Page 735 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 713

TABLE 33.8 Circulating (Serum/Plasma) Biomarkers as Prognostic Indices in Dogs with Lymphoma
Biomarker Comments References
VetBooks.ir Lactate dehydrogenase activity Increased: unfavorable 202,210

Thymidine kinase activity
202,205,206,396,397
Increased: unfavorable
Haptoglobin Increased: unfavorable 202–204
Serum VEGF Increased: unfavorable 213,417
Glutathione-S-transferase Increased: unfavorable 418
Hypercalcemia Unfavorable 116,395,419,420
Serum cobalamin Decreased: unfavorable 395
Serum albumin Decreased: unfavorable 375,377
Serum C-reactive protein Although it may be used to characterize remission status, variable levels 202–205,294
preclude utility.
VEGF, Vascular endothelial growth factor.

immunophenotype. 12,170,180,394,399–402 The simplest classifica-
Percentage of dogs that had not relapsed 75 flow cytometric and molecular assays can further characterize these
100
tion divides leukemia into two groups: chronic (small cells with a
mature cytologic phenotype) and acute (large cells with an imma-
ture cytologic phenotype). Immunophenotypic assessment using
two major subtypes.
Of the CLLs, approximately two-thirds are T cell (T-CLL) and
50
one-third are B-CLL. Three primary subtypes of CLL, based primar-
ily on immunophenotyping, have been reported
106,164,170,394,400
:
(1) T-CLL, which is the most common form, with cells in the
25
+
majority of cases being CD3 /CD8 granular lymphocytes; (2)
+
+
atypical CLL, which represents a combination of immunopheno-
0
+
−
+
−
types (CD3 , CD8 ; CD3 , CD4 , CD8 ; CD3 , CD4 , CD8 ,
+
+
+
−
0 100 200 300 400 500 600 B-CLL (CD21 ), which is the next most common subtype; and (3)
+
and CD3 + CD21 ). This is in contrast to CLL in humans, which
+
Time (days)
is primarily a disease of B cells. In CLL, lymphocytes often are
• Fig. 33.12 Kaplan–Meier curves illustrating time to relapse adjusted for indistinguishable morphologically from normal small lymphocytes
clinical stage and immunophenotype among dogs treated for low-grade (Fig. 33.13) and have a low rate of proliferation; accumulation of
(n = 17) (blue line) or high-grade (n = 51) (red line) Kiel classification lym- lymphocytes likely results from their prolonged lifespan.
phoma. (From Teske E, van Heerde P, Rutteman GR, et al. Prognostic fac- ALL has also been classified as a lymphoid precursor neoplasm
tors for treatment of malignant lymphoma in dogs. J Am Vet Med Assoc. and can be derived from either B cells (B-ALL) or T cells (T-ALL).
1994;205:1722-1728.)
−
−
−
+
The majority are B-ALL (CD21 , CD3 , CD4 , CD8 ), although
a smaller percentage (<10%) are T-ALL (CD3 , CD4 , CD8 ,
+
−
−
is unknown. Overall, CLL is much more common than ALL. CD21 ). In general, these cells tend to be intermediate or large
− 170
Smaller reports state that German shepherd dogs and golden cells with moderate amounts of basophilic cytoplasm. Perhaps the
retrievers may be overrepresented. 170,399 Based on a recent com- most distinguishing feature of the large lymphocytes is the nuclear
pilations of more than 400 dogs with B-cell CLL (B-CLL), chromatin pattern, which typically is less condensed than the chro-
small-breed dogs are much more likely to be affected. 106 Lym- matin in small lymphocytes but more condensed than the chroma-
phocytic leukemia can occur in dogs of any age, but typically tin in myeloblasts. Large lymphocytes are larger than neutrophils,
occurs in middle-aged to older dogs (mean of 7–10 years of have a high nuclear-to-cytoplasmic ratio, and contain basophilic
age); CLL usually occurs in older dogs (mean of 10–11 years cytoplasm (see Fig. 33.13). Nucleoli, although present, are less
of age), 106,170,394,399,400 although a distinct form of B-CLL in prominent in large lymphocytes than in myeloblasts. Nevertheless,
English bulldogs occurs in younger dogs (mean, 6 years of these cells cannot be distinguished easily from immature cells of
age). 106 A significant sex predilection is not reported. As with other hematopoietic lineages, and identification of lineage-specific
lymphoma, the etiology of lymphocytic leukemia is for the most markers by immunocytochemical, flow cytometric, or molecular/
part unknown. Genetic factors likely play a role and have been genetic analysis is required to ascertain their lineage. 401,403,404 If
12
compared between dogs and humans. the cells express CD34, a stem-cell marker, an acute phenotype is
implied 170,394,399 ; however, both myeloid and lymphoid lineages
Pathology and Classification express CD34 and our ability to differentiate ALL from acute
myeloid leukemia relies on detection of other markers, including
Lymphocytic leukemias can be subdivided based on cell size, T- and B-cell markers and myeloperoxidase, a myeloid marker. Fur-
maturity, genetic aberrations, microRNA expression, and thermore, some T-ALLs do not express CD34. 404