Diffuse Small Cleaved Cell Lymphoma Research Articles

Serum-soluble fas level determines clinical symptoms and outcome of patients with aggressive non-Hodgkin's lymphoma.

Soluble Fas (sFas) blocks apoptosis induced by Fas ligand in vitro. The serum concentration of sFas is elevated in lympho-proliferative diseases. We hypothesized that higher levels of sFas worsen the clinical symptoms and outcome of patients with aggressive non-Hodgkin's lymphoma (NHL). We prospectively measured the serum concentrations of sFas in 67 consecutive patients with aggressive NHL (59 with diffuse large cell lymphoma and 8 with diffuse small cleaved cell lymphoma). sFas was significantly elevated in patients with aggressive NHL compared to healthy controls (N = 36, P< 0.005), while sFas in patients with B symptoms (4.20 +/- 2.12 microg/l) was significantly higher than in those without B symptoms (2.66 +/- 1.08 microg/l, P < 0.005). No significant difference was observed between B-cell lymphoma and T-cell lymphoma or between patients with clinical stage I or II and those with clinical stage III or IV. Significant correlations were found between sFas concentration and both soluble interleukin-2 receptor (R = 0.400, P < 0.001) and C-reactive protein (R = 0.340, P < 0.01) levels in patients with aggressive NHL. No correlation was observed between sFas and either white blood cell count or lactate dehydrogenase. Generalized Wilcoxon analysis revealed that NHL patients with sFas less than 4 microg/l had better overall survival than those with sFas above 4 microg/l (P < 0.001). The serum concentration of sFas might be associated with clinical symptoms and the prognosis of patients with aggressive NHL.

High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission.

The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT.

Lymphoid cell aggregates: A useful clue in the fine‐needle aspiration diagnosis of follicular lymphomas

Among the various types of lymphoma, follicular lymphoma (FL) is known to have significant limitations in cytologic diagnosis by the fine-needle aspiration (FNA) method. The diagnostic accuracy (DA) for non-Hodgkin's lymphoma (NHL) by FNA was evaluated by review of 82 cases of histologically proved NHL after prior FNA. The DA for all NHLs was 66% (54/82), and that for low-grade lymphomas, including small lymphocytic lymphoma, follicular small-cleaved cell lymphoma, and follicular mixed cell lymphoma, was 71% (12/17). The DA for FL was 69% (11/16). Review of individual surgical and cytologic materials from FLs revealed a tendency to show fibrosis in the cytologically false-negative group and diffuse areas of lymphoma in the true-positive group. The presence of “aggregation” of uniform lymphoid cells, probably due to cell adhesions with the support of dendritic reticulum cells, was seen in 55% of true-positive FL (6/11). In contrast, only 28% of true-positive diffuse large cell lymphomas (5/18) showed a mild degree of aggregation, and none of 7 cases of true-positive diffuse small-cleaved cell lymphoma showed this feature. The aggregation of cells was not pathognomonic of FL, but its presence with a homogeneous cellular constituent and the paucity of tingible-body macrophages helped us to predict FL. Also, it was a feature distinguishing FL from diffuse small-cleaved cell lymphoma (P = 0.025). Diagn. Cytopathol. 1997;17:467–471. © 1997 Wiley-Liss, Inc.

Lymphoid cell aggregates: A useful clue in the fine-needle aspiration diagnosis of follicular lymphomas

Among the various types of lymphoma, follicular lymphoma (FL) is known to have significant limitations in cytologic diagnosis by the fine-needle aspiration (FNA) method. The diagnostic accuracy (DA) for non-Hodgkin's lymphoma (NHL) by FNA was evaluated by review of 82 cases of histologically proved NHL after prior FNA. The DA for all NHLs was 66% (54/82), and that for low-grade lymphomas, including small lymphocytic lymphoma, follicular small-cleaved cell lymphoma, and follicular mixed cell lymphoma, was 71% (12/17). The DA for FL was 69% (11/16). Review of individual surgical and cytologic materials from FLs revealed a tendency to show fibrosis in the cytologically false-negative group and diffuse areas of lymphoma in the true-positive group. The presence of "aggregation" of uniform lymphoid cells, probably due to cell adhesions with the support of dendritic reticulum cells, was seen in 55% of true-positive FL (6/11). In contrast, only 28% of true-positive diffuse large cell lymphomas (5/18) showed a mild degree of aggregation, and none of 7 cases of true-positive diffuse small-cleaved cell lymphoma showed this feature. The aggregation of cells was not pathognomonic of FL, but its presence with a homogeneous cellular constituent and the paucity of tingible-body macrophages helped us to predict FL. Also, it was a feature distinguishing FL from diffuse small-cleaved cell lymphoma (P = 0.025).

Correlation Between Mutation in P53, p53 Expression, Cytogenetics, Histologic Type, and Survival in Patients With B-Cell Non-Hodgkin's Lymphoma

AbstractIn the biology of a cell, the central role of p53 in controlling functions such as G1/S transition (check point) and DNA damage repair, and as a trigger of apoptosis, is well established. Somatic mutations or other changes in P53 have been reported in numerous tumor types, and in some of these, they are associated with poor prognosis. In this study, we examined 237 cytogenetically characterized B-cell non-Hodgkin's lymphomas (B-NHLs) for somatic changes in P53 by Southern blot analysis, by single-strand conformation polymorphism analysis (SSCP) of exon 5 through 9, and by direct sequencing of SSCP variants to determine the frequency and types of mutations and their clinical significance. In a portion of these (173 tumors), we also studied p53 expression by immunostaining. On Southern blots, no gross change was identified in P53 and no mutation was identified in exon 9. In exons 5 through 8, 27 different mutations were identified in 25 patients (23 single-base substitutions, 3 deletions, 1 duplication). Mutations in P53 were identified in 25 of 237 tumors (10.5%), which included 1 of 45 small lymphocytic lymphomas (SLLs), 2 of 38 follicular small cleaved-cell lymphomas (FSCCs), 2 of 35 follicular mixed small cleaved-cell and large-cell lymphomas (FMxs), 1 of 4 follicular large-cell lymphomas (FLCs), 1 of 14 diffuse small cleaved-cell lymphomas (DSCCs), 2 of 17 diffuse mixed small- and large-cell lymphomas (DMxs), and 16 of 84 diffuse large-cell lymphomas (DLCCs); the difference between the histologic groups was significant (P < .01). Among mantle-cell lymphoma (MC) patients, 3 of 10 had mutations. In 16 patients, the mutation was identified in specimens obtained at diagnosis. Mutation of transition type and transversion type occurred at a relative frequency of 2:1. Thirty percent occurred at CpG dinucleotide sequences and the codon for arginine was most frequently affected. Nineteen of 99 tumors with complex cytogenetic abnormalities, but none of 69 tumors with simple cytogenetic abnormalities, had mutations (P < .001). Similarly, 11 of 25 tumors with an abnormality of 17p and 8 of 143 tumors with apparently normal 17p had mutations (P < .0001). Positive correlations were found between a mutation and p53 expression (P < .001), between missense type mutations and p53 expression (P < .005), and between 17p abnormalities and p53 expression (P < .05). Twenty-two of 49 patients without mutation and 14 of 17 patients with mutations died (P < .05), but there was no significant difference in median survival. Similarly, 21 of 26 p53 positive patients died, whereas only 1 of 24 p53-negative patients died on-study (P < .001). Among p53-negative patients, mutation (P < .01) was positively associated with a fatal outcome. These findings indicate that in B-NHL, somatic changes in P53 were present in diagnostic specimens of all histologic types, but at a higher frequency in DLC and MC tumors. P53 mutation and/or expression has a negative influence on survival, and therefore can serve as prognostic indicators. Immunostaining for p53 is an effective way to screen for P53 changes in these tumors.

Association of Epstein-Barr virus with sinonasal angiocentric T cell lymphoma.

To investigate whether non-Hodgkin's lymphomas arising in the sinonasal region or Waldeyer's ring contain the Epstein-Barr virus (EBV) genome in lesional tissue. Sections from paraffin wax blocks of 22 lymphoid proliferations arising in the sinonasal region or Waldeyer's ring were studied with EBV encoded RNAs (EBER-1 and -2) using in situ hybridisation. EBV was detected in nuclei of tumour cells of five of seven T cell lymphomas and in nuclei of two of seven diffuse, large cell immunoblastic lymphomas of B phenotype in the sinonasal region. Of tumours arising in Waldeyer's ring, two of 10 non-Hodgkin's lymphomas (both large cell) were positive, as was a single case of Hodgkin's disease. Lymphoma of other types, including Western type Burkitt's lymphoma, and nodular and diffuse small cleaved cell lymphoma, were negative. EBV is highly associated with large cell lymphomas especially T cell lymphomas of sinonasal origin in the indigenous Irish population, underlining the importance of this virus in nasopharyngeal lymphomas in Northern European as well as Asian populations.

The Presence of bcl-1 and bcl-2 Gene Rearrangements in Diffuse Small Cleaved-Cell Lymphoma

Clonal rearrangements of the bcl-1 and bcl-2 protooncogenes are found in many B-lineage non-Hodgkin's lymphomas (NHL) and may play a role in their pathogenesis. We investigated rearrangements of the bcl-1 and bcl-2 protooncogenes in 13 cases of B lineage diffuse small cleaved-cell lymphoma (DSCL), and correlated the results with clinical history, immunophenotype, and outcome. Six cases showed bcl-2 rearrangements, including four patients with an antecedent follicular small cleaved-cell lymphoma (FSCL). Two patients had a bcl-1 rearrangement, including one with a previous FSCL. Of the five patients who lacked detectable bcl-1 or bcl-2 rearrangements, one had an FSCL history. Similar to the lack of correlation between clinical history and genotype, there was no correlation between genotype and immunophenotype. Our results indicate that although DSCL is a morphologically uniform disease, different molecular genetic pathways are involved in its genesis. Follow-up showed four of the six DSCL patients with bcl-2 rearrangements were alive with a median survival of 56 months, whereas the median survival of the seven patients lacking a bcl-2 rearrangement was 17 months and included only one survivor. Thus bcl-2 rearrangements in DSCL may define a patient subset with a more indolent genetic abnormality and prolonged survival.

Mantle cell lymphoma

The term mantle cell lymphoma (MCL) has been introduced recently, to describe lymphomas related to the primary B follicle and the mantle of the secondary lymphoid follicle. MCL forms a subset of diffuse small cleaved cell lymphomas according to the Working Formulation and correspond closely to the centrocytic lymphomas described in the Kiel classification. They form a distinct clinico-pathological entity and are associated with a specific cytogenetic abnormality; the t(11;14)(q13;q32), which can be detected at a molecular level by rearrangement of the bcl-1 oncogene. As diagnostic criteria for MCL have now been precisely outlined and the clinical presentation described, it should be possible in the future to develop rational treatment protocols for this group of patients, who have a notoriously poor prognosis.

Orbital and adnexal involvement in systemic non-Hodgkin's lymphoma.

The orbit is rarely a secondary site of lymphoma dissemination, and only few reports exist on the course and characteristics of involvement in these sites. The authors retrospectively reviewed the records of 187 consecutive patients with systemic non-Hodgkin's lymphoma (NHL) diagnosed and treated at Beilinson Medical Center between 1986 and 1992. Ten patients (5.3% of those with NHL) had orbital or adnexal involvement or both. Histologically, six had intermediate-grade lymphoma, three had diffuse small cleaved cell lymphoma, and one had nodular small cleaved cell lymphoma. In all 10 patients, the lymphoma was widespread, and in 6, there were two or more other extranodal sites of involvement, mainly, bone marrow (six) and skin (three). The orbital involvement was found either at presentation or as late as 53 months after primary diagnosis. Various therapeutic approaches were chosen, from local orbital irradiation to different mild to aggressive chemotherapeutic protocols. Complete regression of the orbital or adnexal involvement or both was observed in 9 of 10 patients, but in 6 the systemic disease either persisted or recurred at other sites. Orbital or adnexal involvement or both by NHL may appear at any time during the course of the disease. It responds well to either chemotherapy or radiation therapy with prolonged local remission. The results of this study strongly suggest that every patient with NHL in whom any periorbital or orbital mass, ptosis, proptosis or lid edema develops should be suspected of having orbital lymphoma involvement until proven otherwise.

Mantle-cell lymphoma

Histological subtyping of non-Hodgkin's lymphomas is of prognostic significance. Current classification systems subdivide them into low-, intermediate-, and high-grade malignancies. These subgroups are largely supported by clinical findings, but immunophenotyping and genotyping have shown that several of these histologically defined subcategories are heterogeneous. This is exemplified by the 'diffuse small cleaved-cell lymphoma' which comprises B-cell and T-cell lymphomas. Moreover, within the B-cell lymphomas, several entities have been included, which recapitulate the different compartments present in the reactive B follicle, e.g., the follicle centre, the mantle, and the marginal zone. Mantle-cell lymphomas have been identified in the United States as mantle-zone lymphomas and as intermediate differentiated lymphomas and in Europe as centrocytic lymphomas. Morphology, immunophenotyping, and cytogenetics of these three lymphomas support their similarity and underline their distinction from follicle centre-cell lymphomas as well as from small lymphocytic lymphomas. All three are composed of a mixture of small round and small cleaved cells, expressing several B-cell markers, surface immunoglobulins, and CD5, but lacking CD10 expression. They often carry the translocation t(11;14) with rearrangement of bcl-1/PRAD1 gene. The behaviour and responsiveness to therapy of mantle-cell lymphomas has not been fully documented yet. In order to obtain these data, precise subtyping of non-Hodgkin's lymphomas--not only based on morphology, but supported by immunophenotyping and cytogenetic analysis--is now mandatory.

Bcl-2 Gene Expression in Hematopoietic Cell Differentiation

Nonrandom translocations with breakpoint at band q21 on chromosome 18 might cause bcl-2 gene deregulation and might contribute to neoplastic transformation in human lymphomas. As the pattern of expression of bcl-2 in hematopoietic cells is still unclear, we have measured the level of the corresponding messenger RNA (mRNA) in a variety of myeloid and lymphoid cell malignancies not usually associated with the t(14;18) translocation. Molecular genetic analysis showed that bcl-2 was rearranged in only 2 of 77 patients: one was affected by hairy cell leukemia and one by diffuse small cleaved cell lymphoma with peripheral blood invasion. Although in rare cases of myeloid leukemia fairly high levels can be found, the expression of bcl-2 appears to be typical of certain lymphoid malignancies. High levels of bcl-2 mRNA had been found, previously, in established pre-B-cell lines. However, in fresh specimens, the peak level of bcl-2 expression shifts to a more differentiated cell type, represented by the long-living B lymphocytes that are found in most cases of chronic lymphocytic leukemia. bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder.

Bcl-2 gene expression in hematopoietic cell differentiation

Nonrandom translocations with breakpoint at band q21 on chromosome 18 might cause bcl-2 gene deregulation and might contribute to neoplastic transformation in human lymphomas. As the pattern of expression of bcl- 2 in hematopoietic cells is still unclear, we have measured the level of the corresponding messenger RNA (mRNA) in a variety of myeloid and lymphoid cell malignancies not usually associated with the t(14;18) translocation. Molecular genetic analysis showed that bcl-2 was rearranged in only 2 of 77 patients: one was affected by hairy cell leukemia and one by diffuse small cleaved cell lymphoma with peripheral blood invasion. Although in rare cases of myeloid leukemia fairly high levels can be found, the expression of bcl-2 appears to be typical of certain lymphoid malignancies. High levels of bcl-2 mRNA had been found, previously, in established pre-B-cell lines. However, in fresh specimens, the peak level of bcl-2 expression shifts to a more differentiated cell type, represented by the long-living B lymphocytes that are found in most cases of chronic lymphocytic leukemia. bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder.

Classification and staging of lymphoma by molecular genetics.

Recombinant DNA technology has provided a wealth of new observations in the study of lymphoma. Progress has been enhanced by the unique rearrangement of immune-specific genes during normal lymphocyte differentiation. Because these gene rearrangements are irreversible and are inherited in all cellular progeny, lymphoid tumors have a monoclonal genomic structure. Molecular analysis of genomic structure is a powerful new method of assessing clonality and lineage to supplement histologic examination in achieving accurate diagnosis and staging of lymphomas. Furthermore, the frequent occurrence of translocations in lymphoid neoplasms provides a second pathway for genomic analysis. In 57 B-cell lymphomas tested by Southern blot and polymerase chain reaction, the authors found evidence of bc12 gene translocation in 100% of follicular small cleaved cell lymphomas, 67% of diffuse small cleaved cell lymphomas, 33% of mixed lymphomas, 25% of diffuse large cell lymphomas, and 25% of small noncleaved lymphomas. They also describe their experience with immunoglobulin heavy chain and T-cell receptor beta chain genomic analysis as well as review the published literature on the utility of molecular genetics in the classification and staging of lymphoma. Future applications of molecular diagnostics in the clinical management of lymphoma patients are assessed.

Chromosome 1p Abnormalities in B Non Hodgkin's Lymphoma

Thirteen patients with B-non Hodgkin's lymphoma and abnormalities of the short arm of chromosome 1 were evaluated, to see if this cytogenetic anomaly was associated with a particular subgroup of lymphomas. Large cell lymphoma was found in seven patients (with an immunoblastic component in four cases). Six patients with diffuse small cleaved cell lymphoma of non follicle centre cell origin formed a second group. The chromosome 1 breakpoints in the second group were located between p34 and p36, suggesting that genes located here may be important in the initiation or progression of these lymphomas.

Breakpoints of 11q25 in Three Similar Cases of B Non Hodgkin's Lymphoma

We report three cases of small B cell non Hodgkins lymphoma, two with plasmacytoid differentiation, presenting with a similar clinical picture and identical immunophenotype, who cytogenetically had breakpoints involving band 11q25. We suggest that this breakpoint may define a group of lymphomas closely related to the diffuse small cleaved cell lymphomas with t(11;14)(q13;q32).

Diffuse intermediate lymphocytic lymphoma. A clinicopathologic study and comparison with small lymphocytic lymphoma and diffuse small cleaved cell lymphoma

Controversy has recently arisen as to whether diffuse intermediate lymphocytic lymphoma (ILL) should be considered a low-grade or an intermediate-grade non-Hodgkin's lymphoma for clinical purposes. Therefore, the authors performed a clinicopathologic study to determine the biologic course of diffuse ILL (40 cases) and compared it with small lymphocytic lymphoma (SLL; 51 cases) and diffuse small cleaved cell lymphoma (DSCCL; 14 cases). They found that patients with diffuse ILL having pseudofollicular proliferation centers (PC) had a significantly longer median survival (84 months) than those without PC (46.5 months; P = 0.03). The median survival of patients with SLL was 72 months, whereas those with DSCCL had a median survival of only 18 months. Based on these findings, the authors conclude that diffuse ILL with PC should be included in the low-grade category of SLL for clinical purposes, whereas diffuse ILL without PC (true diffuse ILL) should be considered an intermediate-grade non-Hodgkin's lymphoma. True diffuse ILL is similar to centrocytic lymphoma in the Kiel classification and should be accorded a similar status in a modified Working Formulation.

Cytogenetic analysis of 147 cases of non‐Hodgkin's lymphoma: non‐random chromosomal abnormalities and histological correlations

A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease.

Expression of the activation antigen, 4F2, by non-Hodgkin's lymphomas of B-cell phenotype

The monoclonal antibody, 4F2, which reacts with an antigen expressed by activated and proliferating cells, was applied to frozen sections of nine reactive lymphoid lesions, 146 B-cell non-Hodgkin's lymphomas (NHL), and six plasmacytic neoplasms. In reactive cases, the 4F2 antigen was expressed by germinal center cells and interfollicular immunoblasts, the activated or proliferating lymphoid cells, and histiocytes. In the malignant cases, the 4F2 antigen was expressed by 94 (64%) B-cell NHL and all six plasma cell tumors. The incidence of positivity and intensity of expression loosely correlated with the three morphologic grades of NHL identified in the Working Formulation. Approximately one half of all low-grade lymphomas, two thirds of intermediate-grade lymphomas, and all high-grade lymphomas were 4F2 positive. Similarly, the mean intensity of 4F2 antigen expression increased with higher grade. However, for certain histologic subtypes, 4F2 antigen expression did not correlate with morphologic grade. For example, in the intermediate-grade category less than one half of diffuse small cleaved cell lymphomas were 4F2 positive, and expression was weak, similar to that of low-grade lymphomas. In contrast, all other histologic subtypes of lymphoma in the intermediate-grade category were strongly 4F2 positive. Expression of 4F2 antigen also correlated with plasmacytoid differentiation. Seventy-three percent of plasmacytoid small lymphocytic lymphomas (compared with 31% of cases of non-plasmacytoid small lymphocytic lymphoma/chronic lymphocytic leukemia) and all plasma cell neoplasms expressed the 4F2 antigen, the latter cases strongly.

Break in the BCL1 locus is closely associated with intermediate lymphocytic lymphoma subtype

The t(11;14)(q13;q32) is a recurring translocation associated with some chronic B-cell lymphocytic malignancies; the putative protooncogene BCL1, located at the chromosome band 11q13, can be involved during the translocation process. In order to determine if BCL1 rearrangement is associated with a particular subtype of lymphoma, we analysed 131 B-cell non-Hodgkin's lymphoma samples by Southern blot analysis, using a BCL1 probe. The BCL1 locus was rearranged in 9 out of 25 (36%) cases of intermediate lymphocytic cell lymphomas (ILL), in 1 out of 8 cases of diffuse small cleaved cell lymphoma, in 1 out of 12 cases of diffuse mixed cell lymphoma, and in 1 out of 21 cases of diffuse large cell lymphoma. In contrast, BCL1 was never found rearranged in any of the 46 follicular lymphomas analysed. The BCL2 gene was in germ-line configuration in all ILL. Sequential hybridization of Southern blots with JH, C mu, and BCLI probes identified comigrating fragments in only one case of ILL, which suggests that, in all the other cases, either the rearrangement of BCL1 did not result from a t(11;14) translocation or the break on chromosome 14 occurred outside the JH or C mu regions. These results indicate that rearrangement of the BCL1 locus may be closely associated with ILL and could be considered as a genotypic marker of this lymphoma subtype.

Dendritic Reticulum Cells and Immunophenotype in Aspiration Biopsies of Lymph Nodes: Value in the Subclassification of Non-Hodgkin's Lymphomas

Twenty-seven lymph node aspirates were identified for which histologic confirmation of non-Hodgkin's lymphoma was subsequently obtained. Fifteen aspirates interpreted as reactive hyperplasia were also examined. All aspirates were studied by immunoperoxidase on cytospin preparations with the use of antibodies DRC1, kappa, lambda, CD3, CD5, and CD20. The follicular lymphomas could not be identified reliably by morphologic examination of aspirate smears. Clusters of DRC1-positive (DRC1+) cells were present in seven of seven follicular lymphomas, one of one mantle zone lymphoma, and one of seven small lymphocytic lymphomas. Rare DRC1+ cells were present in one of one diffuse mixed and one of seven large cell lymphomas. One lymphoblastic, one Burkitt's, and two diffuse small cleaved cell lymphomas had no DRC1+ cells. None of the seven follicular lymphomas was CD5 positive (CD5+), whereas five of the seven small lymphocytic lymphomas were CD5+. Conversely, all seven follicular lymphomas were CD20-positive (CD20+), but only one of seven small lymphocytic lymphomas was CD20+. Nineteen of the lymphomas, including all 7 of the follicular lymphomas, were either kappa or lambda positive. The other eight lymphomas were T-cell (1), B-cell (1), true histiocytic (1), or "null" cell (5). The reactive aspirates had both kappa- and lambda-positive B-cells. Seven of the 15 had clusters of DRC1+ cells. To further evaluate these antibodies, the authors studied 29 additional, surgically biopsied, non-Hodgkin's lymphomas that had not been aspirated. Similar results were obtained, except that three of five diffuse small cleaved cell lymphomas had DRC1+ cells. DRC1, in conjunction with antibodies to CD5, CD20, kappa, and lambda, helps to distinguish follicular lymphoma from small lymphocytic lymphoma. DRC1 is not useful in separating reactive hyperplasia from follicular lymphoma.