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

the tissue or extramedullary variant of monocytic leukemia (Chap. esterase or myeloperoxidase. The thrombopoietin receptor gene (MPL)
71). 523,524 The outcome of treatment, once thought to be less favorable is expressed in megakaryocytes (CD116) and exhibits the gain-of-
than with other forms of AML, is comparable to the outcome of other function point mutation W515K/L in approximately 25 percent of cases
subtypes. 525 of acute megakaryoblastic leukemia. 533
The serum lactic acid dehydrogenase level frequently is strikingly
increased and has an isomorphic pattern unlike that seen with other
ACUTE MEGAKARYOBLASTIC acute leukemias. Complex chromosome aberrations are common.
534
(MEGAKARYOCYTIC) LEUKEMIA An association of megakaryoblastic leukemia in infants with t(1;22)
534–537
In 1963, Szur and Lewis reported patients with pancytopenia, low (p13;q13) has been reported. Abnormalities of chromosome 3 have
526
been linked to clonal hemopathies expressing a prominent megakaryo-
percentages of blast cells, and intense myelofibrosis but an absence of cytic phenotype. 538,539 Progression of primary myelofibrosis or essential
teardrop red cells, splenomegaly, leukocytosis, and thrombocytosis, the thrombocythemia to AML may have the phenotype of acute megakary-
usual features of primary myelofibrosis. They designated the syndrome ocytic leukemia. Paradoxically, in children with Down syndrome the
526
malignant myelosclerosis. Reports of similar cases ensued, with some disease can be treated with modified doses of chemotherapy, with a very
investigators referring to the syndrome as acute myelofibrosis. The high remission rate and long-term event-free survival. 540–542 The result
527
development of methods to phenotype megakaryoblasts indicated the is thought to be related to the exquisite sensitivity of the leukemic cells
cases were variants of AML rather than of primary myelofibrosis and to drug-induced apoptosis, whereas the long-term remission rate as
475
have been designated acute megakaryocytic or acute megakaryoblastic a result of chemotherapy in children without Down syndrome or in
leukemia. 391,528,529 This leukemia is referred to as M7 in the FAB classifi- adults are not as good. 543,544
cation. The prevalence of this phenotype is approximately 5 percent of
all AML cases if appropriate cell markers are used in the diagnosis, and
is at least twice that frequency in childhood AML. 530,531 The syndrome ACUTE EOSINOPHILIC LEUKEMIA
is an especially prevalent variant of AML that develops in patients with Acute eosinophilic leukemia is rare. Increased eosinophils in the mar-
Down syndrome 398,532 or in patients with mediastinal germ cell tumors row but not in the blood is a variant of acute myelomonocytic leuke-
and coincident AML. 425–429 mia and inversion 16 or other abnormalities of chromosome 16 but is
Leukemic megakaryoblasts and promegakaryocytes can be diffi- not considered an acute eosinophilic leukemia. 303–306 First described in
cult to identify by light microscopy using polychrome staining. How- 1912, acute eosinophilic leukemia is a distinct entity that can arise
545
ever, with experience, heightened suspicion can be engendered by de novo as AML, with 50 to 80 percent of eosinophilic cells in the blood
blasts in the blood with abundant budding cytoplasm or blasts having and marrow. 546–549 Anemia, thrombocytopenia, and blast cells in blood
a lymphoid appearance, especially if the marrow cannot be aspirated and marrow are present. There is apparent eosinophilic differentiation
because of intense myelofibrosis, the latter evident on the marrow in striking proportions. The eosinophilic cells are dysmorphic and
biopsy. Initially high-resolution histochemistry for platelet peroxidase the cytoplasm hypogranulated with smaller than normal eosinophilic
and identification of the demarcation membrane system using trans- granules. The granules stain less intensely and are less refractile with
mission electron microscopy were required for diagnosis. Now anti- polychrome stains. These findings are the result of the loss of the cen-
bodies to von Willebrand factor or to platelet glycoprotein Ib (CD42), tral crystalloid in the eosinophilic granules that can be identified with
IIb/IIIa (CD41), or IIIa (CD61) can be used to identify very primitive electron microscopic analysis. Biopsy of skin, marrow, or other sites
megakaryocytic cells. 528,529 A small proportion of megakaryoblasts may of eosinophil accumulation often shows Charcot-Leyden crystals. A
be present in other cases of AML, but in megakaryocytic leukemia specific histochemical reaction, cyanide-resistant peroxidase, permits
they are the prominent or the dominant leukemic cells (see Fig. 88–2L identification of leukemic cells with eosinophilic differentiation and
through O). Moreover, the other key features of the syndrome usually diagnosis of acute eosinoblastic leukemia in some cases of AML with
are present, especially severe myelofibrosis. 530 fewer identifiable eosinophils in blood or marrow. Eosinophilia, not
550
Patients usually present with pallor, weakness, excessive bleeding part of the malignant clone, may be a feature of occasional patients with
and anemia, and leukopenia. Lymphadenopathy or hepatosplenomeg- AML, an uncommon reactive phenomenon. In many cases, idiopathic
aly is uncommon at the time of diagnosis. High leukocyte and blood eosinophilia (hypereosinophilic syndrome) is a monoclonal disorder
blast cell counts may be present initially or may develop later. The plate- representing a spectrum of more indolent chronic or subacute eosin-
let count may be normal or elevated in many patients at the time of ophilic leukemia to more progressive acute leukemia (Chaps. 62 and
presentation. Abnormal platelets or megakaryocytic cytoplasmic frag- 89). Acute eosinophilic leukemia may develop in patients having the
551
ments may be found in the blood. Marrow aspiration often is unsuc- chronic form of a hypereosinophilic syndrome. Overexpression of WT
cessful (“dry tap”) because of extensive marrow fibrosis in most cases, gene expression has been proposed as a means of distinguishing acute
although not all. The marrow biopsy contains small blast cells, large eosinophilic leukemia from a polyclonal, reactive eosinophilia. 552
blast cells, or a combination of both. The former have a high nuclear- Patients with acute eosinophilic leukemia do not usually develop
to-cytoplasmic ratio, have dense chromatin with distinct nucleoli, bronchospastic signs, neurologic signs, and heart failure from end-
and resemble lymphoblasts. Cases have been mistaken for ALL. The omyocardial fibrosis as is seen in chronic eosinophilic leukemia, prob-
larger blasts may have some features of maturing megakaryocytes with ably because those tissue changes are the result of release of toxins in
agranular cytoplasm with cytoplasmic protrusions, clusters of plate- the granule crystalloid, absent in most eosinophils in acute eosinophilic
let-like structures, or shedding of cytoplasmic blebs. The blast cells leukemia and because of the shorter duration of survival in acute eos-
are peroxidase negative and tend to aggregate. Confirmation of their inophilic leukemia. Hepatomegaly, splenomegaly, and lymphadenopa-
megakaryoblastic maturation requires immunocytologic studies for thy are more common than in other variants of AML. The treatment
the presence of von Willebrand factor and the immunoreactivity to approach is similar to other types of AML. A combination of cytarabine
CD41, CD42, or CD61. The more mature megakaryocytes, which often and an anthracycline antibiotic is an appropriate choice for treatment.
coexist in the marrow, stain with PAS reagent, contain sodium fluoride- Response to treatment is approximately the same as in other types of
inhibitable nonspecific esterase, and fail to react for α-naphthylbutyrate AML. 550

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