https://orcid.org/0000-0002-0883-3942
![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–Chédiak-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),+mar1[8/20] (panel C). Fluorescence in situ hybridization showed nuc ish(CDKN2Ax1,D9Z3x2)[76/200]/(IGHx2)(3′IGH sep 5′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. 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.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/139/10/10.1182_blood.2021014726/7/m_bloodbld2021014726f1.png?Expires=1769079536&Signature=iStQOeKtlhkgyhpXKTPurTFjH4Q5nsxga91yzELfOVn3alUVsFd0EXNWh7RfAEOYNMp~wCrCvpWyjZ~HwaDnwQ8YFakSaYHVjvy3sLRJSqohuNlv6cnU7ebTNgQ0lJC~RUEBa08XWb0GVe8xLGwLXM-8B7ThK3nQP4VbCavrTj57lNnJ8fbrtyqFCRvNNjVksU95BEGwcheGpNEOdUqhPNzuFKfeg1nXpDfEWB~jZKWFn6195ppuunh8RpP~Vx2UMbQAlGCr2VUecOFs8AYE2fHcY7y2wkdPvDEi~3tY0fCc0YP9JsKxL7pDTC49X5Br3r0-y2zkw4UcCroFpIKB7Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
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–Chédiak-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),+mar1[8/20] (panel C). Fluorescence in situ hybridization showed nuc ish(CDKN2Ax1,D9Z3x2)[76/200]/(IGHx2)(3′IGH sep 5′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. 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–Chédiak-Higashi granules are characterized by large azurophilic cytoplasmic inclusions, similar to those in granulocytes of Chédiak-Higashi syndrome. The combination of prominent vacuolation and pseudo–Chédiak-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.
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–Chédiak-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),+mar1[8/20] (panel C). Fluorescence in situ hybridization showed nuc ish(CDKN2Ax1,D9Z3x2)[76/200]/(IGHx2)(3′IGH sep 5′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. 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–Chédiak-Higashi granules are characterized by large azurophilic cytoplasmic inclusions, similar to those in granulocytes of Chédiak-Higashi syndrome. The combination of prominent vacuolation and pseudo–Chédiak-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.
For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit http://imagebank.hematology.org.
![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–Chédiak-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),+mar1[8/20] (panel C). Fluorescence in situ hybridization showed nuc ish(CDKN2Ax1,D9Z3x2)[76/200]/(IGHx2)(3′IGH sep 5′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. 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.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/139/10/10.1182_blood.2021014726/7/m_bloodbld2021014726f1.png?Expires=1769079537&Signature=dhll-CUgKU33gv-aXqcW1U8uanmjzLf0xB4b4CVYBdd-JyN30Xn4uyQeNqNr4fSsWdidiVejPjEoSwhws2wtMFuqR1hV-rK6Eu7GG7eaqqVHPkc5HbL3XFvhoaHItCShy-wz5mD392WYdjR5XCuO3Pq1xWd-91yWk4nMzOTc~PR7-ls5k-aq8Ij7oHlnRRZiPT2ygpOYbWb5rlixJoEGEio6NvkrOYp-cZMwrh0e6uxKiZAidbA~rF6AKEHVHWRFiz-1x7IYEaOUZunnFmxc7UhPIJ620gvWPHBbHcifd4pOv6F86k6RrwiupWeeVN60FUww~0MWIhw2OSu5Z2fIZA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
