Alpaki ultrasonografia, Publikacje naukowe
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//-->ArticleClinical, ultrasonographic, and laboratory findings in 12 llamas and12 alpacas with malignant round cell tumorsJeanne M. Martin, Beth A. Valentine, Christopher K. CebraAbstract —Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings wereevaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or waseuthanized. 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 duringphysical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia,hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluidor tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or lessprior 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 resultin early detection of MCRT.Résumé —Résultats cliniques, ultrasonographiques et de laboratoire chez 12 lamas et 12 alpacas avec destumeurs à cellules rondes malignes.Les signes cliniques, la durée de la maladie, les résultats clinicopathologiqueset 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 communesétaient l’anorexie, le décubitus ou la faiblesse et la perte de poids et une mauvaise croissance. La lymphadénomégaliepériphérique s’est produite chez seulement 7 animaux et a été détectée plus souvent à la nécropsie que durantl’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 destissus des biopsies a donné lieu au diagnostic dans 5 cas sur 6. Une évolution clinique de 2 semaines ou moinsavant la mort ou l’euthanasie était plus courante chez les animaux âgés de#2 ans (9/11) que chez les animauxplus âgés (6/13). Un examen régulier des camélidés afin d’inclure une pathologie clinique et l’évaluation desganglions lymphatiques périphériques pourra se traduire par un dépistage précoce de TCRM.(Traduit par Isabelle Vallières)Can Vet J 2010;51:1379–1382TIntroductionhe 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 ofcases (6,8,12,14,16). The purpose of this and the prior pathol-ogy report based on this population (10) was to characterizeMRCT in a large series of cases. These tumors frequently occurat a young age in humans (1,2,4,17), and are also common incamelids 2 y of age or less (6,8–14,16). The age of diagnosis ofMRCT 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 commonlyClass of 2009 (Martin), Veterinary Diagnostic Laboratory and Department of Biomedical Sciences (Valentine), and the Departmentof 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.eduThis 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 CVMAoffice (hbroughton@cvma-acmv.org) for additional copies or permission to use this material elsewhere.CVJ / VOL 51 / DECEMBER 20101379Table 1.History and physical findings in 22acamelids with MRCTHistoryAnorexiaRecumbency/weaknessWeight loss/poor growthLymphadenomegaly/subcutaneous massDyspneaRecent abortionAbnormal stoolaTable 2.Clinicopathologic findings in camelids with MRCTFindingHypoalbuminemiaAcidosisHypercreatininemiaAnemiaHyperglycemiaIncrease in BUNNeutrophiliaHypoproteinemiaIncrease in GGTLeukocytosisHypokalemiaIncrease in ASTHypoglycemiaLymphocytosisHyperproteinemiaNumber ofanimals tested128121312128121213121212812Number ofanimals affected1057766455543211% of total8362.5585450505042423833251712.58Number of animals8765422% of total363227211899A R T I C LEData not provided in 2 cases.multicentric, involving both abdominal and thoracic cavities ormultiple peripheral lymph nodes, but tumors confined to organsof the abdomen or of the thorax, primary gastric tumors, and afocal subcutaneous tumor were also identified (10).Reports of chemotherapy for MRCT in camelids are rare (6).It is anticipated that chemotherapeutic approaches for camelidswith MRCT will continue to be explored, and early detection ofneoplasia will be important. The purpose of this retrospectivestudy was to identify clinical, laboratory, and ultrasonographicfindings in a large series of llamas and alpacas with MRCT, andto compare findings in llamas and alpacas.Materials and methodsA retrospective study of the database of the Oregon StateUniversity (OSU) Veterinary Diagnostic Laboratory from 1991to 2008 was conducted to identify animals with a pathologicdiagnosis of lymphoma or malignant round cell tumor. Detailedpathologic findings have been reported (10). A pathologicdiagnosis of MRCT (12 B-cell lymphoma, 6 T-cell lymphoma,6 PMRCT) was made in 12 llamas and 12 alpacas (10 males and13 females; gender of 1 animal was not reported) (10). Seven of8 animals admitted to the OSU Veterinary Teaching Hospitalfor treatment died or were euthanized. All 16 animals thatwere treated by referring veterinarians or owners died or wereeuthanized. The medical histories of all cases were examined andsignalment, history, clinical signs, and ancillary test proceduresand results were recorded.ResultsClinical signs observed prior to diagnosis of MRCT wereextremely variable. Common findings are summarized inTable 1. The most common presenting complaints wereanorexia, recumbency or weakness, and weight loss or poorgrowth. One 4-year-old alpaca that was examined due to a largesoft tissue mass in the ventral cervical area had no other clinicalsigns of disease. Peripheral lymphadenomegaly was detected onphysical examination in 4 animals.The clinical course was also variable, ranging from suddendeath (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 aclinical course that lasted longer than 2 wk. Of 13 animals thatwere.2 y old, 7 had a clinical course that lasted longer than2 wk. Animals with gastric MRCT were often older animals(mean 7.2 y) and presented with severe clinical signs; all died orwere euthanized within 1 wk of onset of signs. The 4-year-old1380alpaca with a focal cervical mass was still alive 20 mo after thediagnosis of PMRCT.Diagnostic procedures including complete blood (cell) count,serum chemistry panel, and blood gas analysis were performedon approximately half of the animals — abnormalities aresummarized in Table 2. The most common findings werehypoalbuminemia, acidosis, anemia, azotemia, increased serumgamma-glutamyl transferase (GGT) activity, and hyperglycemia.Lymphocytosis was detected in only 1 animal, a 2-year-old malealpaca with PMRCT. Hypoglycemia was detected in 2 animalsand 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 ASTactivity occurred in 2 animals with neoplasia involving thegastrointestinal tract and in 1 animal with a tumor involving theliver. Increase in serum GGT activity was found in 5 animals,3 of which had neoplasia involving the liver, and 2 of which hadinvolvement of the gastrointestinal tract.Abdominal or thoracic ultrasound on 6 animals resulted indiagnostic findings in 4 animals. Hepatomegaly was detected byultrasonography in 2 animals and examination of ultrasound-guided biopsy samples revealed MRCT in both cases. A massadjacent to the liver was detected by ultrasonography in 1 caseand confirmed to be MRCT following necropsy. Thoracic ultra-sound revealed pleural effusion confirmed to be MRCT basedon 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 neoplasiawithin liver, lymph nodes, and thoracic duct in another case.Cytologic evaluation of fluid or mass aspirates was performedon 5 animals and was diagnostic for MRCT in 4 cases. Biopsysamples of peripheral lymph nodes or liver were evaluated from5 animals and revealed MRCT in all cases. In total, 5 animalswere diagnosed with MRCT prior to death or euthanasia, and1 animal diagnosed with PMRCT by needle biopsy evaluationof a cervical mass was still alive 20 mo after diagnosis.Treatments were varied. Five animals received anthelminthictherapy and 8 received antibiotics. Two animals were treatedwith corticosteroids with temporary abatement of signs, followedby progression to death. Seven animals received fluid therapywith electrolytes, either by mouth or by slow intravenousCVJ / VOL 51 / DECEMBER 2010administration. One severely anemic animal was given a bloodtransfusion. Other treatments included antacids, H-2 blockers,anti-inflammatory medications, insulin, diuretics, and oxyglo-bin. None were treated with chemotherapy.DiscussionThis study and previous studies indicate that camelids withMRCT can present with a variety of clinical signs and laboratoryfindings, and that the clinical course is variable (6–9,11,12,15).Tumors occur at all ages and many affected animals are less than4 y of age. Tumors are particularly common in young alpacas.No other significant differences between alpacas and llamaswere detected.As in prior reports, presenting complaints in this studyincluded anorexia, weight loss, weakness, and respiratory dis-tress (6–9,11,12,15). Peripheral lymphadenomegaly was themost specific finding, and palpable lymphadenomegaly wasdetected in 9 of 10 camelids with MRCT in a prior study(6). In the current study population lymphadenomegaly wasdetected clinically in only 4 cases, but was detected at necropsyin 7 animals (10). Findings indicate that careful clinical evalua-tion of peripheral lymph nodes is an important part of camelidphysical examination.Clinicopathologic abnormalities were most often non-specific(18,19). Azotemia only rarely reflected renal neoplasia, andincrease 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 reflectsanorexia (18). Hyperglycemia was also common, but camelidsare very prone to stress hyperglycemia (18), and an increasedserum glucose level is not considered to be related to under-lying MRCT in these cases. Low serum glucose levels aresignificant, and the 2 animals with hypoglycemia died within2 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), butwas not detected in any case. Lymphocytosis was detected inonly 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 associatedlymphoma often have persistent lymphocytosis (20). There hasbeen no evidence of a viral cause of lymphoma in camelids,and the variety of cell types of MRCTs in camelids (B-celllymphoma, T-cell lymphoma, and PMRCT) does not supporta viral cause for MRCT in these species.Ultrasonography of 6 animals in this study detected evidenceof neoplasia in 4 cases but did not detect masses in 1 animalwith gastric lymphoma, or in 1 with multicentric lymphoma.The cranial location of gastric neoplasia, particularly that involv-ing compartment 1, may make ultrasonographic detection ofgastric MRCT difficult. Cytologic evaluation of thoracic orabdominal fluid was diagnostic in 3 of 4 cases examined inthis study. Cytologic evaluation of enlarged peripheral lymphnodes was performed in 2 cases and provided a diagnosisof MRCT in both cases. Cytologic evaluation of thoracic,CVJ / VOL 51 / DECEMBER 2010abdominal, or cerebrospinal fluid was reported to be diagnosticin 4 previous cases of MRCT in camelids (6,7,11,15). Biopsy ofenlarged lymph nodes or liver resulted in diagnosis of MRCTin 5/5 cases. Results of the current study and previous studiesindicate that ultrasonographic examination and cytologic evalua-tion of fluid, peripheral lymph nodes, or masses, and evaluationof biopsy samples of liver or other involved organs are useful fordiagnosis of MRCT in camelids.Animals up to 2 y of age often had a course of clinical diseaseof#2 wk. In humans, MRCT of childhood often has a poorprognosis, and tumors often metastasize quickly (5,21). Thisstudy suggests that MRCT affecting camelids up to 2 y of age isassociated with a worse prognosis than MRCT in older camelids,but additional studies are needed.The rapid clinical course seen in most of the animals, andthe size of the masses found on necropsy, suggest that many ofthe animals were in an advanced stage of disease before theyshowed clinical signs. It is more effective to diagnose MRCT incamelids based on physical and diagnostic findings than fromclinical signs. To date, only Cebra et al (6) have reported resultsof chemotherapy in a camelid. The case was a 1-year-old llamawith a diagnosis of lymphoma. The animal showed improvementfor 1 d, then rapidly deteriorated. The likelihood of effectivechemotherapy will be increased by early tumor detection.Based on results of this study, a yearly physical examinationin adult camelids, and more frequent examination of camelidsup to 2 y of age, are recommended, as this should increase thelikelihood of detecting disease early in its course. Physical exami-nation should include a thorough palpation to detect peripherallymphadenomegaly. Mandibular and inguinal lymph nodes inparticular should be examined. Routine clinicopathologic studiesmay not reveal a specific change, but will provide indicators ofthe overall health status of the animal, and should be included inthe regular physical examinations. If abnormalities are detected,especially hypoalbuminemia, anemia, leukocytosis, abnormalliver or kidney values, or leukocytosis, thoracic or abdominalultrasound 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 consistentwith neoplasia are detected with diagnostic imaging, biopsy orcytologic evaluation of the lesions should be done. Abdominalor thoracic effusions should be evaluated cytologically. In casesof MRCT, immunophenotyping with specific antibodies forB-cells, T-cells and, when indicated, primitive neuroectodermalcells should be performed. Early detection of MRCT and accu-rate determination of tumor cell type may allow for developmentof chemotherapeutic regimens for treatment of MRCT in llamasand alpacas.CVJA R T I C LEReferences1. Hicks J, Mierau GW. The spectrum of pediatric tumors in infancy,childhood, and adolescence: A comprehensive review with empha-sis on special techniques in diagnosis. Ultrastruct Pathol 2005;29:175–202.2. O’Sullivan MJ, Perlman EJ, Furman J, Humphrey PA, Dehner LP, PfeiferJD. Visceral primitive peripheral neuroectodermal tumors: A clinico-pathologic and molecular study. Human Pathol 2001;32:1109–1115.3. Parham DM. Neuroectodermal and neuroendocrine tumors principallyseen in children. Am J Clin Pathol 2001;115 Suppl:S112–128.13814. Peydró-Olaya A, Llombart-Bosch A, Carda-Batalla C, Lopez-GuerreroJA. Electron microscopy and other ancillary techniques in the diagnosisof small round cell tumors. Semin Diagn Pathol 2003;20:25–45.5. 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