Submitting Author: Geyer, Julia Turbiner, MD
Institution: Weill Cornell Medical College
Additional authors:Attilio Orazi, MD
Session: Acute leukemias of ambiguous lineage

The patient is an 89 year old woman who presented with increasing fatigue and dyspnea on exertion of several months duration. She was found to have anemia and was treated with vitamin B12 without improvement. She was then referred to an oncologist. On physical exam, she had red scaly skin rash on lower extremities and mild cervical lymphadenopathy. The CBC at the time of the bone marrow biopsy showed: WBC 3.2 x 103/uL, hemoglobin 6.5 g/dL, hematocrit 19.3%, MCV 103.4 fL, platelets 63 x 103/uL. Manual differential: 6% neutrophils, 58% lymphocytes, 1% monocytes, 2% eosinophils, 31% blasts. The patient was treated with 2 cycles of decitabine, without response. She subsequently developed pneumonia and was transferred to hospice care 3 months following the diagnosis.

Right posterior iliac crest bone marrow biopsy was fixed in Bouin's solution, while the clot sections were fixed in formalin. Bone marrow cellularity is increased for patient's age (~80%). Normal bone marrow cells are almost entirely replaced by sheets of small to medium-sized blasts with round to irregular nuclei, dispersed chromatin, several occasionally prominent nucleoli and scant agranular cytoplasm. In addition, there are multifocal discrete aggregates of larger cells with irregular nuclei, variably condensed chromatin and abundant eosinophilic cytoplasm, admixed with many tingible body macrophages. Residual granulopoiesis, erythropoiesis and megakaryopoiesis is virtually absent. Reticulin stain shows a mild increase in reticulin fibers (1+).

Flow cytometric analysis identified a blast population that expresses CD34, CD117(+/-), CD13, CD33 (dim), HLA-DR, TdT, CD11b (dim), CD4, CD7(dim, subset) and cytoplasmic CD22 (dim). The blasts are negative for CD3, CD19, CD20, CD10, CD2, CD5 and MPO.

Cytochemical staining of the bone marrow aspirate reveals that the blasts do not express MPO or NSE.

Immunohistochemical staining showed that the blasts are positive for CD34, CD117(+/-), TdT, CD22 (weak, subset), Pax-5 (subset) and CD79a (subset). They do not express MPO, Lysozyme, CD14, Glycophorin C, CD42b or CD3. The larger cells with eosinophilic cytoplasm are negative for all of the above markers, and in addition do not express CD56, TCL-1, Granzyme B, CD1a or S100. They are positive for CD123, CD68 and CD4, consistent with plasmacytoid dendritic cell immunophenotype.

46,XX[20]

1) The blasts do not express myeloperoxidase, CD3 or CD19 with any modality. They show expression of myeloid antigens: CD117 (partial), CD13, CD33 (dim); B-cell antigens: CD79a (partial), CD22 (partial); and are positive for TdT. Thus, this leukemia is best classified as acute undifferentiated leukemia based on the 2008 WHO Classification criteria. However, if the modified EGIL scoring system is used, the diagnosis is most consistent with a biphenotypic acute leukemia, B/myeloid (2.5 points for the B lineage and 3 points for myeloid lineage).

2) Nodules of plasmacytoid dendritic cells (PDCs) have rarely been described in bone marrow biopsies of patients with acute and chronic myeloid leukemias (Vermi W et al, Am J Surg Pathol 2004; Chen YC et al, Am J Clin Pathol 2003; Orazi A et al, Mod Pathol 2006). They appear to share the chromosomal abnormalities with the myeloid neoplastic cells, suggesting that these cells are clonally related. More recent findings indicate that the relationship between the myeloid tumor cells and the accompanying PDCs is a complex one with evidence of lineage plasticity and potential multidirectional differentiation (Vitte F et al, Am J Surg Pathol 2012). The PDCs in this case do not correspond morphologically or immunophenotypically to either a blastic plasmacytoid dendritic cell neoplasm or a mature plasmacytoid dendritic proliferation. Thus they could represent an example of partial plasmacytoid dendritic cell differentiation of an acute leukemia of ambiguous lineage. Alternatively, this may be a case of “dedifferentiated” acute leukemia arising from high-grade transformation of plasmacytoid dendritic cells.

Acute leukemia of ambiguous lineage with a multifocal proliferation of plasmacytoid dendritic cells.

Additional immunostains performed by the conference consensus group:

OCT2: Positive
CD11c: Plasmacytic dendritic cell clusters positive, subset of leukemic cells positive
CD19: Negative
CD117: Negative

Acute unclassifiable leukemia versus acute myeloid leukemia with minimal differentiation and infiltrates of plasmacytoid dendritic cells

Case 199