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.
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 (ρ= 0.25, P < .05), polluted sites (ρ= 0.36, P < .001), and radioactive waste (ρ= 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.
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.
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 largecell lymphomas, 6 pleomorphic large-cell lymphomas, 11 lymphoblastic lymphomas, and 5 unclassifiable highgrade 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).
Pretreatment D-dimer levels have been reported to predict survival in several types of malignancies in human patients. The objective of this study was to evaluate the prognostic value of pretreatment ...D-dimer level in dogs with intermediate to high-grade non-Hodgkin lymphoma (NHL). In a prospective, randomized, double-blind study of F14512 vs etoposide phosphate, we assessed the prognostic value of pretreatment plasma D-dimer level in 48 client-owned dogs diagnosed with intermediate to high-grade NHL. The correlation between pretreatment plasma D-dimer level and various clinical features, progression-free survival (PFS) and overall survival (OS) was analysed. The median value of pretreatment plasma D-dimer level was 0.4 μg/mL (range: 0.1-14.3 μg/mL). High pretreatment plasma D-dimer level (>0.5 μg/mL) was detected in 44% (21/48) of dogs. High D-dimer levels were not correlated with naive vs relapsed lymphoma, clinical stage, substage, immunophenotype or treatment group. D-dimer levels >0.5 μg/mL were significantly associated with inferior median PFS (54 vs 104 days, P = .011) and OS (93 vs 169 days, P = .003). In the multivariate analysis, high D-dimer levels remained an independent predictor for worse PFS (HR: 3.21, 95% CI: 1.57-6.56, P = .001) and OS (HR: 3.87, 95% CI: 1.88-7.98; P < .001). This study suggests that pretreatment plasma D-dimer level can serve as a predictor of prognosis in dogs with intermediate to high-grade NHL. Further studies are warranted to confirm these findings.
: 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.
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.
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 lymphnode aspirates according to the Kiel classification, and 92 were re-classified according to the Working Formulation and the updates 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.
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.
The aim of this study was to determine the response of different morphological subtypes of canine lymphoma to a standardized therapeutic protocol. Diagnosis of lymphoma was based on cytohistological ...analysis and immunophenotyping with antibodies against CD3 and CD79a of an enlarged lymph node or an extranodal mass. Fifty-seven cases were classified according to the updated Kiel classification adapted to the canine species, into 24 B-cell lymphomas (20 centroblastic polymorphic and four Burkitt-type subtypes), and 33 T-cell lymphomas (10 pleomorphic mixed, 10 lymphoblastic, eight unclassifiable high grade plasmacytoid, and five small clear-cell subtypes). All dogs were clinically staged at diagnosis. The protocol used
l-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisone. First remission duration and overall survival time were evaluated. Although the T-cell phenotype was associated, on the whole, with a poor prognosis, as previously reported in veterinary and human medicine, the study showed significant prognostic differences between the B- and the T-cell subtypes of canine lymphoma and suggests that clinico-morphological characterization of the disease is justified in dogs, as in humans.
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