Case 354

Submitting Author: Schubeck, Andrew Thomas, MD
Institution: University of Michigan
Additional authors:Nathanael Bailey, M.D.
Session: T Lymphoblastic Leukemia/Lymphoma

HISTORY

21 year old G2P1 female at 19 6/7 weeks gestation presenting with pleuritic chest pain and flu-like symptoms. Workup included a chest CT which showed a moderate right pleural effusion with enlarged mediastinal lymph nodes without evidence of a pulmonary embolus. Initial peripheral blood examination revealed a WBC of 14.3 K/μL with 41% circulating blasts. The remainder of the CBC was as follows: HGB 11.3 g/dL, HCT 33.3%, Plt 177 K/μL. A pelvic ultrasound showed a large right ovarian mass, which was consistent with a teratoma by follow-up MRI. A bone marrow biopsy was performed.

DETAILS

Left iliac crest bone marrow core biopsy consisting of three bony cores ranging from 0.3 to 0.6 cm in length (AZF fixation).

The bone marrow is hypercellular (90% cellular) with diminished trilineage hematopoiesis. Sheets of immature mononuclear cells with scant cytoplasm and round to slightly irregular nuclei are present. The aspirate smears demonstrate a predominant population of small to intermediate blasts with immature chromatin, occasional nucleoli and scant agranular cytoplasm without Auer rods or vacuoles.

Bone Marrow Aspirate 500 Cell Differential Count:

Blasts 67.8%

Promyelocytes 1.4%

Other Granulocyte Precursors 12.2%

Erythroid Precursors 12.6%

Lymphocytes 4.0%

Eosinophils and Precursors 0.0%

Basophils and precursors 0.0%

Monocytes and precursors 2.0%

Plasma Cells 0.0%

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometric analysis demonstrates a population of immature cells with the following immunophenotype:

Positive: CD45 (dim), cytoplasmic CD3 dim-moderate, CD5 dim (~ 60% of blasts), CD7 moderate, CD33 dim (30-40% of blasts), CD34 dim (30-40% of blasts), CD38 dim, cytoplasmic CD79a dim-moderate.

Negative: CD117, cytoplasmic MPO, CD1a, CD2, surface CD3, CD4, CD8, CD10, CD11c, CD13, CD14, CD19, CD20, CD22, cytoplasmic CD22 and CD56.

CYTOGENETIC FINDINGS

Normal karyotype, 46,XX in 9 cells examined at initial diagnosis. Repeat karyotype performed on subsequent bone marrow biopsy with persistent leukemia also demonstrated a normal karyotype, 46,XX, in 20 cells examined.

MOLECULAR FINDINGS

FISH results are as follows:

Negative for rearrangement of TLX3 (5q35) gene region.

Negative for rearrangement of TCRB (7q34) gene region.

Negative for deletion of CDKN2A (9p21) gene region.

Negative for t(9;22) BCR/ABL1 rearrangement.

Negative for rearrangement of MLL (11q23) gene region.

Negative for rearrangement of TCRA/D (14q11.2) gene region.

No evidence of isochromosome 12p.

INTERESTING FEATURES

This case has immunophenotypic features of the recently described entity early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), a rare subset of lymphoblastic leukemia that may not respond optimally to standard chemotherapy (Coustan-Smith et al. Lancet Oncol 2009. 10:147-56). Subsequent genetic analysis suggests that although these neoplasms express some T-cell associated antigens, they also have features of early hematopoietic stem cells that retain the capacity for myeloid differentiation (Zhang et al. Nature 2012. 481:157-163). In addition to the unusual phenotypic features, the discovery of leukemia during pregnancy presents unique clinical management challenges.

PROPOSED DIAGNOSIS

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).

CONSENSUS DIAGNOSIS

T-acute lymphoblastic leukemia, early T-cell precursor immunophenotype