Page 148 - Haematologica Vol. 107 - September 2022

ARTICLE - FL3B and simultaneous DLBCL
K. Koch et al.
pression in <50% of cells and 23/49 cases (47%) with ex- pression in >75% of cells. Bcl2 staining was available for 48 cases. Bcl2 was completely negative in 5/48 cases (10%), positive in <50% of cells in 7/48 cases (15%) and positive in >50% of cells in 36/48 cases (75%). Staining for Mum1 was done in 36 cases. Mum1 was completely negative in 3/36 cases (8%), positive in <25% of cells in 9/36 cases (25%), positive in 25% to <50% of cells in 4/36 cases (11%), positive in 50% to <75% of cells in 11/36 cases (31%) and positive in ≥75% of cells in 9/36 cases (25%). Bcl6 staining was available for 29 cases. Of these, seven cases (24%) were positive in 50% to <75% of cells and 22 cases (76%) were positive in ≥75% of cells. The prolifer- ative rate by Ki67 ranged between 30% and 90% with a mean proliferative rate of 63% in the whole cohort. Clas- sification of the cell of origin was available for 26 cases with a DLBCL component. Of these, 19 cases (73%) dis- played a germinal center B-cell-phenotype and seven cases (27%) displayed a non-germinal center B-cell-phe- notype according to the Hans classifier.15 Despite inter- tumoral variability, expression of the above-mentioned antigens did not differ between different growth patterns within an individual patient/lymphoma. Of note, FL3B and
Figure 1. Growth pattern of follicular lymphoma grade 3B and diffuse large B-cell lymphoma. The three patterns observed are shown for exemplary cases in the three columns as a scheme/model, hematoxylin and eosin staining (H&E) and staining for CD3 and CD21. Original magnification 40x.
DLBCL areas in the same specimen showed the same pro- liferative rate according to Ki67 (Figure 2). Comparing FL3B and FL3B+DLBCL, no significant differences between mean proliferative rates were detectable (59% and 65%, respectively, P=0.1349, unpaired t-test). CD21 staining was evaluable in 12 follicular FL3B components, 26 confluent FL3B components and 16 DLBCL components of 34 cases. Meshworks of follicular dendritic cells showed consider- able intercase variability. The highest scores were reached in follicular FL3B (8/12, 67% slightly reduced/intact and 4/12, 33% markedly reduced); DLBCL components mostly showed markedly reduced or absent meshworks (1/16, 6% slightly reduced and 15/16, 94% markedly reduced/absent). Confluent FL3B presented intermediate stages of follicular dendritic cell preservation (14/26, 54% slightly reduced/in- tact and 12/26, 46% markedly reduced/absent mesh- works), supporting the idea that confluent FL3B represents an intermediate stage between follicular FL3B and DLBCL. Within individual cases with evaluable FL3B and DLBCL components (n=14), a reduction of meshworks could be observed between the FL3B and DLBCL com- ponents in 9/14 cases (64%) and the same stage of pres- ervation in 5/14 cases (36%).
Chromosomal aberrations are mostly stable between follicular lymphoma grade 3B and diffuse large B-cell lymphoma
Lymphomas with breaks in IRF4 were excluded since these are considered a distinct entity in the WHO classification. FISH to detect breaks in BCL2, BCL6 and MYC was per- formed for 40 cases, 21 of which contained a DLBCL com- ponent. In any lymphoma containing multiple growth patterns these were analyzed separately. Overall, 27 chro- mosomal breaks were detectable in 25 cases and 15 cases did not show breaks in the above-mentioned genes. One case presented a double-hit constellation with MYC and BCL6 rearrangements (FL3B with confluent pattern). Chro- mosomal breaks occurred at a similar frequency in FL3B and
Table 1. Coexistence of growth patterns in follicular lymphoma grade 3B.
Follicular
Confluent
Diffuse
Total
FL3B (N=22)
+
-
-
4/22 (18%)
-
+
-
11/22 (50%)
+
+
-
7/22 (32%)
FL3B/DLBCL (N=27)
+
-
+
7/27 (26%)
-
+
+
14/27 (52%)
+
+
+
6/27 (22%)
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Numbers and percentages correspond to the respective subgroup. FL3B: follicular lymphoma grade 3B; DLBCL: diffuse large B-cell lymphoma.