Junko Tachibana

A high incidence of rheumatoid factor idiotypes in monoclonal proteins in the serum and in lymphoma cells in patients with Sjögren's syndrome

Patients with Sjögrens syndrome (SS) develop lymphoproliferative disorders such as monoclonal gammopathies and non-Hodgkins lymphomas. Cross-reactive idiotypes (CRI) were studied in 22 serum monoclonal immunoglobulins (Igs) and in cytoplasmic Ig in four B-cell lymphoma cells in patients with SS. This was done by utilizing monoclonal anti-idiotypic antibodies which were produced against monoclonal rheumatoid factors (RF) derived from three patients with SS and one patient with Waldenströms macroglobulinemia. By the Western blotting or dot immunobinding technique, CRI was detected not only in monoclonal RFs but in monoclonal Igs which had different heavy- or light-chains from the original monoclonal RF used for immunization. A higher incidence of CRI was found in 22 monoclonal Igs associated with SS than in 27 monoclonal Igs in patients with Waldenströms macroglobulinemia, multiple myeloma or malignant lymphoma. In four patients with malignant lymphoma associated with SS, three showed one or three CRI in the lymphoma cells, whereas only two out of 20 patients with other malignant lymphoma showed CRI, demonstrating a significant difference between two groups. These data indicate that monoclonal proliferation of B-cell lineage in patients with SS, benign or malignant, takes place more often among RF-producing clones than other B-cell disorders.

Interleukin-7 (IL-7)-induced proliferation of CD8+ T-chronic lymphocytic leukemia cells

Interleukin-7 (IL-7) is a growth factor for pro-B cells, pre-B cells, and thymocytes and is known to induce the proliferation of normal human peripheral T cells. Moreover, human B and T acute leukemia cells with immature surface markers proliferate in response to IL-7. Here we describe a case of T-chronic lymphocytic leukemia, in which the leukemic cells showed a proliferative response to human recombinant IL-7in vitro. The patient was a 74-year-old woman with anemia and thrombocytopenia, whose bone marrow was fibrosed and infiltrated with pathologic cells. Surface markers of the leukemic cells were CD2(+), CD3(+), CD5(+), CD7(+), CD8(+), and CD4(−). Both T-cell receptor β-chain and γ-chain genes were found to be rearranged by immunogenotypic analysis. The leukemic cells proliferated in response to IL-7 dose dependently. The DNA synthesis of CLL cells was stimulated by not only IL-7 but also IL-2 and IL-4. The IL-7-induced proliferation was not inhibited by antibodies to IL-2 receptors or the anti-IL-4 antibody. These findings indicate that IL-7 may induce the proliferation of peripheral CD8+ T cells, even on its pathological counterpart.

Lymphomatous Polyarthritis in Patients with Peripheral T-Cell Lymphoma

Direct involvement of the joints is a rare complication of malignant lymphoma and lymphoma cells in synovium or synovial fluid have been characterized in only a very few cases. We report two cases of CD4-positive, HTLV-I-negative peripheral T-cell lymphomas that manifested polyarthritis infiltrated with lymphoma cells which we further characterized. Patient 1, with a prior 7-year history of cutaneous T-cell lymphoma (mycosis fungoides) and polyarthralgia, developed pain and swelling in the right knee joint and right femoral region. Patient 2 was initially diagnosed with immunoblastic lymphadenopathy, later rediagnosed as the prodromal stage of T zone lymphoma. Seven years later she developed skin eruptions, cervical lymph node swelling, polyarthritis, and pleural effusion. Synovial fluid analysis in both cases showed predominant CD3+ or cytoplasmic CD3+, CD4+, and CD8- atypical lymphoid cell infiltration. In both cases the T-cell receptor beta and gamma chains were rearranged in the synovial fluid mononuclear cells. Analysis of these two cases and a review of the literature suggest that lymphoma cell infiltration of synovium occurs preferentially in patients with CD4+ peripheral T-cell lymphoma.

Electron microscopic morphometry of chronic type lymphoid leukemias

Malignant cells from 1 case of chronic lymphocytic leukemia of the T-cell type (T-CLL), 5 cases of chronic lymphocytic leukemia of the B-cell type (B-CLL), 1 case of prolymphocytic leukemia of the B-cell type (B-PLL), 1 case of lymphocytic lymphoma of intermediate differentiation of the B-cell type (B-ILL), 1 case of splenic B-cell lymphoma with circulating villous lymphocytes (SLVL), and 2 cases of hairy cell leukemia (HCL) were measured on electron micrographs. The area of the cytoplasm, nucleus, nucleoli, and the perimeters of nuclei were measured and the nucleo-cytoplasmic ratio, nucleolo-nuclear ratio, and nuclear contour index (NCI) were calculated. Malignant cells from B-PLL had the largest cytoplasmic, nuclear, and nucleolar areas. The NCI was largest (4.74) in T-CLL. B-ILL, B-PLL, and SLVL had an intermediate (4.5) NCI. HCL and B-CLL had the smallest (4.1) NCI. Lymphoid cells in SLVL were smaller in size than HCL cells and had a higher NCI than that of HCL. Thus, electron microscopic morphometry can provide further information to aid in distinguishing chronic type lymphoid leukemias.

Light and electron microscopic study of vacuolated cells in immunoblastic lymphadenopathy-like T-cell lymphoma

Three cases of immunoblastic lymphadenopathy (IBL)‐like T‐cell lymphoma were analyzed immunologically, and the ultrastructure of mononuclear cells in the lymph nodes and peripheral blood was examined. In the peripheral blood, light microscopic examination revealed vacuolated lymphocytes. These vacuolated lymphocytes formed rosettes with sheep erythrocytes, and they were CD3‐ and CD4‐positive using the avidin‐biotin method in cases 1 and 2. Electron microscopic examination revealed two kinds of abnormal lymphocytes. One kind was of B‐cell nature with rich lamellated rough‐surfaced endoplasmic reticulum and mitochondria. The other kind had a large cytoplasm, in which Golgi apparatus, some endoplasmic reticulum, some mitochondria and a few vacuoles were seen. Some of these vacuoles had remnants of mitochondrial cristae or were enlarged endoplasmic reticulum. The vacuolated T lymphocytes and activated lymphocytes of B‐cell nature disappeared with chemotherapy but reappeared with relapse of the disease. These observations suggest that vacuolated cells are related to pale cells in lymph node sections. In other words when these vacuolated cells are found in the peripheral blood of patients with lymphoid malignancies, IBL‐like T‐cell lymphoma can be suspected.