Malignant Lymphoma Cells Research Articles

Acquired Pure Red Cell Aplasia Associated with B Cell Malignant Lymphoma

Acquired Pure Red Cell Aplasia Associated with B Cell Malignant Lymphoma

上顎歯肉歯槽部に原発し診断が困難であった悪性リンパ腫の１例

A case of malignant lymphoma of the maxillary gingiva-alveolar region is documented. This case presented difficulty in histopathological differential diagnosis from squamous cell carcinoma.The patient was a 46 year-old man.He had a lesion from the upper gingiva of the molar region on the left side to the paranasal sinuses. On first biopsy examination, the lesion was diagnosed as poorly differentiated squamous cell carcinoma. He was treated with radiation and chemotherapy. After this treatment, a rapid growth of the left supramandibular lymph node was seen.The histopathological diagnosis of the extirpated tumor was non-Hodgkin's lymphoma, pleomorphic type. Retrospectively, the lesion of the gingiva-alveolar region, which was diagnosed previously as poorly differentiated squamous cell carcinoma, was considered to be malignant lymphoma. Special attention should be paid to the fact that the figure of malignant lymphoma's cells can be similar to that of poorly differentiated squamous cell carcinoma's cells.

Significance of non-lymphoid ('accessory') cells in malignant lymphomas and pseudolymphomas of the skin.

We investigated the co-distribution of lymphocyte subpopulations and non-lymphoid 'accessory' cells in 35 cases of cutaneous lymphoproliferative diseases (T-cell lymphoma, 10 cases; B-cell lymphoma, 17 cases; pseudolymphoma, 8 cases) using immunohistochemical methods. T-zone histiocytes and particularly Langerhans cells were abundant in all cutaneous T-cell lymphomas, but were also found in B-cell lymphomas. T-zone histiocytes were associated with T-lymphocytes, especially T-helper cells, but not with T-suppressor cells. Dendritic reticulum cells were essentially confined to well differentiated germinal centres. Macrophages occurred in both lymphomas and pseudolymphomas without definite relationship with either B- or T-cells. In malignant lymphomas of high grade malignancy, macrophages represented the only non-lymphoid cell type. Our results indicate that malignant lymphoid cells, like normal lymphocytes, require definite micro-environments which are, at least in part, maintained by certain non-lymphoid cells.

Flow cytometric analysis of DNA in diagnostic cytology.

Flow cytometric analysis of nuclear DNA content and cell surface immunologic phenotyping were used in the evaluation of cytologic samples obtained from four patients. In each sample, a lymphoid cell population was present, which was difficult to evaluate by traditional cytopathologic methods. In two of the cases, the flow cytometric demonstration of monoclonal populations of lymphoid cells characterized by abnormal amounts of nuclear DNA gave support to the cytologic interpretation of malignancy. In a third sample, a lymphoid cell population that could not be cytologically distinguished from malignant lymphoma cells of small lymphoid cell type was shown to be composed of euploid, polyclonal cells. In the fourth case, the demonstration of euploidy in morphologically distinctive cell populations was helpful in interpreting the fine-needle aspirate of the thyroid gland. The authors conclude that flow cytometry can be used to great advantage in the evaluation of cytologic samples as well as in predicting biologic behavior.

Use of novel chemical supplements in the establishment of three human malignant lymphoma cell lines (NU-DHL-1, NU-DUL-1, and NU-AMB-1) with chromosome 14 translocations.

Three new cell lines have been established from patients with malignant lymphoma utilizing a human diploid feeder layer, pooled human serum, and the chemical supplements L-cysteine, iron-saturated transferrin, and bathocuproine disulfonate, a copper chelator. After a short period of growth, the 3 cell lines were successfully weaned from the feeder layers but continued to require human serum and the chemical supplements for up to 9 months of culture. The cell lines are currently grown in RPM1-1640 medium and fetal calf serum without further supplementation. The NU-DHL-1 cell line was established from the involved lymph node of a 73-year-old White male with diffuse large-cell lymphoma. The cell line expresses cytoplasmic IgM/lambda heavy and light chains, is Epstein-Barr virus (EBV)-negative, and is positive for several B-cell markers, indicating that it is derived from a mature-B-cell neoplasm. The NU-DUL-1 cell line was established from the cerebrospinal fluid of a 42-year-old White male with undifferentiated lymphoma, non-Burkitt's type, who initially presented with a mediastinal mass and had subsequent involvement of the central nervous system. The cell line is EBV-negative, but surprisingly it is positive for early B-cell markers. The NU-AmB-1 cell line was established from the abdominal mass of a 12-year-old Hispanic male with undifferentiated lymphoma, Burkitt's type. The cell line is EBV-positive and expresses early B-cell markers. All 3 cell lines are aneuploid or pseudodiploid and contain chromosome 14q+ abnormalities including a newly described complex translocation t(?;1;8;14) in the NU-AmB-1 cell line. The establishment of these cell lines was made possible by refinements in the cell culture of the human malignant lymphomas. The availability of well-characterized lymphoma cell lines with specific chromosomal translocations will aid molecular and cellular studies designed to identify the biological significance of genomic rearrangements.

Tubular structures in S49 mouse lymphoma are regulated through in vivo host-cell interaction and in vitro interferon treatment.

Malignant S49 mouse lymphoma cells that grow in suspension culture demonstrate in their cytoplasm characteristic tubular structures. These structures also appear in immunogenic, substrate-adherent variants of S49 cells that grow in culture. Upon transfer of both cell types into nude mice, the tubular structures of the adherent variants (and not the suspension-growing cells) undergo a profound alteration whereby their tubular components disappear and clusters of viruslike particles appear. These very closely resemble, on morphological grounds, precursors of B-type retroviruses. This specific in vivo interaction between the host and the S49 variant can be mimicked in culture by treatment of these cells for 24 h with 500 U/ml of mouse interferon. The suspension-growing S49 cells are unresponsive to interferon in this respect. Immunohistochemical analysis reveals that both tubular structures and the viruslike particles represent stages in the morphogenesis of mouse mammary tumor virus. A working hypothesis is advanced relating the regulation of the tubular system to the impaired tumorigenic potential of adherent S49 cells in syngeneic Balb/c hosts.

Combined Cytotoxicity Effect of Hyperthermia and Anthracycline Antibiotics on Human Tumor Cells<xref ref-type="fn" rid="FN2">2</xref>

The effects of temperature on the anthracycline antibiotics-induced cell kill of DND-1A human malignant melanoma (MM) and DND-39A Burkitt's lymphoma (BL) cell lines were studied by means of a clonogenic assay. The two cell lines differed in sensitivity when exposed to heat: The MM cells were unaffected by hyperthermia (42 degrees C), whereas BL cells were sensitive to this temperature. With the MM cells, hyperthermia potentiated the cytotoxic effects of doxorubicin (ADM), daunorubicin, mitoxantrone (DHAD), and quelamycin but did not enhance that of aclacinomycin (ACM). Conversely, the exposure of cells to the anthracycline compounds at 0 degree C resulted in almost complete disappearance of cell kill effects except with ACM; ACM retained substantial cell kill effects even at the given low temperature. For BL cells, ADM- or DHAD-induced cell lethality was also potentiated by hyperthermia; ACM produced only additive cell kill. At 0 degree C, ACM's effects virtually disappeared. These data indicate that human tumor cell lines have a substantial variety in heat sensitivity and that not every anthracycline antitumor agent is potentiated by temperature. ACM's thermoresponse is unique among anthracycline antibiotics studied. Additionally, it was shown that normothermic cell kill by ADM was not affected by hyperthermic preheating; however, preheating of appropriate duration produced important influence on subsequent hyperthermic ADM-induced cell kill.

Clinical significance of the subsets of lymphocyte in the peripheral blood of the head and neck cancer patients

Clinical utilities of the measurement of the subsets of the lymphocyte in peripheral blood of the 47 head and neck cancer patients were investigated.Lesion of the subjects were larynx (21), paranasal sinus (8), epipharynx (4), mesopharynx (4), tongue (4), parotis (3), cervical esophagus (2) and ear (1). Histologies of them were squamous cell carcinoma (38), adenocarcinoma (5), malignant melanoma (3) and malignant lymphoma (1). Lymphocytes of the patients were incubated with monoclonal antibody marked with fluorecent substances, then were counted by fiuorocytometer EPICS V(C). Most useful parameter was the numbers of OKT4+ lymphocytes, because they were well correlated with clinical course and prognosis. Although percentage of OKT8+ lymphocytes was elevated in the condition with cancer, the numbers of OKT8+ lymphocytes did not changed. So the elevation of percentage of OKT8+lymphocytes was caused by the decrease of the numbers of OKT4+ lymphocytes. Then for units of the subsets of lymphocytes as parameter, absolute numbers were better than percentage. According to the examination of the change of the subsets in radiation therapy, it was supposed that the best preoperative dose was 2000 rads.

Growth fractions in malignant non-Hodgkin's lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67.

The proportion of proliferating cells in malignant non-Hodgkin's lymphomas (NHL) was determined in situ by immunostaining with the monoclonal antibody Ki-67, which reacts with a nuclear antigen that is present only in proliferating cells. A highly significant correlation could be demonstrated between the proportion of Ki-67 positive cells and the classification into high and low-grade NHL according to the Kiel classification. 93.8 per cent of high-grade and 88.5 per cent of low-grade malignancies were correctly allocated to these groups using the percentage of Ki-67 positive cells as discriminant parameter. On the basis of the medians, the degree of proliferation also paralleled the succession of entities within the Kiel classification. Within most of these different entities, however, the ranges of Ki-67 positive cells varied considerably, indicating that the growth fractions within these groups are rather heterogeneous. Thus it might be useful to determine the growth fraction of each individual case of NHL, because this might be of prognostic value.

Preparation and characterization of monoclonal antibodies recognizing three distinct differentiation antigens (BL1, BL2, BL3) on human B lymphocytes.

We report in this paper the generation and characterization of three monoclonal antibodies, designated alpha BL1, alpha BL2, and alpha BL3, that recognize distinctive antigens unrelated to complement, Fc, and mouse erythrocyte rosette receptors, which are preferentially expressed on B lymphocytes. alpha BL1 recognizes a heat stable nonimmunoprecipitable antigen, possibly glycolipid in nature. Alpha BL2 recognizes a nonreducible single polypeptide with a m.w. of 68,000 that occasionally co-precipitates with a p29,34 complex of HLA-DR antigens. Alpha BL3 recognizes a nonreducible single polypeptide with a m.w. of 105,000 with an acidic pI point. We demonstrated that BL1 is expressed on fetal liver hematopoietic cells, a small subset (5 to 15%) of Ficoll-Hypaque-separated normal bone marrow cells, and on a subpopulation of nonadherent, non-E rosette-forming cells and granulocytes. BL2 is expressed on fetal liver hematopoietic cells, on 3 to 7% of normal bone marrow cells, and on a majority (40 to 70%) of nonadherent, non-E rosette-forming cells with a distinctive pattern similar to that of HLA-DR. BL3 is expressed on a subpopulation of nonadherent, non-E rosette-forming cells, and on occasional cells in the monocyte-enriched adherent cell population. The peak fluorescence for BL2 is substantially higher than that of BL1 and BL3, indicating higher BL2 antigen density. All three antigens are absent from thymocytes and E rosette-positive T cell fractions obtained from various lymphoid tissues. Cellular distribution of the BL antigens on various well-characterized established hematopoietic cell lines, leukemias, and malignant lymphomas, in conjunction with the results of the in vitro activation and TPA-induction experiments, suggest that BL1 is expressed during early developmental stages of B cell differentiation, whereas BL3 is expressed at the later stages. BL2 expression spans immature and mature stages of B cell differentiation, with the exception of mature plasma cells. The alpha BL antibodies described here should prove to be useful in the investigation of B cell differentiation and in the clinical diagnosis of lymphoid neoplasms.

Cytophotometric Measurements of the DNA in Hodgkin Lymphomas and Non-Hodgkin Lymphomas

In smear preparation of lymph nodes excised from 36 patients with a malignant lymphoma the DNA content was estimated in different tumor cells following Feulgen staining by means of quantitative cytophotometric measurements. The tumors investigated included 11 Hodgkin lymphomas and various types of Non-Hodgkin lymphomas (altogether 25). Whereas the small lymphoid cells found in Hodgkin lymphomas show a diploid DNA content with a wide scattering, in the large mononuclear reticular cells (Hodgkin cells) as well as in Sternberg's giant cells only aneuploid DNA values are seen lying in the hyperdiploid, hypertetraploid and hyperoctoploid regions. DNA stemlines are found in the aneuploid regions, but in some cases they are missing. This indicates that we are dealing with malignant tumor cells. In Non-Hodgkin lymphomas with a low grade of malignancy (centrocytic-centroblastic lymphoma, centrocytic lymphoma, CLL) an aneuploid DNA content is found particularly in the large cells (centroblasts, lymphoblasts) with or without a DNA stemline. These cells must be considered as primary malignant tumor cells. In the immunoblastic lymphoma of high malignancy only aneuploid tumor cells are present showing a particularly intense DNA content in the large immunoblasts, whereas a DNA stemline is usually missing. The range of aneuploid values, the number of polyploid tumor cells and the presence or absence of a DNA stemline are important criterions in determining the degree of malignancy. By means of cytophotometric measurements of the DNA content in the tumor cells of malignant lymphomas it is possible to assertain the degree of malignancy and to establish an objective prognosis.

The Detection of Human T Cell Leukemia Virus Proviral DNA and Its Application for Classification and Diagnosis of T Cell Malignancy

Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.

The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy

Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.

Natural killer (Leu 7+) cells in reactive lymphoid tissues and malignant lymphomas.

Leu 7 (HNK-1) is a monoclonal antibody reported to identify human natural killer/killer cells. The frequency and distribution of Leu 7+ cells in 14 reactive lymphoid tissues and 47 malignant lymphomas were studied using the frozen section immunoperoxidase technic. In reactive lymphoid tissues, Leu 7+ cells were concentrated in the pale zone of germinal centers and usually were relatively scarce in the interfollicular areas. Of the malignant lymphomas, follicular lymphomas most consistently had numerous admixed Leu 7+ cells and lymphoblastic lymphomas the least. The authors' findings suggest that Leu 7+ cell accumulation in normal and neoplastic lymphoid tissue is associated at least in part with something shared by the pale zone of the normal germinal centers and the presence of neoplastic germinal centers. This association does not appear to be a simple response to lymphoid proliferation.

Titers of Epstein-Barr virus-related antibodies in nasopharyngeal carcinoma in Japan.

It is thought that nonkeratinizing or undifferentiated squamous cell carcinoma in the nasopharynx (NPC) is intimately correlated with Epstein-Barr Virus (EBV). Twenty-one patients with NPC were followed in Kyoto University Hospital and 4 in Osaka Red Cross Hospital during the past 2 years from 1980 to 1981. These patients were classified histopathologically according to the WHO classification in 1978 and staged with the TNM classification in Union Internationale Contre le Cancer (UICC) in 1978. The incidence rate of NPC among the head and neck tumors was 5.6% in the authors' university from 1980 to 1981. The sex ratio of male to female was nearly equal. The mean age of NPC patients was 56.7 years. Sera from these 25 patients with nasopharyngeal carcinoma were collected at intervals of 3 to 8 months over a 2-year period, and were examined for their spectra and titers of antibodies of EBV-related antigens. They were titrated for IgG, IgA and IgM antibodies to EB viral capsid antigen (VCA), for IgG and IgA antibodies to early antigen-DR component (EA) and for antibodies to EBV-associated nuclear antigen (EBNA). All of these patients were primarily treated with radiation, while a few who did not respond to this therapy were subsequently treated with surgery or chemotherapy. EBV antibodies of VCA-IgG, -IgA, EA(DR)-IgG, and -IgA and EBNA were elevated in 73% and 90% of the nonkeratinizing and undifferentiated NPC patients, respectively. The VCA-IgM was elevated in almost none of the cases. In contrast to this, these values were all in a normal range in the NPC patients with keratinizing squamous cell carcinoma and malignant lymphoma. Also 9% and 10% of nonkeratinizing and undifferentiated carcinomas showed the normal ranges of EBV antibodies, possibly indicating a nonassociation with EBV. When NPC disappeared with radiation therapy, EBV antibodies became normal for 6-18 months. However, those whose NPC did not respond to the combined therapy with radiation, surgery and chemotherapy maintained high titers of EBV antibodies. The prognosis was the poorest in the patients with undifferentiated carcinoma, 40% of whom died within 4 years after diagnosis.

Effects of Large Granular Lymphocytes on Malignant Lymphoma Cells

Effects of Large Granular Lymphocytes on Malignant Lymphoma Cells

腰つい硬膜外くうに原発した悪性リンパしゅの一例

Primary malignant lymphoma in spinal epidural space is a rare case.We have experienced one patient with primary malignant lymphoma in lumbar epidural space. The patient is a 57 years old male who has bladder and rectal paralysis, left foot numbness and left sciatica. Myelogram demonstrated an epidural compression mass at the left side of L5-S1 vertebrae. A wide laminectomy of L4 and L5 spine was performed and the ossification of ligamentum flavum at the L4-5 level, compressing the cauda equina from left side, was removed. The neurological symptoms improved remarkably soon after operation, but the plantar numbness remained. About six months after the laminectomy, he complained of left gluteal and foot pain. Seven months after the operation, he was unable to pass urine on his own. Myelogram revealed an epidural tumor at the level of L5-S1 spine, compressing from the left posterolateral side. Dura and left L5 nerve root were decompressed completely by the operation.The tumor was diagnosed at the malignant lymphoma (non-Hodgkin's type), diffuse and large cell type by histological examination.Three months after the resection of the tumor, scintigram discovered the bone bone metastasis at the sacrum and the right temporal bone.He was given radiotherapy and chemotherapy with a combination of VEMP.

Insulin Receptors on Leukemia and Lymphoma Cells

AbstractTumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125l-labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohe-magglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I-labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.

Subcutaneous leiomyosarcoma with lymphomatous elements: Histogenetic implications of an unusual sarcoma

A 49-year-old woman had an unusual sarcoma that recurred three times in four years. The tumor manifested initially as a subcutaneous abdominal wall nodule composed of lymphohistiocytic malignant lymphoma and spindle cell sarcoma with epithelioid and clear cell elements. The neoplasm recurred first as a spindle cell sarcoma in the lumbar area, second as a malignant lymphoma in the subcutaneous tissue of the right shoulder, and third as a spindle cell sarcoma with lymphohistiocytic areas in the abdominal wall. Ultrastructural studies of this last tumor nodule demonstrated the unequivocal smooth muscle features of the spindle cells. Histogenetic implications of this neoplasm are discussed. It is proposed that the tumor represents an unusual variant of malignant mesenchymoma of soft tissues.