Intestinal tumors

Question 1

What is the incidence of intestinal tumors in dogs and cats?

Answer 1

Rare tumors in dogs (8%) and cats (13%).

Question 2

What is the most common intestinal tumor in dogs and cats?

What is the second most common for both?

Third most common in dogs and cats?

Answer 2

LSA is most common in dogs (6%) and cats (30%, also most common form of LSA);

second is adenocarcinoma for both

third is MCT in cats and leiomyosarcoma or GIST in dogs.

Question 3

Mean age in cats? Increased risk?

Mean age in dogs? Leiomyosarcoma

Answer 3

Mean age: 10-12 years in cats (increased risk after 7); and 6-9 years in dogs (12 for leiomyosarcoma).

Question 4

Sex predilection for intestinal tumors?

Answer 4

slight predilection for males in both species.

Question 5

Breed predilection for intestinal tumors in cats?

Dogs?

Answer 5

Siamese cats are 1.8x more likely to develop intestinal neoplasia (8x for intestinal adenocarcinoma). No clear breed predilection in dogs (but, large breeds - smooth muscle tumors, Collies and GSD - adenocarcinomas, and Maltese - MCTs).

Question 6

Etiology for intestinal tumors?

Answer 6

Not known with two exceptions: 1) Retroviral influence on feline LSA, and +/- 2) Association between Helicobacter spp and the development and site determination of poorly differentiated large intestinal adenocarcinomas in cats (Swennes, et al; J Med Microbial, 2016) vs part of the normal feline fecal flora.

Question 7

What is the behaivour of small intestinal tumors in dogs? Rectum?

Answer 7

In dogs most tumors of the small intestine are malignant while most in the rectum are benign or “in situ”.

Question 8

Where does feline and canine intestinal ACAs and canine LMSA usually first spread?

What is the second site for metastasis?

Third?

Answer 8

regional mesenteric LNs (50%, especially adenocarcinoma),

second to the liver in dogs (especially leiomyosarcoma), then the peritoneal cavity/carcinomatosis (30%) and lastly lungs (<20%).

Question 9

Where does GI LSA typically occur in dogs?

System involvement in dogs and cats?

Answer 9

most commonly found in the stomach and intestines (I% large intestine) in dogs.

LSA is a systemic disease, with 25% of dogs and 80% of cats having further organ involvement.

Question 10

What are the 4 subtypes of GI intestinal LSA in cats?

Answer 10

Subtypes in cats include lymphocytic, lymphoblastic, epitheliotropic and large granular lymphocyte.

Question 11

What is the most common location for GI adenocarcinoma in cats and dogs?

Answer 11

Most commonly found in the SI in cats and the colon/rectum in dogs.

Histological classifications include adeno-mucinous, signet ring and undifferentiated/solid, these differentiations may have behavior and prognostic value.

Question 12

Where are adenomatous polyps and carcinomas in situ found in dogs?

In cats?

Answer 12

Colon (polyps and in situ) and rectum (polyps) in dogs

Duodenum in cats (polyps).

Dachshunds were overrepresented for inflammatory colorectal polyps in one study. Most lesions are solitary (but can be multiple or diffuse).

Question 13

Where are GIST most commonly found?

GIST arise from what cells?

IHS stains used for GIST?

Answer 13

SI and LI cecum in dogs

Mesenchymal tumors that arise from the malignant
transformation of multipotential stem cells (— Cajal cells) activated by driver mutations at the c-Kit oncogene (60-70% at exon 11). Historically misdiagnosed as leiomyosarcomas (although do not show smooth muscle differentiation), but can be distinguished mainly by being KIT (CD117)+, but also vimentin+ and actin- and desmin-

Question 14

What is the metastatic rate for GIST?

Answer 14

Metastatic rate varies from 7-27%

Question 15

Leiomyomas and leiomyosarcomas are most commonly found in the what location in dogs?

IHC stains?

Answer 15

stomach (leiomyomas) and SI of dogs.

Real incidence is confounded by misdiagnosis of GISTs.

These tumors are smooth muscle actin+ and desmin+, KIT-.

Question 16

How common are intestinal MCT in cats?

Answer 16

Third most common GI tumor in cats (after LSA and adenocarcinoma), but behavior is poorly understood

Question 17

Where are intestinal carcinoids commonly found?

Arise from what cells and what do these cells secrete?

How do these behave?

Answer 17

Found in the SI and LI.

Histologically resemble carcinomas but arise from the endocrine enterochromaffin cells

Secrete serotonin, secretin and gastrin.

Aggressive behavior (frequent metastasis to the liver).

Question 18

Other GI tumors?

Answer 18

GI solitary extramedullary plasmacytomas (EMPs), GI extraskeletal OSAs in cats and GI HSA in cats (deadly).

Question 20

What is the average time clinical signs are present?

What else can chronic GI signs in cats indicate?

Answer 20

Duration of signs varies days to months but averages 6-8 weeks.

Chronic GI signs in cats can indicate GI LSA or IBD (do not ignore).

Question 21

What are the associated clinical sings with the corresponding location?

Proximal lesion?

SI lesions?

LI lesions?

Answer 21

Clinical signs: depend on the location of the tumor in the GI tract

Proximal lesions = vomiting

SI lesions = weight loss

LI lesions =hematochezia and tenesmus

If obstruction occurs = i%anorexia, vomiting and weight; if peritonitis (secondary to perforation) occurs = signs of acute abdomen (25-32% of dogs with cecal GIST in one study). Other signs are diarrhea, and less frequently melena and anemia.

Question 22

Hypoglycemia is a praneoplastic sign associated with what tumor?

Answer 22

Reported with 55% of intestinal smooth muscle tumors (leiomyosarcomas) in dogs, due to insulin-like growth factor secretion by tumors cells.

Question 23

Eosinophilia is a paraneoplastic sign associated with what tumor in cats and dogs?

Due to secretion of what?

Answer 23

Intestinal T cell LSA, due to tumor cell-IL-5 secretion

Question 24

Reversible neutrophilic leukocytosis is reported in what tumors in dogs?

Answer 24

reported in dogs with rectal tumors which resolved after surgery

Question 25

Other paraneoplastic signs?

Answer 25

o Other: case reports link alopecia and metastasizing feline colonic carcinoma, EMP and hyperviscosity syndrome (due to hyperglobulinemia), erythrocytosis and canine cecal leiomyosarcoma (due to tumor cell-erythropoietin production), and opportunistic Cheyletiella infection and intestinal carcinoma (due to immunosuppression).

Question 26

Physical examination can reveal an abdominal mass in what % of dogs with LSA?

Non-LSA tumors?

Answer 26

20-40% of dogs with LSA

20-50% of dogs with non-LSA tumors and most cats with both),

Question 27

Pain and fever is noted in what % of dogs with LSA?

Mass on rectal exam?

Dehydration?

Answer 27

20% of dogs with LSA

63% of dogs with rectal tumors

Dehydration (30-60% of cats with non-LSA intestinal tumors).

Question 28

What are the common findings on CBC in dogs with intestinal tumors?

Answer 28

o CBC: commonly notes anemia (40% of dogs, 15-70% of cats, and usually with ?BUN +/- history of melena)

leukocytosis (25-70% of dogs and 40% of cats, with eosinophilia in cases of T cell LSA and neutrophilia in rectal tumors).

Question 29

What are the common findings on chemistry profile?

Answer 29

hypoproteinemia due to malabsorption (25-33%), I liver enzymes (I%ALP in 33% of dogs and 85% of cats), IBUN (13% of dogs and 30% of cats with intestinal carcinoma, due to GI bleeding, dehydration +/- concurrent renal disease), paraneoplastic hypoglycemia +/- hypercalcemia in LSA patients

Question 30

A large abdominal mass can be seen on radiographs in what % of patients?

Obstructive pattern?

Answer 30

40% of patients (non-LSA > LSA)

obstructive pattern in 10-75% of cases

Question 31

What findings can be notedon AUS with intestinal tumors?

Answer 31

neoplastic vs inflammatory disease: > lcm intestinal thickening (4x likely to be a tumor)

loss of layering (50x)

focal distribution of lesions (20x)

symmetry and concurrent lymph node enlargement (greater with neoplasia)

Question 32

Patterns of intestinal masses on AUS

Feline adenocarcinoma

GI MCT

Smooth muscle tumors

LSA

Answer 32

Some patterns: feline adenocarcinomas –> masses of mix echogenicity; canine adenocarcinomas 4 hypoechoic masses associated with decreased GI motility;

GI MCTs 4 eccentric appearance with alteration but not loss of wall layering;

smooth muscle tumors –> large anechoic to hypoechoic masses with an identifiable muscle layer origin;

LSA 4 wall thickening and loss of normal layering (although normal appearance does not completely rule out LSA)

Question 33

Surgery for small intestinal masses?

Answer 33

most common technique is R&A

Question 34

Surgery for Large Intestine?

Benign tumors?

Malignant tumors?

Answer 34

rectal polyps, techniques include mucosal eversion/submucosal resection or transrectal endoscopic removal depending on the location of the tumor. Known complications of the latter technique are rectal perforation and incomplete resection.

For (suspected) malignant tumors: e.g., rectal adenocarcinomas, full thickness resections (subtotal colectomy) through perineal or perineal/abdominal rectal-pull through are recommended. Better outcome reported in cats with rectal adenocarcinomas after subtotal colectomy (MST=138 days vs 68 days with mass excision). Complications are common and include fecal incontinence (57% total, 40% permanent), diarrhea (43%), tenesmus (31%), stricture (21%), rectal bleeding (11%), dehiscence (8%) and infection (8%).

Question 35

What COX-2 inhibitor can be used in rectal polyps?

Answer 35

Cox inhibitors: Cox-2 has been identified in benign and malignant GI neoplasia, but at variable -sometimes very low- levels; thus, the use of NSAIDs remains questionable in these tumors. Nonetheless, piroxicam have been used in dogs with rectal polyps noting a reduction in size and clinical signs.

Question 36

What are 5 prognostic factors for intestinal masses?

Answer 36

Gross appearance, metastasis at time of surgery, surgery, adjuvant chemotherapy, intestinal perforation

Question 37

Gross appearance as prognostic factor

MST associated with obstructing masses?

MST with noduler or pedunculated masses

Answer 37

Dogs with annular/obstructing masses noted a shorter MST (1.6 months)

Nodular or single pedunculated masses (MST=12 and 32 months). Not statistically examined.

Question 38

Metastasis at time of surgery as prognostic factor

Answer 38

Negative prognostic indicator that resulted in significantly shortened ST. e.g., MST=3 months and 1 year-survival rat20% with mets vs 15 months and 67% w/o mets in dogs with non-LSA SI tumors; and MST=280 days w/o LN mets vs MST=49 days w LN mets in cats with rectal adenocarcinoma; and MST=200 vs 340 days with distant metastasis.

Question 39

Surgery as prognostic factor for intestinal tumors

Answer 39

o Surgery: Local excision results in significantly better outcome than palliative care in dogs with colorectal tumors (MST=2 to >4 years vs MST=15 months).

In cats with rectal adenocarcinoma subtotal colectomy noted significantly longer survival vs mass excision (138 vs 68 days).

For dogs or cats without evidence of local or distant metastasis long­term survival after surgery is possible, although some may later metastasize.

Question 40

Adjuvant chemotherapy as prognostic factor?

Answer 40

Adjuvant chemotherapy: in cats with rectal adenocarcinoma treated with surgery the addition of doxorubicin after
surgery noted a superior MST=280 days vs MST=56 w/o chemo. RTKi have elicited good responses on GISTs.

Question 41

Intestinal perforation as prognostic factor?

Answer 41

Intestinal perforation: does not appear to have a negative impact on OS if surviving surgery for leiomyosarcomas; occurred in 25-37% of cecum GISTs in one study.

Question 42

What is the prognosis for canine SI ACA?

MST with treatment? w/o treatment?

Answer 42

Guarded, MST=12 days w/o treatment, MST=114 days with surgery in one study and 7-10 months in other studies.

Question 43

Prognosis for feline SI adenocarcinoma

MST?

Answer 43

significant peri-operative risk, but cats that live beyond 2 weeks may experience long-term survival after surgery alone (MST=2.5 month if surgical complications or 15 months).

Question 44

Prognosis for canine SI leiomyosarcoma?

MST?

Answer 44

Good with surgery

MST=8-10 moths to up 2 years after surgery (if surviving the perioperative period, the finding of visceral metastasis did not affect this MST significantly) (Cohen et al, JVIM, 2003).

Question 45

Prognosis for GIST vs leiomyosarcoma?

Answer 45

conflicting information on which one carries a better prognosis, due to reports being confounded by misdiagnosis.

Post-op 1-year survival rate for both GIST and leiomyosarcomas was 80% (Maas et al, Vet Surg, 2007). For GISTs overall MST=-38 months after surgery (12 months with peri-op deaths) and the Palladia and Imatinib seem to benefit (PFI=110 weeks for gross disease and 67 weeks for microscopic disease with Palladia).

Question 46

Prognosis for canine SI MCT?

Answer 46

benefit from surgery is questionable, with most dogs dying within 1 month after surgery (only 2 of 49
dogs lived past 180 days, also pred was not helpful (Takayashi et al, JAVMA 2000 and Ozaki et al, Vet Pathol, 2002).

Question 47

Prognosis for canine LI neoplasia?

MST with colorectal ACA?

Colorectal EMPs?

Polyps?

Answer 47

Colorectal adenocarcinoma has a MST=2 to >4 years after surgery (vs only 15 months with stool softeners alone),

Colorectal EMPs have a MST=15 months after surgery,

Polyps have a MST=>2 years after surgery and local recurrence of signs=41% and 18% carcinoma in situ noted malignant transformation

Question 48

Prognosis for cats with rectal adenocarcinoma

Answer 48

prolonged survival may be achieved in cats without metastasis at the time of surgery (MST=259 vs 49 days with mets) and treated multimodally with subtotal colectomy (MST =138 days vs 68 days with mass resection) and adjuvant doxorubicin chemotherapy (MST=280 vs 56 days w/o). Surgery is curative for polyps.

Question 49

Carcinomatosis: should not always be an indication for euthanasia as two cats with malignant effusion lived 4.5 and 28 months after surgical removal (Ksovsky, et al; JAVMA, 1988).

Question 50

Comparative aspects

· In humans LUcolorectal neoplasia is one of the most common cancers in men and women, and is more common than SI neoplasia (rare, usually malignant), in contrast to veterinary patients where in cats (and sometimes dogs) malignant neoplasia is more common in the SI than the LI.

· Human GIST: IHC for a protein called DOGI seems to be more sensitive than KIT for the diagnosis of GIST. Both KIT and DOG I are used in combination to increase accuracy of diagnosis.

· Most clinically important aspect of comparative oncology for GI tumors is the use of COX-inhibitors in the treatment and prevention of colorectal neoplasia and the use of TKi (e.g., Imatinib for GIST). Surgical resection is still the mainstay of therapy for GI tumors in both human and veterinary patients.