Institution: Mayo Clinic
Additional authors:Kaaren K Reichard, Rhett P Ketterling
Session: B Lymphoblastic Leukemia/Lymphoma
HISTORY
The patient is an 11 y.o. female who presented to her primary care provider for evaluation of fatigue. A CBC showed a Hgb of 8.2 g/dl, with WBC and platelets normal. However, she recently had the first onset of menses just prior to this visit. Three months later, while on a trip with her family to Sweden, she became profoundly anemic and needed to be carried up the stairs, During this time she had a febrile illness of 5-6 days duration which resolved. Upon returning home she presented for re-evaluation and was found to now have a Hgb 4.5 g/dL, WBC 2.0 x 10^9/L, Plts 357 X 10^9/L. A bone marrow examination was done for further evaluation.
DETAILS
Apart from marked anemia and neutropenia, the peripheral blood was notable only for prominent polychromasia (Fig 1). The bone marrow was very cellular with a predominance of erythroid precursors and megakaryocytes. There was a small population of immature lymphoid appearing cells present, but these accounted for only 5-10% of the cellularity (Fig 2-4). Given the age of the patient, as well as the regenerative features of the bone marrow, these immature lymphoid cells were initially felt to be hematogones.
Bone marrow biopsy fixed in B5.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemistry confirmed that the immature cells were precursor B-cells, as there were scattered Pax-5 (Figure 5), CD 34 (Fig 6), and Tdt (Fig 7) positive cells. However flow cytometry studies (Fig 8) demonstrated that there was a population of cells that had dim CD 45 expression, and slightly brighter CD19 and much brighter CD10 expression than normal hematogones. These cells were also CD20 and CD 38 positive.
CYTOGENETIC FINDINGS
Routine cytogenetics studies were normal. However, ALL FISH studies demonstrated that 12.5 % of nuclei had an IgH rearrangement, and 5.2% of nuclei had three intact ABL1 signals at chromosome 9q34.
MOLECULAR FINDINGS
Both Immunoglobin and T-cell receptor gene rearrangements studies were positive.
INTERESTING FEATURES
With the marked erythroid hyperplasia present, an increase in hematogones would be expected. Flow cytometry studies however showed two distinct CD19/CD10 positive populations, one population representing normal hematogones. Both FISH and gene rearrangement studies indicated the clonal nature of the other small precursor B population.
Due to the very small size of the clonal precursor B population, the hematologists elected close observation. A repeat bone marrow examination six weeks later showed 80% blasts which expressed CD19, CD10, CD20, Tdt, CD34 (partial) and HLA-DR (Fig 9-11).PROPOSED DIAGNOSIS
Minimal involvement by a clonal precursor B cell population which subsequently progressed to B Lymphoblastic Leukemia/Lymphoma.
CONSENSUS DIAGNOSIS
B-acute lymphoblastic leukemia/lymphoma, with initial oligoblastic presentation