Institution: University od Arkansas Medical system
Additional authors:Zeba Singh
Session: B Lymphoblastic Leukemia/Lymphoma
HISTORY
A 67-year-old female presented with worsening anemia in 2005, work up revealed IgA kappa multiple myeloma. Karyotype revealed abnormal karyotype and GEP score was 0.635. Started on VTD-PACE treatment followed by Velcade, thalidomide, and dexamethasone maintenance. Achieved complete remission on 5/2007 with normal physical, laboratory and radiological findings, continued until 2/2011. In 2/2011 patient started c/o of worsening fatigue and progression of neuropathy, discontinued velcade and continued maintenance with revlimid and dexamethasone, however patient continued to have fatigue with neuropathy got slightly better.
A CBC analysis in august 2011 is within normal limits with additional labs at this time revealed normal LDH, B2M and serum protein analysis. However, Bone marrow evaluation revealed immature B- lymphoid population (15-20%) with an aberrant immunophenotype.Patient returned to clinic in 11/11, at that time CBC analysis was significant for minimal macrocytic anemia. BM biopsy analysis revealed increased immature B-lymphoid population (35% B- lymphoblast) in the background of mild trilineage dyspoiesis.DETAILS
Bone marrow biopsy (H&E) and aspirate (wright Geimsa): small to intermediate sized blasts with scant basophilic cytoplasm, irregular nuclear contour, immature chromatin and inconspicuous nucleoli, comprising 30- 35% of cellularity in the background of mild trilineage dyspoiesis.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemistry showed blasts are positive for CD20, TdT, CD99, and negative for CD3 and PAX5.
Flow cytometric analysis performed on the bone marrow aspirate showed 35% of lymphoblasts, with uniform expression of CD19, CD20, CD34, CD10, and TdT. This population is negative for CD3, MPO, CD33 and other tested myeloid and lymphoid markers.CYTOGENETIC FINDINGS
Bone marrow aspirate cytogenetic revealed 46,XX,del(9)(p12),del(20)(q11.2q13.1)[2]/46,XX[cp38].
FISH analysis detected 20q deletion in 40% of analyzed cells and showed no evidence of t(9;22), t(11q23) (MLL), t(8q24) (c-MYC).MOLECULAR FINDINGS
PCR analysis for B-cell gene rearrangement and T cell receptor rearrangement studies detected clonal immunoglobulin and TCR gene rearrangement.
INTERESTING FEATURES
Most of the therapy related neoplasms are therapy-related acute myeloid leukemia (t-AML) or myelodysplasia (t-MDS), or a small subset of therapy-related acute lymphoblastic leukemia (t-ALL). Majority of the therapy-related acute lymphoblastic leukemia (t-ALL) reportedly associated with translocations involving chromosome 11q23 and/or complex karyotype. This patient’s case is unusual with rapid onset of acute B- lymphoblastic leukemia with only 20q deletion in the background of trilineage dyspoiesis, within 6 months of morphologically and cytogenetically unremarkable bone marrow.
PROPOSED DIAGNOSIS
Therapy-related B- lymphoblastic leukemia.
CONSENSUS DIAGNOSIS
Therapy-related B-acute lymphoblastic leukemia