Submitting Author: Patel, Keyur Pravinchandra, MD PhD
Institution: The University of Texas M D Anderson Cancer Center
Additional authors:Sa Wang MD, Jeffrey Jorgensen MD PhD, Carlos Bueso-Ramos MD PhD
Session: Acute leukemias of ambiguous lineage

A 44-year-old male was in his normal state of health till 2 months ago, when he presented to his local primary care physician with complaints of fevers, chills, night sweats, and initially was treated for upper respiratory infection and flu-like symptoms with, Tamiflu. However, the patient had a routine CBC drawn, which did reveal that he was pancytopenic. Also, on physical exam, the patient was found to have an enlarged spleen, which was concerning for further evaluation. Therefore, further workup was done with bone marrow aspiration and biopsy.

CBC:

WBC: 4.8, HGB: 9.7, MCV: 89, Platelet: 20, Neutrophils: 27.0, Lymphs: 20.0, Monos: 19.0, Blasts: 34.0

Site: Left iliac

Findings: Bone marrow aspirate and biopsy (1.6 cm) were of good quality and showed hypercellular marrow with replacement of normal trilineage hematopoiesis by sheets of blasts. Increased blasts, 84% in a 300 cell differential count, are intermediate in size with round to oval nuclei, finely dispersed chromatin, occasionally distinct nucleoli, scant agranular cytoplasm. Occasional blasts with cytoplasmic granules noted. No Auer rods noted.

Blasts are negative for myeloperoxidase and butyrate esterase expression by cytochemistry studies performed on aspirate smears.

Immunohistochemistry studies performed on the bone marrow biopsy section shows that a subset of blasts is positive for CD3 expression (variable intensity). The blasts are negative for PAX5, TdT, TCL-1, TIA-1 and Granzyme B expression.

Flow cytometric immunophenotyping of bone marrow aspirate shows increased blasts (dim CD45 versus low side scatter gate) that constitute 71% of total cells. The blasts are positive for CD34, CD19, CD33, CD56, HLA-DR(subset), CD49d, cytoplasmic CD79a, CD123(partial), CD45(dim), CD38(bright) and cytoplasmic CD3(subset). They are negative for CD1, CD2, surfaceCD3, CD4, CD5, CD7, CD8, CD10, CD13, CD14, CD15, CD20, CD22, CD25, CD36, CD41, CD64, CD66c, CD81, CD117, TdT, surface immunoglobulin light chain (kappa and lambda), cytoplasmic IgM and myeloperoxidase expression.

Hyperdiploid clones:

50,XY,dup(1)(p22p36.1),+4,+10,-15,+21,+22,+mar[12]

50,idem,del(11)(q12),add(19)(q13.1)[3]

Diploid male karyotype 46,XY[5]

1. Negative for t(8;21)(q22;q22); RUNX1-RUNX1T1, inv(16)(p13.1q22), t(15;17)(q22;q12); t(9;22)(q34;q11.2); ETV6-RUNX1, t(1;19)(q23;p13.3); E2A-PBX1, and t(4;11)(q21;q23); MLL-AF4 and t(6;9)(p23;q34); DEK-NUP214

2. Negative for mutations in IDH1, IDH2, JAK2, KIT, KRAS, NPM1, NRAS, FLT3 (including ITD) and CEBPA

Overall, the findings are consistent with involvement by an acute lymphoblastic leukemia. The immunophenotype is unusual for showing both B-lineage (CD19, cytoplasmic CD79a), majority of the blasts, and, T-lineage (cytoplasmic CD3), subset of blasts, marker expression in the blasts. The acute leukemia is best classified as acute lymphoblastic leukemia with B- and T-lymphoblastic immunophenotype. Acute leukemia with mixed T- and B-lymphoblastic markers are rare. This specific case poses challenges with accurate subclassification using the 2008 WHO classification. Using the 2008 WHO classification, the leukemia can be classified as mixed phenotype acute leukemia, not otherwise specified (NOS) that shows both B-lymphoblastic and T-lymphoblastic makers. There is no immunophenotypic evidence of myeloid lineage differentiation.

ACUTE LYMPHOBLASTIC LEUKEMIA WITH MIXED B- AND T-LYMPHOBLASTIC PHENOTYPE, 84% BLASTS

Mixed phenotype acute leukemia, B/T (with hyperdiploidy)

Case 359