Histopathologic classification of 171 cases of canine and feline non-Hodgkin lymphoma according to the WHO.

A retrospective collection of 171 lymphoid neoplasms (123 dogs and 48 cats) was classified according to the Revised European-American Lymphoma (REAL) classification, adopted in 2002 by the World Health Organization (WHO), to evaluate the WHO system for categorization of canine and feline neoplasms. Microscopic examination was performed after standard hematoxylin-eosin staining and immunohistochemical labelling for B (CD79a) or T (CD3) cell phenotypes. B-cell lymphomas were prevalent in dogs and T-cell lymphomas in cats. B-Large cell lymphoma (B-LCL) frequently showed plasmacytoid differentiation; notably, two canine plasma cell tumours (PCT) expressed both CD79 and CD3. There were difficulties in differentiating B-lymphoblastic lymphoma (B-LBL) from Burkitt-type lymphoma. Furthermore, intestinal T-cell lymphoma (ITCL) exhibited a huge morphologic variability. Finally, multicentric mature small and thymic T-cell lymphomas were diagnosed, although these categories are not codified by the WHO classification.

[Anthropozoonoses and other inter-specific infections: breaches in the "species barrier"]. / Anthropozoonoses et autres infections interspécifiques: des brèches dans la "barrière d'espèce".

Infectious outbreaks in human populations frequently occurred during the last decades. Most of these epidemics were emerging or re-emerging diseases and about 75% of them were caused by animal pathogens mainly from wild animal species. Thus the "species barrier" dogma seems to be frequently in the wrong. Many factors are probably involved in this failure. Among them, genetic mutations mainly in viruses which are more and more frequently discovered. On the other hand, anthropic factors are the major causes of this species barrier breaches. Closer contacts with domestic and/or wild animals, dramatic growth of human populations, poverty, numerous immunodepressed people, international travels and trading are facilitating or determining factors of the inter-specific transmission of pathogens. International mobilization is mandatory to efficiently anticipate and control the emergence of such zoonoses. According to their unpredictable emergence and their rapid potential worldwide spreading, their control requires an international cooperation both in a permanent epidemiological surveillance and a rapid efficient riposte. Human and veterinary medical institutions have to closely cooperate in this issue.

Sclerosing peritoneal mesothelioma in a dog - a case report.

A case of peritoneal sclerosing mesothelioma in a 3-year-old German shepherd dog is reported. The dog presented a severe abdominal distension. Cytological examination of the peritoneal fluid revealed anaplastic epithelioid cells. Necropsy findings revealed an irregular-shaped mass attached to the pancreas and stomach with numerous nodules covering the intestinal and urinary bladder serosa. The diagnosis was made by histology and immunohistochemistry, with cytokeratin, vimentin and calretinin antibodies. Differential diagnosis with chronic peritonitis and spreading of abdominal primary carcinoma is discussed.

Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes. Proceedings of a pathology workshop held at the Fraunhofer Institute of Toxicology and Aerosol Research Hannover, Germany, May 7-9, 2001.

A Panel of medical and veterinary pathologists reviewed published and unpublished reports dealing with studies of various white mineral oils and waxes in F344 and Sprague-Dawley rats. They also had available and studied histologic slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax (LMPW) in female Fischer 344 and Sprague-Dawley rats; 90-day studies of P15H* and P70H white oil and high melting point wax (HMPW) in male and female F344 rats and 24 month study of P70H white oil in male and female F344 rats. The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The Panel agreed that certain of the mineral hydrocarbons produced lesions in the mesenteric lymph nodes and liver of the F344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of mineral hydrocarbons. The Panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of LMPW and the lesions were confined to F344 rats and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose LMPW-fed F344 rats. The microgranulomas were similar in subchronic and chronic studies. Also, little difference existed between controls and treated F344 rats in the incidence and severity of the lesions after 2 years of feeding P70H white oil. The Panel agreed that some slight reversibility existed for these lesions, but also agreed that complete resolution was unlikely as regression of the lesions in the rat would likely be slow. The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the mitral valve in a slightly increased incidence in F344 rats fed LMPW. The Panel concluded that these mitral valve alterations had little if any toxicologic significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy, and were unlike the responses in the liver and mesenteric lymph nodes. The Panel agreed that the lesions observed in the liver and mesenteric lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy. The MHC-induced lesions can be considered incidental and inconsequential in humans.

[Animal transmissible subacute spongiform encephalopathies: scrapie in sheep and bovine spongiform encephalopathy]. / Encéphalopathies spongiformes subaiguës transmissibles animales: la tremblante du mouton et l'encéphalopathie spongiforme des bovins.

In veterinary medecine, the field of animal Transmissible Subacute Spongiform Encephalopathies (TSSE) has been suddenly enlarged in 1986, by the dramatic outbreak of the Bovine Spongiform Encephalopathy (BSE) in the UK. Since this first observation BSE was recognised in various EU countries. BSE is largely considered, at the present time, as a food born infectious disease, resulting from the feeding of bone and meat meals (BMM) of bovine, after a rendering process modification. It is largely agreed that the ovine Scrapie prion could be transmitted to bovine through the alimentary way. Unlike Scrapie, BSE is characterized by its remarkable pathological monomorphism and the absence of obvious relationship between the prion infectivy and the recipient genotype. Another feature of BSE agent is its broad spectrum of interspecies infectivity, including through the alimentary route, raising very important questions both for animal and public health. The new variant of Creutzfeldt-Jakob disease (nv CJD) which was described in the UK, results certainly from a human contamination by bovine products. Regulation have been made in the EU, in order to stop the infectious spreading (BMM banning for Ruminants feeding) and to protect the consumer (banning of "specified risk materials" in human alimentation).

Feeding heated soyabean flour increases the density of B and T lymphocytes in the small intestine of calves.

The effect of dietary antigens on the gut morphology and density of immune cells was studied in preruminant calves fed milk substitutes containing skim milk powder (SMP), non-antigenic hydrolysed soya protein isolate (HSPI) or antigenic heated soyabean flour (HSF) as their main protein source for 3 months. The height and perimeter of proximal jejunum villi were highest in the calves fed SMP and lowest in those fed HSF (P < 0.05). In contrast, the crypt depth and perimeter were apparently not influenced by the dietary treatments studied. This morphological alteration was associated with a dramatic infiltration of the lamina propria by B and T lymphocytes in the calves fed HSF (P < 0.01). Increased B cell density was essentially accounted for by IgA-, IgG1- and IgG2-bearing cells. The density of CD2-positive T lymphocytes increased (P < 0.01) in the jejunal lamina propria of HSF calves, involving helper (CD4+) and suppressor-cytotoxic (CD8+) T cell subsets. The density of gamma-delta (WC1+) T cells also increased (P < 0.01). The major change concomitantly observed in the villus epithelium was an increased density of CD8+ cells (P < 0.05) and WC1 + cells (P < 0.01).

Histopathological changes in lymph nodes of cats experimentally infected with the feline immunodeficiency virus (FIV).

Twelve specific-pathogen-free (SPF) kittens aged 8-12 weeks were serially infected in pairs every 6 weeks, by the intraperitoneal route, with the feline immunodeficiency virus (FIV). Three additional SPF kittens were kept as controls. The infected animals were killed 10 weeks after inoculation, during the primary phase of the FIV infection. Generalized lymphadenopathy (GL) was observed in the first three pairs of cats. All lymph nodes examined from the 12 infected cats showed histological changes. These included severe follicular hyperplasia with hyperactive follicular centres (FCs) which were either (1) naked, (2) infiltrated by lymphocytes, (3) seen to contain islets of lymphocytic mantle cells, or (4) disrupted by lymphocytes. The presence of both CD4+ and CD8+ T lymphocytes was demonstrated in the FCs immunocytochemically. The distribution of CD4 lymphocytes resembled that in control lymph nodes, but the CD8 cells were increased in number and either scattered or clustered in the follicles. In addition, varying degrees of interfollicular proliferation and medullary plasmacytosis were observed in the lymph nodes. These findings, which were common to all infected animals, represented distinct prodromal manifestations of FIV infection. The changes in lymphocyte subpopulation distribution observed in early FIV infection were reminiscent of findings encountered in human immunodeficiency virus (HIV) infection and reinforce the suggestion that FIV infection is an appropriate model for the study of HIV pathogenesis.

Comparative histopathology of draining lymph node after infection with virulent or attenuated strains of Salmonella abortusovis in lambs.

Histological responses to the early phase of infection were compared in parotid lymph nodes of lambs infected by the subcutaneous route into the right eyelid with either a virulent or an attenuated strain of Salmonella abortusovis. The right parotid lymph nodes showed a massive PMN infiltration for the first days of infection for both strains. From day 6, the infected lymph nodes developed a lymphoid hyperplasia with prominent germinal centers independent of strain type. The virulent strain of S. abortusovis induced focal lesions in 2 out of 6 lambs necropsied on days 6 and 10, and provoked a systemic infection evidenced by the regular colonization of spleen on day 6. In contrast, no focal lesion and a restricted bacterial dissemination were observed in lambs infected with the vaccinal strain.

Early haematological and pathological abnormalities of pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV).

Twelve 8-12-week-old specific-pathogen-free (SPF) cats were inoculated intraperitoneally with feline immunodeficiency virus, or with blood from inoculated cats. Three cats of the same age were used as controls. All animals were sacrificed 10 weeks after inoculation. The inoculated cats seroconverted between the 3rd and 6th weeks after inoculation. For 6 infected cats, a decrease in the CD4/CD8 lymphocyte ratio was observed as early as the 6th to the 10th week after inoculation. Granular lymphocytes and atypical cells with cytoplasmic vacuoles and very irregular nuclei were observed in the blood from the 1st to the 10th weeks after inoculation. The only statistically significant differences were obtained 10 weeks after inoculation. Mean leucocyte and lymphocyte numbers were decreased (8000 and 3200 per microliter respectively compared with 14500 and 7200 per microliter before inoculation). The mean CD4/CD8 ratio was also decreased (from 2.60 to 1.50). The percentage of lymphocytes in the bone marrow was increased, reaching 34% as a mean for infected cats as opposed to 20% for control animals. The atypical cells found in the blood were not observed in the marrow. The sternebral bone marrow did not contain lymphoid follicles, as described for HIV infection. Severe follicular hyperplasia was only found in the lymph nodes, but no viral particles could be observed in them.

Partial characterization of a familial B lymphosarcoma with a thymic localization in cattle.

We recently described an original epidemiological form of bovine leukosis in cattle. In the young female offspring of one bull, more than 3% of animals developed a thymic lymphoblastic lymphosarcoma. Of these, 31 cases, together with a lymphoid cell line established from one of the tumours, were phenotypically characterized. Characterization was done using a large combination of well clustered monoclonal antibodies, and monoclonal antibodies prepared in our laboratory by immunizing mice either with bovine normal lymphocytes or with tumour thymic cells. The thymic tumours and the cell line did not express any T lymphoid antigens but they did express some B lymphoid markers. The phenotype of the tumour cells was CD45+/-, CD44+/- TdT+, class II-DR+/-, CD19+/-, CD21-, Ig- and HBM 57+ (recognizing the mb-1 chains of the B-cell receptor). The cell line expressed a more mature phenotype: TdT-, CD45-, CD44+, class II-DR+, CD19+, CD21+/- and sIgG+. These results allow us to consider these tumours as B-cell derived. These B lymphosarcomas with a thymic localization are reminiscent of a human mediastinal non-lymphoblastic lymphoma reported as a primary mediastinal clear cell lymphoma. The possibility of a thymic or extrathymic origin for this B lymphosarcoma is discussed.

[Preparation and characterization of a monoclonal antibody directed against bovine leukocytes]. / Préparation et caractérisation d'un anticorps monoclonal dirigé contre des leucocytes bovins.

A monoclonal antibody (MAb-M25) was obtained by immunizing BALB/C mice with tumour cells isoled from a familial thymic lymphosarcoma observed in Friesian cattle. The specificity of this MAb was assessed using PBL, lymphoids organs (lymph node, spleen, tonsil, Pleyer's patch) and non lymphoid tissues (liver, skin) from clinical normal cattle. Immunofluorescence and immunohistochemistry methods were used to characterise this monoclonal antibody. It reacted with 27% of peripheral blood lymphocytes and a large proportion of mononuclear cell in the lymphoid organ, in the thymic cortical, in the dermis and in the liver. It also stained lymphocytes of the mantle of follicules and thymocytes of the thymus cortex. The tissue distribution of M25 have a similarity with the human CD1c Mab and the bovine 20-27 MAb.

Histopathology of the early phase during experimental Corynebacterium pseudotuberculosis infection in lambs.

Histological responses during experimental Corynebacterium pseudotuberculosis infection in lambs were investigated in parotid lymph nodes for ten days following inoculation. Lambs were infected by the subcutaneous route into the right eyelid with a virulent strain of C. pseudotuberculosis. Multiple microscopic acute abscesses, predominantly infiltrated with polymorphonuclear (PMN) leucocytes, were seen in the right parotid lymph node on the 1st day post-inoculation (PI). This massive PMN infiltration coincided with a peripheral blood granulocytosis. On day 3 PI, an influx of histiocytes was observed, while the microabscesses became confluent. From day 3 to day 10 PI, these lesions became enlarged and transformed into typical pyogranulomas with a central necrosis and a peripheral mantle of mononuclear cells composed of macrophages, epithelioid cells and lymphocytes; these histological changes were associated with a bacterial dissemination limited to the superficial lymph nodes. A lymphoid hyperplasia with prominent germinal centers was observed in the draining lymph nodes from day 3 PI. These results illustrate the dual role of granulomatous lesions in chronic bacterial infections: although they limit bacterial dissemination, the granulomas do not impair the persistence of infectious organisms in the host, leading to focal tissue damage.

Immunocytochemistry of canine thyroid tumors.

Immunocytochemical studies using the peroxidase-antiperoxidase method with commercial antibodies against thyroglobulin, calcitonin, calcitonin gene-related peptide (CGRP), neuron specific enolase (NSE), somatostatin, and neurotensin were performed on 38 Bouin-fixed, paraffin-embedded canine thyroid tumors obtained from necropsy and surgical files from 2 Ecoles Nationales Vétérinaires (Alfort and Nantes, France) and from the Laboratoire d'Histo-Cytopathologie Vétérinaire, Maisons-Alfort (France). The tumors consisted of two follicular adenomas, nine follicular carcinomas, nine solid carcinomas, 12 follicular-compact-cellular carcinomas, and six C-cell carcinomas. All 32 follicular-cell tumors were stained positively for thyroglobulin, half of them had weak to moderate positive immunoreactivity for NSE, and all histologic patterns were represented. They had no immunoreactivity for somatostatin or neurotensin. Four C-cell carcinomas had a solid alveolar pattern, while two had a pseudo follicular pattern characterized by uneven, often coalescent, pseudo-follicular formations with a multilayered epithelium surrounding a cavity that often contained red blood cells. Four C-cell carcinomas had uneven immunoreactivity for calcitonin, while all six were positive for CGRP or NSE. Immunoreactivity for CGRP was stronger or more widespread than positivity for calcitonin when both occurred in the same tumor. Some cells of three C-cell carcinomas had positive immunoreactivity for somatostatin. No immunoreactivity for neurotensin was detected. Seven tumors of follicular cell origin contained a few cells positive for calcitonin or CGRP, while three C-cell carcinomas had a few cells positive for thyroglobulin. These tumors were considered to contain entrapped remnants of normal thyroid tissue rather than being dual hormone producing tumors.

Epidemiological and pathological studies of a familial thymic lymphosarcoma in bovine species.

A total of 216 cases of the thymic form of bovine leukosis were observed in Holstein calves in several departments of France over a period of 18 months. Almost all of these calves were sired by the same bull. The calves were negative for bovine leukemia virus-specific antibodies. Morphological studies, including light and electron microscopic cytology, and immunophenotyping were performed in 38 cases. The tumor cells exhibit membrane markers (T-cell antigens) at variable levels, which indicate that they are T-lymphoid derived. The cells are maintained at a very early stage of differentiation as indicated by TdT enzyme activity and the presence of MHC class II antigen.

Preparation and characterization of a monoclonal antibody against bovine CD5 lymphocyte surface antigen.

The M1 monoclonal antibody (mAb) was proved to recognize 51-70% of Bovine peripheral blood lymphocytes (PBL). The M1+ cells were SIg-. In spleen and lymph nodes, the M1 positive lymphocytes were located within the T cell areas. All the lymphoid follicles remained negative. In the thymus, 10% of thymocytes were M1+, most of them were located in the medulla. The M1 mAb did not inhibit spontaneous rosette formation by sheep erythrocytes and bovine lymphocytes. On the other hand, biochemical analysis of membrane antigen with bovine thymic tumor cell line LB203 gave a molecular weight of 75 kDa. Despite a slight difference in biochemical results (75 vs 67-69 kDa). Our data permit us to consider M1 mAb as a possible homologous of human anti-CD5 mAb. Finally, M1 cross-reacted with sheep peripheral blood T lymphocytes.

Immunological aspects of mammary tumors in dogs and cats: a survey including own studies and pertinent literature.

Naturally occurring cancer in companion animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals. In dogs and cats, as in man, a role for immune responses is indicated in the development of tumors. A survey is presented based on the literature and our own studies concerning the immunological and immunotherapeutic aspects of canine and feline mammary neoplasia. In dogs bearing mammary neoplasms, circulating immune complexes appear to play a negative role in the generation of effective antitumor immune responses. The functional role of peripheral blood lymphocytes and tumor-infiltrating lymphocytes in dogs and cats with mammary tumors is not yet fully established. No tumor antigen responsible for humoral or cellular responses has yet been identified. Extracorporeal perfusion of serum of dogs with mammary tumors and subcutaneous administration of mitomycin- and neuraminidase-treated autologous tumor cells are associated with improved prognosis. The opposite was true for i.v. treatment with BCG or Corynebacterium parvum vaccine in our study, in contrast to a previous report. A number of other treatment modalities in cats and dogs with mammary carcinomas failed to induce tumor regression. Canine and feline mammary carcinomas are good candidates for modern immunotherapeutic approaches.

[Bovine spongiform encephalopathy: a new entity caused by a non-conventional transmissible agent]. / L'encéphalopathie spongiforme bovine: une nouvelle entité provoquée par un agent transmissible non conventionnel.

In 1986, a new neurologic disease appeared in the Great Britain's Cattle. According to its histological lesions, this condition belongs to the group of transmissible encephalopathies known as spongiforme encephalopathies (SE). These SE are associated with no-conventional transmission agent (NCTA) or Prion. At the time of writing, over 13,000 cases of Bovine spongiforme encephalopathy (BSE) have occurred in UK. The most likely origin of this dramatic outbreak would be an oral contamination of Cattle by the feeding of sheep carcasses or of all infected with scrapie, another SE, incorporated to concentrates. Possible factors as changes (lower temperatures and reduced use of organic solvents to extract fats) in the rendering process could have preserved the very resistant Prion in these concentrates. The important lessons resulting from our present knowledge and hypothesis are there would be no species barrier to impede transmission of the NCTA through oral route. The question concerns the public health risks posed by BSE. Two related diseases of human are Kuru and Creutzfeldt-Jacob disease. At the present time, based upon epidemiological datas on scrapie, BSE is unlikely to be a major threat to humans. Nevertheless, precautionary steps to reduce a potential risk to an absolute minimum were taken by British regulations and more recently, by European directives.