Childhood de novo CD5+ Diffuse Large B-cell Lymphoma: a Separate Entity? (original) (raw)
Related papers
De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients
Blood, 2002
De novo CD5 ؉ diffuse large B-cell lymphoma (CD5 ؉ DLBCL) is known to have phenotypically and genotypically different characteristics than CD5 ؊ DLBCL and mantle cell lymphoma (MCL). To further characterize CD5 ؉ DLBCL, 109 patients with CD5 ؉ DLBCL were reviewed, and the results were compared with those of 384 CD5 ؊ DLBCL and 128 cyclin D1 ؉ MCL patients. Patients with CD5 ؉ DLBCL showed a higher age distribution (median, 66 years; P ؍ .0083) and a female predominance (male-female ratio, 49:60, P ؍ .011) compared with those with CD5 ؊ DLBCL. CD5 ؉ DLBCL was more closely associated with many aggressive clinical features or parameters than CD5 ؊ DLBCL: 69% older than 60 years (P ؍ .039), 34% with performance status greater than 1 (P ؍ .0016), 69% with serum lactate dehydrogenase level higher than normal (P < .0001), 62% with stage III/IV disease at diagnosis (P ؍ .0023), 35% with more than one extranodal site (P ؍ .023), and 40% with B symptoms (P ؍ .0031). The overall International Prognostic Index score was thus significantly higher for the patients with CD5 ؉ DLBCL than for those with CD5 ؊ DLBCL (P ؍ .00005). The most frequent site of extranodal involvement was bone marrow (28%), a higher frequency than that for CD5 ؊ DLBCL (P < .0001) but lower than that for cyclin D1 ؉ MCL (P ؍ .0015). Histopathologically, CD5 ؉ DLBCL showed centroblastic morphology except for 3 patients with immunoblastic disease, and interfollicular growth pattern (7%) and intravascular or intrasinusoidal infiltration (19%) were observed. Immunophenotypically, CD5 ؉ DLBCL was characterized by a CD5 ؉ CD10 ؊ CD19 ؉ CD20 ؉ CD21 ؊ CD23 ؊ cyclin D1 ؊ phenotype and a predominance of surface IgM. Of particular interest is that CD5 ؉ DLBCL was characterized by a survival curve significantly inferior to that for patients with CD5 ؊ DLBCL (P ؍ .0026). These findings suggest that CD5 ؉ DLBCL may constitute a unique subgroup of DLBCL.
CD5-Positve Diffuse Large B-Cell Lymphoma Presenting in Bone Marrow without Lymphadenopathy
Journal of Clinical and Experimental Hematopathology, 2001
In this study, we reported five cases of CD5+ diffuse large B-cell lymphoma (DLBCL) which initially presented as bone marrow involvement without lymphadenopathy. The cases involved two males and three females, with an average age of 73.8 years. The patients had fever and showed general fatigue. Three of the five cases presented hepatosplenomegaly. Laboratory examination highlighted anemia, thrombocytopenia, presence or absence of leukopenia, hypoalbuminemia as well as a considerable elevation of serum lactate dehydrogenase, soluble IL-2R and ferritin. Bone marrow aspiration smears showed large-sized lymphoma cells, which were found to aggregate, and clot sections showed many clusters of lymphoma cells, which had a large and round or indented nucleus with vesicular chromatin and occasional small nucleoli. Mitotic rate was high. In the bone marrow clot section, whereas three cases exhibited a diffuse infiltration of the lymphoma cells (diffuse type), two cases exhibited a sinusoidal proliferation (intravascular type). Cytogenetic analysis showed many and complex abnormalities in all 3 cases examined. The lymphoma cells were positive for CD5, CD19, CD20, CD38, IgM, bcl-2 and bcl-6, while they were negative for CD3, CD10, CD23, CD30, cyclin D1 and TdT. In four cases, after a semi-nested PCR amplification of the immunoglobulin heavy chain (IgH) gene, a discrete band could be detected. All the cases exhibited an in-frame sequence and the frequency of somatic mutations ranged from 2.1 to 11.1% with no intraclonal diversity. These DLBCL may have derived from the same counterpart as CD5+ B-CLL. There were no differences in laboratory, immunological and molecular examination between the diffuse type and the intravascular type. Recurrences in the bone marrow and an aggressive clinical course were also observed in both types. Key words CD5, bone marrow, diffuse large B-cell lymphoma, immunoglobulin heavy chain gene
A rare case of de novo CD5+ diffuse large B-cell lymphoma in leukemic phase and positive for CD13
Hematology Reports
We report a case of de novo diffuse large B-cell lymphoma (DLBCL) in leukemic phase, positive for both CD5 and CD13. Morphologic evaluation, flow cytometric immunophenotyping, karyotyping and polymerase chain reaction studies were performed. Neoplastic lymphocytes appeared as blast-like cells, positive for CD19, CD20, CD5, CD13, CD79a, HLADR, and with restriction for surface immunoglobulin K light chains. Rearrangement of IgH gene, BCL2/IgH translocation and complex karyotype were found. The patient was treated with RCOMP regimen and achieved complete remission. However, only one month after the first restaging of disease, the patient presented with symptoms attributable to central nervous system involvement and her clinical conditions worsened rapidly. While both CD5 expression and leukemic presentation are uncommon findings in DLBCL, positivity for CD13 is very rare. The outcome of our patient shows the poor prognosis of CD5+ DLBCL with leukemic presentation. The possible role of ...
Follicular Origin of a Subset of CD5+ Diffuse Large B-Cell Lymphomas
American Journal of Clinical Pathology, 2005
10% of DLBCLs, showing prognostic value, whereas expression is rare in FL. We present 6 cases with coexisting features of CD5+ FL and CD5+ DLBCL, supporting a follicular origin for some CD5+ DLBCLs. The follicular areas showed a meshwork of CD21+ follicular dendritic cells that were lacking in the DLBCL areas. All cases showed a clonal CD19+, CD20+, CD5+, and CD10+ population in both follicular and diffuse areas. Molecularly, 4 of 6 cases demonstrated immunoglobulin heavy chain rearrangements and 1 case, a bcl-2/immunoglobulin heavy chain gene rearrangement. Somatic hypermutations were high in all 4 cases, in keeping with their germinal center origin. Four of five patients died of disease within 42 months, consistent with the proposed prognostic value of CD5 expression in DLBCL. Our data describe an aggressive variant of CD5+ FL suggesting the follicular origin of some CD5+ DLBCLs.
Leukemia, 1999
Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5 + type, n = 11), group II (CD5 − CD10 + type, n = 19), and group III (CD5 − CD10 − type, n = 33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P = 0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5 − CD10 + type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.
De Novo CD5-Positive Diffuse Large B-Cell Lymphoma
International Journal of Surgical Pathology
D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma.
Blood, 2006
Diffuse large B-cell lymphoma (DLBCL) in adults is a heterogeneous disease. Biologic subgroups of DLBCL with a favorable prognosis (germinal center B-cell–like, GCB) and with a poor prognosis (activated B-cell–like, ABC) have been defined by gene expression profiling and can be distinguished by immunohistochemistry. In contrast to their adult counterparts, children with DLBCL have an excellent prognosis. We analyzed 63 cases of DLBCL in pediatric patients by immunohistochemistry and fluorescence in situ hybridization (FISH) and found a striking predominance of a GCB subtype, which might explain the good clinical outcome in these lymphomas. Interestingly, FISH applied to 50 of these cases, as well as conventional cytogenetics available in 3 cases, revealed absence of the translocation t(14;18) involving the BCL2 gene, which is present in about 15% of adult GCB subtype DLBCL. Our data indicate that pediatric DLBCL differs from adult DLBCL and might comprise a biologically unique subgr...
Polish Journal of Pathology
The aim of the study was to assess the incidence of CD5-positive diffuse large B-cell lymphoma (DLBCL) in the Polish population and to describe its morphologic and clinical characteristics. The study included 36 patients with CD5-positive DLBCL, diagnosed and treated in the Maria Skłodowska-Curie Institute and Oncology Centre, Warsaw, Poland and the Medical University of Warsaw, Poland in the years 2002-2013. The control group consisted of 28 patients with CD5-negative DLBCL. CD5-positive DLBCL accounted for 6.26% of all DLBCL cases diagnosed in the Maria Skłodowska-Curie Institute and Oncology Centre in the years 2008-2012. The incidence is comparable to other European countries, lower than noted in Japan and higher than in the US. Patients with CD5-positive DLBCL, in comparison to the CD5-negative group, were characterized by: (1) older age (≥ 60 vs. younger) and worse general status (ECOG ≥ 2 vs. < 2), (2) lower frequency of complete remission (CR), (3) higher expression of unfavorable prognostic factors (BCL2, FOXP1, CD44) and MMP-9, and (4) lower expression of CD30, cyclin D1, cyclin D3 and TIMP-2.