A comparative study of the value of immunohistochemistry and the polymerase chain reaction in the diagnosis of follicular lymphoma

We have compared the value of immunohistochemical and polymerase chain reaction (PCR) techniques in distinguishing follicular lymphoma from follicular hyperplasia in formalin-fixed paraffin-embedded tissues of 41 follicular lymphomas, 15 reactive lymph nodes and 5 reactive tonsils. Immunohistochemistry demonstrated bcl-2 protein in the follicle centre cells of 97% of follicular lymphomas whereas monoclonal immunoglobulin light chain was detected in 83% of cases. Assessing the lowest proliferating follicle of each case by MIB-1 immunostaining, proliferation fractions in the lymphomas varied from 0.5% to 59% (mean 15.6%). Over 80% of lymphomas had proliferation fractions of less than 25%. PCR detected gene rearrangement either at the bcl-2 locus, or at the IgH locus, or at both loci in 32%, 44% and 61% of lymphomas, respectively. The follicle centre cells of the reactive lymph nodes and tonsils were all bcl-2 protein negative and polytypic for kappa and lambda light chains. Proliferation fractions of the lowest proliferating follicle in each reactive case ranged from 30.5% to 86.8% (mean 64.9%). Rearrangements of the bcl-2 or IgH loci were not detected in any reactive case. This study demonstrates that bcl-2 and light chain immunostaining are the most consistently helpful aids to diagnosing follicular lymphoma. A low proliferation fraction also indicates lymphoma but a high proliferation fraction does not exclude the diagnosis. Immunostaining with a combination of anti bcl-2 and MIB 1 antibodies is a sensitive and specific method for identifying follicular lymphoma, is technically simple to perform and easy to interpret. In occasional cases, where immunostaining gives equivocal results, PCR analysis can confirm lymphoma, but a negative result does not exclude the diagnosis.     

Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异.Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤(MCL)、慢性淋巴细胞白血病(CLL)、边缘区淋巴瘤(MZL)、弥漫大B细胞淋巴瘤(DLBCL)等」中均有表达.多数B细胞淋巴瘤[滤泡性淋巴瘤(FL)、DLBCL等]都能可见易位活化的bcl-2表达增强.Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值.     

Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors

Little is known about stepwise deregulation of specific genes leading to lymphoid malignancy. Aberrant myc gene expression in transgenic mice is correlated with B cell lymphomagenesis. We generated a unique transgenic mouse model in which deregulated murine E mu-N-myc transgene expression leads to development of indolent B cell lymphoma. Tumor cells were monoclonal, morphologically mature and surface immunoglobulin expressing B cells. Tumors arose in a disease course and exhibited a cytoarchitectural appearance reminiscent of human follicular lymphoma. Yet tumor cells were staged as preB since they failed to rearrange the immunoglobulin light chain genes. Retroviral insertion mutagenesis analyses of adult transgenic mice infected as newborns with murine leukemia virus revealed decreased disease latency, increased lymphoma incidence and a histologically more mature tumor type. Proviral insertion sites were not equivalent when accelerated E mu-N-myc indolent lymphomas were compared to accelerated c-myc preB cell lymphomas. The bcl-2 gene was not disrupted in either spontaneous or provirally accelerated E mu-N-myc lymphomas. These findings suggest that tumor progression in N-myc-associated indolent B cell lymphoma can proceed along diverse pathways involving distinctly different combinations of deregulated and/or intact genes than those pathways described in highly aggressive forms of myc-related murine preB cell disease.     

The morphologic spectrum of non-Hodgkin's lymphomas with BCL1/cyclin D1 gene rearrangements

BCL1/PRAD1 gene rearrangements involving the cyclin D1 gene are a feature of about 70% of centrocytic/mantle-cell lymphomas (CC/MCL) but are identified in only a small proportion of other B-cell non-Hodgkin's lymphomas. Of 37 lymphomas found to have BCL1/cyclin D1 (PRAD1, CCND1) gene rearrangements, 30 fit the morphologic and immunophenotypic criteria for typical CC/MCL. Seven cases with morphologic features atypical for CC/MCL were identified. CD5+ monoclonal B cells were documented in all these cases. Six cases were subsequently stained for cyclin D1 protein, and all showed nuclear positivity. Five cases had variably sized foci of cells with moderately abundant pale cytoplasm resembling parafollicular/monocytoid B cells, marginal zone cells, hairy cells, or even proliferation centers. Transformed-appearing cells were also present in some lymphomas. In one case, striking follicular colonization created a markedly nodular growth pattern mimicking a follicular lymphoma. A sixth case had a marked predominance of small, round lymphocytes at some sites, mimicking a small lymphocytic lymphoma. Five of these six cases also had areas more typical of CC/MCL. The seventh case was a CD5-positive splenic marginal zone-like lymphoma (SMZL) with plasmacytic differentiation and circulating villous lymphocytes consistent with a splenic lymphoma with villous lymphocytes (SLVL). These cases illustrate the morphologic spectrum of small B-cell lymphoid neoplasms that have BCL1/cyclin D1 gene rearrangements and overexpression of cyclin D1. Despite the BCL1 translocation and cyclin D1 overexpression, the splenic lymphoma with plasmacytic differentiation was definitely not a CC/MCL and fit the clinicopathologic entity of SMZL/SLVL. The other six cases are best considered CC/MCL variants based on a combined morphologic, immunophenotypic, and genotypic evaluation. Genotypic or immunophenotypic studies to identify cyclin D1 rearrangements and overexpression, although not pathognomonic, are useful in recognizing these variant CC/MCL cases, which can mimic almost any of the other well-described but more indolent low-grade B-cell lymphomas and leukemias. Some of the variant CC/MCL cases had features in common with the CD5+ cyclin D1+ SMZL/SLVL, suggesting a possible relationship between these two otherwise distinct entities.     

Abundance of heat shock proteins (hsp89, hsp60, and hsp27) in malignant cells of Hodgkin's disease

Heat shock proteins (HSPs) or stress proteins are synthesized by cells in response to environmental stress. Expression of HSPs by cells may have important physiological or pathological implications. In this study, we carried out an immunohistochemical and biochemical examination of low (hsp27), intermediate (hsp60), and high (hsp89) molecular weight HSP expression in reactive lymph nodes and in lymph nodes of patients with various types of lymphomas. In normal or reactive lymphoid tissues, hsp89 is abundant in large "transformed" lymphoid cells and immunoblasts. Hsp60 is widely distributed in lymphoid tissues, whereas hsp27 is absent in all lymphoid cells and histiocytes. Among lymphomas, the Hodgkin's Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) had the greatest abundance of hsp89 and hsp60 and, in 20% of cases, hsp27, in contrast to a much weaker staining of anti-hsp89 and -hsp60 in the background reactive lymphoid cells. The large lymphoid cells in small lymphocytic lymphoma are also rich in hsp89, but not hsp60 and hsp27. In contrast, the malignant cells in anaplastic large cell lymphoma and most high-grade tumors, including immunoblastic lymphomas, expressed minimal amounts of hsp89 and hsp60 and virtually no hsp27. Thus, the cellular level of HSPs was neither correlated with the proliferative capacity nor with the aggressiveness of the lymphomas. Hsp89, hsp60, and hsp27, as well, serve critical roles in the chaperoning of cellular proteins (e.g., a Mr 43,000 protein) in H-RS cells. The known interactions of HSPs with Rb, p53, peptide-MHC class II complexes, and cofactors of the glucocorticoid hormone receptor have further broadened the importance of HSPs in cell metabolism and in response to extracellular signals for proliferation, differentiation, or growth suppression (or apoptosis) of H-RS cells. Abundant HSP expression is seen only in HD, but not in other lymphomas. Such expression could have vital roles in the pathogenesis of HD.     

Evaluation of CD23 expression in paraffin-embedded gastric lymphomas of mucosa-associated lymphoid tissue

The CD23 antigen is expressed in a normal subset of B lymphocytes and in some non-Hodgkin's lymphomas. Reactivity for anti-CD23 (BU38) is present in paraffin-embedded tissue in the large majority of nodal small lymphocytic lymphomas, as well as in follicular center cell lymphomas. Most studies of gastric lymphomas of mucosa-associated lymphoid tissue (MALT) reported a lack of CD23, but these studies were performed on frozen tissue. We evaluated CD23 staining in paraffin-embedded tissue in a large series of gastric MALT lymphomas, as well as in cases of chronic gastritis. We assayed 49 well-characterized gastric lymphomas (9 high-grade non-MALT and 40 MALT [20 low grade, 13 mixed low and high grade, and 7 high grade]). High-grade MALT lymphomas without a low-grade component were distinguished from high-grade non-MALT lymphomas by the presence of lymphoepithelial lesions composed of large cells. In addition, we studies nine cases of chronic gastritis containing B-cell aggregates. We used anti-CD23 (BU38) in formalin-fixed, paraffin-embedded tissue. All of our low-grade gastric MALT lymphomas lacked CD23 immunoreactivity. One of the 13 mixed low-grade and high-grade lesions showed CD23 expression in the high-grade component. All of the high-grade MALT and high-grade non-MALT lesions lacked CD23. All of the nine cases of chronic gastritis lacked CD23. CD23 highlighted residual follicular dendritic cells and gastric epithelium. We concluded that gastric MALT lymphomas lacked CD23 (BU38) in paraffin-embedded tissue, with rare exceptions. This lack of CD23 expression might represent a useful feature in small or partially crushed biopsy specimens, particularly in the differential diagnosis with follicular small cleaved cell lymphoma presenting in the gastrointestinal tract.     

Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas

BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and progression of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor suppressor gene in MALT lymphomas of the stomach and colon. METHODS: Tumor samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA was extracted from microdissected areas with at least 80% tumor cells. To detect homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated sequence as internal control. RESULTS: Homozygous p16 deletions were found in 2 of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had Helicobacter pylori-associated gastritis; however, DNA extracted from areas of gastritis showed a normal p16 complement. No deletion was found in any of the low-grade gastric or the colonic MALT lymphoma specimens. CONCLUSIONS: In a subset of gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute to the transformation from a low-grade to a high-grade malignancy.     

Histologic criteria for the diagnosis of gastric low-grade malt lymphoma

Low-grade B cell lymphoma of the stomach have the features of mucosa-associated lymphoid tissue (MALT) and is characterised by lymphoid hyperplasia and infiltrations of lymphocytes into glandular epithelium or lymphoepithelial lesions. It may be difficult to distinguish low-grade lymphomas from benign inflammatory lymphoid infiltrates. Nine primary gastric lymphomas and 20 benign lymphoid hyperplasia were investigated for the type of tumour cells, lymphoepithelial lesions. Dutcher bodies, cytologic atypia, the density of lymphoid infiltrates, invasion of the muscularis mucosae, germinal centers, reactive epithelial atypia and acute inflammation. Our results suggest that B cells proliferation, lymphoepithelial lesions, cytologic atypia and Dutcher bodies are very important for the diagnosis of low-grade MALT lymphoma. None of these was seen in inflammatory infiltrates. The presence of germinal centers, acute inflammation and reactive epithelial atypia does not exclude a diagnosis of low-grade gastric lymphoma.     

CNA.42, a new monoclonal antibody directed against a fixative-resistant antigen of follicular dendritic reticulum cells

A new monoclonal antibody (MAb), CNA.42, was generated using the CEM T-cell line. It recognizes a 120-kd formalin-resistant glycosylated antigen that is mainly expressed by follicular dendritic reticulum cells (FDRCs). This antigen is also expressed by a few mononuclear cells in the paracortical area of reactive lymph nodes and by some cortical thymocytes. Two hundred and eighty-nine cases of hematopoietic tumors of various types were tested with this antibody. They showed either intact FDRC networks or FDRC networks dispersed among malignant cells. In follicular lymphomas, the follicular pattern was highlighted by CNA.42 MAb. Expanded FDRC networks were found in angioimmunoblastic T-cell lymphomas. Neoplastic cells were positive in 43.6% (24/55) of T-cell and 4.6% (6/129) of B-cell lymphomas. The highest percentage of cases with positive neoplastic cells was found in anaplastic large-cell lymphomas (62.5%; 15/24). In Hodgkin's disease, FDRC networks, sometimes encasing Hodgkin and Reed-Sternberg (HRS) cells, were found. HRS cells were also stained by this antibody in 23 (21.9%) of the 105 cases examined. A variety of normal nonlymphoid tissues and nonhematopoietic tumors, such as some neurogenic tumors, carcinoma, and occasional sarcomas, were found to be positive. Analysis of the reactivity of CNA.42 antibody with FDRCs of lymphoid tissue from different animal species showed similar reactivity to that observed in humans, suggesting widespread evolutionary conservation of the antigen recognized by this antibody. In daily diagnostic practice, CNA.42 MAb seems to be a suitable FDRC marker and possibly has an auxiliary role in recognizing T-cell lymphomas.     

Loss of p16/INK4A protein expression in non-Hodgkin's lymphomas is a frequent finding associated with tumor progression

The CDKN2A gene located on chromosome region 9p21 encodes the cyclin-dependent kinase-4 inhibitor p16/INK4A, a negative cell cycle regulator. We analyzed p16/INK4A expression in different types of non-Hodgkin's lymphoma to determine whether the absence of this protein is involved in lymphomagenesis, while also trying to characterize the genetic events underlying this p16/INK4A loss. To this end, we investigated the levels of p16/INK4A protein using immunohistochemical techniques in 153 cases of non-Hodgkin's lymphoma, using as reference the levels found in reactive lymphoid tissue. The existence of gene mutation, CpG island methylation, and allelic loss were investigated in a subset of 26 cases, using single-strand conformational polymorphism and direct sequencing, Southern Blot, polymerase chain reaction, and microsatellite analysis, respectively. Loss of p16/INK4A expression was detected in 41 of the 112 non-Hodgkin's lymphomas studied (37%), all of which corresponded to high-grade tumors. This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas. Analysis of the status of the p16/INK4A gene showed different genetic alterations (methylation of the 5'-CpG island of the p16/INK4A gene, 6 of 23 cases; allelic loss at 9p21, 3 of 16 cases; and nonsense mutation, 1 of 26 cases). In all cases, these events were associated with loss of the p16/INK4A protein. No case that preserved protein expression contained any genetic change. Our results demonstrate that p16/INK4A loss of expression contributes to tumor progression in lymphomas. The most frequent genetic alterations found were 5'-CpG island methylation and allelic loss.     

Immunohistochemistry in apparently normal bone marrow trephine specimens from patients with nodal follicular lymphoma

AIM: To establish the role of immunohistochemistry (using a limited panel of antibodies) in detecting minimal involvement by follicular lymphoma in routinely processed bone marrow trephine specimens, which show no obvious morphological (light microscopic) evidence of lymphoma; to determine whether bcl-2 immunostaining in bone marrow distinguishes between benign and malignant infiltrates in a patient with nodal follicular lymphoma. METHODS: Twenty seven consecutively selected paraffin wax embedded, formalin fixed bone marrow trephine specimens were stained with the following antibodies: anti-bcl-2, anti-CD79a, anti-CD3, and kappa and lambda light chains, using the Streptavidin biotin complex technique. RESULTS: Five of the 27 cases, which showed no evidence of involvement by follicular lymphoma on routine stains, showed monotypic B cells on immunohistochemistry. Two of the cases were diffuse, while the remaining three showed mini-aggregates around bony trabeculae. In all five cases the lymphomatous infiltrates were strongly bcl-2 positive. Reactive B lymphoid nodules did not show the same degree of bcl-2 positivity, and negative cells could be discerned within the reactive nodules. CONCLUSIONS: There is merit in studying so-called negative bone marrows immunohistochemically in order to detect minimal involvement by follicular lymphoma. A limited panel of antibodies including anti-bcl-2, anti-CD79a and anti-CD3 is usually adequate to accomplish this. Strongly bcl-2 positive lymphoid aggregates in the bone marrow of patients with nodal follicular lymphoma are indicative of lymphoma.     

Application of multilocus enzyme electrophoresis in studies of the epidemiology of Listeria monocytogenes in Denmark

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is expressed on follicular dendritic cells (FDC), and the ICAM-1/LFA-1 pathway is essential for affinity selection of activated B-cells in germinal centers (GC). The expression of ICAM-1 has been studied by immunostaining methods in GC, but not in neoplastic follicles (NF). METHODS: The authors studied the expression of ICAM-1 by the avidin-biotin-peroxidase complex (ABC) method with frozen sections in GC of reactive nodes (n = 22) and NF of follicular lymphomas (n = 19), in comparison with FDC staining. RESULTS: GC stained uniformly for ICAM-1, with staining intensity varying little from node to node, and follicular borders were well demarcated from the surroundings. Endothelial cells within GC did not stain whereas those outside stained strongly. In contrast, NF stained variably from tumor to tumor, and in any given tumor. Characteristically, follicular borders were not demarcated, and stained areas were difficult to define due to the lack of demarcation, with the exception of large cell type with diffuse areas (n = 2). Endothelium of intrafollicular vessels stained prominently (12 of 19), and appeared to contribute to the staining intensity of the follicles. FDC staining revealed a meshwork pattern in GC which was similar to that of ICAM-1. The FDC mesh-work pattern was present in 15 tumors. The pattern was remarkably uniform with sharply defined borders, which contrasted starkly to the variable staining and lack of follicular borders in the ICAM-1 stain of the same tumors. CONCLUSIONS: The staining pattern of follicles for ICAM-1 was similar to that for FDC in reactive nodes, but distinct from the latter in follicular lymphomas. An appropriate expression of ICAM-1 appears to be essential for normal GC, as the alteration of the expression coincides with the malignant transformation of GC. The altered expression of ICAM-1 may be useful in distinguishing NF from reactive GC.     

Telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas

Activation of telomerase seems to be a prerequisite for immortalization and is found in permanent cell lines and most malignant tumors. Normal somatic cells are generally telomerase negative, except for bone marrow stem cells. Weak activity is also present in peripheral blood cells. In the present study strong telomerase activity was demonstrated in vivo in normal mature cells of the immune system, as well as in malignant lymphomas. Benign lymph nodes had lower telomerase activity than benign tonsils, which exhibited intermediate to high activity comparable with findings in malignant lymphomas. In benign tonsils the activity seemed to be restricted to germinal center B cells. In benign lymphoid tissues telomerase activity correlated with B-cell numbers and cell proliferation, but this was not observed in the lymphoma group. High-grade lymphomas exhibited higher levels of telomerase compared with low-grade cases. The data showed that in vivo activation of telomerase is a characteristic feature of germinal center B cells. Different signals for activation of telomerase are likely to exist, one of them being immune stimulation. The data suggest that telomerase activity in malignant lymphomas can be explained by an "induction and retention" model, ie, transformation occurs in a normal, mature B cell with reactivated telomerase, which is retained in the neoplastic clone.     

The role of mucosal biopsy in the diagnosis of chronic diarrhea: value of multiple biopsies when colonoscopic finding is normal or nonspecific

The CTLA4 receptor is a CD28 homologue which induces inhibitory effect on activated T-cells. Peripheral T-cells proliferate spontaneously in CTLA4-deficient mice. These results led to an analysis of CTLA4 expression in human lymphomas (n = 82) including Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs), using immunohistochemistry. CTLA4 was present in neoplastic cells from most (10/11) T-cell malignancies, except for anaplastic and lymphoblastic subtypes (0/4). Malignant B-cells from rare (3/55) B-NHLs (all of follicular subtype) were also CTLA4-positive. Other B-NHLs (52/55) were negative in malignant B-cells and occasionally positive in T-cells. Reactive small lymphocytes, but not Reed-Sternberg cells, from all (12/12) HD cases were strongly CTLA4-positive. The CTLA4 ligands CD80 and CD86 were simultaneously expressed in most CTLA4-negative lymphoma cases. CTLA4 is thus expressed either in the reactive or in the malignant cell populations, depending on the lymphoma subtype. These results provide new insights leading towards therapeutic strategies based either on enhancement of anti-tumour immunity by CTLA4 blockade in reactive lymphocytes or on triggering of a CTLA4-mediated inhibitory pathway in lymphoma cells.     

Peculiarity of soleus motor potentials evoked by transcranial magnetic stimulation and electrical stimulation of tibial nerve

Fas (Apo-1/CD95) ligand (FasL) is a cytotoxic molecule used by T lymphocytes and natural killer cells for target-cell killing and by nonmalignant and malignant cells in the suppression of immune responses. In this study, FasL expression in B- and T-cell non-Hodgkin's lymphomas was investigated by paraffin immunohistochemical analysis. FasL expression was found to be weak in nonaggressive lymphomas (chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, Grade 1 follicular center cell lymphoma) and mantle cell lymphoma but strong in aggressive B-cell lymphomas (diffuse large B-cell lymphoma, Burkitt's-lymphoma). Precursor B-lymphoblastic lymphomas were more heterogeneous, with expression varying from weak to strong. In T-cell lymphomas (anaplastic large-cell lymphoma; peripheral T-cell lymphoma, unspecified), strong FasL expression was observed. Apparently, FasL expression is not limited to neoplasms derived from T cells or natural killer cells, and it might play a supporting role in the progression of non-Hodgkin's lymphomas.     

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells

We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TIMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells.     

Biased VH family usage in primary gastric B cell lymphoma of mucosa-associated lymphoid tissue-type and the selected V beta expression of T cells infiltrating into the lymphoma cells

Seven cases of primary gastric low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, two cases of high-grade B cell lymphoma with a low-grade component and three cases of pure high-grade lymphoma were selected for the current study. The Ig VH gene use of lymphoma cells and the V beta repertoires of infiltrating T cells were investigated. The VH gene analysis showed multiple VH family usage in 12 cases, but the MALT-type lymphoma cell usage was found to be biased for the families that have a low number of VH genes (VHIV and V). Another analysis of lymphoma-infiltrating T cells showed restricted expressions of the V beta repertoire in all seven low-grade cases and three high-grade cases. In those 10 cases, a considerable number of CD4-positive T cells infiltrated into lymphoma cells and RAG-1 was also prominently expressed. Based on these findings, it was thus assumed that the normal counterpart of gastric B cell lymphoma of MALT type is different from the conventional B cell lymphoma, and the restricted expression of V beta repertoires is therefore considered to be a characteristic finding in low-grade B cell lymphomas of MALT type as well as in a proportion of high-grade lymphomas (the so called 'high-grade lymphoma of MALT type').