Cadherins in reactive lymph nodes and lymphomas: high expression in anaplastic large cell lymphomas

Using a polyclonal pan-cadherin antibody and a monoclonal E-cadherin antibody (HECD-1) we have investigated cadherin expression in lymphomas and reactive lymph nodes. Routinely processed tissue from nine reactive lymph nodes and 48 lymphomas (six T-cell, six high-grade B-cell, 15 low-grade B-cell, 13 anaplastic large cell and eight Hodgkin's disease) were immunostained. The reactive cases showed pan-cadherin membrane associated staining of endothelium and epithelioid granulomas. No staining of lymphoid cells was seen. Pan-cadherin immunostaining was present in three of six T-cell lymphomas, two of six high-grade B-cell lymphomas, 12 of 13 anaplastic large cell lymphomas and three of eight cases of Hodgkin's disease. No staining of low-grade B-cell lymphomas was identified with the pan-cadherin antibody. E-cadherin was not detected in any of the lymphomas that showed pan-cadherin expression. The frequent and strongest cadherin expression in anaplastic large cell is noteworthy. The tumour cells of this lymphoma subtype are characterized by copious cytoplasm and a cohesive appearance, features which impart a superficial resemblance to carcinoma cells. Since cadherin molecules are known to have major morpho-regulatory functions our data suggests that the expression of cadherin molecules by anaplastic large cell lymphomas may play an important role in determining their characteristic epithelioid phenotype.     

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.     

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.     

Immunophenotypic and genotypic characterization of primary non-Hodgkin's lymphoma of the gastrointestinal tract

Antigen receptor gene rearrangement studies have been applied to gastrointestinal (GI) lymphoid proliferations in only a limited number of cases, and their use and contribution to the diagnosis and characterization of GI lymphomas is unknown. We retrospectively studied 17 cases of primary GI lymphoma using fresh/frozen tissue with a combination of immunophenotypic and genotypic techniques. The vast majority of the neoplasms were B-cell lymphomas (88%) with rare T-cell tumors. The most common B-cell immunophenotype was IgM-kappa (40%), while five of the B-cell lymphomas (33%) lacked surface light chain immunoglobulin. Immunophenotypic evidence of histiocytic differentiation was not identified. Clonality was confirmed in 59% (10/17) of the neoplasms by immunophenotyping and 88% (15/17) by antigen receptor gene rearrangement studies. All of the 15 B-cell lymphomas (100%) demonstrated clonally rearranged immunoglobulin gene rearrangement. The two lymphomas with T-cell immunophenotypes did not demonstrate T-cell receptor beta-chain gene rearrangement. Antigen receptor gene rearrangement data can be useful and may even be necessary in certain cases for the proper classification and/or diagnosis of GI lymphoid proliferations.     

Primary lymphomas of the lung: morphological, immunohistochemical and clinical features

Sixty-two cases of primary malignant lymphoma of the were investigated. Fifty-eight lymphomas were of B- and two of T-cell type. Two cases of high-grade homa could not be further classified. The largest group (43 cases) consisted of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. These showed features similar to low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue of the stomach. The low-grade lymphomas showed a peak occurrence in the sixth decade, the high-grade lymphomas in venth decade. Males predominated slightly. Three-quarters of the patients with low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue showed solitary or multiple sharply defined nodules of the lung. The prognosis of the B-cell-derived lung lymphomas without constitutional symptoms was relatively favourable, regardless of whether they were of low- or high-grade malignancy, whereas patients with constitutional symptoms and the two patients with T-cell lymphomas showed a bad prognosis. However, recurrences and metastases in the lung, stomach, lymph nodes and salivary glands were seen in about 46% of the cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue.     

Leu-M1--a marker for Reed-Sternberg cells in Hodgkin''s disease. An immunoperoxidase study of paraffin-embedded tissues.

Monoclonal antibody to Leu-M1, a granulocyte-related differentiation antigen, represents a highly effective reagent for detection of diagnostic Reed-Sternberg (R-S) cells and variants in paraffin-embedded tissues of Hodgkin's disease. In 69 of 73 cases of Hodgkin's disease (41 nodular sclerosis, 25 mixed cellularity, 4 lymphocyte predominance, and 3 lymphocyte depletion types), R-S cells were strongly immunoreactive for Leu-M1. Four cases of lymphocyte predominance Hodgkin's disease (nodular) were uniformly nonreactive for Leu-M1. In most of the positive cases (57/69, 83%), the majority (60-90%) of R-S cells and variants exhibited immunoreactivity for Leu-M1. A characteristic staining pattern included granular and/or vesicular cytoplasmic immunoreactivity, often with a prominent globular paranuclear reaction product, and membrane staining with highly irregular cytoplasmic borders. Evaluation of B-cell (37 specimens), T-cell (20 specimens), and true histiocytic (3 specimens) neoplasms and a case of mastocytosis revealed immunoreactivity for Leu-M1 only in 1 B-cell and 4 T-cell malignancies. The staining patterns in these cases, however, clearly differed from that observed for R-S cells. Studies of nonneoplastic lymphoid tissues (38 total) demonstrated that lymphoid cells were typically nonreactive; histiocytes revealed variable reactivity for Leu-M1. Occasional histiocytes of the sinusoidal network of lymph nodes, particularly in toxoplasmic lymphadenitis, exhibited a staining pattern (membranous/cytoplasmic/paranuclear) similar to that observed for R-S cells. Leu-M1 represents a potentially helpful diagnostic discriminant in the assessment of Hodgkin's disease and its distinction from non-Hodgkin's lymphomas and other lymphoid proliferations.     

Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin''s lymphomas.

The immunophenotypes of 74 malignant lymphomas (9 Hodgkin's disease, 19 low-grade B-cell, 20 high-grade B-cell, 8 T-cell, and 18 large cell anaplastic lymphomas [LCAL]) have been characterized with antibodies against leucocyte differentiation antigens, keratin, and vimentin. All the non-LCAL were CD45 positive and keratin negative. The LCALs had a more varied immunophenotype, with CD45 present only in 11 of 18 cases and keratin present in 5 of 18 of these rare lymphomas. The lymphoid origin of these latter cases was proven by gene rearrangement studies. All LCALs were CD30+, and, where tested, vimentin positive. Of four different vimentin monoclonal antibodies tested, V9 and MVI stained the highest number of lymphomas. Positive staining of tumor cells was seen in 61 of 71 cases. Vimentin-negative cases included Burkitt's as well as some follicular lymphomas.     

Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin sections

The leukocyte antigen CD23 is expressed during B-cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B-cell, and seven T-cell non-Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B-cell and one of the T-cell tumours. CD23 may be important in mediating the mixed cellular infiltrate characteristic of Hodgkin's lymphoma.     

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.     

Gastrointestinal lymphomas of T- and B-cell types.

Gastrointestinal lymphomas comprise a group of distinctive clinicopathological entities of B- or T-cell type, with primary gastrointestinal Hodgkin's disease being extremely uncommon. Most low-grade B-cell gastrointestinal lymphomas are of mucosa-associated lymphoid tissue (MALT) type, so called because they recapitulate the features of MALT rather than those of lymph nodes. Paradoxically, however, most MALT lymphomas arise in the stomach, which normally contains no organized lymphoid tissue. Gastric MALT lymphomas appear to arise in MALT acquired as a reaction to infection of the stomach by Helicobacter pylori and their growth can be inhibited by eradication of this organism from the stomach. Low-grade MALT lymphomas, which usually have a very favorable clinical course, may undergo high-grade transformation but high-grade diffuse large B-cell lymphomas may also arise de novo. Immunoproliferative small intestinal disease (IPSID) is a special form of MALT lymphoma characterized by synthesis of alpha heavy-chain immunoglobulin and a restricted geographic distribution. Other B-cell lymphomas that tend to arise in the gastrointestinal tract include mantle cell lymphoma, which presents as lymphomatous polyposis, Burkitt's lymphoma, and B-cell lymphomas associated with immunodeficiency states. Enteropathy (celiac disease)-associated T-cell lymphoma (EATL) is the most common primary gastrointestinal T-cell lymphoma This is a clinically aggressive tumor that arises from the intraepithelial T-cell population.     

Leu-22: a preferential marker for T-lymphocytes in paraffin sections. Staining profile in T- and B-cell lymphomas, Hodgkin's disease, other lymphoproliferative disorders, myeloproliferative diseases, and various neoplastic processes

Monoclonal antibody Leu-22 represents an effective reagent for detection of neoplastic and nonneoplastic T-cells in paraffin sections of routinely processed tissues (242 specimens evaluated). In nonneoplastic tissues, immunoreactivity was localized mainly to lymphoid cells corresponding to a T-cell distribution. Immunoreactivity in lymphoid neoplasms, however, was preferentially, but not exclusively, limited to T-cell populations. Fifty-four of 60 T-cell neoplasms (90%) of various histologic types were Leu-22 positive. The pattern of immunoreactivity consisted mainly of membrane staining, with focal weak cytoplasmic positivity. Twenty-five of 67 B-cell neoplasms (37%) were also Leu-22 positive, with low-grade lymphomas (well/moderately well-differentiated lymphocytic types) representing most immunoreactive cases. In Hodgkin's disease, although most small lymphoid cells were Leu-22 positive, only rare Reed-Sternberg cells were immunoreactive. In all cases, histiocytes and myeloid cells exhibited variable immunoreactivity. The epitope identified by Leu-22 was detectable in formalin- and B5-fixed tissues but apparently was denatured after fixation in Zenker's-acetic acid solution used for bone marrow biopsies. Evaluation of a wide variety of nonhematopoietic neoplasms (64 total) revealed diffuse cytoplasmic staining in a few cases. However, membrane staining, typically noted for lymphoid cells, was not observed. Leu-22 potentially represents a useful marker for lymphoid cells, preferentially of T-cell origin, with optimal applicability as part of a panel that includes an effective pan-B-cell marker.     

Rare expression of T-cell markers in classical Hodgkin's lymphoma.

Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphoma are primarily of B-cell origin, although there are instances of T-cell antigen expression suggesting T-cell origin. We comprehensively analyzed expression of various T-cell antigens in 259 classical Hodgkin's lymphoma cases using the tissue microarray technique. Expression of the T-cell antigens CD2, CD3, CD4, CD5, CD7 and CD8 was assessed by immunohistochemistry. Hodgkin's and Reed-Sternberg cells of T-cell marker-positive cases were microdissected and analyzed by a multiplex polymerase chain reaction for clonal immunoglobulin heavy chain- and T-cell receptor gamma gene rearrangements. In all, 12 cases (5%) expressed at least one T-cell marker in the following order: CD2 in 11 cases, CD4 in five, CD3 in two, and CD5 and CD8 in one case each; there were no CD7-positive cases, and five cases (2%) expressed more than one T-cell antigen. In positive cases, a mean fraction of 40% of the Hodgkin's and Reed-Sternberg cells (range 20-100%) expressed the analyzed T-cell markers. Two cases (<1%) evidenced clonal T-cell receptor gamma gene rearrangement. Phenotypic expression of T-cell antigens in Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphoma is rare (5%), while genotypically, less than 1% of classical Hodgkin's lymphomas are of possible T-cell origin. Therefore, T-cell antigen expression on Hodgkin's and Reed-Sternberg cells is aberrant in the majority of cases and only infrequently classical Hodgkin's lymphomas are of T-cell origin.     

Detection of B- and T-cells in paraffin-embedded tissue sections. Diagnostic utility of commercially obtained 4KB5 and UCHL-1

Although many recent studies have begun exploring the diagnostic utility of anti-B- and anti-T-cell antibodies that work on paraffin-embedded tissue sections, the most optimal panel to use remains uncertain. In addition, many of the published reports have used antibodies obtained before their commercial formulation and distribution. For these reasons, B5-fixed paraffin-embedded tissue samples from 174 reactive or neoplastic lymphoid and hematopoietic proliferations were immunostained with the commercially obtained antibodies 4KB5, UCHL-1, and, in selected cases, L26. In reactive nodes, 4KB5 stained B-cell areas and UCHL-1 T-cell areas. Seventy-nine percent of the B-cell neoplasms were 4KB5 positive, and only 2% were UCHL-1 positive. Two cases of myeloma were 4KB5 and UCHL-1 negative. The 4KB5-negative B-cell lymphomas (ML-B) were all L-26 positive. UCHL-1 stained 78% of the T-cell lymphomas (ML-T), and 4KB5 stained 14%. In the five 4KB5-positive putative T-cell lymphomas, immunoglobulin and T-cell receptor gene rearrangement studies were performed. In Hodgkin's disease (HD), Reed-Sternberg (RS) cells were UCHL-1 negative in 75% of cases and occasionally positive in 25%. Definite 4KB5 positivity of RS cells was identified in both cases of lymphocyte predominant HD and in one case of nodular sclerosing HD with monomorphic large cell areas. With the exception of 1 of 15 acute nonlymphocytic leukemias that was UCHL-1 positive, all acute leukemias were 4KB5 and UCHL-1 negative. In summary, commercially obtained 4KB5 and UCHL-1 form a useful but not absolutely specific or sensitive paraffin section immunoperoxidase panel for the categorization of B- and T-cell lymphoid neoplasms. Addition of L26 appears to add to the sensitivity and specificity of the panel. Definite immunophenotypic distinction of HD from non-Hodgkin's lymphomas, particularly of T-cell type, often was not possible.     

Distribution of lymphocytes with interleukin-2 receptors (TAC antigens) in reactive lymphoproliferative processes, Hodgkin''s disease, and non-Hodgkin''s lymphomas. An immunohistologic study of 300 cases.

The authors investigated the distribution of interleukin-2 receptors (TAC antigen) in the lymph nodes of 300 patients with lymphoproliferative disorders. They used fresh-frozen sections to evaluate a possible correlation between the immunophenotype of specific lymphoid disorders and the presence or absence of TAC expression and to determine whether the TAC positivity of lymphoid cells contributes to the characterization of lymphoproliferative processes. All of the cases had previously been studied with a large screening panel of monoclonal antibodies and polyclonal antisera. Among 85 patients with a variety of benign reactive processes, the lymph nodes from 47 contained TAC-bearing lymphocytes in various patterns of distribution. Of 41 patients with Hodgkin's disease, 37 had TAC-bearing lymphocytes. Of 26 B-cell, well-differentiated lymphocytic lymphomas (WDL), 14 were diffusely TAC-positive and one had TAC-bearing cells in random distribution. Six cases of intermediate lymphocytic lymphoma were also studied, and three showed randomly distributed TAC-bearing lymphocytes. Of 19 patients with follicular or follicular and diffuse, poorly differentiated lymphocytic (PDL) lymphoma, 14 were TAC-positive. All 3 diffuse PDL lymphomas studied were TAC-negative. Among 23 cases of B-cell and 5 cases of T-cell mixed cell lymphoma, 15 and three, respectively, had TAC-positive lymphocytes. Of 39 large cell lymphomas (B-cell, 33; T-cell, 6), 14 were TAC-positive. All 13 cases of hairy cell leukemia were diffusely positive. Of 23 T-lymphoblastic lymphomas, only 1 showed positive TAC reactivity, which was focal. Of 5 cases of cutaneous T-cell lymphoma, 2 had TAC-bearing lymphocytes. Our study indicates that the TAC antigen is not lineage-specific, and that it may be expressed by lymphoid cells regardless of their phenotype.     

Pathologic and immunologic characterization of malignant lymphoma in Taiwan. With special reference to retrovirus-associated adult T-cell lymphoma/leukemia

One hundred four cases of malignant lymphomas, including 90 cases of non-Hodgkin's lymphoma, 5 cases of histiocytic malignancy, and 9 cases of Hodgkin's disease were analyzed pathologically and immunologically using a panel of monoclonal and conventional antibodies for T-, B-, histiocyte, and Hodgkin's neoplastic cells. Our results revealed a high frequency of T-cell lymphoma (42.3%), a low percentage of follicular lymphoma (10.5%), and Hodgkin's disease (8.7%) in Taiwan. More than half of the malignant lymphomas belonged to the high-risk unfavorable group. Peripheral T-cell lymphomas (33 cases) showed characteristic clinical and histologic features, which can sometimes be confused with Hodgkin's disease. Monoclonal antibodies Leu-M1 and 2H9 were an important aid for their differential diagnosis. Five of the 33 peripheral T-cell lymphomas were positive for antibody to adult T-cell lymphoma/leukemia (ATL) virus associated antigen (ATLA). Four patients were from the northeast coast of Taiwan, I-Lan county. Five (4.8%) were diagnosed as true histiocytic malignancies, including two true histiocytic lymphoma and three malignant histiocytosis. Two cases each of large cell lymphoma and immunoblastic lymphoma showed no identifiable marker expression. The distribution of lymphoproliferative disorders in Taiwan is similar to that in Japan but much different from western countries.     

Immunohistochemistry and gene rearrangement studies in the diagnosis of malignant lymphomas: a comparison of 152 cases.

One hundred fifty-two cases (155 specimens) of lymphoproliferative disorders were studied by immunohistochemistry and gene rearrangement analysis. Ninety-five of 96 B-cell lymphomas (99%) showed genotypic B-cell monoclonality. Of these, five cases had rearranged T-cell receptor (TCR) beta chain gene in addition to immunoglobulin heavy chain (IgH) and kappa light chain (Ig-K), one case had rearranged IgH and TCR-gamma chain but not Ig-K or TCR-beta, and two cases had only Ig-K rearrangement. One exceptional case in the B-cell lymphoma group had unrearranged, germline genotypes. In contrast, only 10 of 19 (53%) phenotypic T-cell lymphomas had rearranged TCR-beta, eight with concurrent TCR-gamma rearrangement. Of the remaining nine cases, six had germline configuration, two had rearranged Ig-K only, and one had both IgH and Ig-K rearrangement. This last case was reclassified as T-cell predominant, B-cell lymphoma. Thirteen of 16 cases of Hodgkin's disease had germline configuration; three cases had rearranged IgH and Ig-K, of which two were lymphocyte predominant with light chain monoclonality and one was a recurrence. Among 21 reactive lesions, 17 had germline configuration and four had rearranged IgH and Ig-K genes. Of these four cases, two were orbital lesions, one was a partially involved lymph node, and one developed a nodular lymphoma 9 months later. Our results indicate that almost all B-cell lymphomas have IgH and/or Ig-K rearrangement. In contrast, peripheral T-cell lymphomas have greater genotypic heterogeneity, and germline patterns for TCR genes are not uncommon. Reactive lesions and Hodgkin's disease tend to retain germline configuration, and any exception is often associated with an unusual clinical setting and/or histology. Genotypic analysis is thus most indicated in B-cell lymphomas with equivocal immunohistochemistry findings, T-cell lymphomas, and atypical cases of Hodgkin's disease and reactive lesions.     

Expression of TCL1 in hematologic disorders.

OBJECTIVE: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. METHODS: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. RESULTS: TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin's disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. CONCLUSIONS: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin's lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.     

Primary CNS lymphomas. Morphology and diagnosis

Diagnostically primary central nervous system lymphomas (PCNSL) have to be differentiated from glioblastoma and brain metastases. Histologically the overwhelming majority of PCNSL is represented by diffuse large B-cell lymphomas, in this series with a BCL6 expression in 80% of the cases detected by immunohistochemistry. Stereotactic biopsy is the method of choice in establishing the definite diagnosis and intraoperative smear cytology will detect the lymphoid blasts. To confirm the B-cell lineage, immunohistochemistry is needed (CD20, CD79a). Small reactive T-lymphocytes and monohistiocytic cells and activated "microglia" are found within and at the periphery of PCNSL foci. The infiltrated brain tissue shows partially pleomorphic reactive astrocytes that can be confused with neoplastic astrocytes, especially in small specimens. In contrast to high-grade gliomas, however, PCNSLs do not show endothelial proliferations. Subtypes or variants of diffuse large B-cell lymphomas can also be observed in cases of PCNSL: the anaplastic variant with large multinucleated tumour cells resembling Reed-Sternberg cells, T-cell rich B-cell lymphoma and intravascular B-cell lymphoma with primary manifestation within the brain or the spinal cord. HIV/AIDS-associated PCNSLs are characterised by large plasmoblastic or small Burkitt-like cells and tumour necrosis. Primary leptomeningeal large B-cell lymphomas do occur very rarely and are diagnosed by cerebrospinal fluid cytology.     

RECEPTORS FOR HELIX POMATIA AGGLUTININ ON NORMAL AND NEOPLASTIC LYMPHOCYTES

In order to investigate the distribution and significance of receptors for Helix pomatia agglutinin (HPA), paraffin sections from several reactive and 71 neoplastic lymphoid tissues were utilized for a histochemical study after neuraminidase treatment. Lymphocytes in the germinal center and thymic cortex were mostly negative for the receptors, while most of the lymphocytes in the thymus-dependent area, some of those in the primary follicle or in the marginal zone and most of the plasma cells in the medulla possessed the receptors on their surfaces. Nodular lymphomas, thymomas and diffuse lymphoblastic lymphomas were mostly negative in contrast to the positive reaction in diffuse poorly differentiated lymphomas of B-cell type and plasmocytomas. Diffuse histiocytic lymphomas and diffuse mixed lymphocytic and histiocytic lymphomas occasionally possessed the receptors, irrespective of their immunological markers. Hodgkin's cells were negative on their surfaces, but were occasionally positive in their cytoplasms as seen in case of histiocytes. From these results, HPA receptors could be neither T-cell nor B-cell differentiation marker. The possibility that HPA-receptor-negative lymphocytes may have a quick turn-over rate or a short life span is also discussed.