Case 164

Submitting Author: Oliveira, Jennifer Leigh, MD
Institution: Mayo Clinic
Additional authors:David Viswanatha MD, Matthew T. Howard MD
Session: B Lymphoblastic Leukemia/Lymphoma

HISTORY

14 YO boy with history of complicated congenital heart disease (tricuspid atresia with transposition of the great arteries). Presented to cardiologist with increasing fatigue. CBC showed very high WBC (300K), anemia and thrombocytopenia. The patient was treated with intense induction chemotherapy (non-study ALL) without response (marrow cellularity and blast percentage did not decrease). Chose palliative care with dasatinib. Surprisingly experienced complete morphologic and molecular remission. Remains in remission (2 year follow-up).

DETAILS

Peripheral blood smear showed marked leukocytosis, composed of 85% blasts (some primitive, others more cytoplasm, no Auer rods) but some left shifted granulocytes and circulating basophils and eosinophils with primary granules were present. No dysplastic features or increased monocytes were noted. Iliac crest bone marrow biopsy (decalcified, formalin fixed), and bone marrow aspirate smears showed mostly blasts with a decreased but residual left shifted myeloid population with some maturation. No definitive micromegakaryocytes were noted.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometry, peripheral blood: Relatively dim CD19, negative to partial CD10, CD34, CD13, partial CD56, HLA-DR, TdT positive; CD33, CD20, Ig, CD117, CD15, cMPO negative Immunohistochemistry, core biopsy: TdT (diffusely strong), CD19, CD79a (partial), CD22 (partial), CD10 (partial), CD56 (partial) positive; MPO, CD68 negative.

CYTOGENETIC FINDINGS

Cytogenetic karyotype, bone marrow: t(9;22)(q34;q11.2) and monosomy 7 [20/20 metaphases]
FISH, bone marrow: 98.0% fusion BCR/ABL
FISH, peripheral blood: 99% nuclei have monosomy 7 and BCR/ABL fusion. Both round and multilobed nuclei (blasts and mature granulocytes) have these anomalies.

MOLECULAR FINDINGS

PCR, BCR/ABL mRNA, p190: Positive.
PCR, BCR/ABL mRNA, p210: Negative.

INTERESTING FEATURES

The blasts in the peripheral blood expressed both myeloid and B-cell associated markers and the CD19 was dim and CD10 expression partial to negative. The left shifted granulocytes circulating with the blasts (including basophils and eosinophils with primary granules) raised the possibility of B-lymphoblastic phase presentation of CML; however, a B/myeloid mixed phenotype acute leukemia with t(9;22) remains in the differential diagnosis. The FISH demonstrating the BCR/ABL translocation in the mature neutrophils as well as the blasts has been postulated to support the blastic presentation of CML; however, the p190 is more suggestive of ALL. The most interesting aspect of this case is the complete refractory nature of the neoplasm to ALL induction chemotherapy and what seems to be an exquisite and durable moprhologic and molecular response to dasatinib therapy given initially for palliation.

PROPOSED DIAGNOSIS

B-lymphoblastic phase presentation of chronic myelogenous leukemia vs B/myeloid mixed phenotype acute leukemia with t(9;22) vs B-lymphoblastic leukemia, BCR/ABL positive.

CONSENSUS DIAGNOSIS

B-acute lymphoblastic leukemia, Philadelphia chromosome positive (BCR/ABL1; p190)