Tomoo Takiguchi

Sweet's syndrome during therapy with granulocyte colony-stimulating factor in a patient with aplastic anaemia

Summary. A patient with aplastic anaemia developed Sweets syndrome (a febrile neutrophilic dermatosis) during granulocyte colony‐stimulating factor (G‐CSF) therapy. Three repeated episodes of appearance and disappearance of erythematous nodules after administration and withdrawal of G‐CSF confirmed that G‐CSF induced Sweets syndrome in the patient. Sweets syndrome has been reported in patients with myelodysplastic syndrome and acute leukaemia, but not in patients with aplastic anaemia. This is the first report of a patient with aplastic anaemia who developed G‐CSF‐induced Sweets syndrome.

Monoclonal gammopathies in Japanese patients with Sjögren's syndrome

We report 10 Japanese patients with Sjögrens syndrome (SS) who developed monoclonal gammopathies (MG). One was of the IgG class, five of IgA, three of IgM, and one of IgG/IgM. The monoclonality of 7 of 10 M proteins was studied using antiidiotypic (Id) antibodies against M proteins. Four (three IgA and one IgM) of 10 M proteins had rheumatoid factor (RF) activity. Hemagglutination inhibition tests and enzyme-linked immunosorbent assays (ELISA) showed that the RF activity was inhibited by anti-Id antibodies in all four monoclonal RFs. In two patients examined, many cells infiltrating into the salivary glands were stained with anti-Id antibodies. Our review of 19 Japanese SS patients with MG revealed that the non-IgM class predominated (13/19). This contrasts with 19 reported non-Japanese SS patients, among whom 14 were IgM. In both Japanese and non-Japanese patients there was a higher incidence of MG in primary than in secondary SS. The difference in the dominant heavy-chain class may reflect a difference in the genetic factors affecting B cell differentiation in immunologically disordered states.

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.

Aggressive natural killer cell lymphoproliferative disorder associated with Epstein-Barr viral RNA.

Lymphoproliferative disorder of natural killer cells is a heterogeneous disorder, and an association with Epstein‐Barr virus (EBV) is suggested in some cases. A Japanese male presenting with recurrent nasopharyngeal problems developed fever, generalized lymphadenopathy, and hepatosplenomegaly. Separated cells from lymph nodes were shown to have a natural killer (NK) cell, CD2(+), CD3(−), CD16(+), CD56(+), HLA‐DR(+) phenotype. A progressive abnormality of hepatic function was associated with hepatorenal failure and death. A serologic study suggested reactivated EBV infection. In situ hybridization (ISH) studies showed Epstein‐Barr virus‐encoded RNA (EBER)‐1 in lymph nodes, with lymphocytes infiltrating the liver and tissue from ethmoid sinus surgery 3 years prior to development of obvious lymphoproliferative disease. Polymerase chain reaction performed on lymph node DNA, using oligonucleotide primers specific for the EBV lymphocyte‐determined membrane antigen (LYDMA) gene, revealed a single band, suggesting monoclonal proliferation of the tumor. NK activities of the lymphocytes from the lymph node and peripheral blood were markedly decreased. These findings suggest a close relationship between EBV infection and development of NK cell lymphoproliferative disorder. Am. J. Hematol. 54:314–320, 1997.

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.

Nodal EBV-positive Hodgkin's disease following extranodal EBV negative non-Hodgkin's lymphoma of B-cell lineage.

To the Editor: In some cases of Hodgkin’s disease (HD), the EBV genome has been found in Reed-Sternberg cells and Hodgkin’s cells (RS/H cells) ( 1, 2). The origin of RS/H cells is still controversial. Immunologically suppressed patients tend to develop non-Hodgkin’s lymphomas (NHLs), usually of B-cell lineage, as in the cases of NHLs in acquired immunodeficiency syndrome (AIDS) (3) and in a post-organ transplantation state (4). Patients with Hodgkin’s disease also have the risk of developing subsequent NHLs because they are known to have immunological defects. There are reported cases of NHL associated with HD involving different anatomic sites before or after the occurrence and treatment of HD ( 5 ) . The frequency of detection of EBV in NHL associated with HD is low (5). We have experienced a patient who developed HD while the patient was on treatment for NHL. We performed in situ hybridization (ISH) to detect EBV encoded RNA (EBER 1) and a polymerase chain reaction study to detect the BamHI W fragment of EBV DNA to investigate the association of EBV with both NHL and HD and to detect lymphocyte determined membrane antigen (LYDMA) in order to investigate the clonality of EBV-infected cells. We also performed immunohistochemical studies to clarify the origin of RS/H cells. A 62-yr-old Japanese male had been well until October 1993, when he noted epigastric discomfort. He was admitted to the Surgical Department of Kanazawa Medical University Hospital, where fiberscopic examination of the upper gastrointestinal tract was performed. A mass lesion was found in the duodenum. He had one palpable lymph node of 3 cm diameter in the right cervical area. The biopsy of the duodenal mass lesion revealed a nonHodgkin’s lymphoma of the nodular, medium-sized, cleaved cell type. A lymph node biopsy was not performed at this stage. He was started on chemotherapy with cyclophosphamide 500 mg, vincristine 1.5 mg, prednisolone 100 mg and doxorubicin 40 mg weekly for 5 wk. Subsequently, the same chemotherapy was given monthly for 7 months. In November 1994, his abdominal mass became enlarged and he developed fever and was transferred to the hematology service. He had cervical, axillary and inguinal lymphadenopathy at this point. The liver and spleen were not enlarged. On 7 February 1995 a lymph node biopsy was performed from the right inguinal node, which was diagnosed as Hodgkin’s disease of the mixed cellularity type. On 2 March 1995 he was referred to the surgery service for resection of the duodenal mass. Gastrectomy of the pyloric side was performed on 9 March. Multiple enlarged lymph nodes were present in the para-aortic area, mesenteric area and along the large curvature of the stomach. He developed spiking fever from 27 March 1995. He was again referred back to the hematology service to receive chemotherapy for Hodgkin’s disease. Chemotherapy was started, but he developed DIC and died on 16 April 1995. EBV serology performed on 7 February 1995 revealed that the VCA IgG titer was 160-fold dilution and VCA IgM was less than 10-fold dilution. The first biopsied specimen obtained in October 1993 from the duodenum showed non-Hodgkin’s lymphoma of the nodular, medium-sized, cleaved cell type. A lymph node biopsy specimen obtained in February 1995 revealed Hodgkin’s disease of the mixed cellularity type. A specimen that was surgically removed from the duodenum on 9 March 1995 was revealed to be non-Hodgkin’s lymphoma of the nodular, medium-sized, cleaved cell type. All the lymph nodes removed at the same time were revealed to be Hodgkin’s disease of the mixed cellularity type. Immunohistochemical examination of the biopsy specimen from the duodenum revealed that the medium-sized, cleaved lymphoma cells were L26