Search

This report offers novel clinical and diagnostic aspects of the association between germline mutations in HAVCR2 and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The patient presented with panniculitis-like T-cell lymphoma involving mesenteric fatty tissue associated with hemophagocytic lymphohistiocytosis (HLH). Five years later, he developed a clonally unrelated SPTCL and underwent hematopoietic stem cell transplantation. Retrospectively, he was found to carry germline mutations in HAVCR2 associated with reduced T-cell immunoglobulin mucin-3 (TIM-3) expression. We show that mesenteric fatty tissue localization of SPTCL can be the presenting manifestation of TIM-3 deficiency, that this condition predisposes to recurrent lymphoma, and that flow cytometry is a possible screening tool.

Mutations in SLC46A1 result in a defect of the proton coupled folate transporter (PCFT) and are the basis of hereditary folate malabsorption (HFM). Patients with HFM frequently present with neurodevelopmental delay and megaloblastic anemia. Some cases may be complicated by additional lymphopenia and immunodeficiency. We report a patient with a new homozygous mutation in the SLC46A1 gene. The boy presented with early-onset pancytopenia and secondary immunodeficiency. We provide clinical and molecular observations that extend the phenotypic description of HFM and highlight diagnostic as well as therapeutic pitfalls in this rare condition.

Juvenile myelomonocytic leukemia (JMML) has a poor prognosis in general, with hematopoietic stem cell transplant (HSCT) remaining the standard of care for cure. The hypomethylating agent, azacitidine, has been used as a bridging therapy to transplant. However, no patients have been treated with azacitidine without an HSCT post azacitidine. We report on an infant with JMML with somatic KRAS G12A mutation and monosomy 7 who achieved sustained remission following azacitidine monotherapy. He also developed an aberrant B-lymphoblast population which declined with similar kinetics as his JMML-associated abnormalities, suggesting that a B-lymphoblast population in JMML does not always progress to acute leukemia.

Pediatric fibrotic myelodysplastic syndromes (ped-MDS-MF) and pediatric primary myelofibrosis (ped-PMF) are rare, and the molecular changes which mediate fibrosis have never been investigated. Histology and gene expression profile of 119 fibrosis/angiogenesis/inflammation/megakaryopoiesis-related factors in bone marrow biopsies were performed (two ped-MDS-MF and one ped-PMF). In one progressive ped-MDS, comparison of MF grade 0 (no myelofibrosis) and MF grade 2 (dense network of reticulin fibres) after 4 months showed that expression of fibrosis-related transcripts increased and dysplastic megakaryocytes formed a dense net of CD42b+ proplatelets. These changes were not observed in another ped-MDS-MF, whereas ped-PMF showed a similar proplatelet pattern. These findings indicate that fibrotic changes in ped-MDS may involve proplatelet-related and unrelated pathways.

Background Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics. Procedure In this retrospective multi-institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5–16 years with thrombocytosis and a suspected diagnosis of ET. Results Median follow-up was 59 months (range 10–72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325 × 109/L (range 600–3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAKV617F allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow-up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count. Conclusions In JAK2 mutation negative cases, long-term follow-up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear. Pediatr Blood Cancer 2007;49:52–55. © 2006 Wiley-Liss, Inc.

Epithelioid hemangioendothelioma (EHE) is a rare, vascular sarcoma. Visceral forms arise in the liver/ lungs. We review the clinical and molecular phenotype of pediatric visceral EHE based on the case of a 9-year-old male child with EHE of the liver/lungs. His tumor expressed the EHE-specific fusion oncogene WWTR1-CAMTA1. Molecular characterization revealed a low somatic mutation rate and activated interferon signaling, angiogenesis regulation, and blood vessel remodeling. After polychemotherapy and resection of lung tumors, residual disease remained stable on oral lenalidomide. Literature review identified another 24 children with EHE of the liver/lungs. Most presented with multifocal, systemic disease. Only those who underwent complete resection achieved complete remission. Four children experienced rapid progression and died. In six children, disease remained stable for years without therapy. Two patients died from progressive EHE 21 and 24 years after first diagnosis. Natural evolution of pediatric visceral EHE is variable, and long-term prognosis remains unclear.

This report documents the clinical activity of caspofungin in a 13-year-old girl with acute myeloid leukemia (AML) and chronic disseminated candidiasis (CDC), refractory to amphotericin B and fluconazole. Caspofungin was started at 50 mg/d resulting in a temporary response. With no further clinical improvement and radiological progress after 2 months of therapy, the dose of caspofungin was increased to 100 mg/d, leading to a sustained clinical response. Therapy was given for a total of 12 months and had no attributable adverse effects. This approach resulted in successful treatment of refractory CDC with caspofungin. Pediatr Blood Cancer 2007;49:360–362. © 2006 Wiley-Liss, Inc.

We report a 6-year-old female with congenital bone marrow failure, who was referred for allogeneic stem cell transplantation. An initial work-up in infancy had not revealed any consistent symptoms associated with an inherited syndrome. Computed tomography of her abdomen for gastrointestinal bleeding after transplantation incidentally revealed a fat-replaced pancreas and led to the molecular diagnosis of Shwachman–Diamond syndrome (SDS) in the absence of clinical exocrine pancreatic insufficiency. We conclude that SDS may escape the clinical consensus criteria for the disease. Increased awareness of unusual presentations may allow confirming the suspected diagnosis by molecular analysis and ensure optimal management. Pediatr Blood Cancer 2010;55:177–179. © 2010 Wiley-Liss, Inc.