Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
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Although diffuse large B cell lymphomas (DLBCL) are considered in the WHO classification a specific histopathological type, their diversity in the clinical features, morphology and molecular aberrations strongly suggest that these tumors represent a heterogeneous group of neoplasms rather than a single clinicopathological entity. There have been various approaches to differentiate between separate nosological entities within DLBCLs based on various methods, such as the microarray technique or immunohistochemistry. Although it has been proven that gene expression profiling using cDNA microarrays could identify prognostically important subgroup of DLBCL: germinal center B-cell (GCB)-like DLBCL and activated B-cell (ABC)-like DLBCL, this method is impractical as a clinical tool. Therefore, investigators have started using immunohistochemistry in their studies. Employing various immunohistochemical antibodies, such as CD10, CD138, anti-Bcl-2, anti-Bcl-6, MUM1 and anti-p53, several groups have aimed at subclassifying DLBCL into the GCB and ABC subgroups with comparable differences in clinical behavior. This review summarizes these data and indicates their impact on DLBCL classification.
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PMID:Usefulness of immunohistochemistry in identification of prognostically important subgroups (GCB and ABC) in a heterogeneous group of diffuse large B-cell lymphomas--a review article. 1909 55

Diffuse large B-cell lymphoma is the most common type of primary central nervous system (CNS) lymphoma(PCNSL) with poor prognosis. Relapse occurs early and most commonly in CNS, whereas systemic relapse solely in skin is exceptional. We presented a unique case of PCNSL in an 82-year-old man with 2 consecutive skin relapses without concomitant local failure or other systemic involvement. The lymphoma cells of all 3 specimens were of the same histology and immunophenotype with expression of CD20, IgM, bcl-2, bcl-6, and MUM1 but not CD3, CD10, CD30, IgD, cyclin D1,or cutaneous lymphocyte-associated antigen. The skin tumors were in the dermis and subcutis with a spared grenz zone. The brain and skin tumors demonstrated the same clonal origin by B-cell clonality study followed by cloning and sequencing. To our knowledge, this is the first case of PCNSL relapsed solely in the skin with proven clonal identity.
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PMID:Primary cerebral diffuse large B-cell lymphoma relapsed solely in the skin with the same clonal origin. 1911 86

A case of CD30-positive microvillous lymphoma (MVL) in an 87-year-old man who was encountered generalised lymphadenopathy is presented. Histopathologically, the tumour showed a morphological mimic of anaplastic large cell lymphoma (ALCL) with sinusoidal growth pattern. Immunohistochemically (IHC), the tumour cells were CD30(+), CD20(+), CD45(+), BCL-2(+), BCL-6(+), MUM1(+), Ki-67(+), CD45RO(-), CD3(-), CD10(-), CD15(-), CD56(-), EMA(-), TIA-1(-) and ALK(-). Flow cytometry confirmed the IHC. In situ hybridisation for Epstein-Barr virus RNA was negative. Electron microscopically, the tumour cells were similar to large transformed lymphocytes and had circumferentially profuse microvillous projections resembling those of epithelial mesothelioma cells. In conclusion, CD30-positive MVLs are indistinguishable from ALCLs that have ultrastructural microvillous projections by morphology alone. However, the lack of EMA, TIA-1 and ALK expression in this MVL case facilitated a definite distinction from ALCLs. The results of a panel of three markers (CD10(-), Bcl-6(+) and MUM1(+)) suggested that the present case of CD30-positive MVLs has an activated non-germinal centre B-cell origin.
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PMID:CD30-positive diffuse large B-cell lymphoma with microvillous features: so-called microvillous lymphoma. 1912 65

Primary effusion lymphoma (PEL) is very rare type of non-Hodgkin's lymphoma (NHL) usually confined to the body cavities such as the pleural space, pericardium, and peritoneum. PEL is a human herpes virus-8 (HHV-8)-associated lymphoma and commonly observed in human immunodeficiency virus (HIV)-infected patients. However, HIV-infected patients are extremely fewer in Japan in comparison with those in Western countries; PEL is usually not associated with HIV infection in Japan. This report presents seven Japanese cases of PEL. In situ hybridization revealed that the PEL cells were negative for EBV in all cases. An immunocytological analysis showed that only one case was positive for HHV-8, and PEL cells were positive for CD20 in all cases. MUM1 was positive, but CD10 and CD138 were negative in six cases. One case each was positive for CD30 and BCL-6. The phenotypic patterns of HIV-related is BCL6-/MUM1+/CD138+, thus, the phenotypic findings observed by immunocytochemistry in this study were somehow different from those reported in Western countries. However, the cytomorphological features of PEL cells showed large cell size, abundant basophilic cytoplasm, coarse chromatin, and occasional binucleated or multinucleated cells, similar to a large cell immunoblastic and anaplastic large cell lymphoma, indicating that the cytomorphological characteristics of PE cells in Giemsa and Papanicolaou stain were consistent with those reported abroad. The prognosis for PEL in these cases was poor, but the survival time was variable ranging from 1 month to 54 months, and was different from that of Western cases. No p16/CDKN2A expression was observed, and one case showed PEL cells with a BLIMP1 mutation.
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PMID:Cytologic and immunocytochemical features of EBV negative primary effusion lymphoma: report on seven Japanese cases. 1921 41

Plasmablastic lymphoma (PBL) is very rare, and predominantly occurs in Human immunodeficiency virus (HIV)-positive individuals. It shows a strong affinity for the oral cavity and for the Epstein-Barr virus (EBV) positive. We investigated the clinicopathologic characteristics of six cases of PBL in Koreans. All patients were HIV-negative and without underlying immunodeficiency. The age distribution was bimodal, and four patients were older than 60 years. Male predominance was observed with male to female ratio of 5:1. The organs primarily involved were the terminal ileum, stomach, oral cavity, tonsil, nasal cavity and meninges. The tumors were histologically typical of PBL. Three of them were composed of monomorphic large immunoblastic or plasmablastic cells, and classified as PBL of the oral mucosa type. Another three cases were classified as PBL with plasmacytic differentiation. Five cases revealed loss of B-cell antigens with CD138 or MUM1 substitution. CD10 was positive in two cases (PBLs of the oral mucosa type), and one of them unexpectedly expressed cytokeratin. EBV was detected in one case (PBL with plasmacytic differentiation). Four patients succumbed to PBL in a relatively short period of time. We suggest that PBL is not strongly associated HIV or EBV in Koreans, and that it shows a variable organ distribution without an oro-nasal predilection.
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PMID:Human immunodeficiency virus-negative plasmablastic lymphoma in Korea. 1937 56

Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high- and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P=0.048, overall survival 69 vs 85%, P=0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P=0.041, overall survival 67 vs 82%, P=0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients.
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PMID:Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP. 1944 93

We report a case of extranodal CD20-positive peripheral T-cell lymphoma (PTCL). A 59-year-old man was admitted because of a right testicular mass in April 2006. CT scan revealed bilateral adrenal masses and he underwent right orchiectomy. The enlarged testis showed diffuse infiltration of large CD20-positive lymphocytes with slight CD3-positive cells. These cells were negative for CD10 and showed a high MIB-1 index. The pathological diagnosis was diffuse large B-cell lymphoma. He received R-CHOP, but developed brain involvement. He received whole brain radiotherapy following high-dose methotrexate, but he died of disease progression in August 2007. At autopsy, lymphoma cells were definitely positive for CD3 and negative for CD20. Monoclonal TCR gamma gene rearrangement was detected in the brain specimen without IgH rearrangement by PCR. The testicular tumor also showed the same clonal bands. Immunohistochemical re-evaluation of the testis showed CD20+, CD79a-, PAX5-, MUM1-, CD3 p+, CD5 p+, CD4-, CD8-, CD7 p+, granzyme B+, and TIA1+. Based on the clinical course and immunohistology, we finally diagnosed this case as extranodal PTCL-nos (not otherwise specified) with aberrant CD20 expression, which is extremely rare. The detection of gene rearrangement, plural immunohistochemical markers and knowledge of the possibility of CD20+ PTCL-nos are necessary for such cases.
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PMID:Extranodal CD20-positive peripheral T-cell lymphoma presenting with adrenal and testicular masses. 1948 2

Among the diffuse lymphomas of B-cell origin, we have encountered one variant displaying blastoid features that morphologically mimic lymphoblastic lymphoma, the blastoid variant of mantle cell lymphoma, and the so-called blastoid transformation of follicular lymphoma. To better characterize this entity, we studied eight cases morphologically, immunohistochemically, and by fluorescence in situ hybridization (FISH) for cytogenetic abnormalities commonly associated with follicular lymphoma and B-cell lymphomas exhibiting high-grade histological features. All eight cases were presented as de novo neoplasms, and displayed an entirely diffuse (five cases) or only minimal follicular (three cases) growth pattern. The neoplastic lymphoid cells were of medium size with round nuclei, fine chromatin, inconspicuous nucleoli, and high mitotic rate; they expressed CD10, BCL6, and BCL2-a phenotype consistent with follicle center cell origin. A proportion of cases expressed MUM1. Their lack of TdT and CYCLIN D1 distinguished them from lymphoblastic lymphoma and the blastoid mantle cell lymphoma, respectively. The neoplastic lymphoid cells consistently expressed CD43 (seven of eight cases) and occasionally other T-cell-associated antigens, including CD5, CD7, CD8, and CD57. Although all cases overexpressed BCL2, t(14;18) was not detected in any of the five cases examined by FISH; instead, extra copies of chromosome 18 were found in four of five cases. Finally, other cytogenetic abnormalities, including structural abnormalities of BCL6 (allelic loss/gain, rearrangement), monosomy 7, del(13)(q14), and MYC allelic loss, were frequently detected. The combination of a B-cell CD10+ BCL6+ BCL2+ phenotype in the presence of structural abnormalities of BCL6 is consistent with a follicular center cell derivation for our cases. The lack of t(14;18) seen in our cases, although rare in most cases of follicular lymphoma, has been nevertheless reported in cases of follicular lymphoma with a predominantly diffuse growth pattern. The molecular pathogenesis, clinical manifestations, and prognostic significance of these lesions remain to be elucidated.
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PMID:Diffuse blastoid B-cell lymphoma: a histologically aggressive variant of t(14;18)-negative follicular lymphoma. 1963 42

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) +/- rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
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PMID:Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. 1965 56

Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-kappaB (NF-kappaB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.
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PMID:Prognostic impact of C-REL expression in diffuse large B-cell lymphoma. 1966 19


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