A unique AML1 (CBF2A) rearrangement, t(1;21)(p32;q22), observed in a patient with acute myelomonocytic leukemia.

The AML1 (CBFA2) gene is the most frequent target of chromosomal rearrangements observed in human acute leukemia. These rearrangements include the commonly reported t(8;21)(q22;q22) or AML1/ETO fusion in AML-M2, the t(3;21)(q26;q22) or AML1 fusion with one of three genes, MDS1, EAP or EVI1, in therapy-related AML and MDS, as well as in blast crisis in CML and the t(12;21)(p13;q22) or TEL/AML1 fusion in B-cell ALL. In addition to the t(3;21), other AML1 translocations have also been reported in therapy-related MDS and AML, particularly after treatment with topoisomerase II inhibitors. AML1 gene rearrangements have also been observed less frequently with numerous other chromosomal partners. Here, we describe a patient with AML-M4 and a previously unreported rearrangement involving the AML1 locus and an unknown locus on the short arm of chromosome 1 at 1p32.

Natural killer cell precursor acute lymphoma/leukemia presenting in an infant.

Lymphoma/leukemia derived from immature natural killer (NK) cells occur most commonly in adults and are characterized by blastic cytologic features and an aggressive outcome. Predilection for extranodal sites and absence of the Epstein-Barr virus associated with mature NK cell malignancies further distinguish this entity. We present a NK precursor acute lymphoma presenting with multiple masses in an infant without circulating blasts or marrow replacement by disease. The diagnostic difficulty arose from several factors, including young age, presentation with multiple masses, blastic cytologic features mistaken for a small, round, blue cell tumor, and the absence of lineage-specific markers. The CD56+, CD34+, CD33+, MPO-, cytoplasmic CD3+, CD45-, CD7-, HLA-DR-, and TdT- immunophenotype of this neoplasm overlaps with previously reported cases of myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This case emphasizes the need for a strong index of suspicion to recognize this rare entity and to distinguish it from solid tumors and other hematolymphoid neoplasms that occur in infancy.

Spindle cell lipoma of the foot and the application of CD34 immunohistochemistry to atypical lipomatous tumors in unusual locations.

Spindle cell lipoma demonstrates a distinctive histologic appearance and characteristic clinical presentation. We recently observed two cases of solitary subcutaneous neoplasm of the foot with histologic features of spindle cell lipoma that in one case includes a minor component of the overlapping tumor, pleomorphic lipoma. Because the foot is an unusual location for these neoplasms, immunoperoxidase and cytogenetic studies were performed. In both cases, staining was strongly positive for CD34 and negative for smooth muscle actin. Cytogenetic studies from the tumor with a pleomorphic component revealed features consistent with a lipomatous neoplasm, but are otherwise diagnostically nonspecific. An analysis of the literature reveals that although CD34 immunoreactivity is characteristic of spindle cell lipoma and helps exclude nonlipomatous neoplasms, it does not clearly eliminate other well-differentiated lipomatous tumors. Accordingly, without the aid of classic tumor location, the diagnosis of the spindle cell/pleomorphic lipoma group relies primarily on histologic features, with supportive but not definitive information provided by immunoperoxidase and cytogenetic studies. Obscuring this issue, however, are the imprecise histologic distinction between these tumors and those of the atypical lipoma/atypical lipomatous tumor/ well-differentiated liposarcoma group and the nomenclature controversy that surrounds the latter group of neoplasms. Despite these obstacles, both groups of well-differentiated lipomatous tumors are clinically benign when subcutaneously located.

Compound genetic factors as a cause of male infertility: case report.

A 40 year old healthy Chinese male with primary infertility was seen in a university male infertility and genetic counselling clinic. He presented with congenital bilateral absence of the vas deferens (CBAVD) and the finding of testis atrophy. Fine needle aspiration mapping of the testis identified and localized sperm production within the testicles for in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Careful evaluation of testicular cytology revealed late maturation arrest of spermatogenesis. Cystic fibrosis gene mutation analysis revealed heterozygosity for the 5T variant within the polypyrimidine tract of intron 8. Cytogenetic analysis revealed a pericentric inversion of chromosome 6 with break points at p12 and q21 [46,XY,inv(6)(p12q21)]. This case illustrates that spermatogenesis is not necessarily normal with congenital bilateral absence of the vas deferens. Compound genetic defects may coexist and underlie male infertility.

Human endothelial cell life extension by telomerase expression.

Normal human endothelial cells, like other somatic cells in culture, divide a limited number of times before entering a nondividing state called replicative senescence. Expression of the catalytic component of human telomerase, human telomerase reverse transcriptase (hTERT), extends the life span of human fibroblasts and retinal pigment epithelial cells beyond senescence without causing neoplastic transformation (Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., and Wright, W. E. (1998) Science 279, 349-352; Jiang, X., Jimenez, G., Chang, E., Frolkis, M., Kusler, B., Sage, M., Beeche, M., Bodnar, A., Wahl, G., Tlsty, T., and Chiu, C.-P. (1999) Nat. Genet. 21, 111-114). Here, we show that both human large vessel and microvascular endothelial cells also bypass replicative senescence after introduction of hTERT. For the first time, we report that hTERT expression in these life-extended vascular cells does not affect their differentiated and functional phenotype and that these cells maintain their angiogenic potential in vitro. Furthermore, hTERT(+) microvascular endothelial cells have normal karyotype, and hTERT(+) endothelial cell strains do not exhibit a transformed phenotype. Relative to parental cells at senescence, hTERT-expressing endothelial cells exhibit resistance to induction of apoptosis by a variety of different conditions. Such characteristics are highly desirable for designing vascular transplantation and gene therapy delivery systems in vivo.

The treatment of quinine poisoning with charcoal haemoperfusion.

Quinine poisoning is rare but serious. Attempts at treatment by active removal have proved unsuccessful because of its high degree of protein binding. We describe two cases of non-accidental overdose of quinine (19.5 g and 15 g) with potentially fatal serum quinine levels. Both patients were treated by 2 periods of charcoal haemoperfusion during which quinine clearances of up to 125 ml/min were obtained. Both patients recovered, though one had some residual visual disturbance. We suggest that in cases of quinine poisoning, charcoal haemoperfusion may be a safe and effective method of drug removal, to be used with stellate ganglion block.