Page 484 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

462 PART IV Specific Malignancies in the Small Animal Patient

inflammatory polyps presented as multiple small polyps, whereas histologic similarity to carcinomas. Carcinoid cells arise from
other colorectal polyps generally presented as either solitary or mul- enterochromaffin cells of the intestinal mucosa and contain secre-
476,477
In cats, polyps are more common in the duode-
tory granules that may contain substances such as 5-hydroxytryp-
tiple lesions.
VetBooks.ir num and intestinal obstruction resulting from a duodenal Brunner’s tamine (serotonin), secretin, somatostatin, and gastrin, among
478
472
IHC for cytokeratin and for secretory substances, such
gland adenoma has been reported in a dog.
others.

as serotonin, may be positive, and serum concentration of sero-
Leiomyomas, Leiomyosarcomas, and GISTs tonin has been documented at 10 times the normal range in one
dog with a carcinoid. 489 Carcinoids have been described in many
Leiomyomas occur more commonly in the stomach, but have species and may occur in both the large and the small intestines
also been reported in the esophagus, small intestine, and colorec- and frequently metastasize to the liver. 434,473,489 Carcinoids may
tum. 457 GISTs are well documented in humans and have been follow an aggressive and debilitating clinical course. 489
reported in dogs and cats. 479–481 These nonlymphoid tumors of Extramedullary plasmacytomas (EMPs) are solitary tumors with
mesenchymal origin were originally diagnosed as leiomyosar- no evidence of systemic multiple myeloma and the reader is referred
comas and some, but not all, were leiomyomas. Histologically, to Chapter 33, Section D , where they are covered in detail. Another
GISTs are highly cellular mesenchymal tumors that do not show uncommon tumor type is extraskeletal OSA, which has been
ultrastructural characteristics consistent with smooth muscle dif- reported in the duodenum of a cat. 490 This cat had no evidence of
ferentiation. GISTs are thought to arise from multipotential stem metastasis at diagnosis and did well for 4 months after surgery when
cells phenotypically similar to interstitial cells of Cajal, driven clinical signs recurred and the cat died. 490 Three of 55 extraskeletal
by activating mutations of c-Kit (a proto-oncogene). Although and 145 total cases of feline OSA were of intestinal origin. 491 A
these cells can differentiate into smooth muscle cells if deprived series of four cats was reported with intestinal hemangiosarcoma
of KIT (a receptor tyrosine kinase), GISTs are a discrete clini- arising from four different locations within the intestines; no cat
cal entity from leiomyosarcoma. 482 Leiomyosarcomas are posi- survived greater than 1 week. 492 Finally, one dog was diagnosed
tive for smooth muscle actin and desmin and negative for KIT. with ganglioneuroma of the rectum and experienced long-term sur-
GISTs are distinguished by high vimentin immunoreactivity, low vival after surgical resection. 493 Small intestinal ganglioneuromato-
alpha smooth muscle actin reactivity, and CD117 (KIT) reactiv- sis has also been reported in a dog with a similar good outcome after
ity, and arise primarily in the small and large intestine. 457,483,484 surgical resection. 494
c-Kit exon 11 mutations have been found to occur frequently in
canine GISTs, which is similar to human GISTs, where exon 11 Molecular Aspects
mutations occur in 60% to 70% of cases and mutations in exon 9
occur in 5% to 10% of cases. 457,485 To date, only one dog with an With an increasing armamentarium of molecular diagnostics,
exon 9 mutation has been reported. 486 CD117 (KIT) reactivity is insights into the pathogenesis, progression, and prognosis of
considered a major diagnostic criterion and is used to distinguish tumors are constantly emerging. Cellular adhesion and invasion
GISTs from leiomyosarcomas in many studies. 487,488 When strati- (e.g., Tenascin-C, 463,495 versica, hyaluronan, 496 β-catenin, and
fied as such, 28 of 42 leiomyosarcomas in dogs were reclassified as E-cadherin 497–499 ), stromal remodeling, and alterations in tumor
GISTs and only 2 of the 28 cases of GIST metastasized (7%), with suppressor genes (e.g., p53 497,499–501 ) may play a role in the devel-
those dogs living longer than dogs with leiomyosarcoma. 487 These opment and progression of intestinal neoplasia. The importance
investigators also found that GISTs were significantly more likely of the relationship between a tumor cell and its stroma should
to occur in the large intestine, specifically the cecum, and leio- not be underestimated. Although molecular markers/targets likely
myosarcomas in the stomach and small intestine, 487 yet a recent play an important role in intestinal tumors, the utility of these in
study contradicted this finding with GISTs occurring primarily in diagnostics, prognostication, and therapy in companion animal
the small intestine. 484 Considering these findings, the incidence species, with the exception of GIST and CD117 expression, is
of true leiomyosarcoma is likely low because many previously limited. 481
reported cases may have actually been GISTs. The inclusion of COX enzymes are responsible for prostaglandin synthesis and
GISTs as leiomyosarcomas will also have caused confounding of COX-2 is overexpressed in many head/neck and genitourinary
clinical behavior in these studies. In addition to the effect on inci- tumors, creating a possible therapeutic target. COX-2 has been
dence, conflicting reports of biologic behavior are problematic. identified in both benign and malignant small intestinal and
Although the study cited earlier found a 7% rate of metastasis for colorectal epithelial tumors in dogs, although the number of posi-
dogs with GISTs and a worse prognosis for dogs with leiomyosar- tive cells varies and was very low in some studies. 502,503 In addi-
coma, a recent study reported a higher rate of metastasis (27%) in tion, one study found no COX-2 staining in 13 intestinal tumors
GISTs and no metastasis in dogs with leiomyosarcomas. 484 in cats. 504 COX inhibitors are thus of questionable value in treat-
ing intestinal tumors.
Mast Cell Tumors
History and Clinical Signs
Intestinal MCTs are the third most common tumor after lym-
phoma and adenocarcinoma in cats, but their incidence and The duration of clinical signs before presentation typically
behavior are poorly reported. For further details, the reader is averages 6 to 8 weeks, but can range from less than 1 day
referred to Chapter 21. to several months. 441,450,451 Clinical signs include (in vary-
ing order of frequency): weight loss, diarrhea, vomiting, and
Other Tumor Types anorexia, and, less frequently, melena, anemia, and hypogly-
cemia (with smooth muscle tumors). 434,441,444,453,460,461,505–508
The term carcinoid refers to tumors that arise from the diffuse Clinical signs often relate to location of the tumor within the
endocrine system rather than the intestinal epithelium, despite GI tract. Proximal lesions more commonly result in vomiting;