Submitting Author: Raza, Adeel M, MD
Institution: The Methodist Hospital, Texas Medical Center
Additional authors:April Ewton, MD
Session: B Lymphoblastic Leukemia/Lymphoma

The patient is a 35-year-old male with no significant past medical history. He was in his usual state of health until he began having perineal pain. The patient initially went to an urgent care clinic and felt that his pain was related to hemorrhoids. On initial evaluation, labs were drawn which revealed a white blood cell count of 14.6 k/uL, hemoglobin of 10 g/dL and platelets of 49 k/uL. He was advised to consult hematologist. A bone marrow biopsy was done at the outside hospital showed findings consistent with AML. The patient was then transferred to our hospital for a higher level of care.

Flow Cytometry performed in our hospital on peripheral blood revealed 79% poorly differentiated blasts after which he received cytarabine and idarubicin. The patient underwent bone marrow biopsy on day 24 after induction chemotherapy. Cerebrospinal fluid was also sent for flow cytometry.

Peripheral blood, Bone marrow biopsy and aspirate.

The marrow cellularity was approximately 15 % with an M:E ratio of 1:2. Erythroid elements were present with adequate maturation .Myeloid were decreased with left shifted maturation. Megakaryocytes were decreased with normal morphology.

There were increased blasts with variable morphology, ranging from very small with round nuclei to large with moderate cytoplasm and round to irregular nuclei. No cytoplasmic granules or Auer rods were identified. No ringed sideroblasts were seen.

Peripheral blood revealed marked pancytopenia.

Cerebrospinal fluid revealed blasts. (Figure 1)

Flow Cytometric findings on cerebrospinal fluid showed two abnormal populations: (Figure 2, 3,4,5)

First abnormal population (32% of total cellularity) immunophenotypically consistent with myeloid blasts were positive for CD34, CD45dim, CD33dim, CD13, CD38, HLA-DR, MPO and negative for CD117, CD15, CD22, TdT, CD19, CD10

Second abnormal population (39% of total cellularity) immunophenotypically consistent with lymphoid blasts were positive for CD34 (dim), CD45(dim), CD33, CD13, CD38, HLA-DR (variable), TdT, CD22 (variable), CD15 and negative for CD117, CD19, CD10, MPO

Flow Cytometric findings on bone marrow revealed abnormal blast population (11% of total cellularity).

The blasts express B cell marker CD19 and myeloid markers CD13 and CD33. The blasts also variably express CD25.

Immunohistochemical stains performed on bone biopsy showed increased blasts positive for CD34 and negative for CD79a, CD117, and PAX-5. It could not be determined with certainty whether the neoplastic blasts were positive or negative for MPO; however, the initial peripheral blood blasts were negative for MPO by flow cytometry. The blasts showed variable nuclear staining for TdT.

46,XY,t(9;22)(q34;q11.2)[1]/46,idem,del(20)(q11.2q13.2)[7]/46,XY[12]

PCR for IgH/IgK on CSF was clonal

The patient has acute leukemia with myeloid and lymphoid blast populations. The dual populations can be appreciated by morphology, immunohistochemistry, and CSF flow cytometry. However interestingly the blasts did not express intracytoplasmic CD22 or MPO in the initial peripheral blood specimen. PCR for IgH gene rearrangement showed a clonal rearrangement. The blasts also variably expressed CD25, which is seen in Ph-positive B- ALL or mixed phenotype acute leukemia

Philadelphia-chromosome positive mixed phenotype acute leukemia

Philadelphia-chromosome positive acute leukemia, myeloid versus mixed lineage, favor myeloid

Case 410