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Page 2 of 9 Othman et al. J Cancer Metastasis Treat 2018;4:50 I http://dx.doi.org/10.20517/2394-4722.2018.41

INTRODUCTION
Lymphoblastic lymphoma (LBL) is a rare and aggressive form of non-Hodgkin’s lymphoma (NHL). LBL de-
velops from immature B cells committed to the B- (B-LBL) or T-cell lineage (T-LBL). LBL is morphologically
indistinguishable from acute lymphoblastic leukemia (ALL) and 90% of it have a T-cell phenotype. LBL also
accounts for approximately 2% of all NHL cases and occur in adult, children and adolescent, with a male
[1-2]
predominance (three time more male are affected) .
Chromosomal abnormalities in T-LBL are not well defined and cytogenetic data in T-LBL is limited. How-
ever, a few published cytogenetic studies revealed that typical chromosomal aberrations identified in T-cell
ALL (T-ALL) are also present in T-LBL. These include translocations of T-cell receptor (TCR) gene to genes
encoding transcription factors such as TAL1, TLX1, LMO2, and LYL1. In particular, the translocation t(9;17)
[1-4]
(q34;q22~23) is typically found in T-LBL . However, no single recurrent and typical genetic alteration for
T-LBL could be identified. This is in contrast to other malignancies like translocation of ALK gene in ana-
plastic large cell lymphoma, MYC gene in Burkitt lymphoma or BCL2 gene in follicular lymphoma.

Here we present the comprehensive analysis of a T-LBL case with a normal karyotype, according to standard
G-banding with trypsin-Giemsa (GTG)-banding, using high resolution molecular methods, identifying also
some intra-tumor genetic heterogeneity besides unusual acquired genetic alterations. Also here we report
NUP214-ABL1 gene fusion in this patient, which appears cryptic due to its localization in episomes.

CASE REPORT
A seventeen-year-old female patient, who was initially diagnosed in South Africa with T-ALL, presented
in the clinic in Poland with abdominal pain, accompanied by diarrhea and vomiting; she was here initially
9
treated only symptomatically. A few days before, a blood test already revealed hyperleukocytosis (589 × 10 /l)
9
with presence of 94% lymphoblasts in blood smear, hemoglobin 8.5 g/dl, and platelet count 53 × 10 /l. Bone
marrow findings were: hypercellularity with 95% lymphoblasts, lack of megakaryocytes and Periodic-Acid-
Schiff (PAS) staining identified in 70% of the blasts thick grains (data not shown). Ultrasound of abdomen
showed enlargement of the spleen to 152 mm, and presence of fluid in the lower pelvis. Cervical lymph nodes
were bilaterally enlarged with diameters of 3-4 cm, and small submandibular nodes were bilaterally enlarged
to 2 cm in diameter.

Cytogenetic and immunophenotypic analyses were done. The latter characterized a T-LBL due to high ex-
pression of CD45 (100%), CD2 (96.6%), CD4 (97.3%), CD8 (90%), CD7 (77.1%), CD5 (76.0%), sCD3 (71.2%),
CD1a (70.0%) and the lack of TdT, CD19, CD34 and CD38.

Banding cytogenetic analyses were done in unstimulated bone marrow cells according to standard proce-
[5]
dures from the material taken at initial diagnoses. A total of 20 metaphases were available and analyzed on
a banding resolution of 300 bands per haploid karyotype, revealing a normal female karyotype. Molecular
diagnostic polymerase chain reaction (PCR)-based tests for presence of gene fusions BCR/ABL (p190 and
p210), TCF3/PBX1, MLL/AF4 and SIL/TAL1 were negative (results not shown).

Also genomic DNA isolated from cells fixed in acetic acid-methanol (1:3) was subjected to array-comparative
genomic hybridization (aCGH) as well as the multiplex ligation probe amplification (MLPA) studies, as pre-
[6]
[6-8]
viously reported , Finally, fluorescence in situ hybridization (FISH) was done , revealing a highly complex
karyotype [Figure 1 and Table 1] with gene-amplification due to episomes (abbreviated here as epi), which
can be reported as:

46,XX,der(2)t(2;7)(q37.3;q25.1),del(4)(p14p16),t(7;10)(q34;q24),del(9)(p21.3p21.3),epi(6;9)(q23.3;q34.12)
x20~30[20%]/46,XX,der(2)t(2;7)(q37.3;q25.1),del(4)(p14p16),der(7)(7pter->7q34::10q24.1->10q25.1::2q37.3-
>2qter),del(9)(p21.3p21.3),der(10)t(10;7)(q23;q34),epi(6;9)(q23.3;q34.12)x20~30[40%]/46,XX[40%].