Adhesion receptor profile of thymic B-cell lymphoma.

Primary thymic B-cell lymphoma is clinically characterized by aleukemic, highly aggressive local growth, infrequent distant metastasis, and infrequent secondary lymph node involvement. VLA-1 to VLA-6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. VLA-4 additionally binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion. Other molecules involved in cell/cell adhesion are LFA-1 (CD11a/CD18), Mac-1(CD11b/CD18) and their ligand ICAM-1 (CD54), p150,95 (CD11c/CD18), LFA-3 (CD58), CD44, and LECAM-1. Twenty-three tumors, together with normal lymphoid tissue, were immunohistochemically examined to investigate the expression pattern of these molecules in thymic B-cell lymphomas and in their putative normal counterparts, namely thymic medullary B cells. Thymic B-cell lymphomas consistently lacked VLA-1,-2,-3,-5,-6, and CD11b, expressed ICAM-1 in 21 of 23 cases but were heterogenous for VLA-4, LFA-1, CD11c, LFA-3, CD44, and LECAM-1. Presence of LFA-1 correlated with LFA-3 expression (P = 0.029). The receptor profile of thymic B-cell lymphoma was reminiscent of the expressional status of normal thymic medullary B cells in some aspects but deviated in others: Assuming that, in terms of differentiation, thymic B-cell lymphoma is related to the asteroid variant of thymic medullary B cells, a propensity to down-regulate/lose VLA-4, CD11a, CD44, and LECAM-1 would have to be supposed in conjunction with a tendency to overexpress ICAM-1 and LFA-3. Sclerosis as an inconsistent phenomenon in thymic B-cell lymphoma was absent in 8 of 23 tumors. Presence of sclerosis correlated with LECAM-1 expression of the tumor cells (P = 0.038). Recent studies suggest that a locally growing/aleukemic phenotype of a B-cell neoplasia might be determined by the phenotype VLAs-, LFA-1+, ICAM-1+, CD44-, and LECAM-1-. Our data corroborate this view.     

Primary non-Hodgkin's lymphoma of the intestine: a morphological, immunohistochemical and clinical study of 31 Chinese cases

Thirty-one cases of primary non-Hodgkin's lymphoma of the intestine were investigated. Twenty-one were of B-cell and 10 of T-cell origin. The B-cell lymphomas comprised two cases of low-grade B-cell lymphoma of mucosaassociated lymphoid tissue (MALT), one of centroblastic/centrocytic type, three of high-grade B-cell lymphoma coexisting with a low-grade B-cell lymphoma of MALT, nine of centroblastic, three of immunoblastic and three of Burkitt type. Of the T-cell lymphomas, eight were of pleomorphic medium-to large-sized cell type and two of large cell anaplastic type. All the B-cell lymphomas expressed CD20 (L26) and/or Ki-B5; in six there was monotypic immunoglobulin light chain restriction. Membrane positivity for CD45RO (UCHL1) was observed in the 10 cases of T-cell lymphoma, but the tumour cells did not express monocyte-macrophage markers. Clinically, the patients with T-cell lymphomas were usually young males with constitutional symptoms and their prognosis was significantly worse than those of patients with intestinal B-cell lymphoma.     

Morphological characteristics of malignant T-cell lymphomas in baboons

Fifteen cases of generalized peripheral T-cell non-Hodgkin's lymphoma in baboons were phenotyped immunologically and morphologically. Using the updated Kiel classification the cases included low-grade and high-grade lymphomas and low-grade lymphomas that had transformed into high-grade lymphomas. In the low-grade group there were seven cases of lymphocytic type, partly corresponding to chronic lymphocytic leukaemia of T type and to T-zone lymphoma in man. In addition there were four cases of prolymphocytic-lymphocytic type, which show large nodules (proliferation centres) and which have no equivalent in the Kiel classification. In four cases there was a progression to an immunoblastic lymphoma and in one case to a large cell anaplastic lymphoma. In addition, three cases of large cell anaplastic lymphoma without a low-grade component were found. Both the immunoblastic lymphomas and the large cell anaplastic lymphomas corresponded well with the same types in the Kiel classification. The cases of large cell anaplastic lymphoma were also CD30 positive. Most of these lymphomas were CD4 positive, but there were rare cases that were either CD8 positive, showed both CD4 and CD8 positivity or had lost both antigens. Antigens associated with cell activation were often revealed. All but one baboon had antibodies in the blood against the retrovirus STLV-1 (simian T-cell leukaemia virus 1), which is very similar to human T-cell leukaemia virus 1 (HTLV-1) in man. Despite this virological resemblance, the morphology of these T-cell lymphomas does not resemble that of the HTLV-1-positive Japanese T-cell lymphomas but is like that of the HTLV-1-negative European cases.     

Analysis of adhesion molecules in Ki-1 anaplastic large-cell lymphoma

We analysed the expression of adhesion molecules on lymphoma cells in 13 patients with Ki-1 (CD30)-positive anaplastic large-cell lymphoma (Ki-1 ALCL; lymph nodes in 6, extranodal tumours in 6, and both lymph nodes and bone in 1). Very late activation antigen (VLA)-4 (CD49d) and Hermes lymph node homing receptor (CD44) were constantly expressed in all specimens, and intercellular adhesion molecule-1 (ICAM-1; CD54) was frequently expressed in 10 of the 14 specimens. The expressions of lymphocyte function-associated antigen-1 (LFA-1; CD11a) and VLA-5 (CD49e) occurred in 5 of 14 and 4 of 14 specimens, respectively. The expressions of VLA-2 (CD49b), endothelial leukocyte adhesion molecule-1, neural cell adhesion molecule (CD56) and E cadherin were always lacking. VLA-6 (CD49f) was absent in all but one specimen. The expression of VLA-5 on Ki-1 ALCL was high in subcutis-cutis but absent in lymph nodes. Furthermore, in one case, LFA-1 was detected in the primary lymph node, but was absent in a metastatic bone lesion. These results suggest that the expression of ICAM-1 is partially responsible for aleukemic behaviour in Ki-1 ALCL and, moreover, that the Ki-1 ALCL cells modify their expression of adhesion molecules at each of the involved organs.     

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in highgrade non-Hodgkin''s lymphoma

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.     

Editorial

The family of CD44 glycoproteins has diverse functions in cell–cell and cell–matrix interactions. The standard form of CD44 is of importance in the dissemination of lymphoma, whereas the clinical significance of the variant exon v6-containing forms of CD44 (CD44v6) is not known. The expression of different forms of CD44 was investigated by using antibodies against the constant part of CD44 (CD44c) and CD44v6 in 56 primary and 17 recurrent non-Hodgkin's lymphomas and correlated with several clinicopathological parameters and with prognosis. Fifty-seven per cent of the primary non-Hodgkin's lymphomas expressed CD44v6 and 73 per cent expressed the constant epitope. Expression of both CD44c and CD44v6 was associated with low histological grade of malignancy. CD44c expression was associated with a low cellular proliferation rate as assessed by DNA flow cytometry. Of several factors tested, high expression of the variant from v6 was the only factor that was associated with unfavourable recurrence-free survival (P=0·04). We conclude that CD44v6 is associated with a low histological grade, but, on the other hand, with an unfavourable outcome, which suggests that the combination of CD44v6 and histological grading may form a particularly strong prognostic parameter in non-Hodgkin's lymphoma.     

Primary malignant lymphomas of the central nervous system: a histological and immunohistological study of 12 cases

Paraffin sections of surgical and autopsy material from 12 cases of primary non-Hodgkin's lymphomas of the central nervous system were examined for histopathological diagnosis and for the demonstration of cytoplasmic immunoglobulins. According to the Kiel classification, there were five cases of lymphoplasmacytoid polymorphous lymphoma, five of immunoblastic lymphoma, one of lymphoblastic lymphoma of convoluted cell type. There was also one of the recently described multilobated lymphoma. An immunohistological study of light and heavy chains by peroxidase-antiperoxidase (PAP) technique and avidin-biotin complex (ABC)technique was performed. Intracellular immunoglobulins were demonstrated in seven cases: four cases were classified as immunoblastic lymphomas and three cases as lymphoplasmacytoid lymphomas. Negative immunoglobulin staining was observed in five cases: two lymphoplasmacytoid lymphomas, one immunoblastic, one lymphoblastic of convoluted cell type and one multilobated. A 'monoclonal' pattern of immunoglobulin staining was detected in six cases. One case, classified as immunoblastic lymphoma, showed 'bitypic' staining for kappa and lambda chains. It was concluded that primary CNS non-Hodgkin's lymphomas of the present series showed morphological and immunohistological features similar to those of malignant lymphomas arising in extraneural sites. In particular, the presence in our series of a multilobated lymphoma, as a primary CNS tumour, is emphasized.     

Role of beta 1-integrins in epidermotropism of malignant T cells.

To better understand the molecular mechanisms of epidermotropism, we immunohistochemically analyzed the expression pattern of adhesion molecules belonging to the integrin and immunoglobulin superfamilies in cases of mycosis fungoides (MF) (n = 15), pleomorphic T cell lymphoma (n = 10), and high-grade T cell lymphoma (n = 7). The cutaneous T cell lymphomas (CTCLs) investigated were categorized into cases with or without epidermotropism. Focal neoexpression of ICAM-1 on keratinocytes was restricted to epidermotropic lymphomas. Both LFA-1 and LFA-3 were expressed on infiltrating cells in all cases investigated. In contrast, beta 1-integrins showed differential expression, most prominent in the case of VLA-1 and VLA-6: These molecules were present on infiltrating cells in most cases with epidermotropic MF and absent in most other CTCLs. We conclude that the phenomenon of epidermotropism might involve different sets of adhesion molecules in different entities of CTCL, with VLA-1 being the most influential beta 1-integrin in the case of MF.     

Expression of cytotoxic molecules in intestinal T-cell lymphomas

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from αβ intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial αβ cytotoxic T-lymphocytes. © 1997 John Wiley & Sons, Ltd.     

The Development of AIDS-Associated Burkitt's/Small Noncleaved Cell Lymphoma Is Preceded by Elevated Serum Levels of Interleukin 6

B cell hyperactivation accompanies HIV infection and is believed to contribute to the increased incidence of B cell lymphoma in persons with AIDS. To examine B cell activation which precedes the development of AIDS-associated lymphoma, we measured levels of two B cell stimulatory molecules, soluble CD23 (sCD23) and interleukin 6 (IL6), in the serum of HIV-infected individuals prior to the diagnosis of lymphoma. Serum sCD23 was elevated in those subjects who developed lymphoma, compared to AIDS, HIV+, and HIV- controls (P = 0.001). Serum IL6 was significantly elevated in subjects who developed Burkitt's/small noncleaved cell lymphoma (BL/SNC, P = 0.01), but not in those subjects who developed large cell, immunoblastic, or central nervous system lymphomas, compared to CD4-matched AIDS controls who did not have lymphoma. These results suggest that lymphomagenesis of the BL/SNC subtype of AIDS lymphoma reflects B cell hyperactivation of a different nature from that which precedes other subtypes of AIDS-associated B cell lymphoma.     

CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics

Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.     

Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases

Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non-Hodgkin's lymphoma (15 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin-embedded sections disclosed that 17 lymphomas were B-cell type and two were T-cell type. The plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement.     

Diffuse aggressive B-cell lymphomas of the gastrointestinal tract. An immunophenotypic and gene rearrangement analysis of 22 cases.

Twenty-two diffuse aggressive B-cell lymphomas of the gastrointestinal tract were studied using light microscopic examination, immunohistochemical methods, and Southern blot analysis. The results suggest that diffuse aggressive B-cell gastrointestinal tract lymphomas may be divided into two groups: large cell lymphomas and small noncleaved cell lymphomas. Large cell lymphomas often involve the stomach; commonly express the lymphocyte adhesion molecules CD44, LFA-1 (CD11a and CD18), and CD54; and may express monotypic cytoplasmic immunoglobulin in approximately one third of cases. Southern blot analysis demonstrates rearrangements of the c-myc gene that do not co-migrate with rearrangements of the immunoglobulin heavy chain gene, as detected with a JH probe in approximately one half of the cases. Small noncleaved cell lymphomas typically involve the ileocecal region. In these lesions, monotypic cytoplasmic immunoglobulin is not detected, and the CD44 and LFA-1 molecules usually are not expressed, particularly in small noncleaved cell lymphomas of the Burkitt type. The CD54 antigen is positive in fewer than one half of cases. Southern blot studies often demonstrate rearrangements of the c-myc gene that co-migrate with immunoglobulin heavy chain gene rearrangements indicative of the t(8;14) chromosomal translocation, with the c-myc region translocated into the immunoglobulin heavy chain gene joining region. Thus, immunohistochemical and genotypic results, in accordance with the site of involvement and histologic findings, suggest a different pathogenesis for large cell lymphomas and small noncleaved cell lymphomas. The findings in large cell immunoblastic lymphomas are more akin to those of the large cell group. In addition, immunophenotypic and molecular data may be helpful in improving histologic classification when the morphologic findings are equivocal.     

CD30 expression in non-Hodgkin''s lymphoma

The CD30 antigen has been reported as the immunophenotypic hallmark of a recently described category of non-Hodgkin's lymphoma, termed anaplastic large cell lymphoma. From a series of approximately 500 lymphomas, 17 cases showing typical anaplastic features have been identified. They were strongly labelled by monoclonal antibodies recognizing CD30 (Ki-1 or BerH2). However, 36 other lymphomas, mainly high-grade, of non-anaplastic cytology also expressed CD30, either diffusely or focally, with a staining pattern identical to that seen in anaplastic large cell lymphomas. This clearly suggests that such lymphomas cannot be identified solely on the basis of being high-grade non-Hodgkin's lymphomas showing CD30 positivity. From the present results, the distinction between the anaplastic and non-anaplastic types would be better made with antibodies to epithelial membrane antigen than to CD30. Clinical data, available for 48 of the patients (16 with anaplastic large cell lymphomas and 32 with non-anaplastic) revealed no significant differences with regard to age at presentation, sex or clinical signs. A short-term follow-up study of 25 patients revealed that for the first 2 years after diagnosis there were no significant differences in patient survival between anaplastic large cell lymphoma, other CD30+ high-grade lymphomas and all high-grade non-Hodgkin's lymphomas considered together. These findings, which must be confirmed by larger studies, suggest that in a general lymphoma clinic there is probably little justification for differentiating anaplastic large cell lymphomas or CD30+ lymphomas from other high-grade non-Hodgkin's lymphomas.     

Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T-cell lymphomas

Lymphomas involving the nasal and nasopharyngeal region mainly include CD56-positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma, presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and South American patients. NK cells are proposed to be closer developmentally to T cells than to other lymphoid cells, because bipotential common progenitor cells of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of nasal lymphoma and investigated the phenotypic difference between NK/T-cell lymphoma and PTL by examining the pattern of the developmentally differentially expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an essential regulator of the cell cycle in G1 progression, was over-expressed in a subset of cortical thymocytes, but absent in mature thymocytes. In contrast, CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but present in mature thymocytes and peripheral activated T cells. We found both over-expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56-positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without evidence of gene rearrangement. Thus, there seems to be a useful distinction between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-) and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of Epstein-Barr virus does not seem to be a good marker for distinguishing between NK/T lymphoma and PTL involving the nasal region.     

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.     

The challenge of the microenvironment in B-cell lymphomas

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant lymphoid neoplasms, with the majority of these arising from germinal centre or post-germinal centre B cells, due to (at least) a disruption of the different phases of normal B-cell development. The most common B-cell lymphoma subtypes include follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma and mantle cell lymphoma. As with other malignancies, it has been demonstrated that the development and progression of B-cell lymphomas involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, including stromal cells, the intratumoral vasculature, the various types of macrophages, as well as T-cells, including regulatory T-cells (also termed T-regs). The complex communications between the cell populations involves interplay between chemokines, chemokine receptors and adhesion molecules, and the balance between these determines whether there is a tumour cell growth promotion or inhibition. The demonstration of the importance of the microenvironment in B-NHL has been shown recently using methodologies such as gene expression profiling, and has been validated in some B-NHL lymphoma subtypes using other techniques, such as immunohistochemistry. This is particularly in the case of follicular lymphomas, in which both T-regs and macrophages have been demonstrated to have prognostic value. As such, the microenvironment of B-cell lymphomas represents a challenge to the development of therapeutic agents, requiring re-direction and inclusion of these non-neoplastic supportive cells into future treatment strategies.     

Immunohistochemical analysis of HLDA9 Workshop antibodies against cell-surface molecules in reactive and neoplastic lymphoid tissues

The study of human leukocyte antigens, predominantly by monoclonal antibody (mAb) techniques, has become a fundamental part of basic research and clinical investigation. In particular, mAbs have allowed a more precise phenotypic dissection of lymphocyte subsets and have increased our understanding of the mechanisms that regulate humoral immunity and tumour transformation. In the present study we have investigated the expression, in both reactive and neoplastic lymphoid tissues, of a panel of HLDA9 mAbs (TRAIL-R2 (CD262), CCR6 (CD196), HVEM (CD270), Galectin-3 and BAFF-R (CD268)) capable of recognizing their target molecules in paraffin-embedded tissue sections. A series of reactive lymphoid tissues and B and T cell lymphomas (151 cases) were studied, using whole sections and tissue microarrays (T.M.A.). The most interesting results were obtained from the Galectin-3 study. In human lymphomas our data are consistent with the results previously described that showed that Galectin-3 is expressed in anaplastic large cell lymphoma (ALCL). Moreover, we provide additional information of Galetin-3 expression in other lymphoma types. In T cell lymphomas, Galectin-3 was strongly expressed by a significant number of peripheral (PTCL 12/43) and cutaneous T cell lymphomas (CTCL 6/24) while in B cell lymphoma only a small proportion of follicular (FL 2/10) and diffuse large B cell lymphomas (DLBCL 3/10) were positives. Our study encourage further investigations into the potential role that TRAIL-R2, CD196, HVEM, Galectin-3 and BAFF-R proteins may play in lymphocyte development and differentiation, but also constitute an additional tool for the study of lymphoid subpopulations and lymphoproliferative disorders.     

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Some of the HML-1 positive ATLL cases co-expressed CD30. Furthermore, three of six cases of Ki-1 lymphoma (large anaplastic cell lymphoma) were positive for HML-1. We conclude that expression of HML-1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.     

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.