Page 759 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 737

abnormalities are being identified in animal leukemias; cytoge-
Bone marrow erythroid cells
netic analysis may yield important diagnostic and prognostic
information and become a valuable tool for identifying targeted
VetBooks.ir 50% 50% therapeutic approaches.
Although morphologic and cytochemical analyses have
formed the mainstay of cell identification, newer technologies
now are routinely used to classify leukemias by using mono-
Blast cells Blast cells Blast cells clonal antibodies to detect antigens associated with certain cell
(% of ANC) (% of NEC) including rubriblasts types. Cells can be immunophenotyped using flow cytometric
(% of ANC) analysis or immunocytochemistry. 618–621,671,677,722,729–732 Cells
from both acute lymphoid leukemia and AML are positive
30% 30% 30% 30% 30% 30% for CD34. Many lymphocyte markers, including CD3, CD4,
CD8, CD21, CD79, and IgG, are available for dogs and can
be used to rule out lymphoblastic leukemia in dogs with acute
leukemias. Other markers include myeloperoxidase (MPO) and
AUL MDS M6 MDS-Er M6Er CD11b for myeloid cells and CD41 for megakaryoblasts. There
AML CML
is some overlap in expression of these cellular antigens. For
• Fig. 33.22 A scheme to classify myeloid neoplasms and myelodysplas- example, canine (but not human) granulocytes express CD4. It
tic syndromes in dogs and cats. AML, Acute myeloid leukemias M1–M5 is highly recommended to use a panel of antibodies (similar to
and M7; ANC, all nucleated cells in bone marrow, including lymphocytes, using a battery of cytochemical stains) because antigens are often
plasma cells, macrophages, and mast cells; AUL, acute undifferentiated expressed on multiple lineages, and lineage infidelity can occur.
leukemia; Blast cells, myeloblasts, monoblasts, and megakaryoblasts; These tests have become more valuable with the availability of
CML, chronic myeloid leukemias, including chronic myelogenous, chronic canine reagents. Currently, the ACVP Oncology Committee
myelomonocytic, and chronic monocytic leukemias; M6, erythroleuke- recommends that the following immunophenotyping panel be
mia; M6Er, erythroleukemia with erythroid predominance; MDS, myelo- done on bone marrow and/or blood smears to characterize ani-
dysplastic syndrome; MDS-Er, myelodysplastic syndrome with erythroid
predominance; NEC, nonerythroid cells in bone marrow. (Reprinted with mal leukemias: for B lymphocytes, CD79a; for T lymphocytes,
permission from Jain NC, Blue JT, Grindem CB, et al. Proposed criteria for CD3; for myeloid cells, MPO and CD11b; for megakaryo-
classification of acute myeloid leukemia in dogs and cats. Vet Clin Pathol. blasts, CD41; for dendritic cells, CD1c; and for acute leuke-
1991;20(3):63-82.) mias, CD34. 632 In 2 large reports of 60 cases of AML in dogs,
most were CD45/CD18/CD34 positive and, in one report, 64%
had clonal or biclonal rearrangements of either the T- or B-cell
sodium fluoride, mark monocytes. Canine monocytes may also receptor. 619,621
contain a few peroxidase-positive granules. Acetylcholinesterase is Because of the degree of differentiation of cells in MPN,
a marker for megakaryocytes in dogs and cats. In addition, positive these disorders must be distinguished from nonneoplastic
immunostaining for von Willebrand’s factor (factor VIII–related causes of increases in these cell types. To make a diagnosis of
antigen) and platelet glycoproteins on the surface of blasts iden- PV, it must first be established that the polycythemia is abso-
tifies them as megakaryocyte precursors. 648,658,659,661,665,667 Alka- lute rather than relative. In relative polycythemias, plasma
line phosphatase (ALP) only rarely marks normal cells in dogs and volume is decreased from hemoconcentration, dehydration,
cats, but is present in blasts cells in acute myeloblastic and myelo- or hypovolemia, and the absolute RBC mass is not increased.
monocytic leukemias. However, owing to reports of ALP activ- Splenic contraction can also result in relative polycythemia.
ity in lymphoid leukemias in dogs, its specificity as a marker for Absolute polycythemia, in which RBC mass is increased, is
myeloid cells is not certain. A recent study indicated that ALP was usually secondary to tissue hypoxia, causing appropriately
a useful marker for the diagnosis of AML if neoplastic cells express increased production of erythropoietin. Rarely, erythropoi-
only CD34. 728 Omega exonuclease is a specific marker for baso- etin may be produced inappropriately by a tumor (e.g., renal
phils, which are also positive for chloracetate esterase activity. 707 cell carcinoma) or in renal disease (pyelonephritis) or local-
Blood and bone marrow differential counts and cytochemical ized renal hypoxia. 733–735 These causes of polycythemia should
staining should be performed and interpreted by experienced vet- be eliminated by appropriate laboratory work, thoracic radio-
erinary cytopathologists. If erythroid cells are less than 50% of graphs, arterial blood gas analysis, and renal ultrasonography.
ANC and the blast cells are greater than 20%, a diagnosis of AML In humans with PV, plasma erythropoietin (EPO) concentra-
or AUL is made. If erythroid cells are greater than 50% of ANC tions are low. EPO concentrations in dogs with PV tend to be
and the blast cells are greater than 20%, a diagnosis of erythro- low or low-normal, whereas in animals with secondary absolute
leukemia (M6) is made. If rubriblasts are a significant proportion polycythemia, the levels are high. 736,737 Samples for determina-
of the blast cells, a diagnosis of M6Er, or erythroleukemia with tion of EPO concentrations should be taken before therapeutic
erythroid predominance, can be made. It should be noted that phlebotomy used to treat hyperviscosity and, owing to fluctua-
in the human AML classification system, the blast threshold has tions in EPO concentrations, should be repeated if results are
been lowered from 30% to 20%, and similar recommendations incongruous with other information.
are now made for AML in dogs and cats. There are no pathognomonic features of CML in dogs, and
In some cases, electron microscopy is required to identify the other common causes for marked leukocytosis with a left shift
lineage of the blast cells. For example, megakaryocyte precursors (extreme neutrophilia) and granulocytic hyperplasia of bone mar-
are positive for platelet peroxidase activity and contain demarca- row must be eliminated. These include infections, especially pyo-
tion membranes and alpha granules. 648,665 Both of these features genic infections; immune-mediated diseases; and some neoplasms
are detected at the ultrastructural level. Increasingly, cytogenetic that cause neutrophilia by elaborating CSFs. In CML, maturation