Dai Keino

Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2

Acroscyphodysplasia (OMIM250215) is a distinctive form of metaphyseal dysplasia characterized by the distal femoral and proximal tibial epiphyses embedded in cup‐shaped, large metaphyses known as metaphyseal scypho (“scypho” = cup) deformity. It is also associated with severe growth retardation and brachydactyly. The underlying molecular mechanism of acroscyphodysplasia has not yet been elucidated, although scypho‐deformity of the knee has been reported in three patients with acrodysostosis due to a mutation in the PDE4D gene. We report on the clinical, radiological, and molecular findings of five female patients with acroscyphodysplasia; two were diagnosed as pseudohypoparathyroidism (PHP) or Albright hereditary osteodystropy, and the other three as acrodysostosis. They all had radiological findings consistent with severe metaphyseal scypho‐deformity and brachydactyly. Heterozygous mutations were identified in the PHP patients consisting of one novel (p.Q19X) and one recurrent (p.R231C) mutation of the GNAS gene, as well as, in the acrodysostosis patients consisting of two novel mutations (p.T224I and p.I333T) of the PDE4D gene. We conclude that metaphyseal acroscyphodysplasia is a phenotypic variation of PHP or acrodysostosis caused by either a GNAS or PDE4D mutation, respectively.

Infective endocarditis associated with acute leukemia: Report of two cases

There have been few reports regarding infective endocarditis (IE) in patients with leukemia. In the first case, a 15‐year‐old girl with Down syndrome was diagnosed with acute lymphoblastic leukemia. On admission, methicillin‐sensitive Staphylococcus aureus (MSSA) was detected on blood culture. Echocardiography was performed because MSSA was detected repeatedly even after treatment. Vegetation in all of the atria and ventricles met the Duke criteria defining IE. She died of multiple organ failure 21 days after diagnosis. In the second case, an 11‐year‐old boy with acute myeloid leukemia underwent peripheral blood stem cell transplantation (PBSCT). He had fever 68 days after PBSCT, and methicillin‐resistant S. aureus (MRSA) was detected on blood culture. Echocardiography showed vegetation in the right atrium and ventricle. Daptomycin was administered for 7 weeks, and recurrence was not observed. IE should be considered when S. aureus bacteremia is documented even in patients with leukemia.

T-cell large granular lymphocyte leukemia in a child with anemia and Crohn's disease

T‐LGL leukemia has been rarely reported in children. We report a child with T‐LGL leukemia who presented with anemia and went on to develop Crohns disease. Although prednisolone treatment proved effective in the treatment of anemia, large granular lymphocyte counts increased as the doses were tapered. T‐cell rearrangement studies revealed a clonal rearrangement of the TCR Vβ/jβ2 gene. Concurrently, the patient developed severe diarrhea. Inflammatory changes across the upper and lower intestines led to the diagnosis of Crohns disease. This case highlights that T‐LGL leukemia could be occurred in children. Flow cytometry and/or T‐cell gene rearrangement studies are recommend in patients of anemia and various kind of autoimmune diseases including Crohns disease, even in children.

A child with myeloid/natural killer cell precursor acute leukemia treated successfully with acute myeloid leukemia-oriented chemotherapy incorporating l-asparaginase

Myeloid/natural killer (myeloid/NK) cell precursor acute eukemia was initially identified as a leukemia of natural killer (NK) ells, with co-expression of both myeloid and NK cell precursor ntigens [1]. The leukemic cells of myeloid/NK cell precursor acute eukemia are negative for myeloperoxidase staining (<3% of total ells) but positive for CD7, CD56, and myeloid antigens [1]. In comarison with other types of NK malignancy, this disease entity is onsidered to be caused by immature leukemic cells, in terms of orphology, phenotype, and genotype [1]. The prognosis of myeloid/NK cell precursor acute leukemia is eportedly poor. Although chemotherapeutic regimens designed or acute myeloid leukemia (AML) can effective induce comlete remission in patients with myeloid/NK cell precursor acute eukemia, most of them subsequently relapse, and there have been o reports of patients surviving for more than 4 years [1]. To ur knowledge, all previous reports of long-term remission have nvolved patients who underwent hematopoietic stem cell translantation (HSCT) at the time of initial complete remission [2,3]. ecently, l-asparaginase (l-asp) has been shown to induce selective poptosis of NK cell lymphoma cells in vitro [4]. Indeed, successful

Hypocellular acute myeloid leukemia treated with bone marrow transplantation

Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11‐year‐old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo‐BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low‐dose cytarabine induced reduction of blasts, it did not lead to complete remission. He subsequently received myeloablative conditioning and allo‐BMT. Graft‐versus‐host disease (GVHD) prophylaxis included short‐course methotrexate and cyclosporine. Neutrophil engraftment (>5 × 108/L) and platelet recovery (>10 × 1010/L) were achieved on days 13 and 27, respectively. He developed acute GVHD of the skin (grade 2), which responded well to treatment with prednisolone. He has remained in complete remission for 5 years since allo‐BMT. We consider allo‐BMT to be feasible for children with hypocellular AML.

High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15‐yr‐old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW‐MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto‐PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto‐PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.