Clinicopathological Features of Malignant Lymphoma in JAPAN- Data From the Miyagi Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4997-4997
Author(s):  
Yukiko Miura ◽  
Joji Yamamoto ◽  
Katsura Kohata ◽  
Kenichi Ishizawa ◽  
Ryo Ichinohasama ◽  
...  

Abstract Abstract 4997 Background Malignant lymphoma comprises a diverse group of histologic categories. To date, several epidemiological studies in Japan have been reported, however, the data were collected from selected representative institutions, therefore, the results might not reflect the actual incidence and characteristics of malignant lymphoma in Japan. The Miyagi Study is a comprehensive epidemiologic study of malignant lymphoma, including immunologic and genetic information, constructed by a population-based registration system covering Miyagi prefecture, Japan. The population composition by age group and the population growth rate in Miyagi resembles national average figures, therefore, the clinicopathological features of in the Miyagi Study are likely representative of Japan. The purpose of this study was to determine the relative incidences and features of malignant lymphoma subtypes in Japan, compared to that of other countries. Methods A total of 1546 cases of malignant lymphoma newly diagnosed between 2002 and 2008 in Miyagi prefecture, of which the population is about 2.5 million, were enrolled in the Miyagi Study. Clinical and histopathological data including results of flow cytometry(FCM), immunohistochemistry (IHC), G-banding analysis with or without bicolor fluorescence in situ hybridization(FISH), southern blot analysis with or without polymerase chain reaction(PCR) were collected, and analysed. Results The median age of onset was 66 years and the male/female ratio was 1.13. Of the 1546 cases of newly diagnosed malignant lymphoma, 1160 cases (75%) were B-cell lymphomas, 287 cases (19%) were T-cell lymphomas, and only 81 cases (5%) were Hodgkin lymphomas. The most frequent subtype of B-cell lymphoma was diffuse large B-cell lymphoma (DLBCL), accounting for 52% of all B-cell lymphoma cases, followed by follicular lymphoma (FL) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), accounting for 24% and 8% of B-cell lymphoma cases, respectively. The most frequent subtypes of T/NK-cell lymphoma were peripheral T-cell lymphoma, unspecified (PTCLU), angioimmunoblastic T-cell lymphoma(AILT) and adult T-cell lymphoma, accounting for 30%, 15% and 14% of cases, respectively. The relative frequency of malignant lymphoma subtypes was similar to that of Japan reported in 2000 by Lymphoma Study Group of Japanese Pathologists, though there were some differences, such as the high incident rate of FL. There was not a notable time trend in the proportion of FL in B-NHL through 7 years, since it accounted for 20.3% in 2002 and 24.0% in 2008. Within the B-cell lymphoma group, there was a higher frequency of indolent B-cell lymphomas in women (39.8%) compared to men (29.8%). The rates of CD20 and CD22 positivity, as analysed by FCM, were 94.9% and 96.3% in DLBCL, 99.2% and 98.4% in FL, and 98.4% and 100% in MALT lymphoma, respectively. The t(14;18) translocation, a frequent chromosomal abnormality of FL, was present in 63.9% of FL patients, which is less frequent compared with the reports from western countries. De novo CD5+ DLBCL, which is known to have poor outcome, accounted for 21.6% of DLBCL, a frequency higher than previously reported. Conclusions The relative frequency of the subtypes of malignant lymphomas in Miyagi is distinct from that of Western countries and shares some similarities with other Asian countries. In the present study, FL was found to be the second largest subtype of malignant lymphoma, consistent with previous reports that FL is increasing in Far East Asia including Japan, Korea and Taiwan. The results of this study reveal the clinicopathologic characteristics of malignant lymphomas in Japan. Disclosures No relevant conflicts of interest to declare.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17566-17566
Author(s):  
B. Beltran ◽  
A. Carrasco ◽  
L. Vera ◽  
E. Salinas ◽  
M. Ticona ◽  
...  

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4146-4146
Author(s):  
Soranobu Ninomiya ◽  
Hisashi Tsurumi ◽  
Takeshi Hara ◽  
Masato Hoshi ◽  
Naoe Goto ◽  
...  

Abstract Abstract 4146 Background: Indoleamine 2,3-dioxygenase (IDO) exerts powerful immunomodulatory effects through its enzymatic activity that leads to catabolism of the essential amino acid l-tryptophan. Some metabolites derived from tryptophan generated by IDO such as L-kynurenine, block Ag-driven specific T-cell proliferation and induce T-cell death. Therefore, IDO activity might play an important role in regulation of the immune response exerted by antigen presenting cells and also provide transformed cells with a potent tool to help escape from assault by the immune system. The activity of IDO can be estimated by measuring the serum concentration of l-tryptophan and l-kynurenine. We have previously described that high serum l-kynurenine level is associated with poor prognosis of diffuse large B-cell lymphoma (DLBCL) (Yoshikawa et al. Eur J Hemat 2009). Here, we investigated the tryptophan catabolism in malignant lymphoma. Patients and methods: The study protocol comprised a prospective, consecutive entry design that was approved by our Institutional Review Board. We investigated 163 patients between December 2002 and March 2010 who were histologically diagnosed with malignant lymphoma and 20 healthy adult volunteers. L-tryptophan and l-kynurenine were measured by high performance liquid chromatography. Patients with CD 20 positive NHL received 6 to 8 cycles of either R-CHOP therapy. Each regimen consisted of rituximab, cyclophosphamide, doxorubicin or tetrahydropyranyl-adriamycin, an anthracycline derivative of DOX, vincristine, and prednisolone. Patients with CD 20 negative NHL aged received 6 to 8 cycles of either CHOP therapy. Patients with Hodgkin lymphoma received ABVD therapy. Patients with bulky disease received radiotherapy ranging from 30 to 40 Gy. Some patients with refractory or relapsed NHL who responded to (R)-P-IMVP-16/CBDCA received high-dose chemotherapy followed by autologous stem cell transplantation. Results: The pathology of underlying comprised Hodgkin lymphoma (n=10), DLBCL (n=75), lymphoblastic lymphoma (LBL, n=3), Burkitt lymphoma (Burkit, n=2), follicular lymphoma (FL, n=28), mantle cell lymphoma (MCL, n=4), mucosa-associated lymphoid tissue lymphoma (MALT, n=14), small lymphocytic lymphoma (SLL, n=2), lymphoplasmacytic lymphoma (LPL, n=4), anaplastic large cell lymphoma (ALCL, n=4), peripheral T-cell lymphoma, unspecified (PTCL-U, n=13), and NK/T cell lymphoma (NK/T, n= 4). The median serum l-kynurenine levels in patients (2.29 ± 4.97 mM) were significantly higher than in healthy volunteers (1.13 ± 0.32 mM). The ratio of l-kynurenine/l-tryptophan levels in patients with ML (0.040 ± 0.487) was significantly higher than in healthy volunteers (0.022 ± 0.009). We found no significant correlations between l-kynurenine or l-tryptophan and lymphoma histology. Regardless of the pathologic classification, median l-kynurenine levels in lymphoma patients were higher than in healthy volunteers. We established the cut-off value of l-kynurenine at 2.2 mM which was essentially the median for all patients. In the aggressive B cell lymphoma patients (DLBCL, Burkit, and LBL, n=81), the 3-year OS rates with l-kynurenine < 2.2 mM and ≥ 2.2 mM were 69.5% and 43.6%, respectively (P <0.05). While, in the indolent B cell lymphoma patients (FL, MALT, MCL, LPL and SLL, n=51), the 3-year OS rates with l-kynurenine < 2.2 mM and ≥ 2.2 mM were 95% and 90.6%, respectively (N.S). In the T cell lymphoma patients (ALCL, PTCL, and NK/T n=21), the 3-year OS rates with l-kynurenine < 2.2 mM and ≥ 2.2 mM were 75% and 55.2%, respectively (N.S). Conclusion: Serum l-kynurenine was a significant predictor for the survival of aggressive B cell lymphoma patients. The increase in serum l-kynurenine levels is thought to be caused by enhanced l-tryptophan catabolism, which inhibits tumoral local immunity. The result of a poor prognosis among patients with high l-kynurenine levels indicates that depressed local immunity due to enhanced IDO activity contributes to becoming refractory to treatment. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4553-4553
Author(s):  
Xiang-Nan Jiang ◽  
Yang Shi ◽  
Xiao-Qiu Li

Abstract Background: CD30 is emerging as an important biomarker guiding the clinical diagnosis, treatment, and evaluating the efficacy and prognosis of lymphoma. However, there is no standard procedure for specification and interpretation of the pathological detection of CD30 in China. This study intends to evaluate the staining and interpretation concordance of CD30 expression detected by the VENTANA CD30 assay and other multiple immunohistochemistry (IHC) assay in Chinese malignant lymphoma patients. Design: This is a multi-center, observational study enrolling 1,000 adult patients with a diagnosis of histologically confirmed malignant lymphoma in China. Patients, aged 18 years or older at diagnosis and who provided available formalin-fixed paraffin-embedded (FFPE) samples stored within 2 years, with diagnosis of classical Hodgkin's lymphoma, anaplastic large-cell lymphoma, large cell transformation of mycosis fungoides, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, extranodal NK/T-cell lymphoma, peripheral T cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, and pcCD30+ T-cell lymphoproliferative disease were eligible to participate. Exclusion criteria included sample insufficiency for CD30 testing, incomplete sample information, lack of written informed consent. Methods: Each eligible patient provides an available r FFPE sample. Tissue slides obtained from each eligible FFPE sample will be stained by the VENTANA CD30 assay and at least one of the following IHC assays [umAB256 (zhongshanjinqiao) + Ventana BenchMark; Ber-H2 (Maixin) + Ventana BenchMark;Ber-H2 (Maixin) + DAKO; Ber-H2 (DAKO) + DAKO; Ber-H2 (DAKO) + Ventana BenchMark;umAB256 (Zhongshanjinqiao) + Leica; JCM182 (Leica) + Ventana BenchMark;JCM182 (Leica) + Leica; Ber-H2 (DAKO) + Leica]. CD30 expression of all immunostained slides will be independently interpreted as a percentage of CD30 positive cells by trained pathologists. The primary endpoint will be the staining concordance of percentages of positive cells for CD30 expression detected by each of the nine IHC assays and VENTANA CD30 assay (interpreted by expert panel) Secondary endpoints will be the interpretation concordance of pathologists at sites and the expert panel by assessing CD30 expression detected by various IHC assays. Both primary and secondary endpoint will be evaluated by intraclass correlation coefficient ICC, Bland-Altman, and Pearson correlation method. Discussion: This planned study will explore more equivalent testing methods to detect the expression of CD30 in Chinese patients with lymphoma. Disclosures Shi: Takeda Pharmaceuticals: Current Employment. Li: Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Receiving lecture fees.


2011 ◽  
Vol 61 (11) ◽  
pp. 662-666 ◽  
Author(s):  
Sho Yamazaki ◽  
Yosei Fujioka ◽  
Fumihiko Nakamura ◽  
Satoshi Ota ◽  
Aya Shinozaki ◽  
...  

1989 ◽  
Vol 7 (6) ◽  
pp. 725-731 ◽  
Author(s):  
A L Cheng ◽  
Y C Chen ◽  
C H Wang ◽  
I J Su ◽  
H C Hsieh ◽  
...  

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.


2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Shin Nagai ◽  
Junji Hiraga ◽  
Noriyuki Suzuki ◽  
Naruko Suzuki ◽  
Yusuke Takagi ◽  
...  

We report a rare case of composite lymphoma comprising extranodal NK/T-cell lymphoma, nasal type, (ENKL) and diffuse large B-cell lymphoma (DLBCL) in a 70-year-old man complaining of fatigue. Computed tomography showed multiple consolidations in both lungs, and ENKL was diagnosed from transbronchial lung biopsy. Positron emission tomography also detected abnormal uptake in the stomach, and DLBCL was diagnosed from subsequent gastroscopy. Two courses of chemotherapy including rituximab achieved reduction in DLBCL, but ENKL proved resistant to this treatment and progressed. Concomitant ENKL and DLBCL have not been previously described among reports of composite lymphomas.


2015 ◽  
Vol 8 (4) ◽  
pp. 235-241 ◽  
Author(s):  
Yi Zhou ◽  
Marc K. Rosenblum ◽  
Ahmet Dogan ◽  
Achim A. Jungbluth ◽  
April Chiu

2008 ◽  
Vol 88 (4) ◽  
pp. 434-440 ◽  
Author(s):  
Katja C. Weisel ◽  
Eckhart Weidmann ◽  
Ioannis Anagnostopoulos ◽  
Lothar Kanz ◽  
Antonio Pezzutto ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4637-4637
Author(s):  
Gerald G. Wulf ◽  
Anita Boehnke ◽  
Bertram Glass ◽  
Lorenz Truemper

Abstract Anti-CD45 mediated cytoreduction is an effective means for T-cell depletion in rodents and humans. In man, the CD45-specific rat monoclonal antibodies YTH24 and YTH54 are IgG2b subclass, exert a predominantly complement-dependent cytolytic activity against normal T-lymphocytes, and have been safely given to patients as part of conditioning therapies for allogeneic stem cell transplantation. The efficacy of such antibodies against human lymphoma is unknown. Therefore, we evaluated the cytolytic activity of YTH24 and YTH54 by complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), as well as by direct apoptotic and antiproliferative effects, against a panel of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cell lines, and against primary specimens. Significant CDC activity (&gt;50% cytolysis) of the antibodies YTH54 and YTH24 was observed against three of five T-cell lymphoma lines, but against only one of nine B-cell lymphoma lines and none of four HD cell lines. The combination of YTH54 and YTH24 induced ADCC in all T-cell lymphoma cell lines and three primary leukemic T-cell lymphoma specimens, but were ineffective in B-cell lymphoma and HD cell lines.There were only minor effects of either antibody or the combination on lymphoma cell apoptosis or cell cycle arrest. In summary, anti-CD45 mediated CDC and ADCC via the antibodies YTH24 and YTH54 are primarily effective against lymphoma cells with T-cell phenotype, and may be an immunotherapeutic tool for the treatment of human T-cell lymphoma.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2686-2686 ◽  
Author(s):  
Bertrand Joly ◽  
Valerie Frenkel ◽  
Philippe Gaulard ◽  
Karim Belhadj ◽  
Taoufik El Gnaoui ◽  
...  

Abstract AITL, as most T cell lymphomas, follows an aggressive clinical course with a 5-year overall survival of about 30%. Features consistent with B cell hyperstimulation including hypergammaglobulinemia with M component, autoimmune manifestations and B blast expansion in the tumoral tissue (sometimes culminating in overt B-cell lymphoma) are frequently seen. Clonal immunoglobulin gene rearrangements are detected in 20 to 40% of AITL. We postulated that AITL might benefit from a treatment with anti-CD20 monoclonal antibody (rituximab) combined to the standard CHOP regimen (R-CHOP). Between january 2001 et august 2004, 9 consecutive patients older than 60 years with newly diagnosed AITL were treated in our institution with a combination of rituximab (375mg/m2 given at day 1 of each cycle) and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone at day 1) chemotherapy delivered every 3 weeks. Patients were planned to receive 8 cycles, if a good response (at least partial response) was observed after the first 4 cycles. All patients presented characteristic features of AITL with generalized lymphadenopathy and poor performance status. Elevated LDH were seen in 6 patients. Four out of 9 patients had a serum M-component. Autoimmune hemolytic anemia was concomitantly diagnosed in 3 patients. Histopathological analysis revealed features of AITL in all cases associated with a significant expansion of large CD20+ B cells in 5 patients, CD10 positivity of tumor cells in 7 cases and EBV association in 5 cases (LMP-1 expression and/or EBER in situ hybridization positivity). DNA extracted from the biopsies was amplified using PCR and analyzed on a ABI 310 sequencing analyser. B and T-cell clonality analyses were performed according to the Biomed 2 procedure (Dongen et al. Leukemia 2003). Analysis of tumoral lymph node were available in 8 patients: a dominant T-cell clone was present in 5 cases, 2 of them showing also a dominant B-cell clone and 3 an oligoclonal B-cell repertoire. The 3 remaining cases had oligoclonal T-cell populations with a polyclonal B-cell repertoire. Eight patients achieved a complete remission at the end of treatment and one patient progressed after 3 cycles. Two patients relapsed at 13 and 14 months. Among these 3 refractory/relapsed patients, two were salvaged with additional treatment (alkylating agent alone or MabCampath). In July 2005, with a median follow-up of 12 months (7 to 53 months), all the patients are alive, 8 of them without evolutive disease. No additionnal toxicity was observed in this population of T-cell lymphoma patients as compared to that observed in elderly patients with diffuse large B-cell lymphoma treated with R-CHOP (Coiffier, N Engl J Med 2002). These results led us to consider that rituximab adjunction to CHOP could improve the prognosis of AITL in elderly patients. This approach is currently evaluated in an ongoing multicentric phase II study led by the GELA.


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