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1392 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1393

ACUTE BASOPHILIC AND MAST HISTIOCYTIC AND ACUTE MYELOID
CELL LEUKEMIA DENDRITIC CELL LEUKEMIA
First described in 1906, basophilic differentiation as a feature of Chapter 71 discusses histiocytic and myeloid dendritic cell leukemia.
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AML is an uncommon event, occurring in approximately one in 100
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cases of AML. Most cases of acute basophilic leukemia evolve from DIFFERENTIAL DIAGNOSIS
the chronic phase of CML, but de novo acute basophilic leukemia, in
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which the cells do not contain the Ph chromosome, does occur. 549,535–560 Acute leukemia in infants with Down syndrome should be differen-
The cells stain with toluidine blue, and the basophilic granules can be tiated from TMD (see “Neonatal Myeloproliferation and Leukemia”
most striking in myelocytes. In some cases of acute myelomonocytic above). In adults, the term pseudoleukemia has been applied to circum-
leukemia associated with t(6;9)(p23;q34), basophils may be increased stances that mimic the marrow appearance of promyelocytic leukemia.
in the marrow but not in the blood. Because CML with t(9;22)(q34;q11) Recovery from drug-induced or Pseudomonas aeruginosa–induced
has the same breakpoint (q34) on chromosome 9 as AML with t(6;9) and agranulocytosis is characterized by a striking cohort of promyelocytes
both diseases are strongly associated with marrow basophilia, a gene(s) in the marrow, which upon inspection of the marrow aspirate or biopsy
at the breakpoint on chromosome 9 may influence basophilopoiesis. 448 mimics promyelocytic leukemia. 568–570
Anemia, thrombocytopenia, and blast cells in the blood are present In pseudoleukemia, the platelet count may be normal; the degree
at the time of diagnosis. The blood leukocyte count usually is elevated, of leukopenia often is more profound (<1.0 × 10 /L) than usually seen
9
and proportions of the cells are basophils. The marrow is cellular with in AML 511,512 ; promyelocytes contain a prominent paranuclear clear
a high proportion of blasts and early and late basophilic myelocytes. (Golgi) zone not covered with granules; and promyelocytes do not have
Special staining with toluidine blue or Astra blue often is necessary to Auer rods. 570–572 Similar reactions have been reported after granulocyte
distinguish basophilic from neutrophilic promyelocytes and myelo- colony-stimulating factor (G-CSF) administration. In patients sus-
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cytes. Immunophenotyping may show myeloid markers (CD33, CD13) pected of having pseudoleukemia, observation for a few days usually
that are not specific. Presence of CD9, CD25, or both is characteristic clarifies the significance of the marrow appearance, because progressive
of basophilic differentiation. Cells may have granules with ultrastruc- maturation to segmented neutrophils normalizes the marrow and leads
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tural features of basophils and mast cells. Electron microscopy can to an increased blood neutrophil count.
be useful in identifying basophilic granules in cases where no granules In patients with hypoplastic marrows, careful examination of
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are evident by light microscopy and the phenotype simulates M0. specimens is required to distinguish among aplastic anemia, hypoplas-
Basophilic leukemia can be confused with promyelocytic leukemia if tic acute leukemia, 350–352 and hypoplastic oligoblastic myelogenous
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the basophilic early myelocytes are mistaken for promyelocytes. On leukemia (MDS). Leukemic blast cells are evident in the marrow
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the contrary, promyelocytic leukemia may have basophilic maturation in hypoplastic leukemia, and islands of dysmorphic cells, especially
and can be mistaken for basophilic leukemia. However, if the cells con- megakaryocytes, are present in hypoplastic oligoblastic leukemia.
tain t(15;17), the disease should respond to ATRA and an anthracycline Leukemoid reactions and nonleukemic pancytopenias can be dis-
antibiotic. 474,477,478 Prolonged clotting time, intravascular coagulation, tinguished from AML by the absence of leukemic blast cells in the blood
and hemorrhage are uncommon presenting features in patients with or marrow. In older children and adults, myeloblasts usually do not
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basophilic leukemia, but are common in patients with promyelocytic constitute more than 2 percent of marrow cells except in patients with
leukemia. Coagulopathy can occur after chemotherapy. Cluster head- a myeloid neoplasm, and the proportion of blast cells usually decreases
aches, skin rashes, often with an urticarial component, and gastroin- in the marrow as a result of exaggerated expansion of the myelocyte
testinal symptoms may be present. Elevated blood and urine histamine compartment with neutrophilic leukemoid reactions.
and urinary methylhistamine levels are characteristic features. Rare
cases of a chronic course in BCR-ABL–negative basophilic leukemia
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preceding the onset of rapid progression have occurred. Treatment THERAPY
for acute (Ph-negative) basophilic leukemia is similar to that for other
variants of AML. OVERVIEW OF TREATMENT PLAN
Mast cell leukemia is a rare manifestation of systemic mast cell The usual treatment of AML includes an initial program termed the
disease (Chap. 63). 549,563 It can be related to a mutation of the KIT induction phase. Induction may involve the simultaneous use of mul-
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gene. The leukemic mast cells are KIT (CD117) positive, naphthol tiple agents or a planned sequence of therapy called timed sequential
AS-d-chloracetate esterase positive, tryptase positive, myeloperoxidase treatment. Once a remission is obtained, further treatment is indicated
negative, and CD25-negative. 564,565 Plasma tryptase is elevated. In some to preserve the remission state. Remission is defined as elimination of
cases, electron microscopy of the granule-containing cells, which dem- the leukemic cell population in marrow as judged by microscopy and
onstrates the characteristic scroll-like granules of mast cells, may aid in flow cytometry and the restitution of marrow hematopoiesis resulting
distinguishing basophils from mast cells (Chap. 63). Extensive, appar- in a normal or virtually normal white cell, hemoglobin, and platelet
ently reactive, mast cell tissue infiltrations may be provoked by cytok- concentrations in the blood. The postinduction treatment can consist
ines during the course of AML. 566,567 of cytotoxic chemotherapy, HSC transplantation, or low-dose mainte-
The key laboratory distinctions between acute basophilic leukemia nance chemotherapy, depending upon patient performance status and
and acute mast cell leukemia are that the cells in the former are naphthol risk factors. If relapse occurs, treatment options may include differ-
AS-d-chloracetate esterase negative, CD11b positive, CD117 negative ent chemotherapy regimens, allogeneic HSC transplantation, or other
or weakly positive, CD123 positive, have no increase in cell or plasma investigational regimens, often as part of a clinical trial.
tryptase, and have basophilic-like granules on electron microscopy;
whereas, the cells in mast cell leukemia are naphthol AS-d-chloracetate DECISION TO TREAT
esterase positive, CD11b-negative, CD117-positive, CD123-negative,
have an increase in cell and plasma tryptase, and have mast cell-like Most patients with AML should be advised to undergo treatment
granules on electron microscopy. 549 promptly after diagnosis. Patients younger than 60 years of age have a

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