Masaei Onuma

Vincristine-resistant Kasabach–Merritt phenomenon successfully treated with low-dose radiotherapy

In 1940, Kasabach and Merritt reported the case of an infant with a huge angioma causing thrombocytopeniarelated purple spots. This condition became known as the Kasabach–Merrit phenomenon (KMP), characterized by a huge hemangioma associated with thrombocytopenia and microangiopathic hemolytic anemia due to consumption coagulopathy [1]. The incidence of KMP in infants with a huge hemangioma is approximately 0.3%, but it is said that the mortality rate exceeds 30% among patients. A number of therapies have been reported for the treatment of KMP, but none have been uniformly effective. We report a case of life-threatening KMP, in which hemangioma of the right thigh (tufted angioma type) was successfully treated by low-dose radiotherapy after concurrent therapy with the agents prednisolone (PSL), interferon a-2a (IFN a-2a), and vincristine (VCR) failed to control it. 2 Case report

Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities

Genetic mosaicism for somatic mutations of oncogenes is common in genodermatoses, which can be complicated with extra‐cutaneous abnormalities. Here we describe an infant with a congenital anaplastic astrocytoma, a linear syringocystadenoma papilliferum, and ocular abnormalities. The BRAF c.1799T>A p.V600E mutation was detected in both the brain and skin tumor cells but not in the blood or normal skin cells, suggesting somatic mosaicsism for the mutation. Clinically, the brain tumor gradually became life threatening without any response to conventional chemotherapies including carboplatin, etoposide, and temozolomide. Vemurafenib, a BRAF p.V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single‐agent therapy was dramatically effective against the anaplastic astrocytoma; the tumor regressed, the cerebrospinal fluid cell count and protein levels decreased to normal levels, and hydrocephalus resolved. Moreover, other lesions including a corneal cyst also responded to vemurafenib. The brain tumor continued shrinking after 6 months of treatment. We present a genodermatosis syndrome associated with BRAF c.1799T>A p.V600E mosaicism. This syndrome may represent a new entity in the mosaic RASopathies, partly overlapping with Schimmelpenning‐Feuerstein‐Mims syndrome, which is driven by mosaicism of HRAS and/or KRAS activating mutations. Screening for BRAF c.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most‐druggable targets.

Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystrophy at advanced and early stages.

Niizuma H, Uematsu M, Sakamoto O, Uchiyama T, Horino S, Onuma M, Matsuhashi T, Rikiishi T, Sasahara Y, Minegishi M, Tsuchiya S. Successful cord blood transplantation with reduced‐intensity conditioning for childhood cerebral X‐linked adrenoleukodystrophy at advanced and early stages. 
Pediatr Transplantation 2012: 16: E63–E67.

Refractory chronic immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia

Immune thrombocytopenic purpura (ITP) has been associated with several hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas and chronic lymphocytic leukemia, but it is rare in children with acute lymphoblastic leukemia (ALL). Here, we report a 7-year-old girl with chronic ITP during early intensive phase of chemotherapy for ALL. She underwent splenectomy because thrombocytopenia had persisted even after treatment with intravenous immunoglobulin (IVIG), steroids, vincristine, rituximab, and anti-D antibody. After splenectomy, her platelet count had recovered, and maintenance therapy could be resumed with a support of IVIG. To our knowledge, this is the first child case of chronic ITP during chemotherapy for ALL and splenectomy was effective in this patient.

Mesenchymal chondrosarcoma diagnosed on FISH for HEY1‐NCOA2 fusion gene

Mesenchymal chondrosarcoma (MC) is an extremely rare subtype of chondrosarcoma that has a small round‐cell sarcoma with focal cartilaginous differentiation, often with a pericytomatous vascular pattern. The non‐cartilaginous components are usually dominant, and such lesions might be confused with other small round‐cell tumors. Recently, a tumor‐specific HEY1‐NCOA2 fusion gene was identified in MC. Here we report the case of a 9‐year‐old boy who was diagnosed with MC by detection of HEY1‐NCOA2 fusion signals in almost 50% of tumor cells in tissue sections on fluorescence in situ hybridization (FISH). In this way, the tumor was definitively diagnosed as MC. This case suggests that the detection of the HEY1‐NCOA2 fusion gene on FISH is of diagnostic value for MC.

A case series of CAEBV of children and young adults treated with reduced‐intensity conditioning and allogeneic bone marrow transplantation: a single‐center study

Epstein–Barr virus (EBV)‐infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial.

Clinicopathological features of melanotic neuroectodermal tumor of infancy: Report of two cases.

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, pigmented neoplastic entity of neural crest origin. Histological and immunohistochemical profiles indicate the presence of two components, small rounded neuroblast-like cellular areas and areas with large melanin-containing cells which consist of combination of neural, melanocytic, and epithelial cell types. Here we present two interesting cases of infants with MNTI which have different clinicopathological features. The first case is a 3-month-old female with rapidly growing MNTI involving the lacrimal sac and inferior wall of the orbital cavity, treated with total maxillectomy without orbital exenteration followed by chemotherapy. The second case is a 7-month-old male with slow-growing maxillary MNTI treated with complete surgical excision. In the female patient, histological findings revealed a predominance of neuroblast-like cellular areas and a high Ki67 index indicating rapid cellular proliferation. In the male patient however, large melanin-containing cells were dominant in this slow-growing tumor. These findings support the presence of two different types of MNTI, rapid-growing and slow-growing types, determined by the component of neuroblast-like cellular areas.

Unilateral Phrenic Nerve Plasy: A Rare Manifestation of Vincristine Neurotoxicity: Correspondence

To the Editor: We read with interest the article written by Dhingra et al. entitled “Unilateral phrenic nerve palsy: A rare manifestation of vincristine neurotoxicity” [1]. Here we present a patient with mesenchymal chondrosarcoma (MC) who developed hiccups repeatedly after receiving vincristine infusion. In addition to our case, several agents such as corticosteroid and cyclophosphamide infusion are also known to cause drug-induced hiccups [2–4]. A 9-y-old boy presented with pain and swelling in the right knee for 1 mo. Limb-sparing operation with wide excision of the tumor and pasteurized autologous bone graft was performed. He was given six courses of adjuvant chemotherapy, of alternative course of combination of vincristine, doxorubicin, cyclophosphamide (VDC), combination of ifosfamide, etoposide (IE), every 3 wk intervals. When he received 1.5 mg/m of vincristine and granisetron as an anti-emesis, intravenously on the first day of the VDC regimen, he developed hiccups for half an hour after vincristine infusion. The event occurred reproducibly, never occurred at IE regimen, when the patient also received granisetron. The hiccups improved spontaneously later without any treatment. The temporal profile of hiccup disappearance, 6 h after vincristine administration spontaneously, might be explained exponential regression curve of blood concentration of vincristine, although the mechanism still remains unknown [5]. Impaired peripheral nerve functions and bowel movement are well known adverse effects caused by vincristine. Vincristine could cause hiccups as a part of combination chemotherapy.