Page 715 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 693

morphology (centroblastic, centrocytic, or immunoblastic), and • BOX 33.2 World Health Organization’s Clinical

immunophenotype (B or T cell) of the tumor cells. 104 In both sys- Staging System for Lymphoma in
tems, the tumors can then be categorized as low-grade, interme-
VetBooks.ir diate-grade, or high-grade malignancies. Low-grade lymphomas Domestic Animals
composed of small cells with a low mitotic rate typically progress
slowly and are associated with long STs, but are ultimately incur- 1. Anatomic site

A. Generalized
able. High-grade lymphomas with a high mitotic rate progress B. Alimentary
rapidly, but are more likely to respond initially to chemotherapy C. Thymic
and, in humans, are potentially curable. In the REAL/WHO sys- D. Skin
tem, each subtype of lymphoma is classified as a distinct disease E. Leukemia (true) a
based on characteristics that include biologic behavior (indolent F. Others (including solitary renal)
versus aggressive, response to treatment). 90 2. Stage (to include anatomic site)
Several features of canine lymphomas become apparent when I. Involvement limited to a single node or lymphoid tissue in a single
organ
b
these classification systems are applied. The most striking difference II. Involvement of many lymph nodes in a regional area (± tonsils)
between canine and human lymphomas is the scarcity of follicular III. Generalized lymph node involvement
lymphomas in the dog. The most common form of canine lym- IV. Liver and/or spleen involvement (± Stage III)
phoma is DLBCL, a high-grade tumor. 90,98,99,105 A small percent- V. Manifestation in the blood and involvement of bone marrow and/or
age of canine lymphomas (5.3%–29%) are considered low-grade. other organ systems (± Stage I–IV)
A documented difference exists in the prevalence of the various Each stage is subclassified into:
immunophenotypes based on breed. 32,106,107 For example, cocker a. Without systemic signs
spaniels and Doberman pinschers are more likely to develop B-cell b. With systemic signs
lymphoma, boxers are more likely to have T-cell lymphoma, and a Only blood and bone marrow involved.
golden retrievers appear to have an equal likelihood of B- and b Excluding bone marrow.
T-cell tumors.
To be clinically useful, these classification systems in the end
must yield information about response to therapy, maintenance To summarize, it is important to determine the histologic grade
of remission, and survival. In most studies, high-grade lympho- of canine lymphomas as low (small lymphocytic or centrocytic
mas achieve a complete response (CR) to chemotherapy signifi- lymphomas), intermediate, or high (diffuse large cell, centroblastic,
cantly more often than low-grade tumors. However, dogs with and immunoblastic lymphomas), and the architecture as diffuse or
low-grade tumors may live years without aggressive chemother- nodular/follicular. Furthermore, determining the immunopheno-
apy. 100–102,108–111 Dogs with T-cell lymphomas have shown a type of the tumor provides useful information and is essential to
lower rate of CR to chemotherapy and shorter remission and STs accurately subtype lymphoma. Response rates to chemotherapy
than dogs with B-cell tumors (with the exception of low-grade are, in general, better in animals with B-cell tumors and interme-
T-cell subtypes). 68,69,112,113 Furthermore, T-cell lymphomas are diate- to high-grade lymphomas. Dogs with low-grade indolent
more commonly associated with hypercalcemia. 8,114,115 lymphomas can have long STs without aggressive therapy.
In the veterinary literature, 60% to 80% of canine lymphomas
are of B-cell origin; T-cell lymphomas account for 10% to 38%; History and Clinical Signs
mixed B- and T-cell lymphomas account for as many as 22%; and
null-cell tumors represent fewer than 5%. 8,68,69,116–118 The devel- The clinical signs associated with canine lymphoma are variable
opment of monoclonal antibodies to detect specific markers on and depend on the extent and location of the tumor. Multicen-
canine lymphocytes has made immunophenotyping of tumors in tric lymphoma, the most common form, is usually distinguished
dogs routinely available in many commercial laboratories. Such by the presence of generalized peripheral lymphadenopathy (see
techniques can be performed on paraffin-embedded samples, Fig. 33.1). Enlarged LNs are usually painless, rubbery, and dis-
from tissue microarrays, on cytologic specimens obtained by fine- crete. In addition, hepatosplenomegaly and bone marrow involve-
needle aspiration (FNA) of lesions, or by flow cytometric analy- ment can be associated with generalized lymphadenopathy. Most
sis of cellular fluid samples (e.g., peripheral blood, effusions) and dogs with multicentric lymphoma are presented without dramatic
lesion aspirates. signs of systemic illness (WHO substage a) (Box 33.2); however, a
One criticism of the Kiel and WF classification systems is that diversity of nonspecific signs such as anorexia, weight loss, vomit-
they fail to include extranodal lymphomas as a separate category. ing, diarrhea, emaciation, ascites, dyspnea, polydipsia, polyuria,
The REAL/WHO system does include anatomic location as a and fever can occur (WHO substage b). Dogs with T-cell lym-
factor in determining certain categories. Although differences phoma are more likely to have constitutional (i.e., substage b)
between nodal and extranodal tumors in biologic behavior and signs. Most veterinary oncologists consider mild-moderate sever-
prognosis are well recognized, comparative information about the ity of clinical signs sufficient for a substage b designation. 120 Poly-
histogenesis of these tumors is lacking. For example, in humans, dipsia and polyuria are often evident in dogs with hypercalcemia
small-cell lymphomas arising from MALT are composed of cells of malignancy. Dogs may also be presented with clinical signs
with a different immunophenotype than that of other small-cell related to blood dyscrasias secondary to marked tumor infiltra-
lymphomas (i.e., MALT lymphomas typically are negative for tion of bone marrow (myelophthisis) or paraneoplastic anemia,
both CD5 and CD10). With the exception of cutaneous lym- thrombocytopenia, or neutropenia. These could include fever,
phoid neoplasms, detailed characterization of extranodal lympho- sepsis, anemia, and hemorrhage. Diffuse pulmonary infiltration,
mas in dogs has not been done. Although cutaneous lymphoma is as detected by radiographic changes, is seen in 27% to 34% of
a heterogeneous group of neoplasms that includes an epitheliotro- dogs with the multicentric form (Fig. 33.4). 121,122 Based on bron-
pic form resembling mycosis fungoides and a nonepitheliotropic choalveolar lavage, the actual incidence of lung involvement may
form, most cutaneous lymphomas have a T-cell phenotype. 119 be higher. 123,124