Prognostic significance of morphotypes in canine lymphomas: A systematic review of literature.

Correlation between morphotypes and prognosis of canine lymphomas presented discordant results in literature, leading to some dilemma for application in clinical practice. The aim of this study was to present a systematic review of literature on the prognostic significance of morphotypes in canine lymphomas. Standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were applied. Retrospective and prospective studies were included. Level of evidence was determined for each study. Some acceptable evidence suggested a significant prognostic impact of morphotypes in canine lymphomas. However, the evidence is not sufficiently robust to determine with precision the most appropriate classification scheme. Updated Kiel and World Health Organization (WHO) classifications seem to remain the most appropriate classification systems with regards to the number of available studies and their levels of evidence. Limitations included lack of randomized control trial, and relative lack of prospective studies available. Current recommended classification of canine lymphoma is the systematic determination of morphotype in each new case. The Updated Kiel and the WHO classifications adapted to dog both remain the schemes with the most valuable interest. Prospective studies in larger population, and international consensus to define precisely each morphotype, are warranted, with application of standardized staging method and treatment.

A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology.

This study reports cytomorphological, histomorphological, and immunological characterization of 608 biopsy cases of canine malignant lymphoma, with epidemiological and clinical data, collected from 7 French veterinary pathology laboratories. It compares morphological characteristics of malignant lymphoma in canines, per the updated Kiel classification system, with those reported in humans, per the World Health Organization (WHO) classification system. Of tumors described, 24.5% and 75.5% were classified as low- and high-grade malignant lymphomas, respectively. Presenting clinical signs included generalized or localized lymphadenopathy (82.4%) and extranodal diseases (17.6%) involving the skin (12.34%) and other sites (5.26%). Immunohistochemistry confirmed 63.8% B-cell (CD3-, CD79a+), 35.4% T-cell (CD3+, CD79a-), and 0.8% null-cell (CD3-, CD79a-) lymphomas. Most B-cell cases (38.49%) were of high-grade centroblastic polymorphic subtype; most T-cell cases (8.55%), high-grade pleomorphic mixed and large T-cell lymphoma subtypes. Some B-cell tumors showed morphologic characteristics consistent with follicular lymphomas and marginal zone lymphomas per the Revised European American Classification of Lymphoid Neoplasms and WHO canine classification systems and the WHO human classification system. Unusual high-grade B-cell subtypes included an atypical high-grade small B-cell lymphoma (0.66%), Burkitt-type B-cell lymphoma (1.64%), plasmacytoid lymphoma (0.99%), and mediastinal anaplastic large B-cell lymphoma (0.16%). Unusual T-cell subtypes included a previously undescribed high-grade canine immunoblastic T-cell type (1.15%), a rare low-grade prolymphocytic T-cell lymphoma (0.16%), and a recently described high-grade canine T-cell entity--aggressive granulocytic large-cell lymphoma (0.16%). Marginal zone lymphomas were common (10.86%); follicular lymphomas were rare (0.49%). Canine primary cutaneous malignant lymphoma subtypes were present (11.84%). There was no significant difference between B- and T-cell malignant lymphoma in regard to canine age and sex. A significant overrepresentation of Boxers (24.19%) was found for T-cell lymphomas.

Genetic and environmental risk indicators in canine non-Hodgkin's lymphomas: breed associations and geographic distribution of 608 cases diagnosed throughout France over 1 year.

BACKGROUND: The etiology of non-Hodgkin's lymphomas (NHL) is multifactorial. Environmental and genetic factors are frequently incriminated both in humans and dogs. OBJECTIVES: Our purpose was to study the geographic distribution of canine NHL (CNHL) in France and to evaluate genetic and environmental influences. ANIMALS: Six hundred and eight cases of CNHL, diagnosed throughout France over 1 year, were collected from 7 Veterinary Histopathologic Laboratories. METHODS: Retrospective study. Breeds affected by lymphomas were compared with the national population and associations between breed and immunophenotype were studied. The distribution of CNHL and canine T-cell NHL per 100,000 dogs per department was compared with the distribution of waste incinerators, polluted sites, and radioactive waste. RESULTS: The breeds significantly overrepresented among lymphoma cases were Boxer, Setter, and Cocker Spaniel (P < .001). There was a significant association between Boxer and T-cell NHL (P < .001), and between German Shepherd and Rottweiler and B-cell NHL (P < .01). The geographic distribution of CNHL and canine T-cell NHL indicated significant heterogeneity. Significant association between distributions of CNHL and waste incinerators (rho= 0.25, P < .05), polluted sites (rho= 0.36, P < .001), and radioactive waste (rho= 0.51, P < .001) was found. CONCLUSIONS AND CLINICAL IMPORTANCE: Influence of genetics in the development of CNHL was supported by the existence of an association between breed and immunophenotype. Waste incinerators, polluted sites, and radioactive waste could just be considered as risk indicators of CNHL, but not as risk factors. Case-control studies around critical sites are necessary to confirm the implication of those environmental factors in the development of CNHL.

Establishment of the European College of Veterinary Clinical Pathology (ECVCP) and the current status of veterinary clinical pathology in Europe.

After 5 years of development, the European College of Veterinary Clinical Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the European Board of Veterinary Specialisation (EBVS), the European regulatory body that oversees specialization in veterinary medicine and which has approved 23 colleges. The objectives, committees, basis for membership, constitution, bylaws, information brochure and certifying examination of the ECVCP have remained unchanged during this time except as directed by EBVS. The ECVCP declared full functionality based on the following criteria: 1) a critical mass of 65 members: 15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto diplomates, 7 diplomates certified by examination, and 5 elected honorary members; 2) the development and certification of training programs, laboratories, and qualified supervisors for residents; currently there are 18 resident training programs in Europe; 3) administration of 3 annual board-certifying examinations thus far, with an overall pass rate of 70%; 4) European consensus criteria for assessing the continuing education of specialists every 5 years; 5) organization of 8 annual scientific congresses and a joint journal (with the American Society for Veterinary Clinical Pathology) for communication of scientific research and information; the College also maintains a website, a joint listserv, and a newsletter; 6) collaboration in training and continuing education with relevant colleges in medicine and pathology; 7) development and strict adherence to a constitution and bylaws compliant with the EBVS; and 8) demonstration of compelling rationale, supporting data, and the support of members and other colleges for independence as a specialty college. Formal EBVS recognition of ECVCP as the regulatory body for the science and practice of veterinary clinical pathology in Europe will facilitate growth and development of the discipline and compliance of academic, commercial diagnostic, and industry laboratories in veterinary clinical pathology. Future needs are in developing sponsorship for resident positions, increasing employment opportunities, increasing compliance with laboratory, training, and continuing education standards, and advancing relevant science and technology.

Mycobacterium tuberculosis infection in a dog from Africa.

A 4-year-old male Boxer dog with a history of vomiting, diarrhea, and weight loss moved from West Africa to Lyon, France, where it was further evaluated. Radiographs revealed pleural effusion and enlargement of tracheobronchial lymph nodes and liver. Cytologic examination of the pleural effusion and a fine needle aspirate specimen of the liver showed mixed mononuclear inflammation with nonstaining rod structures within epithelioid histiocytes. At necropsy, the main gross pathologic findings were exudative pleuritis, nodular hepatitis, and infarcts and caseous nodules in the kidneys. The main histologic lesions were granulomatous hepatitis, granulomatous pneumonia, fibrinous leukocytic pleuritis, necrotic and fibro-calcified granulomatous lymphadenitis, and granulomatous nephritis. A Ziehl-Neelsen stain applied to both cytologic and histologic samples was positive for acid-fast bacilli. Bacterial culture of the pleural fluid was positive for Mycobacterium tuberculosis. Cytology is a valuable tool in the diagnosis of this important zoonotic disease.

High-grade canine T-cell lymphoma/leukemia with plasmacytoid morphology: a clinical pathological study of nine cases.

The aim of this study is to determine the clinical, morphological, and immunophenotypical presentation of 9 cases of a particular type of canine T-cell lymphoma/leukemia. The morphological presentation was a diffuse infiltration of small, medium-sized, or large blast cells with eccentric nuclei, hyperbasophilic cytoplasm, and a juxtanuclear, pale cytoplasmic area, giving a plasmacytoid appearance and suggesting a B-cell morphology. Surprisingly, all 9 cases were of T-cell phenotype (CD3+). Among the 7 immunophenotyped cases, 4 were CD4-/CD8+, 2 CD8+/CD4+, and 1 CD4+/CD8-. The median Ki-67 index was 65.7%, which placed this lymphoma in the high-grade group. This type of lymphoma/leukemia was found in dogs between 1 and 11 years of age, with a median age of 5.8. The male-female ratio was 0.8 for a reference population of 1.04. The most significant clinical findings were lymphadenopathy either generalized or localized in all cases, a mediastinal mass in 4 cases, bone marrow involvement in 7 cases, hypercalcemia in 4 cases, along with an aggressive clinical course and a poor response to chemotherapy in all cases, with a median disease-free survival time of 3 months.

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).

Cytohistological and immunological classification of canine malignant lymphomas: comparison with human non-Hodgkin's lymphomas.

Non-Hodgkin's lymphomas (NHLs) in man are on the increase. They are also common in dogs, which, as close companions of man, may constitute a useful experimental model. However, comparisons cannot be made without a reliable morphological and immunological classification of canine NHL. Canine NHLs (n = 134) were classified on the basis of fine-needle lymph-node aspirates according to the Kiel classification, and 92 were re-classified according to the Working Formulation and the updated Kiel classification, in a histological and immunological study. The immunophenotype was determined (1) in 92 cases by the use of the pan-T anti-CD3 polyclonal antibody and the pan-B anti-mb1 monoclonal antibody on paraffin wax-embedded tissue sections, and (2) in 47 cases by the use of a panel of polyclonal and monoclonal antibodies on fresh preparations and frozen tissue. Cytological analysis showed a predominance of high-grade lymphomas (73.9%) over low-grade lymphomas (26.1%); it also demonstrated forms not reported in other species (small-cell variants, lymphomas with macronucleolated medium-sized cells [MMCs], and polymorphic lymphomas with a centroblastic component). Histological examination revealed the rarity of follicular lymphomas (2.2% of cases), an appearance suggestive of T-cell neoplasia (8.7% of cases), and evidence that some MMC lymphomas originated in the marginal perifollicular zones. Some (26%) of the lymphomas were of the T-cell phenotype: the majority of these consisted of small-cell, low-grade lymphomas and mycosis fungoides, the rest being either high-grade pleomorphic lymphomas (mixed or large-cell) or, rarely, high-grade, small noncleaved-cell, plasmacytoid lymphomas. No lymphoma expressed a double (T and B) phenotype. This study revealed similarities with, but also notable differences from, human NHL. In particular, the MMC lymphomas may constitute an interesting equivalent of human marginal zone B-cell lymphomas.

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.