A pediatric case with hemolytic uremic syndrome associated with COVID-19, which progressed to end-stage kidney disease.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a serious cause of acute kidney injury in children. There is a suggestion that coronavirus disease 2019 (COVID-19) may be a trigger for HUS. In this study, we present a pediatric case diagnosed with HUS associated with COVID-19, which progressed to end-stage kidney disease. CASE: A previously healthy 13-year-old girl with fever and vomiting was referred to our hospital. Laboratory investigations revealed direct Coombs-negative hemolytic anemia, thrombocytopenia and renal impairment accompanied by COVID-19 infection. Although anemia and thrombocytopenia showed improvement on the seventh day after admission, the renal impairment persisted. The histopathological findings of a renal biopsy were compatible with both HUS and COVID-19. One month later, the patient had a recurrence of HUS, again testing positive for COVID-19. Kidney function improved with plasma exchange therapy. Eculizumab treatment was recommenced after COVID-19 PCR became negative. Anemia and thrombocytopenia did not recur with eculizumab, while renal impairment persisted. Eculizumab was discontinued after three months when genetic analysis for HUS was negative. Subsequently, the patient was diagnosed with end-stage kidney disease. CONCLUSIONS: COVID-19 can be associated with HUS relapses, leading to chronic kidney disease. Further studies should investigate the mechanism of HUS associated with COVID-19.

Pathological findings directing immunotherapy in renal cell carcinomas.

Tweetable abstract Immunotherapy options in RCC treatment are increasing day by day. In pursuit of this objective, we have explored the role of pathology throughout the process, from the development to the implementation of immunotherapy in this paper.

Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature.

Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.

Mineralogy, geochemistry, and micromorphology of human kidney stones (urolithiasis) from Mersin, the southern Turkey.

This study describes the primary characteristics of the selected kidney stones surgically removed from the patients at the Mersin University Hospital in the southern Turkey and interprets their formation via petrographic, geochemical, XRD, SEM-EDX, and ICP-MS/OES analyses. The analytical results revealed that the kidney stones are composed of the minerals whewellite, struvite, hydroxyapatite, and uric acid alone or in different combinations. The samples occur in staghorn, bean-shaped composite, and individual rounded particle shapes, which are controlled by the shape of the nucleus and the site of stone formation. The cross-section of the samples shows concentric growth layers due to variations in saturation, characterizing the metastable phase. Kidney stone formation includes two main stages: (i) nucleation and (ii) aggregation and/or growth. Nucleation was either Randall plaque of hydroxyapatite in tissue on the surface of the papilla or a coating of whewellite on the plaque, or crystallization as free particles in the urine. Subsequently, aggregation or growth occurs by precipitation of stone-forming materials around the plaque or coating carried into the urine, or around the nucleus formed in situ in the urine. Urinary supersaturation is the main driving force of crystallization processes; and is controlled by many factors including bacterially induced supersaturation.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.

Deep learning as a new tool in the diagnosis of mycosis fungoides.

Mycosis Fungoides (MF) makes up the most of the cutaneous lymphomas. As a malignant disease, the greatest diagnostical challenge is to timely differentiate MF from inflammatory diseases. Contemporary computational methods successfully identify cell nuclei in histological specimens. Deep learning methods are especially favored for such tasks. A deep learning model was used to detect nuclei Hematoxylin-Eosin(H-E) stained micrographs. Nuclear properties are extracted after detection. A multi-layer perceptron classifier is used to detect lymphocytes specifically among the detected nuclei. The comparisons for each property between MF and non-MF were carried out using statistical tests the results are compared with the findings in the literature to provide a descriptive analysis as well. Random forest classifier method is used to build a model to classify MF and non-MF lymphocytes. 10 nuclear properties were statistically significantly different between MF and non-MF specimens. MF nuclei were smaller, darker and more heterogenous. Lymphocyte detection algorithm had an average 90.5% prediction power and MF detection algorithm had an average 94.2% prediction power. This project aims to fill the gap between computational advancement and medical practice. The models could make MF diagnoses easier, more accurate and earlier. The results also challenge the manually examined and defined nuclear properties of MF with the help of data abundance and computer objectivity.

Pediatric EBV Positive Mucocutaneous Ulceration in Stomach a Rare Entity.

Epstein Barr virus (EBV) related lymphoproliferative diseases may occur in immunocompromised patients or patients with a history of drug use causing immunodeficiency. EBV positive mucocutaneous ulceration in the new classification of lymphoproliferative diseases in 2016 is very rare in children. Involvement occurs in the skin, oral mucosa, and gastrointestinal system. Gastric involvement is very rare in the literature. There is no case of gastric involvement in children. There are no specified modalities in the treatment of EBV positive mucocutaneous ulceration. We presented our pediatric patient with ataxia telangiectasia who presented with abdominal pain and difficulty swallowing and diagnosed with EBV positive mucocutaneous ulceration in the stomach. We started brentuximab vedotin during the treatment process, and complete remission was achieved after 6 cures of treatment. Our patient is the first case of EBV positive mucocutaneous ulceration in the pediatric case series.

The role of CD1a expression in the diagnosis of cutaneous leishmaniasis, its relationship with leishmania species and clinicopathological features.

Cutaneous leishmaniasis is caused by a flagellated protozoan transmitted by the bite of a female sandfly. The clinical and demographic details of this disease, predominantly affecting immunocompetent individuals, are recognized by the WHO as a Neglected Tropical Disease. We sought to determine the usability of CD1a immunohistochemical staining to detect amastigotes especially in cases where leishmaniasis is suspected but evident amastigotes could not observed. We also evaluated the relationship between CD1a expression and leishmania subtypes. A total of 84 cases diagnosed with leishmaniasis or suspected leishmania on histo-morphological evaluation of skin biopsies were included in the study. Amastigotes were easily detected in hematoxylin eosin in 18 of 84 cases. In 23 cases, amastigotes could not detect in hematoxylin eosin sections. The immunostains for CD1a are demonstrated amastigotes in 60 of 84 cases. However, a small number of amastigotes became visible by positive staining with CD1a in 43.4% of the cases in that amastigotes could not detected in hematoxylin eosin. A statistically significant correlation was found between amastigote amount in hematoxylin eosin and CD1a expression. In addition, a significant correlation was observed between CD1a expression, age and clinical pre-diagnosis of the cases. It was observed that amastigotes were easily detected in hematoxylin eosin in Leishmania Infantum / donovani positive cases in polymerase chain reaction (PCR), and at the same time, it was found that CD1a expression was significantly higher. Using histopathology examination with CD1a staining and/or PCR methods, a diagnosis of leishmaniasis can be established and early treatment initiated. This contributes to reduce transmission and prevalence.

Metachronous Wilms Tumor, Glioblastoma, and T-cell Leukemia in an Child With Constitutional Mismatch Repair Deficiency syndrome due to Novel Mutation in MSH6 (c.2590G>T).

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer predisposition syndrome results from biallelic germline mutations affecting the key DNA mismatch repair gene: MLH1, MSH2, MSH6, or PMS2. CMMRD is associated with a high risk of developing early onset of central nervous system tumors, hematologic, and intestinal tract tumors. Clinical manifestations, genetic screening, and cancer prevention strategies are limited. In this report we present a patient with metachronous Wilms tumor, glioblastoma, and acute T-cell lymphoblastic leukemia. He had cutaneous features of neurofibromatosis type 1 (NF1). Molecular testing revealed a novel homozygous mutation in MSH6 (c.2590G>T; p.G864*) that has not been reported previously. CMMRD should be considered in patients with cutaneous features similar to NF1 if tumor is found other than expected tumors in NF, early onset cancer, and strong family history of cancer.

Shear wave elastography findings in Immunoglobulin A Nephropathy patients: is it more specific and sensitive for interstitial fibrosis or interstitial fibrosis/tubular atrophy?

Background: Prediction of prognosis in Immunoglobulin A Nephropathy (IgAN) and taking appropriate precautions may reduce annual incidence of chronic kidney disease. This may be possible by close follow-up for the development and progression of interstitial fibrosis (IF) or interstitial fibrosis/tubular atrophy (IFTA) in IgAN patients.Aim: To investigate whether Young's elastic modulus (YM) which measured shear wave elastography (SWE) might be used for follow-up of IF or IFTA in IgAN patients.Methods: Prospective study was approved by Human Research Ethics Committee. Group 1 consisted of patients with IgAN. Group 2 consisted of healthy control participants. Young's elastic modulus which is a value of stiffness along with longitudinal stiffness was used to evaluate tissue elasticity. Specificity, sensitivity, positive predictive value (PPV) of YM for the presence of IF and IFTA were evaluated.Results: Group 1 consisted of 30 participants, and group 2 consisted of 32 participants. Sensitivity and specificity of SWE to diagnose presence of IF for YM > 15 kPa were 89% and 90%, respectively. PPV among the ones whom IF was diagnosed by YM >15 kPa was 91%. Sensitivity and specificity of SWE to diagnose presence of IFTA for YM > 15 were 65% and 51%, respectively. PPV among the ones whom IFTA was diagnosed by YM >15 kPa was 78.1%.Conclusions: YM which measured SWE is highly specific and sensitive in the diagnosis of IF, but not for IFTA in IgAN patients. Therefore, progression for IF in IgAN may be followed by SWE.

The role of COL6A1and PD-1 expressions in renal cell carcinoma.

OBJECTIVE: The COL6A1 is a gene encoding the alpha 1 polypeptide subunit of collagen 6 (COL6A1), an extracellular matrix protein subunit. Programmed cell death receptor-1 (PD-1) and its ligand, programmed cell death receptor ligand-1 (PD-L1) have been shown to have a prognostic significance in clear cell renal cell carcinomas (RCCs). In this study, we evaluated the expressions of COL6A1 and PD-1 in four different RCC subtypes. MATERIALS AND METHODS: A total of 161 radical nephrectomy and nephron-sparing surgery cases with RCCs from five different health care centers were included in this study. Clinical data of the cases were taken from electronic records of the institutions. The pathological data were collected by an expert uropathologist and re-evaluated with slides obtained from paraffin blocks of the cases. The correlation of COL6A1 and PD-1 expression with sex, age, tumor type, lymphovascular invasion (LVI), World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, and tumor stage (pT) was analyzed with the Pearson chi-squared test. RESULTS: Patients with sarcomatoid RCC and clear cell RCC had significantly higher COL6A1 scores and intensities than in other types of RCC (p=0.004 and p=0.002, respectively). WHO/ISUP grade and, COL6A1 and PD-1 staining scores also showed positive correlation (r=0.230, p=0.004 and r=0.277, p=0.001, respectively for COL6A1 and r=0.191, p=0.018 and r=0.166, p=0.041, respectively for PD-1). The staining scores and intensities of COL6A1 and PD-1 were not different between the patients with positive and negative LVI (p>0.05). CONCLUSION: In high-grade RCCs, we found the relationship between immunohistochemical staining scores of COL6A1 and PD-1 proteins and clinical, demographic, and histopathological parameters. Our results proved that COL6A1 and PD-1 are really promising proteins as prognostic parameters and for targeted immunotherapy.

Topical Application of High-Dose Mesna Prevents Adhesion Formation: An Experimental Animal Study.

BACKGROUND: Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats. MATERIALS AND METHODS: Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed. RESULTS: Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna. CONCLUSIONS: This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.

Effective High-dose Interferon-α Therapy in a 13-Year-Old Girl With Erdheim-Chester Disease.

Erdheim-Chester disease (ECD) is a proliferative disorder of non-Langerhans histiocytes with a higher incidence in the fifth to seventh decades and rarer occurrence in the pediatric population. Although ECD typically involves bone, it can also affect the central nervous system, cardiovascular system, retro-orbital space, retroperitoneal space, and kidneys, lungs, and skin. A 13-year-old Syrian girl who presented with multisystemic involvement was diagnosed with ECD. The B-Raf proto-oncogene V600E mutation was not detected in ECD lesions. Response to the high-dose interferon-α therapy was excellent in this pediatric patient. In this article, pediatric ECD case reports are also reviewed.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

The histopathological evaluation of healing effects of vitamin C administered before methotrexate therapy on testicular injury induced by methotrexate.

OBJECTIVE: Methotrexate (MTX) leads to acute toxic side effects in tissues or organs containing rapidly dividing cells such as seminiferous tubules. In this study, we investigated the protective effects of vitamin C against MTX-induced injury in rat testis. MATERIAL AND METHODS: A total of 31 rats were divided into 4 groups, including the control group. The study was completed within 4 weeks and the rats received daily doses of 2 mL/kg SF, 100 mg/kg vitamin C and 10 mg/kg/day MTX i.p according to their groups. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each group. RESULTS: The vitamin C + MTX group showed more similarity with the control group. Statistically significant results were achieved between groups as for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score. When compared with the group which received vitamin C after MTX therapy, values for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were significantly higher in the group which received vitamin C before initiation of MTX therapy. CONCLUSION: Vitamin C decreased MTX-induced testicular histological injuries, especially when used before MTX therapy.

Cholesteatoma in ectopic kidney.

Cholesteatoma in the urinary system is a rarely seen benign condition. Rosina firstly defined this condition in the year 1953. Histopathologically it is characterized with keratinization, and squamous metaplasia of urothelial epithelium associated with desquamation of keratinized layers. Flank pain is the most common symptom that is caused by elimination of keratinous material. In our case we will discuss cholesteatoma developed in an ectopic kidney which has not been described in the literature before.

Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

Intranodal palisaded myofibroblastoma - a rare case report and literature review.

Intranodal palisaded myofibroblastoma (IPM) is a benign mesenchymal neoplasm originating from smooth muscle cells and myofibroblasts. The inguinal region is the most common site of this rare tumor. As there are only about 89 such cases reported in the literature, the precise etiology and pathogenesis have yet to be explained adequately. It is characterized by spindle cells, amianthoid fibers, and by the proliferation of hemosiderin-containing histiocytes in the lymph node. A nodular lesion was excised from the inguinal region of a 47-year-old female patient with the clinical diagnosis of lymphoma and/or metastase. Macroscopic examination of a section of the lesion demonstrated a solid appearance. Microscopic examination revealed spindle-cell proliferation, amianthoid fibers, hemosiderin pigment, and extravasated erythrocytes. Nuclei of the spindle cells displayed a palisaded appearance. Compressed lymphoid tissue was observed around the lesion. Neoplastic cells were identified by the presence of vimentin, SMA, Cyclin D1, and beta-catenin. The Ki67 index was less than 1%. Histological examination confirmed the diagnosis of IPM. Although IPM is benign, it is frequently confused with metastatic lesions and lymphomas.