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Pseudo–Chediak-Higashi inclusions in
BCR::ABL1-like B-lymphoblastic leukemia with
IGH::EPOR rearrangement
Rithin Nedumannil and Surender Juneja, Victorian Comprehensive Cancer Centre
C
1
2
3
6
7
8
13
14
15
19
20
4
9
5
mar
10
11
12
16
17
18
X
Y
- Vacuoles
- Pseudo-ChédiakHigashi inclusions
22
100%
0%
D
21
50%
B
MB-G213026.006
Normal
chromosome 19
100%
0%
A 21-year-old woman presented with 6 weeks of progressive
exertional dyspnea. Initial testing showed normocytic anemia
(hemoglobin, 56 g/L) and 14% circulating blasts, with normal
neutrophil and platelet counts. Bone marrow aspirate revealed
an excess of medium-sized blasts with a high nucleus-to-cytoplasm ratio, fine nuclear chromatin, inconspicuous nucleoli, frequent large vacuoles, and prominent azurophilic inclusions
resembling pseudo–Ch
ediak-Higashi granules (panels A-B;
Wright-Giemsa; original magnification x1000). Flow cytometry
demonstrated a blast population expressing CD19, CD22,
CD24, CD10, CD34, and CD38, but no myeloid or T-cell
markers.
Karyotyping
revealed
45,XX,-4,add(9)(p24),add
(9)(p12),add(12)(q13),add(14)(q32),-19,der(21)t(4;21)(q13;p11.2),1
mar1[8/20] (panel C). Fluorescence in situ hybridization showed
nuc ish(CDKN2Ax1,D9Z3x2)[76/200]/(IGHx2)(39 IGH sep 59 IGHx1)
[115/200], indicating loss of 1 CDKN2A signal per cell in 76 of
200 cells and IGH signal rearrangement in 115 of 200 cells.
50%
MB-G213026.006
Derivative
chromosome
14 showing
involvement of
chromosome
19p13.2
Whole-genome sequencing revealed IGH::EPOR rearrangement;
copy number loss of IKZF1, CDKN2A, CDKN2B, PAX5, and
BTG1; and no changes consistent with t(4;21)(q13;p11.2).
Multicolor banding confirmed der(14)t(14;19)(q32;p13.2),
corresponding to IGH::EPOR (panel D). BCR::ABL1-like
B-lymphoblastic leukemia (B-ALL) was diagnosed based on the
IGH::EPOR rearrangement. The patient remained in complete
remission at 6 months after diagnosis following commencement
of chemoimmunotherapy.
Pseudo–Ch
ediak-Higashi granules are characterized by large
azurophilic cytoplasmic inclusions, similar to those in granulocytes
of Ch
ediak-Higashi syndrome. The combination of prominent
vacuolation and pseudo–Ch
ediak-Higashi inclusions in lymphoblasts in this case is unique, as neither finding has been described
in either pediatric or adult patients with the uncommon variant of
BCR::ABL1-like B-ALL with IGH::EPOR rearrangement.
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DOI 10.1182/blood.2021014726
1598
blood® 10 MARCH 2022 | VOLUME 139, NUMBER 10
© 2022 by The American Society of Hematology
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