Page 491 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 23 Cancer of the Gastrointestinal Tract 469

tendency to be locally invasive and to recur after surgical exci- They may be single, multiple, or diffuse (similar to generalized
sion. 574,575 To date, there is little clinical information to support a hyperplasia or hypertrophy of the perianal tissue). 558 Most occur
on the hairless skin around the anus, although they may extend
distinction between adenoma and epithelioma.
VetBooks.ir glands, occurs much less frequently than its benign counterpart, to haired regions and can develop on the prepuce, scrotum, or tail
Perianal adenocarcinoma, a malignant tumor of the perianal
558
head (stud tail or “caudal tail gland”).
Benign lesions may ulcer-
representing only 3% to 21% of all tumors in this region. 558,568 The ate and become infected but are rarely adherent or fixed to deeper
mean age of affected dogs is 11 years. 568,576 Tumors occur in cas- structures. 558 They are usually fairly well circumscribed, on aver-
trated or intact males, as well as in females, implying no hormonal age 0.5 to 3 cm in diameter, and elevated from the perineum. 558
dependency; however, this does not preclude earlier hormonal initi- Perianal adenocarcinoma may have a similar gross appearance
ation. 569,576 Large-breed male dogs appear to be overrepresented. 576 to perianal adenoma; however, they tend to have a faster growth
rate, present more commonly as a larger and firmer mass with
Pathology and Natural Behavior some degree of ulceration and fixation to deeper tissues, and they
are more likely to recur after conservative surgical resection. 576
Perianal adenoma is benign. These are slow-growing tumors Perianal adenocarcinomas can be multiple. 573 Obstipation,
and, although local disease may be extensive, metastasis does not dyschezia, or perianal pain or irritation can be seen with larger
occur. 558,576 masses. 576 Rarely, clinical signs are related to obstruction of the
Perianal adenocarcinoma is generally associated with a low rate pelvic canal by LN metastasis. Castrated male dogs with a new or
of metastasis (<15%) at the time of diagnosis. 576 Metastasis may be recurrent perianal tumor may have an increased risk for malignant
more likely to develop later in the course of disease as the primary rather than benign disease because, unlike perianal adenoma, peri-
tumor becomes larger and more invasive. 576 The most frequent site anal adenocarcinomas are not hormonally dependent.
of metastasis is the regional LNs. 558,576 Distant metastasis is rare,
but has been reported in the lungs, liver, kidney, and bone. 569,576 Diagnostic Techniques and Workup
This tumor tends to be more rapidly growing, fixed, and firmer
than the more common benign perianal adenoma. Signalment, history, and physical examination findings will assist
The pathogenesis of canine perianal tumors is not known. In a in developing a preliminary suspicion of tumor type as well as treat-
large study evaluating tumor growth characteristics of 240 perianal ment planning. The mass should be palpated and a rectal exami-
gland tumors, cell proliferation and apoptosis were quantified by nation performed to assess the degree of fixation and extent of the
proliferating cell nuclear antigen (PCNA) IHC and microscopic mass as well as the presence of enlarged LNs. Physical examination
detection of apoptotic corpuscles. 577 Increases in both parameters findings may provide some indication of whether a perianal mass
were observed in perianal adenocarcinomas compared with perianal is benign or malignant; however, there is a degree of overlap in
adenomas. 577 Ki67 immunoreactivity has also been evaluated and the gross appearance of perianal adenoma and adenocarcinoma.
was found to increase from benign to malignant lesions, being high- FNA cytology to differentiate benign from malignant tumors can
est in perianal adenocarcinomas and recurrent tumors. 574,575,578 Col- be unrewarding, although it is helpful in ruling out other tumor
lectively, these results suggest that a high proliferative index may be types. Incisional biopsy is recommended for definitive diagnosis
related to tumor aggressiveness. Other IHC studies have attempted and to better direct clinical staging tests and treatment options. 584
to elucidate possible molecular mechanisms involved in canine peri- Malignant disease is more likely in tumors showing invasiveness
anal gland tumorigenesis. Nuclear p53 accumulation was detected into surrounding tissue, disorderly arrangement of cells, increased
in 50% of perianal sebaceous gland adenocarcinomas in one study, nuclear pleomorphism, and increased numbers of mitotic fig-
suggesting that expression of a mutated p53 tumor suppressor pro- ures. 584 In some cases, a definitive diagnosis may not be possi-
tein may play a role. 579 Discordant results were reported in another ble histologically, and IHC with monoclonal antibodies against
study in which p53 reactivity was found in none of 11 perianal carcinoma-associated antigens 4A9, 1A10, as well as PCNA, and
gland adenocarcinomas and in only a small percentage of adeno- Ki67 may assist in differentiating perianal adenoma from adeno-
mas. 580 In the same tumor samples, Mdm2 expression was observed carcinoma. 573–578,585 In the rare event that differentiation from
in both adenomas and adenocarcinomas. 580 A study that evaluated AGASAC is needed, cytokeratin expression patterns may be help-
androgen receptor expression found no difference between peri- ful. 586 Clinical validation is needed to confirm the utility of these
anal adenomas and adenocarcinomas; the authors concluded that IHC approaches.
the mechanism by which androgens influence carcinogenesis is still For dogs with perianal adenocarcinoma, abdominal and tho-
unknown. 581 Vascular endothelial growth factor (VEGF) may also racic imaging is recommended to investigate for the presence of
be involved in tumorigenesis. Serum VEGF levels corresponded metastatic disease. Up to 15% of dogs with perianal adenocarci-
with tumor aggressiveness and tumor burden in one study. 575 The noma have evidence of metastatic disease at the time of diagno-
same study suggested a correlation between serum 17-β-estradiol sis, and the regional LNs and lungs are the most common sites
and VEGF levels, supporting the role of hormones in carcinogenesis of metastasis. 558,569,576 Based on studies of canine AGASAC,
in some perianal tumors. 575 Another proposed mediator of tumor advanced imaging modalities, such as CT andMRI, are superior
development is growth hormone. Growth hormone was detected to abdominal ultrasonography for the detection of enlarged LNs,
with IHC in 96% of perianal adenomas and 100% of perianal seba- particularly those within the pelvic canal. Although distant metas-
ceous gland adenocarcinomas. 582 Finally, serum magnesium levels tasis is uncommon, three-view thoracic radiographs or thoracic
were found to be higher in dogs with malignant perianal tumors CT is recommended for the detection of pulmonary metastasis.
than in those with benign tumors. 583
Treatment
History and Clinical Signs
Surgical resection is the recommended treatment for dogs with
Benign perianal adenomas tend to be slow-growing (over months perianal adenomas and adenocarcinomas. Perianal adenomas can
to years) masses that are nonpainful and usually asymptomatic. be excised with minimal margins of less than 1 cm, whereas larger