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Lymphoid leukemia in five bearded dragons (Pogona vitticeps)
Abstract
Case description:
2 male and 3 female adult bearded dragons (Pogona vitticeps) were evaluated at the North Carolina State University College of Veterinary Medicine's Exotic Animal Medicine Service between September 2018 and October 2019 because of severe lymphocytosis.
Clinical findings:
All 5 bearded dragons had nonspecific clinical signs, including lethargy, poor appetite, ocular discharge, and weight loss. Clinicopathologic testing revealed extremely high lymphocyte counts with morphological findings consistent with lymphocytic leukemia.
Treatment and outcome:
All 5 patients were treated with lomustine, prednisolone, and antimicrobials. In addition, 1 or 2 doses of L-asparaginase were administered when the drug was available. Partial remission was achieved in all 5 patients. One patient, after disease progression was documented, was treated with cyclophosphamide and achieved a second partial remission. One of the 5 patients was still alive and continuing to receive chemotherapy at the time of final follow-up 244 days after the initial diagnosis. Survival times (ie, times from initial diagnosis to euthanasia) for the other 4 patients were 57, 157, 330, and 416 days.
Clinical relevance:
The present report represented the first description of lomustine as a primary chemotherapeutic agent for the treatment of lymphocytic leukemia in bearded dragons and provided information on response to treatment, adverse effects, and survival times.
... 35 However, an increase in the mice's food intake and weight after treatment with NLP is due to the appetite-enhancing feature of its phenylpropanoids such as elemicin, myristicin and methyl eugenol. 36 In addition, the LA caused toxicity in the liver function as it elevated the liver enzymes and bilirubin. In a study by Lee et al., 37 it is reported that LA led to liver malfunction through elevation in ALT and AST serum levels. ...
In this study, nanoniosome-loaded Myristica fragrans' (MF) phenolic compounds (NLMP) were synthesized and characterized for their physical properties, and hepatoprotective effects on mice with liver toxicity induced by L-asparaginase (LA) injection. According to the results, NLMP has a spherical shape with a 263 nm diameter, a zeta potential of −26.55 mV and a polydispersity index (PDI) of 0.192. The weight and feed intake of mice induced with hepatotoxicity were significantly (p ≤ 0.05) increased after they were treated with NLMP (2.5 mg/kg body weight of mice). In addition, the blood levels of triglyceride (TG), cholesterol (Chol), liver enzymes (aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)) and total bilirubin were significantly (p ≤ 0.05) decreased. A significant increase (p ≤ 0.05) in the blood levels of the antioxidant defence system (glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)) were also reported after NLMP treatment. NLMP was also led to a significant decrease (p ≤ 0.05) in inflammatory-related gene expression of inducible nitric oxide synthase (iNOS) and Interferon-gamma (IFN-γ) in the liver, as well as a meaningful (p ≤ 0.05) increase in the expression of SOD as an antioxidant status biomarker. Consequently, the NLMP is recommended as a potential dietary supplement to alleviate the symptoms of LA-induced hepatotoxicity.
The bearded dragon (Pogona vitticeps), an omnivorous Agamid lizard native to inland Australia, is one of the most popular reptile pets due to their sociable behavior, tame demeanor, low-maintenance care, and relative ease of breeding. Because they are generally stoic animals, thorough physical examination in conjunction with routine clinicopathologic data can prove invaluable in identifying disease and implementing appropriate therapy in a timely manner. The goal of this article is to assist the practicing clinician, based on literature review, on how to approach the diagnostic challenge encountered in everyday practice when working up various conditions in bearded dragons.
Evaluation and interpretation of avian blood cell morphology and counts are used to rule in or rule out disease, monitor response to therapy, establish a prognosis, or develop a database. This chapter deals with the procedures of assessing the avian hemogram with blood film evaluation. Variations in the normal erythrocyte morphology occur in blood films from normal healthy birds as well as those with medical disorders. Reticulocytes are the penultimate cell in the erythrocyte maturation series, and their presence in the peripheral blood of normal birds suggests that the final stages of red cell maturation occur in circulating blood. Heinz bodies have been reported rarely in birds and are the result of hemoglobin denaturation. Toxicosis is a frequent cause of hemolytic anemia in birds. Leukopenia is associated with either consumption of peripheral leukocytes or decreased production. Thrombocyte concentrations are influenced by environmental factors, seasonal changes, and physiologic factors.
The present paper reports the case of a 3 years old, female Bearded Dragon ( Pogona vitticeps ) presenting lethargy, anorexia, weight loss, and anemia and marked leukocytosis at CBC. The majority of leukocytes were lymphocytic/lymphoblastic cells (97%). Immunocytochemical staining of blood smears marked for CD3 (neg) and CD79a (pos) suggested immunophenotype B. The patient died after one month from diagnosis. Histology evidenced lymphoid infiltration in the heart, spleen, liver, kidneys and gut. In addition, in the bone marrow a massive infiltration of lymphoid cells confirmed the diagnosis of leukemia. Immunohistochemistry confirmed the CD79a positivity of a large part of infiltrating lymphoid cells indicating a B cells immunophenotype of the neoplastic population. The presence of lymphocytosis and multiorgan infiltration supported the diagnosis of lymphocytic leukemia. Finally, a revision of the literature has also been made.
Background:
Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs.
Objectives:
To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics.
Animals:
Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64).
Methods:
Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 103 /μL, 2.0 × 103 /μL, and 2.5 × 103 /μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC <1.5 × 103 /μL but above the criteria for prophylactic antibiotics were evaluated.
Results:
Chemotherapy was not administered in 7% of visits with an ANC cutoff of 1.5 × 103 /μL; chemotherapy would not have been administered in 10% and 16% of visits with an ANC cutoff of 2.0 × 103 /μL or 2.5 × 103 /μL, respectively. There was no association among the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75-1.5 × 103 /μL recovered spontaneously without medical intervention.
Conclusion and clinical importance:
The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 103 /μL, and the prechemotherapy ANC class 1.5-1.99 × 103 /μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 103 /μL in which to prescribe prophylactic antibiotics is indicated.
A 5-year-old male Australian bearded dragon (Pogona vitticeps) was presented with a 2-month history of a periocular mass. The clinical evaluation included a physical examination, hematology, biochemistry, and radiographs. The mass was treated surgically and diagnosed as myxosarcoma. Strontium-90 plesiotherapy was attempted, but the mass recurred 5 mo later.
ABSTRACT: An 8-yr-old male bearded dragon (Pogona vitticeps) was presented for evaluation of a mass involving the right eyelid. The mass was surgically removed in conjunction with enucleation of the right eye. Tissues were submitted for histopathology, which revealed that the eyelid mass was a squamous cell carci- noma (SCC). A review of the records from two separate zoological pathology laboratories identified a total of 12 reports of SCC in bearded dragons; this represented 6% of the neoplasms documented in bearded dragons from the two laboratories over a 10 yr period. Nine (75%) of the 12 SCCs were located in the eye- lids or periocular tissues; one (8.3%) was located on the rostral mandible; one (8.3%) was located adjacent to the vent; and one (8.3%) was on the proximal right rear leg. These findings suggest a predilection of SCCs in bearded dragons in proximity to a mucocutaneous junction (11/12, 91.6%), particularly in the periocular tissues (9/12, 75%).
BLV is the etiological agent of enzootic bovine leukosis (EBL), which emerges as B-cell lymphomas. Previously, we found one of tumor-associated antigens (TAAs), which is a useful tool not only for diagnosing EBL but also for screening of BLV-infected cattle with the potential to develop tumor in the future, by using the mono-clonal antibody (MAb) c143. We here performed biochemical characterization of c143 TAA such as two-dimensional electrophoresis, sequential immunoprecipi-tation and tryptic peptide mapping with c143 MAb as well as MAbs against bovine major histocompatibility complex (BoLA) class II antigens, and flow cytometry and immunofluorescence staining of cells transiently transfection with a combination of BoLA-DRA,-DRB3,-DQA and-DQB cDNAs. First, it was found that the c143 TAA is BoLA-DR consisting of alpha and beta chains. Furthermore, the altered expressions of c143 TAA were observed in infected animal with lymphoma at various stages as follows: 1) The number of cells positive for the c143 TAA and 2) glycosylation of the beta chain increased with the progression of EBL. 3) The beta chain was specifically phosphorylated at serine resi-due(s) during the lymphoma stage. Finally, we tested an association of microsatellite markers using 86 cattle with lymphoma and 320 asymptomatic cattle. We identified that seven genomic markers which located in chromosomes 1, 3, 9, 15 , 21, 23 and 24, and, in addition, BoLA-DRB3 gene in chromosomes 23, showed suggestive linkage to development of the BLV-induced EBL. Collectively, our results strongly indicate that BoLA-DR plays a key role in BLV-induced diseases progression.
There is little information in the literature regarding the use of chemotherapy to treat cancer in exotic animals. This article provides a historical perspective on the use and utility of the body surface area scheme for dosing chemotherapy in animals. Normogram-based recommendations for arriving at a proper chemotherapy dose for the management of cancer in exotic animals are made. It is realistic to offer treatment for many neoplastic diseases in exotic animal species, as long as the limitations are realized and informed consent of the owner is obtained.
Case Description —A 2-year-old female green iguana was examined for anorexia and swelling and pain on palpation in the cranial cervical area.
Clinical Findings —Marked soft tissue swelling in the cranial cervical area with corresponding cystic swellings in the pharynx were noted. The iguana was considered to be 50% under the expected body weight, given diet and husbandry conditions. The WBC count was markedly elevated, characterized by heterophilia and lymphocytosis. Surgical exploration of the cranial cervical area and histologic and microbial testing identified lymphoma with secondary infection as the cause of the swelling.
Treatment and Outcome —The tumor was initially treated with a single 10-Gy fraction of radiation directed at the masses in the neck. A vascular access port was placed in the ventral abdominal vein, and a canine chemotherapy protocol was modified for use in the iguana. During the course of treatment, the protocol was modified twice. At 1,008 days from the initiation of treatment, the iguana appeared to be in remission.
Clinical Relevance —To our knowledge, this is the first reported use of radiation with doxorubicin, vincristine, cyclophosphamide, and prednisone to successfully manage lymphoma in a reptile. A vascular access port was used effectively for drug administration for an extended period. The doxorubicin, vincristine, cyclophosphamide, and prednisone protocol appeared to be safe and effective in this iguana for the management of lymphoma.
In this study, synchronous spontaneous, independent liver and gallbladder tumours were detected in a Bearded dragon (Pogona vitticeps). The multiple tumours consisted of intrahepatic cholangiocarcinoma as well as in situ adenocarcinoma and two adenomas of the gallbladder. The biliary epithelial cells and the cholangiocarcinoma showed membranous cross-immunoreactivity for claudin-7. The gallbladder epithelial cells, its adenoma and adenocarcinoma showed basolateral cross-reactivity for claudin-7. We think that the humanised anti-claudin-7 antibody is a good marker for the detection of different primary cholangiocellular and gallbladder tumours in Bearded dragons. The cholangiocytes, the cholangiocarcinoma, the endothelial cells of the liver and the epithelial cells and gallbladder tumours all showed claudin-5 cross-reactivity. The humanised anti-cytokeratin AE1-AE3 antibody showed cross-reactivity in the biliary epithelial cells, cholangiocarcinoma cells, epithelial cells and tumour cells of the gallbladder. It seems that this humanised antibody is a useful epithelial marker for the different neoplastic lesions of epithelial cells in reptiles. The humanised anti-α-smooth muscle actin (α-SMA) antibody showed intense cross-reactivity in the smooth muscle cells of the hepatic vessels and in the muscle layer of the gallbladder. The portal myofibroblasts, the endothelial cells of the sinusoids and the stromal cells of the cholangiocarcinoma and gallbladder tumours were positive for α-SMA. The antibovine anti-vimentin and humanised anti-Ki-67 antibodies did not show crossreactivity in the different samples from the Bearded dragon.
This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.
Sera from 353 cats with naturally occurring feline leukemia virus (FeLV) infection were collected in Boston, Los Angeles, New York City, and Seattle between 1968 and 1988. These sera were retrospectively assayed by enzyme-linked immunosorbent assay for antibodies to feline immunodeficiency virus (FIV). Fifty-one (14.4%) of the FeLV-positive sera had antibodies to FIV, indicating dual oncovirus and lentivirus infections. FIV infections were confirmed by Western blot analysis, antibodies against the 15 and 27 kDa proteins being used as definitive markers. FIV infection was diagnosed in one cat sampled in 1968 and in eight other cats sampled before 1975 in New York City. Illnesses exhibited by coinfected cats were similar to those of cats infected with FeLV only. Two unrelated cats with multicentric fibrosarcomas were found to be simultaneously infected with FIV, FeLV, and feline sarcoma virus. FIV was less contagious than FeLV in 73 cats residing in an exposure household between 1977 and 1980 as determined by evaluation of sera collected sequentially. In this household, 15 resident cats became FeLV infected whereas no cats contracted FIV infection. Comparison of serologic results from 53 cats with leukemia/lymphoma and matched controls confirmed a strong correlation between FeLV viremia and leukemia/lymphoma. A significant correlation between FIV infection and lymphoproliferative malignancies was also found independent of FeLV infection.
A consensus primer PCR method which amplifies a region of herpesviral DNA-directed DNA polymerase (EC 2.7.7.7) and which uses degenerate primers in a nested format was developed. Primers were designed to target sequences coding for highly conserved amino acid motifs covering a region of approximately 800 bp. The assay was applied to 22 species of herpesviruses (8 human and 14 animal viruses), with PCR products obtained for 21 of 22 viruses. In the process, 14 previously unreported amino acid-coding sequences from herpesviral DNA polymerases were obtained, including regions of human herpesviruses 7 and 8. The 50 to 60 amino acid-coding sequences recovered in the present study were determined to be unique to each viral species studied, with very little sequence variation between strains of a single species when studied. Template dilution studies in the presence of human carrier DNA demonstrated that six human herpesviruses (herpesviruses 1, 2, 3, 4, 5, and 6B) could be detected at levels at or below 100 genome equivalents per 100 ng of carrier DNA. These data suggest that consensus primer PCR targeted to herpesviral DNA polymerase may prove to be useful in the detection and identification of known herpesviruses in clinical samples and the initial characterization of new herpesviral genomes.
Treatment options for animals with cancer are rapidly expanding, including in exotic animal medicine. Only limited information is available, however, about treatment effects in exotic pet species beyond individual case reports. Consequently, most cancer treatment protocols in exotic animals are extrapolated from those described in humans, dogs, and cats. Practical limitations, however, as well as anatomic or physiologic differences can complicate the application of certain cancer treatment modalities in exotic species. This review provides an overview and update on cancer treatment in exotic animal species, including the various considerations that are important during the initial diagnosis, therapeutic planning, and monitoring of the exotic cancer patient.
Based on necropsy review, neoplasia in reptiles has a comparable frequency to that of mammals and birds. Reptile neoplasia is now more frequently diagnosed in clinical practice based on increased use of advanced diagnostic techniques and improvements in reptilian husbandry allowing greater longevity of these species. This article reviews the current literature on neoplasia in reptiles, and focuses on advanced diagnostics and therapeutic options for reptilian patientssuffering neoplastic disease. Although most applied clinical reptile oncology is translated from dog and cat oncology, considerations specific to reptilian patients commonly encountered in clinical practice (turtles, tortoises, snakes, and lizards) are presented.
Diagnoses of neoplasia in exotic animals have historically been made at death or just before euthanasia. Routine physical examinations are enabling early diagnosis while accessibility and affordability of advanced diagnostics are improving. With increasing expectations for care, treatment options are more frequently explored. Numerous oncologic medications have been adopted from human and small animal medicine and successfully used in exotic animals. Although there is a need for extended research, this article evaluates which medications have been used thus far for treatment protocols in zoologic and exotic animal species.
A 4.5-year-old female bearded dragon (Pogona vitticeps) presented for periorbital swelling affecting the left eye. A well-organized, hypoechoic mass was noted ventral and medial to the globe on ocular ultrasound. The mass continued to grow despite antibiotic therapy, and an exenteration was performed. The mass was diagnosed via histopathology and immunohistochemical staining as a probable lacrimal gland carcinoma, although a Harderian gland origin could not definitively be ruled out. The tumor recurred following removal, and the lizard died 2 months postoperatively.
A 4.5-yr-old, captive-bred, male bearded dragon (Pogona vitticeps) presented for lethargy, anorexia, and increased mucoid salivation with upper respiratory clicks. Diagnostics were declined and the bearded dragon was prescribed ceftazidime 20 mg/kg i.m. q 72 hr. The patient presented again 1 wk later with a marked monocytosis, heterophilia, and lymphocytosis, and a clinical diagnosis of chronic monocytic leukemia was made. Chemotherapy with cytosine arabinoside (100 mg/m2 over 48 hr i.v.) was initiated. Forty-four hours into the treatment the dragon became acutely unresponsive and died within 1 hr. Adverse effects as a result of i.v. cytosine arabinoside therapy were not identified despite previous reports suggestive that the drug induces renal failure.
Adding lomustine to the standard combination of idarubicin and cytarabine for the treatment of old patients with acute myeloid leukemia improves complete response rates and overall survival. These findings emphasize the importance of dose intensity and raise the question of a unique role for nitrosoureas in the treatment of this disease.
A 3-yr-old bearded dragon (Acanthodraco vitticeps) presented with lethargy, a swollen right elbow joint, inability to move its rear limbs normally, and marked leukocytosis. The majority of leukocytes were an abnormal mononuclear lymphoid-type cell with a high nuclear to cytoplasmic ratio, a slightly blue cytoplasm, nuclei with coarsely granular chromatin, and some nuclear clefts. Acute leukemia of lymphoid or myeloid origin was tentatively diagnosed. The abnormal mononuclear leukocyte cell population stained positively for the myeloid cytochemical stains: peroxidase, chloroacetate esterase, and L1-calprotectin. The abnormal cell population of the peripheral blood did not stain with the lymphoid cytochemical stains: alpha-naphthyl butyrate esterase, CD3, and CD79a.
The majority of information on oncology therapies has been reported in humans, canine, and feline patients, and laboratory animals with experimentally induced tumors. A variety of treatments,including radiation therapy, chemotherapy, photodynamic therapy, and others have been used with exotic animals. There are many species of exotic pets, and anatomic differences, as well as husbandry and nutritional requirements, must be taken into account to provide optimal care. By providing a broad overview of therapies and considerations for treatment, this article is intended to provide the practitioner with an overview of approach and options when addressing oncology cases in exotic animals.
This retrospective study appears to be the largest publication to date regarding the prevalence of neoplasia in reptiles. As in previous publications, neoplasia is most common in snakes, followed by lizards, chelonians, and crocodilians. Several interesting trends were documented in this study, some of which appear to be previously unidentified, and some that support the findings of previous publications.
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