Canine T-cell lymphomas: a morphological, immunological, and clinical study of 46 new cases.

The aim of this study is to report 46 new cases of canine T-cell lymphomas among a series of 140 lymphomas studied by immunophenotyping (incidence 32.8%). According to the updated Kiel classification adapted to the canine species, 13 were classified as low-grade and 33 as high-grade lymphomas. Among the low-grade lymphomas, five were small clear-cell lymphomas, three were pleomorphic small-cell lymphomas, and five mycosis fungoides. Among the high-grade cases, there were 11 pleomorphic mixed-, small-, and large-cell lymphomas, 6 pleomorphic large-cell lymphomas, 11 lymphoblastic lymphomas, and 5 unclassifiable high-grade plasmacytoid lymphomas. The cytohistologic features were highly suggestive of a T-cell phenotype on the basis of cell morphology (irregular nuclei and clear cytoplasms) (30/46 cases), a T-cell zone pattern, and the presence of hyperplastic postcapillary venules (22/46 cases). All 46 cases were CD3+ CD79a-, and among 34 cases investigated for CD4 and CD8 expression, 13 were CD4+CD8-, 13 were CD8+CD4-, and 8 were CD4CD8 double positive or double negative. The pleomorphic mixed lymphomas were mainly CD4+CD8- (6/7) and the lymphoblastic lymphomas were double positive or double negative (6/8). The main clinical, hematologic, and biochemical features were generalized (28/46) or regional lymphadenopathy (16/46), hepatosplenomegaly (15/46), extranodal involvement (11/46), mediastinal mass (9/46), and leukemia (8/46), which were mainly present in cases of lymphoblastic lymphomas and hypercalcemia (16/46).

Canine large granular lymphocyte leukemia and its derived cell line produce infectious retroviral particles.

We describe a case of large granular lymphocyte (LGL) leukemia in a dog that we followed over a period of 2 years. Analysis of a hematological profile revealed lymphocytosis (19,500 lymphocytes per microliter; reference values, 1,000-4,800 lymphocytes per microliter), with a majority of LGL on the blood smear. LGL is defined as a lymphoid subset comprising 10% of peripheral blood mononuclear cells and corresponding to either CD3- CD8- NK cells or CD3+ CD8+ T cells. The cells are characterized by abundant basophilic cytoplasm containing distinct granules of variable size and number. The characteristic phenotype of our leukemic LGL is of a cytotoxic T cell, CD3+ and CD8+. A new cell line, DLC 02, was established from the peripheral lymphocytes of the leukemic dog. Particles with type C retroviral morphology were found in ultrathin sections of DLC 02 cell pellets. These particles were found to have a sucrose gradient density of 1.17 g/liter and a reverse transcriptase activity with an Mn2+ preference, suggesting that they correspond to a mammalian type C oncovirus.

Characterization of a canine long-term T cell line (DLC 01) established from a dog with Sézary syndrome and producing retroviral particles.

The canine DLC 01 cell line derives from a lymph node of a dog with Sézary syndrome. The DLC 01 cell phenotype is CD4-, CD8+, CD45+, DQ+, similar to that of original cells after treatment with dimethylsulfoxide or phorbol myristate. Canine cutaneous T cell lymphoma are usually CD4-, CD8+ in contrast to their human counterparts which are CD4+, CD8-. Therefore, the DLC 01 cell line appears to be a unique model to study the mechanism of all surface molecule expression in vitro. Viral particles with retrovirus type-C morphology were found in ultrathin sections of DLC 01 cell pellets. Retroviral particles are spontaneously produced after the 50th cell passage or after induction with 0.5% dimethylsulfoxide. This is the first description of a dog lymphoid cell line spontaneously growing and producing a retrovirus. It was found to share several features in common with feline and murine leukemia viruses.

Growth fractions in canine non-Hodgkin's lymphomas as determined in situ by the expression of the Ki-67 antigen.

The proportion of proliferating cells in non-Hodgkin's lymphomas (NHLs) as determined in situ by the expression of the Ki-67 antigen, has prognostic value in human oncology, and is strongly related to the different grades of malignancy. The evaluation of the Ki-67 index in canine NHLs may be useful in assessing the individual variability of the growth fraction in the different sub-types of lymphoma, and also the validity of the classification in terms of grade of malignancy. The growth fraction was evaluated in 92 canine NHLs, previously classified according to the Kiel classification (as adapted to the canine species), by determining the expression of the Ki-67 antigen with the MIB1 antibody on (1) paraffin-wax tissue sections in all 92 cases, and (2) fine-needle aspirates or tumour imprints in 30 cases. The labelling appeared satisfactory in 88% of the cases, with good concordance between the histological and cytological data. A highly significant correlation (P < 0.001) was established between the proportion of Ki-67+ cells and the classification into low-grade (Ki-67 index < 21%) and high-grade malignancy (Ki-67 index > 21% and usually > 29%). In the low-grade lymphoma group, a macronucleolated medium-sized-cell lymphoma not found in man had the lowest proliferation index. In the high-grade malignancy group, the number of Ki-67+ cells seemed to be proportional to cell size, whatever the phenotype, with the rare exceptions of some unclassifiable small-cell Burkitt-type or plasmacytoid lymphomas, which were highly proliferating. The classification of lymphomas into low-grade and high-grade appears to correlate well with their proliferative index. The existence of individual variations, within given categories of canine NHL, suggests that, as in human medicine, prognosis may be assisted by determining the growth fraction at initial diagnosis, and by fine-needle aspiration at relapses.

[Clinical, morphologic and immunophenotypic data based on 10 cases of canine muco-cutaneous epidermotropic T-lymphoma (analogous to Mycosis Funcgoïde). Important of an animal model of spontaneous pathology]. / Données cliniques, morphologiques et immunophénotypiques à partir de 10 observations de lymphome T cutanéo-muqueux épidermotrope du chien (analogue au Mycosis Fongoïde). Intérêt d'un modèle animal de pathologie spontanée.

Our serie of ten canine cutaneous epitheliotropic T-cell lymphomas (CTCL), is found in old dogs, belonging mainly to the Boxer breed. Site on the mucous membranes (especially buccal), the muco-cutaneous junctions, their clinical expression is polymorphous. Lesions, follow on one after another (erythema, plaques, nodules) and are diversely associated in a given animal, the borders between the different stages often being difficult to establish. Adenopathies noted at the time of the diagnosis or during the course of the condition are accompanied by an involvement of the blood and organs (analogous to Sézary's disease). The progression of the disease can be very rapid in the buccal forms, which are generally aggressive, and in cases of violent, uncontrollable pruritus, which may be disturbing for the owner (with requests for euthanasia). The neoplastic infiltrate is constituted of small lymphocytes with hyperchromatic, convoluted nuclei (incipient stages), then large cells with a "histiocytic" appearance for the nodules. Epitheliotropism, which is maximal for the infiltrated plaque stage, shows up either in the form of a flux of totally epitheliotropic isolated cells (Ketron-Goodman type) or in that of Pautrier abscess-like collections. THe veterinary literature is in agreement that the CTCL cell expresses CD3, but two recent studies are in contradiction as regards its membership of helper or cytotoxic/suppressor populations. For our 10 cases, all the cells of lymphocytic morphology were, without exception, CD3+ and CD45+, irrespective of their situation within the epithelium or the chorion. The CD3+ cells in the epithelium were systematically CD8+, CD4- (confirming P.F. Moore's observations), expressing CD5 in a variable way, and, mostly, the Ki-67 nuclear proliferation Ag. The CD3+ cells of the chorion were exclusively, or mainly, CD8+, and occasionally CD4+. They expressed CD5 in a variable way, and, for a minority, the Ki-67 nuclear proliferation Ag. On the pathogenic level, it may be suggested that a T clone, CD8+, undergoes the "homing" phenomenon within the epithelium, enters the cell cycle, then manifests a tropism towards the chorion, which it infiltrates. Despite some particularities, which may be clinical (serious mucous attacks), cytological (the "histiocytic" appearance of the nodule cells) or immunophenotypic (expression of CD8, similar to what is observed in man in a considerable number of Pagetoid reticulosis), CTCL constitutes an interesting model of spontaneous pathology, and could prove useful in: - identifying various etiological factors (given that the dog, as a close commensal of man, is subject to the same environmental factors).