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Can Vet J. Dec 2010; 51(12): 1379–1382.
PMCID: PMC2978991
Clinical, ultrasonographic, and laboratory findings in 12 llamas and 12 alpacas with malignant round cell tumors
Jeanne M. Martin, Beth A. Valentine, and Christopher K. Cebra
Class of 2009 (Martin), Veterinary Diagnostic Laboratory and Department of Biomedical Sciences (Valentine), and the Department of Clinical Sciences (Cebra), College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331, USA
Address all correspondence to Dr. Beth Valentine; e-mail: Beth.Valentine/at/oregonstate.edu
Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings were evaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or was euthanized. Common clinical findings were anorexia, recumbency or weakness, and weight loss or poor growth. Peripheral lymphadenomegaly occurred in only 7 animals and was detected more often at necropsy than during physical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia, hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluid or tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or less prior to death or euthanasia was more common in animals ≤ 2 y of age (9/11) than in older animals (6/13). Regular examination of camelids to include clinical pathology and evaluation of peripheral lymph nodes may result in early detection of MCRT.
Résultats cliniques, ultrasonographiques et de laboratoire chez 12 lamas et 12 alpacas avec des tumeurs à cellules rondes malignes. Les signes cliniques, la durée de la maladie, les résultats clinicopathologiques et ultrasonographiques ont été évalués chez 12 lamas et 12 alpacas avec des tumeurs à cellules rondes malignes (TCRM). Tous les animaux, sauf 1, sont morts ou ont été euthanasiés. Les caractéristiques cliniques communes étaient l’anorexie, le décubitus ou la faiblesse et la perte de poids et une mauvaise croissance. La lymphadénomégalie périphérique s’est produite chez seulement 7 animaux et a été détectée plus souvent à la nécropsie que durant l’examen physique. Les anomalies clinicopathologiques courantes étaient l’hypoalbuminémie, l’acidose, l’azotémie, l’anémie, l’hyperglycémie et la neutrophilie. L’ultrasonographie a détecté des tumeurs chez 4 animaux sur 6. L’évaluation cytologique des échantillons de liquides ou de tissus prélevés par aspiration ou l’histopathologie des tissus des biopsies a donné lieu au diagnostic dans 5 cas sur 6. Une évolution clinique de 2 semaines ou moins avant la mort ou l’euthanasie était plus courante chez les animaux âgés de ≤ 2 ans (9/11) que chez les animaux plus âgés (6/13). Un examen régulier des camélidés afin d’inclure une pathologie clinique et l’évaluation des ganglions lymphatiques périphériques pourra se traduire par un dépistage précoce de TCRM.
(Traduit par Isabelle Vallières)
The classification of malignant round cell tumors (MRCT) includes lymphoma, neuroblastoma, Ewing’s sarcoma, rhabdomyosarcoma, and primitive neuroectodermal tumor (15). The MRCT reported in llamas and alpacas are lymphoma (616) and a primitive malignant round cell tumor (PMRCT), considered to be a primitive neuroectodermal tumor (10,12). Most reports are of a single case (7,9,11,15) or small series of cases (6,8,12,14,16). The purpose of this and the prior pathology report based on this population (10) was to characterize MRCT in a large series of cases. These tumors frequently occur at a young age in humans (1,2,4,17), and are also common in camelids 2 y of age or less (6,814,16). The age of diagnosis of MRCT in this study population was significantly less in alpacas (mean 3.1 y; range: 0.21 to 11 y) than in llamas (mean 8.0 y; range: 0 to 23 y) (10). Tumor distribution was most commonly multicentric, involving both abdominal and thoracic cavities or multiple peripheral lymph nodes, but tumors confined to organs of the abdomen or of the thorax, primary gastric tumors, and a focal subcutaneous tumor were also identified (10).
Reports of chemotherapy for MRCT in camelids are rare (6). It is anticipated that chemotherapeutic approaches for camelids with MRCT will continue to be explored, and early detection of neoplasia will be important. The purpose of this retrospective study was to identify clinical, laboratory, and ultrasonographic findings in a large series of llamas and alpacas with MRCT, and to compare findings in llamas and alpacas.
A retrospective study of the database of the Oregon State University (OSU) Veterinary Diagnostic Laboratory from 1991 to 2008 was conducted to identify animals with a pathologic diagnosis of lymphoma or malignant round cell tumor. Detailed pathologic findings have been reported (10). A pathologic diagnosis of MRCT (12 B-cell lymphoma, 6 T-cell lymphoma, 6 PMRCT) was made in 12 llamas and 12 alpacas (10 males and 13 females; gender of 1 animal was not reported) (10). Seven of 8 animals admitted to the OSU Veterinary Teaching Hospital for treatment died or were euthanized. All 16 animals that were treated by referring veterinarians or owners died or were euthanized. The medical histories of all cases were examined and signalment, history, clinical signs, and ancillary test procedures and results were recorded.
Clinical signs observed prior to diagnosis of MRCT were extremely variable. Common findings are summarized in Table 1. The most common presenting complaints were anorexia, recumbency or weakness, and weight loss or poor growth. One 4-year-old alpaca that was examined due to a large soft tissue mass in the ventral cervical area had no other clinical signs of disease. Peripheral lymphadenomegaly was detected on physical examination in 4 animals.
Table 1
Table 1
History and physical findings in 22a camelids with MRCT
The clinical course was also variable, ranging from sudden death (2 animals), to a clinical course of 1 d (3 animals), 2 wk (10 animals), and longer than 2 wk (9 animals). Among 11 animals ≤ 2 y old that were diagnosed with MRCT, only 2 had a clinical course that lasted longer than 2 wk. Of 13 animals that were > 2 y old, 7 had a clinical course that lasted longer than 2 wk. Animals with gastric MRCT were often older animals (mean 7.2 y) and presented with severe clinical signs; all died or were euthanized within 1 wk of onset of signs. The 4-year-old alpaca with a focal cervical mass was still alive 20 mo after the diagnosis of PMRCT.
Diagnostic procedures including complete blood (cell) count, serum chemistry panel, and blood gas analysis were performed on approximately half of the animals — abnormalities are summarized in Table 2. The most common findings were hypoalbuminemia, acidosis, anemia, azotemia, increased serum gamma-glutamyl transferase (GGT) activity, and hyperglycemia. Lymphocytosis was detected in only 1 animal, a 2-year-old male alpaca with PMRCT. Hypoglycemia was detected in 2 animals and both animals died within 2 d of veterinary examination. Azotemia was a common finding in this study, but renal neoplasia was found in only 1 of these cases. High serum AST activity occurred in 2 animals with neoplasia involving the gastrointestinal tract and in 1 animal with a tumor involving the liver. Increase in serum GGT activity was found in 5 animals, 3 of which had neoplasia involving the liver, and 2 of which had involvement of the gastrointestinal tract.
Table 2
Table 2
Clinicopathologic findings in camelids with MRCT
Abdominal or thoracic ultrasound on 6 animals resulted in diagnostic findings in 4 animals. Hepatomegaly was detected by ultrasonography in 2 animals and examination of ultrasound-guided biopsy samples revealed MRCT in both cases. A mass adjacent to the liver was detected by ultrasonography in 1 case and confirmed to be MRCT following necropsy. Thoracic ultrasound revealed pleural effusion confirmed to be MRCT based on cytologic findings in 1 animal. Abdominal ultrasound examination failed to identify gastric neoplasia in 1 case and ultrasound examination of the urinary tract did not detect neoplasia within liver, lymph nodes, and thoracic duct in another case. Cytologic evaluation of fluid or mass aspirates was performed on 5 animals and was diagnostic for MRCT in 4 cases. Biopsy samples of peripheral lymph nodes or liver were evaluated from 5 animals and revealed MRCT in all cases. In total, 5 animals were diagnosed with MRCT prior to death or euthanasia, and 1 animal diagnosed with PMRCT by needle biopsy evaluation of a cervical mass was still alive 20 mo after diagnosis.
Treatments were varied. Five animals received anthelminthic therapy and 8 received antibiotics. Two animals were treated with corticosteroids with temporary abatement of signs, followed by progression to death. Seven animals received fluid therapy with electrolytes, either by mouth or by slow intravenous administration. One severely anemic animal was given a blood transfusion. Other treatments included antacids, H-2 blockers, anti-inflammatory medications, insulin, diuretics, and oxyglobin. None were treated with chemotherapy.
This study and previous studies indicate that camelids with MRCT can present with a variety of clinical signs and laboratory findings, and that the clinical course is variable (69,11,12,15). Tumors occur at all ages and many affected animals are less than 4 y of age. Tumors are particularly common in young alpacas. No other significant differences between alpacas and llamas were detected.
As in prior reports, presenting complaints in this study included anorexia, weight loss, weakness, and respiratory distress (69,11,12,15). Peripheral lymphadenomegaly was the most specific finding, and palpable lymphadenomegaly was detected in 9 of 10 camelids with MRCT in a prior study (6). In the current study population lymphadenomegaly was detected clinically in only 4 cases, but was detected at necropsy in 7 animals (10). Findings indicate that careful clinical evaluation of peripheral lymph nodes is an important part of camelid physical examination.
Clinicopathologic abnormalities were most often non-specific (18,19). Azotemia only rarely reflected renal neoplasia, and increase in serum GGT or aspartate aminotransferase (AST) occurred in animals with neoplasia involving the gastrointestinal tract as well as in animals that had tumor in the liver. Hypokalemia was a common finding, which most likely reflects anorexia (18). Hyperglycemia was also common, but camelids are very prone to stress hyperglycemia (18), and an increased serum glucose level is not considered to be related to underlying MRCT in these cases. Low serum glucose levels are significant, and the 2 animals with hypoglycemia died within 2 d of examination. These animals had extensive hepatic neoplasia. Hypoglycemia associated with MRCT may be an indicator of a poor prognosis, but additional studies are needed. Hypercalcemia may be associated with lymphoma (20), but was not detected in any case. Lymphocytosis was detected in only 1 animal in this study and in 3 animals in previous studies (6,9,15), suggesting that lymphocytosis is uncommon in camelids with MRCT. Cattle with bovine leukemia virus associated lymphoma often have persistent lymphocytosis (20). There has been no evidence of a viral cause of lymphoma in camelids, and the variety of cell types of MRCTs in camelids (B-cell lymphoma, T-cell lymphoma, and PMRCT) does not support a viral cause for MRCT in these species.
Ultrasonography of 6 animals in this study detected evidence of neoplasia in 4 cases but did not detect masses in 1 animal with gastric lymphoma, or in 1 with multicentric lymphoma. The cranial location of gastric neoplasia, particularly that involving compartment 1, may make ultrasonographic detection of gastric MRCT difficult. Cytologic evaluation of thoracic or abdominal fluid was diagnostic in 3 of 4 cases examined in this study. Cytologic evaluation of enlarged peripheral lymph nodes was performed in 2 cases and provided a diagnosis of MRCT in both cases. Cytologic evaluation of thoracic, abdominal, or cerebrospinal fluid was reported to be diagnostic in 4 previous cases of MRCT in camelids (6,7,11,15). Biopsy of enlarged lymph nodes or liver resulted in diagnosis of MRCT in 5/5 cases. Results of the current study and previous studies indicate that ultrasonographic examination and cytologic evaluation of fluid, peripheral lymph nodes, or masses, and evaluation of biopsy samples of liver or other involved organs are useful for diagnosis of MRCT in camelids.
Animals up to 2 y of age often had a course of clinical disease of ≤ 2 wk. In humans, MRCT of childhood often has a poor prognosis, and tumors often metastasize quickly (5,21). This study suggests that MRCT affecting camelids up to 2 y of age is associated with a worse prognosis than MRCT in older camelids, but additional studies are needed.
The rapid clinical course seen in most of the animals, and the size of the masses found on necropsy, suggest that many of the animals were in an advanced stage of disease before they showed clinical signs. It is more effective to diagnose MRCT in camelids based on physical and diagnostic findings than from clinical signs. To date, only Cebra et al (6) have reported results of chemotherapy in a camelid. The case was a 1-year-old llama with a diagnosis of lymphoma. The animal showed improvement for 1 d, then rapidly deteriorated. The likelihood of effective chemotherapy will be increased by early tumor detection.
Based on results of this study, a yearly physical examination in adult camelids, and more frequent examination of camelids up to 2 y of age, are recommended, as this should increase the likelihood of detecting disease early in its course. Physical examination should include a thorough palpation to detect peripheral lymphadenomegaly. Mandibular and inguinal lymph nodes in particular should be examined. Routine clinicopathologic studies may not reveal a specific change, but will provide indicators of the overall health status of the animal, and should be included in the regular physical examinations. If abnormalities are detected, especially hypoalbuminemia, anemia, leukocytosis, abnormal liver or kidney values, or leukocytosis, thoracic or abdominal ultrasound may be warranted. The liver is often involved in camelids with MRCT (6,10), and careful ultrasonographic evaluation of this organ is recommended. If abnormalities consistent with neoplasia are detected with diagnostic imaging, biopsy or cytologic evaluation of the lesions should be done. Abdominal or thoracic effusions should be evaluated cytologically. In cases of MRCT, immunophenotyping with specific antibodies for B-cells, T-cells and, when indicated, primitive neuroectodermal cells should be performed. Early detection of MRCT and accurate determination of tumor cell type may allow for development of chemotherapeutic regimens for treatment of MRCT in llamas and alpacas. CVJ
Footnotes
This study was supported in part by the Merck-Merial Veterinary Scholars Program.
Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office (hbroughton/at/cvma-acmv.org) for additional copies or permission to use this material elsewhere.
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