Follicular dendritic cell tumor of the spleen associated with diffuse large B-cell lymphoma

We report the case of a 50-year-old woman with an isolated large mass of the lower pole of the spleen. Splenectomy was performed and revealed a follicular dendritic cell (FDC) tumor associated with diffuse large cell lymphoma. Dendritic cells were CD21(+), CD35(+), CNA42(+), CD20(-), and Epstein-Barr virus (EBV)(+). They contained a clonal EBV genome as shown by polymerase chain reaction analysis of the LMP-1 gene polymorphism. Interestingly, the lymphoma cells were intermingled with the neoplastic FDCs and displayed a germinal center cell phenotype (CD20(+), CD10(+), Bcl2(+), and EBV(-)). Double staining confirmed that EBV was restricted to the FDCs. Clinical, radiologic, and pathologic staging showed no other lymphoma localization. To the best of our knowledge, this association has never been reported. Based on the well-established role of FDCs in B-cell survival and proliferation, this observation suggests that the FDC tumor represented a favorable microenvironment for lymphoma cells with germinal center phenotype.     

Dendritic reticulum cell sarcoma? Four cases of a lymphoma probably derived from dendritic reticulum cells of the follicular compartment

This paper describes the histological picture of four tumours of the follicular compartment of the lymph node, in which the proliferating cell appeared to be the dendritic reticulum cell (DRC). This assumption was based on the results of light microscopical, ultrastructural, immunological, and enzymehistochemical investigations. The tumour cells resembled DRC's closely in (1) the striking pattern of interdigitations and occasional tight junction-like contacts between the neoplastic cells on electron microscopical analysis; (2) presence of receptors for the activated third component of complement on the membrane of the cells; (3) absence of monoclonal immunoglobulins and T-cell antigen on the surface and of lysozyme, alpha 1-antitrypsin or alpha 1-antichymotrypsin in the cytoplasm of the neoplastic cells. Moreover, (4) the tumour cells showed moderate alpha-naphtyl acetate esterase, weak to absent acid phosphatase and (with one exception) strong 5-nucleotidase activity. Furthermore, (5) the neoplastic cells expressed Ia-like antigens on the surface in all four cases. The relation with follicle centre cell lymphomas, the differential diagnosis and clinical data are discussed.     

Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas

Growth factor receptor-bound protein 2 is an adaptor molecule that mediates B-cell receptor (BCR) signaling pathways, but the expression of growth factor receptor-bound protein 2 in lymphoma tissues has not been reported. We sought to characterize growth factor receptor-bound protein 2 protein expression in reactive tonsillar tissues and lymphoma tissues obtained from diagnostic biopsies of classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and 20 low-grade B-cell lymphomas. Growth factor receptor-bound protein 2 expression was assessed in tissues by immunohistochemistry and in lymphoma cell lines by immunoblotting. In reactive lymphoid tissues, growth factor receptor-bound protein 2 was expressed in the cytoplasm of B-cells and histiocytes but not T-cells. Strong, cytoplasmic growth factor receptor-bound protein 2 expression was seen in the neoplastic cells of follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma. In contrast, only 10% of the classical Hodgkin lymphomas showed growth factor receptor-bound protein 2 expression in the neoplastic cells. Growth factor receptor-bound protein 2 protein expression was detected by Western blotting in all lymphoma cell lines tested with higher levels in primary mediastinal large B-cell lymphoma compared with classical Hodgkin lymphoma cell lines. These findings support a role for growth factor receptor-bound protein 2 in the diagnostically challenging workup of classical Hodgkin lymphoma versus primary mediastinal large B-cell lymphoma and warrant further studies to evaluate the biologic significance of growth factor receptor-bound protein 2 in the pathogenesis of classical Hodgkin lymphoma.     

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.     

Molecular and immunohistochemical characterization of B-cell lymphoma-2-negative follicular lymphomas

Aberrant expression of the antiapoptotic protein BCL (B-cell lymphoma)-2 in neoplastic germinal centers is one of the diagnostic hallmarks of follicular lymphoma. If BCL-2 cannot be detected by immunohistochemistry, the distinction between florid follicular hyperplasia and follicular lymphoma might become a diagnostic challenge. Most of those cases also lack the typical t(14;18), and the underlying pathophysiologic conditions of follicular lymphoma that lack BCL-2 protein expression are largely unknown. Here, we collected 18 BCL-2-negative follicular lymphoma cases from 5 different institutions. After restaining, 9 cases proved to be truly BCL-2 negative (6 follicular lymphoma grade 2, 2 follicular lymphoma grade 3a, and 1 follicular lymphoma grade 3b). In 4 additional cases, BCL-2 was very faint (all grade 2). Of the 9 BCL-2-negative follicular lymphoma cases, 2 were negative for CD10 (22%); all showed expression of BCL-6. Apoptotic level as determined by caspase 3 was the lowest in the BCL-2-positive follicular lymphoma group (15 ± 8 mm(2)), the highest in the normal/reactive group (n = 7, 60 ± 12 mm(2)) and very similar in the BCL-2 low follicular lymphoma and BCL-2-negative follicular lymphoma groups (25 ± 13 and 33 ± 19 mm(2), respectively), assuming an intermediate position between reactive follicles and BCL-2-positive neoplastic follicles (P < .001 [Kruskal-Wallis]). Also noted was a difference in proliferation fractions between the BCL-2-positive follicular lymphoma (27% ± 15%), the BCL-2 low follicular lymphoma (30% ± 20%) and the BCL-2-negative follicular lymphoma groups (30% ± 22%). Regarding the network of follicular dendritic cells, 8 (89%) of 9 cases from the BCL-2-negative subgroup showed disrupted, weakly developed networks, whereas all of the follicular lymphoma BCL-2 low-expression cases showed a well-defined and strongly developed follicular dendritic cell network. Among BCL-2-negative follicular lymphoma, BCL-2 and BCL-6 breaks were found in 1 case each, whereas in the follicular lymphoma BCL-2 low group, only 1 case with a BCL-6 break was recorded. No statistically significant result was achieved upon assessment of BCL-2α or BCL-2β RNA or the ratio of α/β isolated by real-time-polymerase chain reaction. Taken together, BCL-2-negative follicular lymphoma did not show a BCL-2 break on the genetic level and showed both increased apoptotic and proliferation rates compared with BCL-2-positive follicular lymphoma. In our series, BCL-6 breaks were infrequent in BCL-2-negative follicular lymphoma.     

One patient with double lymphomas: simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma

Multiple different lymphomas in a single person are very rare. The author herein reports the case of a 69- year-old Japanese woman with double gastrointestinal lymphoma. The patient presented with epigastralgia. Endoscopic examination revealed erosions and elevation of the gastric body and a large ulcerated tumor of the terminal ileum. Biopsies were obtained from these lesions. The gastric lesion was MALT lymphoma with monocytoid B-cell proliferation and lymphoepithelial lesions. Light chain restriction was present. Helicobacter pylori were present on Giemsa stain. The gastric lesions did not regress despite of therapy, which were confirmed by follow-up biopsy. The ileal lesion was obvious diffuse large B-cell lymphoma. The lesion regressed by chemotherapy. The patient is now alive 3 years after the first presentation.     

Immunohistochemistry of laminin in early chicken and quail blastoderms

Summary We have used immunohistochemical techniques to study laminin in quail blastoderms milked from the oviduct and the distribution of laminin in laid chicken and quail blastoderms. Laminin is a constituent of the basement membrane in both chicken and quail blastoderms. It is found at the ventral side of the upper layer cells. Laminin is first observed under individual upper layer cells in prelaid quail blastoderms 15 h post-ovulation, but is absent at the ingression site of endophyll cells. The presence of a continuous laminin layer coincides with the epithelialization of the epiblast after 5–10 h incubation. The laminin layer is discontinuous at the primitive streak and at Hensen's node. It is thinner and partly discontinuous at the median part of the neural plate. By induction, either of an ectopic primitive streak or a neural plate, we have demonstrated, using the chicken-quail nucleolar marker technique, that at these sites the laminin layer is interrupted. A laminin layer might confer rigidity onto the epiblast, whereas disruption of a laminin layer seems to be correlated with ingression of cells or bending of the neural plate.     

Primary diffuse large B-cell lymphomas of the bone: prognostic relevance of protein expression and clinical factors

Diffuse large B-cell lymphomas can be considered primary bone tumors if they are monostotic or polyostotic, affecting multiple skeletal sites without visceral or lymph node involvement. They are rarely considered as extranodal lymphomas or as bone tumors, respectively. To elucidate the prognostic relevance of clinicopathologic characteristics in such disease, we collected a cohort of primary diffuse large B-cell lymphomas of the bone and retrospectively investigated 33 patients. The cohort encompassed the years 1975 to 2004. Protein expression patterns were identified by immunohistochemistry applied to a tissue microarray. The patients included 23 males (mean age, 37 years) and 10 females (mean age, 54 years). Disease stage was I and II in 30 and IV in 3 patients. Within the mean follow-up of 28 months, 6 patients died. Median overall survival was reached after 78 months. Clinical factors favoring a good prognosis were age younger than 53 and administration of chemotherapy. Of the phenotypic markers analyzed (CD10, CD44s, CD138, Bcl-2, Bcl-6, MUM1, and Ki-67), MUM1 expression in more than 10% of the tumor cells and CD10 expression in less than 55% as well as a nongerminal center signature substantiated adverse outcome in a univariate model. In summary, poor survival in PB-DLBCL was clearly predicted in patients older than 53, who had not received chemotherapy, and who demonstrated MUM1 expression and nongerminal center phenotype.     

Ultrastructural localization of type IV collagen and laminin in the seven-day-old mouse embryo

Summary The localization of the basement membrane components type IV collagen and laminin was investigated in seven-day-old mouse embryos (NMRI) fixed with formaldehyde, using an immunoperoxidase technique. Posttreatment of the embryos with TBS (trishydroxymethylaminomethane buffered saline) buffer was prerequisite for restoration of the antigenicity after fixation. The localization of the peroxidase (PO) positive reaction after treatment with anti-type IV collagen and anti-laminin antibodies in the embryos has been compared with results obtained after fixating embryos with the addition of tannic acid. Tannic acid stained the basement membrane of the ectodermal cell layer, in particular the lamina densa. After immunostaining for type IV collagen and laminin, a strong PO-positive reaction in the lamina densa of the ectodermal basement membrane was observed.A basement membrane of the endodermal cell layer had not yet been formed at this developmental stage. In this region, which is where a basement membrane was to develop in later stages, a tannic acid positive material consisting of granules with a diameter of about 25 nm was found near the surface of the endoderm. Moreover, PO-positive patches were seen in this part of the embryo after staining for laminin as well as after staining for type IV collagen. These PO-positive patches were mainly localized in areas where mesodermal cells lay adjacent to the surface of the endodermal cell layer. No positive staining for type IV collagen and laminin was found in the cytoplasm of either cetodermal or endodermal cells.     

Ultrastructural localization of collagen type IV and laminin expression in the epithelial basement membrane of oral carcinomas

Epithelial basement membrane in oral carcinomas was examined by immunoelectron microscopy using anticollagen type IV and antilaminin antibodies. Intense and irregularly increased immunostaining was observed at the boundary between carcinoma cells and stromal tissue. Heterotopic immunostaining was found in the enlarged intercellular spaces of peripheral carcinoma cells. In addition, rough endoplasmic reticulum (rER) and vesicles in these cells were frequently stained. These findings suggest an increased synthesis and secretion of basement membrane components at the invading edge of the tumor, and also suggest that some oral carcinomas may spread into the surrounding tissue without apparent loss of the basement membrane.This study was presented in part at the 26th annual meeting of the Clinical Electron Microscopy Society of Japan, Kochi, October 6, 1994     

Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas

Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress cell death, in part, through their ability to directly inhibit caspases. Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas. The functions of some IAPs are counteracted by the cell death inducer, second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO). In this study, we investigated the expression levels of Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed 247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was differentially expressed in various NHL types. In most NHLs, from 29% to 68% of tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25 (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although nodular sclerosis was least often positive. The differential expression of Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially involved in their pathogenesis. These results may also have implications for using Smac/DIABLO or its agonists as therapeutic agents.     

Clinicopathological study of gene rearrangement and microRNA expression of primary central nervous system diffuse large B-cell lymphomas

We studied the clinicopathological and imaging characteristics of primary central nervous system diffuse large B-cell lymphomas (PCNS-DLBCL). Imaging, pathologic histology, and immunohistochemical staining characteristics were analyzed, and the immunoglobulin heavy and light chain gene rearrangement of 25 PCNS-DLBCL cases was examined. MicroRNA was extracted from 10 cases each of PCNS-DLBCL, extracerebral germinal center DLBCL (GC-DLBCL), and extracerebral non-GC-DLBCL (NGC-DLBCL); we conducted chip hybridization and comparatively analyzed the difference among the three. PCNS-DLBCLs typically involved no less than two cerebral lobes (10/25); the frontal lobe was affected most often (6/25). Target-shaped structures were observed in all PCNS-DLBCLs due to the proliferation of centroblast-like large lymphocytes surrounding the vessels. There was strong and diffuse immunostaining for CD20 and CD79a, and negative immunostaining for CD3, CD5, CD23, and cyclin D1 for all PCNS-DLBCLs. The percentage of cells with nuclear positivity for anti-Ki67 antibody ranged 50-90% (mean, 80%). Three, 19, and 22 PCNS-DLBCLs were CD10-, Bcl-6-, and melanoma ubiquitous mutated 1-positive, respectively. Twenty-four PCNS-DLBCLs were B-cell monoclonal. MicroRNA hybridization showed that 788 PCNS-DLBCL microRNAs/segments increased to at least twice that of NGC-DLBCLs, and 401 PCNS-DLBCL microRNAs/segments declined to less than half of that of NGC-DLBCLs. Six hundred and eleven PCNS-DLBCL microRNAs/segments increased to at least twice that of GC-DLBCLs, and 229 PCNS-DLBCL microRNAs/segments declined to less than half of that in GC-DLBCLs. PCNS-DLBCL typically affected multiple sites, tended to occur in older men, arose from activated B cells, had high B-cell monoclonality; its microRNA expression differed from that of NGC-DLBCL and GC-DLBCL.     

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type

Extranodal lymphomas of the thyroid (n=19), kidney (n=15) and testis (n=30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDC1P. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n=18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia,n=2; immunocytoma,n=4; centroblastic lymphoma,n=9) and of the testis (immunocytoma,n=2; centroblastic lymphoma,n=27; immunoblastic lymphoma of B-cell type,n=1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkin's lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.     

Diagnostic utility and prognostic significance of the Ki-67 labeling index in diffuse large B-cell lymphoma transformed from follicular lymphoma: a study of 76 patients

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.     

弥漫大B细胞淋巴瘤中Prdx6的表达及其预后意义

目的 探讨过氧化物酶6(peroxiredoxin-6,Prdx6)在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及其预后意义.方法 回顾性分析286例DLBCL中Prdx6的表达及与临床病理特征和预后之间的关系.结果 Prdx6在DLBCL中的表达高于正常淋巴结...     

Expression of TCL1 and CD27 in primary cutaneous B-cell lymphomas

AIMS: To investigate by immunohistochemical analysis the expression of the TCL1 oncogene product and of CD27 in 25 cases of primary cutaneous B-cell lymphomas (PCBCL) classified according to the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. In B-cell ontogenesis TCL1 is mainly expressed by 'naive' B lymphocytes and by a subset of germinal centre B cells, whereas CD27 is expressed by a subset of germinal centre B cells, 'memory' B lymphocytes and plasma cells, suggesting that their expression in physiological conditions is mutually exclusive. METHODS AND RESULTS: Overall, TCL1 was expressed in 5/25 cases (20%) and CD27 in 15/25 cases (60%). Furthermore, 7/25 cases (28%) were TCL1- and CD27- and 2/25 cases (8%) were TCL1+ and CD27+. In particular, primary cutaneous follicle-centre lymphomas (10 cases) showed a variable expression of both TCL1 and CD27, whereas primary cutaneous marginal-zone B-cell lymphomas (eight cases) showed, with the exception of a single case, a definite CD27+/TCL1- profile. CONCLUSIONS: These findings indicate: (i) the TCL1 oncogene product is uncommonly expressed in PCBCL (20% of cases, mainly of the follicle-centre subtype); (ii) in contrast, CD27 is often expressed in PCBCL (60% of cases), mainly of the marginal-zone subtype; (iii) the coexpression of TCL1 and CD27 may be seldom observed in PCBCL (8% of cases); (iv) PCBCL does not seem to show, in terms of either TCL1 or CD27 expression, significant differences compared with its systemic counterparts.     

Expression of TNF-receptor associated factor 2 correlates with poor progression-free survival time in ABC-like primary nodal diffuse large B-cell lymphomas

Aims:  Tumour necrosis factor (TNF)-receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)-κB activation, which is characteristic of in vitro activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL) and may result in expression of anti-apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti-apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC-like DLBCL, and whether expression correlates with clinical outcome.
Methods and results:  TRAF2 was expressed in nine of 20 tested ABC-like DLBCLs and in only one of 13 tested germinal centre B-lymphocyte (GCB)-like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression-free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC-like DLBCL only, TRAF2 expression was significantly associated with poor progression-free survival time.
Conclusions:  TRAF2 might be involved in activation of NF-κB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.     

Immunohistochemical analysis of cleaved caspase-3 detects high level of apoptosis frequently in diffuse large B-cell lymphomas of the central nervous system

The purpose of the present paper was to examine the level of apoptosis and the relationships among apoptosis, apoptosis-associated proteins, and proliferating potential in lymphoma tissues to clarify the characteristics of apoptosis in diffuse large B-cell lymphomas (DLBCL) of the central nervous system (CNS). The formalin-fixed, paraffin-embedded tissues of CNS and non-CNS DLBCL (20 cases each) were studied by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) and immunohistochemistry, using antibodies against single-stranded DNA (ssDNA), cleaved caspase-3, bcl-2, bax, p53, Fas and Ki-67. The cleaved caspase-3 immunohistochemistry detected apoptosis of the lymphoma cells most sensitively compared to TUNEL and ssDNA immunohistochemistry. High expression (grade + + or + + +) of cleaved caspase-3 was found more frequently in CNS DLBCL (11 cases, 55%) than non-CNS DLBCL (three cases, 15%; P = 0.009). Bax-positivity of lymphoma cells was increased in six cases of CNS DLBCL, which also showed high positivity of cleaved caspase-3. There was no significant correlation between the cleaved caspase-3-positivity and the Ki-67 positivity. The present study indicates that the number of apoptotic cells and expression level of cleaved caspase-3 were significantly higher in CNS DLBCL than non-CNS DLBCL, and that the correlation of bax and cleaved caspase-3 expression was often present in CNS DLBCL.     

Expression of transmembrane adaptor protein PAG/Cbp in diffuse large B-cell lymphoma: immunohistochemical study of 73 cases

PAG/Cbp is a transmembrane adaptor protein involved in proximal immune signaling. It is expressed in reactive germinal centers (GC) of secondary lymphatic follicles and related malignant lymphomas. We studied PAG/Cbp expression in GC-like and non-GC-like diffuse large B-cell lymphoma (DLBCL) subtypes. Seventy-three cases of DLBCL identified among 155 malignant lymphomas were classified as GC-like DLBCL (CD10+ or CD10-, bcl-6+, and MUM1-) and non-GC-like DLBCL (CD10-, MUM1+ or CD10-, bcl-6+, MUM1+). PAG/Cbp was detected by monoclonal antibody MEM-255 following routine immunohistochemical procedures. Thirty-five of 40 GC-like DLBCLs (88%) and 20 of 33 non-GC-like DLBCL cases (61%) expressed PAG/Cbp. Four of 12 bcl-6-negative non-GC-like DLBCL cases (33%) were PAG/Cbp positive, and only 4 of 20 bcl-6-positive non-GC-like DLBCL cases (25%) were PAG/CBP negative. All 37 FL and all 5 Burkitt's lymphomas (BL) expressed PAG/Cbp, whereas all 6 mantle cell lymphomas (MCL) and 4 of 5 chronic lymphocytic leukemias (CLL/SLL) were PAG/Cbp negative. PAG/Cbp is a reliable GC marker. Its expression correlates with GC-like DLBC phenotype in a significant majority of cases. It is typically absent in MCL and SLL/CLL.