ASH Image Bank (2002); doi:10.1182/ashimagebank-2002-100401
Copyright © 2002 by the American Society of Hematology.
Acute Biphenotypic Leukemia
Peter Maslak
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Figure 1. Acute Biphenotypic Leukemia. Peripheral blood shows undifferentiated blasts with a high nucleocytoplasmic ratio (1000X MacNeal tetrachrome).
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Figure 2. Acute Biphenotypic Leukemia. The bone marrow reveals a hypercellular aspirate replaced by blasts (400X MacNeal tetrachrome).
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Figure 3. Acute Biphenotypic Leukemia. High-power view of blasts show they are basophilic with scant cytoplasm (1000X MacNeal tetrachrome).
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Figure 4. Acute Biphenotypic Leukemia. Another high power view of the bone marrow aspirate. Although most of the blasts are small, occasional large blasts (arrow) were noted (1000X MacNeal tetrachrome).
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Figure 5. Acute Biphenotypic Leukemia. Hypercellular bone marrow biopsy replaced by blasts (400X H&E).
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Figure 6. Acute Biphenotypic Leukemia. Blast population as defined by scatter (a) expresses both the myeloid marker CD13 and the lymphoid marker CD19 (b).
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Figure 7. Acute Biphenotypic Leukemia. Following chemotherapy, all cell lineages are noted and normal hematopoiesis has been once again established. (400X MacNeal tetrachrome).
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Clinical Summary
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The patient is a 58 year-old-white woman who presented for evaluation of pancytopenia. The patient was in her usual state of good health until two months prior to presentation when she sought medical attention for an infected right upper wisdom tooth. She received several courses of antibiotics for this and ultimately underwent extraction of the wisdom tooth. The extraction was accompanied by significant bleeding which required "packing" the wound. The bleeding prompted a complete blood cell count (CBC) which revealed pancytopenia.
The physical examination revealed a thin, well-developed woman in no acute distress. Her vital signs were stable. Small (approximately 1.5 cm) submandibular and right cervical lymph nodes were noted. A 1cm axillary lymph node was also appreciated. No other significant lymphadenopathy was noted. The abdominal exam was negative for organomegaly. No peripheral edema was noted and the neurologic exam was nonfocal.
CBC was obtained and revealed: white blood cell count (WBC)- 2.7 k/ml with an absolute neutrophil count of 0.7 k/mL, hemoglobin (Hgb)- 7.5 g/dL, hematocrit (Hct)- 21.5%, and platelets- 70 k/ml. Review of the peripheral smear confirmed the leukopenia but also detected rare basophilic blasts with a thin rim of cytoplasm (Figure 1). Blood chemistries were obtained: Na- 142 mEq/L, K- 4.0 mEq/L, Cl- 109 mEq/L, CO2- 25 mEq/L, BUN-13 g/dL, creatinine - 0.6 mg/dL, glucose- 95 mg/dL, P- 3.0 mg/dL, T.B.- 0.6 mg/dL, and lactate dehydrogenase (LDH)- 206 U/L.
Bone marrow aspiration and biopsy were performed. The aspirate was hypercellular, with the predominant component composed of blasts (Figure 2). The blasts had scant cytoplasm and varied in size (Figure 3, Figure 4, and Figure 5). No granules or Auer rods were noted in these cells. Histochemical staining for Sudan black, naphthol AS-D chloroacetate esterase, and a-naphthyl acetate esterase were negative. Immunophenotyping revealed the blasts expressed CD13, CD33, CD11b, CD34, HLA-DR, CD10, CD19, CD20, CD22, CD7, CD5, and CD2. Dual parameter plots demonstrated that the cells co-expressed CD19 and CD13 (Figure 6). Cytogenetic analysis subsequently revealed a normal karyotype.
All treatment options, including investigational therapies, were discussed. The patient was admitted to the hospital and underwent induction therapy with mitoxantrone and high-dose Ara-C. The patient tolerated the therapy well but required the usual blood product support and antimicrobials. Following the recovery of the peripheral blood counts about four weeks later, bone marrow aspiration was performed. The aspirate was normocellular with all cell lineages present. No evidence of leukemia was seen (Figure 7). HLA typing failed to reveal a related donor and an unrelated search was begun.
Sex
Female
Age
58
Ethnicity
White
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Diagnosis
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Acute biphenotypic leukemia
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Discussion
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Biphenotypic leukemias have been increasingly reported because immunophenotyping and molecular analyses have been expanded as clinical tools and incorporated into the standard diagnostic work-up. The characterization of these diseases based on morphology alone can be difficult. Blasts are often undifferentiated with no distinguishing characteristics such as granules or Auer rods. However, some cases have been described based on the detection of two distinct populations of blasts that vary in size.
Immunophenotyping is the most important tool in characterizing acute biphenotypic leukemia. Diagnostic criteria have been defined, including those outlined by the European Group for the Immunological Characterization of Leukemia (EGIL) and the Royal Marsden group. Common to these diagnostic systems is the ability to ascribe multiple lineage associated characteristics to the disease in question. Scoring systems have evolved which define the minimum number of phenotypic characteristics necessary to be considered true biphenotypia. Patients who do not meet these criteria are instead thought to have a variant of either acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) with minimal lineage infidelity.
Although diagnostic criteria exist, clinical data regarding this entity remains rather sparse. Patients have generally been treated with AML-like regimens. Some investigators have reported a worse prognosis in adults.
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Differential Diagnosis
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Acute myelogenous leukemia (AML [with lymphoid antigens particularly t(8:21), which may express CD19 or CD56]) acute lymphocytic leukemia (ALL) with myeloid antigens, particularly t(9;22), acute undifferentiated leukemia.
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Chapter 10: Acute myeloid leukemia
Copyright © 2002 by the American Society of Hematology.
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