B-Cell Lymphoproliferative Disorders with t(11;14)(q13;q32) or t(14;18)(q32;q21) Can Be Subdivided into 4 Distinct Categories Based on Their Pattern of Additional Cytogenetic Aberrations and Antigen Expression.
Authors: Haferlach Claudia , Reindl Lena , Dicker Frank , Schnittger Susanne , Haferlach Torsten , Kern Wolfgang 
Published: April 2020

The t(11;14)(q13;q32) is considered a marker of mantle cell lymphoma (MCL), while the t(14;18)(q32,q21) is associated with follicular lymphoma. However, both translocations have also been reported in other B-cell malignancies. We evaluated immunophenotypic characteristics as well as cytogenetic aberrations occurring in association with t(11;14) and t(14;18) in order to define specific entities. 51 B-cell lymphoproliferative disorders with t(11;14) and 26 with t(14;18) were studied by chromosome banding, FISH, and immunophenotyping. Based on immunophenotyping 13 of 26 t(14;18)+ cases were classified as NHL and 13 cases as CLL (9 CLL and 4 CLL/PL). The mean number of cytogenetic aberrations observed in addition to t(14;18) was 1.1 in CLL cases and 4.2 in NHL cases (p=0.016). While 9 of 13 B-NHL cases (69.2%) revealed a complex karyotype (≥3 aberrations in addition to t(14;18)), none of the 13 CLL cases did (p=0.0002). In CLL the only recurring aberrations occurring in addition to t(14;18) were +12 (n=7) and −13q (n=5). In B-NHL cases additional aberrations were +1q (n=3), –4q (n=2), –6q (n=5), +7 (n=3), +12 (n=4), –15q (n=2), +der(18)t(14;18) (n=2), +21 (n=2), +22 (n=2), and +X (n=2). Notably, deletion 13q was not detectable in t(14;18)+ B-NHL compared to t(14;18)+ CLL (n=5) (p=0.044). Two antigens were significantly higher expressed in t(14;18)+ B-NHL as compared to t(14;18)+ CLL: CD10 (mean positivity (mp) 34.9% vs. 1.7%, p=0.006), and CD38 (60.9% vs. 29.8%, p=0.014), while 3 antigens were significantly lower: CD11c (38.6% vs. 14.5%, p=0.005), CD23 (66.6% vs. 24.0%, p=0.001), and CD5 (80.8% vs. 29.5%, p&lt;0.001). In cases with t(11;14)+ 39 of 51 cases were classified as NHL and 12 were classified as CLL (3 CLL and 9 CLL/PL). The mean number of aberrations observed in addition to t(11;14) was 2.1 in CLL cases and 5.8 in NHL cases (p=0.011). While 26 of 39 NHL cases (67%) revealed a complex karyotype, only 3 of the 12 CLL cases (25%) did (p=0.011). In CLL the only recurring aberrations occurring in addition to t(11;14) were +3q (n=3), +12p (n=2), –13q (n=2), +15q (n=2), –17p (n=4). In NHL cases the following aberrations were observed in at least 5 cases: –1p (n=8), +3q (n=20), –6q (n=5), –8p (n=11), +8q (n=12), –9p (n=8), –9q (n=8), +11q (n=8), –11q (n=9), –13q (n=11), +13q (n=8), +15q (n=5), and –17p (n=13). 17p/TP53 deletion was significantly associated with a complex aberrant karyotype (12 of 29 (41%) vs. 2 of 22 (9%) p=0.01). An ATM deletion was detected in 9/29 with complex karyotype and in 0/17 without a complex karyotype (p=0.004). CD23 was significantly higher expressed in t(11;14)+ CLL as compared to t(11;14)+ B-NHL: (mp 48.8% vs. 20.8%, p=0.0001). CD22 was significantly higher expressed in t(11;14)+ B-NHL as compared to t(11;14)+ CLL (mp 72.3% vs. 56.9%, p=0.036). In conclusion, t(14;18)+ CLL were characterized by a low number of additional chromosome aberrations. In contrast, t(14;18)+ NHL frequently demonstrated a complex karyotype. t(14;18)+ CLL were further characterized by a higher expression of CD11c, CD23, and CD5 and a lower expression of CD10 and CD38 compared to t(14;18)+ NHL. Also t(11;14)+ CLL are characterized by a lower number of additional chromosome aberrations as compared to t(11;14)+ NHL and show a higher expression of CD23 and a lower expression of CD22. Therefore, two different biological subgroups can be distinguished within t(14;18)+ and t(11;14)+ B-cell lymphoproliferative disorders.