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Tsuyoshi Nakamaki,
Kunihiko Fukuchi,
Hidetoshi Nakashima,
Hirotsugu Ariizumi,
Takashi Maeda,
Bungo Saito,
Kouji Yanagisawa,
Shigeru Tomoyasu,
Mayumi Homma,
Eisuke Shiozawa, Toshiko Yamochi-Onizuka,
Hidekazu Ota
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ABSTRACT: In diffuse large B-cell lymphoma (DLBCL), a CD20-negative relapse is clinically significant because it is associated with chemo-refractory phenotypes and loss of a therapeutic target. The alteration of the CD20 gene is reported as infrequent in CD20-negative relapse in B-cell lymphoma. We established a DLBCL cell line with loss of CD20 expression (SD07) from a patient at CD20-negative relapse. She was initially diagnosed with CD20-positive DLBCL and received repeated immuno-chemotherapy that included rituximab. SD07, which has an immunoglobulin κ rearrangement identical to that of lymphoma cells at CD20-negative relapse, showed homozygous deletion of the CD20 gene with loss of the copy number of 11q12. SD07 is the first case in which it is proven that the loss of CD20 expression in relapsed DLBCL is the result of deletion of the CD20 gene. Deletion of the CD20 gene is a molecular mechanism of CD20-negative relapse in a subset of DLBCL.
European Journal Of Haematology 07/2012; 89(4):350-5. · 2.61 Impact Factor
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Norimichi Hattori,
Kunihiko Fukuchi,
Tsuyoshi Nakamaki,
Mayumi Homma,
Hirotsugu Ariizumi,
Hidetoshi Nakashima,
Takashi Maeda,
Bungo Saito, Toshiko Yamochi-Onizuka,
Kouji Yanagisawa,
Isao Matsuda,
Hidekazu Ota,
Shigeru Tomoyasu
Acta Haematologica 02/2011; 125(4):242-6. · 1.35 Impact Factor
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ABSTRACT: We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1alpha in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-alpha, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1alpha significantly stimulated (3)H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1alpha. In the present case, MIP-1alpha, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1alpha is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1alpha is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma.
European Journal Of Haematology 05/2010; 84(5):448-52. · 2.61 Impact Factor
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Mayumi Homma, Toshiko Yamochi-Onizuka,
Eisuke Shiozawa,
Masafumi Takimoto,
Hirotsugu Ariizumi,
Hidetoshi Nakashima,
Isao Matsuda,
Tsuyoshi Nakamaki,
Toshiaki Kunimura,
Miki Kushima,
Shigeru Tomoyasu,
Hidekazu Ota
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ABSTRACT: We report a case of primary pulmonary classical Hodgkin lymphoma (CHL) in a 58-year-old woman. Twelve years ago, the patient complained of slight fever and weight loss. A mass of about 5 cm in diameter was seen in the right lung on radiography and computed tomography (CT). Right total pneumonectomy and resection of mediastinal lymph nodes were performed. A pathological examination led to a strong suspicion of Hodgkin disease (HD) (now referred to as CHL), but a definite diagnosis could not be made at the time. Six years later, a chest CT showed a tumor around the ascending aorta, which was treated successfully by radiation therapy. Six years later, the chest CT revealed a tumor in the anterior mediastinum. CHL was diagnosed based on an immunohistochemical re-examination of lung specimens resected 12 years earlier and CT-guided fine needle tumor biopsy specimens of the second recurrent tumor in the anterior mediastinum were compatible with the recurrence of CHL. Therefore, we diagnosed this case as primary pulmonary CHL that later relapsed in the mediastinum. The tumor size was reduced by radiation therapy and the patient is currently under observation as an outpatient.
Journal of Clinical and Experimental Hematopathology 01/2010; 50(2):151-7.
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Journal of Gastroenterology and Hepatology - J GASTROENTEROL HEPATOL. 01/2009; 24(2):307-315.
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ABSTRACT: Background and Aim: The World Health Organization (WHO) has adopted criteria for the histological differential diagnosis of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (GML) based on the criteria proposed by Wotherspoon in 1993 (WHO/Wotherspoon score). These histological criteria are commonly used by pathologists for initial diagnoses, but have not been adopted uniformly for the post-treatment evaluation of GML. In 2003, the Groupe d'Etude des Lymphomes de l'Adult (GELA) proposed a new histological grading system (GELA grade) in preference to use of the WHO/Wotherspoon score for post-treatment evaluation. In the present study, we compared the WHO/Wotherspoon and GELA systems to examine which histological criterion is better for post-treatment evaluation. Methods: Fourteen cases of GML under long-term follow up were initially diagnosed according to the WHO criteria with detailed immunohistology, and were periodically evaluated with both histological criteria after anti-Helicobacter pylori treatment. They were also evaluated based on histological stromal changes accompanying the disappearance of lymphoma tissue. Results: The study showed strong similarities between the WHO/Wotherspoon and GELA systems and no clear advantage of either system for post-treatment evaluation. The GELA grade could not be used for the evaluation of changes in the degree of lymphoma infiltration from pre- to post-treatment because the four-item scale is not comparable with the formal six-point WHO/Wotherspoon scale. Stromal changes in the lamina propria, including an empty appearance and fibrosis, were correlated with lymphoma reduction after treatment and appear to be good indicators for post-treatment evaluation. Conclusion: We propose the utilization of the WHO/Wotherspoon score accompanied by the assessment of stromal changes for the post-treatment evaluation of GML.
Journal of Gastroenterology and Hepatology 12/2008; 24(2):307-15. · 2.87 Impact Factor
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Takashi Maeda,
Eisuke Shiozawa,
Homma Mayumi,
Takako Usui,
Hidetoshi Nakashima,
Norimichi Hattori,
Daisuke Adachi,
Bungo Saito,
Kouji Yanagisawa,
Isao Matsuda,
Tsuyoshi Nakamaki,
Shigeru Tomoyasu, Toshiko Yamochi-Onizuka,
Masafumi Takimoto,
Hidekazu Ota
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ABSTRACT: To study hematopoietic reconstitution in umbilical cord blood transplantation (CBT), bone marrow (BM) histology was investigated in 35 biopsies after bone marrow transplantation (BMT) and in 40 biopsies after CBT. BM biopsies were obtained at different times after transplantation and were evaluated for cellularity, number of megakaryocytes and CD34-positive cells, and fibrosis. In biopsies up to 29 days after BMT, cellularity was increased and megakaryocytes were observed, but at 29 days after CBT, biopsies showed severe cellular depletion and almost no megakaryocytes. In addition, fewer CD34-positive cells were observed after CBT compared to after BMT. After day 30 after CBT, hematopoietic recovery of the BM was gradually observed and after day 100 after transplantation, no essential differences were observed between BMT and CBT. Hematopoietic recovery of the BM after CBT was delayed compared to that after BMT, but engraftment of donor cells after CBT was also observed in histopathologically. To the best of the authors' knowledge this is the first histopathological description of BM reconstitution after CBT.
Pathology International 03/2008; 58(2):126-32. · 1.62 Impact Factor
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ABSTRACT: Patients with the germinal center B-cell-like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL) have a significantly better survival rate than those with non-GCB DLBCL. Several studies have examined the proportions of GCB and non-GCB subtypes in large series of DLBCL patients, but it remains unclear if these proportions are the same in different countries. We performed an immunohistochemical analysis of the numbers of GCB and non-GCB subtypes in a large number of patients with DLBCL in Japan and compared the results with literature data for other countries. We found that 71 of 248 patients (29%) had the GCB phenotype and 177 patients (71%) had the non-GCB subtype of DLBCL among our patient population. Assessment of data collected from other studies showed that 31% of DLBCL patients (102/330) have the GCB subtype in Asian countries, but 50% (206/416) express GCB phenotypes in Western countries; based on these data, the occurrence of the GCB subtype of DLBCL was significantly less in Asian countries (p<0.001). Since patients with the GCB phenotype of DLBCL have better survival, future studies of DLBCL should recognize the difference in the proportions of GCB and non-GCB subtypes of DLBCL between Asian and Western populations.
Leukemia Research 11/2007; 31(11):1579-83. · 2.92 Impact Factor
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ABSTRACT: Senile EBV-associated B-cell lymphoproliferative disorder (LPD) was proposed as a new disease entity in 2003. This condition has a high incidence in elderly people without underlying immunodeficiencies, and is characterized by EBV-positive B-cell proliferation with a polymorphic composition. Histologically, the disease has two subtypes. The polymorphic LPD (PLPD) subtype has a preferable prognosis, whereas the large cell lymphoma (LCL) subtype involves aggressive disease progression. Reported herein is a case of senile EBV-BLPD with indolent clinical features and PLPD subtype in the initial phase that recurred as an aggressive lymphoma 3 years after the initial diagnosis. In the recurrent phase, Southern blotting confirmed monoclonal proliferation of large lymphoid B-cells. In both the initial and recurrent phases, polymerase chain reaction (PCR) yielded a single discrete band of a similar size due to an immunoglobulin heavy-chain gene rearrangement, indicating that the large lymphoid B-cells retained identical monoclonality throughout the histological progression and over the whole clinical course. These results suggest that the PLPD subtype is a histological finding in early phase senile EBV-BLPD and that the LCL subtype reflects the progressive phase of the disease.
Pathology International 11/2007; 57(10):688-93. · 1.62 Impact Factor
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Takashi Maeda,
Eisuke Shiozawa,
Bungo Saito,
Takako Usui,
Hidetoshi Nakashima,
Norimichi Hattori,
Daisuke Adachi,
Kouji Yanagisawa,
Keiichiro Kawakami,
Tsuyoshi Nakamaki,
Shigeru Tomoyasu, Toshiko Yamochi-Onizuka,
Masafumi Takimoto,
Hidekazu Ota
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ABSTRACT: Allogeneic stem cell transplantation (allo-SCT) is used as curative therapy for malignant lymphoma, and reduced-intensity hematopoietic stem cell transplantation (RIST) is sometimes performed to avoid the toxicity and mortality associated with myeloablative allo-SCT. RIST is generally preferred for elderly patients with malignant lymphoma. A 62-year-old woman with follicular lymphoma (FL) involving bone marrow (BM) suffered relapse after autologous SCT. RIST was performed; cells were from an unrelated, fully human leukocyte antigen-matched donor. To study the hematopoietic reconstitution, BM biopsy specimens that were obtained at different times after RIST, were evaluated. Engraftment of donor cells was observed on days 19 and 48 after RIST, and residual FL in BM had completely disappeared by day 73 after RIST. This is the first report to document histological BM regeneration after RIST and disappearance of FL involving the BM.
Pathology International 07/2007; 57(6):378-82. · 1.62 Impact Factor
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Eisuke Shiozawa,
Masafumi Takimoto,
Reiko Makino,
Daisuke Adachi,
Bungo Saito, Toshiko Yamochi-Onizuka,
Tadanori Yamochi,
Junko Shimozuma,
Takashi Maeda,
Yohko Kohno,
Keiichiro Kawakami,
Tsuyoshi Nakamaki,
Shigeru Tomoyasu,
Akira Shiokawa,
Hidekazu Ota
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ABSTRACT: The aim of the study was to analyze the methylation status of the promoter regions of p15 and p16 and to assess the prognostic significance of promoter hypermethylation in diffuse large B-cell lymphoma (DLBCL).
DLBCL was diagnosed by morphology and immunohistochemical analysis according to the World Health Organization (WHO) classification. The methylation status of CpG islands in the p15 and p16 promoters was analyzed by methylation-specific polymerase chain reaction in 49 DLBCLs.
Hypermethylation of the p15 and p16 promoters was detected in 20 (41%) and 22 (45%) of the 49 DLBCLs, respectively. Among all patients with DLBCL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated p15 (P=0.442) or between those with hypermethylated and unmethylated p16 (P=0.468). Therefore, methylation was analyzed in combination with evaluation of clinical features using the international prognostic index (IPI). In the high-intermediate-risk and high-risk groups, patients with hypermethylated p16 had significantly lower survival rates than those of patients in the same risk group with unmethylated p16 (P=0.010).
Our results suggest that hypermethylation of the p16 promoter indicates a poor prognosis in high-intermediate-risk and high-risk DLBCL patients, and may be a useful marker for selection of appropriate treatment when used in conjunction with the IPI.
Leukemia Research 08/2006; 30(7):859-67. · 2.92 Impact Factor
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ABSTRACT: Pagetoid reticulosis is a rare cutaneous T-cell lymphoma with striking epidermotropism similar to that present in Paget's disease. There are two forms of pagetoid reticulosis: localized and disseminated. Reported herein is an autopsy case of disseminated pagetoid reticulosis with CD4(-)/CD8(-) phenotype T cells and massive invasion of the lungs and pancreas. The abnormal cells in the epidermis expressed a protein derived from a rearranged T-cell receptor beta gene, and this feature was used to confirm the monoclonality of these cells by polymerase chain reaction. At present, the World Health Organization (WHO) classification system considers pagetoid reticulosis to be an indolent form of primary cutaneous T-cell lymphoma and a variant of mycosis fungoides/Sezary syndrome with prominent epidermotropism. Some differences have been observed between pagetoid reticulosis and mycosis fungoides in terms of clinical course, tumor cell phenotype, and genetic findings; and these differences are highlighted in the present case. The relation between disseminated pagetoid reticulosis, CD4(-)/CD8(-) cutaneous T-cell lymphoma, and gammadelta T-cell lymphoma, including whether pagetoid reticulosis is a variant of mycosis fungoides, remains unclear.
Pathology International 02/2005; 55(1):32-9. · 1.62 Impact Factor
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ABSTRACT: We report an intraplacental germ cell tumor that was an incidental finding in the placenta of a 34-year-old woman. On pathologic examination, the 4.0-cm tumor was well circumscribed with a thin fibrous capsule. It exhibited three major histologic patterns within a mesenchyme-like myxoid background: a primitive endodermal component, a well-differentiated enteric glandular endodermal component, and a component of fetal hepatic tissue. The primitive endodermal component, the hepatic component, and many parts of the enteric endodermal glandular component were immunoreactive for alpha-fetoprotein. We considered the lesion to be a unique example of a placental yolk sac tumor and only the second reported case of a placental yolk sac tumor.
International Journal of Gynecological Pathology 11/2004; 23(4):398-402. · 1.45 Impact Factor
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ABSTRACT: Rituximab is widely used for the treatment of B-cell non-Hodgkin's lymphoma (NHL), and encouraging results have been obtained. However, some CD20-positive NHL show minimal response to rituximab, indicating that the treatment effect depends on the presence or absence of an unidentified factor. We analyzed the relationship between the effect of rituximab plus chemotherapy and expression of Ki-67, p53 and bcl-2 and several clinical variables in cases of B-NHL, particularly follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Forty-four patients were included in the present study, and the overall treatment response rate was 68%. Twelve of 30 patients (40%) achieved a complete response, five (16%) reached an unconfirmed complete response and 13 (43%) achieved a partial response. A high serum lactate dehydrogenase level and International Prognostic Index of high or high intermediate risk were associated with a decreased response in the case of FL. Immunohistochemical assays were performed in 18 FL patients (55%) and 15 DLBCL patients (45%). Significant correlation was found between an inferior response to treatment and high Ki-67 expression in the cases of FL (P = 0.006). p53 and bcl-2 expression did not correlate significantly with the response rate. The cell cycle appears to be an important factor in the efficacy of rituximab treatment. Ki-67 expression might be a predictor of efficacy of rituximab plus chemotherapy.
Pathology International 10/2004; 54(9):667-74. · 1.62 Impact Factor
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Yutsuki Yamamoto, Toshiko Yamochi-Onizuka,
Eisuke Shiozawa,
Miki Kushima,
Tsuyoshi Nakamaki,
Shigeru Tomoyasu,
Kazuhiro Kaneko,
Keiji Mitamura,
Mitsunori Hoshino,
Hiroshi Ishii,
Mitsuo Kusano,
Hidekazu Ota
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ABSTRACT: More than one histological type of malignant lymphoma can occur simultaneously in an individual. The entity is classified as either composite or discordant lymphoma. Both types of lymphoma, particularly discordant lymphoma comprised of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT-L) and follicular lymphoma (FL), are rare. We report a case of discordant lymphoma comprising MALT-L in the stomach and FL in the parotid gland. The patient was a 50-year-old Japanese woman who visited the University Hospital of Showa (Tokyo, Japan) because a barium study showed erosive gastric lesions. A gastro-intestinal endoscopy was performed 2 months after the barium study, which showed irregular erosions throughout the stomach body. A gastric biopsy showed MALT-L, and Helicobacter pylori (H. pylori) infection was confirmed. The patient had noticed a painless and elastic hard tumor mass of about 2 cm in diameter in the area of the left parotid gland 6 months before the barium study. We removed the parotid gland tumor and diagnosed it as FL 6 months after the barium study. We were able to diagnose the MALT-L and FL by morphological, immunohistochemical and molecular analyses of paraffin-embedded sections. This appears to be the first reported case of MALT-L and FL occurring together as a discordant lymphoma.
Pathology International 09/2003; 53(8):557-62. · 1.62 Impact Factor
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ABSTRACT: Some follicular lymphomas histologically transform into diffuse aggressive lymphomas, the prognosis of which is poor. There are, however, no reliable histological criteria for predicting which cases will later undergo such transformation. In low-grade B-cell lymphomas, follicular dendritic cells form dense mesh-like networks that contain accumulating neoplastic B-cells. These are rare in high-grade lymphomas. We immunohistochemically analyzed CD21-positive follicular dendritic cells in 32 follicular lymphomas, including 3 transformed lymphomas, in addition to immunohistological study using P-glycoprotein, p53, and Ki-67. We found that the mesh-like networks in follicles are more clearly defined in low-grade lymphomas than in high-grade lymphomas (p = 0.015). Neoplastic follicles in 2 transformed lymphomas lost the networks of follicular dendritic cells before transformation despite the existence of morphologically clear follicles. This differed from the non-transformed cases of the same cytological grades. Prognosis was statistically better for patients with low-grade tumor than for those with high-grade tumor (p = 0.026), and there was a trend toward poorer survival among CD21-negative cases (p = 0.186). P-glycoprotein, p53, and Ki-67 expressions did not provide sufficient information to predict the transformation of follicular lymphoma. The presence of CD21-positive follicular dendritic cells in neoplastic follicles might help predict the potential of follicular lymphoma to transform to diffuse large B-cell lymphoma.
Pathology - Research and Practice 02/2003; 199(5):293-302. · 1.21 Impact Factor
