Lymphoid leukemia in five bearded dragons (Pogona vitticeps).

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.

Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T-cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia.

BACKGROUND: Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population. Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V-D-J (IGH-VDJ) and T-cell receptor gamma (TRG) gene rearrangements. OBJECTIVES: We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH-VDJ and TRG rearrangements, as well as incomplete IGH-DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls. METHODS: Fluorescently labeled PCR primers were designed to amplify complete IGH-VDJ, incomplete IGH-DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B-cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B-cell origin, 30 flow cytometrically confirmed T-cell leukemias, and 11 negative control cats were tested. RESULTS: Using four immunoglobulin primer sets (IGH-VDJ, IGH-DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B-cell neoplasms. The IGH-VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T-cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements. CONCLUSIONS: The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH-DJ, Kde, and IGL rearrangements helped identify clonal B-cell neoplasms not detected with complete IGH-VDJ PARR alone.

Pulmonary oedema as a suspected adverse drug reaction following vincristine administration to a cat: a case report.

This report describes recurrent respiratory distress following vincristine administration to a cat with chronic lymphocytic leukaemia. The cat was treated with a combination of vincristine, chlorambucil and prednisolone with initial success. After approximately 4 months, dyspnoea developed within 6 h of vincristine administration. Emergency therapy was instituted resulting in a full recovery. Further vincristine was administered; dyspnoea was similarly noted after all but one of these treatments. Dyspnoeic episodes were not attributable to alterations in vincristine dose or method of administration. The repeated temporal association was consistent with a suspected adverse drug reaction to vincristine.

Immunochemical and biochemical study of an abnormal heavy chain of bovine IgG1.

An abnormal heavy chain (HC) protein of IgG1 was isolated from the serum of a leukemic cow by gel filtration on a Sephadex G-200 column with the following ion-exchange chromatography. The HC protein migrated electrophoretically in the anodic region. The molecular weight of the untreated HC protein was about 48,000. Enzymatic treatment with papain and reduction with beta-mercaptoethanol showed no effect on the protein. Antigenic analysis of the HC protein using a specific rabbit antiserum against bovine IgG1 showed a complete identity with the Fc fragment and a partial identity with the intact bovine IgG1. Antigenic determinants of the light-chain were not found. The HC protein consisted of only one polypeptide chain.

Comparison of the tissue distribution of reverse transcriptase, p30 and type-C virus in a gibbon ape with lymphocytic leukemia.

Tissues obtained at necropsy from a 7 year old male gibbon ape with malignant lymphoma and leukemia were analyzed by electron microscopic, immunological and enzymological techniques to determine the comparative localization of tumor cells and virus throughout the body. In general, the different assays correlated well; the reverse transcriptase (RT) assay and p30 radioimmunoassay (RIA) being the most sensitive, although the RT assay was able to detect activity in one tissue scored negative by p30 RIA. Tissues were infiltrated with tumor cells to varying degrees which correlated well with the level of virus markers in most cases with the exception of the liver and kidney. In these 2 organs there was marked infiltration of free virus and tumor cells but there was no evidence of virus infection or production by these cells.

Murine monoclonal antibodies cross-reactive with feline peripheral blood mononuclear cells.

Twelve murine monoclonal antibodies (MAB), specific for canine, human, and mouse cell surface determinants on lymphohemopoietic cells, were tested for reactivity (using indirect immunofluorescence) with peripheral blood mononuclear cells (PBMC) from 3 normal cats and 3 FeLV-positive cats with lymphoblastic leukemia. MAB DLy6 and 1H3, specific for canine lymphocytes, MAB HB57S, specific for human mu(IgM) chain, MAB J-118 40.164.3 and H81.98.71, specific for murine and human Ia, all had higher binding levels with PBMC from FeLV-positive cats compared to normal cats. Two MAB (S-78, S-24), specific for human class I determinants, cross-reacted with PBMC from both groups of cats. This panel of MAB may be useful for characterizing immunologically reactive cell subsets in normal as well as retrovirus-diseased animals.

Partial characterization of bovine leukemic cell populations.

Peripheral blood lymphocytes (LL) from cows with chronic lymphocytic leukemia (CLL) have been studied using a number of surface markers. Cell populations were obtained by partial enrichment and depletion using Sephadex G-200-anti-F(ab')2 and Sephadex G-200-anti-LL-Ig immunoadsorbent columns. It was shown that cell populations having different markers, i.e., surface immunoglobulins (sIg) and leukemia-associated antigens (LAA), are characterized by similar parameters. Thus the adherent cells obtained by both fractionation methods formed 1.1-4.0% of rosettes with sheep red blood cells, while 90.6-94.3% were sIg positive cells. The cytotoxicity test (CTT) performed with anti-B and anti-LL sera indicated that a vast majority of adherent cells reacted to the sera. Thus the adherent cells represent a population with a high percentage of B-cells.

Quantitative studies of Fc receptors on bovine leukemic blood lymphocytes: characterization by binding of homologous IgG1 and IgG2.

Receptors for IgG1 and IgG2 (FcR) on peripheral blood lymphocytes from cows with chronic lymphocytic leukemia (CLL) were detected by their ability to bind homologous IgG1 and IgG2 in fluorometric binding assay. Scatchard plots at 4 degrees C demonstrated that IgG1 bound the same number of FcR per cell (3.12 +/- 0.69 X 10(5)) as IgG2 (2.89 +/- 0.69 X 10(5)). The receptors bound IgG2 with an affinity of 4.09 +/- 1.08 X 10(5) 1/M and IgG1 with an affinity of 2.73 +/- 0.55 X 10(5) 1/M, although the difference was not of statistical significance (0.1 greater than P greater than 0.05). Inhibition studies demonstrated that the two ligands could inhibit each other. It might be assumed that FcR for the two subclasses were identical.

Genetic, endocrine, and viral aspects of AKR leukemogenesis.

In the AKR strain of mice a high incidence of spontaneous lymphoid leukemia develops before 12 months of age. Genetic, viral, and endocrine factors interact during development to produce the syndrome. Many of the deficiencies of AKR mice are associated with gene action in chromosome 17, at or near the major histocompatibility locus. It is suggested that low steroid levels and high thyroxin levels during an early period of development are an essential part of the syndrome. Specifically, induction of a polymerase enzyme and regulation of the extent of its action by hormones are postulated to favor appearance of C-type particles and accumulation of a population of undifferentiated lymphoid stem cells. Immunodeficiency and leukemic transformation result.

Lympholeukemia in madai Pagrus major in Japan.

Lympholeukemia has been occurring to an epizootic extent with mass mortality in 1 and 2 yr old madai (= Japanese red sea bream) Pagrus major in the winter season (October-May) in the western regions of Japan since 1975. Diseased fish displayed severe anemia and markedly increased numbers of neoplastic lymphocytoid and lymphoblastoid cells in the blood. Neoplastic cells originated in the splenic lymphatic cells and systemically caused severe metastatic lesions in the heart, liver, kidney, digestive tracts, gills and the lateral musculature. Electron microscopy revealed adeno-like viral particles (78 to 83 nm in diameter) in the nucleus of lymphoblastoid cells which appeared in the early prevalent stage but no viral particles in the lymphocytoid cells or plasmacytoid cells, which subsequently increased in number. In this paper, we describe light and electron microscopic features of neoplasms and neoplastic cells.

Haematopoietic malignancies in zoo animals.

Myelogenous leukaemia was found in a Russell's viper, a Honduran milk snake, a marine toad, a Byrne's marsupial mouse and an African hedgehog. Lymphocytic leukaemia was present in a broad banded copperhead and an Indian lion. Visceral lymphomatosis was observed in a snowy owl.

Changing manifestations of a chronic feline haematopoietic proliferative disease during immunotherapy with staphylococcal protein A.

A cat with feline leukaemia virus-associated malignant disease was treated by ex vivo immunoadsorption using staphylococcal protein A coated filters. During the 12-week course of treatment, the morphological manifestations of the haematopoietic disease showed a progressive transition from erythroid to myeloerythroid to myeloid predominance, and the disease was preceded by and associated initially and terminally with a blast transformation of lymphoblastic morphology. Necropsy revealed massive meningo-cerebral, as well as hepatic, renal, myeloid, lymphoid, peritoneal and pelvic infiltrations largely consisting of lymphoblastic cells. Evidence of myeloid and erythroid differentiation was present in all the infiltrates. The several possible bases for this shift of morphological expression are considered.

Observations on the pathology of non-alimentary lymphomas in the horse.

A retrospective study was carried out on post-mortem and biopsy tissue samples from 26 horses with non-alimentary lymphoma. On the basis of their histopathology and cytology, the cases were grouped into several categories: (1) Lymphoblastic lymphomas (6 cases) and primary lymphoblastic leukaemia (2 cases). (2) Histiolymphocytic lymphomas involving the skin (6 cases) or lymph nodes (3 cases). (3) Lymphomas showing follicular development (4 cases). (4) Plasmacytic lymphomas (4 cases). (5) Lymphocytic lymphoma (1 case). Most affected horses were middle-aged or old but lymphoblastic neoplasms tended to affect younger horses than other forms. The course of the disease was highly variable. The most rapidly progressive forms were of lymphoblastic cytology, whereas some cases with histiolymphocytic skin nodules appeared to be only slowly progressive. Further information is needed on the pathology and clinical behaviour of some types of lymphoma, particularly those manifesting in the skin. Elucidation of the histogenetic relationships of the different cytological types of lymphoma will involve the development of immunohistochemical and other techniques which are specifically applicable to the horse.

Neoplasia in ferrets: eleven cases with a review.

Records from a veterinary diagnostic laboratory in south Florida, U.S.A. were reviewed for cases of neoplasia in pet ferrets. Twelve ferret tumours were received over a four-year period; one case, a ferret with lymphocytic leukaemia and multi-organ involvement, had been reported previously. The other eleven tumours were: two chordomas of the tail, two sebaceous adenomas of the skin, a sebaceous epithelioma of the skin, a cutaneous mastocytoma, a malignant fibrous histiocytoma from the eyelid, a malignant mesenchymoma and an undifferentiated sarcoma from the dorsal abdominal cavity, a leiomyosarcoma found unattached in the abdominal cavity and an interstitial cell tumour of the testicle. A review of the literature yielded reports of 83 other tumours in domestic ferrets, black-footed ferrets and European polecats. Of the 95 ferret tumours, 46 were considered malignant. Tumours occurred in all organ systems except the respiratory tract and central nervous system. Affected ferrets ranged in age from 209 days to 12 years. The most frequently occurring tumours were ovarian stromal tumours (24 of 95), haemangiomas/haemangio-sarcomas (15 of 95). This information indicates that, contrary to previous opinion, ferrets appear to be subject to a similar incidence and variety of tumours as other animals.

[Bovine enzootic leukemia and study of c-type particles in a cow with acute lymphatic leukemia and in cattle of the same herd with persistent lymphocytosis]. / Leucosi enzootica dei bovini e studio di particelle di tipo (C) in una bovina adulta con leucemia linfatica acuta e in bovine dello stresso allevamento con linfocitosi persistento

A case of acute lymphatic leukemia in a 7-month-pregnant Italian Friesian cow, aged about 6 years and belonging to a small dairy herd of 11 cows is described. Hematologic, histopatologic and ultrastructural examinations were performed, the ultrastructural studies were confined to the lymphnodes, thymus and buffy-coat cultures from peripheral blood. The remaining animals were subjected to hematologic examination and electron microscopy examination of buffy-coat cultures from peripheral blood. C-type particles were found in phytohemagglutinin (PHA)-treated and untreated buffy-coat cultures from the leukemic cow and from the animals with persistent lymphocytosis. C-type particles were also found in milk samples from 3 cows with persistent lymphocytosis.

Reverse transcriptase activity in a case of ovine lymphoblastic leukaemia.

Tissues taken post mortem from a sheep suffering from lymphoblastic leukaemia were examined for retroviral reverse transcriptase (RT) activity and for particles of retroviral density. Cultured bone marrow and lymph node cells were found to release into the medium particles of 1.16 and 1.21 g/ml density, and poly rC-oligo dG templated activity could be detected in cell-free supernatants. Tissues from two normal sheep were not found to exhibit these characteristics. Electron microscopic observation failed to reveal any retrovirus-like particles in the RT positive tissues. In vitro transmission studies indicated that the RT activity could not be transmitted to either sheep choroid plexus or lamb trachea cells, but was transmitted, at low efficiency, to both bovine kidney and mink lung cells.

Variable expression of major histocompatibility complex class II in the domestic cat.

This paper describes the characterisation of six independently produced monoclonal antibodies (mAbs) specific for non-polymorphic determinants of feline major histocompatibility complex (MHC) class II. One mAb is an anti-sheep class II which cross-reacts with the cat and five have been produced in response to immunisation with purified feline immunodeficiency virus. Despite their independent source all the mAbs have identical reactivities, immunoprecipitating two complex groups of polypeptides of M(r) 33 to 36.000 (MHC class II alpha chains) and M(r) 28 to 31,000 (MHC class II beta chains). Immunoblot analysis showed them to be beta chain-specific. One and two-dimensional electrophoresis revealed the complexity of feline class II mass and charge and implied the expression of multiple class II loci in the cat. Furthermore, it was demonstrated that distinct cell populations expressed a distinct range of class II variants. This suggesting either the differential expression or the distinct post-translational modification of lymphocytes from different sites. The mAbs have also been used for the detailed examination of the cellular distribution and tissue localisation of MHC class II in the cat.

[Mast cell-affinity lymphocytes as indicator cells of the forms of hemoblastoses]. / Mastotsitaffinnye limfotsity kak indikatornye kletki nekotorykh form gemoblastozov.

The formation of mastolymphocyte rosettes was used to determine that in chronic lymphocytic leukemia and bovine leukemia, unlike healthy people and animals as well as patients with solid tumours of different localization and Hodgkin's disease, a large amount of cells appear among peripheral blood lymphocytes having membrane affinity for mast cells. This may be used as an additional criterion in laboratory diagnosis of these diseases.

[The activity of growth-regulating substances isolated from the spleen and thymus of healthy cows and of those with hemoblastoses]. / Issledovanie aktivnosti rostreguliruiushchikh veshchestv, vydelennykh iz selezenki i timusa zdorovykh i bol'nykh gemoblastozami korov.

Certain agents of the proteoglycan nature possessing organ-specific rather than the species-specific antimitotic chalone activity have been obtained from the normal bovine spleen and thymus. The preparations obtained by the same method from the spleen and the thymus of animals affected by lympholeukemia and lymphosarcoma did not reveal the antimitotic activity; moreover, they were of high mitogenic organ-specific character. A connection between the mitogenic factor produced by lymphocytic cells and the bovine leukemia virus is possible.