-

-

-

3 yrs

F

-

-

-

-

3.2

9.8

52

29 Neutrohils 8%, Lymphocytes 61%, Eosinophils 2%, atypical lymphocytes 29%

Hypercellular, with 70% lymphoblasts replacing normal marrow elements

ALL

Positive for CD10 (90%), CD19 (81%), CD22 (81 %), 13 (61%), 33 (82%), 79a (38%), 34 (82%), HLDR (90%) and TdT (56%)

B-lineage ALL

01-2011

01-2011

Bone marrow

24h

G-band

48,XX,+16,+18

Fluorescence in situ hybridization with LSI TEL-AML1 (ETV6-RUNX1), LSI IGH/BCL2 and LSI CBFB probes

Applying the LSI TEL-AML1 probe on bone marrow cells we detected in 70% of cells fusion signal for TEL-AML1. Applying the LSI IGH/BCL2 and LSI CBFB probes on metaphases we detected 3 copies for BCL2 and CBFB confirming the presence of extra chromosomes 16 and 18.

RT-PCR for TEL-AML1

Positive

Current evidence suggests that in childhood acute lymphoblastic leukemia (ALL) with t(12;21), while the translocation may initiate the leukemic process, secondary genetic events are believed to be pivotal in disease promotion. We report a case of a patient displaying trisomy 16 and 18 as the sole cytogenetic anomaly detected by karyotyping. The patient, a previously healthy 3 years old female presented with fever and pancytopenia. Immunophenotyping showed B-lineage ALL, with aberrant expression of myeloid markers. Chromosome analysis performed at diagnosis revealed extra copies of chromosomes 16 and 18 in all the 20 examined metaphases. Fluorescence in situ studies revealed ETV6-RUNX1 fusion signal in 70% of cells and the rearrangement was confirmed by reverse-transcriptase polymerase chain reaction. While extra copies of chromosomes 16 and 18 may be observed in pediatric ALL patients with hyperdiploid karyotypes suggesting that they may exists as an evolutionary change, isolated trisomy 16 or 18 have been reported only rarely. A case similar to ours was previously reported in a child cytogenetically characterized by an isolated trisomy 16 and ETV6-RUNX1 fusion. Our case together with the previously reported case of B-cell ALL with ETV6-RUNX1 rearrangement suggests that trisomy of chromosome 16 and is an important additional or secondary genetic event in childhood ALL with ETV6-RUNX1 fusion. In addition, several cases of pediatric ALL with isolated trisomy 16 or 18 were reported potentially harboring the ETV6-RUNX1 rearrangement. As the translocation t(12;21) usually escapes diagnosis on conventional karyotyping, our case further reinforces the importance of fluorescence in situ hybridization studies in pediatric leukemias to reveal cryptic genomic rearrangements in addition to visible cytogenetic changes.