Conference 01 - 2012 Case: 01 20120919

Signalment:

15-year-old female alpaca, (Lama pacos).The patient presented with a history of 2 weeks loss of appetite, apathy and weight loss. An intra-abdominal neoplasia was suspected at ultrasound examination.

Gross Description:

The alpaca was in a poor body condition. At necropsy, in the second compartment of the stomach (C2), there was a 30x20x15 cm, non-encapsulated, infiltrative, and relatively well demarcated mass which on cut surface contained abundant fibrous connective tissue. The mucosa was focally, extensively ulcerated and covered by a thick layer of necrotic material and pus. In the mesentery and intestinal serosa, there were multiple white nodules of firm consistency, approximately 1x1x1cm size. White nodules were also present within the liver capsule and parenchyma, approximately 1.5x1x1cm size. In the colon and third compartment of the stomach (C3), there were multiple chronic mucosal ulcerations. The abdomen and thorax contained approximately 500 ml of red, transparent (serosanguinous) fluid.

Histopathologic Description:

Stomach, C2: The wall of C2 is severely disrupted by an ulcerated, infiltrative growing, non-encapsulated, poorly demarcated, densely cellular neoplasm, projecting from the mucosa and extending transmurally to the serosa, consisting of islands, nests and anastomosing cords of neoplastic epithelial cells separated by a moderate to large amount of fibrovascular stroma. The cells are polygonal, up to 30μm in diameter with abundant eosinophilic to amphophilic fibrillar cytoplasm with a large vesicular, central oval nucleus and prominent, single to multiple nucleoli. Some nests of neoplastic cells exhibit gradual individual cell keratinization, prominent concentrically lamellated keratin pearls, or contain cellular debris admixed with inflammatory cells, mainly lymphocytes and degenerate neutrophils. Intercellular bridges between keratinized cells are prominent. There are approximately 5 mitoses per 400x field with frequent bizarre mitotic figures. There is severe anisocytosis and anisokaryosis. Multifocally within the neoplasm there are large areas of necrosis, hemorrhage and a mixed inflammatory infiltrate of lymphocytes, plasma cells, neutrophils and some macrophages. Many submucosal and subserosal vessels contain clusters of neoplastic cells (tumor emboli) as well as fibrin thrombi. Overlying the ulcerated mucosa, there is abundant fibrillar eosinophilic material (fibrin exudation) and hemorrhage, admixed with cellular and karyorrhectic debris (necrosis) and bacterial colonies. Throughout the mass, but especially along the serosa, there are multiple nodules or bands of abundant fibrous connective tissue (scirrhous response).

Morphologic Diagnosis:

C2: Gastric squamous cell carcinoma.

Condition:

Squamous cell carcinoma

Contributor Comment:

This was an interesting case of a rare presentation of gastric squamous cell carcinoma (SCC) with carcinomatosis and metastases to the liver and mesenteric lymph nodes in an alpaca.

There are numerous reports of neoplasia in South American camelids, including lymphoma, urogenital tumors, cutaneous and mucocutaneous neoplasia, oral, intraocular, gastrointestinal, pulmonary, neuroendocrine and brain neoplasia (Table 1).(5)

Gastric squamous cell carcinoma in ruminants is usually quite rare and only few have been reported in llamas and alpacas.(3,5) However, in a 5 year (2001-2006) study at Oregon State University it was reported that cutaneous and mucocutaneous squamous cell carcinoma (SCC) was the most frequent malignant neoplasm identified, although in previous studies lymphoma was most commonly reported.(5)

Histologically, C1 and portions of C2 are composed of non-keratinized stratified squamous epithelium, whereas the rest of C2 and all of C3 have a mucinous glandular epithelium.

In previous cases, neoplastic cells most commonly originated from squamous mucosal epithelium of compartments 1 and 2, but it could arise also from the glandular mucosa of compartment 3.(3) In this case, the neoplasm was most closely related to the stratified squamous epithelium of C2. SCC of glandular mucosa could derive from metaplasia of glandular epithelium, from growth of heterotopic squamous cell rests, or from multipotent cells of the crypt gland base, as suggested in prevous reports in dogs.(3)

Commonly described sites of metastases are the liver, diaphragm, mesentery, and myocardium. The mode of metastatic spread is by implantation and vascular dissemination, as seen in horses with gastric SCC.(3)

Several factors have been associated with the development of gastric papillomas and squamous cell carcinomas in humans and other species including host, dietary, genetic, environmental conditions and infectious agents. In cattle, papillomas of the esophagus and reticulorumen are caused by bovine papillomavirus 4 (BPV-4), whereas fibropapillomas of the esophagus, esophageal groove and rumen are caused by bovine papillomavirus (2). It is very seldom for viral particles to be seen in the tumor. Malignant neoplasia of bovine esophagus and forestomach is extremely rare.(2,3) On the contrary, SCC involving male and female genitalia, ocular and periocular tissue and stomach is most commonly reported in the horse. Equine gastric SCC metastasized most frequently to retropharyngeal lymph nodes.(4)

The frequency of llamas and alpacas as patients in the veterinary hospital is increasing; therefore it is important to improve the knowledge about possible lesions, prevalence and predisposing factors causing diseases in these animals. Table 1. Summary of 40 tumors reported in 20 llamas and 18 alpacas between 2001-2006 at Oregon State University.(5)

Tumor type		Total no. tumors	Alpacas (no.)	Llamas (no.)	Mean age alpacas (yrs)*	Mean age llamas (yrs)	Location(s)
Fibroma/fibropapilloma		12	8	2	5.6	11.5	Face; nose; lips; dista limb; gingiva; hard palate
Carcinoma
	Cutaneous Ocular Mammary Un-differentiated	4 2 2 1	0 1 0 1	4 1 2 0	-- U -- 12	13.5 14 17 --	Perineum trunk; limb 3rd eyelid Metastatic to local lymph node; disseminated Disseminated
Adenocarcinoma
	Biliary Pancreas Intestine	2 1 1	0 1 0	2 0 1	-- 10 --	10.5 -- 8	Disseminated Disseminated Disseminated
Lymphoma		5	4	1	1.5	15	Disseminated
Fibrosarcoma		4	1	3	6	13	Lips; gingiva; maxilla; cornea
Lipoma		2	0	2	--	12	Mesentery; subcutis
Melanocytoma		1	0	1	--	11	Pectoral skin
Leiomyosarcoma		1	0	1	--	12	Uterus
Interstitial cell tumor		1	1	0	9	--	Ovary
Primitive stromal tumor		1	1	0	U	--	Testis
* U = unknown

JPC Diagnosis:

C2: Squamous cell carcinoma.

Conference Comment:

The contributor provided a very good characterization of squamous cell carcinomas (SCC) in alpacas, as well as comparisons to other species such as the horse, in which SCC is the most common gastric tumor. Conference participants readily agreed upon the diagnosis; however, during the discussion a question was raised regarding histological determination of the location of the specimen (C2).

Following is a brief summary of new world camelid gastric anatomy and histology: As the contributor described, new world camelid stomachs are composed of three compartments :C1, C2, and C3, which are sometimes referred to as the proximal compartment (PC), intermediate compartment (IC) and the distal compartment (DC), respectively. C1 is often compared with the rumen, and constitutes the largest chamber (comprising approximately 83% of the gastric volume). C2 is somewhat kidney-shaped and is the smallest of the three compartments. C3 is tubular and elongated and accounts for approximately 11% of the gastric volume. Histologically the majority of C1 is nonglandular, covered by stratified squamous epithelium which is supported by a dense collagenous lamina propria. This tissue is arranged in folds (rather than papillae as in ruminants) which are more prominent when the stomach is contracted. Smaller, more ventral portions of C1 (known as cranial and ventral glandular saccules) are lined by columnar epithelium and deep tubular glands which are supported by a smaller amount of looser connective tissue. C1 communicates with C2 through the ventricular furrow. C2 has thick walls, and histologically is divided into two regions: a dorsal nonglandular and a ventral glandular portion, each of which are similar to those described for C1. Lymphoid tissue may be found in the lamina propria of the glandular portions of C2. The muscularis mucosae is absent in the nonglandular regions of both C1 and C2, and is present in glandular areas, but is incomplete. C2 communicates with C3 via the channel of isthmus, a small tubular continuation of the ventricular furrow that is lined by stratified epithelium. C3 is otherwise covered by a glandular mucosa, with 3 regions differing histologically: the proximal region has abundant lymphoid tissue in the mucosa and submucosa; the central region has simple mucous-secreting tubular glands; and the caudal region has fundic glands in the ventral portion and simple tubular glands in the dorsal (pyloric) region. C3 has a well-developed muscularis mucosae and a thin submucosa. Surrounding all three gastric compartments is a muscularis comprised of inner circular and outer longitudinal layers. (1)

References:

1. Alzola RH, Ghezzi MD, Gimeno EJ, et al. Topography and morphology of the llama (Lama galma) stomach. Int J Morphol. 2004;22 (2):155-164.
2. Mckenzie EC, Mills JN, Bolton JR. Gastric squamous cell carcinoma in three horses. Aust Vet J. 1997;75(7):480-483.
3. Sartin EA, Waldridge BM, Carter DW, et al. Gastric squamous cell carcinoma in three llamas. J Vet Diagn Invest. 1997;9:103-106.
4. Schuh JCL. Squamous cell carcinoma of the oral, pharyngeal and nasal mucosa in the horse. Vet Pathol. 1986;23:205-207.
5. Valentine BA, Martin JM. Prevalence of neoplasia in llamas and alpacas (Oregon State University, 2001-2006). J Vet Diagn Invest. 2007;19:202-204.