Iranian Journal Of Pathology
Volume:13 Issue: 3, Summer 2018

Acute myeloid leukemia (AML) as a distortion of blood cells involves the differentiation of hematopoietic stem cells. Several studies established the irregular overexpression of specific genes is a common finding in patients with AML. The ectopic viral integration site-1 (EVI1) gene is a proto-oncogene subject to alternative splicing, and encodes a zinc-finger protein that acts as a transcriptional regulator in early development. Forced overexpression of EVI1 in hematopoietic progenitors later induced a myeloid differentiation block. The current review aimed at determining the prognostic value of EVI1 expression in patients with AML in the age range of one month to fifteen years.
The scientific databases including PubMed, Google Scholar, EMBASE, Scopus, and ISI published up to January 2016 were searched using the conformity keywords and a total of four articles were studied.
Three articles declared higher overexpression of EVI1 in patients with mixed-lineage leukemia (MLL) rearrangements. The percentage of overall survival (OS), reported in two articles, decreased in AML patients with high EVI1 expression. A study reported that the relationship between EVI1 expression and OS was negligible in cases with and without EVI1 expression. Another study showed significant differences in event free survival (EFS) and OS in the group of patients with positive MLL-AF9 between EVI1+ and EVI1- patients.
The current study revealed that high EVI1 expression was not a poor prognostic factor in pediatric patients with AML. And this gene expression was mainly prognostic concomitantly by other factors such as MLL rearrangement, MEL1 expression, and white blood cell (WBC) count.

Acute microbial diarrheal diseases are the major public health problems in the developing countries. People affected by diarrheal diseases have the lowest financial resources and poorest hygienic facilities. Children under five, primarily in Asian and African countries, are mostly the subjects affected by microbial diseases transmitted through water.
The current study aimed at investigating the comparative inhibitory effect of Lactocare (commercial probiotic) on clinical samples and standard strains of Vibrio cholerae. A total of 20 clinical samples and a standard strain (ATCC 14035) were provided by Health Reference Laboratory and Biotechnology Institute, respectively. In order to confirm the samples, biochemical analysis and the polymerase chain reaction (PCR) were performed on intergenic space. Afterward, agar well diffusion method was performed in order to measure the minimum inhibitory concentration to monitor the antimicrobial activity of Lactocare. Colony count of V. cholerae for the standard strain in 30% and mean for clinical samples in 50% concentration of Lactocare treatment revealed that it would propel to death phase. Since the number of colonies decreased to 100, it was considered that higher concentrations of Lactocare would completely inhibit the growth of V. cholera. Probiotics are employed to develop new pharmaceutical preparations and functional foods in order to promote the public health.

The currentstudy aimed at investigating the histomorphological spectrum of cervical intraepithelial and invasive lesions assessing the diagnostic significance of P16/INK4a and Ki-67 in such lesions, andcorrelatingP16/INK4a and Ki-67 immunoexpression with histologic type and grade. A total of 60 cases were selectedcomprising 10 cases withchronic cervicitis, 29 cases withcervical intraepithelial neoplasia(CIN), and 21 cases withsquamous cell carcinoma. These cases were evaluated morphologically and immunohistochemically with P16 and Ki-67. There was no expression of P16 and Ki-67 in 10 (100%) cases withchronic cervicitis while in CIN, it was expressed in 25 (86.20%) cases and in carcinoma it was expressed in 20 (95.23%) cases. Ki-67 was expressed in 28 (96.55%) cases withCIN and in 100% of cases withcarcinoma. Cervical carcinoma is a significant contributor to cancer-related morbidity and mortality worldwide. Identification of bio-markers in cervical neoplasia is necessary to distinguish CIN from other non-neoplastic cervical lesions to prevent under treatmentor overtreatment as the histomorphological features alone are not sufficient.Significant upregulation of P16, cyclin dependent kinase inhibitor, and Ki-67, a nuclear non-histone protein, was observed in carcinoma cervix and with the increasing severity of CINs. Correlation between grades of P16 and Ki-67 among cervical pre-neoplasia and neoplasia showed an increasing P16 expression with consistently increasing Ki-67 labelling index in the groups with theincreasing severity.

Non-scarring alopecia is a challenge in the diagnosis and treatment, rarely studied in Asian countries.
The current study aimed at evaluating histopathological features including hair count of different subtypes of non-scarring alopecia in Iranian patients. The current study was conducted on 114 cases diagnosed with non-scarring alopecia in Molecular Dermatology Research Center and Pathology Department of Shiraz University of Medical Sciences, Shiraz, Iran. Cases with two 4-mm scalp punch biopsies were selected. Patients’ clinical data were compared with histological findings. Androgenetic alopecia (AGA) was the most common subtype Followed by alopecia areata (AA) and combined AGA/telogen effluvium (TE). Perifollicular inflammation was observed in 21% of AGA with a significant difference in males and females (66.7% vs. 33.3%; P-value <0.05). Clinical and histopathologic diagnoses were correlated in 55% of cases. Maximum correlation was observed in combined AGA and chronic TE (88%). For vertical sections, the diagnostic rate was 33.6%, while 88% for transverse sections. Transverse together with vertical sectioning provides most of the information in non-scarring alopecias, while transverse sectioning is enough to diagnose the majority of non-scarring alopecias. Perifollicular inflammation was observed in a significant number of cases with AGA, more common in males. It is suggested to report such cases as possibly curable.

Helicobacter pylori infection is one of the most common chronic bacterial infections in the world, especially in the developing countries. This bacterium is the cause of many diseases such as lymphoma, gastritis, peptic ulcers, and stomach cancer. According to recent reports, H. pylori infection can potentially increase the risk of colon cancer. The current study aimed at investigating the association of H. pylori infection and the risk of colorectal cancer and adenomatous polyps. The current study was conducted on 50 patients with colon cancer and adenomatous polyps as the case group and 100 subjects with no specific pathologies (i e, polyps, neoplasms, or inflammatory diseases) as the control group. Blood samples were collected from the patients in order to assess the presence of anti-Helicobacter pylori infection antibodies, and the serum titer levels of anti-Helicobacter pylori IgG and IgA antibodies were measured using indirect enzyme-linked immunosorbent assay (ELISA) and a kit procured by Pishtaz Teb Company (Iran). A total of 33 patients in the current study had adenomatous polyps and 17 had colon cancer. H. pylori infection (IgA >20 U/mL and IgG >10 U/mL) was significantly more prevalent in the patients with colon cancer and adenomatous polyps compared with the healthy controls (P= 0.003, P= 0.039, respectively). The obtained results suggested that H. pylori infection can be considered as a risk factor for colon cancer and adenomatous polyps.

Prostate cancer is considered as one of the most common malignancies in males. Despite the decreasing trend during the past decade, the incidence continues to rise in adolescents worldwide. Recently, new emerging technologies beside TRUS-guided prostate biopsy were introduced and showed high potential in the diagnosis of prostate cancer. The current study aimed at investigating the role of blood cell count and its prognostic value on pathologic findings. The current prospective analysis was conducted on patients with abnormality from January 2013 to January 2015. A total of 168 CBC tests including absolute Neutrophil and lymphocyte counts were performed on males at the Department of Urology, Razi University Hospital (Guilan, Iran). Of these, all males had both CBCs and free:total (F/T) prostate-specific antigen (PSA) ratio. Average age of patients was 63.5±7. It was observed that Neutrophil count and Neutrophil percentage was not significantly different among the groups with different pathologies. In comparison to biopsy findings none of the cell count had suitable specificity and sensitivity. In the multivariate analysis to predict malignancy, only age (B=0.1, S.E=0.04, EXP [B]) =1.1 and sig=0.00) and PSA level (B=0.1, S.E=0.04, EXP [B]) =1.1 and sig=0.00) were significant. In comparison to biopsy findings, none of the cell counts (absolute or percent) had suitable specificity and sensitivity, and the cell count and percentage before biopsy were not different among the groups with different pathologies. Powerful and long-term studies are required to evaluate prognostic values of cell count on adenocarcinoma.

The current study aimed at observing the cytomorphological patterns in patients presenting with enlarged cervical lymphnodes, diagnosed by fine needle aspiration cytology (FNAC), their distribution with respect to age and gender, and determining the accuracy of FNAC as a diagnostic procedure incases with cervical lymphadenopathy. Out of all patients presenting with cervical lymphadenopathy from September 2015 to September 2016, in the Department of Pathology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India 100 consecutivecases were enrolled into the current study, following the exclusion of all cases where FNAC smears were inadequate or suboptimal for diagnostic interpretation. Histopathological examination was conducted on small excision biopsy specimens/radical neck dissection, where ever possible and diagnostic efficacy of FNACwas evaluated. Theoverall age range of the enrolled patients, presentingwith enlarged cervical lymph nodes, was 1-72 years withthe mean age of 35.7 years and male-femaleratio of 1.6:1.Out of the 100 cases, benign and malignant lesions comprised 77 and 23 cases, respectively.The most common observed benign lesion was reactive hyperplasia(29%), while squamous cell carcinoma was the most common malignant lesion.The overall sensitivity, specificity, positive predictive value, negative predictive value,andthe diagnostic accuracy was 100%, 91.67%, 92%, 100%, and 95.7%, respectively. FNAC in the diagnoses of inflammatory and neoplastic diseases serves as a reliable,low-cost, rapid diagnostic tool with reasonably good accuracy that caninfluence patient management in terms of early diagnoses, treatment, and prevention of unnecessary surgery in patients.

Pseudomonas aeruginosa (P. aeruginosa) causes serious nosocomial and non-nosocomial infections. blaOxacillinases (OXA)-23 and blaOXA24/40 provide resistance to carbapenem antibiotics. The aim of this study was assessment of blaOXA-23 and blaOXA-24/40 in P. aeruginosa isolated from patients with nosocomial and non-nosocomial infections. In this descriptive cross-sectional study performed in Sanandaj, Iran (Kurdistan province) in a period from December 2015 to August 2017, 146 isolates of Pseudomonas spp. were collected from patients’ specimens. Microbiological methods and polymerase chain reaction (PCR) with gyrB were applied for P. aeruginosa detection. Disk diffusion method with imipenem (IMP) (10µg) was performed for detection of resistant bacteria, and multiplex PCR of OXA-23 and OXA-24/40 were performed as well. Stata 12 with Fisher’s exact test and logistic regression were used for data analysis (P≤0.05). PCR gyrB gene proved the existence of 91.78% P. aeruginosa isolates. Nosocomial infection with P. aeruginosa was observed in 41.79%. 27.61% of P. aeruginosa strains were resistant to IMP. blaOXA-23 and blaOXA24/40 were detected in 11.19% and 2.24% of the strains, respectively. 2.23% strains of P. aeruginosa showed a co-existence of blaOXA-23 and blaOXA24/40. There were no significant relationships between antibiotic resistance and presence of genes, and between IMP resistance and age, sex, city of residence, inpatient/outpatient, and specimen’s type (P≥0.05). Resistance to IMP and the presence of resistant genes in this study were observed in patients. More precautions should be taken in prescribing antibiotics and applying molecular techniques to detect genes, since they can cause antibiotic resistant.

Phototherapy is one of the therapy methods for jaundice caused by hyperbilirubinemia. Vitamin D and bilirubin have two distinct routes of metabolism yet part of their syntheses is common in the liver and thus they may influence each other’s synthesis. One of the consequences of phototherapy not previously studied in detail is hypocalcaemia and hypomagnesaemia. The current study aimed at investigating the effect of phototherapy on serum level of calcium, magnesium, and vitamin D. The current semi-experimental investigation was conducted on 50 term infants with jaundice that had phototherapy indication. Bilirubin, calcium, magnesium, and vitamin D were measured in their blood samples at admission and then 48 hours after beginning the phototherapy. Data were analyzed with SPSS version 16 using paired-samples t test. The serum calcium was 9.85 mg/dL before phototherapy and significantly decreased after it (9.51 mg/dL) (P<0.001). Also, the mean serum magnesium was 2.21 mg/dL before phototherapy and significantly decreased after it (2.06 mg/dL) (P=0.047). The mean of serum vitamin D significantly increased after phototherapy (before 17.44 mg/dL and after 21.77 mg/dL) (P<0.0001). The current study showed that phototherapy could decrease the level of calcium and magnesium and increase the level of vitamin D.

Primary fallopian tube carcinomas (PFTC) are rare tumors with non-specific clinical presentations. The current case was unique since the tumor was first detected on endometrial curettage and clinicoradiologically was misdiagnosed as endometrial carcinoma.
Case Report: A 48-year-old, post-menopausal female presented with one episode of vaginal bleeding. Endometrial curettage showed poorly differentiated carcinoma, while cervico-vaginal Papanicolaou (Pap) smear was negative for malignant cells. Right sided fallopian tube carcinoma in-situ was diagnosed on histopathological examination of surgical hysterectomy with B/L salpingo-oophorectomy specimen. As observed in the current case, unusual tumor histology with broad papillary fronds lined by pleomorphic cells showing nuclear stratification and focal involvement of endometrial curettage specimen may be considered a useful pointer for tubal malignancy.

Prolonged inflammation or irritation due to renal calculi can induce glandular metaplasia of the urothelium and even malignant neoplasm. Primary adenocarcinoma in pelvicalyceal system is a rare tumor in such patients. Here, a case of carcinoembryonic antigen (CEA) positive primary tubulovillous adenocarcinoma in pelvicalyceal system is reported. A 57-year-old male with right abdominal pain and microscopic hematuria and the history of nephrolithotomy for recurrent renal calculi referred to our center. Radiological findings showed well-defined lobulated mass with calcification in interpolar region of right kidney extending up to pelvicalyceal system along with calculi in pelvicalyceal system and ureter with moderate hydroureteronephrosis. Laparoscopic right radical nephrectomy was performed. Histopathological examination revealed tubulovillous adenocarcinoma of renal pelvicalyceal system with CEA positivity. Patient was asymptomatic and had no recurrence after one and a half years. Primary tubulovillous adenocarcinoma in renal pelvis though rare, is usually associated with intestinal metaplasia of urothelium induced by prolonged chronic inflammation and renal calculi.

Xanthogranulomatous oophritis is an uncommon, non-neoplastic, chronic process in which the affected organ is destroyed by massive cellular infiltration of foamy histiocytes admixed with multinucleated giant cells, plasma cells, fibroblasts, neutrophils, and foci of necrosis. The etiology of this entity is unknown, but it shares histopathological findings similar to those of xanthogranulomatous change occurring in various organs, including the gallbladder and kidney.
Case Report: The current case was a 20-year-old female presenting with a tubo-ovarian mass with suspicion of malignancy on clinicoradiological findings and final diagnosis of xanthogranulomatous oophritis established on histopathology. Clinically and radiologically, xanthogranulomatous oophritis mimics tumor of the ovary and fallopian tube, thereby making it an important entity. A vigilant histopathological evaluation is important to diagnose the disease.

Malignant melanoma is a tumor arising from melanocyte; this tumor rarely occurs before puberty, with higher mortality rate in males and better survival rate in female patients affected by metastatic melanoma (1, 2). These facts propose that a relationship and association may exist between estrogens and melanoma. The effects of estrogens are mediated by estrogen receptor alpha and beta (3) that are members of the nuclear hormone receptor family. Estrogen receptors act by ligand-dependent binding to the estrogen-response element, leading to transcriptional regulation of target genes (4). Although these receptors have a high degree of homology in the DNA-binding domain, they are different in their N-terminal and ligand-binding domain (E-domain) (5). Moreover; the effects of these two receptors are also different, while estrogen receptor alpha is associated with stimulation of growth. Estrogen receptor beta (ERbeta) is associated with suppression of stimulation or inhibition of cells from multiplying (2). A number of reports show either a decreased expression of ERbeta messenger RNA and ERbeta protein or an increased estrogen receptor alpha/beta mRNA ratio in tumor versus normal tissue in several cancers such as breast, ovary, colon, and prostate (6, 7). As the expression of ERbeta in melanocytic lesions is controversial and finding new diagnostic methods to differentiate between benign and malignant melanocytic lesions is essential, the current study was conducted using immunohistochemical staining to characterize the expression of ERbeta in dysplastic nevi and melanoma. The expression of ERbeta was investigated in 10 patients with melanoma (five male and five female) and 10 patients with dysplastic nevi (seven male and three female) at the Department of Dermatology, Shahid Beheshti University of Medical Science, Tehran, Iran. All cases underwent immunohistochemical analysis according to the method described by de Giorgi et al. (2, 8). Only one of the patients with melanoma had ERbeta expression of grade III and the other nine patients had grade I, but all the dysplastic nevi had grade III staining. Comparison of melanocytes staining levels in the two mentioned groups with the Mann-Whitney U-test revealed a significant difference between estrogen receptor beta staining samples (P-value=0.0002). Results of the current study suggested a probable role for estrogen receptors in melanoma; in addition, it proposed ERbeta as a valuable diagnostic marker to differentiate between benign and malignant melanocytic lesions; however, according to the relatively small number of patients, further comprehensive studies should be conducted to confirm the current study

An important problem to manage diabetes mellitus is controlling the patients` blood glucose. Fluctuation of blood glucose results in molecular biochemistry change and can result in unwanted diabetic complications (1). In clinical practice, hemoglobin A1C (HbA1C) is a common useful laboratory test to follow-up patients with diabetes (2). Sometimes, an unexpected laboratory result can be observed. Here, the authors presented a case of extremely low hemoglobin A1C level and discussed its clinical importance.
The current study was a consultation case of an abnormally low HbA1C level. The patient was a 40-year-old male with the history of cerebral stroke and on control of diabetes mellitus. The patient was firstly diagnosed with diabetes mellitus at the time of diagnosis of stroke. The HbA1C level of this patient at the first time on the first diagnosis of diabetes mellitus was 7.2% (fasting plasma glucose 218 mg/dL). This case was on strict diet control and took oral metformin 2000 mg/day. The HbA1C levels at the 1st, 2nd, 3rd, 4th, 5th, and 6th months after the first diagnosis were 6.4%, 6.4%, 6.1%, 6.1%, 5.9%, and 5.9%, respectively. However, the aberrant result was observed on the 7th month that the HbA1C was 3.2% (the fasting blood glucose level at this time was 92 mg/dL). The laboratory already checked and validated the result. The other laboratory investigations including complete blood count, blood lipid, uric acid, liver function test, and renal function test were within normal limit. Focusing on the performance of HbA1C test, the precision and accuracy of the test, coefficient of variation (CV) was 1.2% and mean bias +0.4 %, which were according to the clinical pathology standards (3). All tests were performed at an ISO15189 certified laboratory. Therefore, the main question is “What is the cause of abnormally low HbA1C in this case?”
To confirm the problem, repeated HbA1C test was performed and the fructosamine test was also performed in parallel. The low HbA1C level was still observed (3.3%). The fructosamine test was also performed and the abnormally low fructosamine level was observed. Hence, this case was consulted to a clinical pathologist expert. The expert verified and confirmed the correctness of laboratory analysis. The possible causes of the cases with abnormally low HbA1C are listed as a) extremely diet control of the patient, b) excessive use of antidiabetic drugs, and c) laboratory error. Also, hemolytic anemia or hemorrhage might be a cause of reduced HbA1c. Nevertheless, in the current case, there was no evidence of hemolytic anemia or hemorrhage (the reticulocyte count and serum bilirubin were within normal limits and the blood smear examination showed normal appearance). In the current case, laboratory error was excluded. History taking showed that the patient extremely practiced food restriction and avoided any fruit and sugar products after his onset of stroke. Also, the patient consumed only one-sixths of food amount that he did before the stroke. Under such circumstances, the patient felt fainting in the afternoon every day. He was suggested not to be too much diet restricted and the dosage of antidiabetic drug was reduced to 500 mg daily. After modification, the patient had no problem and the follow-up visits showed the normal HbA1C in the next three months and he never had the problem of extremely high or low HbA1C level to date (24th month after diagnosis of stroke).
Laboratory investigation is a tool of family physician to manage primary care for common diseases. The diabetes mellitus is a very common problem. The basic practice is to monitor the glucose control. Of several laboratory tests, hemoglobin A1C is a very good test that can be useful in clinical practice. The abnormally high HbA1C level can be observed in cases with underlying hemoglobinopathy, although there is no problem of poor diabetes control (4). However, there are also some limitations in using due to the possibility of incorrect high result. The aberration of laboratory result can be observed in the area with high prevalence of hemoglobinopathy such as Southeast Asia (5).
In general practice, the abnormally high HbA1C level is commonly observed in the patients with diabetes and poor diabetes control. However, the opposite case of the abnormally low HbA1C level is rarely mentioned. In the current case, an abnormally low HBA1C level was observed, which is not common in clinical practice. There are many possible causes as already mentioned, but the important concern is usually the laboratory error. Sometimes, the patients take herbal products with glucose lowering effects that can induce unwanted hypoglycemia. Nevertheless, in the current case, the patient did not take any additional herbal products, but excessively and strictly controlled intake of food. The excessive control can result in low blood glucose accumulation and low HbA1C. In the current case, although there is no clinical problem yet, the problem could exist if there were no detection of the abnormally low HbA1C level.