Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.     

B- and T-cell subsets in follicular centroblastic/centrocytic (cleaved follicular center cell) lymphoma: an immunohistologic analysis of 26 lymph nodes and three spleens

Follicular centroblastic/centrocytic (CB/cc/F), or cleaved follicular center cell, lymphomas are known to contain admixtures of B cells and, often, numerous T cells. To analyze the presence and distribution of B and T cells and their subsets in CB/cc/F lymphomas, 26 lymph nodes and three spleens (from 24 patients) were studied with a panel of monoclonal antibodies and peanut lectin by the avidin-biotin immunoperoxidase technique on frozen sections. Immunoglobulin studies revealed monoclonal neoplastic follicles in most cases, although cells of the nondominant light chain were occasionally present. Rarely, the follicles showed both kappa and lambda light chains or were immunoglobulin-negative. Although monoclonal mantles were observed in only one case, more than half of the nodes demonstrated monoclonal interfollicular infiltrates. In most cases the phenotype of the follicular cells was similar to that of the predominant cells in the normal follicles. Interfollicular lymphomatous cells had variable phenotypes that, unlike the normal situation, sometimes resembled those in the follicles. Phenotypic variation was present within single neoplastic clones and sometimes suggested more mantle-like differentiation. Phenotypic changes were also observed in repeat biopsies. T cells, usually predominantly of the T-helper phenotype, were present in variable numbers in all cases. Although present in the neoplastic follicles, they were usually more common in the interfollicular areas. Six nodes and two spleens had definite rims composed predominantly of T cells around neoplastic follicles. Apparently "activated" (Tac-positive) T cells were often present and showed accentuation around the follicles in some cases. Thus, CB/cc/F lymphoma is a malignant lymphoma that closely resembles follicular hyperplasia but that also has distinctive features.     

CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease.

Although CD40 has been extensively studied in B- and T-cell non-Hodgkin's lymphomas (NHLs)/leukemias, and more recently in Hodgkin's disease (HD), little is known about the expression of its ligand (CD40L) in lymphoproliferative disorders other than T-cell NHLs/leukemias. A series of 121 lymphoma/leukemia samples, including 35 cases of HD, 34 T-cell and 39 B-cells NHLs, 2 cases of adult T-cell leukemia/lymphoma, and 11 cases of T-cell acute lymphoblastic leukemia, were evaluated for CD40L expression by immunostaining of frozen tissue sections and flow cytometry with the anti-CD40L monoclonal antibody M90. CD40L was constitutively expressed by neoplastic cells in 15 of 36 (42%) T-cell NHLs/adult T-cell leukemia/lymphomas, almost invariably those displaying the CD4+/CD8- phenotype, whereas no CD40L-expressing tumor cells could be found in B-cell NHL and HD. Among T-cell acute lymphoblastic leukemias, CD40L was detected only on 2 cases displaying a stem-cell-like phenotype. In follicular B-cell lymphomas a large number of CD40L-expressing CD3+/CD4+ T lymphocytes were found admixed with tumor cells within the neoplastic follicles and in their surrounding areas. In the nonfollicular B-cell lymphomas, CD40L-positive CD3+/CD4+ T lymphocytes were few or absent. In all HD subtypes other than the nodular lymphocytic predominance, CD40L-expressing CD3+/CD4+ T lymphocytes were numerous in the HD-involved areas and were mainly located in close proximity to the Reed-Sternberg cells. Our data indicate that in human lymphomas CD40L is preferentially expressed by a restricted subset of T-cell lymphomas, mostly with CD4 immunophenotype. Finally, we have provided morphological evidence that CD40L may play an important role in the cell contact-dependent interaction of tumor B-cells (CD40+) within the neoplastic follicles or Reed-Sternberg cells (CD40+) in HD-involved areas and the microenvironmental CD3+/CD4+/CD40L+ T lymphocytes.     

IMMUNOHISTOCHEMICAL STUDIES ON B CELL LYMPHOMAS WITH SPECIAL REFERENCE TO T CELL INFILTRATION AND ITS SIGNIFICANCE AS A PROGNOSTIC FACTOR

Twenty-eight cases of B cell lymphoma were studied immunohistochemically utilizing a panel of monoclonal antibodies. Of 27 cases tested, 26 were B-1-positive and 22 of 24 cases were HLA-DR positive. There were eight BA-1-positive cases, including one follicular lymphoma, and 10 J-5-positive cases including five diffuse large cell lymphomas. Some of the J-5-positive diffuse large cell lymphomas were considered to be of follicular center cell origin. Infiltration and distribution of non-neoplastic T cell subsets, BA-1-positive B cells, dendritic reticulum cells, Langerhans cells and HNK cells showed close similarity between the structure of follicular lymphomas and that of the reactive follicles. Such similarity to the normal counterpart structure was less apparent in diffuse lymphomas, especially in the large cell type. These findings were interpreted to be an expression of different degrees of neoplastic deviation. There was evidence to suggest that, regardless of the histological classification, a large number of infiltrating non-neoplastic T cells was related to good prognosis. ACT A PATHOL JPN 38: 47–58, 1988.     

Follicular large cell lymphoma. An immunophenotype study.

The authors investigated 17 cases of follicular large cell lymphoma using monoclonal antibodies applied to frozen sections. The neoplastic cells in 11 cases (65%) showed evidence of immunoglobulin expression similar to the reported percentage of immunoglobulin expressing diffuse large cell lymphomas and lower than seen in low grade follicular lymphomas. All cases showed expression of the B lineage markers T015, B1, and 4G7, and HLA-DR. CALLA was present in all but 1 case, similar to that reported for follicular lymphomas, and much higher than reported for diffuse large cell lymphoma. Approximately one-half of the cases showed weak expression of Tac, 5 cases expressed B2 (C3d), and 3 cases expressed T05 (C3b). Variable expression was seen for the Ki-67 antigen. A CR4/23+, B2+, T05+ dendritic population was identified in all cases. An interfollicular host T-cell infiltrate was noted, mainly phenotypic helper cells. This study demonstrates that follicular large cell lymphoma has immunologic similarities to both diffuse large cell lymphoma and the low grade follicular lymphomas.     

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 AlLD- 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.     

Intratumoral T lymphocytes from small cleaved follicular center cell lymphomas show unrestricted T-cell receptor alpha-chain variable region gene usage.

The relationship between the reactive T cells and neoplastic B cells of follicular center cell lymphomas is unclear. It is not known whether the T cells are recruited nonspecifically by the neoplastic B cells or are responding through the T-cell antigen receptor (TCR), to tumor-related antigen(s). This question was addressed by polymerase chain reaction analysis of TCR alpha chain variable (V) region gene expression in intratumoral T lymphocytes from three cases of small cleaved follicular center cell lymphoma. In all three cases studied, the tumor-associated T cells showed unrestricted expression of all 18 alpha-chain V region genes. These findings imply that the T cells admixed with the neoplastic B cells of small cleaved follicular center cell lymphomas are not recruited based on TCR recognition of a single or limited number of tumor-related antigens.     

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.     

Expression of a T-cell antigen (Leu-1) by B-cell lymphomas.

The Leu-1 antigen has been defined by monoclonal antibodies (L17F12, T101, and OKT-1) as a pan-T-cell antigen present on all human peripheral blood T cells and thymocytes. Although originally thought to be confined to T-cell lineage, some cases of B-cell chronic lymphocytic leukemia have been found to react with these antibodies. Using a frozen section immunoperoxidase staining technique, 125 lymphomas with B-cell differentiation were examined for the presence of Leu-1 antigen. Leu-1 antigen was detected in 4 of 11 cases of diffuse small lymphocytic lymphoma (Rappaport''s DWDL) and 3 of 4 cases of diffuse intermediate lymphocytic lymphoma. Follicular lymphomas less often expressed this antigen--2 of 29 cases of the small cleaved cell type (Rappaport''s NPDL), none of 13 cases of mixed small cleaved and large cell type (Rappaport''s NM), and 1 of 6 cases of large cell type (Rappaport''s NH). Diffuse lymphomas of presumed follicular center cell origin expressed this antigen infrequently as well--1 of 3 cases of the small cleaved cell type (Rappaport''s DPDL), neither of 2 cases of mixed small cleaved and large cell type (Rappaport''s DM), and 3 of 43 of large cell type (cleaved/noncleaved) (Rappaport''s DH). Diffuse large cell, immunoblastic lymphoma of B-cell type expressed Leu-1 in 1 of 6 cases. None of the 3 cases of Burkitt''s lymphoma or of the three small noncleaved non-Burkitt''s lymphoma (Rappaport''s undifferentiated) expressed detectable Leu-1. B-lymphoblastic lymphoma (1 case) and B-cell unclassified lymphoma (1 case) both failed to express detectable Leu-1. It appears that this pan-T-cell antigen is mainly found on those B-cell lymphomas composed predominantly of small lymphocytes. This finding may be of use in distinguishing extranodal neoplastic collections of small lymphocytes from lymphocytic hyperplasias.     

Immunohistologic characterization of two malignant lymphomas of germinal center type (centroblastic/centrocytic and centrocytic) with monoclonal antibodies. Follicular and diffuse lymphomas of small-cleaved-cell type are related but distinct entities

The relationship between follicular lymphomas and diffuse lymphomas of small-cleaved-cell type was investigated with the use of a panel of antibodies against B-cell differentiation antigens. Follicular lymphomas, regardless of histologic subtype, were immunologically homogeneous: Ig+ B1+ B2+ CALLA+ Ia+. Two cases were Ig-negative, and 4 were CALLA-negative. Diffuse small-cleaved-cell (centrocytic) lymphomas were more heterogeneous. The majority were Ig+ B1+ B2+ Ia+ T1+ CALLA-. A minority were B2-negative, T1-negative, or CALLA-positive. An increased frequency of Ig heavy chain class switching and loss of T1 antigen suggest that follicular lymphomas are at a later stage of differentiation than most centrocytic lymphomas. The differences in immunologic phenotype provide further justification for a classification that distinguishes between follicular and diffuse lymphomas of small-cleaved-cell types. The expression of Ig, Ia, B1, and B2 on neoplastic follicular center cells correlates with expression of these antigens on normal B cells. In addition, anti-B2 appears to stain a nonlymphoid dendritic cell present in normal germinal centers and in both follicular and diffuse germinal center cell lymphomas in this study. In follicular lymphomas, the dendritic pattern was similar to that of normal follicles, while in centrocytic lymphomas a more irregular dendritic pattern was seen. Dendritic staining was seen in both nodal and extranodal lymphomas, suggesting that these nonlymphoid cells either migrate with neoplastic B cells or are present in a variety of normal tissues.     

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 immunoperox-idase 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.     

Common acute lymphoblastic leukemia-associated antigen (CALLA)-positive B cell lymphoma

We analyzed the expression of common acute lymphoblastic leukemia-associated antigen (CALLA) in 134 cases of non-Hodgkin's lymphoma of the B cell type using an immunohistochemical method. The incidence of CALLA expression in B cell lymphomas was higher in follicular lymphomas (29%) than in diffuse lymphomas (15%). Malignant lymphoma (ML), follicular small cleaved cell (FSC) according to the histologic type, showed a considerably high incidence of CALLA (43%), whereas ML, diffuse small cleaved cell (DSC) displayed a very low incidence (5%). These findings suggest the possibility that these two morphologically similar lymphomas may be derived from distinct populations of B cells [CALLA+-germinal center (GC) cells, CALLA- -germinal center (GC) cells or mantle zone (MZ) cells]. In addition, one case of DSC expressed surface immunoglobulin D (SIgD) and alkaline phosphatase (ALPase) as well as CALLA. This indicates that CALLA-positive small cleaved cell lymphoma expressing SIgD or ALPase may represent neoplastic proliferation of CALLA-positive MZ cells of secondary follicles in lymph nodes.     

Monoclonal antibody 4C7 recognizes an endothelial basement membrane component that is selectively expressed in capillaries of lymphoid follicles

In order to define compartment-related structures within the extracellular matrix of human lymphoid organs, monoclonal antibodies (MAbs) were generated by immunizing mice with stromal fragments of human tonsils. One MAb (4C7) was selected which recognized an endothelial basal membrane component that is selectively expressed in capillaries of lymphoid follicles. The epitope was also present in follicles within chronically inflamed synovial membrane and in a hyperplastic thymus of a patient with myasthenia gravis. B-cell non-Hodgkin's lymphomas with a follicular growth pattern expressed the antigen in neoplastic follicles, whereas diffuse growing lymphomas lacked the antigen. The restricted distribution pattern suggests involvement of the 4C7-defined antigen in the organization of the follicular compartment within human lymphoid tissue.     

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.     

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.     

Common Acute Lymphoblastic Leukemia-associated Antigen (CALLA)-positive B cell lymphoma

We analyzed the expression of common acute lymphoblastic leukemia associated antigen (CALLA) in 134 cases of non Hodgkin's lymphoma of the B cell type using an immunohistochemical method. The incidence of CALLA expression in B cell lymphomas was higher in follicular lymphomas (29%) than in diffuse lymphomas (15%). Malignant lymphoma (ML), follicular small cleaved cell (FSC) according to the histologic type, showed a considerably high incidence of CALLA (43%), whereas ML, diffuse small cleaved cell (DSC) displayed a very low incidence (5%). These findings suggest the possibility that these two morphologically similar lymphomas may be derived from distinct populations of B cells [CALLA⁺-germinal center (GC) cells, CALLA⁻-germinal center (GC) cells or mantle zone (MZ) cells]. In addition, one case of DSC expressed surface immunoglobulin D (SlgD) and alkaline phosphatase (ALPase) as well as CALLA. This indicates that CALLA-positive small cleaved cell lymphoma expressing SlgD or ALPase may represent neoplastic proliferation of CALLA positive MZ cells of secondary follicles in lymph nodes. Acta Pathol. Jpn. 39: 503∼508, 1989.     

Paraffin-immunohistochemical analysis of 226 non-Hodgkin's malignant lymphomas in the endemic area of human T-cell leukemia virus type 1

A study was conducted to evaluate the usefulness of paraffin-immunohistochemistry for histopathological classification of non-Hodgkin's malignant lymphomas (NHML). the phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B-cell lymphomas (B-ML) and 132 T-cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB-1, Mx-pan B, L26, LN-1, LN-2 and anti-immunoglobulin light chain antibodies characterized each subtype of B-MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B-MLs (82.8%). B-cell chronic lymphocytic leukemia (B-CLL) was labeled most frequently by MB-1. MzML was characterized by reactivity of lymphoma cells with LN-2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN-1 and LN-2, although a small number of proliferating cells were labeled by LN-1 in B-CLL, MzML and the immunocytoma lymphoplasmacytic/cytoid variant. MT-1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T-cell pleomorphic lymphomas of Suchi and Lennert, the adult T-cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p less than 0.05) with anti-phosphokinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN-2 and Leu M1. In T-zone lymphomas without hyperplastic follicles, angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B-cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T-cell leukemia virus type 1 is endemic.     

The Leukocyte Semaphorin CD100 Is Expressed in Most T-Cell, but Few B-Cell, Non-Hodgkin’s Lymphomas

The 150-kd transmembrane protein CD100 is the first semaphorin protein shown to be expressed in lymphoid tissue. CD100 is present in the interfollicular T cell zones and is also expressed by B cells in the germinal centers of secondary lymphoid follicles, but not in the mantle zones. The CD100 molecule was recently cloned, and CD100 transfectants were shown to induce homotypic aggregation of human B cells and improve their viability in vitro, suggesting that CD100 may play a role in lymphocyte aggregation and germinal center formation. We studied the expression of CD100 in 138 clinical cases representing a range of lymphoproliferative disorders, to determine whether this molecule is expressed in these neoplastic processes. In general, we found CD100 expression to be common in peripheral T-cell non-Hodgkin’s lymphomas but rare in B-cell non-Hodgkin’s lymphomas. CD100 expression was not detectable in low-grade B-cell non-Hodgkin’s lymphomas, including cases of small lymphocytic lymphoma (18 cases), marginal zone lymphoma (10 cases), and mantle cell lymphoma (10 cases), as might be expected for these neoplasms that are not of follicular center cell origin. Surprisingly, we found that the vast majority of follicular lymphomas (37 of 40 cases) as well as diffuse large-cell lymphomas of B-cell type (35 cases) did not express CD100. The neoplastic cells in 3 of 11 cases of predominantly large-cell-type follicular lymphoma did express CD100. In contrast, all five cases of high-grade, small non-cleaved (Burkitt-like) B-cell lymphoma were immunoreactive for CD100 expression, as were 18 of 20 cases (90%) of malignant T cell neoplasms. Northern blot analysis of CD100 expression correlated with immunohistochemical findings. Absence of expression of CD100 by neoplastic follicular center B cells is a common feature in follicular lymphomas, but expression of CD100 by T cells is maintained in T-cell lymphoproliferative disorders.     

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.     

The dendritic reticulum cell pattern in B cell lymphomas of the small cleaved, mixed, and large cell types: an immunohistochemical study of 48 cases

An immunohistochemical study was designed to study the dendritic reticulum cell (DRC) patterns in 48 cases of B cell non-Hodgkin's lymphomas of the small cleaved, mixed, and large cell types, both follicular (20 cases) and diffuse (28 cases), in order to evaluate the possible influence of DRCs on homing and the differentiation of neoplastic B cells. Three DRC patterns were observed. In the follicular lymphomas, DRCs constituted nodular networks of variable density. In the diffuse lymphomas, DRCs were present either as isolated and scattered cells (17 cases) or constituted irregular meshworks of variable sizes (11 cases). These DRC patterns correlate with B cell immunophenotypes. Like follicular lymphomas, and unlike diffuse lymphomas without DRC networks, diffuse lymphomas with DRC networks constantly expressed the pan B antigens and one marker characteristic of normal germinal center cells, CD21 antigen, the C3d receptor. The finding of organized DRC networks in a significant number of diffuse lymphomas does not substantiate the hypothesis that DRCs may play a role in the homing of neoplastic B cells. The correlations observed between DRC patterns and B cell immunophenotypes suggest that the persistence and/or the development of DRC networks within follicular center cell-type lymphomas are related to the degree of functional differentiation of neoplastic B cells.