Page 740 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

718 PART IV Specific Malignancies in the Small Animal Patient

after transplant and associated immunosuppressive therapy. 472–474 signalment, FeLV antigenemia, immunophenotype, and frequency
In these studies, approximately 10% of transplanted cats developed of anatomic sites has occurred in cats with lymphoma in the “post-
FeLV” era (see Table 33.9). Because of this shift, characteristics of
de novo malignant lymphoma and, in one report, all cats had inter-
VetBooks.ir mediate- or high-grade multicentric B cell lymphoma. feline lymphoma discussed in this chapter will be primarily limited
to reports collected from cases presenting after 1995.
Chronic Inflammation
Several anatomic classifications exist for lymphoma in the cat,
Although definitive proof is lacking, there is a growing body of and some categorize the disease as mediastinal, alimentary, multi-
indirect evidence to suggest that lymphoma can be associated with centric, nodal, leukemic, and individual extranodal forms. Others
the presence of chronic inflammation, which theoretically could have combined various nodal and extranodal forms into categories
be the case with intestinal and nasal lymphoma. In particular, an of atypical, unclassified, and mixed, and others have combined
association has been suggested between intestinal lymphoma and intestinal, splenic, hepatic, and mesenteric nodal forms into one
inflammatory bowel disease 427,475 ; however, others have not found category termed intraabdominal. Some discrepancies in the dis-
support for this concept. 476 In addition, an association between cussion of frequency will inevitably result from the variations
gastric Helicobacter infection and gastric mucosa-associated lym- in classification used in the literature. The relative frequency of
phoid tissue (MALT) lymphoma in cats is suggested in one study, anatomic forms and their associated immunophenotype may also
and it warrants further investigation because this is a recognized vary with geographic distribution and may be related to genetic
syndrome in humans. 477,478 In a case-control study investigat- and FeLV strain differences, as well as prevalence of FeLV vaccine
ing mucosa-invading and intravascular bacteria in feline intes- use. For the purposes of this chapter, the feline lymphomas will be
tinal lymphomas, statistically significant differences were found discussed in three separate sections: alimentary/gastrointestinal,
in prevalence of mucosa-invading bacteria, which were identified peripheral nodal, and extranodal. Signalment, clinical presenta-
in 82%, 18% and 3% of large cell lymphoma, small cell lym- tion, diagnosis, treatment, and prognosis will be discussed indi-
phoma and lymphocytic-plasmacytic enteritis biopsy samples, vidually under each of these three sections.
respectively. 477 Furthermore, intravascular bacteria were only
present in cases of large cell intestinal lymphoma (29% of cases). Alimentary/Gastrointestinal Lymphoma
The etiologic significance of this has not been explored, but is also
warranted. Finally, a suggestion that chronic inflammation from Lymphoma is the most common tumor type found in the GI tract
injection sites may be involved in the risk of developing subcuta- of cats, representing 55% of cases in an epidemiologic survey of
neous lymphoma in cats, 431 similar to its documented association 1129 intestinal tumors in the species. 432 The Siamese breed is
with subcutaneous soft tissue sarcomas. reported at increased risk; however, the majority of cases occur
in DSH cats. 427,432,436,441 Although lymphoma may occur in cats
Diet and Intestinal Lymphoma of any age, it is primarily a disease of aged cats with a mean of
Although no direct evidence exists, a link between diet and the 10 to 13 years for T-cell alimentary lymphoma and 12 years for
development of intestinal lymphoma in cats has been suggested. 427 B-cell lymphoma. 427,432,441,486,487 Alimentary/GI lymphoma can
Support is offered by the relative and absolute increase in the ali- be confined to intestinal/gastric infiltration or a combination of
mentary form of lymphoma in the past 20 years and the fact that intestinal, mesenteric lymph node, and hepatosplenic involve-
several dietary modifications in cat food have occurred in a similar ment. Uncommonly, cats may be presented with extraabdominal
timeframe in response to diseases, such as urinary tract disease. Fur- coinvolvement. The tumors can be solitary, but more commonly
ther investigation is warranted to prove or disprove such assertions. are diffuse throughout the intestines. No consistent sex bias is
noted. Anatomically, alimentary lymphoma is nearly four times
Pathology and Natural Behavior more likely to occur in the small intestine than the large intes-
tine. 486 In a series of colonic neoplasia in cats, lymphoma was the
Lymphoma can be classified based on anatomic location and histo- second most common malignancy (41%), second only to adeno-
logic and immunophenotypic (flow cytometric or immunohisto- carcinoma. 459 Most feline GI lymphomas can be categorized into
chemical) criteria; often, the two are intimately associated because one of three types based on histopathology and immunohistopa-
certain histologic and immunophenotypic types are commonly thology: (1) low-grade alimentary lymphoma (LGAL), (2) inter-
associated with specific anatomic locations (see Table 33.9). The mediate- or high-grade alimentary lymphoma (I/HGAL), and (3)
interrogation of lymphoma subtypes by flow cytometric analysis, large granular lymphoma (LGL). Salient, generalizable character-
PARR clonality analysis and genetic characterization, as is the stan- istics of each are presented in Table 33.10.
dard of practice for human lymphoma and becoming so in canine
lymphoma, is less well described and applied in the feline lym- Pathology and Natural Behavior
phomas, partly due to the prevalence of intrabdominal anatomic
forms making sampling more difficult and partly due to variable Low-Grade Alimentary Lymphoma
PCR primer availability and sensitivity. 479,480 The largest compila- It is now clear that the vast majority of LGALs represent mucosal,
tion of feline cases subjected to rigorous histologic classification epitheliotropic, small T-cell immunophenotypes that arise primar-
was reported by Valli and others using the NCI Working Formula- ily from MALT. 436,441,487–492 Thus the major differential for LGAL
tion. 481 The WHO has also published a histologic classification is benign lymphocytic-plasmacytic enteritis (LPE; commonly
system that uses the REAL system as a basis for defining histologic referred to as inflammatory bowel disease [IBD]), which is also
categories of hematopoietic tumors in domestic animals. 482,483 This most commonly characterized by a small, T-cell, epitheliotropic
system incorporates both histologic criteria and immunohistologic infiltration. The largest compilation of LGAL (n = 120) classified
criteria (e.g., B- and T-cell immunophenotype) and was discussed GI lymphoma based on immunophenotype, then as either muco-
in length in Section A of this chapter. The updated Kiel classifica- sal (infiltrate confined to mucosa and lamina propria with mini-
tion system has also been used to classify feline lymphoma. 484,485 mal submucosal extension) or transmural (significant extension
Regarding anatomic location, a profound change in presentation, into submucosa and muscularis propria). 487 They then compared