Page 490 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

468 PART IV Specific Malignancies in the Small Animal Patient

animals, although advanced imaging modalities, such as CT, are but without a convincing increase in overall STs. 557 RT is used
more often used. Most diagnoses are made at surgery and 5-year primarily for areas of the GI tract that are not very mobile, such as
548
survival rates average approximately 20%.
the stomach and rectum.
VetBooks.ir diagnosed cancers in both men and women. Risk factors include
Large bowel/colorectal cancer is one of the most frequently
genetic predisposition/familial history, tobacco and alcohol SECTION H: PERIANAL TUMORS
intake, advanced age, and predisposing medical conditions,
among others. Colorectal cancer development may further be JULIUS M. LIPTAK AND
influenced by intake of red meat (especially fried), low-fiber MICHELLE M. TUREK
and/or high-fat diets, obesity, fecal pH, and fecal mutagens.
Among genetic risk factors, polymorphism in colonic enzymes The perianal area of dogs contains several glands and structures
and mutations leading to familial adenomatous syndromes are from which tumors may develop. Perianal, or circumanal, glands
uncommon but are important as models of carcinogenesis. In are located in the dermis in a circular fashion around the anus and
most familial polyposis syndromes, the adenomatous polyposis are also scattered in areas on the prepuce, tail, pelvic limbs, and
coli (APC) gene is mutated. The multistage progression from trunk. 558 These are commonly referred to as hepatoid glands as
benign polyp to carcinoma is well understood and underscores a result of their cellular morphologic resemblance to hepatocytes
the importance of early detection. 549 Recently, the APC gene and are considered nonsecretory sebaceous glands in the adult
was found to be altered in about 70% of tested canine colorectal dog. 558,559 The anal sacs represent blind cutaneous diverticula that
tumor samples, suggesting a similar molecular pathogenesis. 550 are located on each side of the anus at the 4 o’clock and 8 o’clock
In contrast, hereditary nonpolyposis colon cancer develops with- positions. Located in the connective tissue surrounding these
out known premalignant polyps; this is inherited via autosomal diverticula are distinct apocrine sweat glands that empty their
dominance with high penetration and is characterized by micro- secretions into the lumen of the anal sacs. The most frequently
satellite instability. 551 observed tumors of this region in dogs include perianal sebaceous
In human medicine, GISTs are also subcategorized by the his- adenoma, perianal sebaceous adenocarcinoma, and apocrine
topathologic morphology, a recent publication on canine intesti- gland anal sac adenocarcinoma (AGASAC). Other tumors arising
nal tumor classification divided canine GISTs into 2 morphologic from the anal sacs include squamous cell carcinoma (SCC) and
groups: spindlyloid/storiform and epitheloid, with the majority malignant melanoma, 560–563 but benign tumors of the anal sac are
of GISTs in this study being spindlyloid. 484 In addition, it has rare. 564 Any cutaneous or subcutaneous tumor can affect the peri-
been suggested in humans there may be a subset of GISTs that anal region, including mast cell tumor, soft tissue sarcoma, squa-
are KIT negative. 484 A recent study evaluated the use of protein mous cell carcinoma, hemangiosarcoma, lymphoma, melanoma,
1 (DOG1) IHC marker to identify GISTs and it was found to leiomyoma, and transmissible venereal tumor.
have an increased specificity and sensitivity compared with KIT Because cats do not have glands analogous to the perianal
IHC. 552 In this study, 2 tumors were negative for KIT and positive sebaceous glands in the dog, perianal adenoma and perianal ade-
for DOG1. This may indicate there is a subpopulation of GISTs nocarcinoma are uncommonly recognized in this species. Apo-
in dogs that are also KIT negative. The authors concluded that crine gland adenocarcinoma of the anal sac occurs rarely in the
utilizing diagnostic panels with KIT and DOG1 markers would cat. 565–567
improve the accuracy of diagnosis. 552
The most clinically important aspects of comparative oncol-
ogy when considering intestinal neoplasia in humans are the use Perianal Adenoma and Adenocarcinoma
of COX inhibitors in the treatment and prevention of colorec- Incidence and Risk Factors
tal neoplasia, and the use of TKIs. In people, KIT mutations
in GISTs have led to the use of imatinib mesylate, a TKI that Perianal adenomas (circumanal, hepatoid tumors) represent the
inhibits KIT. 553 This illustrates the notion of therapy directed at majority of canine perianal tumors (58%–96%). 558,568 Develop-
the molecular defect rather than the histologic diagnosis. KIT ment and progression of these benign tumors appear to be sex
is mutated in some canine GISTs and thus TKIs may benefit hormone–dependent, with growth stimulated by androgenic hor-
this population as well. COX inhibition byNSAIDs decrease the mones and supressed by estrogenic hormones. 558,569,570 Older,
incidence of colorectal cancer and mortality by 40% to 50%. 554 intact male dogs are at higher risk. 558,568,569 The mean reported age
Among the proposed mechanisms of action, prostaglandin is 10 years. 568 A high incidence of associated testicular interstitial
production may be related to tumor progression and therefore cell tumors has been reported for males with perianal adenomas,
inhibition leads to cancer prevention. In addition, non-COX supporting testosterone production as a cause 569 ; however, a true
pathways include inhibition of transcription factors and induc- cause-and-effect relationship has not been clarified because inter-
tion of nuclear hormone receptors that lead to cellular differentia- stitial cell tumors are also a common incidental finding in non–
tion. 554 Interestingly, a retrospective study found a significantly adenoma-bearing, older intact males. Perianal adenomas in the
reduced incidence of cancer in dogs with a history of NSAID use female occur almost exclusively in ovariohysterectomized animals
(71% reduced risk). 555 in which low levels of estrogen do not suppress tumor growth.
Therapy in humans is similar to that in companion animals. Rarely, androgenic steroid secretion from the adrenal glands,
Surgical resection is the primary mode of therapy with adjuvant occasionally accompanied by signs of hyperadrenocorticism,
targeted or traditional chemotherapy in many cases, especially if may stimulate perianal adenoma formation in female dogs. 571,572
patients present with LN metastasis or unresectable disease. TKIs Cocker spaniels, beagles, bulldogs, and Samoyeds may be predis-
may improve prognosis for unresectable and metastatic GISTs. 556 posed. 558,569 Some authors have proposed the term epithelioma
Adjuvant chemotherapy is used in colon cancer, with oxaliplatin to describe a subset of perianal sebaceous gland tumors. 573 Epi-
in combination with capecitabine or with leukovorin and 5-FU, theliomas are considered low-grade malignancies with a greater