013_5357_SA(09_79Clinical).indd

CVJ / VOL 51 / DECEMBER 2010

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Article

Clinical, ultrasonographic, and laboratory findings in 12 llamas and

12 alpacas with malignant round cell tumors

Jeanne M. Martin, Beth A. Valentine, Christopher K. Cebra

Abstract — 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.

Résumé — 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)

Can Vet J 2010;51:1379–1382

Introduction

he classification of malignant round cell tumors (MRCT)

includes lymphoma, neuroblastoma, Ewing’s sarcoma,

rhabdomyosarcoma, and primitive neuroectodermal tumor

(1–5). The MRCT reported in llamas and alpacas are lymphoma

(6–16) 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 pathol-

ogy 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 (6,8–14,16). 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

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@oregonstate.edu
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@cvma-acmv.org) for additional copies or permission to use this material elsewhere.

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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.

Materials and methods

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.

Results

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.

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 ani-

mals # 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 neo-

plasia 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.

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 ultra-

sound revealed pleural effusion confirmed to be MRCT based

on cytologic findings in 1 animal. Abdominal ultrasound exami-

nation failed to identify gastric neoplasia in 1 case and ultra-

sound 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

Table 1. History and physical findings in 22

camelids with MRCT

History

Number of animals % of total

Anorexia

Recumbency/weakness

Weight loss/poor growth

Lymphadenomegaly/subcutaneous mass 5

Dyspnea

Recent abortion

Abnormal stool

Data not provided in 2 cases.

Table 2. Clinicopathologic findings in camelids with MRCT

Number of

Finding

animals tested

animals affected

% of total

Hypoalbuminemia

Acidosis

62.5

Hypercreatininemia

Anemia

Hyperglycemia

Increase in BUN

Neutrophilia

Hypoproteinemia

Increase in GGT

Leukocytosis

Hypokalemia

Increase in AST

Hypoglycemia

Lymphocytosis

12.5

Hyperproteinemia

CVJ / VOL 51 / DECEMBER 2010

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administration. One severely anemic animal was given a blood

transfusion. Other treatments included antacids, H-2 blockers,

anti-inflammatory medications, insulin, diuretics, and oxyglo-

bin. None were treated with chemotherapy.

Discussion

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 (6–9,11,12,15).

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 dis-

tress (6–9,11,12,15). 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 evalua-

tion 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 gastrointes-

tinal 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 under-

lying 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 neo-

plasia. Hypoglycemia associated with MRCT may be an indi-

cator 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 cam-

elids 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 involv-

ing 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 evalua-

tion 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 exami-

nation 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 cam-

elids with MRCT (6,10), and careful ultrasonographic evalua-

tion 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 accu-

rate determination of tumor cell type may allow for development

of chemotherapeutic regimens for treatment of MRCT in llamas

and alpacas.

CVJ

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