Residency Program - Case of the Month

Clinical History

This patient is a 21-year-old female who initially presented with epistaxis, severe back pain and fatigue. She was found to be neutropenic with increased blasts and subsequently diagnosed with BALL with t(9;22)(q34;q11) BCR/ABL1. She received 8 cycles of hyper-CVAD with rituxan and dasatinib and achieved remission. However, 3 months later, the patient complained of frontal headache withauras. Lumbar puncture performed demonstrated an increased intracranial pressure and CSF analysis revealed increased white blood cell count of 361. She received intrathecal Methotrexate along with augmented Hyper-CVAD+Dasatinib. After two months of treatment, her CSF showed “rare immature mononuclear cells with undetermined significance”.  Since then, the patient had multiple relapses while undergoing various therapies, including triple intrathecal therapy (methotrexate, cytarabine, corticosteroid), craniospinal radiation and RMOpAD based clinical trial. Although radiologic work-up was unremarkable, relapse was confirmed by a large population (98%) of blasts in CSF. As this portended a poor prognosis, bone marrow transplant was deemed as a futile treatment option. The patient succumbed to her disease one month later

Microscopic Description and Flow Cytometry Analysis

The bone marrow biopsy showed fibrotic hypocellular marrow with aplastic hematopoiesis and a large population of blasts (~90%). The blasts were medium-sized with prominent invaginated nuclei, fine nuclear chromatin, conspicuous nucleoli and moderate amount of basophilic agranular vacuolated cytoplasm (Figure 1A). Flow cytometry demonstrated dim CD45, HLA-DR, CD34, dim CD38, CD19, CD10, heterogenous CD20, TDT, CD22 and CD79a without T-cell or myeloid antigens consistent with B-ALL. Similar findings were seen in the subsequent CSF relapse (Figure 1B).

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Figure 1A. A large population (~90%) of blasts was identified in the bone marrow aspirate smear (A) and cerebral spinal fluid (B) from this patient.

Cytogenetic and Molecular Findings

Cytogenetic analysis of bone marrow cells showed a very complex abnormal female karyotype:
47, XX, del(3)(p21), del(6)(q13q21), t(8;9)(q13;p13),der(9)del(9)(p13)t(9;22)(q34.1;q11.2),der(22)t(9;22),+mar[4]46,XX[16]. Four of the 20 cells analyzed showed multiple chromosome alterations, including t(9;22)(q34.1;q11.2) with the derivative 9 containing a deletion of its short arm. FISH analysis confirmed t(9;22) or BCR/ABL1 fusion and additional copies of chromosome 4.

What are the morphological differential diagnoses when AML-like blasts in CSF are encountered?

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