Angio-immunoblastic lymphadenopathy with fibrosis of bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph nodes

We report a 47-year-old man diagnosed as angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with fibrosis of the bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph node. He was admitted to a hospital in May, 1980 because of general fatigue, cough, fever and systemic lymphadenopathy. The diagnosis of AILD was based on a biopsy of right cervical lymph node. His symptoms were improved but recurred with the addition of icterus and progressive pancytopenia with decrement of prednisolone. He was referred to our hospital in July, 1980 and his physical examination revealed generalized lymphadenopathy, icterus and hepatosplenomegaly. Hemogram showed pancytopenia, and needle biopsy of the bone marrow disclosed fibrosis. Sections from the lymph node showed AILD with proliferation of epithelioid cells. Administration of 60 mg/day of prednisolone improved the fever, lymphadenopathy and hepatosplenomegaly. However he died suddenly of acute respiratory failure on July 30. Autopsy showed fibrosis of bone marrow, lymph node, liver and spleen with infiltration of abnormal lymphocytes, and pulmonary aspergillosis.     

Detection of monoclonal plasma cells in bone marrow and spleen of primary amyloidosis]

A 53-year-old man was diagnosed as primary amyloidosis by biopsy specimens of the mucosa in rectum, spleen and bone marrow (BM). BM examination showed 5.5% of plasma cells with some dysplasia. Immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction using third-complementary-determining region (CDR 3) specific primers in BM mononuclear cells and spleen cells embedded in paraffin. The sequence analysis revealed that monoclonal B cells existed in the both, BM and spleen. Flowcytometric analysis using two-color staining showed the phenotype of plasma cells with the expression of CD19+/-, CD27+/-, CD56+/- and CD138+ and CD38++. This phenotype is similar to those of monoclonal gammopathy of undetermined significance (MGUS). Therefore, primary amyloidosis is considered to have two plasma cell populations including normal plasma cells and monoclonal plasma cells in BM. Given that there are two types of plasma cells in patients with primary amyloidosis, amyloid protein is expected to originate from immunoglobulin light chain produced by monoclonal plasma cells.     

Different composition of the erythropoietic tissue in bone marrow, spleen and liver in myelofibrosis.

Aspirates from bone marrow, spleen and liver were analysed in 10 untreated patients with idiopathic myelofibrosis (MF). The proportion of erythroblasts was higher in the spleen and the liver than in the bone marrow. The mitotic indices of the erythropoietic precursor cells were subnormal in the extramedullary sites and significantly lower in the liver compared with the spleen. There was a "shift to the left" within the liver erythropoiesis and a significant megaloblastosis in the spleen. The same tendencies have formerly been found in patients with chronic myeloid leukemia and it is suggested that the discrepancies may be due to differences in the microenvironment of the erythropoietic cells.     

Sequential maturation stages of monoclonal B lineage cells from blood, spleen, lymph node, and bone marrow from a terminal myeloma patient.

In order to fully understand the complexity of the monoclonal B lineage cells in multiple myeloma, it is necessary to evaluate the extent to which these cells are resident in solid lymphoid tissues and the phenotypic differences and similarities as compared to the circulating or bone marrow derived B lineage cells. Peripheral blood mononuclear cells from a patient with multiple myeloma were obtained 8 and 3 days prior to death, and mononuclear cells from lymph nodes, spleen, and bone marrow were obtained at autopsy. Rapid changes in the stage of differentiation of blood late-stage B lineage cells towards mature end-stage plasma cells were observed during the last week prior to death. Lymphoid cells within the blood comprised very few T cells, sub-normal numbers of monocytes, and 80% of B lineage cells which were at a late stage of differentiation. Shortly before death, plasma cells were found in the peripheral blood, indicating progression to plasma cell leukemia. At autopsy, the monoclonal B lineage cells in lymph node, spleen, and bone marrow represented different stages of terminal B cell differentiation. In each tissue, the B lineage cells were at an earlier differentiation stage, as defined phenotypically, than the circulating B lineage cells found in blood 3 days prior to death. Analysis of B cell markers and CD45 was used to define the differentiation stage of the relevant B cell populations, revealing a series of differentiation stages. The least mature B lineage cells (CD45hi) were found in lymph node. However, the CD45 isoform expressed was CD45R0, unlike most normal lymph node B cells. More differentiated B lineage cells (CD45med) were found in the bone marrow, and three sequential stages of pre-plasma cells were found in the spleen (CD45bright, CD45moderate, and CD45low-neg), all of which were CD45R0+. The B cells in normal spleen and bone marrow are CD45RA+. The presence of monoclonal B lineage cells in spleen was confirmed by Southern blotting. The B lineage cells from peripheral blood 3 days prior to death were approaching an end-stage plasma cell stage (CD45low/-). On B lineage cells from the various myeloma tissues, a concomitant loss of CD11b and increasing density of CD29 were observed as a function of progression to terminally differentiated stages.     

Evaluation of trisomy 12 by fluorescence in situ hybridization in peripheral blood, bone marrow and lymph nodes of patients with B-cell chronic lymphocytic leukemia

BACKGROUND AND OBJECTIVE: Trisomy 12 is the most common numerical chromosomal aberration in patients with B-cell chronic lymphocytic leukemia (B-CLL). Fluorescence in situ hybridization (FISH) has improved the detection of this cytogenetic abnormality and has made detection possible in all phases of the cell cycle. The presence of the trisomy 12 positive (+12) cell population has generally been investigated in leukemic cells obtained from the peripheral blood of CLL patients. To ascertain whether trisomy 12 is expressed homogeneously in cells of different hemopoietic tissues, we applied FISH to lymph node, peripheral blood and bone marrow samples obtained simultaneously from 23 untreated B-CLL patients. DESIGN AND METHODS: Twenty-three newly diagnosed patients with B-CLL, 15 in stage B and 8 in stage C, were included in the present study. Peripheral blood smears, bone marrow aspirate smears and lymph node touch imprints were collected from each patient at diagnosis. Cytologic preparations were examined by light microscopy in order to assess the lymphocyte morphology. Immunophenotyping was performed by cytofluorimetric analysis of the peripheral blood, bone marrow and lymph node mononuclear cell suspensions. The diagnosis was supported in all cases by histologic findings in bone marrow biopsy and lymph node biopsy specimens. Fluorescence in situ hybridization was performed on smears of blood and aspirated bone-marrow and lymph node touch imprints obtained by fresh tissue apposition. RESULTS: In 6 of the 23 cases (26%) trisomy 12 was clearly present in all tissues examined. A comparative analysis of the three different hemopoietic tissues was performed. A higher percentage of leukemic CD5+CD23+ cells was detected in lymph nodes than in peripheral blood and bone marrow. A significantly higher proportion of trisomic cells was observed in lymph nodes samples than in peripheral blood or bone marrow smears of trisomy 12 positive CLL patients. INTERPRETATION AND CONCLUSIONS: Several previous reports show that only a proportion of malignant B-CLL cells carry trisomy 12 when analyzed by interphase FISH. The higher proportion of +12 cells in lymph nodes than in peripheral blood or bone marrow of CLL patients with trisomy 12 could reflect different cell distributions in different tissues, or lymph node specific tropism, or proliferative advantage in selected tissue. At present, the role of trisomy 12 in the pathogenesis of lymphoproliferative disorders is unclear.     

Lodging of CFU(S) under various circumstances in bone marrow, spleen and liver

Treatment of mice with high doses of endotoxin (ET) affected the CFU(S) population in bone marrow, spleen and liver. By 7 days after injection the number of CFU(S) in bone marrow had decreased and the number in spleen and liver had increased. The experimental data show that if mice were irradiated and reconstituted with bone marrow 7 days after ET treatment, the lodging pattern of injected cells followed qualitatively the same changes as the changes in numbers of CFU(S) present before irradiation in these organs. However, elevated numbers of CFU(S) cannot be maintained in the liver and can only partly be maintained in the spleen. In retransplantation experiments, CFU(S) from bone marrow and from bone marrow or liver after treatment of mice with ET have the same seeding efficiency in the spleen, indicating that there is no preferential homing of subclasses of CFU(S) in bone marrow or liver. It is concluded that the presence of CFU(S) and hemopoietic tissue may be an expression of the capability of the tissues for the maintenance of lodging CFU, but the initial lodging in these organs is also affected by other trapping mechanisms.     

Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE

A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.     

Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen

Talin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.