Page 736 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

714 PART IV Specific Malignancies in the Small Animal Patient

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A B

• Fig. 33.13 (A) Peripheral blood from a dog with acute lymphocytic leukemia (ALL). Note the large lymphoid
cells with visible nucleoli. Chromatin from disintegrated cells also is visible. (Wright’s stain, ×60 objective.)
(B) Peripheral blood from a dog with chronic lymphocytic leukemia (CLL). Note the small lymphocytes of
normal mature morphology (smaller than the neutrophil). (Wright’s stain, ×60 objective.)

History and Clinical Signs Diagnostics and Clinical Staging
Dogs with CLL are often asymptomatic and a diagnosis is pursued Consideration of signalment, history, physical findings, and
based on an incidental finding of increased circulating mature lym- morphologic appearance and immunophenotype of cells is
phocytes on routine CBCs. In more advanced disease, some owners essential in making an accurate diagnosis. It is helpful to know
report lethargy and decreased appetite. Mild lymphadenopathy and the profile of lymphocyte subsets in the peripheral blood of nor-
splenomegaly may be present, although late in the disease spleno- mal dogs to determine whether a particular subset has expanded.
megaly may be marked. 405 In a compilation of nearly 500 dogs with Approximately 80% of circulating lymphocytes in normal dogs
B-CLL, 50% had some degree of peripheral lymphadenopathy, are T cells and about 15% are B cells. NK cells and double-
−
50% had splenomegaly, 30% had hepatomegaly, 23% had visceral negative (CD4 , CD8 ) T cells constitute the remaining frac-
−
lymphadenopathy, and 3% had a mediastinal mass. 106 The white tion. In the T-cell fraction, helper T cells (CD4 ) outnumber
+
+ 407
blood cell (WBC) count is usually >30,000 cells/μL but can vary cytotoxic T cells (CD8 ). Lymphocytic leukemia should be
from normal to more than 100,000 cells/μL because of an increase a consideration if atypical lymphocytes are in circulation, the
in circulating mature lymphocytes. Lymphocytosis is persistent, and immunophenotype of the lymphocytes in circulation is homo-
granulocytes are usually present in normal numbers. Other than geneous as determined by flow cytometric analysis, a phenotype
lymphocytosis, hemograms of dogs with CLL tend to have few typically present in low frequency has increased, or if clonality is
abnormalities when lymphocytes are less than 30,000/μL. 170,394,400 documented (e.g., by PARR analysis). Other differential diagno-
Mild anemia, neutropenia, and thrombocytopenia are common, ses for lymphocytosis include infectious diseases, such as chronic
but may become marked as the disease progresses and lymphocyte ehrlichiosis, postvaccinal responses in young dogs, IL-2 admin-
counts increase above 30,000/μL. In B-CLL, the median lympho- istration, and transient physiologic or epinephrine-induced lym-
cyte count was 24,600/μL and neutropenia and thrombocytopenia phocytosis. In some cases, reactive and neoplastic lymphocytoses
were uncommon (1% and 7%, respectively). 106 Despite the well- are difficult to distinguish.
differentiated appearance of the lymphocytes in CLL, these cells Expansion of neoplastic lymphocytes in bone marrow is the
may function abnormally. Paraneoplastic syndromes include mono- hallmark of ALL and, in most cases, CLL. Careful examination of
clonal gammopathies, immune-mediated hemolytic anemia, pure peripheral blood and bone marrow by an experienced cytopatholo-
red cell aplasia, and, rarely, hypercalcemia; 80% of dogs with B-CLL gist is important in establishing a diagnosis of lymphocytic leuke-
were reported to be hyperglobulinemic and 13% were hypercalce- mia; in cases of marked lymphocytosis with atypia, peripheral blood
mic. 106,406,407 In 22 dogs with CLL, 68% had monoclonal gam- can be used for analysis of immunophenotype and clonality, and
mopathies (usually IgM or IgA). 407 The immunophenotypes were examination of bone marrow is not essential. If diagnostic bone
not reported in this latter report, but a monoclonal gammopathy marrow cannot be adequately obtained by aspiration, bone mar-
would be more likely to occur in B-CLL. row core biopsy should be performed. In ALL, large lymphocytes
Dogs with ALL usually present with clinical signs of anorexia, predominate in the bone marrow and are also present in peripheral
weight loss, and lethargy. Splenomegaly is typical and other blood, and other lineages are decreased. In B- and T-cell CLL, lym-
physical abnormalities may include hemorrhage, lymphade- phocytes are small mature cells that occur in excessive numbers in
nopathy, and hepatomegaly. 408 Infiltration of bone marrow by bone marrow (≥30% of all nucleated cells) early in the disease. 405
neoplastic lymphocytes may be extensive, resulting in significant In T-CLL, lymphocytes may contain pink granules. Infiltration
depression of normal hematopoietic elements or myelophthi- becomes more extensive as the disease slowly progresses, and even-
sis. 170,394,399,404,408,409 Anemia, neutropenia, and thrombocyto- tually the neoplastic cells replace normal marrow.
penia are typically much more severe than with CLL and may A separate clinical staging system has not been developed for
become life threatening. Infiltration of extramedullary sites, such lymphocytic leukemias. Currently, all dogs with leukemia are
as the CNS, bone, and GI tract, may also occur and can result in classified as stage V based on the WHO Staging System for lym-
neuropathies, bone pain, and GI signs, respectively. phoma as presented in Box 33.2.