Page 754 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

732 PART IV Specific Malignancies in the Small Animal Patient

Clonal disorders of bone marrow include myeloaplasia (usually In 1985, the Animal Leukemia Study Group was formed
referred to as aplastic anemia), myelodysplasia, and myeloprolifer- under the auspices of the American Society for Veterinary Clinical
Pathology to develop specific morphologic and cytochemical cri-
ation. A preleukemic syndrome, characterized by peripheral pan-
VetBooks.ir cytopenia and bone marrow hyperplasia with maturation arrest, is teria for classifying acute nonlymphocytic leukemias. Recognition
of specific subtypes of leukemia is required to compile accurate
more correctly termed myelodysplasia because the syndrome does
not always progress to overt leukemia. This syndrome has been and useful information about prognosis and response to treat-
described in cats, usually in association with FeLV infection, but ment, as well as to compare studies from different sites. In 1991
is rarely recognized in dogs. 638–641 These clonal disorders may be this group proposed a classification system following adaptation of
manifested by abnormalities in any or all lineages because hema- the FAB system and criteria established by the NCI Workshop. 615
topoietic cells share a common stem cell. In addition, transforma- Group members examined blood and bone marrow from 49 dogs
tion from one form to another may occur. 642 and cats with myeloid neoplasms. Romanowsky-stained speci-
Myeloid neoplasms are classified in several ways. The terms mens were examined first to identify blast cells and their percent-
acute and chronic refer to the degree of cellular differentiation of ages. Lineage specificity was then determined using cytochemical
the leukemic cells, but these terms also correlate with the biologic markers. The percentage of blasts and the information about lin-
behavior of the neoplasm. 643 Disorders resulting from uncon- eage specificity were used in combination to classify disorders as
trolled proliferation or decreased apoptosis of cells incapable of acute undifferentiated leukemia (AUL), AML (subtypes M1–M5
maturation lead to the accumulation of poorly differentiated or and M7), and erythroleukemia with or without erythroid pre-
“blast” cells. These disorders are included under the umbrella term dominance (M6 and M6Er). A description of these subtypes is
of AML. Disorders resulting from unregulated proliferation of presented in Table 33.13.
cells that exhibit progressive, albeit incomplete and defective, mat- Because the modified FAB system has been adopted only
uration lead to the accumulation of differentiated cells and thus recently, the names given to these disorders in the literature vary
are called chronic disorders. These disorders are termed myelopro- considerably. In addition, in the absence of cytochemical stain-
liferative neoplasms (MPN) and include polycythemia vera, CML ing, immunophenotyping, or electron microscopic evaluation,
and its variants, essential thrombocythemia, and possibly primary the specific subtype of leukemia has often been uncertain, making
myelofibrosis. Myeloid neoplasms are further classified by the lin- retrospective analysis of epidemiologic information, prognosis,
eage of the dominant cell type(s), defined by Romanowsky stains, and response to therapy confusing at best. Although defining spe-
special cytochemical stains, ultrastructural features, flow cyto- cific subtypes may seem to be an academic exercise owing to the
metric analysis, molecular genetic analysis, and immunologic cell uniformly poor prognosis of acute leukemias, this information is
markers, and they have been classified into subtypes. critical to improving their management. Because of the low inci-
AML has a more sudden onset and is more clinically aggressive. dence of AML, national and international cooperative efforts will
In both acute and chronic disorders, however, abnormalities in be required to accumulate information on the pathogenesis and
proliferation, maturation, and functional characteristics can occur response to different treatment modalities of specific subtypes.
in any hematopoietic cell line. 613 In addition, normal hematopoie- Utilization of a uniform classification system is an essential first
sis is adversely affected. Animals with acute leukemias usually have step. Different forms of AML are demonstrated in Fig. 33.21.
decreased numbers of circulating normal cells. The pathogenesis With the exception of acute promyelocytic leukemia or M3, all
of cytopenias is complex and may result in part from production AML subtypes have been described in dogs. Combining three
of inhibitory factors. Eventually, neoplastic cells displace normal recent compilations of 85 dogs with AML, the relative frequency
hematopoietic cells, termed myelophthisis. Anemia and thrombo- of subtypes in decreasing order were: 42% monocytic leukemia
cytopenia are particularly common. Neutropenia and thrombo- (M5a, M5b), 33% myelomonocytic leukemia (M4), 13% myelo-
cytopenia result in infection and hemorrhage, respectively, which blastic leukemia without differentiation (M1), 5% megakaryo-
may be more deleterious to the animal than the primary disease blastic leukemia (M7), and one each of myeloblastic leukemia
process. with some differentiation (M2) and erythroleukemia (M6). 619–621
AML of mixed lineages comprised 5% of cases. Many single
Acute Myeloid Leukemia case or small case series reports also exist describing various sub-
types in dogs. 617,632–637,639–671 Monocytic leukemias have likely
AML is rare and is characterized by aberrant proliferation and/ included those with and without monocytic differentiation (M5a
or decreased apoptosis of a clone of cells without maturation. and M5b), 672,673 but in some cases the diagnosis may have been
This results in accumulation of immature blast cells in bone chronic myelomonocytic or chronic monocytic leukemia. There
marrow and peripheral blood (Fig. 33.21). The white blood cell are few reports in dogs of spontaneously occurring erythroleu-
(WBC) count is variable and ranges from leukopenia to counts kemia (M6) in which the leukemic cells include myeloblasts,
greater than 250,000/μL. Spleen, liver, and lymph nodes are fre- monoblasts, and erythroid elements. 674–676 AULs have uncertain
quently involved, and other tissues, including tonsils, kidney, lineages because they are negative for all cytochemical markers.
heart, and the CNS, may be infiltrated as well. 621 The median These leukemias should be distinguished from lymphoid leuke-
age is approximately 7 to 8 years; however, young dogs may be mias by flow cytometric analysis of the leukemic cells for cellular
affected. 618–621,644 The clinical course of these disorders tends to antigens that identify their lineage. 620,677 In addition, examina-
be rapid. Production of normal peripheral blood cells is usually tion of blast cells by electron microscopy may reveal characteristic
diminished or absent, and anemia, neutropenia, and thrombocy- ultrastructural features.
topenia are common with infection and hemorrhage occurring as Canine karyotyping is difficult, but with advancements in
frequent sequelae. Occasionally, neoplastic blasts are present in molecular cytogenetic analysis, chromosome painting, and
bone marrow, but not in peripheral blood. This is termed aleuke- genomic hybridization, AML in dogs can now be analyzed at the
mic leukemia, whereas subleukemic suggests a normal or decreased base-pair level, 626,628,629 and missense mutations in flt3, c-kit, and
WBC count with some neoplastic cells in circulation. ras sequences have been identified in dogs with AML, similar to