cytoplasmic expression of IDH1 R132H was downregulated in tumor cells compared to adjacent normal tissues. A statistically significant association was found between a low level of cytoplasmic expression of IDH1 R132H protein and an increase in histological grade (p < 0.001), perineural invasion (p = 0.019), and lymph node involvement (p < 0.001). The exon4 sequencing results showed that only one sample was positive for IDH1 R132H mutation. IDH1 R132H expression was observed in 39 (78.0%) LSCC samples. CONCLUSION: These findings indicate that low cytoplasmic expression of IDH1 R132H may have clinical significance in LSCC patients and is associated with more aggressive tumor behavior and progression of the disease, which can help improve potential treatment in patients with LSCC. Further investigations are needed to understand the biological function of IDH1 R132H and larger sample size to confirm our findings.

A case report of an extremely rare type of cardiac tumor: Primary cardiac angiofibroma.

Cardiac angiofibroma is a very rare diagnosis when a patient develops an intracardiac mass. It is a primary benign cardiac tumor with a scarcity of information in the literature. This case report illustrates a 26-year-old man with a complaint of chronic chest tightness who was first diagnosed with right ventricle tumor by echocardiography then underwent cardiac magnetic resonance imaging (CMR) which confirmed the presence of a highly-vascular tumor with radiologically benign behavior. Then his tumor was excised, his postoperative course was uncomplicated and he was well within almost 2 months after discharge. Ultimately the histopathologic findings demonstrated vascular and stromal tissue in favor of angiofibroma and excluded the other diagnoses with immunohistochemical and trichrome staining. Angiofibroma is a benign, highly vascular tumor, mostly discovered in the nasopharynx. When it is found in the heart, CMR and pathology are pivotal to rule in its diagnosis. It is isointense in T1 weighted and hyperintense in T2 weighted sequences with intense enhancement following contrast injection. Its pathology contains an admixture of vasculatures with CD31 positive immunoreactivity for endothelial cells and fibrotic tissue with bluish coloration in trichrome staining. Eventually, its treatment includes merely surgical excision given its benign nature.

Pre-analytical Practices in the Molecular Diagnostic Tests, A Concise Review.

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 that 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.

Investigating Human Papilloma Virus Types in Sinonasal Papilloma Using Polymerase Chain Reaction: Is It Really a Prerequisite for Nasal Papilloma Formation?

Sinonasal papilloma is a relatively rare disease. However, it is prevalent enough for every otorhinolaryngologist to encounter it several times throughout one's medical practice. The aim of this study was to identify the presence of Human Papilloma Virus in sinonasal specimens of patients with sinonasal papilloma. A cross sectional analytical study was performed on fresh tissue samples from 36 patients with sinonasal papilloma. Samples were studied by polymerase chain reaction for of Human Papilloma Virus detection. In conclusion, the majority of patients were of Human Papilloma Virus negative and there was no statistically significant difference in presence of squamous cell carcinoma in of Human Papilloma Virus positive and negative patients. Thus, further studies are needed to assess other potential factors that may influence the development of sinonasal papilloma.

A presentation of ulcerative colitis after rituximab therapy in a patient with multiple sclerosis and literature review.

Multiple sclerosis (MS) is one of the most important demyelinating diseases that affects the central nervous system. Its treatment often involves a long-term disease modifying therapy. According to some studies, the prevalence of autoimmune disorders, such as autoimmune hepatitis (AIH) and ulcerative colitis (UC) is higher in MS patients than in the normal population. There are also few studies that have reported the onset of UC after rituximab therapy. The present study presents a report of a 31-years old female patient suffering from aggressive multiple sclerosis, which developed into autoimmune hepatitis during the MS therapy. Thereafter, she received rituximab for the treating both MS and AIH. One week after the third cycle of rituximab (6 doses of 1000 mg), she experienced abdominal pain, fever, and severe bloody diarrhea; finally, she was diagnosed with ulcerative colitis (UC). It seems that the administration of certain immunomodulators or immunosuppressive drugs may have a main role in the exacerbation of some autoimmune diseases.

MiR-21 Expression in Wilms' Tumor.

BACKGROUND AND OBJECTIVE: Wilms' tumor (WT) is the most common genitourinary tract tumor in children. MicroRNAs (miRNAs) are small non-coding RNAs; their role in the pathogenesis of many types of human cancers has been identified. We aimed to evaluate the expression of miR-21, a well-known oncomir, in WT tissue samples which is a very common urinary tract malignancy in children. METHODS: We performed chromogenic in situ hybridization (CISH) to detect the sub-cellular localization of miR-21 in 25 formalin-fixed, paraffin-embedded (FFPE) samples of WT. We also evaluated miR-21 expression in 24 of these blocks and 6 normal kidneys as controls using quantitative real-time PCR technique. RESULTS: While our real-time PCR analysis showed miR-21 significant overexpression in 4 tumors compared to the normal kidney samples, we could not detect significant ISH signal in any of these samples. CONCLUSION: Low expression of miR-21 in WT might pinpoint the weak involvement of this miRNA in the pathogenesis of this cancer.

The Correlation Between Serum Vitamin D Level and Total Antioxidant Capacity in Diabetic and Non-diabetic Subjects in Iran.

BACKGROUND & OBJECTIVE: Increase in intraand extracellular glucose levels can cause oxidative stress, and theprolonged imbalance between prooxidants and antioxidantscan lead to cell damage and the associated complications in patients with diabetes. Vitamin D acts as a strong antioxidant in the body and several studies emphasized on its important role to preventoxidative stress in prediabeticand diabetic subjects. The current study aimed at determining and comparingthe total antioxidant capacity (TAC) in individuals with hemoglobin A1c(HbA1c) below and above 6.5%, and its correlation with vitamin D levels. METHODS: The current cross sectional study was conducted on a total of 107patients with diabetes (HbA1c >6.5%) and 107 non-diabetic subjects (HbA1c<6.5%)referred toRassoolAkram Hospital, Tehran, Iranfrom2015 to 2016, as the sample population. The two groups were compared regarding their TAC and vitamin D serum levels and the association between vitamin D concentration and TAC was evaluated. RESULTS: Age and body mass index (BMI)were significantly higher in patients with diabetes,comparedwiththe serum levels of vitamin D and TAC (P<0.001 for both). Both TAC and vitamin D levels were significantly lower in the group with diabetesand a weak significant correlation was observedbetween the two factors (r=0.2, P=0.003). In multivariate regression model, the duration of diabetes was also significantly associated with TAC level (beta coefficient=-0.82, P <0.001). CONCLUSION: The low serum levels of TAC and vitamin D in patients with diabetescould be indicative of oxidative stress in the presence of high blood glucose levels. Supplementation of vitamin D in patients with diabetes might be effective to control thenegative impacts of the disease and decreasecells' exposure to oxidative environment in prediabetes.

Fever,Weight Loss and Early Satiety due to Gastric Inflammatory Myofibroblastic Tumor; Case Report and Literature Review.

Gastric inflammatory myofibroblastic tumor (IMT) is a rare tumor with and unpredictable prognosis usually find in young adults. We present an 18-yearold man with gastric IMT. He complained of epigastric pain, intermittent fever and night sweating associated with weight loss since two years ago. Physical examination showed anemic and cachestic features with mild abdominal tenderness in palpitation as well as an abdominal mass in epigastrium. Abdominal CT scan revealed a huge mass that was arising from the stomach. Upper endoscopy revealed a submucosal lesion in fundus of stomach of approximately 8cm. Endoscopic ultrasound showed a large sub-mucosal non homogenous fundal mass with areas of calcification. The patient underwent laparoscopic partial gastrectomy. Histopathologyand immunohistochemistryevaluation revealed an IMT.

Does routine repeat testing of critical laboratory values improve their accuracy?

BACKGROUND: Routine repeat testing of critical laboratory values is very common these days to increase their accuracy and to avoid reporting false or infeasible results. We figure that repeat testing of critical laboratory values has any benefits or not. METHODS: We examined 2233 repeated critical laboratory values in 13 different hematology and chemistry tests including: hemoglobin, white blood cell, platelet, international normalized ratio, partial thromboplastin time, glucose, potassium, sodium, phosphorus, magnesium, calcium, total bilirubin and direct bilirubin. The absolute difference and the percentage of change between the two tests for each critical value were calculated and then compared with the College of American Pathologists/Clinical Laboratory Improvement Amendments allowable error. RESULTS: Repeat testing yielded results that were within the allowable error on 2213 of 2233 specimens (99.1%). There was only one outlier (0.2%) in the white blood cell test category, 9 (2.9%) in the platelet test category, 5 (4%) in the partial thromboplastin time test category, 5 (4.8%) in the international normalized ratio test category and none in other test categories. CONCLUSION: Routine, repeat testing of critical hemoglobin, white blood cell, platelet, international normalized ratio, partial thromboplastin time, glucose, potassium, sodium, phosphorus, magnesium, calcium, total bilirubin and direct bilirubin results does not have any benefits to increase their accuracy.

Left sided colorectal adenomatous polyps have more risk for high grade dysplasia.

Colorectal cancer is the second leading cause of cancer death worldwide. Through risk assessment of malignancy in polyps, screening programs can achieve the best results. This study aimed to determine the association between the grade of dysplasia and the location of colorectal polyps. 240 colorectal adenomatous polyps which were referred to department of pathology at Rasoul-e-Akram Hospital between 2005 and 2009 met the inclusion criteria. Demographic data and information about size of polyps, grade of dysplasia and location of polyps were collected and analyzed by Chi-square and t-test. 124 (58.8%) patients were male and 87 (41.2%) were female. The mean age of the patients was 61.6 years. 47 (19.6%) polyps were right-sided and 193 (80.4%) were left sided. 39 (16.2%) polyps had high grade dysplasia. 27 (12.8%) patients had 56 synchronous polyps (23.3%). 176 (73.3%), 39 (16.2%) and 25 (10.5%) polyps were of tubular, tubulovillous and villous types respectively. The greatest dimension of 110 (45.8%) polyps was <0.5 cm, 97 (40.4%) 0.5-1 cm, 22 (9.2%) between 1 and 2 cm and finally 11 (4.6%) >2 cm. High grade dysplasia was detected in 3 (6.3 %) of right-sided and 36 (18.6%) of left-sided polyps. The obtained results revealed that size of polyp and amount of villous component were strongly associated with high grade dysplasia. Left side location of polyps was independently associated with high grade dysplasia. Left-sided colorectal polyps must be treated more seriously, especially the larger ones with villous component. There was no association between age and gender and the grade of dysplasia.

Bilateral ovarian involvement: a rare presentation of disseminated multiple myeloma.

Extramedullary spread of multiple myeloma is extremely rare. This paper reports a case of bilateral ovarian involvement in plasma cell myeloma. The patient was a 48-year-old Persian woman who experienced constitutional symptoms, bone pain and flashing for one year. Her condition showed multiple myeloma with lytic lesions of the skull, plasma cell infiltration in bone marrow and positive light chain lambda type in serum. Workup showed huge bilateral ovarian masses, and ovarian metastasis from plasma cell myeloma was confirmed after pathologic assessment. Multiple myeloma spread to ovary is rare and according to our knowledge, this is the fourth reported case of bilateral ovarian involvement in extramedullary multiple myeloma.

Head and neck squamous cell carcinoma in Iranian patients and risk factors in young adults: a fifteen-year study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 8th most common cancer worldwide. Although older age, male gender, smoking and alcohol consumption are known risk factors, an increasing number of HNSCC patients are without typical risk factors. Our aim was to define demographics of HNSCC in Iran and the potential risk factors related to Iranian ethnicity and lifestyle. METHODS: We conducted a cross-sectional analytical study on 262 patients with primary SCC of the larynx, hypopharynx or tongue referred to our pathology department during 1995-2010. Patients' demographics, tumor characteristics and risk factors such as smoking, alcohol consumption and anemia were analyzed and compared in two groups of patients: over 40 years (older group) and 40 years or less (young group); Chi-square and Mann-Whitney analytical tests were employed. RESULTS: 5.7% of patients were young adults. The male to female ratio was 1.5 in the younger group and 5.6 in the older group. In young adults, 40% of tumors were located in larynx and 40% in the tongue. Age >40 was significantly associated with laryngeal location (P<0.001). History of smoking and drinking was significantly associated with age >40 and SCC of larynx in both age groups. Cervical lymph node involvement was significantly correlated with SCC of tongue (P<0.001), however, considering young adults only, SCC of hypopharynx was most frequently accompanied by lymph node involvement (60%). The most prevalent tumor among men was SCC of larynx whereas SCC of hypopharynx was the most prevalent tumor among women (61%), of whom 18.2% were ≤40. CONCLUSIONS: The incidence of HNSCC among young adults seems to be higher in Iran compared to other countries. Reduction in exposure to known risk factors, especially tobacco smoking in forms of cigarettes and bubble pipes, and search for other causative agents of HNSCC in young population is recommended.

Analysis of colonic mucosa mast cell count in patients with chronic diarrhea.

BACKGROUND/AIM: Chronic diarrhea is defined as a decrease in fecal consistency lasting for four or more weeks. Prevalence of this complication in the general population is 5%. Mast cells that play an important role in the regulation of gastrointestinal visceral sensitivity and vascular permeability may be involved in functional chronic diarrhea. In this study we tried to evaluate mast cells density in colonic mucosa of patients with chronic diarrhea. PATIENTS AND METHODS: 50 patients with chronic diarrhea and 50 persons as control group were investigated. All specimens were immunohistochemically stained for mast cell tryptase (MCT) with monoclonal mouse anti-human MCT as well as toluidine blue. Mean number of mucosal mast cells were counted in 10 high power microscopic fields of patients and control groups. RESULTS: In patients group (age range, 15-78 years; 26 females), the number of mast cells per high power field in the immunohistochemistry staining was 21.3 ± 4.8 compared to 14.2 ± 3.4 in the control group (age range, 18-78 years; 24 females) [P < 0.001]. Also number of mast cells in toluidine blue staining was 10.3 ± 3.6 per high power field in cases and 7.1 ± 2.4 in the control group (P < 0.001). CONCLUSION: Elevated number of colonic mast cells exist in patients with chronic diarrhea. Further research should be considered on application of these findings for new therapeutic opportunities.

The frequency of latent prostate carcinoma in autopsies of over 50 years old males, the Iranian experience.

BACKGROUND: Latent adenocarcinoma of prostate refers to cases who present no obvious sign or symptom during their life spans and the tumor is incidentally found at postmortem examination. Its frequency can be very important in epidemiologic investigations, prevention and treatment. No previous study has been done in this regard in Iran and the studies performed in other countries show various results. The aim of present study is to determine the frequency of latent prostate carcinoma by studying the corpora of men above 50 years old referred to forensic medicine organization in Tehran in 2008 and 2009. METHODS: In this study, 149 men aged above 50 who had died of different reasons and undergone autopsy were examined. Their prostates were excised and the slides were studied for the presence of adenocarcioma and prostatic intraepithelial neoplasia (PIN). In each case, age, weight of prostate, location of lesion, and grading according to Gleason's system were determined and the results were analyzed by SPSS software (version 16). RESULTS: Out of 149 cases, 34(22.8%) had low grade PIN, 26(17.4%) high grade PIN, and 14(9.4%) invasive adenocarcinoma. Most of the tumors were located in posterior lobe of prostate and they were more frequent in older cases (>65 years of age) and heavier prostates (p value <0.05). All invasive adenocarciomas were accompanied by PIN. CONCLUSION: Worldwide studies show lower prevalence of latent carcinoma of prostate in Asian men than white European ones. Considering the absence of such studies in Iran, a larger study to compare and find out the precise rate of this kind of carcinoma, is recommended.

Diagnosis of endometrial nerve fibers in women with endometriosis.

PURPOSE: Recent studies indicated that there is a high density of small nerve fibers in the functional layer of the endometrium in women with endometriosis and that it can be used as a marker to detect endometriosis. In this study, the efficacy assessment of small nerve fibers' density as a diagnostic marker was compared in patients with and without endometriosis. METHODS: In this study, women with history of pelvic pain and/or infertility who were candidates for laparoscopy or laparotomy in Rassoul hospital (2007-2009) were enrolled. Histological sections of endometrial tissue were prepared from endometrial biopsy from women with endometriosis (n = 12) (1) and without endometriosis (n = 15) (2). Protein gene product 9.5 and neurofilament were evaluated as marker from endometrial biopsies by immunohistochemical methods. RESULTS: There was no statistically significant difference between two groups according to age, body mass index. Nerve fibers were detected in all endometrial biopsies from all women with endometriosis but detected only in three women without endometriosis. The mean density of nerve fibers was 2.2 ± 4.7 mm(-2) in group without endometriosis and) 13.1 ± 3.3 (in group with endometriosis (p < 0.001). Women with endometriosis had significantly higher nerve fiber density in comparison with women without endometriosis. CONCLUSIONS: Our findings indicated that endometrial biopsy for detecting density of nerve fibers by usage of protein gene product 9.5, provided a reliable marker for diagnosis of endometriosis.