Bilineal Extramedullary Blast Crisis as an Initial Presentation of Chronic Myeloid Leukemia: A Case Report and Literature Review

Abstract

BACKGROUND Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia chromosome generated by the reciprocal translocation t(9: 22)(q34;q11). CML is usually diagnosed in the chronic phase. Blast crisis represents an advanced phase of CML. Extramedullary blast crisis as the initial presentation of CML with bone marrow remaining in chronic phase is an unusual event. Further, extramedullary blast crisis with T lymphoid/myeloid bilineal phenotype as an initial presentation for CML is extremely unusual. CASE REPORT Here, we report the case of a 49-year-old male with rapidly enlarged submandibular lymph nodes. Biopsy specimen from the nodes revealed a characteristic appearance with morphologically and immunohistochemically distinct myeloblasts and T lymphoblasts co-localized in 2 adjacent regions, accompanied by chronic phase of the disease in bone marrow. The presence of the BCR/ABL1 fusion gene within both cellular populations in this case confirmed the extramedullary disease represented a localized T lymphoid/myeloid bilineal blastic transformation of CML. After 3 courses of combined chemotherapy plus tyrosine kinase inhibitor treatment, the mass was completely regressed with a 3-log decrease in BCR/ABL1 transcript from baseline. Five months after the diagnosis, the patient showed diminished vision, hand tremors, and weakness of lower extremities. Flow cytometric immunophenotyping of cerebrospinal fluid revealed the presence of myeloid blasts. An isolated central nervous system relapse of leukemia was identified. Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. CONCLUSIONS The possibility of extramedullary blast crisis as an initial presentation in patients with CML should be considered. Further, an isolated central nervous system blast crisis should be considered if neurological symptoms evolve in patients who have shown a good response to therapy.

Figure 1.

Morphology, cytogenetics, and molecular features of bone marrow and ¹⁸F-FDG PET/CT imaging analysis. (A) Bone marrow aspiration revealing a hypercellular marrow with the presence of 6.4% immature lymphocytes. (B) A G-banded karyotype of bone marrow showing the Ph chromosome: 46 XY, t(9;22)(q34;q11) (arrows). (C) FISH on the interphase nuclei of bone marrow using the Vysis Extra Signal probe revealing the typical p210 breakpoint in CML yielding 1 green, 1 red, 1 residual red, and 1 red-green fusion signal. (D) RT-PCR analysis of the mRNA extracted from bone marrow demonstrating p210 BCR/ABL1 rearranged bands (397 bp). Lane 1, marker; Lane 2, distilled water; Lane 3, bone marrow. (E) ¹⁸F-FDG PET/CT scanning of the body showing abnormal FDG accumulation in the left side of the neck and submandibular lymph nodes (arrows).

Figure 2.

Histopathology features of the lymph nodes. (A) Microscopic appearance showing the normal architecture of the lymph node substituted by diffuse infiltration of 2 populations of blastic cells with a clear dividing line – the red and sparse staining myeloblasts region (white arrow) and the blue and dense staining T lymphoblasts region (black arrow) (H&E, 4×). The sparse staining region is composed of neoplastic cells with myeloid differentiation, with background rich in blood vessels (H&E, 100×). The cells are strongly positive for MPO and lysozyme, and negative for CD117, CD5, CD3, CD34, and CD99 (immunohistochemistry with hematoxylin counterstain, 40× and 100×). The dense staining region is composed of T lymphoblasts with dense nuclear chromatin and a high nuclear-to-cytoplasmic ratio, and scattered macrophages with starry-sky appearance (H&E, 100×). The cells are strongly positive for CD5, CD3, and CD99; focally positive for CD34; and negative for MPO, lysozyme, and CD117 (immunohistochemistry with hematoxylin counterstain, 40× and 100×). (B) FISH on the paraffin-embedded biopsy specimen using the Vysis Extra Signal probe revealing the presence of p210 breakpoint in both myeloblasts (low cell density area) and T lymphoblasts (high cell density area). Positive cells (arrows) contain 1 green, 1 red, 1 residual red, and 1 red-green fusion signal.