Case 365

Submitting Author: Song, Joo Young, MD
Institution: Department of Pathology and Laboratory Medicine, University of California, Davis
Session: Acute leukemias of ambiguous lineage

HISTORY

The patient is a 41 year old male with generalized weakness and fatigue for the past few weeks. He also had a few episodes of vomiting. Recently, he presented with bilateral lower extremity edema with an elevated white blood cell count.

DETAILS

Bone marrow, left posterior iliac crest, aspirate smear, touch prep, core biopsy, fixed in formalin.

Gross description: One tan core of roughened tissue measuring 1.5 cm in length x 0.2 cm in maximum diameter.

Aspirate/Touch prep: The aspirate was hypercellular with predominately blasts (80%) that were medium in size, had slightly clefted nuclei, granular cytoplasm, fine chromatin, and prominent nucleoli. There was a marked decrease in erythroid precursors and megakaryocytes.

Core biopsy: Markedly hypercellular marrow (>90%) with predominately immature cells consistent with blasts. Erythroid and megakaryocytes were markedly decreased.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Immunohistochemical stains showed the blasts were positive for CD34, CD79a (subset), PAX5 (subset), and negative for CD56.

By flow cytometry, the blasts population was positive for CD34, CD33 (dim), CD38 (partial), MPO (dim), CD7, HLA-DR (dim), CD117, CD64 (dim), CD11b (partial), CD19 (partial), CD79a (dim), and negative for TdT, cCD3, cCD15, CD13, CD20, and CD14.

CYTOGENETIC FINDINGS

45,XY,-7 [20]

FISH analysis detected monosomy 7 (93%) and trisomy 8 in ~2% of the nuclei.

MOLECULAR FINDINGS

Negative for KIT Asp816Val mutation.

Negative for NPM1 mutation.

INTERESTING FEATURES

This case is interesting in that the original immunophenotype by flow cytometry was favoring an acute myeloid leukemia with recurrent cytogenetic abnormalities (i.e. t(8;21)); however this was not detected. The PAX5 and MPO expression in the blasts favors an acute leukemia with ambiguous lineage, B/Myeloid. Monosomy 7 may suggest an AML with MDS related changes; however overt dysplasia was not noted in this case. The patient was treated with Cytarabine and Daunorubicin but died shortly after due to DIC and diffuse alveolar damage (DAD).

PROPOSED DIAGNOSIS

Acute leukemia with ambiguous lineage (B/myeloid).

CONSENSUS GROUP: ADDITIONAL INFORMATION/STUDIES

Additional immunostains performed on bone marrow sections by the conference consensus group:

MPO: Positive in blasts
CD68: Positive in blasts
Lysozyme: Positive in blasts

CONSENSUS DIAGNOSIS

Mixed phenotype acute leukemia, B/myeloid

A- The core biopsy is markedly hypercellular. B-Higher power shows there are sheets of blasts. C- Aspirate smear shows blasts with basophilic granular cytoplasm, some clefted nuclei, fine chromatin, and prominent nucleoli. A- The core biopsy is markedly hypercellular. B-Higher power shows there are sheets of blasts. C- Aspirate smear shows blasts with basophilic granular cytoplasm, some clefted nuclei, fine chromatin, and prominent nucleoli.
A- The blasts are positive for CD34 and PAX5 (B).A- The blasts are positive for CD34 and PAX5 (B).
There are increase blasts (42%) that are positive for CD19 (partial), CD34, CD7, CD33 (dim), HLA-DR (dim), MPO (partial), and cCD79a (partial).There are increase blasts (42%) that are positive for CD19 (partial), CD34, CD7, CD33 (dim), HLA-DR (dim), MPO (partial), and cCD79a (partial).