scholarly journals Epidemiology, clinical and cytological features of lymphoma in Boxer dogs

2019 ◽  
Vol 67 (2) ◽  
pp. 224-240
Author(s):  
Urszula Jankowska ◽  
Dariusz Jagielski ◽  
Michał Czopowicz ◽  
Rafał Sapierzyński

The aim of this study was to evaluate the epidemiology, clinical and laboratory characteristics of canine lymphomas as well as some aspects of treatment outcomes. The study was conducted on Boxer dogs with lymphoma diagnosed by cytology and immunocytochemistry (CD3 and CD79 alpha). During the study period, lymphoma was diagnosed in 63 Boxers; 86.8% were T-cell (based on the Kiel classification: small clear cell lymphoma, pleomorphic small cell lymphoma, pleomorphic mixed T-cell lymphoma, pleomorphic large T-cell lymphoma, lymphoblastic lymphoma/acute lymphoblastic leukaemia) and 13.2% were B-cell lymphomas (according to the Kiel classification: B-cell chronic lymphocytic leukaemia, centroblastic/centroblastic polymorphic lymphoma). Overall survival (OS) was significantly longer in dogs with low-grade than with high-grade lymphoma (median OS of 6.8 and 4.7 months, respectively; P = 0.024). OS was not influenced by WHO clinical stage, WHO clinical substage, presence of splenomegaly, early administration of glucocorticoids or the time from the first presentation to the beginning of chemotherapy. There are no significant differences in clinical and laboratory parameters between low-grade and high-grade lymphomas. Boxer dogs are predisposed to T-cell lymphoma, with a predominance of high-grade tumour, especially pleomorphic, mixed small and large T-cell subtype. It is possible that Boxer dogs may respond less favourably to chemotherapy than patients of other breeds.

2007 ◽  
Vol 44 (4) ◽  
pp. 467-478 ◽  
Author(s):  
S. P. Fosmire ◽  
R. Thomas ◽  
C. M. Jubala ◽  
J. W. Wojcieszyn ◽  
V. E. O. Valli ◽  
...  

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.


1989 ◽  
Vol 7 (6) ◽  
pp. 725-731 ◽  
Author(s):  
A L Cheng ◽  
Y C Chen ◽  
C H Wang ◽  
I J Su ◽  
H C Hsieh ◽  
...  

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3014-3014
Author(s):  
Elias Drakos ◽  
George Z. Rassidakis ◽  
Wei Guo ◽  
L. Jeffrey Medeiros ◽  
Lalitha Nagarajan

Abstract The gene MIXL1 (Mix1 homeobox-like) encodes a paired class homeobox transcription factor involved in early hematopoietic specification during embryogenesis. Previous studies have shown that MIXL1 gene is expressed in hematopoietic cells during adult life (Guo et al. Blood100;1;89–96, 2002). Furthermore 5′ MIXL1 sequences are a target of retroviral insertion in murine T-cell lymphoma (http:RTCGD.ncifcrf.gov), suggesting a selection advantage for aberrant expression of this gene. However, the status of MIXL1 expression in human lymphomas has not been examined. Using a highly specific antibody, we assessed for MIXL1 protein expression in 14 lymphoma cell lines (9 B-cell and 5 T-cell) by immunobloting. MIXL1 was detected predominantly in nuclear extracts of lysates of all cell lines tested, although at a variable level. We also assessed for MIXL1 protein expression in 126 B-cell and 21 T-cell NHLs of various types, as well as 14 Hodgkin lymphomas using immunohistochemical methods. The results of the immunohistochemical studies are summarized in table 1. Once again, MIXL1 immunoreactivity was primarily nuclear in the tumor cells. Based on distribution data (histogram), a 50% cutoff was selected for high versus low MIXL1 expression. Among B-cell tumors, high expression levels of MIXL1 protein were more frequently detected in high-grade NHL and HL compared with low/intermediate grade NHL (p<0.0001, chi-square test). As a continuous variable, the percentage of MIXL1-positive tumor cells was also significantly higher in high-grade B-cell NHL and HL compared with low/intermediate grade NHL (p<0.0001, Kruskal Wallis test). All Hodgkin lymphomas expressed high levels of MIXL1 with 60% to 100% of neoplastic cells being positive for MIXL1. Most T-cell NHLs also expressed high levels of MIXL1. In contrast, most low/intermediate-grade B-cell NHL and multiple myelomas expressed low levels of MIXL1. Frequent overexpression of MIXL1 gene product in most high-grade B-cell NHLs, HL and T-cell NHLs suggests that aberrant expression of MIXL1 may play a role in proliferation, block of differentiation or both. Table 1. HL (n=14) B-NHL (n =126) T-NHL (n =21) N (%) Low/intermediate grade N (%) N (%) Classical HL 12/12(100%) Chronic lymphocytic leukemia /small lymphocytic lymphoma 0/8 (0% T-precursor lymphoblastic leukemia/lymphoma 2/2 (0%) Nodular lymphocyte predominance HL 2/2 (100%) MALT-lymphoma 0/8 (0%) Mycosis fungoides/Sezary syndrome 2/2 (0%) Follicular lymphoma 9/24 (38%) Extranodal NK/T-cell lymphoma, nasal type 3/3 (100%) Mantle cell lymphoma 5/34 (15%) Peripheral T-cell lymphoma, unspecified 6/9 (66% High grade Anaplastic large cell lymphoma 5/5 (100%) B-precursor lymphoblastic leukemia/lymphoma 1/3 (33%) Burkitt lymphoma/leukemia 2/2 (100%) Diffuse large B-cell lymphoma 30/31 (97%) Plasma cell myeloma/plasmacytoma 0/16 (0%)


2001 ◽  
Vol 23 (2) ◽  
pp. 139-142 ◽  
Author(s):  
C. Christopoulos ◽  
A. Tassidou ◽  
S. Golfinopoulou ◽  
G. Anastasiadis ◽  
S. Manetas ◽  
...  

Cancer ◽  
1994 ◽  
Vol 74 (1) ◽  
pp. 164-167 ◽  
Author(s):  
Ami Klein ◽  
Yosef Manor ◽  
Shlomo Abed ◽  
Valery Leytin ◽  
Hava Shapiro ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4527-4527
Author(s):  
Monika Joshi ◽  
Hassan S Sheikh ◽  
Fabian Camacho ◽  
Lisa A Hand ◽  
Michael G. Bayerl ◽  
...  

Abstract Abstract 4527 Background The incidence of lymphoma has doubled in the past 3 decades in the US and most western countries. Since the advent of multi-drug chemotherapy, studies have shown improvement in survival in specific diagnostic groups such as diffuse large B-cell lymphomas. However, there have been few studies showing the impact of evolving therapies on survival for the total burden of lymphoma patients. We assessed survival for an aggregate population of all patients presenting with lymphoma to a regional tertiary university hospital over the past 3 decades. Goal To assess the magnitude of improvement in survival for patients with lymphoma over the past 3 decades. Methods We analyzed data from the Penn State Hershey Medical Center Cancer Registry, selecting all cases diagnosed with lymphoma by ICD-0-3 codes from Jan 1st 1976 to Dec 31st 2006. Five and ten year (yr) absolute survival rates during five time periods [group (gp) 1: 1976-1980, gp 2: 1981-1985, gp 3: 1986-1990, gp 4: 1996-2000, gp 5: 2001-2006] were obtained by using conventional period analysis (PA). In addition, a period Cox Proportional Model (CPH) was fit to the data, allowing for survival risk estimates of 5 yr survival, statistical testing of time periods, and adjustments for age at diagnosis. SAS v 9.1 was used to obtain estimates, with Brenner's PERIOD macro used for PA and PHREG used for CPH. Results Of 2843 patients, Hodgkin's lymphoma accounted for 17%, high grade lymphoma 4%, intermediate grade lymphoma 29%, low grade lymphoma 17%, cutaneous T-cell lymphoma 6%, chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) 13%, malignant lymphoma not otherwise specified (NOS) 14%. Median age was 56 yr and mean was 52 yr with a standard deviation (SD) of 20.9 yr. Median follow up was 4 yr and mean was 6 yr with SD 6.5 yr. Approximately 25% (N=700) survived beyond 10 yr. CPH adjusted for age demonstrated a 5 yr improvement among all lymphomas of 8%, Hazard Ratio (HR)=1.31, 95%, p=0.0192, between gp 5 and gp 1. Consistent improvements in 5 yr survival were detected for intermediate grade lymphoma (15%, HR=1.5, p=0.0219), high grade lymphoma (40%, HR=12.83, p<0.0001), and malignant lymphoma NOS (19%, HR=1.8, p=0.069) comparing gp 5 to gp 1. Changes in survival rates for Hodgkin's lymphoma, low grade lymphoma, CLL/SLL, and cutaneous T-cell lymphoma were not significant. Results for conventional PA were similar. There was a 7% improvement in 5 yr survival between gp 5 and gp 1 for all patients with lymphoma. However, improvement in 10 yr survival between available time intervals was minimal. For the PA, significant improvement in 5 yr survival was seen for intermediate grade lymphoma (24%), high grade lymphoma (28%), malignant lymphoma NOS (19%) comparing gp 5 to gp 1. Interestingly, cutaneous T-cell lymphoma showed a descriptive decline in both 5 yr and 10 yr survival of 29% and 14% respectively. Conclusion There has been a significant improvement of 8% in overall 5 yr survival in lymphoma patients over the past 3 decades after adjusting for age. There was an improvement in survival in both intermediate and high grade groups. There was a trend towards declining survival in cutaneous T cell lymphoma. This could be attributed to diagnostic drift with changing classification and to the fewer number of cases diagnosed in the earlier years as compared to later years. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4450-4450 ◽  
Author(s):  
Colette N Owens ◽  
Jocelyn C Migliacci ◽  
Steven M. Horwitz ◽  
Matthew J Matasar ◽  
Alison J Moskowitz ◽  
...  

Abstract Background: NHL is a disease of older adults and henceforth the oncology community will be increasingly confronted with the challenges of the older lymphoma patient (pt). Phase II data demonstrates dose-adjusted (DA)-EPOCH +/- rituximab is efficacious in high grade and aggressive NHL (J Clin Oncol. 2008 Jun 1;26(16): 2717-24). Additionally, infusional doxorubicin may confer greater safety in elderly pts compared with bolus delivery. A Phase III trial (NCT00118209) comparing DA-R-EPOCH and R-CHOP has been completed, but the results are not currently available. To date, there is limited data on efficacy and safety in elderly patients treated with DA-R-EPOCH. We explored our single center experience to inform therapeutic choices in older adults. Methods: We retrospectively reviewed all pts treated with EPOCH at MSKCC from 2003 to 2014, identifying 181 pts in total, of which 54 pts > 60 yrs (out of 73 pts >60 yr) received DA-EPOCH at initial diagnosis. Data was available regarding their baseline characteristics, dose adjustments/treatment modifications, hospitalizations, and disease related outcomes for all pts. Outcome measures included progression free (PFS) and overall survival (OS), hospitalizations, and dose adjustments. Results: Of 54 patients, histologies included DLBCL (n=42, 78%), T-cell lymphoma (n=8, 15%), and Burkitt lymphoma (BL) (n=4, 7%). The median age of all patients was 70.5 yrs (range 61-93 yrs), with 54% female. Prior malignancy was present in 31% and baseline LVEF was >55% in 98% of pts. For DLBCL patients (n=42): median age 72 yrs (61-92 yr), M:F 24:18, Stage I/II v. III/IV: 21% v. 79%, aaIPI 0-1 v. 2-3: 24% v 76%; cell of origin (Hans) GC/ABC/unknown: 43%/52%/5%. Ki67%: median 90% (range 20-100%). T-cell pts (n=8): median age 68 yrs (61-75 yr), female 50%, histology ATLL(n=4), PTCL (n=3), ALCL ALK- (n=1); 100% adv. stage; BL pts (n=4): ages 65, 69, 82, 81 yrs, 1 early stage, 3 adv. stage, 1 low risk, 3 high risk. Rituximab was given in 96% of b-cell NHL. Peg-GCSF/GCSF was used with each cycle of EPOCH. A full 6 cycles of EPOCH was completed 52% of the time and dose adjusted in 66% of pts with a median of 4 adjusted cycles/pt (range 1-6). Dose increases occurred in 30% of pts, dose decreases 26%; 11% of pts started at dose level -1. Safety: Cardiac events occurred in 22% of pts, with 2 pts experiencing anthracycline induced cardiomyopathy/CHF, the remainder included G ≥3 arrhythmias (n=6) or chest pain/angina (n=4) without change in EF. Hospitalization for G≥3 toxicity occurred in 68.5% (n=37) of pts (41% more than once): neutropenic fever/infection (n=19/9), AKI/dehydration (n=7), syncope (n=2); Treatment related mortality was 4% (n=2). Outcomes: With a median followup of 1.5 yrs, 33 of 54 pts remain progression free (DLBCL 30/42, TCL 1/8, BL 2/4, p=0.007). For all pts, median PFS and OS have not been reached: PFS and OS at 1.5 yr is 57% and 66%, respectively. For DLBCL pts, median PFS and OS is not reached: PFS and OS at 1.5 yr is 69% and 78%, respectively. In log-rank analysis: aaIPI (p=.15), Stage (p=.08) and cell of origin (p=.35) did not predict OS; aaIPI (p=.05) and stage (p=.04) predicted PFS, but cell of origin was not significant. There was no significant difference in outcome based on dose adjustments. Conclusions: DA-EPOCH +/- R is an effective treatment option for pts > 60 yrs with advanced stage, high risk DLBCL; Hospitalizations for toxicity were frequent, but TRM was low. Cardiomyopathy was infrequent. Dedicated efforts to explore initial dose-reductions and optimal number of cycles in this older pt population would be beneficial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5220-5220
Author(s):  
Jad Saab ◽  
Zaher Otrock ◽  
Georges Aftimos ◽  
Fadi Nasr ◽  
Fadi Farhat ◽  
...  

Abstract Abstract 5220 Background: lymphoid neoplasms represent a diverse group of neoplasms that are broadly classified into non-Hodgkin lymphomas (NHL) and Hodgkin lymphoma (HL). Incidence of particular subtypes and pathogenic associations with certain viral infections are derived from data from the Western world. Little is known about such associations in developing countries; accordingly, this prospective study evaluates newly diagnosed cases of lymphomas in Lebanon and evaluates the incidence of particular subtypes and possible association with various viral infections. Patients and Methods: this was a collaborative nationwide study that included all patients diagnosed with lymphoma in Lebanon in 2007. Epidemiological, clinical and histological data were collected. Available lymphoma tissue (stained slides and paraffin-embedded tissue) was reviewed by a panel of pathologists. Blood was collected for serologic testing for the following viruses: hepatitis C (HCV), HIV, EBV, and HTLV-I. Results: 275 cases, 140 (50.7%) males and 136 (49.3%), with lymphoma were diagnosed. Eighty one cases (76 from academic centers and 5 from community hospitals) were reviewed by the pathology panel. The overall concordance rate was 87.6% (71/81); there was discordance in 6 (7.4%) cases: 3 originally diagnosed as diffuse large B cell lymphoma (DLBCL) were revised to high-grade follicular lymphomas, 1 small lymphocytic lymphoma (SLL) previously DLBCL, 1 DLBCL previously low grade lymphoma, 1 DLBCL previously lymphoblastic lymphoma; 4 cases were considered equivocal on revision. The enrolled cases were classified as follows: 183(66.5%) NHL (150 cases B cell lymphoma - 81 DLBCL, 35 follicular, 12 marginal zone/MALT, 11 mantle cell, 7 SLL/CLL, 2 transformed follicular/DLBCL, 2 lymphoblastic; 16 cases T cell lymphoma - 7 peripheral T cell NOS, 4 anaplastic, 2 lymphoblastic, 1 angioimmunoblastic, 1 NK cell, 1 adult T cell leukemia/lymphoma (ATLL); 17 unclassified); and 92(33.5%) HL (60 nodular sclerosis, 5 mixed cellularity, 5 lymphocyte predominant, 1 lymphocyte-rich, 21 unclassified). Blood was obtained from 120 patients. Serology was negative for HCV in all tested cases. HIV was positive in 2 cases (1 NHL, 1 HL). EBV IgG were positive in 106 (88.3%) cases (68/77 NHL, 38/43 HL). Also, 38 EBV seropositive cases (27 NHL (24 B-cell type & 3 T-cell type), 11 HL) were studied for latent membrane protein-1 (LMP-1); LMP-1 staining was positive in 8(21%) cases, of which 6 were HL and 2 were T-cell NHL. Only one case with peripheral T cell lymphoma (ATLL) tested positive for HTLV-1. Conclusions: our epidemiological study showed that two-thirds of lymphoma cases diagnosed over a year were NHL. Reviewing almost one-third of cases showed an 87.6% concordance rate in diagnosis. Serologic testing of viruses did not reveal any specific pattern that suggests an association between the tested viruses (HCV, HIV, EBV, and HTLV-I) and lymphoma. However, LMP-1 testing was positive in 54.5% of IgG positive HL cases and in 66.7% of IgG positive T-cell NHL. These finding confirm a strong association of EBV with HL and T-cell lymphoma. Disclosures: Bazarbachi: Hoffman La Roche: Research Funding.


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