DLBCL in the pediatric group is a rare neoplasm and usually has an extranodal presentation (31
). DLBCL constitutes about 10 to 20% of juvenile and pediatric NHL (7
). There are few reports in the literature dealing exclusively with nodal DLBCL in this age group (31
). This is especially true of studies in which the cases of pediatric DLBCL are divided in GCB and non-GCB types (31
Hans et al. (13
) demonstrated that the expression of CD10, BCL-6, MUM1, BCL-2, and cyclin D2 are each predictive of survival in DLBCL, and that the results for CD10, BCL-6, and MUM1 can be combined to divide DLBCL into GCB and non-GCB subgroups, with an outcome similar to that predicted by cDNA microarray analysis.
CD10 expression in DLBCL varies from 39 to 100% in different series (7
). We found a lower frequency of CD10 expression with 24% of our cases being positive for this marker. However it must be kept in mind that in these series, that used the same anti-CD10 antibody, most of the cases were extranodal without enough data to determine the frequency of expression in nodal cases alone (25
). BCL-6 expression was observed in 75 to 90% of cases in the literature (7
); in agreement, we detected BCL-6 expression in 87% of our cases.
Our cases showed a higher frequency of BCL-2 (63%) expression than previously reported series, 63% vs 29-40%, (7
). It has been reported that BCL-2 expression in pediatric patients does not indicate a poor prognosis (31
), in agreement with what we found in our series. It has also been established in adult patients that the adverse outcome associated with BCL-2 expression is observed only in non-GCB lymphomas (17
). In our series all the patients who had BCL-2 expression and died of disease belonged to the non-GCB type.
The GCB type is more prevalent in our nodal pediatric cases than the non-GCB, but the difference is less evident than in the series of mixed nodal and extranodal pediatric DLBCL (25
Most of the reported cases of DLBCL have a Ki-67 proliferation index greater than 40% (14
). In our cases the mean values of Ki-67-proliferation index was 71%, with a range of 30 to 90%.
According to the literature, c-MYC
translocation has been found in 35% of nodal pediatric DLBCL, a higher frequency than that reported in nodal DLBCL occurring in adult patients (5%) (14
). We found 37.5% of our pediatric cases to have a translocation involving c-MYC
: without a significant negative impact on outcome. Although our results show a tendency for the association between presence of c-MYC
with GCB, it would be necessary to study a larger number of cases to confirm it.
Cytogenetic studies reporting abnormalities in T-cell histiocyte-rich B-cell lymphoma are rare (21
). To the best of our knowledge, no other similar case of a T-cell/histocyte-rich B-cell lymphoma with a c-MYC
translocation has been previously reported in pediatric patients.
In adults c-MYC protein expression in DLBCL has been associated with more aggressive disease, but the protein can be induced by mechanisms other than cytogenetically identifiable translocations (25
). Also a high proliferation index in DLBL in adults is related to a worse prognosis (35
). It is interesting to note that in a series of pediatric DLBCL in which most of the cases presented with a moderate to high proliferation index the cases showed excellent prognosis (25
). Miles et al also found significant differences in survival between the GCB and non-GCB phenotypes of DLBCL, but these differences disappeared after adjustment for risk group (25
TCL-1-positive lymphomas were initially considered to be related to EBV infection (18
), believing that the virus stimulates TCL-1 expression, such as in EBV-positive cases of BL. In our series, there were 5 of 16 cases (31%) of pediatric DLBCL with TCL1 protein expression and all cases were EBV negative. The significance of TCL1 expression should be clarified in a larger series but it has been proposed as a potential therapeutic target based in experimental studies (1
). It has been reported that TCL-1 positive cases show a higher proliferation index (15
). In our series, the TCL-1 positive cases had a mean proliferation index of 85%, significantly higher than TCL-1 negative cases (mean value 61%), although the significance of this difference should be evaluated and confirmed in a larger number of pediatric TCL1-positive DLBCL cases. Similarly, the high frequency of c-MYC
translocation in TCL-1 positive cases may suggest a more aggressive type of lymphoma, but this was not confirmed, since all of our TCL1-positive cases had a good clinical outcome, in contrast to other studies (34
). DLBCL occurring in pediatric patients usually has a good prognosis, with 90% of patients surviving more than two years and 72% surviving more than 5 years (6
). We demonstrated a significantly difference in survival between pediatric DLBCL of GCB and non-GCB types (Kaplan-Meier survival analysis, P < 0.05, log rank test).
In conclusion, in our series of pediatric DLBCL the GCB was the most common phenotype and had a better outcome, which was independent of the presence of c-MYC
translocation or TCL1 expression. When the expression pattern of BCL-2, TCL-1 and MUM-1 is combined with the results of c-MYC
translocation, the cases appeared to cluster into groups. One group had detectable c-MYC
translocation and was mostly TCL1 positive; almost all of these cases belonged to the GCB phenotype and had a good outcome. There was a second group with the worst prognosis, showing expression of MUM1 and BCL-2, corresponding to the non-GCB phenotype. These findings could reflect a spectrum, with one group of cases more related to Burkitt lymphomas and another more related to adult DLBCL, showing that pediatric DLBCL are not as homogeneous as previously suggested (31
). BCL-2 expression alone does not correlate with survival, even when only non-GCB cases are considered, in contrast to results reported in adult patients (30
). TCL-1 expression in pediatric and adolescent DLBCL may be a good prognostic indicator, however this finding needs further confirmation.