Page 758 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

736 PART IV Specific Malignancies in the Small Animal Patient

present, they make up fewer than 30% of all nucleated cells, 614 characterized by anisocytosis and poikilocytosis. In addition, pan-
although this threshold is being changed to less than 20%. 616,722 cytopenia and leukoerythroblastosis, in which immature erythroid
and myeloid cells are in circulation, may be present. These phe-
Myelodysplasia is sometimes referred to as preleukemia because,
VetBooks.ir in some cases, it may progress to acute leukemia. 639–641 Based on nomena probably result from replacement of marrow by fibrous
tissue with resultant shearing of red cells and escape of imma-
reported cases, poor prognostic factors include increased percent-
age of blast cells, cytopenias involving more than one lineage, ture cells normally confined to bone marrow. In PV, the PCV is
and cellular atypia. 616 Primary MDSs are clonal disorders and are increased, usually in the range of 65% to 85%. The bone marrow
considered neoplastic. Complex classification schemes for human is hyperplastic and the M : E ratio is usually in the normal range.
MDS, based on percentages of blasts in bone marrow, cytogenetic Neoplastic cells are often defective functionally. Platelet dysfunc-
analysis, cytopenias, need for transfusions, and other variables, tion has been reported in a dog with acute megakaryoblastic leuke-
comprise at least nine subtypes; their applicability to veterinary mia (M7) 658 ; and, in CML, neutrophils have decreased phagocytic
medicine is unknown. 617 Three subtypes are proposed for dogs capacity and other abnormalities. One exception to this was a report
and cats and include MDS with excessive blasts (MDS-EB), in of CML in a dog in which the neutrophils had enhanced phagocytic
which blast percentages are greater than 5% and less than 20%, capacity and superoxide production. 723 The authors hypothesized
and progression to AML may occur; MDS with refractory cytope- that increased synthesis of granulocyte-macrophage (GM)-CSF
nia (MDS-RC) with blast percentages less than 5% and cytopenias resulted from a lactoferrin deficiency in the neoplastic neutrophils
in one or more lineages; and MDS with erythroid predominance and mediated the enhanced function of these cells.
(MDS-ER) in which the M : E ratio is less than one and prognosis
is poor. 616 Larger studies are needed to determine the utility of this Diagnostic Techniques and Workup
classification scheme and other potential prognostic factors, such
as sex and age and, in cats, FeLV positivity. In addition to accu- In all cases of myeloid neoplasms, diagnosis depends on examination
mulating enough cases, another confounding factor to studying of peripheral blood and bone marrow. AML is diagnosed on the basis
and classifying MDS is the presence of reversible MDSs that occur of finding blast cells with clearly visible nucleoli in blood and bone
secondary to immune-mediated, infectious, and other diseases in marrow. Most dogs with acute leukemia have circulating blasts. These
both dogs and cats. cells may be present in low numbers in peripheral blood, and care-
ful examination of the smear, especially at the feathered edge, should
History and Clinical Signs be made. Even if blasts are not detected in circulation, indications
of bone marrow disease such as nonregenerative anemia or throm-
Dogs with myeloid neoplasms have similar presentations regard- bocytopenia are usually present. Occasionally, neoplastic cells can
less of the specific disease entity, although animals with AML have be found in CSF in animals with invasion of the CNS. Smears of
a more acute onset of illness and a more rapid clinical course. aspirates from tissues such as the lymph nodes, spleen, or liver may
A history of constitutional signs (e.g., lethargy, hyporexia, and contain blasts but usually contribute little to the diagnostic workup.
weight loss) is common. 618–621 Clinical signs include emaciation, Examination of blasts stained with standard Romanowsky
persistent fever, pallor, and petechiation. Peripheral lymphade- stains may give clues as to the lineage of the cells (see Fig. 33.21A–
nopathy is reported in 40% to 75% of cases and hepatospleno- C, and E). In myelomonocytic leukemia, the nuclei of the blasts
megaly in approximately 40% of cases. Shifting leg lameness, are usually pleomorphic, with round to lobulated forms. In some
ocular lesions, and recurrent infections are also seen. Vomiting, cells, the cytoplasm may contain large azurophilic granules or
diarrhea, dyspnea, and neurologic signs are variable features. vacuoles. Blasts in megakaryocytic leukemia may contain vacuoles
Serum biochemical analytes may be within reference intervals, and have cytoplasmic blebs. In addition, bizarre macroplatelets
but can change if significant organ infiltration occurs. Animals may be present. Although these distinguishing morphologic fea-
with MDS may be lethargic and anorectic and have pallor, fever, tures may suggest a definitive diagnosis, cytochemical staining,
and hepatosplenomegaly. In PV, dogs often have erythema of immunophenotyping, flow cytometric analysis, clonality testing,
mucous membranes owing to the increase in RBC mass. Some and genetic analysis are usually required to definitively define the
dogs are polydipsic. In addition, neurologic signs such as disori- lineage of the blasts; the reader is referred to several large compi-
entation, ataxia, or seizures may be present and are thought to be lations for which these methodologies have been discussed and
the result of hyperviscosity or hypervolemia. 690 Hepatospleno- applied in dogs. 618–621,626,671,724–726 Several investigators have
megaly is usually absent. reported modification of diagnoses after cytochemical staining.
Peripheral blood abnormalities are consistently found in more It is especially important to distinguish AML from lymphocytic
than 90% of cases. 615,618–621 In addition to the presence of neo- leukemia to provide accurate prognostic information to the owner
plastic cells, other abnormalities, including bi- and pancytopenia, and institute appropriate therapy.
may be present. Low numbers of nucleated RBCs are present in The Animal Leukemia Group has recommended the follow-
the blood of about half the dogs with acute nonlymphocytic leuke- ing diagnostic criteria, summarized in Fig. 33.22. 615 Using well-
mia. Nonregenerative anemia and thrombocytopenia are present prepared Romanowsky-stained blood and bone marrow films, a
in most cases. Anemia is usually normocytic and normochromic, minimum of 200 cells are counted to determine the leukocyte
although macrocytic anemia is sometimes present. Pathogenic differential in blood and the percentage of blast cells in bone mar-
mechanisms include effects of inhibitory factors leading to inef- row and/or blood. In bone marrow, blast cells are calculated both
fective hematopoiesis, myelophthisis, immune-mediated anemia as a percentage of all nucleated cells (ANC) and nonerythroid
secondary to neoplasia, and hemorrhage secondary to thrombocy- cells, and are further characterized using cytochemical mark-
topenia, platelet dysfunction, or disseminated intravascular coag- ers. 724,725,727 Neutrophil differentiation is identified by positive
ulation. Anemia is most severe in AML, although both anemia staining of blasts for peroxidase, Sudan Black B, and chloracetate
and thrombocytopenia may be milder in animals with the M5 esterase. Nonspecific esterases (α-naphthyl acetate esterase or
subtype (acute monocytic leukemia). In myelofibrosis, anemia is α-naphthyl butyrate esterase), especially if they are inhibited by