Enamel remineralization on teeth adjacent to Class II glass ionomer restorations

We describe a patient with mantle cell lymphoma (MCL) associated with BCL6 gene rearrangement. MCL is a distinct subtype of non-Hodgkin's lymphoma characterized by CD5+, CD10-, CD20+, t(11;14)(q13;q32) and PRAD1/cyclin D1 overexpression. Although rearrangement of the BCL6 gene is the most frequent genetic change among diffuse lymphomas and some follicular lymphomas this is the first report of a patient with MCL associated with BCL6 rearrangement.     

Newly designed computer controlled knee-ankle-foot orthosis (Intelligent Orthosis)

AIMS: Splenic marginal zone lymphoma (SMZL) is characterized by a micronodular infiltrate of the splenic white pulp, centred on pre-existing follicles, with a peripheral rim of 'marginal' zone B-cells, always accompanied by a variable degree of red pulp infiltration. These histological features can be closely mimicked by a variety of other small B-cell lymphomas when they involve the spleen, which makes recognition of SMZL difficult. We therefore have compared the histopathological and immunohistochemical features of other non-Hodgkin's lymphoma (NHL) types with those of SMZL. METHODS AND RESULTS: We selected cases of splenic involvement by different types of B-cell lymphoma, including mantle cell lymphoma (MCL), follicular lymphoma (FL), immunocytoma (IM) and lymphocytic lymphoma (B-CLL). A micronodular pattern and marginal zone differentiation were both found to be frequently present in FL and MCL, and with lesser frequency in IM and B-CLL. The main morphological feature useful for differential diagnosis was the cytological composition of the white pulp tumoral nodules. SMZL is distinguished by characteristic dimorphic cytology, different from the monomorphic cytology of MCL, and the distinctive mixture of centroblasts and centrocytes which is the rule in FL. B-CLL could also be identified on the basis of the polymorphic cytology including small lymphocytes and prolymphocytes, whereas cases diagnosed as IM show prominent plasmacytic differentiation, lacking the features of the other lymphoma types. Immunohistochemistry was particularly useful for the differential diagnosis. Thus the recognition of MCL was facilitated by the identification of cyclin D1 and CD43 reactivity, while FL could be recognized by the lack of IgD expression or the distinctive pattern of Ki67 staining found in SMZL. B-CLL cells were CD23+, CD43+. CONCLUSION: The results of this study provide morphological and immunohistological information useful in the recognition of the different varieties of NHLs when involving the spleen and the differential diagnosis of SMZL.     

Phenoloxidase-dependent cytotoxic mechanism in ascidian (Styela plicata) hemocytes active against erythrocytes and K562 tumor cells

The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is important because MCL has a more aggressive clinical course. In bone marrow biopsy specimens, this distinction can be especially difficult. We examined 70 bone marrow biopsy specimens involved by various B-cell lymphoid neoplasms to assess the utility of cyclin D1 immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti-cyclin D1 antibodies and a heat- and sonication-induced epitope retrieval procedure. The neoplasms assessed included MCL (32 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (18 cases), follicular lymphoma (11 cases), hairy cell leukemia (5 cases), splenic marginal zone lymphoma (2 cases), and small lymphocytic lymphoma with plasmacytoid differentiation (2 cases). The diagnosis of MCL in bone marrow was confirmed by review of the original diagnostic biopsy specimens along with additional data, such as immunophenotypic or molecular studies. Most MCL (23/32; 72%) cases expressed cyclin D1 protein. In contrast, one case of small lymphocytic lymphoma/chronic lymphocytic leukemia (1/18; 6%) and one case of hairy cell leukemia (1/5; 20%) expressed cyclin D1 protein. These findings demonstrate that immunostaining for cyclin D1 protein expression is useful in distinguishing MCL from other B-cell lymphoid neoplasms in the bone marrow.     

Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene

Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas composed of lymphocytes presumably derived from follicle mantle cells. In these lymphomas, a specific chromosomal translocation, t(11;14)(q13;q32), has been described. Previous studies suggested an association between t(11;14) chromosomal translocations and BCL-1 rearrangements. To evaluate the association between BCL-1 rearrangements and CC/IDL, Southern blot analysis was performed on a panel of 20 cases of CC/IDL, 22 cases of morphologically similar non-Hodgkin's lymphomas, 11 cases of chronic B-cell leukemias, and 2 cases of myelomas. We used various probes covering a considerable proportion of the 120-kilobase BCL-1 locus, and rearrangements in 50% of CC/IDL (10 of 20) were detected. In CC, all 4 breakpoints were located at the major translocation cluster (MTC). In contrast, in IDL, rearrangements were detected in 3 different cluster regions: 2 cases in the MTC, 2 cases with a breakpoint 24 kilobases outside the MTC, and 2 additional cases with breakpoints found 3 kilobases 5' of the first exon of the PRAD1/CCND1 gene, which is located 120 kilobases outside the MTC. In addition, one leukemia showed a breakpoint 63 kilobases outside the MTC. In all cases, there was comigration of the rearranged 11q13 fragment and the immunoglobulin heavy chain-joining gene complex, indicating a t(11;14)(q13;q32) chromosomal rearrangement. Our results show that Southern blot analysis is helpful to identify CC/IDL, but multiple breakpoints are present over a large region, and therefore, many probes are necessary to cover all breakpoints.     

Echocardiography for the assessment of myocardial viability

Splenic marginal zone lymphoma (SMZL) has recently been proposed as a distinctive type of low-grade B-cell lymphoma. Although there is general agreement that this entity exists, its precise definition is blurred by uncertainty in differential diagnosis from other low-grade B-cell lymphomas. There is even more uncertainty as to the histology of splenic hilar and peripheral lymph nodes involved by SMZL. We therefore reviewed the histological and immunohistochemical features of 19 of these lymph nodes (14 hilar and five peripheral) from 14 cases of classical SMZL and compared them with the features of lymph nodes involved by other B-cell lymphomas. The morphology and immunohistology of the lymph nodes resemble those found in the white pulp of the spleen, showing a distinctive pattern, different from that which is observed in other B-cell lymphomas. In these cases, the overall architecture of the lymph nodes is effaced and replaced by a nodular infiltrate, although the sinuses are preserved in most hilar lymph nodes. Some of the nodules contain a central reactive follicular center, around which there is a broad zone of small lymphocytes. In other cases, the central area is partially infiltrated or, more commonly, totally replaced by these small lymphocytes, which in the periphery of the nodules showed a pale, slightly larger cytoplasm. Scattered nucleolated blasts are present, largely confined to the periphery of the nodules. The tumoral cells express immunoglobulin (Ig)D, IgM, and Ig light chain restriction and show a low proliferation fraction. These findings confirm that SMZL is a real entity, and not merely a morphological pattern of splenic infiltration by different types of low-grade B-cell lymphoma.     

Cyclin D1 overexpression in malignant lymphomas

Cyclin D1, the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle, is now established as a proto-oncogene, with evidence indicating that its derangement may contribute to the uncontrolled cell growth characteristic of tumors. The chromosomal translocation t(11;14)(q13:q32), involving rearrangement of the BCL-1 locus, is closely associated with human lymphoid neoplasia affecting mantle cell lymphomas (MCL). Recently, the putative BCL-1 proto-oncogene turned out to be none other than the cyclin D1 gene. Although the observed break points in the BCL-1 locus are not tightly clustered, its rearrangement has been documented in 40-70% of cases of mantle cell lymphoma, whereas it only rarely occurs in other B cell lymphomas. Of note, all of the known break points leave the cyclin D1 coding region structurally intact and result in increased protein expression, implying that this may provide a highly sensitive and specific marker for MCL. Recent studies demonstrated that immunohistochemical detection in paraffin-embedded material, using a monoclonal antibody, is very useful for routine diagnosis. Current knowledge of cyclin D1 overexpression in malignant lymphomas, with emphasis on its clinicopathologic significance, is reviewed.     

Rearrangements of the BCL6 gene and chromosome aberrations affecting 3q27 in 54 patients with non-Hodgkin's lymphoma

Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was reported. We performed molecular studies of the BCL6 gene in 54 patients with NHL. Twelve patients (22%) with rearranged BCL6 genes were selected for histological, clinical, molecular, and cytogenetic studies. Ten of these cases were diffuse, large cell type lymphoma, one a follicular lymphoma, and one a mantle cell lymphoma (MCL). All cases were of the B-cell type and this is the first time a rearranged BCL6 gene has been found in an MCL. Cytogenetic data for 10 cases were available and the partner sites of the 3q27 translocation were determined in 7 of 10 patients. These locations were variable, including 6p21.3, 9p22, and 14q11 in addition to the immunoglobulin loci 14q32 (IGH), 2p12 (IGK), and 22q11 (IGL). The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements.     

Nurses achieve quality with pre-assessment clinics

Twelve patients with diagnosis of B-cell non-Hodgkin's lymphoma/leukemia and del[7q] were studied for their clinical, cytogenetic, and molecular characteristics. Eleven patients were classified as small cell lymphoma whereas one had a diffuse large cell lymphoma. Lymphoplasmacytic features were observed in six out of eleven small cell lymphomas. Morphologically and immunologically these small cell lymphomas could be classified as chronic lymphocytic leukemia (typical or atypical; 4 cases), marginal zone lymphoma (splenic lymphoma with villous lymphocytes; 1 case), mantle cell lymphoma (2 cases), or nonspecified, non-Hodgkin's lymphoma (4 cases). Eleven of twelve patients presented with peripheral blood and bone marrow involvement. Two of twelve cases showed del[7q] as the sole anomaly. Two different types of deletions were present: ten cases had del(7)(q21q31) and two cases had del(7)(q31q34). Cases that could be molecularly investigated did not show any involvement of BCL2, BCL3, or BCL6, and only one case had BCL1 rearrangement. The data indicate that del(7q) is associated with a subset of mature small B-cell lymphoproliferative disorders of which some but not all show lymphoplasmatic features.     

Expression of CD44 (HCAM) in small lymphocytic and mantle cell lymphoma

Small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) are small B-cell lymphomas that share many morphological and immunophenotypic features, both expressing the T-cell antigen CD5. Because of this, there is speculation that these two lymphomas may have a common origin, both arising from the mantle zone of the lymph node. CD44 (HCAM), a glycoprotein "homing receptor," has been reported as a marker of small B-cell lymphomas for determining behavior as well as the nodal cell of origin. Intensity of CD44 expression also has been correlated with dissemination of lymphoma. We studied 50 cases with classic features of SLL (30 cases) or MCL (20 cases). Immunophenotypic analysis was performed on paraffin sections. All cases of MCL and SLL were CD20 positive; CD5 was expressed in 19 of 25 (76%) SLL and 11 of 15 (73%) MCL. Cyclin D1 was expressed in 11 of 17 (76%) MCL and no cases of SLL. CD43 coexpression was seen in 27 of 29 (93%) SLL and 17 of 19 (89%) MCL. CD23 was positive in 25 of 28 (89%) SLL and 2 of 20 (10%) MCL. Bcl-2 was positive in 18 of 22 (82%) SLL and 15 of 16 (94%) MCL. CD44 was positive with moderate to strong intensity in 11 of 30 SLL and 15 of 20 MCL. Peripheral blood involvement did not correlate with CD44 immunoreactivity. MCL tended to have intense CD44 immunoreactivity, whereas SLL tended to show weaker CD44 intensity. This trend in the intensity of CD44 in MCL suggests that CD44 may be helpful in distinguishing SLL from MCL and possibly elucidating the origin of these CD5-positive B-cell neoplasms.     

Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.     

Structure of Bcl-1 and IgH-CDR3 rearrangements as clonal markers in mantle cell lymphomas

Mantle cell lymphoma represent a clinicopathologically distinct entity of malignant non-Hodgkin's lymphoma (NHL) and are characterized by a specific chromosomal translocation t(11;14)(q13;q32) involving the cyclin D1 gene also designated as bcl-1/PRAD1 gene on chromosome 11 and the heavy chain immunoglobulin joining region on chromosome 14. We have established a PCR method to amplify t(11;14) junctional sequences in DNA from fresh frozen and paraffin-embedded tissue by bcl-1-specific primers in combination with a consensus immunoglobulin JH primer. A total of 65 cases histologically classified as mantle cell lymphoma (MCL) were analyzed for the presence of a t(11;14) translocation and monoclonal IgH-CDR3 rearrangements. From 26 patients with classical MCL and three cases with the anaplastic variant of MCL fresh frozen biopsy material was available for DNA extraction. We detected a bcl-1/JH rearrangement in 12 out of 29 samples (41%). In 36 cases paraffin-embedded lymph node tissue was the only source of DNA. In this material we found a bcl-1/JH rearrangement in six out of 31 samples with intact DNA (20%). To confirm the specificity of the PCR and to determine the bcl-1/JH junctional region sequences as clone-specific marker in individual patients we characterized the junctional DNA sequences by direct PCR sequencing in 16 cases. Interestingly we found that six bcl-1/JH junctions harbored DH segments in their N regions indicating that bcl-1/JH rearrangements can occur in a later stage of B cell ontogeny during which the complete VH to DH-JH joining or VH-replacement takes place. To investigate the suitability of IgH-CDR3 as sensitive molecular marker for those MCL patients in which a t(11;14) translocation can not easily be amplified, we additionally analysed 60 cases for the presence of monoclonally rearranged IgH genes by IgH-CDR3-PCR. A monoclonal IgH-CDR3 PCR product could be identified in 24 out of 29 fresh frozen samples (79%) whereas only 11 out of 31 samples (36%) with paraffin-derived DNA were positive. We demonstrate that automated fluorescence detection of monoclonal IgH-CDR3 PCR products allows the rapid and sensitive monitoring of minimal residual disease also in cases that lack a PCR amplifiable t(11;14) translocation. In combination with allele-specific primers the procedure may improve current experimental approaches for detection of occult MCL cells at initial staging and residual disease during and after therapy.     

Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

Mantle cell lymphomas (MCL) are morphologically and immunophenotypically distinctive lymphoid neoplasms characterised by overexpression of cyclin D1. Recent studies have suggested that co-operating aberrations of cell cycle associated genes may provide a growth advantage to a tumour. To address this issue further, we investigated five typical and three aggressive (blastoid) MCL for alterations in the cell cycle regulating genes p15, p16, CDK4, Rb and p53. In 3/3 aggressive cases with cyclin D1 overexpression we found aberration of at least one additional gene. One case showed diminished expression of the retinoblastoma protein (pRb); one case harboured deletion of both p15 and p16; and one case exhibited both deletion of p16 and point mutation of p53. However, we also identified two typical cases which in addition to cyclin D1 overexpression exhibited diminished pRb expression and p15 and p16 hypermethylation, respectively. Our findings confirm and extend other recent investigations and indicate that co-operating genetic alterations of cell cycle-associated genes may contribute to the pathogenesis of MCL.     

Monoclonal plasmacytic differentiation in small-cell lymphomas of B-cell origin: immunocytoma versus other types

We have studied the morphological and immunohistochemical features of monoclonal cytoplasmic Ig (c-Ig) production in the biopsy material of 161 small B-cell non-Hodgkin's lymphomas to verify a frequency of the plasmacytic/plasmacytoid differentiation of tumor cells for the aims of their differential diagnosis. The analyzed differentiation was identified in all the cases of immunocytoma (n = 20/20), in 2/3 of MALT-lymphomas (n = 24/38) and 1/2 of monocytoid B-cell lymphoma cases (n = 4/7), in 1/5 of centroblastic-centrocytic lymphoma cases (n = 12/60) and rarely in centrocytoma (n = 4/36). We conclude that a plasmacytic differentiation is not an unique feature of the immunocytoma. For the differential diagnosis, a histological analysis and not a proof of monoclonal c-Ig itself seems to be decisive. The obtained results are discussed in relation to the histogenesis of small B-cell lymphomas, which represent a neoplastic counterpart of the reactive B-cells at different stages of their maturation and differentiation.     

BCL6 gene rearrangements also occur in marginal zone B-cell lymphoma

Marginal zone B-cell lymphoma (MZBCL) represents a distinct subtype of B-cell non-Hodgkin's lymphoma (NHL) which has been recently recognized and defined as a disease entity. Cytogenetically, these lymphomas reveal a high prevalence of trisomy 3, and recent data obtained by comparative genomic hybridization indicate that the chromosomal regions 3q21-23 and 3q25-29 might be of particular pathogenetic significance. We identified structural chromosomal abnormalities involving the region 3q27 and rearrangements of the BCL6 proto-oncogene in three out of 34 (9%) well-defined cases of extranodal, nodal and splenic MZBCL using cytogenetic analysis. Southern blot, and fluorescence in situ hybridization (FISH). All three cases were characterized by a t(3;14)(q27;q32). Two of them showed additional chromosomal abnormalities including trisomy 3, which was found in one case. The patients displayed extranodal disease and did not demonstrate any striking clinical and histological differences when compared with MZBCL lacking BCL6 rearrangement. The present study for the first time demonstrates the occurrence of t(3;14)/BCL6 gene rearrangement in MZBCL, thus suggesting a role of the BCL6 proto-oncogene in the pathogenesis of MZBCL.     

Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells

Two patients with plasma cell leukemia (PCL) with a t(11;14)(q13;q32) translocation are reported. Case 1 is a 64-year-old woman diagnosed as having primary PCL (IgA/lambda, Stage III) with high serum LDH and beta 2-microglobulin (beta 2MG) levels. She was treated with combination chemotherapy but died of gastrointestinal bleeding on the 45th hospital day. Case 2 is a 52-year-old man, initially diagnosed with multiple myeloma (IgG/kappa, Stage III) in August 1993. Relapse several months after primary chemotherapy was characterized by a rapid increase in plasma cells in peripheral blood, high serum LDH and beta 2MG levels, and resistance to further chemotherapy. Both cases showed complex karyotypic abnormalities including t(11;14), and Northern analysis revealed overexpression of the PRAD1/ cyclin D1 gene. The PRAD1 gene is found on chromosome band 11q13 and encodes cyclin D1. Cyclin D1 plays an important role in control of the cell cycle, and overexpression of PRAD1/cyclin D1 may be involved in disease progression in these cases.     

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.     

Chronic malaria and splenic lymphoma: clues to understanding lymphoma evolution

In west Africa, splenic lymphoma with villous lymphocytes and hyper-reactive malarial splenomegaly have many clinical and immunological features in common suggesting an aetiopathological link. We hypothesize that in hyper-reactive malarial splenomegaly the dysregulated immune response to repeated malaria infections results in a stimulated, proliferating pool of B cells in which perturbation of cell growth and apoptosis by environmental and other factors promotes the development of SLVL. In Africa these factors are likely to include infectious agents several of which have already been associated with B-cell non-Hodgkin's lymphomas.     

Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas

The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin G1 gene family, and thereby to contribute to tumorigenesis. We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC). We have determined the nucleotide sequence for a portion of the MTC region, and constructed chromosome 11-specific oligonucleotides that were in conjunction with a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to PCR detection. The sizes of the amplified bands, the existence or not of a Sac I site in the PCR products, and nucleotide sequencing of the amplified DNA from four patients showed that the breakpoints share a remarkable tendency to tightly cluster within 300 bp on chromosome 11, some of them occurring at the same nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH. Our findings indicate that a BCL1 rearrangement can be detected using this approach in roughly one half of the MCL patients. This has implications for both the diagnosis and the clinical management of MCL.     

A DR17-restricted T cell epitope from a secreted Mycobacterium tuberculosis antigen only binds to DR17 molecules at neutral pH

Mantle cell lymphoma (MCL) was first described as a distinct biological entity on the basis of its association with the t(11;14)(q13;q32) resulting in over-expression of the cyclin D1 gene. Recognition of the morphological, immunophenotypic and clinical characteristics of MCL has enabled the accurate diagnosis of this entity and appreciation of its poor prognosis. Most published series of patients with MCL have used anthracycline-containing regimens. In contrast the British National Lymphoma Investigation (BNLI) group have treated 65 patients with MCL with non-intensive 'low-grade lymphoma' therapy. The median overall survival of 57 months and progression-free survival of 24 months compares favourably with the more intensively treated series. Although the disease was generally more aggressive than other low-grade lymphomas, some patients were asymptomatic and had indolent disease. When compared to 1853 patients with non-MCL low-grade lymphomas entered on the BNLI database, patients were found on average to be older (P=0.02), to have more extranodal disease (P<0.00001), and a higher proportion to have a raised ESR (P=0.02) and a low serum albumin (P=0.002). Multivariate analysis of significant prognostic markers in all BNLI low-grade lymphomas failed to identify MCL as an independent prognostic factor.