-
Yoshizo Kimura,
Kensaku Sato,
Fumiko Arakawa,
Kennosuke Karube,
Yuko Nomura,
Kei Shimizu,
Ryosuke Aoki,
Keiko Hashikawa,
Shiro Yoshida,
Junichi Kiyasu,
Masanori Takeuchi,
Daisuke Nino,
Yasuo Sugita,
Toshiaki Morito,
Tadashi Yoshino,
Shigeo Nakamura, Masahiro Kikuchi,
Koichi Ohshima
[show abstract]
[hide abstract]
ABSTRACT: Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P < 0.0001). The expression levels of CCND1, Ki-67, p53, and p21(WAF/Cip1) in aggressive MCL (mean 80.1 +/- 27.8%, 73.7 +/- 28.9%, 31.0 +/- 69.0%, and 10.4 +/- 24.8%, respectively) were higher than those in classical MCL (mean 58.1 +/- 36.7%, 25.2 +/- 25.5%, 6.5 +/- 24.3%, and 2.5 +/- 13.0%, respectively) and intermediate MCL (mean 75.7 +/- 31.4%, 30.8 +/- 33.3%, 21.0 +/- 57.4%, and 4.8 +/- 16.5%, respectively). Significantly different levels of Ki-67 and p21(WAF/Cip1) were only recognized between intermediate and aggressive (P < 0.05 and P < 0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P < 0.0001 and P < 0.05, respectively). There were no significant differences in p27(Kip1) among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.
Cancer Science 11/2009; 101(3):806-14. · 3.33 Impact Factor
-
Yuko Nomura,
Masanori Takeuchi,
Shiro Yoshida,
Yasuo Sugita,
Daisuke Niino,
Yoshizo Kimura,
Kei Shimizu,
Ryosuke Aoki,
Nobuko Suefuji,
Shinichi Hirose, Masahiro Kikuchi,
Koichi Ohshima
[show abstract]
[hide abstract]
ABSTRACT: Macrophage polarization is divided into M1 and M2 type based on membrane receptors, cytokines, and chemokines. M1 expresses CD80, interleukin (IL)-6, IL-12, and chemokine receptor (CCR)7, while M2 expresses CD163, IL10, and chemokine ligand (CCL)22. The aim of the present study was to identify the properties of infiltrating tissue macrophages in histiocytic necrotizing lymphadenitis (HNL). Twenty patients with HNL were studied, and immunohistochemistry for CD68 (KP1), CD163, CCL22, CCR7, and CD123 was done, along with myeloperoxidase (MPO). To evaluate the phenotypes of tissue macrophages in HNL, the number of cells stained positively for CD163, CCL22, CCR7, CD123 and MPO concurrently with CD68 was counted, and the ratio was calculated for each antibody to CD68+ cells. There was a high rate of co-expression for CD163 (median, 78%) or CCL22 (80%) and a low rate for CCR7 (5%) in CD68+ cells. It is therefore conceivable that infiltration by M2 macrophages is dominant in HNL. Furthermore, some CD68+ tissue macrophages in HNL co-express MPO or CD123 (range, 5-80%; median, 23% and 40%, respectively). It is suggested that these characteristic tissue macrophages may be associated with the pathogenesis of HNL and that M2 macrophages may infiltrate to repair the lymphoid tissue injured by cytotoxic T cells in HNL.
Pathology International 10/2009; 59(9):631-5. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fourteen thymomas were studied by electron microscopy and immunohistochemistry. Based on the ultrastructure of the neoplastic epithelial cells in comparison with normal thymic epithelium, four cortical-, three mixed-, five medullary-, and two corpuscular-type tumors were categorized. Histologically the tumors of cortical type showed prominent lymphocytic infiltration, but scant interdigitat-ing reticulum cells (IDCs) were demonstrated by immunoperoxidase method on paraffin sections with anti-S-100 protein antiserum. Fewer lymphocytes but more IDCs were present in the tumors of medullary and corpuscular types, although variable in those of mixed type. This corticomedullary difference among thymomas was confirmed in some of them by the immunoperoxidase method on frozen sections with monoclonal antibodies. The cortical-type tumors were HLA-DR positive in tumor cells and infiltrated predominantly with cortical thymocytes (OKT-6+ OKT-3− both Leu 3a/3b+ and OKT-8+), whereas the medullary-and corpuscular-type tumors were HLA-DR positive primarily in IDCs but not in tumor cells and were infiltrated more with medullary thymocytes (OKT-6− OKT-3+ either Leu 3a/3b+ or OKT-8+). The classification of thymomas based on neoplastic epithelial cells will serve to refine the traditional classification based on reactive lymphocytes.
07/2009; 10(2):157-173.
-
[show abstract]
[hide abstract]
ABSTRACT: Both the polymerase chain reaction (PCR) and Southern blot analysis were used to detect bcl-2 gene rearrangement in B-cell lymphoma. Recent molecular studies have shown that the translocation of karyotypic abnormalities t(14;18) results in the juxtaposition of the candidate proto-oncogene bcl-2 on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14. We detected the bcl-2 rearrangement in three of six follicular lymphomas (50%), two of five follicular and diffuse lymphomas (40%), one of 13 diffuse medium-sized cell lymphomas (7.7%) and two of 33 diffuse large cell lymphomas (6.0%) through Southern blot analysis. With PCR, the rearrangement was demonstrated in five of eight follicular (63%), three of five follicular and diffuse (60%), seven of 36 diffuse large cell lymphomas (19%) and two of 13 diffuse medium-sized lymphomas (15%). Diffuse large cell lymphomas with bcl-2 rearrangement detected by PCR have a good prognosis as do cases of follicular lymphoma The bcl-2 gene is closely related to follicular lymphoma as described in previous reports and has general prognostic importance in diffuse large cell lymphoma of B cell type.
06/2009; 5(5-6):305-310.
-
[show abstract]
[hide abstract]
ABSTRACT: We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. νλ and γκ were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients. Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears be an important factor of profound cytopenia in patients of MH and/ or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.
Leukemia and Lymphoma 06/2009; 12(1-2):79-89. · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) therapy achieves a response in more than 60% patients with diffuse large B-cell lymphomas (DLBCLs). However, DLBCL shows a heterogeneous response to chemotherapy, and some patients are refractory to CHOP therapy. This difference in response to therapy is most likely due to differences in biological characteristics. We used cDNA microarray analysis to identify genes differentially expressed in anthracycline containing chemotherapy-resistant DLBCLs (7 patients) compared with anthracycline containing chemotherapy-sensitive DLBCLs (6 patients). Nine genes on the cDNA chip showed increased expression in anthracycline containing chemotherapy-resistant patients. We chose the preferentially expressed antigen of melanoma (PRAME) gene because it showed the highest expression in anthracycline containing chemotherapy-resistant DLBCLs on the cDNA chip, and it has been linked to prognosis of hematological malignancies. We also examined the relationship between PRAME gene expression and progression-free survival (PFS) in 45 patients with DLBCL. The progression-free survival of PRAME-positive patients (n=12) was significantly worse than that of PRAME-negative patients (n=33) (p=0.0373). Our results therefore indicate that PRAME expression in DLBCL correlates with response to anthracycline containing chemotherapy.
Journal of Clinical and Experimental Hematopathology 06/2009; 49(1):1-7.
-
[show abstract]
[hide abstract]
ABSTRACT: A rare case of carclnosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentlatlon occurrlng in the gastric remnant is reported. A 69-year-old Japanese man who had undergone a partial gastrectomy for a duodenal ulcer 30 years earlier, presented with anemla, eplgastralgia, and an abdominal mass. The diagnosls of gastric carcinosarcoma was made based on the findings of endoscoplc biopsies. The patient was thus scheduled to undergo a surgical operatlon, but he died of respiratory failure. At autopsy, a huge polypoid tumor measurlng 2Ox18times8 cm was located on the greater curvature of the gastric remnant. Microscopically, the tumor conslsted of Intimately mixed tubular adenocarcinoma and heterologous mesenchymal elements contalning rhabdomyosarcoma and osteosarcoma. Between these components, a morphological transition from the adenocarclnoma element to the sarcomatous element was observed. Ultrastructually, rhabdomyoblastlc dlfferentlation was conflrmed In the sarcomatous areas. lmmunocytochemlcal expresslons of epithelial markers includlng epithelial membrane antlgen and cytokeratlns (35bHll and 34bE12) were recognlzed not only in the carclnomatous cells but also In the sarcomatous cells. These findlngs suggest that carclnomatous cells appear to transform Into cells wlth sarcomatous features.
Pathology International 12/2008; 47(8):557 - 563. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lymph nodes from 21 cases of malignant lymphoma of a centrocytic (mantle cell) type, (ML, cc (mc)) were examined. All the cases had monoclonal surface immunoglobulin (sig) M and/or D, but were negative for CD 10 (CALLA), and CD11c (LeuM5). Lymphoma cells with CD25 (anti-Tac)+, CD5 (Leu1)+, and alkaline phosphatase (ALPase)-in eight cases showed bone marrow involvement (10–66% of the nucleated cells; mean 32± 18%) but with no leukemic changes. These eight cases has a similar phenotype and were distributed by the lymphoma cells to the examined B-chronic lymphocytic leukemia. Seven cases showed an infiltration of CD25-, CD5+, and AL Pase- lymphoma cells, in which only two cases showed focal bone marrow involvement.There was a close relationship between CD25 expression and bone marrow invasion by the lymphoma cells in ML, cc(mc). Three of the six CD25- and CD5- cases presented zonal proliferation of AlPase+ lymphoma cells with round nuciee and a high anti-proliferating cell nuclear antigen/cyclin (PCNA/c) rate in the mantle zone and paracortex, accompanied by a prominent interdigitating dendritic and histiocytic cell reaction. Examined CD25-, CD5- and ALPase+ lymphoma showed a neoplastic counterpart of so-called marginal zone lymphocytes, which was different from other cases of ML, cc (mc). Lymphoma cells in ML, cc(mc), except for those of the so-called marginal zone lymphoma, might be derived from slgM+, D+/-, CD25+/-, CD5+/-, ALPase-, CD10- and CD11c- lymphocytes present in the mantle zone and primary lymph follicles. Other types of lowgrade B cell neoplasms that were examined had different tumor cell markersfor ig, CD5, CD10, CD11c, a higher PCNA/c rate, and prominent dendritic cells and histiocytic reaction when compared with those of ML, cc (mc).
Pathology International 12/2008; 43(5):244 - 252. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to confirm the histopathological features of aggressive B-cell lymphoma in Papua New Guinea (PNG)-an EBV endemic region. The immunophenotypic features and expression of EBV-encoded proteins and RNA in B-cell lymphomas were analyzed in 21 PNG children, and compared to the corresponding features of 17 Japanese children with Burkitt lymphoma (BL). Histological diagnosis of the lymphomas from the PNG children was BL in nine patients; atypical Burkitt/Burkitt-like variant of BL (BLL) in three; diffuse large B-cell lymphoma (DLBCL) in four; and B-lymphoblastic lymphoma (B-LBL) in five. The lymphomas from the PNG children had a high positive rate on EBV-RNA in situ hybridization (EBV-ISH; 66.7%). With regard to the histological typing, 10 of 12 patients (83%) with BL/BLL, one of four (25%) with DLBCL, and three of five (60%) with B-LBL were positive for EBV-ISH. The findings of EBV-positive B-LBL were surprising because it is commonly considered that lymphoblastic lymphoma is not associated with EBV. EBV positivity was not detected in the 12 Japanese patients who were available for the EBV-ISH evaluation. It is concluded that it is possible that a proportion of DLBCL and B-LBL besides BL/BLL are associated with EBV in endemic region.
Pathology International 12/2008; 58(11):695-700. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Burkitt's lymphoma and atypical Burkitt/Burkitt-like lymphoma (BL/BLL) are considered highly aggressive B-cell lymphomas with a rapid proliferative rate and high rate of apoptosis. The aim of the present study was to confirm whether apoptotic and cell proliferative factors affect BL/BLL clinical outcomes. We retrospectively analyzed the relationship between the clinical and immunophenotypic features of 43 BL/BLL patients by immunohistochemical staining for bcl-2 and double staining for Ki-67 plus caspase-3. In double staining experiments, all patients were divided into high and low groups for the expression of caspase-3, Ki-67, and both Ki-67 and caspase-3, by using the medians of their percentages as limits. The 43 BL/BLL patients were divided into high caspase-3 (n = 19) and low caspase-3 (n = 24) groups. There was a significant difference in the overall survival between the high (77%) and low caspase-3 (33%) groups; the survival rate of patients in the low caspase-3 group who received aggressive short-term chemotherapy (58%) was significantly better than that of patients who received cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) therapy (17%). All patients positive for bcl-2 were in the low caspase-3 group (high caspase-3 group, 0%; low caspase-3 group, 42%). The overall survival tended to be better in the high caspase-3 and bcl-2-negative group (76%) than in the low caspase-3 and bcl-2-negative (50%) group. In addition, the low caspase-3 and bcl-2-positive group tended to show the worst prognosis (16%). We suggest that caspase-3 may function as an indicator of the prognosis of BL/BLL. Furthermore, intensive short-term chemotherapeutic regimens may improve the prognosis of the patients in the low caspase-3 group.
Cancer Science 09/2008; 99(8):1564-9. · 3.33 Impact Factor
-
Kennosuke Karube,
Ryosuke Aoki,
Yasuo Sugita,
Shiro Yoshida,
Yuko Nomura,
Kay Shimizu,
Yoshizo Kimura,
Keiko Hashikawa,
Morishige Takeshita,
Junji Suzumiya,
Atae Utsunomiya, Masahiro Kikuchi,
Koichi Ohshima
[show abstract]
[hide abstract]
ABSTRACT: Adult T-cell leukemia/lymphoma is an aggressive malignant disease associated with regulatory T cells as discussed in some recent reports. We analyzed the expression of FOXP3, a key molecule of regulatory T cells, in adult T-cell leukemia/lymphoma and its association with clinicopathological features. Of 169 adult T-cell leukemia/lymphoma cases examined, 60 (36%) showed FOXP3 expression in lymphoma cells. Morphologically, 22 cases were classified as anaplastic large cell variant and 147 as pleomorphic cell variant. Only 1 (5%) of the anaplastic large cell variant cases and 59/147 (40%) of the pleomorphic cell variant cases expressed FOXP3. Epstein-Barr virus-infected cells were significantly more frequently found in FOXP3(+) cases (23/60; 38%) than in FOXP3(-) cases (12/109; 11%) (P<0.0001). Cytogenetic analysis showed that FOXP3(+) cases had simpler chromosomal abnormalities than FOXP3(-) cases. Clinically, FOXP3(+) and FOXP3(-) cases did not differ significantly in age distribution, clinical stage, lactate dehydrogenase and calcium in serum and overall survival. However, 8 of 34 FOXP3(+) cases suffered a severe infectious state, an indication of immunosuppression, while only 2 of 62 FOXP3(-) cases did so (P<0.005). FOXP3 expression in adult T-cell leukemia/lymphoma thus reflects morphological features and is clinically and pathologically associated with an immunosuppressive state.
Modern Pathology 05/2008; 21(5):617-25. · 4.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The World Health Organization classification was used to conduct an analysis of geographic, age, sex, and lesion primarily biopsied/resected distribution of 2260 lymphoid neoplasms diagnosed during 2001-2006 throughout Japan. B-cell neoplasms accounted for 65% of all lymphoid neoplasms, T/natural killer (T/NK)-cell neoplasms for 25% and Hodgkin lymphoma for 7%. The most common type was diffuse large B-cell lymphoma (DLBCL, 33%), followed by follicular lymphoma (18%), and adult T-cell leukemia/lymphoma (ATLL, 10%). The high rate of 18% for follicular lymphoma was similar to that in Western countries (11-33%). T/NK-cell neoplasms accounted for a higher percentage of lymphoid neoplasms in Kyushu (30%) and Okinawa (38%) compared with other areas of Japan (18-20%). Among T/NK-cell neoplasms, ATLL was the most common type in Okinawa (54%) and Kyushu (59%). Extranodal NK/T cell lymphoma was the second most common type of T/NK-cell neoplasms in Okinawa (15%). This epidemiological study shows that the distribution patterns of malignant lymphoma differ especially in Kyushu and Okinawa, the endemic area of human T-cell leukemia/lymphoma virus type 1.
Pathology International 04/2008; 58(3):174-82. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 7-year-old Japanese boy with Ph1-positive-lymphoblastic lymphoma is described. The diagnosis was based on biopsied tonsils which were enlarged at the time of admission. On the eighth day after admission an enlarged mediastimal mass was detected on a chest X-ray film. The lymphoblasts which appeared in the peripheral blood and bone marrow proved to be T-cells. Chromosome studies on the bone marrow cells revealed two abnormal cell lines; one had a 7; 11 translocation and the other a 7;11 translocation and a 9;22 translocation, forming the Ph1-chromosome. The latter line with the Ph1 chromosome was considered to have been derived from the former line without the Ph1. Our findings show that the Prochromosome may be a secondary change in the course of karyotypic evolution.
British Journal of Haematology 03/2008; 58(3):459 - 464. · 4.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to estimate optimum chemotherapeutic regimens for high-grade mature B-cell lymphoma cases with Burkitt-like morphology (Burkitt's lymphoma [BL]/Burkitt-like lymphoma [BLL]) patients. We analyzed 72 BL/BLL, including 36 with the c-myc translocation (molecular BL [mBL]), 20 without it (mBL-like), and 16 in whom we were uncertain regarding the existence of the c-myc translocation, and compared them with 182 diffuse large B-cell lymphoma (DLBCL) cases. On clinical and immunophenotypic analysis, the typical BL immunophenotype (CD10 positive, bcl-2 negative, and Ki-67 index >or=95%) was noted in 23 (66%) and 11 (55%) of the 35 mBL and 20 mBL-like patients, respectively. The presence of the c-myc translocation and typical immunophenotype in BL did not affect the overall survival of BL/BLL. There were no significant differences between the overall survival of DLBCL (45%) and BL/BLL (50%, P = 0.85). However, the overall survival of BL/BLL patients who received cyclophosphamide, doxorubicin, vincristine, and prednisolone-related therapy (22%) was significantly lower than that of DLBCL patients (P = 0.01). In contrast, the overall survival of BL/BLL patients who received aggressive short-term chemotherapy (75%) was better than that of the patients who received cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy (P < 0.01). The finding was confirmed by multivariate analysis (hazard ratio 4.4; confidence interval 2.0-9.7; P = 0.0003). We concluded that aggressive short-term chemotherapy improves survival in BL/BLL, regardless of its genetic and immunophenotypic features.
Cancer Science 02/2008; 99(2):246-52. · 3.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to estimate the relationship between apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis (HNL). Fifteen patients with HNL were retrospectively analyzed. The patients were divided into three groups according to the proportion of the necrotic area as follows: necrosis (+), necrotic area <25%; necrosis (++), necrotic area 25-50%; and necrosis (+++), necrotic area >50%. Immunohistochemical double staining was performed for CD3 plus caspase-3 and for Ki-67 plus caspase-3 and positive cells were counted in two areas: one without and one with obvious apoptotic features. Most caspase-3-positive cells were also stained for CD3 (area exhibiting obvious apoptotic features: average, 92.3%). Furthermore, various proportions of both Ki-67- and caspase-3-positive cells were detected in all the groups (range, 5-70%). In the area with obvious apoptotic changes, the average percentage of both Ki-67- and caspase-3-positive cells (38.6%) was higher than that in the area without obvious apoptotic features (16.3%). A proportion of cells in HNL undergo proliferation and apoptosis simultaneously, such as neoplastic cells, thereby exhibiting rapid cell cycles.
Pathology International 02/2008; 58(2):98-103. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bcl2 is an important protein involved in the pathogenesis of follicular lymphoma (FL). However, approximately 10% of FL cases do not express Bcl2. The present study was designed to compare gene aberrations, prosurvival gene expression, apoptosis and proliferation rates in Bcl2-positive and -negative FL cases. Bcl2 translocation and Bcl6 translocation were detected and compared using fluorescence in situ hybridization (FISH). A tendency for Bcl6 translocation to occur was found more frequently in Bcl2-negative FL than in the Bcl2-positive cases. The expression of Bcl-X, BAX, p53, Bcl6 was analyzed by immunohistochemistry. Bcl2 family proteins Bcl-X and BAX were expressed similarly in the two FL types. In some cases of Bcl2-negative FL there was high expression of Bcl6 or p53 but no such Bcl2-positive FL cases were detected. Furthermore, there was an inverse relationship between the expression of Bcl6 and p53. These results indicate that the Bcl6 translocation occurs more frequently in Bcl2-negative FL. Furthermore, other prosurvival proteins such as p53 and Bcl6 may play an important role in the pathogenesis of Bcl2-negative FL.
Pathology International 04/2007; 57(3):148-52. · 1.62 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lymphoma of the thyroid is almost exclusively derived from B cells of mucosa-associated lymphoid tissue (MALT), and frequently co-exist with autoimmune thyroiditis in which most infiltrating cells are of Th1 cell origin. We present here two rare cases of peripheral T-cell lymphoma (PTCL) based on chronic thyroiditis with the phenotype CD3+, CD4+, CD8-, TCR+. Furthermore, lymphoma cells in both cases were CXCR3+, CCR5+ and ST2(L)-, suggesting a Th1 cell origin. Eight of 11 cases of PTCL of the thyroid in the literature, including our cases, were associated with thyroiditis. Except for one tumor of T-cell type, all of the five lymphomas analyzed for CD4 expression were positive for the antigen. Among them, both those examined for chemokine receptors were phenotypically of Th1-cell origin with a background of thyroiditis, suggesting that Th1 activation induced by chronic inflammation could lead to PTCL of themselves as well as MALT-lymphoma of B cells.
Haematologica 04/2007; 92(3):e37-40. · 6.42 Impact Factor
-
Kennosuke Karube,
Ying Guo,
Junji Suzumiya,
Yasuo Sugita,
Yuko Nomura,
Kohei Yamamoto,
Kei Shimizu,
Shirou Yoshida,
Hideki Komatani,
Morishige Takeshita, Masahiro Kikuchi,
Naoya Nakamura,
Osamu Takasu,
Fumiko Arakawa,
Hiroyuki Tagawa,
Masao Seto,
Koichi Ohshima
[show abstract]
[hide abstract]
ABSTRACT: CD10 and MUM1 are representative B cell differentiation markers. Follicular lymphoma (FL) is usually positive for CD10 and negative for MUM1. In this study, however, we compared 22 FLs with peculiar phenotype CD10-MUM1+ with 119 typical CD10+MUM1- FLs. All CD10-MUM1+ FL patients exhibited follicular structure with follicular dendritic meshwork, and a high rate of somatic hypermutation and ongoing mutation, similar to typical FL. However, CD10-MUM1+ FLs were encountered frequently in the elderly compared with CD10+MUM1- typical FLs (67.0 versus 58.7 years, P < .01), showed high grade (grade 3A or 3B) morphology (91% versus 17%, P < .001), diffuse proliferation (59% vs 19%, P < .001), and lacked BCL2/IGH translocation (5% versus 92.5%, P < .001), which is the most characteristic aberration in FL, and 88% showed BCL6 gene abnormalities (translocation or amplification). Our results indicate that CD10-MUM1+ FL is different from typical FL with respect to biologic and clinical features.
Blood 04/2007; 109(7):3076-9. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In adult T-cell lymphoma/leukemia (ATLL), the neoplastic lymphoid cells are usually medium-sized to large, often with pronounced nuclear pleomorphism compatible with the diagnosis of diffuse pleomorphic peripheral T-cell lymphoma. We describe here 11 patients with the rare morphologic variant of ATLL, angioimmunoblastic T-cell lymphoma (AILT)-like type. The examined lymph nodes showed proliferation of high endothelial venules and presence of various infiltrating inflammatory cells including plasma cells and eosinophils. The lymphoma cells were medium-to-large size with clear cytoplasm. These findings were suggestive of AILT. However, immunohistochemical features of AILT, namely, CD10 and CXCL13 expression in lymphoma cells and proliferation of CD21-positive follicular dendritic cells, were not detected. Two cases were CXCR3-positive, whereas 9 expressed CCR4, which are usually positive in ATLL. All patients were positive for antiadult T-cell leukemia/lymphoma-associated antigen, which is a specific antibody for human T-cell lymphotropic virus type-I. Southern blot analysis revealed proviral DNA integration in lymphoma cells in 9 patients. The latter was not evident in the first biopsy of 2 patients but in the second biopsy obtained within several months after the first biopsy revealed definite proviral integration. Almost all patients showed aggressive clinical course and poor survival (median survival: 5 mo). This is the first report of ATLL with AILT-like morphologic features.
American Journal of Surgical Pathology 03/2007; 31(2):216-23. · 4.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bcl2 is an important protein involved in the pathogenesis of follicular lymphoma (FL). However, approximately 10% of FL cases do not express Bcl2. The present study was designed to compare gene aberrations, prosurvival gene expression, apoptosis and proliferation rates in Bcl2-positive and -negative FL cases. Bcl2 translocation and Bcl6 translocation were detected and compared using fluorescence in situ hybridization (FISH). A tendency for Bcl6 translocation to occur was found more frequently in Bcl2-negative FL than in the Bcl2-positive cases. The expression of Bcl-X, BAX, p53, Bcl6 was analyzed by immunohistochemistry. Bcl2 family proteins Bcl-X and BAX were expressed similarly in the two FL types. In some cases of Bcl2-negative FL there was high expression of Bcl6 or p53 but no such Bcl2-positive FL cases were detected. Furthermore, there was an inverse relationship between the expression of Bcl6 and p53. These results indicate that the Bcl6 translocation occurs more frequently in Bcl2-negative FL. Furthermore, other prosurvival proteins such as p53 and Bcl6 may play an important role in the pathogenesis of Bcl2-negative FL.
Pathology International 02/2007; 57(3):148 - 152. · 1.62 Impact Factor
