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1386 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1387

the megakaryoblastic variant. 425–430 Mediastinal tumors are rare variants the FAB classification. The WHO has divided acute myeloblastic leuke-
of germ cell tumors. The latter ordinarily occur as testicular teratomas mia into three types: AML without differentiation, AML without mat-
and seminomas in men or as ovarian teratomas in women. They are uration, and AML with maturation. There is no evidence of a clinical
thought to be derived from yolk sac cells that failed to migrate. 428,429 AML distinction in response to therapy or in prognosis within these rarified
is a HSC tumor derived from a cell type that is present in the yolk sac. designations.
Cytogenetic studies are compatible with a clonal relationship (identity) In many cases of myeloblastic leukemia, more prominent granu-
of mediastinal germ cells and myelogenous leukemia cells. 426,427 Appar- locytic maturation is evident (FAB type M2 or WHO designation AML
ently, hematopoietic lineage genes are predisposed to expression in with maturation). This variant is present in approximately 15 percent of
extragonadal (mediastinal) germ cell tumors. Use of etoposide, plati- AML cases; thus, approximately 45 percent of cases of AML are mye-
num, and related cytotoxic drugs for treatment of mediastinal germ cell loblastic leukemia with or without maturation. Blasts usually consti-
tumors may induce secondary AML in a predisposed cell population. 431 tute at least 20 percent of the marrow cells. Auer rods may be present
in blast cells. Promyelocytes, myelocytes, and segmented neutrophils,
GASTROINTESTINAL TUMORS AND ACUTE the latter often with the acquired Pelger-Huët anomaly, may constitute
20 to 60 percent of marrow granulocytes. The anomaly is reflected in
MYELOGENOUS LEUKEMIA bilobed or monolobed neutrophils. Histochemical and surface markers
A study of 1892 patients with KIT-positive mesenchymal gastrointes- of blast cells are typical of myeloblastic leukemia, and monocytic mark-
tinal stromal tumors found a significant subsequent incidence of AML ers are absent or infrequent. Monocytes represent less than 10 percent
(nine patients). The standardized incidence ratio was approximately 3.0 of cells. A translocation between chromosomes 8 and 21 t(8;21)(q22;
(confidence interval: 1.1 to 5.8). The patients had not received prior che- q22), often accompanied by loss of the Y chromosome in men or loss
motherapy or radiotherapy and the median duration of gastrointestinal of an X chromosome in women, is associated with the phenotype and
stromal tumors before onset of AML was 6 years. 432 occurs in younger patients (average age approximately 30 years). 439–441
Patients whose cells contain t(8;21) are more prone to develop myeloid
sarcoma. 263,266
MORPHOLOGIC VARIANTS OF ACUTE
MYELOGENOUS LEUKEMIA ACUTE MYELOMONOCYTIC LEUKEMIA

Morphologic variants of AML (Table 88–5) may occur de novo or may The ability of AML to express cells of the monocytic and granulocytic
be the manifestation of clonal evolution from essential thrombocythe- lineages was first highlighted in the early 1900s by Naegeli. Later, Hal
mia, idiopathic myelofibrosis, CML, or other chronic clonal myeloid Downey, a leading hematologist of the day, proposed the eponym
442
disorders. For example, every phenotypic variant of AML can occur as Naegeli type for myelomonocytic leukemia. Approximately 15 per-
the blast crisis of CML (Chap. 89). cent of patients with AML present with this variant, and they are more
likely to have extramedullary infiltrates in gingiva, skin, or CNS than
are patients with acute myeloblastic leukemia (see “Myeloid [Granulo-
ACUTE MYELOBLASTIC LEUKEMIA cytic] Sarcoma” above). A mixture of myeloblasts and monoblasts is
443
The designation acute myeloblastic leukemia came into existence in the found in the blood and marrow. More than 30 percent of marrow cells
second decade of the 20th century, following the specific description are a mixed population of myeloblasts, which react with peroxidase or
4
of the myeloblast. Approximately 25 percent of AML cases have the chloracetate esterase, and monoblasts or promonocytes, which react
6
features of acute myeloblastic leukemia, a variant in which the leukemic with fluoride-inhibitable nonspecific esterase (see Fig. 88–2F). More
myeloblast is the predominant cell in the marrow. Acute myeloblastic than 20 percent of cells are monoblasts or promonocytes in blood and
leukemia was divided into two forms, designated M0 and M1 in the marrow. In some cases, individual cells react with monocytic and gran-
French-American-British (FAB) Classification. In either type, little evi- ulocytic histochemical stains. Serum and urinary lysozyme levels are
444
dence of maturation of myeloblasts exists, and the marrow is replaced increased in most cases. This variant of AML is referred to as M4 in the
by a monotonous population of blasts. In acute myeloblastic leukemia FAB classification and as acute myelomonocytic leukemia in the WHO
(M0), the patient’s age distribution, presenting white cell count, and classification. Translocations involving chromosome 3 are associated
cytogenetic abnormalities are not distinctive. The blasts are nonreac- with this phenotype. 445
tive when stained for myeloperoxidase activity, and Auer rods are not The proportion of marrow eosinophils or basophils may
447
446
seen. The blasts react with antibodies to myeloperoxidase and antibod- be increased. A particular variant of myelomonocytic leukemia has
ies to CD13, CD33, and CD34. Human leukocyte antigen (HLA)-DR increased numbers of marrow eosinophils (10 to 50 percent), Auer rods
is positive in most patients. Occasional cases require in situ hybridiza- in blast cells, and inversion or rearrangement of chromosome 16 (see
tion to identify the myeloperoxidase gene or genomic profiling for Fig. 88–2G). 304–307 The eosinophils are abnormally large, and the eos-
433
early myeloid-associated genes. Abnormal and unfavorable karyo- inophilic myelocytes contain large basophilic granules. Macrophages
434
types (e.g., 5q–,7q–) and expression of the multidrug resistance (MDR) with ingested Charcot-Leyden crystals may be present. This pheno-
glycoprotein (p170) are more frequent. This phenotypic variant has a typic variant of AML has been designated M4Eo in the FAB classifica-
poor prognosis. 435–438 In the other type of myeloblastic leukemia, desig- tion. Although this variant has an increased risk of CNS involvement,
nated M1, myeloblasts are present in the blood and make up more than it carries a more favorable prognosis than the average case of AML.
70 percent of marrow cells. Less than 15 percent of marrow cells are Fluorescence in situ hybridization (FISH) is a more accurate method
promyelocytes and myelocytes. Auer rods may be present in occasional for detection of cryptic 16q22 gene rearrangements and is useful in
blasts, but azurophilic granules are not evident in the blasts by light conjunction with conventional cytogenetics for patients with M4Eo
microscopy. At least 3 percent, but usually a much higher percentage, AML. AML with t(6;9)(p23;q34) is an uncommon variant, occurring in
of the blast cells, have a positive reaction when stained for peroxidase or approximately 1 percent of cases, and may express itself as acute mye-
with Sudan black or react with monoclonal antibodies specific to mye- lomonocytic or acute myeloblastic leukemia. Anemia, thrombocytope-
loblasts, such as CD33. This morphologic subtype is denoted as M1 in nia, a variable white cell count, and increased myeloblasts are frequent.

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