Pathology in Practice

William Holl Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Daniel Felipe Barrantes Murillo Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL

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Samantha Sommer Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Katharine Lunn Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Michael Mastromauro Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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 DVM, DACVIM (Oncology)
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Alisa Berg Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Negrão Watanabe Tatiane Terumi Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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 DVM, PhD, DACVP

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History

A 14-year-old 5.7-kg female spayed domestic shorthair cat was referred to North Carolina State University for a 2-day history of hyporexia.

Clinical and Gross Findings

On physical examination, the cat was quiet, alert, and responsive. Moderate dehydration (7% to 8%) with bilateral enophthalmos and pale-pink, tacky mucous membranes were detected. Abdominal palpation revealed marked pain and a firm noncompressible mass in the region of the colon. A CBC indicated a moderate, microcytic (MCV, 38 fL; reference interval, 38.2 to 53.5 fL), nonregenerative anemia (HCT, 24.6%; reference interval, 32.8% to 49.8%; reticulocyte count, 0.045 X 106/µL) with Heinz body formation (20/100X hpf), and a marked leukocytosis (WBC, 39.42 X 103 cells/µL; reference interval, 4.29 X 103 to 14.3 X 103 cells/µL) with mature, marked neutrophilia (35.872 X 103 cells/µL; reference interval, 2.773 X 103 to 6.975 X 103 cells/µL), a left shift (bands, 1.183 X 103) with slight toxic change, and a moderate monocytosis (1.577 X 103 cells/µL; reference interval, 0.068 X 103 to 0.78 X 103 cells/µL). A serum biochemistry profile revealed hypoalbuminemia (2.6 g/dL; reference interval, 2.9 to 4 g/dL) with a relative hyperglobulinemia (4.2 g/dL; reference interval, 2.6 to 4.5 g/dL), a moderate hyperbilirubinemia (1.0 mg/dL; reference interval, 0.1 to 0.2 mg/dL), a mild increase in aspartate transaminase activity (87 IU/L; reference interval, 12 to 44 IU/L), a marked increase in CK (1266 IU/L; reference interval, 52 to 594 IU/L), hyponatremia (144 mmol/L; reference interval, 149 to 157 mmol/L), and hypochloremia (106 mmol/L; reference interval, 111 to 120 mmol/L). Treatment with lactated Ringer solution (12 mL/h, IV) supplemented with KCl (0.05 mEq/kg/h, IV), maropitant (1 mg/kg, IV, q 24 h), ondansetron (0.5 mg/kg, IV, q 8 h), lactulose (3 mL, PO, q 8 h), and gabapentin (50 mg, PO, q 8 h) was administered for 24 hours. The cat became obtunded, weak, and bradycardic (heart rate, 150 to 160 beats/min) with hypersalivation and uncontrolled urination. Due to progressive clinical deterioration, humane euthanasia was elected.

Gross postmortem examination revealed a colonic stricture located 7.5 cm aboral to the ileocecocolic junction with marked narrowing of the colonic lumen (< 0.5 cm in diameter; Figure 1). At the level of the stricture, the colonic wall was circumferentially expanded by a focal, irregular, firm, mottled tan-white to pale-pink, ill-defined mass (Figure 1). The associated colonic mucosa had an ulcer measuring 0.4 cm in diameter with omental adherence to the serosa. The proximal colon, cecum, and distal small intestines were markedly distended by abundant malodorous digesta mixed with mucus. The colonic and ileocecal lymph nodes were moderately enlarged. The hepatic parenchyma was diffusely pale brown and had 2 firm, random, pale-tan nodules measuring 3 and 5 cm in diameter.

Figure 1
Figure 1

Postmortem photograph of the colonic mass from a 14-year-old female spayed domestic shorthair cat with hyporexia, hyperbilirubinemia, neutrophilia, and anemia. A—Colonic stricture (arrowhead) located 7.5 cm aboral to the ileocecocolic junction with marked distension of the proximal colon, cecum, and distal small intestines. B—At the level of the stricture, the colonic wall is replaced by an irregular, firm, tan-white to pale-pink, ill-defined mass (arrowhead).

Citation: Journal of the American Veterinary Medical Association 261, 1; 10.2460/javma.22.03.0110

Histopathologic Findings

Histologic examination of the colonic mass revealed an ulcerated, nonencapsulated, infiltrative, poorly demarcated epithelial neoplasm arranged in irregular tubules and acini supported by robust scirrhous stroma (Figure 2). Neoplastic cells were cuboidal to columnar with distinct cell borders and had a moderate amount of eosinophilic cytoplasm, ovoid nuclei with coarsely stippled chromatin, and up to 2 prominent nucleoli. Anisocytosis and anisokaryosis were moderate; 42 mitotic figures were observed in 10 hpf (2.37 mm2). The exposed submucosa was necrotic and infiltrated by moderate numbers of neutrophils, large numbers of mixed bacteria, and fibrin exudate. The colonic lymph node and the hepatic and pancreatic parenchymas were multifocally replaced by a neoplastic population with similar morphological features as described in the colon (Figure 2).

Figure 2
Figure 2

A—Photomicrograph of a section of the colon. Extensive ulceration of colonic mucosa (asterisk) with transmural invasion by a nonencapsulated, epithelial neoplasm. H&E stain; bar = 500 μm. Neoplastic cells form tubules and acini, invading the submucosa, and are supported by robust scirrhous stroma (inset). H&E stain; bar = 100 μm. B—Photomicrograph of a section of the liver. The subcapsular hepatic parenchyma is replaced and expanded by an infiltrative, epithelial neoplasm with similar morphological features as those described in the colon. H&E stain; bar = 500 μm.

Citation: Journal of the American Veterinary Medical Association 261, 1; 10.2460/javma.22.03.0110

Morphologic Diagnosis and Case Summary

Colon: colonic tubular adenocarcinoma (ACA) with secondary colonic stricture and cecocolic distension and metastasis to the liver, pancreas, and regional lymph nodes.

Comments

Before the 1980s, the most common intestinal neoplasm in domestic cats was ACA.1 However, with the advent of FeLV testing and vaccination, along with improved diagnostic techniques and longer lifespans, intestinal lymphoma (54.82% [619/1,129]) surpassed intestinal ACA (31.53% [356/1,129]).1 Feline intestinal ACA can occur in both large and small intestines.2 Although reports vary regarding a predisposing anatomical intestinal localization,2 it is suggested that the colon is the most commonly affected site.1 Other reported intestinal neoplasms are mast cell tumors (4.25% [48/1129]) and leiomyosarcomas (1.24% [14/1129]).1 Cats under 7 years old have the lowest risk for development of intestinal neoplasia, whereas incidence increases with age, with a reported mean age of 13 years.1,3 Siamese cats are overrepresented for the development of gastrointestinal neoplasms, as they have more than a 3-fold increased risk of neoplasia development compared to other breeds.1,4 Sex predisposition is still up for debate, with conflicting evidence among studies.1,3,4 Clinical signs include lethargy, anorexia or hyporexia, vomiting, diarrhea, tenesmus, melena, and weight loss.4,5 Abdominal palpation can reveal a mass effect in the intestines or an abdominal fluid wave.4 Intestinal ACA can cause annular constrictions with varying degrees of stenosis.4 Poststenotic dilation has been seen more in small intestinal ACA; however, mucosal ulceration has been more commonly seen in the affected large intestine.4 Abdominal ultrasound and computed axial tomography are used to target and identify masses in the gastrointestinal system of cats; however, there are no studies to date comparing the accuracy between these diagnostic tests and identification of intestinal masses in feline patients.5

Clinical pathological findings in cats with intestinal neoplasms are nonspecific and related to the location, extension, and progression of the lesions. The CBC and serum biochemistry profiles commonly evidence anemia and increased BUN.6 Leukogram findings reported in 40% of cats with intestinal neoplasms include leukocytosis, left shift, and monocytosis.6 Biochemical abnormalities, such as hypoalbuminemia, are most likely a consequence of malabsorption6; however, in this case, gastrointestinal protein loss, systemic inflammation, or negative acute phase should also be considered. Other frequent changes include increased activity of liver enzymes such as alkaline phosphatase.6 Interestingly, the alkaline phosphatase activity in this patient was not increased, unlike aspartate transaminase, but hyperbilirubinemia was detected. We speculated that these changes could have been related to the systemic illness (decreased perfusion of the liver due to anemia, bouts of anorexia leading to hepatic lipidosis, and reactive hepatitis secondary to intestinal disease).

Feline colorectal epithelial adenomas and ACAs can be histologically classified as tubular, villous, tubulovillous, mucinous, or undifferentiated.3 This case was diagnosed as a tubular ACA. Tubular ACA is the most frequent variant (66% [33/50]), and the lack of tubular formation is associated with malignancy.3 Tubular ACAs are typically composed of columnar to cuboidal cells forming neoplastic ducts with stromal dysplasia and invasion of the submucosa and serosal lining.3 Secondary mucosal erosion or ulceration with inflammation and metastasis to the regional lymph nodes are common.3 Other metastatic sides include the peritoneum, lungs, and liver.7

The pathogenesis of intestinal ACA is complex. Comparative pathology and oncology studies encompassing humans and animal models aim to elucidate the intrinsic factors necessary for the presentation of this neoplasm. In humans, colorectal ACA arises from dysplastic epithelium progressing to neoplasia through various genetic mutations and intracellular enzyme accumulations in an adenoma-carcinoma sequence.8 The progression of neoplastic disease in humans has been associated with mutations of the adenomatous polyposis coli, TP53, and KRAS genes.3,8 Mutations in adenomatous polyposis coli and TP53 genes dysregulate β-catenin accumulation and p53 function, respectively.3,8 Another mechanism of human gastrointestinal carcinoma development is through serrated polyps.9 There are 2 proposed mechanisms by which these polyps can progress to neoplasia: the BRAF serrated pathway and the KRAS serrated pathway.9 The BRAF mutation can directly cause the formation of sessile serrated polyps and traditional serrated adenomas.9 In the KRAS serrated pathway, there is a KRAS mutation in colonic mucosa causing the development of the intestinal goblet cell hyperplastic polyp that leads to KRAS-mutated traditional serrated adenomas.9 The BRAF and KRAS induce traditional serrated adenomas to undergo WNT activation with p53 mutation to form colorectal carcinomas.9 Immunohistochemical assays of feline colorectal tumors have identified a CK20+/CDX2+ immunophenotype.3 CDX2 is a gene regulating intestinal homeostasis that has a weak negative correlation with malignancy.3 Contrasting with human ACA, nuclear β-catenin accumulation and p53 dysfunction are not associated with carcinoma development in cats.3 However, in a comparative study,2 through Sanger sequencing, alterations on CTNNB1 gene encoding β-catenin protein were described in cats, supporting that the Wnt/β-catenin signaling pathway has a role in feline intestinal neoplastic proliferation, as in dogs and humans. KRAS may contribute to carcinoma progression; however, its complete role has yet to be fully elucidated.3

Since feline ACA is locally invasive and metastatic, treatment options often rely on surgical excision and systemic chemotherapy.5 The viability of subtotal colectomies with adjuvant carboplatin in cats with ACA has indicated that the combination results in a median survival time of 269 days with mild chemotherapeutic toxicity.5 Adjuvant doxorubicin may also provide a survival advantage over subtotal colectomy alone (280 vs 56 days) in cats with colonic neoplasia.10 Nodal and distant metastasis has a negative prognostic factor.5 The placement of a colonic stent has provided a better quality of life postprocedure despite continued weight loss.11 However, euthanasia is usually elected 274 days later due to multiorgan failure.11

References

  • 1.

    Rissetto K, Villamil JA, Selting KA, Tyler J, Henry CJ. Recent trends in feline intestinal neoplasia: an epidemiologic study of 1,129 cases in the Veterinary Medical Database from 1964 to 2004. J Am Anim Hosp Assoc. 2011;47(1):2836. doi:10.5326/JAAHA-MS-5554

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Groll T, Schopf F, Denk D, et al. Bridging the species gap: morphological and molecular comparison of feline and human intestinal carcinomas. Cancers (Basel). 2021;13(23):5941. doi:10.3390/cancers13235941

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Uneyama M, Chambers JK, Nakashima K, Uchida K, Nakayama H. Histological classification and immuno-histochemical study of feline colorectal epithelial tumors. Vet Pathol. 2021;58(2):305314. doi:10.1177/0300985820974279

    • Search Google Scholar
    • Export Citation
  • 4.

    Patnaik AK, Liu SK, Johnson GF. Feline intestinal adenocarcinoma: a clinicopathologic study of 22 cases. Vet Pathol. 1976;13(1):110. doi:10.1177/030098587601300101

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Arteaga TA, McKnight J, Bergman PJ. A review of 18 cases of feline colonic adenocarcinoma treated with subtotal colectomies and adjuvant carboplatin. J Am Anim Hosp Assoc. 2012;48(6):399404. doi:10.5326/JAAHA-MS-5807

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Selmic LE, Selting KA, Reagan JK. Cancer of the gastrointestinal tract. Section G: intestinal tumors. In: Vail DM, Thamm DH, Liptak J, eds. Withrow and MacEwen’s Small Animal Clinical Oncology. 6th ed. Elsevier; 2020:432491.

    • Search Google Scholar
    • Export Citation
  • 7.

    Turk MA, Gallina AM, Russell TS. Nonhematopoietic gastrointestinal neoplasia in cats: a retrospective study of 44 cases. Vet Pathol. 1981;18(5):614620. doi:10.1177/030098588101800506

    • Search Google Scholar
    • Export Citation
  • 8.

    Leslie A, Carey FA, Pratt NR, Steele RJC. The colorectal adenoma-carcinoma sequence. Br J Surg. 2002;89(7):845860. doi:10.1046/j.1365-2168.2002.02120.x

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Pai RK, Bettington M, Srivastava A, Rosty C. An update on the morphology and molecular pathology of serrated colorectal polyps and associated carcinomas. Mod Pathol. 2019;32(10):13901415. doi:10.1038/s41379-019-0280-2

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Slawienski MJ, Mauldin GE, Mauldin GN, Patnaik AK. Malignant colonic neoplasia in cats: 46 cases (1990–1996). J Am Vet Med Assoc. 1997;211(7):878881.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Hume DZ, Solomon JA, Weisse CW. Palliative use of a stent for colonic obstruction caused by adenocarcinoma in two cats. J Am Vet Med Assoc. 2006;228(3):392396. doi:10.2460/javma.228.3.392

    • PubMed
    • Search Google Scholar
    • Export Citation
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