Expression of vimentin and epithelial membrane antigen in human malignant lymphomas

Immunoreactivity with monoclonal antibodies against the intermediate filament protein, vimentin, and epithelial membrane antigen (EMA) was examined in 330 cases of lymphoma (317 non-Hodgkin's and 13 Hodgkin's lymphomas), 12 reactive lymph nodes and mononuclear cells of the peripheral blood using either indirect immunoperoxidase staining or the avidin-biotin immunoperoxidase complex technique. The cell origin of each tumor was established using a panel of monoclonal antibodies against lymphocyte differentiation antigens. There were 41 T-cell, 247 B-cell and 29 undetermined lymphomas, and 13 cases of Hodgkin's disease in the series. Vimentin was expressed in 24 T-cell lymphomas (58.5%) and 60 B-cell lymphomas (24.2%). This difference in frequency was statistically significant. Vimentin expression in follicular lymphomas was less frequent than in diffuse B-cell lymphomas. In diffuse lymphomas, small and medium cell types were more reactive with anti-vimentin than large cell types. Reed-Sternberg cells (R-S cells) in Hodgkin's disease were positive for vimentin in 11 cases (84.6%). The frequency of EMA reactivity in lymphomas was low, particularly in T-cell lymphomas. No positive cases were found among follicular lymphomas. In diffuse non-Hodgkin's lymphomas, EMA was expressed only in mixed and large cell types, but never in smaller ones. In conclusion, monoclonal antibodies against vimentin and EMA appear to be of limited usefulness for the diagnosis of non-Hodgkin's lymphomas, but anti-vimentin antibody may be used as an adjunct to the diagnosis of R-S cells in Hodgkin's disease.     

Study of vimentin expression in non-Hodgkin's lymphoma using paraffin sections.

Human non-Hodgkin's lymphomas were studied by means of an avidin-biotin complex immunoperoxidase method using several monoclonal antibodies against the intermediate filament protein, vimentin. The study cases were 61 B-cell lymphomas (including 2 plasmacytomas) and 30 T-cell lymphomas (including 8 cases of mycosis fungoides). Twelve of the 61 B-cell lymphomas were positive for vimentin, and were composed of extrafollicular-center cells such as immunoblastic and plasmacytoid cells. On the other hand, lymphomas of follicular center cell origin were negative for vimentin. All cases of T-cell lymphoma except for 14 (all of 9 AILD-type lymphomas, all of 4 lymphoblastic lymphomas and one diffuse mixed small/large lymphoma) were positive for vimentin. Although vimentin expression appeared to be influenced by various conditions such as the proportion of T- and B-cell subsets, or B-cell proliferation rate, follicular center cells were constantly negative for vimentin.     

The utility of CD20 and CD43 in subclassification of low-grade B-cell lymphoma on paraffin sections.

To identify phenotypic differences among the low-grade lympho-proliferative disorders in paraffin-embedded tissue, we studied 49 cases. All 22 follicular small cleaved cell lymphomas (FSC) were CD43 negative and CD20 positive. In contrast, of 20 small lymphocytic lymphomas (SL), 90% were CD20 positive, 85% were CD43 positive, and 75% were positive for both. Of three lymphomas of intermediate differentiation (IDL), two were CD20 positive and two were CD43 positive. All four monocytoid B-cell lymphomas were positive for CD20 and 50% (two cases) were positive for CD43. Some 86% of 14 chronic lymphocytic leukemias (CLL) (on cytospins) were positive for CD43; all nine of the CLL studied for CD20 were positive and 89% (8/9) expressed both antibodies CD5 expression (on frozen sections or cytospin preparations) was compared to CD43 in 21 cases of SL and CLL. Some 77% were positive for both CD5 and CD20. All seven of the CD5-positive SL also expressed CD43. The antibody MT2 was also examined with the following results: FSC, 16/20 (80%) positive; SL, 18/19 (94%) positive; MBC, 3/3 positive; and ILL, 2/3 positive. All 56 cases tested were CD45RO (UCHL1) negative. We conclude that CD43 is expressed on most cases of low-grade lymphoproliferative disorders with the exception of FSC. Its pattern of expression seems similar to CD5; however, unlike CD5, CD43 can be studied in formalin-fixed tissue. MT2 is not helpful in distinguishing among these lesions.     

Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles.

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.     

Non-Hodgkin's lymphomas of nasal cavity and paranasal sinuses. An immunohistochemical study

The authors studied the immunophenotype of nine sinonasal lymphomas using a panel of monoclonal antibodies that react with fixed, paraffin-embedded material (EMA, CAM 5.2, CD45, CD37 [MB-1], MB-2, L-26, CDw75 [LN-1], CD45RA [4 KB-5], CD43 [MT-1], and CD45RO [UCHL-1]). There were seven men and two women, with a mean age of 64 years (range, 9-89 years) and median age of 56 years. Three tumors were limited to the nasal cavity, and the other six had multiple sites of involvement, including the nasal cavity (five), antrum (six), ethmoid (two), orbit (two), and hard palate (one). Histologically, one was a lymphoblastic lymphoma (LBL), one was small cleaved-cell lymphoma (SCCL), three were mixed-cell lymphomas (MCLs), and four were large cell lymphomas (LCLs). Four cases were T-cell lymphomas (one SCCL, three MCLs), four were B-cell neoplasms (four LCLs), and one was of uncertain lineage (LBL). Angioinvasion, coagulative necrosis, and epitheliotropism were seen in the T-cell lymphomas. Extranasal dissemination was seen in four cases: one LBL that involved the lymph nodes, skin, and testes 15 months after diagnosis; one B-LCL that involved the skin 9 months after diagnosis; and one B-LCL and one T-MCL that involved the gastric mucosa and lung simultaneously with nasal presentation. This study shows a higher predominance of B-cell lymphomas in the sinonasal region than previously reported in Oriental populations. However, the T:B ratio of these lymphomas is still greater than that observed for primary lymph node-based neoplasms.     

My4 antibody staining of non-Hodgkin's lymphomas.

The My4 antibody, one of a number of monoclonal antibodies that react with the CD14 antigen, was originally reported to weakly stain monocytes, macrophages, and granulocytes. However, recent studies have shown that the My4 antibody also stains normal peripheral blood B lymphocytes and some subtypes of B-cell non-Hodgkin's lymphoma. Thus, the authors have studied a large series of non-Hodgkin's lymphomas stained with the My4 antibody. In frozen sections of reactive lymph node biopsy specimens, the My4 antibody strongly stained mantle zone B lymphocytes and weakly reacted with dendritic reticulum cells and histiocytes. In a series of 245 non-Hodgkin's lymphomas, the My4 antibody stained 111 (45%) cases: 108 of 189 (57%) B-cell lymphomas, 3 of 50 (6%) T-cell lymphomas, and 0 of 6 null cell lymphomas. My4-positive B-cell lymphomas occurred in all histologic subtypes with the exception of small noncleaved cell lymphomas. Follicular lymphomas were most often My4 positive (82%). My4 antibody staining showed no correlation with Working Formulation grade. All three My4-positive T-cell lymphomas had a mature T-cell phenotype. Seventy-six of the 111 (68%) My4-positive lymphomas were also analyzed with at least one other anti-CD14 antibody, either Mo2 and/or Leu-M3. In all cases the antigens that react with Mo2 and Leu-M3 were not expressed. Thus, the staining of reactive and neoplastic B cells by My4 appears to be unique to this antibody and is not a feature of all anti-CD14 antibodies.     

Characterization of tumor-infiltrating T lymphocytes in B-cell lymphomas of mucosa-associated lymphoid tissue.

B-cell lymphomas of mucosa-associated lymphoid tissue invariably contain large numbers of reactive tumor-infiltrating T cells. In the stomach, these lymphomas develop secondary to Helicobacter pylori infection, and clinical and in vitro studies have shown that their growth depends on help provided by H. pylori-specific T cells. In this study we characterized tumor-infiltrating T cells in low- and high-grade B-cell lymphomas of mucosa-associated lymphoid tissue using immunohistochemistry. In most cases, CD4+ T cells dominated and almost all T cells were CD45RO+ memory cells. In 11 of 13 cases studied, the proliferating T cells were CD4+ and no proliferation was observed in the CD8+ subset. In low-grade lymphomas, between 7 and 24% of T cells expressed CD40L whereas no CD40L expression was observed in the majority of high-grade tumors. Examination of homing receptor profile showed that both alpha 4 beta 7 integrin+ and L-selectin+ T cells were present. Examination of T cell diversity by a panel of antibodies against different T-cell receptor V beta regions and by analysis of T-cell receptor genes using polymerase chain reaction suggested that the T cells in these tumors were polyclonal. These results show that low-grade B-cell lymphomas of mucosa-associated lymphoid tissue contain a significant population of activated helper T cells that may be important in supporting tumor growth.     

Monoclonal antibody phenotyping of B-cell non-Hodgkin's lymphomas. The Southeastern Cancer Study Group experience

This report describes the experience of the Southeastern Cancer Study Group (SECSG) with the frozen-section immunoperoxidase phenotyping of 162 cases of B-lineage non-Hodgkin's lymphomas. The authors used a panel of 13 different markers with varying degrees of specificity for B lymphocytes and B-cell neoplasms. All lymphomas were classified according to the International Working Formulation. Several antibodies, including anti-immunoglobulin, B1, Leu 12, and Leu 14 were B-cell-specific markers that were generally pan-reactive. Several other monoclonal antibodies, however, were selectively reactive with subpopulations of B-cell lymphomas. Three "selective-B" antigens (BA1, p24, CALLA) were found on about half of the B-cell lymphomas tested, while another three (HB31, transferrin receptor, C3d receptor) were found on about two-thirds of the lymphomas tested. Leu 1 reacted with 18% of the B-cell lymphomas, particularly the small lymphocytic lymphomas. When the reactivity of the monoclonal antibodies was compared with the histologic classification, two important points became apparent. First, with the large panel of antibodies, there was tremendous phenotypic diversity even among histologically similar tumors. Second, however, not all possible combinations of antibody phenotypes were encountered. That is, clusters of antigenic phenotypes were seen, and these phenotypes correlated to some degree with the histologic diagnosis of the tumor. Small lymphocytic and follicular lymphomas tended to be phenotypically distinct, although there was some overlap. Intermediate- and high-grade lymphomas were phenotypically more diverse. The more common phenotypes of lymphomas encountered could not be reconciled with any simple linear scheme of neoplastic B-cell differentiation.     

Immunohistological characterization of malignant lymphomas of the Waldeyer''s ring other than the nasopharynx

Among extranodal lymphomas, the Waldeyer's ring is the second most frequently involved site after the gastrointestinal tract. Fresh tissue from 23 consecutive cases of malignant lymphoma of the faucial tonsil, palate and base of tongue were studied histologically and with a panel of 25 monoclonal antibodies. Twenty cases were primary Waldeyer's ring lymphoma, and all were found to express B-cell phenotype. Most cases were classified as diffuse centroblastic lymphoma, polymorphic subtype, in which there were immunoblast-like, centrocyte-like and/or multilobated centroblasts. All except one case expressed all three B-cell lineage antigens CD19, CD20 and CD22, but they showed inconsistent expression of the B-cell antigens CD9 and CD24. Four cases lacked surface immunoglobulin. Six cases expressed interleukin-2 receptor, suggesting that they were composed of highly activated B-cells. Three cases represented relapse in the tonsil or tongue in patients with known malignant lymphoma in other sites; one case expressed T-cell and two cases B-cell phenotype (both of which also expressed interleukin-2 receptor). The clinical features and immunohistological findings suggest that Waldeyer's ring lymphomas, other than those of the nasopharynx, share some of the characteristics of 'mucosa-associated lymphoid tissue' lymphomas. In contrast, nasopharyngeal lymphomas are more related to nasal lymphomas, and are almost exclusively peripheral T-cell neoplasms.     

Immunocytochemical criteria in the differential diagnosis of malignant melanoma versus carcinoma, lymphoma and sarcoma in fine needle aspirates.

Monoclonal antibodies to keratin, vimentin, leukocyte common antigen (LCA) and S-100 protein have been used in fine needle aspirates of 35 metastatic malignant melanomas, 136 carcinomas, 35 sarcomas and 82 non-Hodgkin's lymphomas in search for immunocytochemical criteria useful in differential diagnosis of melanoma versus carcinoma, non-Hodgkin's lymphoma and sarcoma. All melanomas expressed vimentin and did not express keratin. Six of 14 melanomas contained S-100 protein. All carcinomas were keratin positive. Some were also vimentin positive. All sarcomas expressed vimentin. Synovial sarcomas were also keratin positive. All NHLs were vimentin positive, keratin negative. All NHLs except one expressed also LCA. It is concluded that keratin, vimentin and LCA are useful markers in differential diagnosis of malignant melanoma versus carcinoma and non-Hodgkin's lymphoma in fine needle aspirates when used together with morphologic and clinical data. However, in differential diagnosis of malignant melanoma and sarcoma these markers are of little use.     

Immunohistochemical and genetic analysis of Chinese nasal natural killer/T-cell lymphomas

Nasal natural killer/T-cell lymphoma (N-NK/T-L) is prevalent in China. To further characterize this neoplasm, 36 cases of N-NK/T-L from 304 cases of malignant lymphomas in the north China area were investigated by histopathology, immunophenotyping, and genomic analysis of c-kit, in comparison with 11 cases of B-cell lymphoma (BCL) at the same region and 5 cases of nodal peripheral T-cell lymphoma (PTCL) (unspecified). Histopathologically, N-NK/T-L was characterized by coagulative necrosis, inflammatory background, and angiodestructive growth pattern. In 36 cases of N-NK/T-L, 27 cases (75.0%) were stained for CD45RO and 25 (72.2%) for CD3epsilon. Thirty cases (83.3%) were positive for T-cell intracellular antigen-1, 22 (61.1%) for granzyme B, 18 (50.0%) for CD56, and 11 (30.6%) for CD30, whereas none was positive for CD117. All 5 cases of PTCL displayed positive staining for CD45RO and T-cell intracellular antigen-1, 3 cases for CD3epsilon, but only 1 case for granzyme B. All 11 BCLs presented positive staining for CD20 and CD79a but negative for other antibodies. A significant relationship was observed between neoplastic cells pleomorphism and granzyme B expression (P < .05). Despite the fact that all cases were negative for CD117 staining, genomic sequences of c-kit 11 and exon 17 sequencing showed that 8 (26%) of 31 cases N-NK/T-L proved to contain genomic mutations, including 4 cases in exon 11 and 4 in exon 17. For the control group, only 1 (9%) of 11 BCLs and 1 (20%) of 5 cases of PTCL were detected to harbor mutations in exon 11. All mutations detected in 3 groups were missense by base substitution, and codes 571, 572, and 821 were hot spots. The results suggested that, in addition to histological features and routine immunophenotyping, granzyme B expression should be a more reliable marker in correct diagnosis of N-NK/T-L, and genetic analysis of c-kit mutation should be helpful in the diagnosis of this tumor.     

Expression of the low Mr isoform of CD45 (CD45RO) in B-cell non-Hodgkin's lymphomas.

The CD45 antigen family consists of multiple molecular isoforms ranging from 180 to 220 relative molecular mass (Mr). The highest Mr isoforms are recognized by monoclonal antibodies (MoAbs) designated CD45RA, while those recognizing the low Mr isoform are designated CD45RO. About half of the T-cells in peripheral blood express CD45RA while the remainder express CD45RO. A switch from the high to the low Mr isoform of CD45 has been found in association with the process of T-cell stimulation and acquisition of "memory." B-cells normally express CD45RA, but not CD45RO. However, under stimulatory conditions, B-cells may be capable of undergoing an isoform switch and expressing CD45RO. The expression of this low Mr isoform of CD45 was investigated in lymphomas composed of monoclonal B-cells to determine if such a switch occurs in malignant B-cell populations. The vast majority (110/117 cases) of B-cell lymphomas expressed only CD45RA, while a very small number (7/117 cases) expressed CD45RO, but not CD45RA. There was no relationship between the CD45RO expression and the histologic subtype. The physiological significance of this unusual expression of CD45RO in a subpopulation of B-cell lymphomas is not clear. In that CD45RO, as defined by the MoAb UCHL 1, is typically used as a marker of T-cells in tissue sections, caution must be exercised in interpretation, since not all T-cells are reactive and some B-cell lymphomas are reactive.     

Use of monoclonal antibodies for the typing of malignant lymphomas in routinely processed biopsy samples

Eight antibodies (UCHL1 (CD45RO), MT1 (CD43), MT2 (CD45R), 4KB5 (CD45R), MB1 (CD45R), MB2, L26 (CD20) and LN1 (CDw75)) have been examined for reactivity with routine specimens of normal and hyperplastic lymphoid organs (n = 6), non-Hodgkin's lymphomas (n = 62), Hodgkin's disease (n = 27) and non-lymphoid malignancies (n = 9). In normal and hyperplastic lymphoid organs, UCHL1 and MT1 stained predominantly T cells; 4KB5, MB1, MB2, L26 and LN1 stained predominantly B cells; and MT2 reacted with a subset of B and T cells. The lineage of the neoplastic cells was correctly identified in 24 of 28 (86%) peripheral T-cell lymphomas; and in 31 of 35 (88%) B-cell malignancies. In two cases of lymphocyte-predominant Hodgkin's disease, the Hodgkin's and Reed-Sternberg (H&RS) cells were 4KB5+, L26+ and/or LN1+. The H&Rs cells in nodular sclerosis and mixed cellularity Hodgkin's disease were positive with 4KB5 in 17 of 25 cases. Antibodies UCHL1, MT1, MB1, MB2, L26 and LN1 also labelled some H&RS cells, but in a much smaller proportion of the cases. In three of nine non-lymphoid neoplasms, UCHL1 and MB2 showed a staining of the neoplastic cells, but the staining was cytoplasmic rather than membrane-associated. The remaining antibodies were unreactive with the non-lymphoid malignancies. It is concluded that many non-Hodgkin's lymphomas can be typed in routine specimens, and that antibodies UCHL1, MT1, L26 and LN1 are especially useful in this respect. The antibodies do not provide a means of distinguishing between non-Hodgkin's lymphomas and Hodgkin's disease.     

Dendritic reticulum cells and immunophenotype in aspiration biopsies of lymph nodes. Value in the subclassification of non-Hodgkin's lymphomas

Twenty-seven lymph node aspirates were identified for which histologic confirmation of non-Hodgkin's lymphoma was subsequently obtained. Fifteen aspirates interpreted as reactive hyperplasia were also examined. All aspirates were studied by immunoperoxidase on cytospin preparations with the use of antibodies DRC1, kappa, lambda, CD3, CD5, and CD20. The follicular lymphomas could not be identified reliably by morphologic examination of aspirate smears. Clusters of DRC1-positive (DRC1+) cells were present in seven of seven follicular lymphomas, one of one mantle zone lymphoma, and one of seven small lymphocytic lymphomas. Rare DRC1+ cells were present in one of one diffuse mixed and one of seven large cell lymphomas. One lymphoblastic, one Burkitt's, and two diffuse small cleaved cell lymphomas had no DRC1+ cells. None of the seven follicular lymphomas was CD5 positive (CD5+), whereas five of the seven small lymphocytic lymphomas were CD5+. Conversely, all seven follicular lymphomas were CD20-positive (CD20+), but only one of seven small lymphocytic lymphomas was CD20+. Nineteen of the lymphomas, including all 7 of the follicular lymphomas, were either kappa or lambda positive. The other eight lymphomas were T-cell (1), B-cell (1), true histiocytic (1), or "null" cell (5). The reactive aspirates had both kappa- and lambda-positive B-cells. Seven of the 15 had clusters of DRC1+ cells. To further evaluate these antibodies, the authors studied 29 additional, surgically biopsied, non-Hodgkin's lymphomas that had not been aspirated. Similar results were obtained, except that three of five diffuse small cleaved cell lymphomas had DRC1+ cells. DRC1, in conjunction with antibodies to CD5, CD20, kappa, and lambda, helps to distinguish follicular lymphoma from small lymphocytic lymphoma. DRC1 is not useful in separating reactive hyperplasia from follicular lymphoma.     

Primary natural killer/T-cell lymphomas of the oral cavity are aggressive neoplasms

Thirty-four cases of primary non-Hodgkin’s lymphoma of the oral cavity were investigated for their clinical findings, histopathological features, immunophenotypes and association with Epstein-Barr virus (EBV). Four cases (12%) were natural killer/T-cell lymphomas, 3 (9%) were T-cell lymphomas and 27 (79%) were B-cell lymphomas. Compared with T- and B-cell lymphomas, NK/T-cell lymphomas had a male predominance (M:F 4:0), and most presented as ulceration of the palate and/or maxillary gingiva. Histologically, the lesions showed diffuse infiltration of medium-sized or large lymphoid tumour cells. Angiocentricity and/or angioinvasion were found in all 4 cases. The immunophenotypes of the NK/T-cell lymphomas were CD3+, CD43+, CD45RO+, CD56+ and TIA-1+. EBV was detected in 2 NK/T-cell lymphomas by in situ hybridization (ISH) and polymerase chain reaction (PCR) methods, and was not detected in T- and B-cell lymphomas. The survival rate of patients with NK/T-cell lymphoma was zero, but the survival rates for patients with T-cell and B-cell lymphomas were 67% and 38%, respectively. It appears that NK/T-cell lymphomas of the oral cavity have a predilection for originating in the palate and maxillary gingiva and are aggressive neoplasms. EBV positivity might be associated with more aggressive behaviour. Received: 21 January 1999 / Accepted: 14 April 1999     

Pulmonary B-cell non-Hodgkin's lymphomas. The value of immunohistochemistry and gene analysis in diagnosis

We reviewed 45 pulmonary B-cell non-Hodgkin's lymphomas to determine whether their morphology and immunohistochemical features were those of lymphomas arising from mucosa-associated lymphoid tissue (MALT), as described in other sites. The polymerase chain reaction was used to provide further information on clonality. We found that these lymphomas infiltrate the pulmonary interstitium along bronchovascular bundles and interlobular septa, subsequently spilling out into airspaces and finally destroying the alveolar architecture of the lung. Central hyaline sclerosis and vascular infiltration were common features. All lymphomas stained CD20 positive and were accompanied by variable numbers of reactive CD3 positive T-cells. Cytokeratin staining with CAM 5.2 was useful in identifying lymphoepithelial lesions. CD21 staining of follicular dendritic cells revealed germinal centres where they were not recognizable on H & E staining. The polymerase chain reaction was performed on paraffin tissue from 28 patients. Twenty were low grade, of which 12 showed a clonal band and eight stiowed a polyclonal smear pattern. Eight were high grade, of which one revealed a clonal band. Three produced polyclonal smear patterns and four cases were inadequate samples. In one patient who had lymphoma at a second extranodal site, identical bands were identified, evidence for 'homing' of lymphoid cells towards mucosal epithelium.     

Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease.

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.     

CD23 expression in mediastinal large B-cell lymphomas

AIMS: Mediastinal large B-cell lymphoma (MLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) in the WHO classification with peculiar features, such as female prevalence, young patient age and bulky presentation. It shows a B-cell phenotype with variable expression of surface immunoglobulin, negative CD21 and CD10 and positive CD30 in a large number of cases. An origin from activated thymic B cells has been suggested in several studies. A subpopulation of large, dendritic cells (asteroid cells) strongly expressing CD23 has been identified amongst thymic B cells and these could represent the normal cellular counterpart for this type of primary mediastinal large cell lymphoma. METHODS AND RESULTS: To explore this possibility, we immunostained 24 cases of primary mediastinal lymphomas and 100 cases of non-mediastinal, nodal and extranodal, DLBCLs for CD23 in routinely processed paraffin-embedded tissues. CONCLUSIONS: Our results show that a vast majority (70%) of mediastinal lymphomas strongly express CD23 whilst the same antigen is expressed in only 15% of non-mediastinal nodal DLBCLs and 9% of non-mediastinal extranodal DLBCLs. These results support the hypothesis that most cases of MLBCL arise from activated dendritic thymic B cells. We also suggest that CD23 should be included in the panel of antibodies currently used to characterize this subtype of DLBCL.     

EBV in situ hybridization study for non-Hodgkin's lymphomas.

Epstein-Barr virus(EBV) has been implicated in the pathogenesis of B-lymphoproliferative disorders, T-cell lymphomas and Hodgkin''s disease. In this report, we performed an in situ hybridization study on EBV genome in 10 cases of nasal non-Hodgkin''s lymphoma(NHL), 20 cases of Waldeyer''s ring(WR) NHL, and 20 cases of nodal NHLs to document EBV association with lymphomas in Koreans. For immunophenotyping, monoclonal antibodies for CD 20, MB 2, CD 45Ro & CD 43 were used. For in situ hybridization study, EBV DNA probe for Bam HI ''V'' fragment and EBV RNA probe for EBER and BHLF were used. Twenty two cases(44%) of malignant lymphomas were positive for EBV genome. Generally, T-cell lymphomas showed a higher positive rate(61%) than B-cell lymphomas(24%). Among T-cell lymphomas, nasal lymphomas showed a higher positive rate(80%) than WR(50%) or nodal lymphomas(50%). Of 22 EBV genome positive cases, 10 cases were positive for EBER, 10 cases for BHLF, and 2 cases for both EBER and BHLF. The histologic types by Working Formulation(WF) were not correlated with EBV genome positive rate, whereas lymphomas showing the histologic spectrum of polymorphic reticulosis(PR) showed a higher positive rate(65%) than lymphomas without PR-like features(40%). These results indicate that nasal T-cell lymphomas with the histologic spectrum of PR are strongly associated with EBV and that the anatomic site may be an important factor in this association.