Institution: Cleveland Clinic
Additional authors:Karl S. Theil, MD
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN
HISTORY
The patient is a 42 year-old, previously healthy man who presented to an emergency department with increasing fatigue, 10 lb weight loss and low back pain over 2 weeks, progressing to numbness and weakness in his lower extremities with saddle anesthesia. Complete blood count (CBC) results were: WBC 46.4 K/uL, Hgb 11.1 g/dL, platelets 61 K/uL, with 7% blasts. An abdomen/pelvis computed tomography scan was significant for splenomegaly, a soft tissue mass (13 cm) engulfing the right acetabulum and iliacus muscle, hydronephrosis/hydroureter, and “diffuse osseous metastasis” throughout the axial spine and pelvis with epidural tumor. He was transferred to our hospital and admitted to the leukemia service. A bone marrow biopsy was performed.
DETAILS
Trephine biopsy – Zinc formalin; Clot section – 10% neutral buffered formalin fixed paraffin-embedded tissue.
A peripheral blood smear showed leukocytosis (21.21 K/uL) with absolute monocytosis, basophilia (25%, absolute count= 5,302/uL), and moderate-large sized blasts (16%) with mostly agranular cytoplasm and round to indented nuclei. Normocytic anemia (Hgb 9.2 g/dL) and thrombocytopenia (61 K/uL) were present.The aspirate smear was aspicular (dry tap) with 13% blasts and findings similar to the peripheral blood.The bone marrow biopsy was 2.2 cm in length with variable cellularity but overall hypocellular due to panhypoplasia, ranging from 10-50%. Only rare megakaryocytes were identified. Bony trabeculae showed slight osteosclerosis. Extensive, diffuse stromal fibrosis was present. Reticulin and trichrome stains were performed to further characterize and showed a marked increase in stromal reticulin with collagenous fibrosis (4+/4+; MF-3).IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
There was no significant increase in CD34+ immature cells, although stromal vascularity was increased. Focal clusters of micromegakaryocytes were noted with immunostain for CD61. Immunostain for langerin was negative. A mast cell tryptase highlighted scattered round mast cells; there was no evidence of mast cell disease. Neither CD117, CD123 nor toluidine blue stains were helpful in identifying mast cells or basophils.
CYTOGENETIC FINDINGS
Karyotype (peripheral blood): 46,XY,t(9;22)(q34;q11.2)[17]/46,XY[3].
MOLECULAR FINDINGS
FISH (peripheral blood) for BCR/ABL1 translocation is positive (38%).
INTERESTING FEATURES
The cytogenetic/molecular results were positive for the BCR-ABL1 fusion and Philadelphia chromosome, which was critical in making the diagnosis. Without knowledge of BCR-ABL1 status, the differential diagnosis includes end-stage primary myelofibrosis or the spent-phase of post-polycythemic myelofibrosis. If the blast count were higher, acute myeloid leukemia with t(6;9)(p23;q34) could be considered, but this patient lacked not only the DEK-NUP214 fusion and leukemic blast percentages, but also any appreciable dysplasia. Chronic myelogenous leukemia (CML) presenting in the accelerated phase is uncommon, particularly in the era of tyrosine kinase inhibitor therapy. This patient meets WHO 2008 criteria for accelerated phase, including bone marrow aspirate blasts 10-19%, thrombocytopenia (<100 K/uL), and peripheral basophilia greater than 20%. In addition, the patient has splenomegaly and leukocytosis.
Within days of the bone marrow biopsy, an epidural tumor biopsy showed a diffuse infiltrate of intermediate-sized mononuclear cells with vesicular chromatin, prominent nucleoli, and scant cytoplasm within bands of fibrous tissue. Immunostains were positive for the following: CD45, CD43, CD34, CD33 and muramidase. The presence of this extramedullary blast population (myeloid sarcoma) permits definitive classification as chronic myelogenous leukemia in blast phase.PROPOSED DIAGNOSIS
Chronic myelogenous leukemia, blast phase, BCR-ABL1 positive.
CONSENSUS DIAGNOSIS
Accelerated phase chronic myelogenous leukemia (with osteosclerosis) with progression to myeloid sarcoma
versus Chronic myelogenous leukemia, BCR-ABL1 positive, blast phase