A 32-year-old man presented with skin lesions, leukocytosis (white blood cells, 162 × 10⁹/L), thrombocytopenia (34 × 10⁹/L), and elevated lactate dehydrogenase (1000 U/L). The blood film was consistent with chronic myelogenous leukemia (CML) with 3% “normal” blasts and a few giant basophilic, vacuolated blasts. Bone marrow aspirate revealed 33% giant blasts (panel A; original magnification ×100, May-Grünwald-Giemsa stain), not detected as a distinct population by flow cytometry. Immunohistochemistry showed positivity for CD33, CD56, CD123, CD4, CD163, and lysozyme and negativity for myeloperoxidase, terminal deoxynucleotidyl transferase, CD68, CD14, CD3, and CD19. Fluorescence in situ hybridization (FISH) analysis showed a single Philadelphia chromosome in granulopoiesis (panel B; original magnification ×100) but 3 Philadelphia chromosomes in giant blasts (panel C; original magnification ×100). Molecular analysis revealed a p210 BCR-ABL transcript. FISH analysis for myc (8q24) demonstrated 3 isochromosomes 8 (panel D; original magnification ×100). The complete karyotype of blasts was: 53,XY,i(8)(q10),+i(8)(q10)x2,t(9;22)(q34;q11),+18,+19,+der(22)t(9;22)(q34;q11)x2,+mar,+1-2dim[30] (panel E). Treatment with imatinib resulted in normalization of blood counts. A skin biopsy was not obtained but the lesions resolved with imatinib. The patient is currently waiting for allogeneic stem cell transplantation.

This case of presentation of CML in myeloid blast phase shows abnormal blasts with a complex karyotype, including 3 Philadelphia chromosomes and 3 isochromosomes 8 associated with 14 myc alleles per cell. To our knowledge, this has never before been described.