David S. Brink

Transient leukemia (transient myeloproliferative disorder, transient abnormal myelopoiesis) of Down syndrome.

Transient leukemia of Down syndrome (DS-TL), also known as transient myeloproliferative disorder of Down syndrome (DS) and transient abnormal myelopoiesis of DS, occurs in approximately 10% of DS neonates and in phenotypically normal neonates with trisomy 21 mosaicism. In DS-TL, peripheral blood analysis shows variable numbers of blasts and, usually, thrombocytopenia; other cytopenias are uncommon. Bone marrow characteristics of DS-TL are, likewise, variable, though (in contrast to other leukemias) the bone marrow blast differential can be lower than the peripheral blood blast differential. The blasts of DS-TL typically show light microscopic, ultrastructural, and flow cytometric evidence of megakaryocyte differentiation. DS-TL neonates have a ∼15% risk of developing potentially fatal liver disease and show <10% incidence of hydrops fetalis. Additional manifestations of DS-TL include cutaneous involvement, hyperviscosity, myelofibrosis, cardiopulmonary failure, splenomegaly, and spleen necrosis. Despite its typical transient nature, 20% to 30% of DS-TL patients develop overt (nontransient) acute leukemia, usually within 3 years and typically of the M7 phenotype (acute megakaryoblastic leukemia). The pathogenesis of DS-TL (and of subsequent acute leukemia) involves mutation of GATA1 (on chromosome X), which normally encodes a transcription factor integral to normal development of erythroid, megakaryocytic, and basophilic/mast cell lines. The pathogenetic role of trisomy 21 in DS-TL is unclear. Though indications for chemotherapy in DS-TL have not been firmly established, the blasts of DS-TL are sensitive to low-dose cytosine arabinoside.

Case of lipoblastoma with two derivative chromosomes 8 containing homogeneously staining-like regions and a review of the literature: lipoblastoma and chromosome 8

We report a case of a lipoblastoma in a 10-month-old girl in which the cytogenetic aberration showed a homogeneously staining-like region (hsr) within two derivative chromosomes 8. There was a loss of one normal copy of chromosome 8 and gain of two identical derivative chromosomes 8 with the karyotype designation 47,XX,psu idic(8)(pter-->q12 approximately 13::hsr::q12 approximately 13-->pter),+psu idic (8)(pter-->q12 approximately 13::hsr::q12 approximately 13-->pter). This is the first report of a chromosomal aberration of this type seen in lipoblastoma.

Renal pathology in the pediatric transplant patient.

Renal transplantation is a therapeutic goal for children with advanced chronic kidney disease. There are many causes of renal dysfunction in children with allografts—the transplanted kidney can develop a variety of morphologic alterations leading to dysfunction. Evaluation of the kidney biopsy is one of the best methods of determining the cause of graft dysfunction. Rejection is a major cause of renal allograft failure in children. The morphologic hallmarks of acute antibody-mediated and cell-mediated rejection and chronic allograft nephropathy have been codified in classification strategies that are useful in adults and children. Viral infection and Epstein-Barr virus-driven posttransplant lymphoproliferative disease also occur in the pediatric transplanted kidney. Drug toxicity from immunosuppressive agents also causes characteristic morphologic alterations in the renal allograft. As the survival of pediatric heart and liver transplant patients improves, the incidence of immunosuppression therapy-related disease in the native kidney in these patients will likely become more important clinically. In addition to renal lesions related to the allograft state, glomerular disease can recur or occur de novo in renal allografts. Here, we describe the pathology of the more common morphologic lesions in kidneys of children with a renal allograft.

Trisomy 15 in a case of pediatric hemangiopericytoma and review of the literature

This study reports on a pediatric case of hemangiopericytoma (HPC) showing trisomy 15 as a sole anomaly. Trisomy 15 was observed in a total of 11 cells harvested at a very early passage from two different in-situ cultures. Trisomy 15, as a sole anomaly, has been described in hematologic disorders such as myelodysplastic syndromes but, to our knowledge, has never been documented in solid tumors. This is the first report of HPC with trisomy 15.

Extramedullary hematopoiesis in renal allograft

Extramedullary hematopoiesis (EMH), defined as the presence of hematopoietic elements outside of the medullary cavity of bone, has been reported in patients with various hematopoietic neoplasms including myelofibrosis. EMH commonly occurs in the liver and spleen (resulting in hepatosplenomegaly) and uncommonly involves the kidney. EMH involving the allograft kidney has not been reported in English literature. Herein, we report the first case of EMH in allograft kidney in a patient with myelofibrosis. The clinical and pathological findings are described. Through comparison of the medullary neoplastic infiltrate with the renal allograft infiltrate, we postulate the neoplastic nature of the infiltrate in the allograft kidney.

A novel post-exposure medical countermeasure L-97-1 improves survival and acute lung injury following intratracheal infection with Yersinia pestis.

Yersinia pestis, a Gram-negative bacillus causing plague and Centers for Disease Control and Prevention (CDC) classified Category A pathogen, has high potential as a bioweapon. Lipopolysaccharide, a virulence factor for Y. pestis, binds to and activates A1 adenosine receptor (AR)s and, in animals, A1AR antagonists block induced acute lung injury (ALI) and increase survival following cecal ligation and perforation. In this study, rats were infected intratracheally with viable Y. pestis [CO99 (pCD1 + /Δpgm) 1 × 10 8 CFU/animal] and treated daily for 3 d with ciprofloxacin (cipro), the A1AR antagonist L-97-1, or cipro plus L-97-1 starting at 0, 6, 24, 48, or 72 h post-Y. pestis. At 72 h post-Y. pestis, cipro plus L-97-1 significantly improved 6-d survival to 60–70% vs 28% for cipro plus H2O and 33% for untreated Y. pestis controls (P = 0.02, logrank test). Lung edema, hemorrhage and leukocyte infiltration index (LII) were evaluated histologically to produce ALI scores. Cipro plus L-97-1 significantly reduced lung edema, as well as aggregate lung injury scores vs controls or cipro plus H2O, and LII vs controls (P < 0.05, Student’s unpaired t test). These results support efficacy for L-97-1 as a post-exposure medical countermeasure, adjunctive therapy to antibiotics for Y. pestis.