Page 1339 - Small Animal Internal Medicine, 6th Edition

CHAPTER 80
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Leukemias

DEFINITIONS AND CLASSIFICATION microscope. In veterinary medicine, cytochemical stains are
used in some diagnostic laboratories to establish whether the
Leukemias are malignant neoplasms that originate from blasts are lymphoid or myeloid and also to subclassify
hematopoietic precursor cells in the bone marrow. Because myeloid leukemias, as described later (i.e., myeloid versus
these cells are unable to undergo terminal differentiation or monocytic versus myelomonocytic). These cytochemical
apoptosis, they self-replicate as a clone of usually immature stains reveal the presence of different enzymes in the cyto-
(and nonfunctional) cells. The neoplastic cells may or may plasm of the blasts, which aids in establishing their origin
not appear in peripheral circulation; thus the confusing (Table 80.2); however, in most diagnostic laboratories immu-
terms aleukemic and subleukemic are used to refer to leuke- nophenotyping (see next paragraph) is the standard for
mias in which neoplastic cells proliferate within the bone diagnosis.
marrow but are absent or scarce in the circulation. Immunophenotyping of canine and feline leukemic cells
Leukemias can be classified into two broad categories using monoclonal antibodies via immunocytochemistry or
according to the cell line of origin: lymphoid and myeloid flow cytometry is now available in teaching institutions and
(or nonlymphoid; Table 80.1). The term myeloproliferative most commercial diagnostic laboratories; however, although
disease has also been used to refer to myeloid leukemias there are several validated antibodies for lymphoid cells,
(particularly in acute forms in cats), but we will use myeloid there is a paucity of myeloid markers that work consistently
leukemias throughout this chapter. On the basis of their in dogs and cats. In most laboratories CD3, CD4, CD5 (in
clinical course and the cytologic features of the leukemic cell cats), and CD8 are used as T-lymphocyte markers, whereas
population, leukemias are also classified as acute or chronic. CD21 and CD79a are B-lymphocyte markers. Acute myeloid
Acute leukemias are characterized by an aggressive biologic leukemias (AMLs) are diagnosed in dogs with cells neg-
behavior (i.e., death ensues shortly after diagnosis, some- ative for lymphoid markers and positive for CD45 (pan-
times even if the patient is treated) and by the presence of leukocyte marker) and CD34 (stem cell marker). Monocytic/
immature (blast) cells in bone marrow or blood. Chronic monoblastic leukemias are diagnosed if cells are negative for
leukemias have a protracted, often indolent course, and the lymphoid markers and positive for CD45 and CD14. CD41
predominant cell in the blood is a well-differentiated, late and CD61 are megakaryocyte markers. Recently, ALP cyto-
precursor (i.e., lymphocyte in chronic lymphocytic leukemia chemical staining has been proposed to differentiate AML
[CLL] and neutrophil in chronic myeloid leukemia [CML]). and acute lymphoid leukemia (ALL) (Stokol et al., 2014);
In dogs (and possibly in cats) CML can undergo blast trans- AML cells have more intense ALP staining patterns than
formation (blast crisis), during which the disease behaves those in ALL. Fig. 80.1 depicts flow cytometry dot plots
like an acute leukemia and is usually refractory to therapy. from a cat with CLL. Clinical correlations between immu-
Additionally, CLL can transform into an aggressive high- nophenotype and prognosis have been investigated in few
grade lymphoma, referred to as Richter syndrome; this has studies; however, no definitive difference in prognosis has
recently been described in dogs, where it carries a poor prog- been established among phenotypes (Novacco et al., 2015a).
nosis, with a median survival time (MST) of 41 days reported It is still possible that, with additional investigation, espe-
in a small cohort of dogs (Comazzi et al., 2017). cially with more frequent availability of flow cytometric
As opposed to humans, acute leukemias in dogs and cats analysis, specific phenotypes may be associated with differ-
may be difficult to classify morphologically as myeloid or ent prognoses.
lymphoid on the basis of the evaluation of Giemsa-, Wright-, A classification scheme for acute leukemia in people was
or Diff-Quik–stained blood or bone marrow smears because devised by a group of French, American, and British investi-
poorly differentiated blasts look similar under the light gators (the FAB scheme) and was based on the morphologic

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