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Takashi Oyama,
Kazuhito Yamamoto,
Naoko Asano,
Aya Oshiro,
Ritsuro Suzuki,
Yoshitoyo Kagami,
Yasuo Morishima,
Kengo Takeuchi,
Toshiyuki Izumo,
Shigeo Mori, [......],
Naoya Nakamura,
Masafumi Abe,
Koichi Ichimura, Yumiko Sato,
Tadashi Yoshino,
Tomoki Naoe,
Yoshie Shimoyama,
Yoshikazu Kamiya,
Tomohiro Kinoshita,
Shigeo Nakamura
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ABSTRACT: We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs. To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL).
Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected. We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis.
Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms, and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors).
These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease.
Clinical Cancer Research 09/2007; 13(17):5124-32. · 7.74 Impact Factor
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Takuhei Murase,
Motoko Yamaguchi,
Ritsuro Suzuki,
Masataka Okamoto, Yumiko Sato,
Jun-ichi Tamaru,
Masaru Kojima,
Ikuo Miura,
Naoyoshi Mori,
Tadashi Yoshino,
Shigeo Nakamura
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ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a broad clinical spectrum and immunophenotypic heterogeneity. A series of 96 patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently observed. The International Prognostic Index score was high or high-intermediate in 92%. For 62 patients receiving anthracycline-based chemotherapies, median survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%, 13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10- IVLBCL cases examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1- immunophenotype. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10-IVLBCL. Compared with 97 cases of de novo CD5+CD10-diffuse LBCL, 31 cases of CD5+CD10-IVLBCL exhibited higher frequencies of poor prognostic parameters, except age. Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies (P<.001, hazard ratio [HR]: 9.256), age older than 60 years (P=.012, HR: 2.459), and thrombocytopenia less than 100x10(9)/L (P=.012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior.
Blood 02/2007; 109(2):478-85. · 9.90 Impact Factor
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ABSTRACT: It remains unclear whether or not diffuse large B-cell lymphomas of extranodal sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied the clinicopathological features of MALT lymphoma and diffuse large B-cell lymphoma in the thyroid gland, with special reference to VH usage of immunoglobulin gene rearrangement, to clarify the relationships between these two types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined by multiplex reverse transcription-polymerase chain reaction. We examined 58 patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma. Interestingly, the sequence of VH genes revealed that the two subtypes differed significantly in their use of the VH4 family (P < 0.05). Of the seven MALT lymphomas, three used the VH4 family and the other four used the VH3 family, whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one used the VH1 family, and none used the VH4 family. It was also interesting that, in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse large B-cell lymphoma component used the VH3 family and the MALT lymphoma component used the VH4 family. These data imply that, in a subset of cases, these two subtypes do not share a common origin and that at least some diffuse large B-cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs, large intestine and ocular adnexa. This strongly indicated that the presence of t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.
Modern Pathology 01/2007; 19(12):1578-84. · 4.79 Impact Factor
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Satoko Nakamura,
Koichi Ichimura, Yumiko Sato,
Shigeo Nakamura,
Hirokazu Nakamine,
Hiroshi Inagaki,
Yoshito Sadahira,
Koichi Ohshima,
Sumie Sakugawa,
Eisaku Kondo,
Hiroyuki Yanai,
Nobuya Ohara,
Tadashi Yoshino
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ABSTRACT: The aim of the present study was to examine the clinicopathological presentations of follicular lymphomas (FL) of the salivary glands, as compared to mucosa-associated lymphoid tissue (MALT) lymphomas. A total of 27 primary salivary gland lymphomas were examined: 6 FL (five, grade 1; one, grade 2); 19 MALT lymphomas; and two diffuse large B-cell lymphomas. The FL patients ranged in age from 24 to 73 years, with a mean of 49 years, which was younger than that of MALT patients (mean: 64 years; P < 0.05). Four of the six FL arose from the submandibular gland, which was the origin of only five out of a total of 19 MALT lymphomas. One FL patient was in clinical stage (CS) IE, two in CS IIE, and two in CS III and IV. As regards the MALT lymphoma patients, 13 (68%) were in CS IE and five (26%) in CS IIE. None of the FL patients had clinical diagnosis of autoimmune disease but eight MALT lymphoma patients had autoimmune disease. The present study found a relatively high incidence of FL in the salivary glands. The observed differences in age of onset, background of autoimmune disease, and lesion site suggests that the pathogenesis of FL may differ from that of MALT lymphoma.
Pathology International 11/2006; 56(10):576-83. · 1.62 Impact Factor
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ABSTRACT: We investigated the relationship of gastric mucosa-associated lymphoid tissue (MALT) lymphoma tumorigenesis to Helicobacter pylori infection, the t (11;18) translocation, and alterations in cell cycle regulators. We sought to assess the implications of altered expression of p27(Kip1), a cyclin-dependent kinase inhibitor, on high-grade transformation and responsiveness to eradication therapy. We used immunohistochemistry to examine p27(Kip1), p53, and Ki-67 expression in 23 MALT lymphomas, five diffuse large B-cell lymphomas (DLBCLs), and four DLBCLs with associated MALT lymphoma. All of the MALT lymphomas were positive for p27(Kip1) expression and negative for p53 with a low Ki-67 index, regardless of the sensitivity of these cells to eradication. All DLBCLs were negative for p27(Kip1) and positive for p53, exhibiting a high Ki-67 index. In DLBCLs with MALT lymphoma, p27(Kip1) expression was absent from both the MALT and large cells components. In all of these lymphomas, the MALT components were negative for p53 and displayed a low Ki-67 index, while the large cell components were positive for p53 with a high Ki-67 index. The expression patterns of the DLBCLs differed significantly from those of the MALT lymphomas. p27(Kip1) was not detected in either component of DLBCL with MALT lymphoma, suggesting that decreased expression of p27(Kip1) in the MALT component may be related to high-grade transformation. Thus, p27(Kip1) expression in morphological MALT lymphomas could be useful tool to predict high-grade transformation to DLBCL.
Journal of Clinical and Experimental Hematopathology 04/2006; 46(1):25-30.
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ABSTRACT: A 47-year-old woman presented with headache and left homonymous hemianopsia. T1-weighted magnetic resonance (MR) imaging with contrast medium showed a mass lesion with ring-like enhancement in the right temporo-occipital lobe. The patient underwent surgery, focal irradiation, and chemotherapy. The histological diagnosis was glioblastoma. Four months after the operation, the patient again developed headache and left homonymous hemianopsia in addition to vomiting and mild left hemiparesis. MR imaging showed recurrence of the tumor and hydrocephalus. The patient underwent a second craniotomy and placement of a ventriculoperitoneal shunt. Intraoperative findings revealed that the transverse-sigmoid sinus was occluded by tumor invasion. The patient died of intraventricular dissemination 2 months after the second operation. Autopsy revealed metastases in the spleen and lungs. Glioblastoma with metastases to the spleen is very rare. The prognosis for patients is poor. Excessive therapy should not be used for patients with extracranial metastases from glioblastoma.
Neurologia medico-chirurgica 10/2003; 43(9):452-6. · 0.61 Impact Factor
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ABSTRACT: We report a Japanese case of primary cutaneous marginal zone B-cell lymphoma (PCMZL). This 46-year-old woman presented with a subcutaneous nodule on her right forearm. With the combined morphology,the immunophenotype, and molecular analysis, we diagnosed this lesion as PCMZL. Furthermore, we reviewed the 16 cases of PCMZL in the Japanese literature. The ages of the patients ranged from 26 to 75 years (mean 55.7 years) with a slight female predilection. Clinically, most of the skin lesions were erythematous nodular lesions. The involved regions were the face and neck in eight cases, the trunk in six and the arms in five. None had Borrelia burgdorferi infection or a history of thyroiditis. Two patients had suffered from Sjögren's syndrome. Histopathologically, lymphoepithelial lesions were found in nine cases. The chromosomal aberrations in MALT lymphoma such as t(11;18)(q21;q21), t(14;18)(q32;q21) and t(3;14)(p14.1;q32) were not reported in any of the Japanese cases. Although two patients developed metastasis on the skin after radiation therapy, none died of lymphoma.
European journal of dermatology: EJD 15(6):480-3. · 2.53 Impact Factor
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ABSTRACT: To report a patient who developed systemic malignant lymphoma 17 years after bilateral orbital pseudotumor. CASE. A 24-year-old man developed bilateral orbital pseudotumor. He was stable until 17 years later, when he was afflicted with systemic malignant lymphoma, a diffuse large B-cell lymphoma, and he died of the disease. He showed no new orbital lesion at the presentation of systemic lymphoma. Pathological diagnosis at autopsy was systemic malignant lymphoma with bilateral orbital pseudotumor.
Immunohistochemical reexamination of the paraffin-embedded tissue and polymerase chain reaction of paraffin sections.
Histopathologically, the orbital masses resected on different occasions consisted of small lymphocytes and plasma cells. Immunohistochemical staining revealed an immunoglobulin light chain kappa and lambda bitype of B-cell lymphocytes and plasma cells. In contrast, the cervical lymph node showed large lymphoma cells that were positive only for lambda light chain, indicative of a lambda monotype. Amplification by polymerase chain reaction of the immunoglobulin heavy chain gene from paraffin sections demonstrated clonal rearrangement in the cervical lymph node but showed no clonality in the orbital tumor, supporting altogether the diagnosis of orbital pseudotumor.
Orbital pseudotumor should be carefully followed for possible development of systemic malignant lymphoma.
Japanese Journal of Ophthalmology 48(5):503-6. · 0.92 Impact Factor
