Pediatric inflammatory myofibroblastic tumor of the bladder with ALK-FN1 fusion successfully treated by alectinib.

An inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm characterized by the proliferation of myofibroblasts and inflammatory cell infiltration. Although radical resection is the only established treatment strategy for IMT, it can cause functional disorders when vital organs are affected. We describe a case of pediatric IMT of the bladder with FN1-ALK (fibronectin 1-anaplastic lymphoma kinase) fusion. Radical resection might lead to urinary disturbance due to the large tumor size at diagnosis. However, the tumor was successfully treated with alectinib, a second-generation ALK inhibitor, followed by transurethral resection of the bladder tumor without any complications.

Presence of identical B-cell clone in both cerebrospinal fluid and tumor tissue in a patient with opsoclonus-myoclonus syndrome associated with neuroblastoma.

Opsoclonus-myoclonus syndrome associated with neuroblastoma (OMS-NB) is a refractory paraneoplastic syndrome which often remain neurological sequelae, and detailed pathogenesis has remained elusive. We encountered a pediatric patient with OMS-NB treated by immunosuppressed therapy who showed anti-glutamate receptor δ2 antibody and increased B-cells in cerebrospinal fluid (CSF), and multiple lymphoid follicles containing abundant Bcells in tumor tissue. Unbiased B-cell receptor repertoire analysis revealed identical B-cell clone was identified as the dominant clone in both CSF and tumor tissue. These identical B-cell clone may contribute to the pathogenesis of OMS-NB. Our results could facilitate the establishment of pathogenesis-based treatment strategies for OMS-NB.

Half of 'Micrococcus spp.' cases identified by conventional methods are revealed as other life-threatening bacteria with different drug susceptibility patterns by 16S ribosomal RNA gene sequencing.

Bacterial infection during chemotherapy is a fatal complication, therefore precise identification of the pathogenic microorganism is required for treatment. We report that 2 of 4 pediatric patients with malignancy who were diagnosed with Micrococcus spp. infection by conventional methods were finally revealed to have Kytococcus schroeteri and Kocuria marina infection by 16S ribosomal RNA gene sequence analysis (16S rRNA analysis). Although K. schroeteri is morphologically similar to Micrococcus spp., its drug susceptibility profile is quite different from that of Micrococcus spp. K. schroeteri is resistant to penicillin and cephalosporin, which are effective for Micrococcus spp. In fact, penicillin-resistant lethal pneumonia caused by K. schroeteri has been reported in compromised hosts. Based on our results, Micrococcus spp. determined by conventional methods could contain other life-threatening bacteria with different drug susceptibility patterns from Micrococcus spp. To develop an effective empirical treatment for immunocompromised hosts, accumulation of pathogen data by 16S rRNA analysis is required.

Improvement of refractory acyclovir-resistant herpes simplex virus type 1 infection by continuous acyclovir administration.

Resistant herpes simplex virus type 1 (HSV-1) infection is sometimes fatal for immunocompromised patients. Here, we report 10-year-old girl receiving hematopoietic stem cell transplantation developed refractory HSV-1 infection, which was persisted to intermittent acyclovir (ACV) or foscarnet (FOS) administrations but was improved by continuous ACV administration. The isolates from the lesion were identified with low susceptibilities to ACV and FOS by plaque reduction assay due to DNA pol gene mutation. Continuous ACV administration overcomes the efficacy of intermittent administration and could be the best option to treat severe HSV-1 infectious patients.

Accurate detection of renal leukemic involvement in children using 3-D computed tomography modeling.

BACKGROUND: The rate of renal involvement in pediatric acute lymphoblastic leukemia (ALL) at diagnosis varies between reports because renal involvement is diagnosed on renal size larger than aged-matched standards on conventional modalities. We propose a new method for precise renal involvement detection using 3-D enhanced computed tomography (CT) reconstruction. METHODS: Twenty-five children with ALL were evaluated utilizing 3-D enhanced CT reconstruction to measure renal volume before and after induction therapy, renal mass lesions and renal axis at diagnosis. Renal involvement was defined as a marked decrease of renal volume or the presence of mass lesions. RESULTS: According to the 3D-CT criteria, nine of 25 patients (36%) had renal involvement. All of them had bilateral mass lesions except for one who had diffuse nephromegaly alone. This method detected renal involvement more accurately than ultrasonography. When using conventional criteria based on the length of the renal axis, 19 of 25 (76%) had renal involvement, including many cases of false-positive nephromegaly. Patients with renal involvement had significantly more extramedullary involvement according to the 3D-CT-based criteria. CONCLUSIONS: The use of 3D-CT reconstruction was accurate in detecting renal involvement in childhood ALL, most of which consisted of piled up mass lesions. Patients with renal involvement should be worked up for the detection of other extramedullary lesions.

Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Histopathological maturation in juvenile xanthogranuloma: a blueberry muffin infant mimicking aleukemic leukemia cutis.

Juvenile xanthogranuloma (JXG) is usually identified by Touton giant cells, so their absence can complicate diagnosis. We encountered a case of non-typical neonatal JXG lacking Touton giant cells, which was difficult to differentiate from aleukemic leukemia cutis because of overlapping histopathological characteristics. A 1 month-old girl presented with a blueberry muffin rash and multiple 1-2 cm nodules within the subcutaneous and deeper soft tissues. Blood tests revealed pancytopenia. The initial nodule biopsy showed mononuclear cell infiltration, suggestive of mature monocytes or histiocytes, but no Touton giant cells. Bone marrow examination showed no evidence of leukemia. Despite worsening of the rash, pancytopenia, and weight gain over the following month, the results of the second biopsy remained consistent with the initial findings. Consequently, we provisionally diagnosed aleukemic leukemia cutis and initiated chemotherapy. After two courses of chemotherapy, the pancytopenia improved, but the nodules only partially regressed. A third biopsy of the nodule was performed to evaluate the histological response, and revealed Touton giant cells, confirming the diagnosis of JXG. In conclusion, distinguishing non-typical JXG from aleukemic leukemia cutis is challenging. This case highlights the importance of multiple biopsies and the potential for histopathological maturation.

A case of MYH7 and MYH9 genes variants with cardiomyopathy and macrothrombocytopenia.

Key Clinical Message: A 15-year-old girl developed inherited cardiomyopathy and macrothrombocytopenia revealing pathogenic variants of both MYH7 and MYH9 genes. This underlies the importance of repeated genetic testing in diagnosing and managing inherited disorders. Abstract: The MYH7 and MYH9 genes encode for distinct myosin heavy chain proteins. Our case features a 15-year-old girl, presenting with inherited cardiomyopathy and macrothrombocytopenia, revealing distinct pathogenic variants of both MYH7 and MYH9 genes. This underlines the relevance of genetic testing and personalized medicine in diagnosing and managing inherited disorders.

A case of neurodegenerative Langerhans cell histiocytosis exhibiting high osteopontin in cerebrospinal fluid without specific radiological abnormalities.

Neurodegenerative Langerhans cell histiocytosis (ND-LCH) manifests several years after onset of LCH, with progressive neurological symptoms and characteristic brain imaging features. Although ND-LCH has a dismal neurological prognosis, distinct treatment strategies are not available owing to the unknown pathophysiology. We describe the case of a 6-year-old boy who developed left convergent strabismus four years after onset of multisystem LCH (MS-LCH). Although radiological imaging showed no abnormalities, the osteopontin level in the cerebrospinal fluid (CSF-OPN) was highly elevated without other abnormal CSF findings, leading to a diagnosis of ND-LCH. The patient received monthly intravenous immunoglobulin therapy for four years, without symptoms worsening. To investigate the relevance of OPN levels in LCH, we retrospectively analyzed serum and CSF OPN levels in eight LCH patients. Serum OPN levels were markedly elevated in the two MS-LCH patients with macrophage activation (400 and 445 ng/mL) compared to the other six patients (mean: 59 ng/mL). CSF-OPN levels were elevated in the ND-LCH patient (620 ng/mL) compared to the two patients with pituitary involvement (160 and 182 ng/mL), suggesting that the pathophysiology of ND-LCH reflects its inflammatory status. Analysis of CSF-OPN levels would be a useful tool to detect and treat ND-LCH.

Protocol for a high titer of BaEV-Rless pseudotyped lentiviral vector: Focus on syncytium formation and detachment.

The development of hematopoietic stem cell (HSCs) gene therapy for DNA repair disorders, such as Fanconi anemia and Bloom syndrome, is challenging because of the induction of HSCs apoptosis by cytokine stimulation. Although the Baboon envelope pseudotyped lentiviral vector (BaEV-Rless-LV) has been reported as a non-stimulatory gene transfer tool, the virus titer of BaEV-Rless-LV is too low for use in clinical applications. Transfected 293 T cells with helper plasmids, including the BaEV-Rless plasmid, showed morphological changes, such as syncytium formation and detachment. To establish a novel protocol for producing a high titer of BaEV-Rless-LV, we optimized three aspects of a basic virus production protocol by focusing on modifying culture conditions and the use of reagents: the virus titer increased 3-fold when the amount of BaEV-Rless plasmid was increased 1.2-fold; the highest titer was obtained when the viral supernatant was harvested at 48-h post-transfection, despite complete syncytium formation and detachment of the 293 T cells; and the use of poly-L-lysine-coated culture plates to enhance the adhesion and proliferation of 293 T cells and prevent detachment doubled the titer. Collectively, our novel protocol resulted in a 10-fold titer increase compared to the basic protocol and may be useful in clinical applications for treating DNA repair disorders.

L-asparaginase as an efficient salvage therapy for refractory acute myeloid leukemia with chromosome 7 abnormalities: a case series.

Acute myeloid leukemia (AML) with chromosome 7 abnormalities has a dismal prognosis due to a poor complete remission (CR) rate after induction chemotherapy. Although various salvage therapies for refractory AML have been developed for adults, few salvage therapies are available for children. Here, we report the cases of three patients with refractory AML with chromosome 7 abnormalities (Patient 1, with inv(3)(q21;3q26.2) and monosomy 7; Patient 2, with der(7)t(1;7)(?;q22); patient 3, with monosomy 7) who were successfully treated with L-asparaginase (L-ASP) as salvage therapy. All three patients achieved CR several weeks after L-ASP treatment, and two patients successfully underwent hematopoietic stem cell transplantation (HSCT). Patient 2 relapsed after the second HSCT in the form of an intracranial lesion, but achieved and sustained CR for 3 years with weekly L-ASP maintenance therapy. Immunohistochemical staining for asparagine synthetase (ASNS), whose gene is located at 7q21.3, was performed for each patient. The result was negative in all patients, which suggests that haploid 7q21.3 and other chromosome 7 abnormalities leading to haploinsufficiency of ASNS contribute to a high susceptibility to L-ASP. In conclusion, L-ASP is a promising salvage therapy for refractory AML with chromosome 7 abnormalities, which are associated with ASNS haploinsufficiency.

Refractory gastroduodenal ulcers: A rare complication with Bloom syndrome.

Bloom syndrome patients often develop severe gastrointestinal symptoms mainly caused by gastric tumors due to DNA repair disorder. Here, we report 31-year-old Bloom syndrome patient suffering persistent abdominal pain due to refractory gastroduodenal ulcers which required gastroduodenectomy. Various causes should be considered, and the accumulation of their reports is warranted.

A subarachnoid pleural fistula with massive crystal-clear pleural fluid caused by a lumbar epidural teratoma.

A subarachnoid pleural fistula - a connection between the pleural cavity and the subarachnoid space - generally presents after trauma or surgery. A 1-year 11-month-old girl without a history of trauma or surgery presented with fatigue, cyanosis and dyspnoea. A chest radiograph and computed tomography (CT) demonstrated a massive pleural effusion in the right hemithorax. About 300 ml of a crystal-clear pleural effusion, which looked like pure water, was removed by insertion of a chest drain, but it continued to collect. Cisternography and CT myelography confirmed leakage of cerebral spinal fluid into the right pleural cavity around the thoracolumbar region. Magnetic resonance imaging demonstrated an 11-mm enhanced nodule in the epidural space around the right lumbar (L) 1/2 intervertebral foramen. The patient underwent surgery and epidural tumours attached to the L1 nerve root foramen were completely resected and a fistula of the dura adjacent to the tumour was sutured. Histopathological examination demonstrated a mature teratoma containing a pancreatic component. On retrospective analysis of stored pleural fluid, a raised level of pancreatic enzymes was detected. It is presumed that digestive enzymes secreted by the pancreatic component of the teratoma lysed the dura, resulting in formation of the fistula. When a crystal-clear pleural effusion is present, even in the absence of trauma or surgery, a subarachnoid pleural fistula should be considered. As far as we know, this is the first report of a subarachnoid pleural fistula caused by a paravertebral teratoma.Abbreviations: CSF: cerebrospinal fluid; CT: computed tomography; 111In-DTPA: indium-111 diethylene triamine penta-acetic acid; MRI: magnetic resonance imaging; NIPPV: non-invasive positive pressure ventilation.