Metastatic Seminoma Presenting in Kidney and Cervical Lymph Nodes after a 25-Year Interval: A Case Report and Literature Review.

Introduction: Seminoma comprises approximately 50% of testicular germ cell tumors. Retroperitoneal lymph nodes are the most common initial metastatic sites but renal metastases are infrequent and the majority of renal tumors represent primary neoplasm. Case Presentation: In this study, we present a 48-year-old male with metastases of seminoma to the cervical lymph nodes and kidney after a 25-year interval. Conclusion: This presentation emphasizes the necessity of advising all patients who are discharged from follow-up that there is a chance of late remote relapse and that if they acquire any illness after discharge, they must inform their doctor about their previous seminoma.

Environmental Risk Factors for Pediatric Acute Leukemia: Methodology and Early Findings.

Background: Acute leukemia is the most common type of malignancy in children, and no major environmental risk factors have been identified relating to its pathogenesis. This study has been conducted with the aim for identifying risk factors associated with this disease. Methods: This study was conducted in 2016-2020 among children aged <15 years residing in Isfahan Province, Iran. Children with newly diagnosed Acute lymphoblastic leukemia, including Acute myeloid leukemia (ALL and AML) were considered a case group. The control group was selected among children hospitalized in orthopedic and surgery wards in the same region. Demographic data, parental occupational exposures and educational level, maternal obstetric history, type of feeding during infancy and parental smoking habits, exposure to pesticides, and hydrocarbons besides dietary habits (using a food frequency questionnaire) were evaluated. Results: Overall, 497 children (195 cases and 302 controls) completed the survey. In the initial analysis, there was no significant difference between case and control groups about type of milk feeding (P = 0.34) or parental age (P = 0.56); however, an association between mothers' education and increased risk for ALL was observed (P = 0.02). Conclusions: The results of this study can be helpful in better understanding the environmental risk factors involved in the incidence of acute leukemia. Future publications based on the analysis of the database created in the present study can lead to recognizing these factors. In addition, evaluating the effect of these factors on treatment outcomes is an important step in reducing the burden of the disease.

Anti-GBM disease with positive serum anti-GBM antibodies but negative IgG deposition: A case report.

Anti-glomerular basement membrane antibodies are significantly specific for detecting anti-glomerular basement membrane disease. These antibodies are typically targeted against the non-collagenous (NC1) domain of the alpha 3 chain of type IV collagen and, to a lesser extent, the α4(IV) or α5(IV) chains, which create a triple-helical structure in the glomerular basement membrane. The modification of the hexameric structure of NC1 (α3(IV)) results in the exposure of new epitopes, leading to an immune reaction and the subsequent deposition of linear antibodies along the glomerular basement membrane, culminating in crescentic glomerulonephritis. Anti-glomerular basement membrane antibodies that are positive are believed to be pathogenic and capable of binding to the glomerular basement membrane in vivo, particularly in the context of rapidly progressive glomerulonephritis. Herein, we present a patient with positive serum anti-glomerular basement membrane antibodies but negative IgG deposition. The current findings are significant for raising physicians' awareness of the probable errors in detecting anti-glomerular basement membrane antibody disease as a possible cause of irreversible kidney failure.

Primary Esophageal Small Cell Neuroendocrine Carcinoma in a Child: A Case Report with Review on Demography, Presentation, Treatment, and Survival.

Primary gastrointestinal small cell carcinoma is reported 0.1%-1.0% of malignant gastrointestinal tumors and predominantly in the esophagus. All reported cases are in the adult population. We present a 9-year-old boy with small cell neuroendocrine carcinoma of the esophagus with mediastinal lymph node involvement, whose chief complaint was progressive dysphagia. He survived for 22 months with chemoradiation but did not have resectional surgery. Although small cell neuroendocrine carcinoma of the esophagus is extremely rare in children, it should be considered in the differential diagnosis of any undifferentiated tumor of the esophagus in any age.

BAT25, ACVR2, and TGFBR2 Mononucleotide STR Markers: A Triplex Panel for Microsatellite Instability Testing in Colorectal Tumors.

Background: Microsatellite instability (MSI) in colorectal cancer (CRC) patients is considered as a diagnostic and prognostic marker. MSI is a consequence of mismatch repair deficiency which is evaluated using the different microsatellite markers on the whole genome. In this pilot study, the diagnostic value of a novel triplex panel including three mononucleotide markers has been evaluated in comparison to the standard Promega kit for MSI testing in CRC patients with Amsterdam II criteria. Materials and Methods: DNA extracted from tumors and normal Formalin-Fixed Paraffin-Embedded (FFPE) tissues of index cases from 37 HNPCC (Hereditary non-polyposis colorectal cancer) families were evaluated for MSI state. Primer design for three markers, including BAT25, ACVR2, and TGFBR2, was performed using 19 nucleotides of the M-13 phage. The instability of each marker was assessed through fragment analysis in comparison with Promega kit markers for all patients. The sensitivity and specificity of each marker have been calculated. Results: The comparative evaluation of MSI in both tumors and normal adjacent FFPE tissues demonstrated a separate sensitivity as 100%, 83.3%, and 76.9% for BAT25, ACVR2, and TGFBR2, respectively, and 100% sensitivity in the form of a triplex. Moreover, the specificity for each of these three markers in MSI testing was estimated as 100%, separately and in the form of the triplex in comparison with the Promega pentaplex standard Kit. Conclusions: A high sensitivity and specificity for the novel triplex panel in MSI-testing were estimated among Iranian patients. More studies are recommended to confirm this panel as a diagnostic kit for MSI testing.

High claudin-4 antigen expression in triple-negative breast cancer by the immunohistochemistry method.

Background: Triple-negative breast cancer is a heterogeneous subtype of breast cancer. Claudin is an epithelial tight junctional protein, and also it is a receptor for clostridium perfringens enterotoxin and shows impairment of expression in several cancers. The chief purpose of this study is to assess the claudin-4 expression in triple-negative breast cancer (TNBC) Iranian patients and evaluate its correlation with some clinicopathological factors. Materials and Methods: In this study, 81 TNBC patients were evaluated for the claudin-4 expression by immunohistochemistry. The slides' staining intensity was examined and scored from 0 to 3. Then, slides were reviewed to assess the percentage of cells with membrane and cytoplasmic staining; the obtaining scores were 1-4. Finally, added the resulting two numbers from two stages, and the final number was a maximum of 7. Final scores of 0-3 were considered the low expression, and 4-7 were considered the high expression. Finally, the collected data were analyzed using the Chi-square test. Results: Eighty-one women with breast cancer and a mean age of 49 ± 12 years participated in the study. In 80% of the patients, there was a high expression of claudin-4 marker, and 20% had low expression. The expression level of the marker was not significantly correlated with age, tumor size, lymph node involvement, tumor grade, disease stage, Ki-67, and metastasis. Conclusion: The present study confirmed the high frequency of claudin-4 antigen expression in TNBC patients, and no significant correlation was observed between the expression of antigen and demographic or clinicopathological factors.

A Simplified Protocol for Microsatellite Instability Evaluation in Iranian Patients at Risk for Lynch Syndrome.

OBJECTIVE: The most important tumor characteristic of Lynch syndrome (LS) is microsatellite instability (MSI). In the current study, BAT34c4 and BAT26 mononucleotide markers were evaluated as part of efforts to test a cost-effective panel for MSI testing in Iranian patients, comparing it with the Promega kit. METHODS: Amsterdam II clinical criteria were used to identify patients at risk for LS. The MSI status of these patients was determined using BAT34c4 and BAT26 markers, as well as the Promega kit. The results of both methods were compared, and the sensitivity and specificity of new short tandem repeat (STR) markers were estimated using statistical formulas. RESULTS: Of the 37 patients we studied who were at risk for LS, 27% showed MSI-high results, via the Promega kit. The same results were achieved for BAT34c4 and BAT26 separately. CONCLUSIONS: The novel 2-marker kit for MSI testing has similar accuracy as the Promega kit at a lower cost, due to fewer markers and a more economical labeling method.

Comparison of expression of CD1a and CD68 markers in skin leishmaniasis samples with positive and negative Leishman body.

BACKGROUND: Leishmaniasis is one of the most important infectious illnesses around the world. Given the high commonness of this disease, specifically its skin type in Iran and due to the role of the Leishman bodies in diagnosis, the aim of present study was evaluating the expression of two CD1a and CD68 markers in cutaneous leishmaniasis lesions with and without Leishman bodies. METHODS: In this case-control study, 70 skin samples of patients with cutaneous leishmaniasis (35 patients with Leishman body as case group and 35 patients without Leishman boy as control group) were investigated during 2018-2019. The expression of CD1a and CD68 markers and immunohistochemistry staining (IHC) were investigated in this study. RESULTS: The expression of CD1a in the group with Leishman body was significantly higher than group without Leishman body (P=0.01), but there was no significant difference between groups as expression of CD68 (P=0.40). The frequency of hyperkeratosis, parakeratosis, exocytosis, acanthosis, spongiosis, hydropic degeneration of basal cell layer, lichenoid reaction, pseudoepitheliomatous hyperplasia, ulcer, thinning of the epidermis, mononuclear cells, and extension of inflammation into lower dermis in the group with Leishman body was higher than group without Leishman body (P<0.05). CONCLUSION: The expression of CD1a and other morphological findings help to diagnose the difference between leishmaniasis with and without Leishman body.

Safety assessment of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

Rice is considered one of the most important staple food crops. Genetically modified (GM) Bt rice, harbored cry1Ab gene expressing the insect-resistance protein has been developed to resistance to the insects. In this study, we assessed the safety of the GM Bt rice on Sprague-Dawley rats for 90 days. Totally, 120 rats in both sexes were used for three different diets, including 50% GM Bt rice, feeding with 50% rice, and standard feeding. Each 40 SD rats including 20 males and 20 females were considered as each diet. The clinical variables such as body weight and food consumption were measured and a range of clinical tests was examined, including hematology, serum chemistry parameters, urinalysis profile, thyroid, and sex hormone levels. Pathological assessments were also done. The results showed that the mean weekly feed utilization (%) had no significant difference among the studied groups. Also, blood biochemistry, hematological parameters, urine analysis, and hormonal levels had no significant differences among the groups. However, alanine aminotransferase was less in males versus female feeding with GM Bt rice. No histopathological changes were observed among the groups. In conclusion, this study demonstrated that GM Bt rice had no obvious adverse effects on rats' health.

Androgen Receptor Expression and Its Correlation with Clinicopathological Parameters in Iranian Patients with Triple Negative Breast Cancer.

BACKGROUND & OBJECTIVE: Our knowledge about correlation of androgen receptor expression and clinicopathological properties of triple-negative breast cancer (TNBC) patients is inadequate, particularly in the Iranian population. The main aim of the present study was to assess the AR expression in TNBC Iranian patients and evaluate its correlation with their clinicopathological parameters. METHODS: Herein, 76 TNBC patients were evaluated for the AR expression by immunohistochemistry. The slides' staining intensity was investigated according to the average degree of nuclear staining and sub-classified into negative (0), weak (1), moderate (2), or strong (3). Subsequently, the positive cells percentage for each slide was assessed and sub-classified into <25% (1), 25-50% (2), 50-75% (3), and >75% (4). The aggregation of these two scores was used as the final score ranging from 0 to 7. While 4-7 scores were selected as positive, the others were included in the AR-negative expression group. Fisher's exact test was used to analyze the AR expression correlation with the clinicopathological parameters. RESULTS: Positive immunoreactivity for AR was observed in 8 out of 76 (11%) specimens. No-correlation (P>0.05) was observed between the AR expression and grade, stage, lymph node status, and Ki-67 level. The AR-positive patients exhibited older age at the time of diagnosis (P=0.0339) and larger tumor size (P=0.0224) in comparison with the AR-negative patients. Low percentage of TNBC patients expressed AR and no significant correlation was observed between its expression and most of the clinicopathological parameters. CONCLUSION: AR may not be a suitable biomarker and treatment target for the Iranian patients with TNBC.

Newly Diagnosed Glomerulonephritis During COVID-19 Infection Undergoing Immunosuppression Therapy, a Case Report.

During the COVID-19 pandemic, we had a 25 years old male case without any underlying disease or history of autoimmune disease in COVID-19 Clinic, Isfahan, Iran. He presented with arthralgia and weakness so we started COVID-19 therapeutic regimen. In his hospitalization, creatinine increases and abnormalities in random urine sediment was seen. Methylprednisolone and cyclophosphamide were prescribed due to suspected glomerulonephritis. After renal biopsy the diagnose was confirmed as crescentic proliferative glomerulonephritis. The patient also, underwent plasmapheresis and intravenous immunoglobulin injection. He was discharged healthy without development of new pulmonary symptoms despite immunosuppressive treatment.

Osseous Metaplasia in Rectal Polyp: A Case Report with Review of Probable Pathogenesis.

Heterotopic bone formation is a rare event in gastrointestinal lesions, especially in the pediatric population. Osseous metaplasia is exceedingly rare in colonic polyps. We present a case of rectal juvenile polyp with stromal osseous metaplasia in a 10-year-old male child. This histologic finding is very rare in children with colorectal polyps.

Renal biochemical and histopathological alterations of diabetic rats under treatment with hydro alcoholic Morus nigra extrac.

Introduction: Morus nigra fruit is known to have antioxidant effects and used to control the blood sugar level in traditional medicine. Objectives: This study was conducted to investigate the biochemical and histopathological changes in the serum and kidneys of diabetic rats treated with hydroalcoholic M. nigra extract. Materials and Methods: In this study, 60 male Wistar rats were divided into five groups of 12 each. After induction of diabetes with alloxan, the diabetic rats were treated with hydroalcoholic extract of M. nigra at different concentrations. Then, the animals were anesthetized and the serum levels of glucose, creatinine, and urea as well as kidney tissue catalase level measured. The kidney tissue was also histopathologically examined. Results: Milder glomerular damage was seen in the group treated with 800 mg/kg of the M. nigra extract compared with diabetic and positive controls, and no difference in the expansion of mesenchymal tissue into renal glomerular vessels observed between the group treated with 800 mg/kg of M. nigra extract and diabetic and positive controls. Furthermore, creatinine levels were significantly higher and urea levels significantly lower in the group treated with 800 mg/kg of M. nigra extract than healthy and positive control groups (P<0.05). Conclusion: Administration of M. nigra extract at 800 mg/kg can prevent kidney tissue damage in diabetic rats and this fruit seems to be beneficial to patients with diabetes.

Immunohistochemical analysis of mismatch repair proteins in Iranian colorectal cancer patients at risk for lynch syndrome.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary cancer predisposing syndrome has molecular and clinicopathological features still have remained ambiguous within Iranian populations. We discuss in this article some molecular and clinicopathological features of the condition. METHODS: The study was a descriptive retrospective and designed on 1659 colorectal cancer (CRC) patients were screened based on early-onset disease and Amsterdam II criteria during 14 years (2000-2013). Immunohistochemistry (IHC) staining was set up to detect expression of mismatch repair (MMR) genes on paraffin-embedded tissue sections of 31 HNPCC-CRC tumors. SPSS 19 software was used to analyze the data. RESULTS: IHC-MMR staining was absent in 7/31 individuals (22.6%) of which 4 cases showed IHC-Absent (IHC-A) in both MSH2 and MSH6 (57.1%), in 2 cases both MLH1 and PMS2 had negative staining (28.6%), and just in one case, MSH6 was defective (14.3%). The frequency of CRC among IHC-A and IHC-Present (IHC-P) families was 67.5% and 27.9%, respectively. Also the most frequent extracolonic cancers in IHC-A group were: stomach (10%), small bowel (5%), and prostate (5%); and in IHC-P group: stomach (18.4%), lung (10.9%), and breast (7.5%). Average age of IHC-A individuals at diagnosis was 38.0 versus 45.3 years in IHC-P individuals. Overall, 20.8% and 57.1% of our index CRCs were localized proximal to the splenic flexure in IHC-P and IHC-A groups, respectively. CONCLUSION: Given the lack of enough information about molecular aspects of hereditary cancer syndromes like HNPCC in Iran, more evaluations are necessary on larger samples using complementary techniques such as MSI-testing and mutation analyses.

Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature.

PURPOSE: Microsatellite instability (MSI) and mismatch repair (MMR) gene expression present a hallmark mutational signature of Lynch syndrome as a common hereditary cancer predisposing condition. Since there is not enough data of molecular and clinicopathological aspects of the disease in Iranian populations, this article is a new description in Central Iran. METHODS: It is a descriptive analytical study in which we screened 1659 colorectal cancer (CRC) patients based on early-onset disease and Amsterdam II criteria during 14 years (2000-2013). MSI testing was applied through a commercial kit evaluating five mononucleotide markers (BAT-25, BAT-26, MON0-27, NR-21, and NR-24) using a fluorescent multiplex PCR method. Immunohistochemistry (IHC) staining was set up to detect expression of four mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2. SPSS 16 software was used to analyze the data. RESULTS: Overall, 31 of 45 screened at-risk families were eventually included to MSI testing of which 9/31 patients (∼29 %) showed MSI in their tumor tissues including 6 (19.4 %) MSI-H (high). BAT-26 was the most instable marker with instability in 7/31 MSI tumors (22.6 %). IHC-MMR staining was absent in 7/31 probands (22.6 %) of which in 4 cases, both MSH2/MSH6 (57.1 %) and, in 2 cases, both MLH1/PMS2 showed deficiency (28.6 %), and just in one case, MSH6 was defective (14.3 %). IHC-MMR was absent in all 6 MSI-H tumors while none of 3 MSI-L tumors were MMR-deficient. Just single MSH6-defective tumor showed MSS state. The frequency of CRC among MMR-deficient and MMR-proficient families was 67.5 and 27.9 %, respectively. The most common extracolonic cancer among both MMR-deficient and MMR-proficient groups was stomach, respectively, with 26.7 and 16.5 %. CONCLUSIONS: A different molecular and clinicopathological phenotype of tumors in CRC Iranian patients at risk for Lynch syndrome could suggest some new molecular mechanisms about which more evaluations are necessary.

Large retroperitoneal paraganglioma concurrent with periampullary adenocarcinoma.

Paragangliomas are tumors that originate from extra-adrenal medullary neural crest derivatives. They are rarely located in retroperitoneal space. These tumors are often discovered incidentally during imaging studies performed for other reasons. Periampullary cancers include adenocarcinomas arising from the pancreas, ampulla of Vater, duodenum or distal common bile duct. The exact site of origin of periampullary tumors is often difficult to ascertain pre-operatively. We report the case of a patient who had a retroperitoneal non-functional paraganglioma, concurrent with periampullary adenocarcinoma. An 81-year-old woman was admitted with progressive abdominal fullness. There was an upper paramedian, left sided, large, palpable mass on the physical examination. Laboratory investigations showed an increase in liver enzyme levels. On abdominal computed tomography the patient found to have a large retroperitoneal mass and dilation in biliary tract, which was confirmed by magnetic resonance cholangiopancreatography. She had a tumoral papi in Endoscopic Retrograde cholangiopancreatography. Which biopsy revealed adenocarcinoma. She underwent surgery for excision of abdominal mass and pancreaticoduodenectomy. And pathologic study showed paraganglioma. This is the first ever reported case of concurrent paraganglioma and periampullary adenocarcinoma.

Ectopic lipoadenoma of parathyroid.

A parathyroid lipoadenoma is a very rare cause of mediastinal mass. The clinical features of this pathologic entity is similar to those of the more common pathologic variants of parathyroid disease associated with primary hyperparathyroidism. A 58-year-old woman presented with huge multinodular goiter. Her thoracic CT scan was done before surgery, showed a posterior mediastinal mass. On microscopic examination, the thyroid was composed of thyroid follicles in varies sizes, compatible with a multinodular goiter and the mediastinal mass, microscopically, was composed of epithelial cells arranged in follicular and cellular nests pattern alter with abundant mature adipose tissue, morphologically closely resembled parathyroid tissue. Thyroid, mesenchymal and neuroendocrine origin for this tumor excluded by immunohistochemistry and the mass was diagnosed as a parathyroid lipoadenoma. In our case, there is a non functional parathyroid lipoadenoma with a very rare presence.

Langerhans cell histiocytosis following Hodgkin lymphoma: a case report from Iran.

The occurrence of Langerhans Cell Histiocytosis (LCH) in a patient with lymphoma is an indication of a probable relationship between them. The two conditions have similarities both clinically and histopathologically. Occurrence of these two conditions in the same patient, particularly not simultaneously, is rare. According to different management and treatment of these conditions, exact histopathologic evaluation and even using immunohistochemistery (IHC) can prevent misdiagnosis. In this report, a 10 year old boy presented who afflicted with LCH 3 years after diagnosis and treatment of mixed cellularity Hodgkin lymphoma.

Expression of basal and luminal cytokeratins in breast cancer and their correlation with clinicopathological prognostic variables.

BACKGROUND: Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer. OBJECTIVE: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma. MATERIALS AND METHODS: Sixty-seven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells. RESULTS: We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression. CONCLUSION: We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.