Adult acute megakaryoblastic leukemia with persistent diarrhea and extreme thrombocytosis: A very unusual case.

ABSTRACT: Acute megakaryoblastic leukemia (AML-M7) is rarely seen in adult patients and patients usually present with cytopenias. Here we discuss diagnostic challenges and pathologic features in a patient with AML-M7 who presented with thrombocytosis and diarrhea. A 63-year-old male patient presented with persistent diarrhea lasting for 2 months, fatigue, and thrombocytosis. The diagnostic workup included a stool analysis, endoscopy colonoscopy, and imaging studies; however, these studies did not reveal any possible etiology. The hematologic evaluation included peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry, and cytogenetic analysis. Eventually, according to pathologic and flow cytometric findings, a diagnosis of AML-M7 was made. Diagnosis of AML-M7 may be challenging, especially in adult patients with atypical presentation. Patients with megakaryoblastic leukemia respond poorly to standard induction regimens and they should be advised to participate in a clinical trial.

The Importance of Sphingomyelin Phosphodiesterase Acid-Like 3b (SMPDL-3b) Levels in Kidney Biopsy Specimens of Children With Nephrotic Syndrome.

OBJECTIVE: It remains unclear whether the low amount of SMPDL-3b required for rituximab binding is the cause of treatment resistance in patients with treatment-resistant nephrotic syndrome with advanced podocyte injury. Given the limited number of studies on the relationship between rituximab and SMPDL-3b, this study was conducted to assess whether SMPDL-3b levels in pretreatment renal biopsy specimens can be used to predict the clinical effectiveness of immunosuppressive drugs, especially rituximab, in children with nephrotic syndrome. METHODS: Kidney biopsy specimens from 44 patients diagnosed with idiopatic nephrotic syndrome were analyzed using immunohistochemical staining with an anti-SMPDL-3b antibody and real-time polymerase chain reaction (PCR) for SMPDL-3b mRNA expression. RESULTS: We showed that SMPDL-3b mRNA expression and anti-SMPDL-3b antibody staining did not differ significantly between the patient groups with different responses to immunosuppressive therapies. CONCLUSION: Our results suggest that SMPDL-3b may actually be an indicator of disease progression rather than a marker for predicting response to a particular immunosuppressive agent.

An exceptionally rare case of Cushing's syndrome caused by ectopic ACTH syndrome due to olfactory neuroblastoma in childhood.

OBJECTIVES: Ectopic adrenocorticotropic hormone secretion/syndrome (EAS) is caused by excess secretion of ACTH leading to hypercortisolism by non-pituitary, commonly malignant origins. We present a rare case of esthesioneuroblastoma (ENB) complicated by EAS in the follow-up period. CASE PRESENTATION: A child presented with nasal obstruction at the age of 10 months. Polypoid mass obstructing the right nasal passage was detected. Magnetic resonance imaging (MRI) showed a lesion limited within the nasal cavity. The lesion was completely removed by nasal endoscopic surgery. The pathologic examination revealed a diagnosis of esthesioneuroblastoma. It was confined to the nasal cavity so chemotherapy/radiotherapy was not administered and began to follow up. At 28 months of age, he presented with rapid weight gain. Laboratory data were consistent with Cushing's syndrome (CS). High-dose dexamethasone suppression test and imaging studies led us to think of ectopic ACTH syndrome originated from ENB relapse. After partial resection of the tumor, ketoconazole treatment was started along with chemotherapy. Hypercortisolemia was kept under control with ketoconazole treatment as long as the treatment was maintained. CONCLUSIONS: Cushing syndrome is a rare endocrine disorder. Adrenal sources of hypercortisolism and ectopic sources of ACTH overproduction should be investigated especially in young children.

Severe acute kidney injury induced by crescentic glomerulonephritis in a child with infective endocarditis.

BACKGROUND: Kidney involvement related to infective endocarditis (IE) may present with different clinical findings. The most common histopathological finding of renal involvement is a combination of proliferative and exudative glomerulonephritis. However, severe acute kidney injury (AKI) induced by crescentic glomerulonephritis (CGN) is extremely rare in children with IE. To date, only 4 pediatric cases with IE-induced CGN had been reported. We present a 14-year old girl with IE-induced CGN. CASE: A 14-year old girl with fever, macroscopic hematuria, oliguria, and acute kidney injury (AKI) was admitted to our clinic. The medical history revealed that the patient had undergone several cardiac interventions due to truncus arteriosus type 1, and she recovered from IE-induced glomerulonephritis following antibiotherapy six months ago. During admission, the patient was diagnosed with IE according to one major (positive imaging finding) and three minor (fever, predisposing cardiac disease, and immunological criterion) criteria. Immediate antibiotic treatment was initiated. A kidney biopsy was performed, which showed crescentic glomerulonephritis (CGN with crescents, > 50%). Daily pulse steroid (3 days), monthly pulse cyclophosphamide (6 doses), and oral steroid (2 mg/kg/day) therapy were initiated with gradual dose tapering. The patient underwent 12 hemodialysis sessions until the 38 < sup > th < /sup > day of the treatment. She was discharged on the 45th day of treatment with normal kidney function tests and negative acute phase reactants. Treatment was maintained with mycophenolate mofetil (MMF) after a 6-month course of cyclophosphamide. MMF was discontinued in the 12th month. At the 18thmonth follow-up visit the patient had mild proteinuria, and was on ramipril therapy. CONCLUSIONS: The occurrence of CGN should be considered in children with predisposing cardiac disease, who develop hematuria, proteinuria, and severe AKI. Although antibiotic therapy alone is often sufficient in this immune complex GN induced by infection, early initiation of additional immunosuppressive therapy in the presence of CGN may be beneficial for long term preservation of kidney functions.

Acute focal bacterial nephritis and prolonged fever.

Acute focal bacterial nephritis (AFBN) is characterised by a complicated upper urinary tract infection ranging from acute pyelonephritis to renal abscess. Timely diagnosis of AFBN is important because antibiotic therapy of longer duration is required. A 10-year-old boy presented with fever for 5 days and bilateral flank pain. He was oriented and cooperative but appeared ill. Physical examination did not reveal any oedema or costovertebral angle tenderness. Acute phase reactants such as erythrocyte sedimentation rate and C-reactive protein were raised, serum creatinine was 1.25 mg/dL (0.31-0.88) and leucocyte esterase was positive in the urine. Ultrasonographic examination demonstrated bilaterally enlarged kidneys with increased echogenicity. Because of the high creatinine level, abdominal magnetic resonance imaging (MRI) was performed instead of computed tomography (CT) for further evaluation. The MRI showed an increase in the size of both kidneys, renal cortical heterogeneity and multiple cortical nodular lesions with diffusion restriction (constrained Brownian movement of water molecules) on diffusion-weighted MRI. A negative urine culture result in children presenting with fever and abdominal pain may mislead the clinicians, causing them to miss a nephro-urological diagnosis. It is therefore recommended that patients in whom the cause of fever cannot be determined be scanned by ultrasound and examined by CT or MRI so that undiagnosed and/or suspected cases of AFBN might be detected.

Comparing human epidermal growth factor receptor 2 amplification and expression using immunohistochemistry and silver in situ hybridisation in gastric carcinoma and lymph node metastasis.

Detecting the amplification and expression of human epidermal growth factor receptor (HER2) is important for planning trastuzumab treatment for patients with gastric carcinoma. The present study aimed to analyse HER2 amplification and expression in primary gastric adenocarcinoma tumours and metastatic lymph nodes using microarray methods, and to assess the potential contribution of these methods to treatment planning. In total, 60 patients with lymph node metastasis were included in the present study. Microarray blocks were obtained from the tissue blocks of primary tumours and metastatic lymph nodes. HER2 expression and amplification were investigated using immunohistochemical and silver in situ hybridisation (SISH) methods, respectively. Following immunohistochemical evaluation of HER2 in primary tumours, the sensitivity and specificity of the microarray method relative to the single block method were 69 and 100%, respectively. For HER2 detection in microarray block sections from primary tumours, the sensitivity and specificity of the SISH method relative to immunohistochemistry were 56 and 100%, respectively. When using SISH in microarray blocked sections, there was a high degree of concordance (98% concordance rate) between HER2 amplification in the primary tumour and the metastatic lymph node. Furthermore, the sensitivity and specificity of metastatic lymph node results relative to those of the primary tumour were 100 and 98%, respectively. Overall, the single block method was more reliable compared with the microarray method for planning treatment. When microarray blocking was used, a large number of samples must be tested to ensure reliable results. The immunohistochemical method is recommended as the first step as SISH alone increases the risk of false-negative results. Assessing HER2 amplification for treatment planning would be beneficial for primary tumours, as well as metastatic lymph nodes.

The importance of IDH1, ATRX and WT-1 mutations in glioblastoma.

Numerous genetic pathways associated with glioblastoma development have been identified. In this study, we investigated the prognostic significance of IDH1 and ATRX mutations and WT-1 and p53 expression in glioblastomas and that of surgical methods, radiotherapy and chemotherapy. 83 patients with glioblastomas were retrospectively evaluated. Immunohistochemical analysis was performed for IDH1, ATRX and WT-1 expression. Tumour cells were positive for IDH1 in 9.6% of the patients. In 4.8% of the patients, loss of ATRX expression was observed in tumour cells; 86.7% of the patients were WT-1 positive, and 12.05% of the patients were p53 positive. No statistically significant difference was found in the progression-free and overall survival according to IDH1, ATRX, WT-1 and p53 expression. There was a statistically significant difference in the progression-free and overall survival according to the radiotherapy status. There was a statistically significant difference in the overall survival according to the chemotherapy status. There was no statistically significant difference in the progression-free and overall survival according to the surgical method. IDH1 and ATRX mutations, p53 overexpression and WT-1 expression alone did not have a significant effect on the prognosis of patients with glioblastoma; however, radiotherapy and chemotherapy had a positive effect on survival.