Signalment:  

10-year-old, female Alpaca (Lama pacos)Alpaca had been healthy until last month, had a successful pregnancy the past year. Started with anorexia, and lethargy with rapid weight loss over the last 2 weeks.


Gross Description:  

Mass within small intestine (jejunum) and small circular white nodules in liver.


Histopathologic Description:

Received 2 fragments of tissue, one a section of liver 5 x 5 cm and the other a fragments of small intestinal tract 16 cm long with attached mesentery. The section of liver has a multifocal infiltrate of neoplastic cells throughout the hepatic parenchyma (not included on the slides). The intestinal sections reveal the origin of the tumor within the mucosa on the majority of the slides. The cells exhibit marked anisokaryosis and have large oval open vesicular nuclei with a variable mitotic rate. This rate is highest in the sections of the mucosa that have the neoplastic process. Necrosis is common to the center of the masses present throughout the supporting mesentery and within the muscle layers. There is a connective tissue reaction within the supporting mesentery and cells in this area vary from nodular masses to individual cells within the connective tissue stroma. A mucinous matrix is apparent mainly with in the supporting mesentery. The cells extend full thickness through the submucoas, muscle layers, serosal surfaces and within the mesentery.


Morphologic Diagnosis:  

Intestinal adenocarcinoma poorly differentiated; jejunum.


Condition:  

Intestinal adenocarcinoma


Contributor Comment:  

Tumors in llamas and alpacas are reported to be relatively rare.5 There are few reported cases in the literature and although this may reflect the population of alpacas in North America, it may also reflect inherent differences within the immune system of New World camelids as compared to other species.

Small intestinal primary epithelial tumors are rare in most species, and in man are more likely to be benign rather than malignant. Extensive research has been done on colonic neoplasia or colorectal neoplasia in man including identification of genetic alterations, familial tendencies and chromosomal abnormalities. The low number of small intestinal adenocarcinomas has precluded this type of evaluation. In man the majority of small intestinal adenocarcinomas can be surgically resected with substantial benefits in terms of 5-year survival. 1

In domestic animals the small intestinal adenocarcinomas are also considered to be rare, but cats do tend to have mid-jejunal and ileocecal origins for this tumor at a higher rate than the other domestic species. Tumors are classified as adenocarcinoma, mucinous, undifferentiated or solid, and signet ring carcinomas.

In the cat, surgical excision of the tumors yields a reasonable prognosis.2


JPC Diagnosis:  

1. Small intestine; mesentery: Carcinoma, anaplastic, alpaca (Lama pacos), camelid.
2. Small intestine: Enteritis, necrotizing, acute, diffuse, severe, with fibrin, hemorrhage, edema, vasculitis, and fibrin thrombi.


Conference Comment:  

According to the World Health Organization International Histological Classification of Tumors of the Alimentary System of Domestic Animals3, there are six categories of malignant intestinal epithelial neoplasia in domestic animals: Acinar adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, undifferentiated carcinoma, and adenosquamous carcinoma.

Adapted from WHO classification of malignant intestinal epithelial neoplasia3
Type of NeoplasmCharacteristic Histologic Features
Acinar adenocarcinomaVariably sized acinar structures replacing intestinal mucosa, arise from hypercellular crypts, infiltrate submucosa and musclular layers, tumor cells may contain occasional goblet cells. In colon, infiltrates Peyer's patches at the primary site
Papillary adenocarcinomaPapillary projections lined by multiple layers of anaplastic columnar cells with little stroma, may have cribriform pattern, mostly intraluminal
Mucinous adenocarcinomaAcinar or irregular crypts filled or distended with mucin replacing the mucosa, mostly goblet cells are seen, infiltrates intestinal wall and mesentery, mostly annular lesions
Signet ring cell carcinomaSignet-ring cells characterized by mucin-filled cytoplasm and peripheralized crescent-shaped nuclei, replace mucosa, infiltrate bowel wall, severe desmoplasia, rare multinucleated cells, must differentiate from adenocarcinoid (which contains neuroendocrine and signet-ring cells)
Undifferentiated carcinomaSolid sheets of large anaplastic or pleomorphic cells with little stroma, desmoplasia, may be rare mucin or signet-ring cells
Adenosquamous carcinomaGlandular forming adenocarcinoma with areas replaced by squamous cells with varying degrees of keratinization

A recent review of neoplasia in llamas and alpaca conducted by Valentine et. al.6 indicated that although the overall prevalence of neoplasia was higher in llamas, the mean age of affected alpacas was significantly lower. The most common malignant neoplasm in camelids was cutaneous and mucocutaneous squamous cell carcinoma with lymphoma being the second most common.6

In intestinal adenocarcinoma cells of sheep, there is altered expression of β-catenin, E-cadherin, cycloxygenase-2, and p53 protein.4 The rates of these altered expressions were lower than that of corresponding rates in human colonic neoplasms, but these findings suggest the use of sheep as potential animal models.4 β-catenin is a component of the WNT signaling pathway, and increased concentrations of this protein promote genes that regulate the cell cycle.4 Neoplasm dedifferentiation, invasion and metastasis are promoted by the loss of E-cadherin.4 COX-2 is often found in increased levels in colonic neoplasm, although the influence it has on tumor behavior is currently under investigation.4 p53 protein is one of the key regulators of cell cycle regulation and apoptosis.4


References:

1. Crawford James M. The gastrointestinal tract: Tumors of the small and large intestine. In: Robbins Pathologic basis of disease. 6th Edition Cotran RS; Kumar V; Collins T. pp 826-835. WB Saunders Co. 1999.
2. Head KW, Else RW, Dubielzig RR. In: Tumors in domestic animals. Ed. Meuten DJ. Chapter 8. Tumors of the intestine pg 461-467. Iowa State Press, 2002.
3. Head KW, Cullen JM, Dubielzig RR, Else RW, Misdorp W, Patnaik AK, Tateyama S, van der Gaag I: Histological Classification of Tumors of the Alimentary System of Domestic Animals, 2nd series, vol. X, pp. 89-94. Armed Forces Institute of Pathology, Washington, DC, 2003
4. Munday JS, Brennan MM, Kiupel M: Altered expression of β-catenin, E-cadherin, cycloxygenase-2, and p53 protein by ovine intestinal adenocarcinoma cells. Vet Pathol 43:613-621, 2006
5. Sartin EA, Crowe DR, Whitley EM, Treat RE Jr, Purdy SR, Belknap EB: Malignant neoplasia in four alpacas. J Vet Diagn Invest 16:226-229, 2004
6. Valentine BA, Martin JM: Prevalence of neoplasia in llamas and alpacas (Oregon State University, 2001-2006). J Vet Diagn Invest 19:202-204, 2007

A virtual slide is not available for this case.



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