Cyto-morphologic evaluation of bone marrow in infants with disseminated neuroblastoma.

We studied the prevalence and degree of tumor cell infiltration (TCI) in bone marrow (BM) aspirates of 89 infants with stage 4/4 S neuroblastoma and correlated them with MYCN gene status and patient outcome. TCI was scored 0, +, ++, and +++, the last corresponding to an infiltration greater than 10%. TCI 0 was more frequent in stage 4 than in stage 4 S.

Differential diagnosis of lipoma-like lipoblastoma.

Lipoblastomas are rare benign tumors of white fatty tissue that occur primarily in young children. Occasionally, heterogeneity of morphological appearance and histological overlap with other lipogenic tumors are described. In such cases fluorescence in situ hybridization (FISH) analysis of PLAG1, a gene specifically rearranged in lipoblastoma, is necessary to prevent misdiagnosis.

Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia.

The inv(11)(p15q22), a rare but recurrent chromosome abnormality that creates a NUP98-DDX10 fusion gene, is associated with de novo or secondary myeloid malignancies. We report a case of acute monocytic leukemia presenting this rearrangement, studied using fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR). We also review the cases of inv(11) associated with NUP98-DDX10 reported in the literature.

Diagnostic identification of malignant cells in the cerebrospinal fluid by tumor-specific qRT-PCR.

Tumor specific quantitative RT-PCRs for two neuroblastoma specific molecular markers, tyrosine hydroxylase (TH) and GD2 synthase, were used to unequivocally demonstrate the neoplastic nature of the cells present in the cerebrospinal fluid of a neuroblastoma patient. After radical surgery of two separate tumoral lesions, localized in the extradural area, the patient presented with meningitis. Common sites of neuroblastoma metastatization, e.

Gain of 1q in pediatric myelodysplastic syndromes.

The presence of acquired clonal cytogenetic abnormalities in hematopoietic cells is one of the diagnostic hallmarks of myelodysplastic syndromes (MDS). Such anomalies may help in defining prognostic groups. We analyzed eight pediatric MDS, and herein describe three new cases, one de novo and two therapy-related, presenting an unbalanced rearrangement of 1q: one of them resulted in a derivative chromosome 6 apparently identical to a previously described one.

MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.

The occurrence of MLL gene rearrangement in acute megakaryoblastic leukemia (AML-M7, acute myeloid leukemia, French-American-British type M7) is very rare and limited to pediatric age: in particular, MLL-MLLT10 fusion, previously reported as characteristic of monocytic leukemia, has been reported in only one case of pediatric megakaryoblastic leukemia. We describe the second case with this association in light of the few reported cases of AML-M7 with MLL and/or 11q23 involvement.

t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia.

The rare t(9;11)(p22;p15) translocation is associated with adult acute myeloid leukemia (AML) with immature forms. We report a novel fusion of the NUP98 and LEDGF genes in a pediatric AML with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes exhibiting the same chromosomal rearrangement. Fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR) studies identified the chimeric transcript product of in-frame fusion of NUP98 exon 8 to LEDGF exon 4.

Detection of neuroblastoma cells in bone marrow and peripheral blood by different techniques: accuracy and relationship with clinical features of patients.

Purpose: Detection of metastatic tumor cells in bone marrow (BM) and peripheral blood (PB) of children with neuroblastoma is crucial for prognosis and planning of therapy. Aims of this large descriptive repeated survey were to evaluate the diagnostic accuracy of different techniques in diagnostic samples obtained at several disease course time points and to correlate positive results with patient clinical features and outcome.

Experimental Design: BM aspirates, trephine biopsies, PB, and peripheral blood stem cell (PBSC) samples from Italian children with neuroblastoma were analyzed by morphological and histologic techniques, as well as by immunocytochemistry (IC) for disialoganglioside GD(2) and reverse transcription-PCRs (RT-PCRs) for tyrosine hydroxylase (TH) and pgp9.

MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity.

Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10 (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We present two new pediatric cases (French-American-British type M5) with MLL-MLLT10 fusion, which we studied with fluorescence in situ hybridization. In both we detected a paracentric inversion of the 11q region that translocated onto chromosome 10p12; one case displayed a variant complex pattern.

HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2).

PDGFRB, a transmembrane tyrosine kinase receptor for platelet-derived growth factor, is constitutively activated by gene fusion with different partners in myeloproliferative/myelodysplastic disorders with peculiar clinical characteristics. Six alternative partner genes have been described thus far. In this study, we report the molecular cloning of a novel translocation t(5;17)(q33;p11.

Uneventful outcome of unrelated hematopoietic stem cell transplantation in a patient with leukemic transformation of Kostmann syndrome and long-lasting invasive pulmonary mycosis.

Kostmann syndrome (KS) is an inherited hematological disorder characterized by an absolute neutrophil count (ANC) <0.2 x 109/L and life-threatening bacterial infections. Granulocyte-colony stimulating factor (G-CSF) makes it possible to reach an ANC of 1.

Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia?

Congenital, or perinatal, leukemias are rarely observed, but retrospective molecular studies seem to suggest a more frequent onset in prenatal life. Myelocytic types are common, and chromosome band 11q23 rearrangements at the MLL locus are characteristic genetic markers. The fusion of the MLL gene with one of its partners, ABI-1, has recently been described in two infant leukemia patients with monocytic involvement and good clinical outcome.

Cryptic translocation t(5;11)(q35;p15.5) with involvement of the NSD1 and NUP98 genes without 5q deletion in childhood acute myeloid leukemia.

The cryptic translocation t(5;11)(q35;p15.5), which creates a NSD1-NUP98 fusion gene, has been associated with a deletion of the long arm of chromosome 5, del(5q), in pediatric acute myeloid leukemia (AML) patients with differentiated phenotype. We screened five pediatric cases of AML with apparently normal karyotype by use of fluorescence in situ hybridization analysis and detected one case with early myeloid phenotype and poor clinical outcome, but with the same breakpoints and no del(5q).

XY female with a dysgerminoma and no mutation in the coding sequence of the SRY gene.

We report a 46,XY 11-year-old girl with pure gonadal dysgenesis who developed a dysgerminoma. The testis-determining gene SRY, a candidate for sex reversal, whose alterations seem to correlate with dysgerminoma, was analyzed and found to be normal; its coding sequence was negative for deletions and mutations. DMRT-1 gene mapping on 9p and DAX-1 on Xp21 were also normal.

Meiotic origin of trisomy in neoplasms: evidence in a case of erythroleukaemia.

Trisomic cells in neoplasms may represent abnormal clones originated from a tissue-confined mosaicism, and arise therefore by a meiotic error. We report on a 16-month-old child with erythroleukaemia (AML-M6), whose marrow karyotype at onset was 48,XX,del(13)(q12q14),del(14)(q22q32),+21,+21. The parental origin of the supernumerary chromosomes 21 was investigated by comparing 10 polymorphic loci scattered along the whole chromosome on the patient's marrow and her parents' leukocytes.

17q21-qter trisomy is an indicator of poor prognosis in acute myelogenous leukemia.

A reciprocal translocation (9;11) is often found in acute myeloid leukemia (AML), mostly of the M5a type. We report a case of a child with AML, in whom t(9;11) was observed at diagnosis as the sole structural abnormality, together with trisomies 19 and 21. The diagnosis was AML evolving from a myelodysplastic syndrome (MDS), and the blast morphology was undifferentiated.

Full cytogenetic characterization of a new neuroblastoma cell line with a complex 17q translocation.

Recent studies have shown that structural abnormalities of chromosome 17 resulting in gain of material are the most frequent genetic changes in neuroblastoma. We have established a new neuroblastoma cell line from a patient whose disease had evolved from stage 4s to 4, without evidence of deletion of the short arm of chromosome 1 and MYCN amplification, which are considered the most typical genetic indicators of aggressive disease. The cytogenetic study allowed a full characterization of the chromosome changes, and revealed a complex translocation of chromosome 17 leading to a derivative marker which may be described as follows: der(11)t(11;17)(p15;q12)t(11;17) (q22;q12).

[The identification of minimal residual disease in the bone marrow and peripheral blood in neuroblastoma. The prognostic and therapeutic implications].

A highly sensitive and specific methodology to detect neuroblastoma cells in the bone marrow and peripheral blood of children with neuroblastoma is of critical importance for proper staging and treatment of these patients. In addition, patients with bone marrow infiltration at diagnosis need to undergo regular investigation to measure the effectiveness of chemotherapy (so called "in vivo" purging). Finally, the evaluation of autologous stem cells taken from bone marrow or peripheral blood is necessary to rule out or minimise the possibility of reinfusing tumor cells to the patient following myeloablative therapy.

[The morphological assessment of bone marrow infiltration in neuroblastoma].

Bone marrow biopsy is very important in diagnosis and follow-up of children affected by neuroblastoma (NB). Between June 1995 and May 1997 we studied 55 patients with NB stage 4. Specimens were obtained at the diagnosis (in 8 patients) and after chemotherapy (in 55 patients) in order to evaluate the effects of treatment on bone marrow disease.

Lipoblastoma: a case with t(7;8)(q31;q13).

Lipoblastoma is a rare benign adipose tumor which, in all of the cases so far described, presents an involvement of chromosome 8 in the region 8q11-13. We hereby report the results of the second case of lipoblastoma studied by fluorescence in situ hybridization (FISH), in a 13-month-old boy. An abnormal karyotype 46,XY,t(7;8)(q31;q13) was found in 90% of the metaphases examined, in agreement with the previously reported observations.

Massively diffuse multifocal granulocytic sarcoma in a child with acute myeloid leukemia.

A case of granulocytic sarcoma in an 8-year-old boy with acute myeloid leukemia and t (8; 21) is reported. The case is of interest due to massive extension of the tumor, which may raise different diagnostic difficulties with other solid tumors such as lymphoma, Ewing sarcoma, and soft tissue sarcoma. Furthermore, the tumor was localized in some sites, such as the parotid region and peripheral nerves, which are not usually involved in granulocytic sarcoma.

Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias.

We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months.