Cases reported "Chromosome Disorders"

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1/39. 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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2/39. 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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3/39. 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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4/39. The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia.

    A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line.
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5/39. A human B-cell lymphoma line with a de novo multidrug resistance phenotype.

    A human diffuse large cell lymphoma line (WSU-DLCL) expressing multidrug resistance (MDR) was established from a patient with primary chemotherapy-resistant disease. This cell line has the same phenotypic features as malignant cells from the patient. The established cell line has features of a mature B-cell neoplasm with no evidence for commitment to other lineages. WSU-DLCL grows in suspension forming relatively large clumps of cells with a doubling time of 20 hours. By light microscopic examination, the cells are very large with primitive lymphoid features, have a large amount of cytoplasm containing numerous vacuoles and an irregular outline. Immunophenotypic characterization by monoclonal antibodies and flow cytometric analysis showed a monoclonal IgM kappa B-cell phenotype with high expression of the multidrug-resistant p-glycoprotein compared with either normal peripheral blood lymphocytes or cells of the REH cell line. The cells were negative for T-cell and myeloid/monocyte antigens as well as Epstein-Barr virus nuclear antigen (EBNA). In addition, the cell line expressed high levels of MDR rna. dna histogram generated by flow cytometry indicated a dna index of 1.83. cytogenetic analysis confirmed hypertriploidy and showed complex chromosomal abnormalities including 14q . This cell line should be a valuable tool to study the role of the MDR gene in the primary resistance of lymphomas to chemotherapy and to facilitate therapeutic investigations.
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6/39. Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization.

    Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% /- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% /- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% /- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% /- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.
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7/39. Establishment and characterization of a new Ewing's sarcoma cell line.

    A new human Ewing's sarcoma cell line (CADO-ES1) was established from the malignant pleural effusion of a 19-year-old woman. These cells grew both anchorage dependently and anchorage independently. When cultured in bacteriologic dishes, they grew as tightly packed multicellular tumor spheroids; they were also capable of proliferating in soft agar. Flow cytometric dna analysis demonstrated a nearly diploid dna content (dna index = 0.902). Chromosomal studies of cultured cells showed an isodicentric chromosome 8 in all examined cells, but t(11;22)(q24;q12), a translocation reported previously in Ewing's sarcoma, was not detected. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. In addition, immunocytochemical studies showed that vimentin was intensely positive, whereas neurofilament (NF) and neuron-specific enolase (NSE) were weakly positive. Treatment with cyclic amp (cAMP) induced pronounced morphologic evidence of neural differentiation and strong expression of NF in cultured cells. S-100 protein, glial fibrillary acidic protein (GFAP), desmin, cytokeratin, and epithelial membrane antigen were not detected immunohistochemically in either untreated or cAMP-treated cells, however. These data suggest that this cell line is derived from a highly undifferentiated neural cell with high chromosomal clonality, differentiating into neural features under certain conditions.
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8/39. Characterization of a newly established human Burkitt's lymphoma cell line, OMA-BL-1.

    Using culture techniques, we have been able to grow occult tumor cells from the bone marrow from cancer patients and have developed a new malignant lymphoid cell line, OMA-BL-1, from the bone marrow of a 17-year-old patient with recurrent Burkitt's lymphoma. The tumor cells grew rapidly in vitro in suspension culture, and very aggressively in vivo in athymic nude mice with metastases to the liver and abdominal cavity. The morphological, chromosomal, immunophenotypic and molecular biologic characteristics of fresh uncultured tumor cells from the patient and tumor cells grown in culture and in athymic nude mice were very similar. The cells were positive for Epstein-Barr virus-associated nuclear antigens (EBNA) and chromosome analysis of the cells revealed an atypical chromosomal abnormality of 45,X,-X,i(8q), HSR(18)(q21),t(8;14)(q24;q32). Southern analysis demonstrated that c-myc was rearranged and amplified in these cells. Immunophenotypic analysis of the cells using flow cytometry showed monoclonal B cells expressing a surface IgG-kappa isotype. The tumor cells grown in nude mice had a significant decrease in CD24 expression when compared to cultured tumor cells. Electron microscopy of the fresh and cultured cells revealed Herpes virus, most likely Epstein-Barr virus, particles. This cell line has been maintained in culture for over 18 months. The aggressive growth and metastatic properties of this cell line in athymic nude mice make it a potentially useful experimental model to study the biology of human lymphoma.
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9/39. Presence of h-y antigen and testis in 46, XX true hermaphroditism, evidence for Y-chromosomal function.

    Endocrinologic and serologic studies of a 2-year-old child with the chromosomal complement 46,XX and ambiguous genitalia suggested the preoperative diagnosis of true hermaphroditism. Urinary and serum androgen production in response to human chorionic gonadotrophin was in the range expected for normal males, implying presence of cryptic testicular tissue. Moreover, detection of h-y antigen, a cell surface component associated with testicular differentiation and coded or regulated by a Y-chromosomal gene, indicated presence of Y-chromosomal material. The diagnosis of true hermaphroditism was confirmed at surgery. Assuming a constant association of h-y antigen and testicular differentiation is established, human H-Y serology may be an important adjunct to the endocrinologic evaluation of intersex patients. Our studies support the interpretation that a Y-chromosomal translocation too small for cytologic detection accounts for testicular differentiation in 46,XX true hermaphroditism. Expression of h-y antigen remained positive after castration.
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10/39. Acute leukemia evolving from multiple myeloma and co-expressing myeloid and plasma cell antigens.

    This report describes the development of acute myeloblastic leukemia in a patient after long-term alkylator therapy for multiple myeloma. Despite chromosome deletions -5, -7, the patient lacked the histochemistry and clinical findings characteristic of therapy-induced leukemia. In double-labeled surface marker studies by flow cytometry, the leukemic blast cells co-expressed myeloid and plasma cell surface markers. The findings may support the hypothesis of a single stem cell abnormality's being responsible for both the malignant plasma cells and the myeloid leukemic cells.
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