ALK‐positive diffuse large B‐cell lymphoma

Abstract

Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been established in addition to congenital multiple enchondromatosis. Immunohistopathological evaluation of tumor biopsy established the final diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant expression of ALK in the present case was demonstrated by interphase fluorescence in situ hybridization (FISH) using break-apart rearrangement probes for ALK and CLTC. The disease in this patient was highly resistant to applied chemotherapy regimens and to radiotherapy. Analysis of the disease course in our patient and review of other cases reported previously show that ALK + DLBCL can be an aggressive malignancy that can be cured with conventional chemotherapy protocols only at stage of localized disease.

Hyperactivated STAT3 in ALK–positive diffuse large B-cell lymphoma with clathrin-ALK fusion

“…On review of the literature, among 20 ALK-positive DLBCL cases [5][6][7][8][9][10][22][23][24][25] including the current 2 cases, 17 cases had CLTC-ALK translocation and 3 cases had NPM-ALK translocation. Therefore, the CLTC-ALK translocation would be the most common cytogenetic feature of this disease entity, although 10 other ALK-positive DLBCL cases had not been subjected to the ALK rearrangement study [9].…”

ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature

“…Thus, ALK gene rearrangements, originally thought to be uniquely associated with T-/null cell ALCL, have now been convincingly shown to occur in rare cases of B-cell lymphoma. [2][3][4][5][6][7][8][9][10][11][12][13] Of note, prior to the initial series by Delsol et al, 1 Arber et al 17 in 1996 reported NPM/ALK fusion transcripts (by RT-PCR) in four of 33 cases of large B-cell lymphoma. Interestingly, and in contrast to the cases of ALK-DLBCL reported thus far, these four cases had a conventional B-cell immunophenotype (CD20 þ and CD79a þ ).…”

“…1 Recently however, Clathrin/ALK (CLTC/ALK) and NPM/ALK gene rearrangements have been identified in 16 and three cases of ALK-DLBCL, respectively. [2][3][4][5][6][7][8][9][10][11][12][13] All of these cases display the morphologic and immunophenotypic features of ALK-DLBCL, as originally described by Delsol et al Importantly, ALK positivity and ALK gene rearrangements can be seen in B-cell lymphomas and are now no longer uniquely restricted to the T-cell lymphoma, ALCL. To our knowledge, only 29 cases of ALK-DLBCL have been reported thus far in the literature.…”

Oncogenic Anaplastic Lymphoma Kinase Rearrangements in Lymphoma

“…23 Similar to ALK + ALCL, the aberrant ALK expression in ALK + LBCL is also driven by 2p23/ALK translocations, of which t(2;17)(p23;q23) is the most frequent (65%). This aberration leads to a chimaeric CLTC-ALK protein and manifests as a distinctive granular cytoplasmic expression of ALK [27][28][29][30][31][32][33][34][35] (see Table 1 and Figure 3). Interestingly, only a few ALK + LBCL cases (13%) showed the t(2;5)(p23;q35)/NPM1-ALK rearrangement, commonly occurring in ALK + ALCL 25,[36][37][38] (see Table 1).…”