History
A 12-year-old 54.8-kg (120.6-lb) sexually intact female Huacaya alpaca (Vicugna pacos) was evaluated because of acute anorexia and suspected colic. The animal was recumbent, and physical examination revealed a lack of gastrointestinal sounds. The mucous membranes were pink; thoracic auscultation findings and rectal temperature were considered normal. Treatment was not effective, and 2 months after initial evaluation, blood samples were collected and analyzed with point-of-care hematologya and serum biochemicalb analyzers at the primary veterinarian's office. Clinicopathologic abnormalities included hypoproteinemia, hypoalbuminemia, hyponatremia, hyperkalemia, hypocalcemia (7.1 mg/dL; reference interval, 8.2 to 10.1 mg/dL), and hyperbilirubinemia. No definitive clinical diagnosis was made. Three months later (5 months after initial evaluation), the alpaca was euthanized by IV injection of pentobarbital owing to continued decline in condition. The carcass was submitted for necropsy.
Gross Findings
The animal was in poor nutritional condition with marked muscle wasting and serous atrophy of adipose tissue. There were scattered, 2- to 4-mm-diameter, translucent to opaque, white, firm plaques throughout the visceral pleura with scant pleural effusion. The abdomen was distended by 6 to 8 L of colorless, nonviscous fluid; there were many strands of easily exfoliated, pale yellow fibrin on the serosa. The mesentery of the intestinal tract, spleen, pancreas, and omentum were diffusely, irregularly thickened, firm, nodular, and cavitated. The serosa of the gastrointestinal tract was similarly altered (Figure 1) The capsular surfaces of the spleen and liver were multifocally thickened by interwoven, firm, white streaks of fibrosis. There was transmural thickening of the distal region of the jejunum, ileum, and colon with associated tan discoloration. The mucosal surface of the distal region of the jejunum and ileum was corrugated and multifocally covered by fibrin mats and contained discrete foci of mucosal loss and hemorrhage.
Photographs of the portion of the gastrointestinal tract of a Huacaya alpaca (Vicugna pacos) that was evaluated because of acute anorexia and suspected colic. A—View of the serosal surface of the spiral colon and aboral ileum (IL). There is multifocal fibrosis of the serosa with an interwoven network of firm, nonfriable, off-white streaks. Notice the multiple foci of pitting of the serosa and fibrosis (black arrows). Bar = 5 cm. B—View of the mucosal surface of the ileum. The mucosal surface is corrugated with multifocal areas of mucosal loss and associated hyperemia (white arrows). The serosa contains fibrosis and pitting (black arrow). Bar = 5 cm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.49
There were infrequent, 1.5-cm-long, red-and-white striped, thin threadlike nematodes, consistent with Haemonchus contortus, in the mucosa of the third stomach compartment. The mucosal surface of the aboral portion of the esophagus had multifocal to coalescent, 3-mm- to 2-cm-diameter off-white plaques.
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Segments of the mucosa, submucosa, muscularis, and serosa of the affected gastrointestinal tract were expanded by multiple, occasionally coalescent foci of a poorly demarcated, nonencapsulated, infiltrative proliferation of neoplastic epithelial cells amid a moderate fibrous to scirrhous stroma (Figure 2) The neoplastic cells were oval to polygonal with distinct borders. Just over half of the neoplastic cells were individualized with a peripheralized nucleus and cytoplasm distended by abundant pale basophilic mucin. The remainder of the neoplastic cells had small to moderate amounts of eosinophilic cytoplasm. The nuclei of the neoplastic cells were oval with moderately to densely stippled chromatin and 1 to 3 nucleoli. There was 1 mitotic figure/10 hpf (400×). The neoplastic cells and scirrhous stroma extended into the mesentery. There were areas of mucosal ulceration and necrosis with associated mixed neutrophilic, lymphoplasmacytic, and histiocytic infiltrates.
Photomicrographs of a section of the colon in the alpaca in Figure 1. A—The mucosa (Muc) of the colon contains multiple foci where the native tissue is replaced by disorganized neoplastic epithelial cells (asterisk). The underlying muscularis mucosa (mm) and submucosa (SM) have infiltrates of neoplastic cells that expand and partially obliterate the native tissue (arrows). A portion of the tunica muscularis (M) is visible. H&E stain; bar = 300 μm. B—Higher-magnification view of the boxed area in panel A. Neoplastic cells and associated scirrhous stroma have infiltrated and mostly obliterated the mucosa, muscularis mucosa, and submucosa. The neoplastic cells are largely individualized. H&E stain; bar = 120 μm. C—Higher-magnification view of the boxed area in panel B. Approximately half of the neoplastic cells have copious cytoplasmic basophilic mucin and peripheralized nuclei (signet-ring appearance [arrowheads]). H&E stain; bar = 80 μm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.49
Small foci of similar neoplastic cells and stroma were present throughout other areas of the mesentery, visceral peritoneum, and visceral pleura and scattered throughout the pulmonary interstitium (Figure 3) Other findings included ova from Nematodirus sp and strongyles detected during qualitative fecal examination and fungal organisms consistent with Candida sp identified in the esophageal mucosa on histologic examination.
Photomicrographs of a section of lung tissue. A—The lung tissue has multifocal microscopic interstitial metastases, which are visible as small foci wherein the interstitium is expanded with basophilic cells amid eosinophilic stroma (arrows). H&E stain; bar = 350 μm. B—Higher-magnification view of the boxed area in panel A. A focus of expanded interstitium contains ample eosinophilic stroma with embedded individualized neoplastic cells that have a signet-ring appearance (arrowheads). H&E stain; bar = 90 μm.
Citation: Journal of the American Veterinary Medical Association 257, 1; 10.2460/javma.257.1.49
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: signet-ring cell intestinal adenocarcinoma with peritoneal carcinomatosis, pulmonary metastasis and carcinomatosis, and severe fibrinous ascites in an alpaca.
Comments
For the alpaca of the present report, the differential diagnoses based on gross lesions included infection with Mycobacterium avium paratuberculosis (Johne disease), lymphoma, and disseminated adenocarcinoma. Histologic findings indicated that the lesions were neoplastic. The infiltrative neoplastic epithelial cells contained abundant cytoplasmic mucin, and greater than half appeared as a class ring would when viewed from the side, which is indicative of a signet-ring cell carcinoma (Figure 2). In humans, signet-ring cell carcinoma is associated with a particularly poor prognosis and aggressive phenoptype.1 There is no verified prognostic importance associated with this categorization in veterinary medicine.2 The pulmonary metastases in the alpaca of the present report were grossly subtle, highlighting the usefulness of a thorough gross examination and collection of a complete set of tissue specimens for histologic examination.
Neoplasia in New World camelids (NWCs) is reported at a frequency of 1.0% to 11%, with llamas approximately twice as likely to develop neoplasia as alpacas.3,4 In alpacas, lymphoma is the most commonly reported tumor.4,5 Alpacas develop T-cell or non-B-cell, non-T-cell lymphoma.6 There is a bimodal distribution of lymphoma in both alpacas and llamas: juvenile alpacas (< 2 years old) develop disseminated lymphoma, whereas adult alpacas develop multicentric disease or leukemia. Llamas < 7 years of age develop multicentric B-cell lymphoma, and llamas ≥ 7 years develop T-cell or non-B-cell, non-T-cell lymphoma.6 Uncommon cancers of alpacas include metastatic melanoma, such as osteogenic intraocular melanoma.3,7 Rhabdomyosarcoma in 1 alpaca has also been described.8
Although uncommon in NWCs, adenocarcinoma has been identified in the uterus, lungs, and mammary tissue of llamas.9–11 Results of 1 study4 of NWCs indicate that the mean age of onset of any carcinoma (12.36 years) is significantly higher than that for the more common lymphomas (4.24 years). In that study,4 only 6 of 72 NWCs with neoplasia had carcinomas that were not squamous cell in origin; 2 of those 6 carcinomas had a gastrointestinal location, including a single intestinal adenocarcinoma in a llama and a pancreatic adenocarcinoma in an alpaca. Gastric squamous cell carcinoma, which is usually rare in veterinary medicine, has been reported for several llamas.12
In general, intestinal adenocarcinomas are uncommonly reported in the veterinary medical literature. Development of intestinal adenocarcinomas in horses is rare and limited to older animals13,14; in cattle and sheep, it is infrequent but the incidence of intestinal adenocarcinoma increases with ingestion of bracken fern and herbicides.13 Dogs and cats typically develop large intestinal adenocarcinomas, which are usually treated by resection as opposed to radiation or chemotherapy.13 Excision is not often performed on larger animals, such as horses, because of, at least in part, the aggressive nature of the neoplasm.14
Intestinal ulceration and absorptive deficiency secondary to intestinal neoplasia likely led to hypoalbuminemia in the alpaca of the present report, and this in combination with carcinomatosis likely caused the observed ascites. Hypoproteinemia may have been complicated by H contortus infection, although the parasite load was subjectively not very high. The observed hyponatremia and hyperkalemia were probably attributable to the ascites. The measured hypocalcemia was most likely an artifact of the hypoalbuminemia, and the value was within the reference interval following application of either of the 2 commonly applied concentration correction formulas (formula 1, adjusted calcium concentration [mg/dL] = 3.5 – albumin concentration [g/dL] + measured calcium concentration [mg/dL]; formula 2, adjusted calcium concentration [mg/dL] = measured calcium concentration [mg/dL] – [0.4 × serum protein concentration {g/dL}] + 3.3). The hyperbilirubinemia was likely secondary to anorexia.
Disease of the digestive tract is the most frequent diagnosis in NWCs > 1 year of age, with parasitic disease being most common.15,16 Some prominent gastrointestinal parasites in NWCs include nematodes, trematodes, cestodes, and protozoa.17 The alpaca of the present report had H contortus infection as well as Candida infection. The mycotic esophagitis was interpreted to be a result of poor body condition and decreased immune competence secondary to the longstanding and severe systemic disease. Adenovirus infections are rare in camelids but have been reported to be associated with enteritis.18 Infections with enteric coronaviruses are also occasionally responsible for cachexia and diarrhea.19
Mycobacterium avium paratuberculosis, the causative agent of Johne disease, is a well-known infectious agent in sheep and cattle. This bacterium has reportedly infected NWCs, causing lesions similar to those associated with Johne disease in ruminants. Such cases are uncommon in NWCs and are more likely among younger animals.20 The clinical signs in alpacas with Johne disease include weight loss and diarrhea, although some infections can be subclinical.21 Johne disease was excluded in the case described in the present report on the basis of a lack of appropriate histopathologic lesions (granulomatous enteritis) and absence of acid-fast organisms on microscopic examination of feces and histologic examination of affected tissue sections.
The alpaca of the present report had a rare signet-ring cell carcinoma that led to carcinomatosis, severe ascites, and pulmonary metastases. The findings of carcinomatosis and pulmonary metastases suggested that this neoplasm may have spread through both direct seeding and lymphatic or vascular invasion. Digestive diseases of alpacas are common, but this particular neoplasm has seldom been described in the veterinary medical literature and, to the authors' knowledge, has not previously been described in an alpaca. Although intestinal adenocarcinoma and M avium paratuberculosis infection are uncommon in NWCs, they should both be considered as differential diagnoses for NWCs with clinical signs of weight loss, diarrhea, and enteritis, especially in association with segmentally thickened intestines. Intestinal adenocarcinoma should be considered for aged animals, and M avium paratuberculosis infection should be considered for young animals.
Footnotes
VetScan HM5, Abaxis Veterinary Services, Union City, Calif.
VetScan VS2, Abaxis Veterinary Services, Union City, Calif.
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