Page 738 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

716 PART IV Specific Malignancies in the Small Animal Patient

• BOX 33.4 Key Clinical Summary Points: Feline shorthair (DSH) cats are most commonly affected and Siamese
Lymphoma cats appear overrepresented in some reports. A 1.5:1 male-to-
female ratio was observed in two studies, with no association with
VetBooks.ir • A varied group of lymphoid cancers discussed in three major groups gender or neutering status observed in one. 427,428 In a large com-
pilation of Australian cases, male cats and the Siamese/oriental
based on varied presentation, diagnosis, management, and outcome
(Table 33.9): Alimentary/Gastrointestinal, Peripheral Nodal, and breeds were overrepresented, 434 and similar breed findings have
Extranodal. been observed in North America, although similar gender predi-
• Feline leukemia virus (FeLV) infection, a major etiologic agent of the lections have not been found. Within the Siamese/oriental breeds,
disease, is no longer relevant in the majority of cases because of viral there appears to be a predisposition for a mediastinal form that is
elimination and vaccination programs instituted in the 1980s. not FeLV-associated and represents a younger population (median
• The alimentary/gastrointestinal forms predominate, and distinct
subtypes exist representing both indolent (majority) and aggressive of 2 years).
(intermediate-/high-grade) lymphomas (Table 33.10).
• Indolent (low-grade) subtypes in any anatomic site are managed with Etiology
conservative chemotherapy (chlorambucil and prednisolone), with high
response rates and durable survival durations (≥1.5–3 years) expected. Viral Factors
• Intermediate- or high-grade subtypes of any anatomic site are managed FeLV was the most common cause of hematopoietic tumors in the
with more aggressive CHOP- or COP-based chemotherapy protocols cat in the so-called “FeLV era” of the 1960s through the 1980s,
(Tables 33.11, 33.12), with moderate response rates (50%–65%) and when approximately two-thirds of lymphoma cases were associ-
less durable (<1 year) survival durations expected. ated with FeLV antigenemia. Several studies have documented the
• Cats with intermediate- or high-grade lymphoma that achieve a potential molecular means by which FeLV can result in lymphoid
complete response with chemotherapy (approximately 35% of cases) neoplasia (see Chapter 1, Section C). As one would predict, along
often enjoy more durable (>1 year) survival durations.
• Solitary forms of lymphoma may be managed with local therapies (i.e., with a shift away from FeLV-associated tumors came a shift away
surgery, radiation therapy) provided thorough staging has ruled out systemic from traditional signalment and relative frequency of anatomic
spread and active surveillance for identifying recurrence is instituted. sites. This is also supported outside of North America by simi-
lar signalment and anatomic frequency data observed in Austra-
lia, where FeLV infection is less common, and in Europe, where
FeLV incidence has declined and signalment and anatomic site
myeloid) represent approximately one-third of all feline tumors, it prevalence has shifted accordingly. 426,431,434,435 The median age
was estimated that lymphoid neoplasia accounted for an incidence of approximately 11 to 12 years now reported in North America
of 200 per 100,000 cats at risk. 423 In one series of 400 cats with and Europe is considerably higher than the median ages of 3 to 5
hematopoietic tumors, 61% had lymphoma and 39% had leuke- years reported in the FeLV era. 421,422,426–429,431 The median age of
mias and myeloproliferative diseases (MPDs), of which 21% were cats within various anatomic tumor groupings has not changed,
categorized as undifferentiated leukemias, most likely myeloid in and anatomic forms traditionally associated with FeLV, such as the
origin. 424 However, a significant change in the epidemiology and mediastinal form, may still occur in younger, FeLV antigenemic
characteristics of lymphoma in cats coincided with the widespread cats. Similarly, the alimentary form and extranodal forms occur
integration of feline leukemia virus (FeLV) diagnostic assays and most often in older, FeLV-negative cats. 436–441 Table 33.9 presents
affected animal elimination regimens of the late 1970s and 1980s, an overview of the characteristics of the various anatomic sites of
and was further enhanced by the commercially available FeLV vac- lymphoma in cats. As our ability to interrogate FeLV associations
cines appearing in the late 1980s. The decline in FeLV-associated on a molecular basis has improved (e.g., PCR amplification and
lymphoma is mirrored by a global decline in the overall prevalence fluorescent in situ hybridization), several reports exist defining the
per year of FeLV positivity in cats tested. 425–429 Importantly, many role or potential role of FeLV in cats with and without FeLV anti-
of these studies reveal that despite a sharp drop in FeLV-associated genemia. 442–447 Collectively, these studies indicate FeLV proviral
lymphoma, the overall prevalence of lymphoma in cats is increas- insertion exists in a proportion of feline lymphoma tissues and is
ing. The increased prevalence appears because of an increase in more common in those of T-cell origin, particularly the thymic
the number and relative frequency of the alimentary (and, in and peripheral lymph node anatomic forms. They also suggest
particular, the intestinal) and extranodal anatomic forms of lym- that several common FeLV integration sites exist.
phoma. 426,430–433 This is supported by an epidemiologic survey of There is also evidence that feline immunodeficiency virus (FIV)
several hundred cases of feline intestinal lymphoma; 534 (86%) infection can increase the incidence of lymphoma in cats. 425,448–456
were from the 20 years after 1985 and only 14% were from cases In contrast to the direct role of FeLV in tumorigenesis, most evi-
diagnosed in the 20 years before 1985. 432 This change in inci- dence suggests an indirect role for FIV secondary to the immuno-
dence has also been observed in Europe. 426,431 suppressive effects of the virus. Shelton et al determined that FIV
The true annual incidence rate for lymphoma in cats is cur- infection alone in cats was associated with a five-fold increased risk
rently unknown. With respect to feline pediatric (<1 year of age) for development of lymphoma. 454 Coinfection with FeLV further
tumors, a study in the United Kingdom (n = 233 pathology speci- potentiates the development of lymphoproliferative disorders.
mens) found that 73 (31%) represented hematopoietic tumors, Experimentally, cats infected with FIV have developed lymphoma
of which 51 (70%) were lymphoma; note that FeLV status was in the kidney, alimentary tract, liver, and multicentric sites. FIV-
unavailable for this compilation of cases. 433 associated lymphoma is more likely to be of B-cell immunophe-
The typical signalment for cats with lymphoma cannot be uni- notype, as opposed to the T-cell predominance associated with
formly stated as it varies widely based on anatomic site and FeLV FeLV. It has been suggested that FIV infection may be associ-
status, and therefore will be discussed individually under site- ated more commonly with alimentary lymphoma of B-cell ori-
specific discussions. In general, based on two large compilations gin, 449,457 and this may be related to chronic dysregulation of the
(n = 850) of cases in North America and Europe, 427,428 domestic immune system or the activation of oncogenic pathways; however,