Cases reported "Chromosome Aberrations"

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1/128. Indeterminate-cell histiocytosis: immunophenotypic and cytogenetic findings in an infant.

    BACKGROUND: The authors report the immunohistochemical, ultrastructural, and cytogenetic findings in a case of malignant histiocytic proliferation in an infant. PROCEDURE: The patient presented initially with bone lesions without skin or systemic involvement. Multiple biopsies were studied extensively by immunohistochemistry and electron microscopy. Cytogenetic studies of cell cultures supplemented with granulocyte-monocyte colony stimulating factor (GM-CSF) were also performed. RESULTS: Morphologically, the cells resembled langerhans cells, although with greater pleomorphism, as evinced by cells with usual polylobated nuclei. These cells expressed markers for macrophages and antigen presenting cells and were CD1a- and S-100-positive, but lacked Birbeck granules. The cells grown in culture supplemented with GM-CSF showed a unique combination of numerical and structural abnormalities affecting chromosomes 1, 6, 8, and 10. The disease followed a malignant course leading to the patient's demise despite aggressive chemotherapy and bone marrow transplant. CONCLUSIONS: The findings suggest a malignant hematopoietic stem-cell neoplasm with a capacity for macrophage or dendritic-cell differentiation. Morphology and immunophenotypic features place this neoplasm within the group recently conceptualized as indeterminate-cell histiocytosis.
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2/128. Discordant expression of myeloid antigens and myeloperoxidase in a case of t(8;21) positive AML expressing CD7.

    We describe a case of acute myeloid leukemia (AML) showing myeloperoxidase (MPO)-positive and myeloid antigens negative. Although the leukemic cells showed few granules in May-Grunwald Giemsa staining, cytochemical MPO staining revealed that most of the blast cells strongly reacted with MPO. The leukemic cells did not express myeloid antigens (CD13, CD33), nor B-lymphoid or T-lymphoid antigens on the cell surface using flow cytometry, however. The cells did express CD34 and CD7. Discordant expression of MPO and myeloid antigens was also confirmed by electron microscopic MPO staining and by immunocytochemistry using a streptoavidin-biotin alkaline phosphatase labeling technique. Cytogenetic studies showed 46, XX, t(8;21) (q22;q22), del (9) (q22) in the bone marrow cells. In addition, AML1/ETO chimeric mRNA was detected from these cells. We summarize eight reported cases of MPO positive and myeloid antigens negative AML. Five of nine cases including our case had the same chromosomal abnormality of t(8;21) (q22;q22) and showed better prognosis than the other cases.
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3/128. Diffuse large B cell lymphoma expressing the natural killer cell marker CD56.

    The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10 , CD19 , CD20 , CD45RO-, CD3- and CD56 . On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.
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4/128. Antibody responses to leukemia-associated antigens during immunotherapy of chronic myelocytic leukemia.

    We have studied immunologic reactivity to leukemia-associated antigens in patients with chronic myelocytic leukemia (CML) treated with chemotherapy and adjunctive immunotherapy. All patients were immunologically competent as measured by skin test reactivity to dinitrochlorobenzene. immunotherapy consisted of allogeneic irradiated leukemic myeloblasts injected intradermally, with bcg vaccine (research Foundation, chicago, Ill.) given by multiple puncture at the same site. 10(9) cells plus BCG were given weekly for 4 wk, and 10(8) cells plus BCG were given at monthly intervals thereafter. Eight patients judged clinically to be in the stable phase of their disease developed circulating antibody against the immunizing blast cells demonstrable by cytotoxicity and immunofluorescence assays. The antibody also showed reactivity against a panel of myeloblasts (12 paients) but not against the corresponding remission lymphocytes (five patients) or normal lymphocytes (20 donors). In two cases the antibody showed reactivity against the patient's own leukemic blasts. Seven of these eight patients have maintained a steady clinical course ranging from 20 to 40 mo, while one entered the blastic phase and died. Six patients were judged to be in the aggressive phase of CML because of progressive leukocytosis and splenomegaly or increasing myeloblastosis; five died an average of 16 mo after diagnosis. Humoral antibodies were not detected in these patients after repeated courses of BCG and allogeneic leukemic cells. We conclude that specific active immunotherapy of patients with CML can abet the production of humoral antibody against blast cell antigens and that this response may be impaired during the aggressive phase of the disease.
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5/128. Morphologically normal, CD30-negative b-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?

    A recent study observed that numerical chromosome abnormalities in Hodgkin's disease (HD) are detected not only in morphologically abnormal Hodgkin/reed-sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morphologically normal cells and their relationship to the malignant Hodgkin/reed-sternberg cells could not be established in the earlier cases studied, because of the low frequency of these cells. The present study investigated two cases of classical Hodgkin's disease containing a relatively large population of such apparently normal cells with aberrant chromosome copy numbers. The phenotype and their position within the developmental route of the malignant compartment were examined by a combined in situ hybridization and immunocytochemistry approach. Numerical abnormalities for chromosome 1 in one case and for chromosomes X, Y, and 1 in the other case were observed not only in CD30-positive Hodgkin/reed-sternberg cells, but also in CD30-negative, morphologically normal cells. It was shown that these genetically aberrant cells expressed the B-cell antigen CD19, thus confirming their B-cell nature. These studies indicate a relationship between the genome aberrations in these genetically abnormal, morphologically normal B-cells and the Hodgkin/reed-sternberg cells, suggesting that they are progenitor cells of the malignant cell fraction.
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6/128. Atypical chronic myeloid leukemia with der(20)t(17;20)(q21;q13).

    We present a case of atypical chronic myeloid leukemia that developed blastic transformation four months after initial presentation, with the blast cells showing multilineage antigen expression. A novel karyotypic abnormality, der(20)t(17;20)(q21;q13), was found in bone marrow cells at diagnosis. The potential role of such an aberration in leukemogenesis is discussed.
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7/128. Maternal uniparental disomy (UPD) for chromosome 2 discovered by exclusion of paternity.

    Serological and molecular (dna-STR) analysis of a paternity case demonstrated exclusion of paternity of the presumptive father in two markers (ACP and Apo B, both localized on chromosome 2, region 2p25.2 and 2p23/24, respectively) in a phenotypically normal girl with a normal karyotype 46,XX (by GT-banding). The index of paternity calculated for other serological (seven erythrocyte antigens, six serum protein systems, and seven isozymes, as well as the A- and B-HLA loci) and nine dna markers, excluding ACP and Apo B, gives a very high (virtually certain) degree of paternity for the presumptive father. Maternal uniparental disomy (UPD) for chromosome 2 was suspected. Evaluation of polymorphic dna markers (STRs) spanning chromosome 2 of the child, mother, and presumptive father demonstrated that the girl had inherited two maternal chromosome 2 homologues, whereas alleles for markers from other chromosomes were inherited from the father in a Mendelian fashion. The girl was homoallelic for informative markers mapping to the chromosomal regions 2p23-25, but she was heteroallelic for informative markers on the long arm of chromosome 2, establishing that the maternal UPD with partial isodisomy of the short arm was caused by a meiosis I nondisjunction event with genetic recombination (chiasmata in this region 2p23-25) during oogenesis.
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8/128. A new human pleomorphic rhabdomyosarcoma cell-line, HS-RMS-1, exhibiting MyoD1 and myogenin.

    A number of human cell lines derived from alveolar or embryonal rhabdomyosarcoma (RMS) have been described. To our knowledge, however, no cell line established from pleomorphic RMS has been reported. We describe here the establishment and characterization of a new human cell line, HS-RMS-1, which originated from a typical pleomorphic RMS arising in the gluteal muscle of a 26-year-old man. HS-RMS-1 cells had pseudotetraploid complex karyotypes with no specific abnormalities. Both in vitro and in vivo the cells on light microscopic examination exhibited pleomorphic features with immunopositive reaction for myogenic antigens including MyoD1 and myogenin, although no Z band-like structures were detected electron-microscopically. RT-PCR demonstrated the expression of MyoD1 and myogenin in HS-RMS-1 cells at the mRNA level, and direct sequencing analysis revealed cDNAs of MyoD1 and myogenin identical to those previously reported. This cell line, HS-RMS-1, established from pleomophic RMS will be useful for further studies including the molecular aspects of human RMS.
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9/128. Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer.

    Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.
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10/128. association of a renal papillary carcinoma with a low grade tumour of the collecting ducts.

    This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, 7 <7> and 45, XY, -8, add(12)(q-ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished.
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