Clinicopathological Findings in Pediatric Tubulointerstitial Nephritis: Iranian Experience

Introduction: Tubulointerstitial disorders are characterized by diseases that affect the vascular and interstitial compartments of the kidney with relative sparing of the glomeruli. They might be either acute or chronic. Acute tubulointerstitial nephritis (TIN) is associated with acute renal failure due to either acute infection of the kidneys or reaction to medication. Chronicinterstitial nephritis is characterized by many syndromes of renal tubular dysfunction that may be primary or secondary due to renal tubular damage from a wide variety of causes. The aim of this study was to evaluate the pathologic characteristics of acute and chronic TIN and their probable causes.Materials and Methods: All native kidney biopsy specimens with a diagnosis of tubulointerstitial nephritis admitted to Ali-Asghar Hospital, a pediatric referral center in Tehran, from 1983 to 2013 were retrospectively re-evaluated. The demographic data of the patients were collected and pathologic findings were reviewed.Results: Forty-four patients, 18 males and 26 females with a mean age of 8.8 years (SD=4), were enrolled in this study. Thirty-seven (84%) patients had chronic and 7 (16%) had acute TIN. The disease was primary in 32 (72%) patients with a diagnosis of familial nephronophthisis and medullary cystic disease and 12 (28%) had other diseases. Kidney biopsy showed similar pathologic findings including periglomerular fibrosis (72%), different scores of interstitial fibrosis/tubular atrophy (91%), infiltration of inflammatory cells, and segmental and global glomerular sclerosis (89%).Conclusions: Acute and chronic tubulointerstitial nephritis with different etiologies has similar pathologic findings. The patients mostly present in the late stages of the disease; therefore, determining the etiology is impossible. Many cases are congenital.Keywords: Nephritis, Interstitial, Child, Renal Insufficiency

Brain Tumor as a Late Outcome of a Child with Nephrotic Syndrome - Is There Any Association with Immunosuppression?

The association of idiopathic nephrotic syndrome with some malignancies has been reported. We hereunder report a child with focal segmental sclerosis who presented with brain tumor eleven years after renal presentation. A 16- year-old boy presented with nephrotic syndrome since was 5 years old. He was a steroid responder at first but became steroid dependent after subsequent relapses. He received cyclosporine for two years and then mycophenolate mofetil was added for three years. After that, he received losartan and enalapril. Four years later, he developed glioblastoma multiforme.  He passed away two years after surgical resection and chemo-radiotherapy. The occurrence of brain tumor after immunosuppressive therapy in this child might be a late sequel or a coincidence. This might be an alarm for using immunosuppressive agents more cautiously.Keywords: Glioblastoma; Immunosuppression; Mycophenolate Mofetil; Cyclosporine; Losartan; Enalapri; Nephrotic Syndrome.

Diagnostic and prognostic accuracy of miR-21 in renal cell carcinoma: A systematic review protocol

Introduction: Renal cell carcinoma (RCC) is the most common neoplasm in adult kidneys. One of the most important unmet medical needs in RCC is a prognostic biomarker to enable identification of patients at high risk of relapse after nephrectomy. New biomarkers can help improve diagnosis and hence the management of patients with renal cancer. Thus, this systematic review aims to clarify the prognostic and diagnostic accuracy of miR-21 in patients with RCC. Methods and analysis: We will include observational studies evaluating the diagnostic and prognostic roles of miR-21 in patients with renal cancer. The index test and reference standards should ideally be performed on all patients. We will search PubMed, SCOPUS and ISI Web of Science with no restriction of language. The outcome will be survival measures in adult patients with RCC. Study selection and data extraction will be performed by two independent reviewers. QUADAS-1 will be used to assess study quality. Publication bias and data synthesis will be assessed by funnel plots and Begg's and Egger's tests using Stata software V.11.1. Ethics and dissemination: No ethical issues are predicted. These findings will be published in a peerreviewed journal and presented at national and international conferences. Trail registration number: This systematic review protocol is registered in the PROSPERO International Prospective Register of Systematic Reviews, registration number CRD42015025001

Chromogenic in situ hybridisation test for breast cancer patients with equivocal IHC results - A study from Iran

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3) and 246 were CISH negative (73.7). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9 concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90 and 53.8, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing

Učestalost hipertenzije i kardiovaskularnih rizika u djece s ožiljcima na bubrežnom tkivu nakon mokraćne infekcije

Hypertension is a late outcome of refl ux nephropathy and renal parenchymal scar secondary to urinary tract infection (UTI). We presumed that it might be detected much earlier after episodes of UTI and the associated cardiovascular risk factors assessed. Between 2009 and 2011, 85 (67 female and 18 male) children aged 5-15 years with a history of febrile UTI, followed-up for at least one year from the fi rst episode of febrile UTI, were enrolled in the study. The variables included 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, carotid sonography, renal 99mcTc-DMSA, glomerular fi ltration rate, and microalbuminuria. Masked hypertension was detected in 18.8%, hypertension in 7.1% and white coat hypertension in 9.4% of cases. Prehypertension was seen in 20% of children. Out of 85 cases, 43.5% were non-dippers. Out of 56 children with hypertensive and prehypertensive parameters on ABPM, 9.1% showed left ventricular mass index >51g/m2.7 (p>0.05). Signifi cant correlation was only recorded between abnormal blood pressure and the severity of renal parenchymal scar (p<0.05). In conclusion, ABPM is suggested for early detection of masked hypertension and abnormal blood pressure pattern in all normotensive children with a history of recurrent UTI.Hipertenzija je kasni ishod refl uksne nefropatije i ožiljaka na bubrežnom parenhimu koji nastaju nakon mokraćne infekcije. Pretpostavili smo da bi se to moglo otkriti znatno ranije nakon epizoda mokraćne infekcije te procijeniti pridružene kardiovaskularne čimbenike rizika. Od 2009. do 2011. godine, u ispitivanje je uključeno 85 (67 Ž, 18 M) djece u dobi od pet do 15 godina s anamnezom febrilne mokraćne infekcije koja su bila praćena najmanje jednu godinu od prve epizode febrilne mokraćne infekcije. Praćene su sljedeće varijable: 24-satno ambulatorno praćenje krvnog tlaka (ambulatory blood pressure monitoring, ABPM), ehokardiografi ja, karotidni ultrazvuk, 99mcTc-DMSA bubrega, glomerularna stopa fi ltracije i mikroalbuminurija. Maskirana hipertenzija otkrivena je u 18,8%, hipertenzija u 7,1% i hipertenzija “bijele kute” u 9,4% slučajeva. Prehipertenzija je zabilježena u 20% djece. Od 85 slučajeva 43,5% ih nije pokazalo odgovarajući pad krvnog tlaka tijekom noći (non-dipper). Od 56 djece s hipertenzivnim i prehipertenzivnim parametrima na ABPM 9,1% ih je imalo indeks lijeve ventrikularne mase veći od 51g/m2.7 (p>0,05). Značajna korelacija zabilježena je između nenormalnog krvnog tlaka i težine ožiljka na bubrežnom parenhimu (p<0,05). U zaključku, ABPM se može preporučiti za rano otkrivanje maskirane hipertenzije i nenormalnog kretanja krvnog tlaka kod sve normotenzivne djece s anamnezom opetovane mokraćne infekcij

Clinicopathological significance of tumor stem cell markers aldh1 and CD133 in colorectal carcinoma

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 ALDH1 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. © 2021, Iranian Society of Pathology. All rights reserved

The Expression of p21 Marker in Bladder Urethral Tumor and its Association with Histopathologic Characteristicslogic charactristics

Background: In addition to clinical and histologic factors that are able to differentiate between low and high grades of bladder's urethral tumor from each other, there are a number of biomarkers that may be helpful in evaluating the degree, outcome, and prognosis of the tumor. The aim of this study was to investigate the relationship between overexpression of p21 marker and histologic status, prognosis, and recurrence of urethral carcinoma of the bladder. Methods: In this cross-sectional study, the paraffin wax blocks of 356 patients were gathered. Tumor points of the tissue were selected from the main block and mounted on the tissue microarray (TMA) of receptor block. Immunohistochemical staining was performed for the p21 marker. The intensity and extent of staining for this marker were determined by two pathologists using the combined and semi-quantitative method [Histochemical Score (H-Score)]. Results: The expression of p21 marker was significantly different in the high- and low-grade tumors. On the basis of H-Score, and in the high-grade tumor group, this expression was significantly higher than the low-grade (153.85 ± 91.06 versus 130.01 ± 82.20). Using the receiver operating characteristic (ROC) curve analysis, the p21 marker (based on the H-Score) had a high degree of precision in distinguishing high-grade items from the low-grade (ROC = 0.596, P = 0.002). Accordingly, the best cut-off value for the marker in differentiation of two grades was 92.5%, at which, the sensitivity and specificity were 67.7% and 44.7%, respectively. Regarding the results of multivariate logistic regression analysis, in the evaluation of factors related to tumor recurrence, the presence of non-papillary pattern predicted the recurrence (likelihood ratio: 6.363, P = 0.001). Conclusion: By determining the H-Score of p21 marker, the high- and low-grade tumors can be discriminated with an acceptable sensitivity and specificity. The presence of non-papillary pattern has a high predictive value for tumor recurrence

Bilateral maxillary, sphenoid sinuses and lumbosacral spinal cord extramedullary relapse of CML following allogeneic stem cell transplant

Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement. © 2016, Tehran University of Medical Sciences (TUMS). All Rights Reserved

Metastatic Melanoma (Secondary Malignancy) after Recovery from Acute Lymphoblastic Leukemia in a 10-year-old Girl: a case report

Acute lymphoblastic leukemia is the most common malignancy in children with a 5-year survival rate, accounting for 80 of cases. Melanoma is rare in children and has been reported as a sporadically occurring secondary malignant neoplasm in children with acute lymphoblastic leukemia. This study presented a 10-yearold Iranian child with pre-B-cell acute lymphoblastic leukemia that was diagnosed at age 6. She was fully recovered after 2 years of treatment. One year and six months after cessation of treatment, she was referred with a 1x2 cm mass in her right parietal region of scalp. Biopsy of the lesion confirmed the diagnosis of malignant melanoma. Computed tomography scan of the chest and abdomen also confirmed extensive liver metastasis which was corroborated by liver biopsy. Bone scan also revealed bone metastases. Early diagnosis and treatment of these tumors is extremely important and these patients should be closely monitored and undergo regular physical examination

Common bile duct stone associated with hemolytic uremic syndrome

Cholelithiasis is an unusual complication of hemolytic uremic syndrome. A 12-year-old boy with hemolytic uremic syndrome, established by renal biopsy, who developed cholestatic jaundice is presented here. Laboratory results for secondary causes of hemolytic uremic syndrome were normal. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed extrahepatic obstruction. A common bile duct stone, discovered by retrograde cholanglopancreatography was extracted by sphincterotomy. In conclusion, cholelithiasis should be considered as a cause of abdominal pain and cholestasis in patients who are diagnosed as having hemolytic uremic syndrome