Canine Multicentric Lymphoma

Question 1

Burton et al. Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric LSA

31 client owned dogs

Overall response rate?

Median PFI?

Dogs with treatment delays had?

Did dose intensity correlate with patient outcome?

Answer 1

100%

140 days (~ 5 months)

Longer PFI and overall survival in multivariable analysis

No

Dogs with delays may receive MTD while dogs with no AE may be underdosed

Question 2

Martini et al. Peripheral blood abnormalities and bone marrow infiltration in canine large B-cell LSA: is there a link?

Determine if blood abnormalities can predict BM involvement assessed by flow cytometry (BM involvement)

Difference between no hematological abnormalities and atleast 1?

Degree of infiltration was correlated with? Negatively correlated with? Positively correlated with?

Answer 2

None

Higher in dogs with thrombocytopenia, leukocytosis, or lymphocytosis and was negatively correlated to platelet count and positively to blood infiltration

Blood abnormalities do not always predict marrow involvement​ - do a BM!

Question 3

Lucas et al. Pilot clinical study of carmustine associated with a lipid nanoemulsion in combination with vincristine and prednisone for the treatment of canine LSA

Safety of LDE as carmustine carrier (50 mg m(-2) , intravenous) combined with vincristine and prednisone for the treatment of dogs with lymphoma was tested and compared with commercial carmustine with vincristine and prednisone.

CR in how many dogs?

PR in how many dogs?

Median PFI?

OS?

Answer 3

5 dogs with LDE-carmustine and 6 with commercial carmustine

2 from each group

119 ( 4 months) and 199 days (6.6 months)

207 (7 mons) and 247 days (8 mons)

No difference between treatments

Question 4

Regan et al. Diagnostic evaluation and treatment recommendations for dogs with substage a-a high grade multicentric LSA: results of a survery of veterinarians

Survey veterinarians about initial diagnostic and treatment recommendations

Most commonly recommended staging diagnostics?

Most common treatment recommendation?

___% of responsed treated B and T cell differently

Protocol lenghts?

Answer 4

CBC (100%), chemistry (100%), UA (85%), LN cytology (88%), CXR (84%), immunophenotyping (76%) and AUS (75%)

L-CHOP (51%), CHOP (30%) other CHOP based protocol (12%)

31%

<16 weeks to > 2 years

Question 5

Elliot et al. Epirubicin as part of a multi-agent chemotherapy protocol for canine LSA

Report outcome in 97 dogs with LSA tx multiagent chemo protocol containing epirubicin

75 dogs received 25-week protocol and non maintenance and 22 got maintenance phase

CR rate?

Time to first relapse (TTR) and OS?

Who had poorer TTR and OS?

Answer 5

96%

216 (7.2 months) and 342 days (11.4 months)

Dogs with T-LSA and substage b

Question 6

Higginbotham et al. 2013. Intermittent Single-Agent Doxorubicin for the Treatment of Canine B cell LSA

Overall CR rate?

Median total doxorubicin remission time

Median OS?

Median # of doxorubicin treatment?

First remission times affected by?

Answer 6

78%

80.5 days

170 days

4.5

Clinical stage and substage of disease

Question 7

Valli et al. Canine LSAs: Association of classification type, disease stage, tumor subtype, mitotic rate, and treatment with survival

Mitotic rates with indolent or low grade vs. high grade?

Most cases were?

Higher mortality rates? Lower motality rates?

MST for low grade T-cell (T-zone) lymphoma? High grade T cell LSA?

MST for centroblastic large B cell LSA?

Answer 7

low vs. high mitotic rate

Centroblastic large B-cell LSA

High grade LSA, low grade T-cell LSA

622 days (1.7 years). 162 days (5.4 months)

127 days with low stage and 221 days with intermediate and 215 with advanced stage

A histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of specific subtype

Question 8

Back et al. Mechlormethamine, vincristine, melphalan, and prednisone (MOPP) for the treatment of relapsed LSA in dogs

MOPP on 28 day tx cycle to 88 dogs with relapsed LSA

ORR for median of?

How many experienced CR for median of how many days?

How many experienced PR for median of how many days?

ORR with T-LSA?

ORR with B-LSA?

OSS?

Toxicity?

Answer 8

51% for a median of 56 days (~2 months)

12% for median of 81 days

38.6% for median of 50 days

55% for median of 60 days

57% for median of 81 days

183 days (~6 months)

54% with majority classified as grade I

Question 9

Kol et al. Serial hemostatic monitoring of dogs with multicentric LSA

Characterize hemostatus of dogs with LSA - 27 dogs

How many had altered hemostatic status consistent with hypercoagulability?

Laboratory evidence of hypercoagulability did not resolve for up to ___ following atainment of clincial remission

What was associated with decreased survival time?

Answer 9

81% (22/27)

1 month

Accelerated rate of clot formation at the time of chemotherapeutic completions

Dogs with multicentric LSA were frequently hypercoagulable though 4 weeks after completion of chemotherapy

Question 10

Arico et el. The role of vascular endothelial growth factor and matric metalloproteinases in canine LSA: in vivo and in vitro study

MTI-MMP, TIMP-1 and RECK mRNA levels were higher in T or B-cell LSA?

Higher mRNA and protein expression of MMP-9 and VEGF-A were observed in?

Positive correlation noted between?

MMP-9, MTI-MMP, VEGF-A were expressed at highest level?

Answer 10

T cell LSA than B cell LSA

T-cell LSA

MMP-9 and VEGF-A in T cell LSA

High-grade T cell LSA

Question 11

Warry et al. 2014. Autologous Peripheral Blood Hematopoeitic Cell Transplantation in Dogs with T-cell LSA

Examine apharesis and PBHCT outcomes in dogs with TCL - 15 dogs

How many died?

Other complication?

Median DFI and overall survival of the 13 dogs transplanted?

Stage and substage effect on OS?

How many were alive long term?

Answer 11

13% died in hospital

1 dog developed B-cell LSA 120 days post-PBHCT

184 days (6 months) and 240 days (8 months)

None

2/13 (15%) - 741 (2 years) and 772 days (2.1 years)

Question 12

Barber et al. Criteria for designation of clinical substage in canine LSA: a survery of veterinary oncologists

What were the most commonly indentified clincial factors?

How may considered metabolic, neurologic, and nutritional parametes?

What was the severity of clincial signs to designate substage B?

Answer 12

GI, constitutional, and respiratory signs - 90% indicating inappetance, vomiting, diarrhea, changes in attitude, weakness, dyspnea were integral in assigning clincial stage

3/4

Mild to moderate

Question 13

Aubry et al. Evaluation of bone marrow aspirates from multiple sites for staging of canine LSA and MCTs

40 dogs enrolled (24 LSA and 16 MCT) but onlt 33 (82.5%) had BM from 2 sites

How many with LSA had BM involvement?

Were neoplastic cells present in both BM sites?

How many with MCT had BM involvement?

Were neoplastic cells present in both BM sites?

Answer 13

31.6%

Yes in all dogs

20%

Yes in 2 dogs and 1 site in 3rd

Multiple sites not needed for LSA but studies needed for MCT

Question 14

Fine et al. 2014. Hemodynamic and Biochemical alterations in dogs with LSA after induction of chemotherapy

Baseline echocardiogram showed significantly ____ chamber dimensions in dogs with LSA compared to control

These changes were reversed by?

Systolic BP and urine Na concentration?

Bromide dilution space, PCV, USG, urine K concentrations?

Answer 14

Smaller - volume depletion due to systemic hypertension and subsequent pressure natriuresis

Fluid administration

Increased

Decreased

Question 15

Canine LSA as a comparative model for human NHL: a recent progress and applications

Question 16

Hwang et al. The effects of oncolytic reovirus in canine LSA cells lines

Treated 10 cell lines with reovirus

Reovirus caused what in cell lines?

The level of Ras activation

Injection of intratumoral reovirus injection?

Answer 16

Cell death, virus replication and infectivity were confirmed in 4 cell lines

Varied among the cell lines

Suppressed growth of LSA SQ tumor

Question 17

Nerschbach et al. Splenic and hepatic US and cytology in canine LSA: effects of findings on stage migration and assessment of prognosis

Stage migration occurs using more sensitive diagnostic methods

186 with LSA and conventional staging with US and cytology of liver and spleen

Addition of cytology lead to?

Findings of hepatic and splenic US and cytology exerted what effect on CR and survival durations?

Answer 17

Shift from Stage IV to Stage III

None

Question 18

Alexandrakis et al. Ultility of a multiple serum biomarker test to monitor remission status and relapse in dogs with LSA undergoing treatment with chemotherapy

Compare clinicians assessement using palpation and cytology to biochemical tests for haptoglobin (hapt) and CRP - termed canine LSA blood test (cLBT)

cLBT of remission and recurrence with clinicians assessment?

cLBT demonstrated prognostic potential based on ___ values on dogs with __ survival times and those achieving lower cLBT score showed ___ survival times

Answer 18

Comparble

pre-treatment, shorter, longer

Potential to assist in monitoring treatment of canine LSA

Question 19

Jankowska et al. The animal dependent risk factors in canine T-cell LSA

Characterize animal-dependent risk factors in canine TCL in Poland

Dogs predisposed to TCL?

Dogs predisposed to BCL?

Age for dogs with low-grade LSA and high-grade LSA?

Answer 19

Boxer and dog de Bordeaux

None

older and younger

Question 20

Gillem et al. Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory LSA (2000-2013)

22 dogs tx carboplatin and 14 tx both

Clinical response rate?

Median time to progression?

Median overall survival time?

Thrombocytopenia and neutropenia occurence?

Grade IV thrombocytopenia and neutropenia?

Response rate for the combination?

Answer 20

18%

18 days

28 days

84% and 52.6%

56% and 60%

28.6%

High toxicity and no durable response

Question 21

Fogle et al. CD45+ and CD45- lymphocyte populations identified by flow cytometry from dogs with LSA exhibit similar morphology and the same clonal (B cell or T cell) lineage

What was the similarity between CD45+ and CD45- samples?

PARR was done on both population, indicating ___ were of same lineage, B cell or T Celll (__%)?

CD45-population identified in dogs with LSA represents a phenotypic variant of CD45+ population

Answer 21

95%

100% 95%

Question 22

Ema et al. Investigation of the cytotoxic effect of flavopiridol in canine LSA cell lines

flavopiridol - CDK inhibitor

Effect on 10 cell lines? Due to?

Mechanims of apoptosis showed?

Answer 22

Cell death in 8/10, apoptosis

Rb phosphorylation was inhibited, possibly due to CDK4 or CDK6 inhibition

Decreased expression of pRb protein and anti-apoptotic proteins, Mcl-1 and XIAP - possibly through transcriptional regulation of CDK7 and CDK9 activation

Question 23

Aresu et al. Canine indolent and aggressive LSA: clinical spectrum with histologic correlation

DLBCL vs. peripheral TCL vs. indolent LSA prevalence?

Stage of disease for dogs with DLBCL?

Dogs with indolent LSA and TCL had what stage?

Liver and BM involvement?

Clinical stage was related to?

Median survival for aggressive and indolent TCL

Median survival for indolent and aggressive BCL

Answer 23

44%, 20% and 30%

Stage IV

Stage V and symptomatic

BCL and TCL

Substage, sex, LDH levels

55 days

200 and 256 days

Prognosis of advanced indolent LSA does not appear to be different from that of aggressive disease

Question 24

Wang et al. Chemotherapy induced neutropenia is associated with prolonged remission duration and survival time in canine LSA

50 dogs with multicentric LSA received CHOP

How many dogs had neutropenia?

What was a negative prognostic factor?

Median first remission duration in the neutropenia and no neutropenia groups?

Answer 24

13 dogs had neutropenia, and 37 had no neutropenia

Bodyweight

812 and 219 days

Induce neutropenia to achive longer remission and survival times!!! HAHAHAHA

Question 25

***Munasinghe et al.* Evaluation of LN aspirates at diagnosis and relapse in dogs with high-grade multicentric LSA and comparison with survival times** Compare cytologic features of LN aspirates at diagnosis and at relapse What was higher at relapse? Nuclear morphology? Presence of ___ at diagnosis was associated with shorter remission and decreased total survival? Increased ___ at relapse was associated with longer remission and total survival? Increased minimum ___ and ___ at diagnosis was associated with decreased time from relapse to death

Answer 25

Mitoses and total cytologic score No difference Binucleated or multinucleated cells mean nucleoli Nuclear radius and diameter

Question 26

***Chikazawa et al.* Hyperferritinemia is associated with short survvial time in dogs with multicentric LSA** MST for dogs with high ferritin (\>3000 ng/ml, n=7)? MST for dogs with low ferritin (\<3000 ng/ml, n=7)?

Answer 26

40 days 360 days

Question 27

***Childress et al.* Inter- and intra-rater reliability of calliper based LN measurements in dogs with peripheral nodal LSA** 3 rates measured LNs from 20 dogs twice prior to and once after chemo ICC for inter-rater and sumTV and sum LD prior to chemotherapy were 0.86 and 0.80 ICC for inter-rater and sumTV and sum LD after chemotherapy were 0.96 and 0.94

Question 28

***Tierny et al.* Phase I clinical pharmacology study of F14512, a new polyamine vectorized anticancer drug, in naturally ocurring canine LSA** New topoisomerase type II inhibitor 23 dogs with stage III-IV LSA - 5 dose levels were evaluated Toxicity? Response rate?

Answer 28

Well tolertaed except for dose-dependent hematologic toxicity 91%

Question 29

***Mutz et al.* Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma** Lymphopenia at diagnosis and N:L ratio\>3.5 are negative prognostic factors for survival 77 dogs What was significant for PFS?

Answer 29

Immunophenotype only

Question 30

***Curran et al. 2016.* Retropsective analysis for treatment of naiive canine multicentric LSA with 15 week maintenance-free CHOP protocol** 134 dogs treated with 15-week CHOP protocol Overall RR? Median PFS Median OS Prognostic factors significant for PFS?

Answer 30

98% 176 days (6 months) 311 days (10 months) Substage, immunophenotype, hospitalization for AEs, need for dose reduction, presence of neutrophilia at diagnosis, anemia and experiencing CR as best response to therapy

Question 31

***Comazzi et al.* CLL transformation into high grade LSA: a secriptions of Richters symdome in 8 dogs** RS - Development of aggressive LSA in patients with CLL 8 dogs with CLL progressed to RS Percent of RS? When RS occured ____ were decreased compared to CLL 5 dogs had anemia and 2 thrombocytopenia Clincical signs - LN swelling, coughing, vomiting, neurological signs, weight loss Survival?

Answer 31

5.2% - with T-cell (2.2%) and 6 with B cell (10.9%) Lymphocytes 41 days

Question 32

Tsuji et al. Anti-tumor effects of perphenazine on canine LSA

Question 33

***Wang et al.* Assessement of temporal association of relapse of canine multicentric LSA with components of the CHOP protocol: Is cyclophosphamide the weakest link?** When did relapse occur more frequently?

Answer 33

Administration of cyclophosphamide compared with vincristine or doxorubicin Relapse cyclophosphamide with other cytotoxic drugs!!!

Question 34

***Romano et al. 2016.* Association between BCS and cancer prognosis in dogs with LSA and OSA** In humans, obesity promotes some cancers 270 with LSA and 54 with OSA Which dogs with LSA had shorter survival? OSA?

Answer 34

Underweight dogs than ideal or overweight dogs No asociation **Obesity is not associated with worse outcome but being underweight for LSA is bad**

Question 35

***Wang et al.* Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine LSA** Treated with either CHOP or CMOP Median PFI for CHOP and CMOP? MST for CHOP and CMOP? Anorexia and diarrhea?

Answer 35

222 days (7.4 months) and 162 days (5.4 months) 318d (10 mo) and 242 d (8 months) Higher in CHOP than CMOP CMOP causes fewer side effects - another tx choice for LSA

Question 36

***Ruple et al.* Differences in the geographic distribution of LSA subtypes in Golden retrievers in the USA** What regions were more likely to be diagnosed with TZL?

Answer 36

Northeast and East north central compared to Mountain regions (B-cell?)

Question 37

***Blake et al.* Hypersentivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012** Hypersentivity were documented in how many dogs? Associated with \_\_% of L-aspraginase doses admnitered? Hypersentivity were documented in how many cats?

Answer 37

5%, 1.6% None HSR are uncommon among dogs and cats even with repeated dosings

Question 38

***Zamani-Ahmadmahmudi et al.* Prognostic efficacy of the human B-cell LSA prognostic genes in predicting DFS in canine counterpart** CCND1 as an important gene that can be used as a potential predictor

Question 39

***Thiman et al.* Prospective evaluation of the safety of compounded bulk material L-asparaginase in dogs with LSA** Manufacturing of ELSPAR was discontinued in 2012 - Evaluate safety of compounded ELSPAR Dogs tx with 10,000 IU/m2 CLASP or Elspar SQ and steroids administered concurrently AE to CLASP? AE to Elspar? Response rate to CLASP and steroids?

Answer 39

None grade I and II AE 80%

Question 40

***Childress et al.* A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal LSAs** Tx was L-CHOP (18) or L-CHO (22) Median PFS?

Answer 40

142.5 days (4.75 months) for L-CHO and 292 days (9.7 months) for L-CHOP

Question 41

***Goodman et al.* Treatment of canine non-indolent T cell using VELCAP-TSC protocol: A retrospective evaluation of 70 dogs (2003-2013)** Evaluate prognostic factors in 70 dogs with T cell LSA Overall remission Dogs that were ____ were more likely to achieve CR? Median PFS? 1-, 2-, 3 year survival Median OST was significantly longer for dogs that \_\_\_\_, and shorter for ___ and \_\_\_ More than 30% of dogs survived \>1 years

Answer 41

73% Neutropenic 175 days. 26.8%, 15%, 12.6% achieved CR, Boxers, substage b disease

Question 42

Lautscham et al. Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric LSA

Question 43

***Lenz et al.* Vinblastine as a second rescue for the treatment of canine multicentric LSA in 39 cases (2005-2014)** 39 dogs - Median starting dose was 2.6 mg/m2 administered weekly until disease progression CR? PR? SD? PD? Most common toxicity? Median PFS? MST? Duration of first remission was identified as positive predictor of outcome

Answer 43

7.7%, 18%, 46%, 28% Grade 3 or 4 neutropenia (25%), grade 2 or 4 thrombocytopenia (10%) 1 month 45 days

Question 44

***Thamm et al. 2017.* Alternating Rabacfosadine/Doxorubicin: Efficacy and tolerability in Naiive Canine Multicentric LSA** 54 dogs with untreated LSA - alternating RAB (1.0 mg/kg 0, 6, 12) and DOX (30mg/m2 3, 9, 15) Overall RR? Median PFI? AEs?

Answer 44

84% 194 days (6.5 months) Mild and self limiting: GI and hematological most common

Question 45

***Jones et al.* CT findings in 12 cases of canine multicentric LSA with splenic and hepatic involvement** Splenic nodule appearance? After contrast? Hepatic nodules? After contrast?

Answer 45

Hypoattenuating in 4/5 dogs and isoattenuating in 1. 3/5 appreaed hypoattenuating and 2/5 isoattenuating Normal liver in 10 dogs and nodules in 2 dogs. All nodules isoattenuating. Hypoattenuating after contrast. **FNA recommended when using CT to stage dogs with multicentric LSA**

Question 46

***Boye et al.* Dose escalation study to evaluate safety, tolerability and efficacy of IV etoposide phosphate administration in 27 dogs with multicentric LSA** Topoisomerase inhibitor, water soluble prodrug MTD? Overall RR at MTD dose? Toxicity?

Answer 46

300 mg/m2 83.3% Moderate reversible GI toxicity

Question 47

***Yamazaki et al.* Effects of toceranib phosphate monotherapy on multidrug resistant lymphoma in dogs** PDGFRa expression in T cell LSA? c-KIT expression? Response to TOC in 5 dogs?

Answer 47

Higher with MDR TCL than those with untreated TCL higher in TCL than in BCL PR in 2/5 (40%)

Question 48

***Fontaine et al.* Evaluation of the modified Glasgow Prognostic Score to predict outcome in dogs with newly diagnosed lymphoma** mGPS assigns score of 0-2 from pretreatment CRP and albumin to predict patient outcome mGPS distribution was associated with? On univariate analysis, mGOS was significantly associated with? What reduced OS and PFS? What was significant on univariate and mulivariate analysis?

Answer 48

Clincial stage, substage b, weight loss, GI disturbances, and lethargy at presentation OS and PFS with shorter times for 2 vs. 0 and 1 Hypoalbuminemia but increased CRP had no effect Clinical stage

Question 49

***Wilson-Robles et al.* Geographical differences in survival of dogs with NHL treated with CHOP based chemotherapy protocol.** Geographic difference in PFS exists Significant differences in sex, weight, stage, immunophenotype and # of doxorubicin doseas were seen between regions On univariate analysis, PFS differed by regions, stage, substage, and immunophenotype Multivariable model showed dogs in wetern regions had significantly shorter PFS when compared to south or east

Question 50

***Riondoto et al.* Identification of peripheral blood involvement in dogs with large B cell LSA: Comparison of different methods** Assessed the aggrement among FC, blood smear evaluation, and ADVIA (LUC and BASO) to quanity PB infiltrastion in 100 dogs with LBCL Significant errors were noted on all methods compared to FC Moderate aggremment between FC and blood smear evaluation, LUC and BASO had excellent specificity but unsatisfactory sensitivity

Question 51

***Brown et al.* LOPP as first-line treatment for dogs with T-cell LSA** LOPP -lomustine, vincristine, procarbazine, prednisolone for treatment of naive T-cell LSA 31 dogs Overall RR? Median DFI MST

Answer 51

97% 176 days (~6 months) 323 days (10.8 mo)

Question 52

***Boss et al.* Potential for a novel manganese porphyrin compound as adjuvant canine LSA therapy** Redox active drugs and superoxidise dismutase mimics that chemosensitize LSA Peak plasma concentrastion occured 30 mins post-injection Toxicity? MTD was 0.25 mg/kg - given 3x/week for 2-3 weeks Highest drug level?

Answer 52

Anaphylactic reaction and tachycardia LNs then kidney and liver

Question 53

***Treggiari et al.* Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric LSA** 26 patients in TMZ group and 11 in TMZ/DOX group Overall MST for both groups? TMZ group TTP? MST? ORR for TMZ group? Toxicity? TMZ/DOX group - TTP, MST - ORR and toxicity?

Answer 53

40 days 15 days and 40 days 32% and 46% 19 days and 24 days, 60% and 63%

Question 54

***Harrington et al.* Preclinical evaluation of the novel BTK inhibitor Acalabrutinib in Canine Modeuls of B cell NHL** Seoncd generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased targert selectivity and potency compared to ibrutinib Acalabrutinib inhibited BTK activity and downstream effectors in CLBL1 (BCL cell line) 20 dogs treated at 2.5 to 20 mg/kg 12 or 24 hours Well tolerated ORR? Median PFS Clinical Benefit?

Answer 54

25% 22.5 days 30% **Safe and effective in canine BCL and supports use of canine LSA as relevant model for human NHL**

Question 55

Deravi et al. 2017. Specific immunotypes of canine T cell LSA are associated with different outcomes

Question 56

***Saba et al.* Rabacfosadine for relapsed canine BCL: Efficacy and adverse event profiles of 2 different doses** Novel prodrug of the acyclic nucleotide phosphate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity Two doses - 0.82 mg/kg or 1 mg/kg as 30 min infusion every 3 weeks for 5 treatments Overall RR and CR? Median PFI for all dogs? all responders? all CR? Response rate and PFI for the 2 groups? Toxicity?

Answer 56

74% with 45% achieveing CR 108 days (3.6 mo), 172 days (6 mo), and 203 days (6.7 mo) Similar Hematologic, GI, dermatologic, and pulmonary

Question 57

Craft et al. Characterization of a low expression haplotype in canine glutathione S-transferase (GSTT1) and its prevalence in golden retrievers

Question 58

***Muir et al.* Prevalence of FoxP3+ cells does not correlate with Ki67 expression in canine DLBCL** FoxP3 cells in DLBCL LNs compared to reactive LNs? Relationship between the number on intratumoral Foxp3 and neoplastic transformation? Foxp3 cells are reduced in LNs effaced by DLBCL and is unrelated to Ki67 expression

Answer 58

Fewer in nodes effaced by DLBCL than in reactive LNs None

Question 59

***Kumar et al.* PDLI is expressed in canine B cell lyphoma and downregulated by MEK inhibitors** PDL1 expression in canine B cell LSA? PDL1 and singal transducer and activator transcription 1 mRNA was reduced in the presence of MEK1/2 inhibitors **PDL1 is expressed in BCL and inhibition by MEK1/2 inhibitors suggest a possible treatment strategy**

Answer 59

Observed

Question 60

***Smith et al.* Clinical response and AE profile of Bleomycin chemotherapy for canine multicentric LSA** Response noted? Toxicity limited to grade 1 GI and grade 1 constitutional toxicity

Answer 60

1PR/10 dogs that died 24 days later

Question 61

***Schopper et al.* Melting curve analysis in canine LSA by calculating maximum flourescence decrease** MCA is used in humans instead of PARR 27/34 cases showed monocloncal rearragement (specificity 93%). Detection limits was 25% for B-cell LSA and 100% of T cell LSA, suggesting PCR consition could still be optimized

Question 62

***Poggi et al.* Prognostic significance of Ki67 evaluated by flow cytometry in dogs with high grade B cell LSA** Assessed prognostic significance of Ki67% evalujated by FC in 40 dogs By multivariate analysis what were prognostic for LSS? Dogs with ___ Ki67% presented longer LSS and RFI?

Answer 62

Ki67% and achivement of CR Intermediate (median 866 and 428 days) low (median 42 days), high (173 days)

Question 63

***Sato et al. 2012.* Evaluation of the prognostic significance of BCL6 expression in canine high-grade B cell lymphoma** 44 dogs with centroblastic or B-cell immunoblastic type LSA PFS and OS between high BCL6 and low BCL6 group? Correlation between BCL6 and prognosis? BCL6 not detected in 11 dogs by IHC Most canine high grade B cell LSA correspond to human DLBCL with no IHC expression of BCL6

Answer 63

No difference None observed

Question 64

***Woldesberger et al.* Angiogenic markers in canine LSA tissues do not predict survival times in chemotherapy treated dogs** VEGF, VEGFR1, VEGFR-2 and MVD (used to evalute angiogensis) evaluated by IHC in 34 dogs VEGF? VEGFR1, VEGFR-2? MST? Relationsthip between markers and OS?

Answer 64

71% positive 62% and negative 266 days (8.9 mo) No relationship found between OS and expression of VEGF, VEGFR1, VEGFR-2 and MVD

Question 65

***Escobar et al. 2012.* Hematologic changes after total body radiation and autologius transplantation of hematopoeitic peripheral blood progenitor cells in dogs with LSA** Hematologic toxicities of TBR in 10 dogs and subsequent recovery of affected cell lines Toxicity?

Answer 65

All peripheral blood cell lines, except RBC, experienced grade 4 toxicities All dogs had \>500 neutrophils by day 12, thrombocytopenia persisted for weeks All dogs clinically normal at discharge

Question 66

***Palus et al. 2012.* MRI features of CNS lymphoma in dogs and cats** 8 dogs and 4 cats Intracranial lesions affected rostrotentorial structures in 6 dogs and caudotentorial in 2 cats. Lesions in SC in 2 dogs and 2 cats

Answer 66

Hyperintesene in T2-weighted when compared to white matter, most were hypointense in T1-weighted (7/12), hyperintense in fluid-attenutating recovery (FLAIR) 5/9 When compared to gray matter, lesions appear isointense (5/12) or hyperintense (7/12) Lesion margins indistinct on T2 (10/12) and has perilesional hyperintesity in FLAIR (7/9) Majority of lesions (10/12) had abnormal meninges and half (6/12) had generalized contrast enhancement Mass effect evident on all lesions

Question 67

Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine LSA

Question 68

***Berlato et al. 2012.* RT in the management of localized mucocutaneous oral LSA in dogs: 14 cases** Surgery and chemotherapy do not provide effective long term control Mean survival Median survival Overall RR to RT?

Answer 68

1129 days 770 days (2.1 years) 67% Survival advantage seen in dogs with no evidence of LN metastasis **Effective treatment for localized oral LSA**

Question 69

***Sharif et al. 2012.* A sensitive and kinetically defined radiochemical assay for canine and human TK1 to monitor canine malignant LSA** Marker of cell proliferation, an optimised 3H-thymidine phosphorylation assay is described Mean S-TK1 activity in healthy dogs? Healthy humans? S-TK1 activity in dogs with hematological malignancy? Sensitivity and specificity? TK1 during chemotherapy? Relapse?

Answer 69

1. 11, 1.15 24. 2 0. 94 and 0.88 Reduced Increased prior to relapse TK1 did not differ in dogs with solid tumors compared to healthy controls

Question 70

***Joetzke et al.* Flow cytometric evaluation of peripheral blood and bone marrow and fine needle aspirate samples from multiple sites in dogs with multicentric lymphoma** Extent of disease can be determined by flow cytometry and to evaluate the suitability of FNA from the liver and spleen of dogs. Logarithmic transformed T-cell-to-B-cell percentage ratio were calculated Log (T:B) values in dogs with BCL Of the samples analyzed how may tested positive via FC? Aggreement with cytology?

Answer 70

Lower than with TCL or control dogs In dogs with TCL, log (T:B) of LN, BM, and spleen samples was significantly higher than in control dogs 70%, 83% **FC may aid in detection of extranodal LSA in dogs**

Question 71

***Wilcox et al. 2012.* Autologous peipheral blood hematopoeitic cell transplatation in dogs with B cell LSA** Peripheral blood CD34+ PBHCT is used to treat human patients - to determine the safety and feasibility to treat canine B-cell LSA How many were engrafted appropriately? Died? Delayed engraftment? Median DFI and OS Relapse?

Answer 71

87.5 (21/24), 2 died (8.3%) 1 dog (5%) and died 45 days after PBHCT 1 dog developed TBI-induced pulmonary fibrosis 8 months after 271 days (9 months) and 463 days (15 months) 33% at median OS 524 days (17 months)

Question 72

***Frantz et al. 2013.* Molecular profiling reveals prognostically significant subtypes of canine LSA** What were the 3 groups identified based on gene expression profiles?

Answer 72

Low grade T cell LSA - T zone LSA High grade T cell LSA - lymphoblastic and peripheral T cell LSA not otherwise specified B cell LSA - marginal BCL, DLBCL, Burkitt's LSA

Question 73

***Di Bella et al. 2013.* Proteinuria in canine patients with LSA** Results?

Answer 73

Canine patients with LSA more likely to be proteinuric compared with healthy dogs Not linked with stage or substage of LSA

Question 74

***Atherton et al. 2013.* Changes in serum proteome of canine LSA identified by electrophoresis and mass spectrometry** 21 dogs with LSA had elevated levels of? Further separation was performed using PAGE

Answer 74

a2 globulins 36 proteins were identified - haptoglobin was identified in 3 dogs which could account for a2 globulins a2 Macroglobulin, a-antichymotrypsin, and inter-a-trypsin were noted in dogs with LSA Kininogen was present in 3 dogs, present in healthy dogs Canine LSA has an inflammatory component

Question 75

***Dettwiler et al. 2013.* Immunohistochemical expression study of proapoptotic BH3-only protein bad in canine nonneoplastic tissues and canine lymphomas** Bad is proapoptotic Bcl-2 family members - contributes to tumorigenesis Expression in nonneoplastic tissues? Of 81 LSA, expression?

Answer 75

Expressed in cytoplasm of nonneoplastic tissues especially epithelial cells 35.8% had moderate to strong Bad labeling, strong increase in B cell LSA compared to nonneoplastic LNs

Question 76

***Dhaliwal et al. 2013.* Clinicopathological significance of histologic grade, pgp, and p53 expression in canine LSA** How may were positive for pgp and p53? OS and remission duration? What was correlated with survival?

Answer 76

80% and 22% 246 days and 137 days Histologic grade was not associated with either survival or duration of first remission Expression of p53 was correlated with survival

Question 77

Mooney et al. 2013. Comparative RNA-Seq and microarray analysis of gene expression changes in BCL of Canis familiaris

Question 78

***Gentilini et al. 2013.* Retrospective monitoring of minimal residual disease using hairpin shaped clone specific primers in BCL** Using hairpin-shaped primers to quantify MRD (minimal residual disease - cause of relapse) - 8 dogs that underwent chemotherapy Median DFI and MST At admission, except 1 had circulating neoplastic cells Persistence of MRD despit CT indicated? What is anticipated with reappearance of MRD?

Answer 78

254.5 days, 313.5 days Worse prognosis and short duration of CR Relapse anticipated with reappearance of MRD in peripheral blood

Question 79

***Marconato et al. 2013.* Assessment of bone marrow infiltration diagnosed by flow cytometry in canine large B cell LSA: prognostic significance and proposal of a cut-off values** Degree of BM infiltrasion by large CD21 cells with LBCL was assessed using FC and related to TTP and LSS BM infiltration was correlated with? In univariate analysis, association between? Multivariate analysis? Cut-off associated with prognostic value?

Answer 79

Peripheral blood infiltration, high LDH, and substage b disease BM infiltration diagnosed by FC and TTP and LSS Substage associated with TTP and substage and anemia associated with LSS 3% - discriminated dogs with poorer prognosis (TTP 69 days and LSS 155 days) and better prognosis 9TTP 149 days and LSS 322 days) **Presence of BM infiltration by FC at diagnosis is a negative prognostic indicator in canine LBCL**

Question 80

***Suran et al. 2014.* Imaging findings in 14 domestic ferrets with lymphoma** Most common malignant neoplasia in domestic ferrets 14 ferrets - radiographs (12), US (14), CT (1), MRI (1) Median age at diagnosis? Clinical signs? Imaging lesions detected in? Appearance of lesions on US? Most common thoracic abnormality?

Answer 80

5.2 years Nonspecific abdomen, intraabdominal lymphadenopathy (12/14), splenomegaly (8/14), peritoneal effusion (11/14) Hypoechoic Pleural effusion (3/12) Imaging characteristics in ferrets are similar to dogs, cats, humans

Question 81

***Zandvliet et al. 2013.* Prednisolone inclusion in a first-line multidrug cytostatic protocol for the treatment of canine LSA does not affect therapy results** Treated with L-CHOP (prednisolone) and 1/2 dogs receiving prednisolone Initial treatment? Rescue treatment? Overall survival and AEs?

Answer 81

CR 75%, disease free period 176 days (6 mo) CR 45% and disease free period 133 days (4.4 mo) Similar in both groups - 283 days (9.4 months) **Prednisolone as part of chemo protocol has no additional effect on treatment results and can be omitted from first line protocols**

Question 82

***Mudaliar et al. 2013.* Comparative gene expression profiling identifies common molecular signatures of NF-kB activation in canine and human DLBCL** Activation of the NF-KB/p65 canonical pathway in human and canine DLBCL - can be used as models to study therapeutic targets for human LSA

Question 83

***Fujiwara et al. 2014.* Prognostic significance of the expression levels of the p16, p15, and p14 genes in dogs with high-grade LSA** Evaluate the relationship between inactivation of p16, p15, and p14 genes and prognosis in canine LSA Of 62 dogs examined, p16, p15, and p14 mRNA levels? CpG methylation of p16 gene? What correlated with OS? p16 mRNA? p15 and p14 mRNA?

Answer 83

Undectable in 21, 18, and 10 dogs 20/68 were methylated p16 expression status and anatomic form/immunopehnotype were found to correlated with OS p16 mRNA over its cutoff correlated with poor prognosis p15 and p14 mRNA and methylation status did not influence prognosis Expression levels of p15 and p14 mRNA and p16 methylation did not influence prognosis in dogs

Question 84

***Childress et al.* 2014. Assessment of folate receptor expression and folate uptake in multicentric LSA in dogs** FR detection by IHC in LN samples an archival specimens? Nuclear scintigraphy? Results of treatment? Strong evidence for folate uptake in substantial protion of multicentric LSA dogs

Answer 84

None detected uptake of radioactive tracer in 6/10 dogs - 5 treated with FR-targeted chemotherapeutic agent CR in 1 dog, SD 2 dogs, PD in 2 dogs

Question 85

***Ferraresso et al. 2014.* Epigenetic silencing of TFPI-2 in canine DLBCL** Tissue factor pathway inhibitor-2 is a tumor suppressor involved in invasiveness inhibition Hypermethylation of the TFPI-2 was found in \_\_% of DLBCL and _ normal LN Gene expression revealed ___ of TFPI-2 in DLBCL compared with normal LNs?

Answer 85

77%, 1 Downregulationn- hypermethylation negatively regulates its transcription A significant positive correlation was found between TFPI-2 methylation and age - age-associated epigenetic modification in canine DLBCL

Question 86

***Aresu et al. 2014.* Minimal residual disease decetion by FC and PARR in LN, peripheral blood and bone marrow, following treatment of dogs with DLBCL** The concordance rate between FC and PARR for LN, PB, BM? At the end of treatment the corcordance rate? Which test was more sensitive in predicting TTR? Which test was more sensitive in predicting LSS?

Answer 86

100%, 78.6%. and 64.3 for LN, PB, BM 35.7%, 50%, 57% LN, PB. BM PARR PARR and FC combination Immunological and molecular techniques should be used in combination when monitoring MRD in canine DLBCL

Question 87

***Mochizuki et al. 2014.* Demonstration of the cell clonality in canine hematopoeitic tumors by X-chromosome inactivation pattern analysis** XCIP has been used in human neoplasms to assess clonality PCR reaction canine XCIP of the androgen receptors was applied in assessement of cell clonality Examined polymorphisms of 2 CAG tandem repeats in aht AT in 25 males and 159 females Of the 150 females, ___ were heterozygous for the first and second polymorphic CAG tandem repeats - indicating utility in these dogs Of the 10 LSA samples, __ showed skewed XCIPs whereas nonneoplastic LN showed balanced XCIP Bone marrow specimen from dog with AML and peripheral leukocyte specimen from CML showed skewed XCIP

Answer 87

49.3% 90% (9) XCIP was successfully employed

Question 88

***Ndikuyeze et al. 2014.* A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like DLBCL** Selective IKK inhibitor, NBD peptide blocls constitutive activity and induces apoptosis in ABC-DLBCL cell in vitro Determine safety and efficacy of NBD peptide in dogs LN biopsies were taken before and 24 hr after peptide administration IV administration of \<2mg/kg NBD peptide was safe and inhibited NF-KB activity in 6/10 dogs Reductions in mitotic index and cyclin D occured in subset of dogs 24 hours post in 3 dogs marked PK suggested rapid uptake of peptide into tissue NBD peptide is safe and blocks NF-KB signaling and reduced malignant B cell proliferation

Question 89

***Graff et al.* Hematologic findings of predictive bone marrow disease in dogs with multicentric large B cell LSA** What were the variable for predicting bone marrow involvement? When considered independently, either positive blood smear or thrombocytopenia had sensitivy and specificty? How did sensitivity increase?

Answer 89

Thrombocytopenia and presence of \>10% neoplastic lymphocytes on blood smears low sensitivity 60% and moderate specificity 89% and 87% When evaluated together - 80%

Question 90

***Tomiyasu et al. 2014.* Evaluation of DNA methylation profiles of the CpG island of the ABCB1 gene in dogs with LSA** 19 chemotherapy sensitive dogs and 8 chemotherapy resistant dogs The CpG island of the ABCB1 gene was ___ in dogs with chemotherapy sensitive and resisatnt groups?

Answer 90

Hypomethylated in dogs with chemotherapy sensitive and resistant groups No significant difference was dected in the methylation rate between the 2 groups, and no correlation between methylation rate and mRNA expression levels Expression of ABCB1 gene was not suppresses by hypermethylation of its CpG island in most dogs with LSA

Question 91

**Arico et al. 2014. PDGF and receptors in Canine LSA** Use of PDGFR antagonits in therapy for aggressive TCL but not in DLBCL

Question 92

***Arico et al. 2014.* Array based comparative genomic hybridization analysis revealed chromosomal copy number aberrations associated with clinical outcome in canine DLBCL** Identify copy number aberration (CNAs) by genomic hybridization in 12 dogs with DLBCL 90 different genomic imbalances were counted, 46 gains and 44 losses Two gains in Chr13 were correlated with clinical stage Losses of IGK, IGL, IGH were always found, and gains along chr13 and chr31 were observed (\>41%) - MYC, LDHB, HSF1, KIT, PDGFRa are annotated

Question 93

***Zandvliet et al. 2015.* A longitudinal study of ABC transporter expression in canine multicentric LSA** ABC transporter mRNA expression was assessed in 63 dogs treated with doxorubicin-based protocol ABC transporter expression was independent of sex, weight, age, stage, substage What were associated with increased ABCB5 expression and decreased ABCC1 mRNA? Drug resistance ocurred how often? What effect did glucocorticoids have?

Answer 93

Hypercalcemia and TCL 55.6% and was associated with increased ABCB1 mRNA expression in dogs with BCL and decreased ABCB8, abCC1, and ABCC3 mRNA expression in T cell LSA No effect on ABC transporter mRNA expression **Drug resistance is due to upregulation of ABCB1 and ABCG2 mRNA**

Question 94

***Zamani et al. 2015.* Reconstruction of canine DLBCL gene resulatory network: detection of functional modules and hub genes** The PI3K, p53 signaling pathway Rac CycD pathway, G1/S checkpoint, chemokine signaling pathway and telomere maintenance were main pathways protein products of hub gene are invovled.

Question 95

***Larsdotter et al. 2015.* Serum TK1 activity in clinically healthy and diseased horses: a potential marker for LSA** TK1 activity in horses with LSA? Non-hematopoeitic neoplasia? Inflammatory disease?

Answer 95

26. 3 2. 3 1. 5 Potentially useful maker for LSA

Question 96

***Rue et al. 2015.* Identification of a candidate therapeutic antibody for treatment of canine BCL** Generation and characterization of rituximab like CD20 Ab 1E4 binds to approximately the same location in the EC domain of CD20 as rituximab 1E4-clgGB and 1E4-clgGC significantly deplete B cell levels in healthy dogs Half life was 14 days

Question 97

***Marconato et al. 2015.* Peipheral blood lymphocyte/monocyte ratio as a useful prognostic factor in dogs with DLBCL receiving chemotherapy** Dogs with LMR of ___ were found to have significantly shorter TTP and LSS

Answer 97

\<1.2 (30% of cases)

Question 98

***Koshino et al. 2016.* Mutation of p53 gene and its correlation with clincial outcome in dogs with LSA** 7 dogs (16%) had p53 mutation and 36 dogs (84%) had no mutation Overall RR was ___ in dogs with LSA having p53 mutation than those without Overall survival was ___ in dogs with p53 mutation

Answer 98

lower - 33% versus 88% lower - 67 days vs. 267 days

Question 99

***Meichner et al. 2016.* Ezpression of Apoptosis regulating Bcl-2 and Bax in LN aspirates from dogs with LSA** 55 dogs with LSA and 5 healthy dogs Bcl2/Bax ratio was higher in dogs with ___ compared to \_\_\_\_ Dogs with Bcl2/Bax ratios higher than the median of the group experienced a median PFS of ___ and dogs with ratio equal and lower than the median had PFS \_\_\_

Answer 99

TCL, BCL 101 days, 130 days

Question 100

***Mani et al. 2017.* Non-immunosuppressive FTY720 derivative OSU-2S mediates reactive oxygen species mediated cytotoxicity in canine BCL** OSU-2S is a FTY720 derivative that lacks immunosuppressive properties and exhibits strong anti-tumor activity OSU-2S mediated apoptosis in canine B cell lines and primary BCL cells obstained from LSA bearing dogs Induced ROS in canine LSA cells and inhibition of ROS rescued from cell death

Question 101

***Thomas et al. 2017.* Integrated immunohistochemical and DNA copy number profiling analysis privides insighe into the molecular pathogenesis of canine follicular LSA** FLs have chromosome translocation that induces constitutive activation of anti-apoptotic bcl2 protein 10 dogs with FL, they exhibit ___ in frequency and intensity of bcl2 protein expression Genomic copy number abberations were \_\_\_\_ None of the canine FL exhibited rearragement consistent with the hallmark translocation of human FL

Answer 101

Marked heterogeneity Infrequent

Question 102

**Siso et al. Canine nervous system lymphoma subtypes display characteristics neuroanatomical patterns** Lymphoma infiltration within which areas were characteristics of DLBCL? Frequent feature with PTCL? Cell counts ___ correlated best with meningeal and periventricular LSA?

Answer 102

Meningeal, perivascular, periventricular Peripheral nerve involvement \>64 cells/uL

Question 103

***Curran et al. 2017.* Bcl2 and Myc are expressed at high levels in canine DLBCL** Canine DLBCL patients with high IHC expression of MYC and BCL2 were ___ with clincial outcome

Answer 103

Not associated

Question 104

***Calvalido et al. 2016.* Comparison of serum cytokine levels between dogs with multicentric LSA and healthy dogs** Multiple cytokines have been linked in development of LSA in people BCL (20) TCL (10) Which cytokines were higher in LSA than healthy dogs? Which were higher in BCL than healthy dogs? Which were higher in TCL than healthy dogs? Which was higher in TCL than BCL?

Answer 104

MCP-1, IL6, IL-10 MCP-1 and IL-10 MCP-1 and IL-6 IL-6

Question 105

***Davis et al. 2017.* Validation of a Multiplexed gene signature assay for diagnosis of canine cancers from FFPE tissues** Significant differenced were found between BCl2, E2F TF1, MDM2, COX-2, MET protooncogene receptor kinase and other biologically relevant gene expression tumor types.

Question 106

***Yamazaki et al. 2017.* Hypoxia activated prodrug TH-302 decreased survival rate of canine LSA cells under hypoxic conditions** Hypoxic stimulation enhances growth potentials of canine LSA cellls by activating HIF-1a and hypoxia actviated prodrug (TH-302) inhibits growth potential Hypoxic cell culture upregulated?

Answer 106

HIF-1a, ABCB1, ATP binding cassette G2 (ABCG2), PDGFF, VEGF, and survivin - an enhanced growth rate, DOX resistance, invasiveness of cells TH-302 decreased survival rate of cells under hyposix condition Hypoxic stimulation may contribute to development of TH-302 based hypoxia targeting therapies for canine LSA

Question 107

Savag et al 2018. Prognostic significance of morphocytes in canine lymphomas: A systematic review of literature

Question 108

***Mastromauro et al. 2018.* Oral melphalan for the treatment of relapsed canine lymphoma** 19 cases of relapsed LSA - 16 high dose protocol and 15 dogs got steroids Clinical benefit? Time to progression for responders and those with SD? Toxicity?

Answer 108

31.6% 14, 24, and 34 days for responders and 20, 28, 103 days for SD Hematological toxicity common (11/17 or 65%) and GI rare (1/17 or 6%)

Question 109

***Lu et al. 2017* JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit canine BCL growth by increasind apoptosis and disrupting cell proliferation** JAK/STAT pathway play a role in hematologic malignancies in humans What was observed after AZD1480 and CYT387 treatments?

Answer 109

Significant decrease in viable canine LSA cells. Decreased prolifration and induced apoptosis.

Question 110

***Pawlak et al. 2017.* Methotrexate induces high level of apoptosis in canine LSA/leukemia cells lines** Evaluate methotrexate concentration-dependent cytotoxicity and capability of inducing apoptoaia in 3 cell lines

Answer 110

Concentration-dependent inhibitory effect on proliferation of all cell lines with different degree of apoptosis. Most sensitive cell line was CL-1 - derived from TCL

Question 111

***Lane et al. 2017*. Low grade GI LSA in 20 dogs: 20 cases (2010-2016)** Common clinical signs? Immunophenotype? Required for definitive diagnosis? Most commonly used drugs? ORR? MST?

Answer 111

Weight loss, vomiting, diarrhea T-cell (95%) and epitheliotrophism commonly described (60%) IHC, or PARR, or both were required for definitive diagnosis CHB and pred 70% and 424 days (14 months)

Question 112

***Assumocao et al. 2018.* STAT3 expression and activity are upregulated in DLBCL of Dogs** 43 dogs diagnosed with DLBCL The % of STAT3 and pSTAT3 immunolabeled cells in DLBCL compared to normal canine LN? In STAT3 immunolabeled cells, STAT3 had ___ in LSA sampled than in normal or reactive LN Mitogen activaed ERK1/2 activation?

Answer 112

Higher percentage Higher nuclear expression Upregulated in DLBCL dogs

Question 113

***Childress et al. 2018.* Retrospective analysis of factors affecting clinical outcome following CHOP-based chemotherapy in dogs with primary nodal DLBCL** Factors associated with achieving partial remission included? Factors associated with PFS in lowest quartile (\<93 days) included?

Answer 113

Thrombocytopenia, baseline globulin concentrations, and greater age Thrombocytopenia, greater age, baseline neutrophil counts

Question 114

***Gavazza et al. 2018.* Fecal microbiota in dogs with multicentric lymphoma** Determine differences in fecal microbiotia between healthy and dogs with multicentric LSA Lower abundance of what organisms in LSA than healthy dogs? What was higher in dogs with LSA? Dysbiosis index?

Answer 114

Faecalibacterium spp., Fusobacterium spp. Turicibacteria spp. Streptococcus spp. Higher in dogs with LSA Significant differences in microbial communities of dogs with LSA compared with healthy dogs

Question 115

***Suenaga et al. 2017.* Comprehensive analysis of gene expression profiles reveals novel candidates of chemotherapy resistant factors in canine LSA** 10 dogs with LSA at chemotherapy sensitive and chemotherapy resistant phases During chemotherapy resistance which genes were decreased compared to chemetherapy sensitive phase?

Answer 115

Immune response and inflammatory reaction

Question 116

***McQuown et al. 2017.* Preliminary investigation of blood concentrations of insulin-like growth factors, insulin, lactate, and B-hydroxybutyrate in dogs with LSA as compared to matched controls** IGF-1, insulin, glucose, and insulin:glucose rate between the 2 groups? What was higher in dogs with LSA compared to control dogs?

Answer 116

Not different Lactate and B-hydroxybutyrate

Question 117

***Cozzi et al. 2017.* Canine nodal maginal zone LSA: Descriptive insight into the biological behaivour** nMZL is an indolent LSA. Describe the clinical features. 35 cases All dogs showed ___ ? How may were systemically unwell? Stage of disease? LN population was composed of? Histology showed? Median TTP and LSS?

Answer 117

Generalized lymphadenopathy 1/3 Stage V, 1/3 had extranodal involvement CD21+ cells diffuse LN involvement - "late-stage" MZL 149 days (5 months) and 259 days (8.6 months) **Oucome is poor despite the indolent designation.**

Question 118

***Davis et al. 2017.* A retrospective review of acute myeloid leukemia in 35 dogs diagnosed by combination of morphologic findings, flow cytometric immunophenotypinc and cytochemical staining results (2007-2015)** Presenting clinical signs? Common hematological findings? Overall median survival from diagnosis? Hematological response to various chemotherapies documented in 3 dogs with associated survival? Dogs treated with prednisone or combination of chemo and prednisone had?

Answer 118

Inappetance (66%), lethargy (57%), peripheral lymphadenopathy (74%), and tachypnea (64%) Circulating blasts (85%), anemia (median hematocrit 24%), theombocytopenia (median 57k) 19 days 62, 103, 121 days Improved survival

Question 119

***Matsumoto et al. 2018.* IgA antibodies against Gliadin and Tissue Transglutaminase in dogs with chronic enteritis and intestinal TCL** Dog with intestinal LSA were likely to have?

Answer 119

High levels of serum IgA against gliadin and tTG and serum IgG Ab against tTG Association between inflammatory stimulation by gliadin peptides and subsequent intestinal LSA in dogs

Question 120

***Davies et al. 2017.* Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic DLBCL in UK** DLBCL treated with either COP-type(35%) or CHOP-type (64%) induction chemotherapy Objective RR to induction therapy? Median PFS What factors were independently predictive of longer PFS? Median OS? 1- and 2- year survival rate? What factors were independently predictive of longer OS?

Answer 120

94% - greater CR vs. PR 182 days (6 months) Absence of anemia at diagnosis and pretreatment neutrophil:lymphocye ratio (NLR) below 9.44 322 days (10.7 mo) - 38% and 9% L:M ratio above 1.43, NLR below 11.44, combination of induction and rescue therapy, and total number of doxorubicin disease

Question 121

***Comazzi et al. 2018.* Effects of preanalytical variables on flow cytometric diagnosis of canine LSA: A retrospective study (2009-2015)** Assess preanalytical variables that might influence LN and FNA specimens from dogs with lymphoproliferative disease What affected having a diagnostic sample? What increased the odds of obtaining a diagnostic sample? Major artifacts affeting the diagnostic utility?

Answer 121

Submitting veterinarian, sample material, sample cellularity and artifacts Specimens from different sites and cytological smears Poor cellularity and presence of dead cells

Question 122

***Bennett et al. 2018.* Demographic risk factors for LSA in Australian dogs: 6201 cases** 30 breeds at increased risk for LSA - 15 not previously reported and 26 breeds at decreased risk and 18 not previously reported Which sex was overepresented? Neuter status?

Answer 122

Males over females with OR 1.1 Neutered animals were at higher risk with OR 3.2 in both males and females

Question 123

***Fournier at al. 2018.* Impact of pretreatment neutrophil count on chemotherapy administration and toxicity in dogs with LSA treated with CHOP chemotherapy** All dogs with ANC ___ recovered without medical treatment? The number of dose delays are minimized with a prechemotherapy ANC cutoff? Prechemotherapy ANC class not associated with increased toxicity? **Further investigation of an ANC cutoff near .75 x 10³/uL in which to prescribed antibiotics is indicated**

Answer 123

.75 x 10³/uL 1. 5 x 10³/uL 1. 5-1.99 x 10³/uL

Question 124

***Moore et al. 2018.* Usefulness of chemotherapy for the treatment of very elderly dogs with multicentric LSA** Duration of remission and survival time in dogs \>14 years of age with stage 2 to 5 multicentric LSA 22 received chemotherapy and 7 got prednisolone alone MST for dogs receiving prednisolone? CR achived in how may dogs? PR? Median duration of remission? Which dogs had briefer remission? MST? 1- and 2-year survival? AEs grade 3 or worse? Chemotherapy should not be withheld, dose adjusted because of age.

Answer 124

27 days 95% and 5% 181 days Anemic dogs (110 days) than nonanemic (228 days) 202 days, 31% and 5% 27%

Question 125

***Moetgi et al. 2018.* Prognostic value of CD44 variant isoform expression in dogs with multicentric high grade BCL** 45 dogs with multicentric BCL and 10 healthy dogs CD44 variants of exons 3, 6, 7 and CD44 whole isoform For all isoforms evaluated mRNA expression in dogs with BCL was ___ that control dogs Dogs with BCL had ___ CD44, ___ ORR, median PFS, and median OST?

Answer 125

Lower High, lower **High expression of 3, 6, 7 was associated with poor prognosis in dogs with BCL**

Question 126

***Ambrosius et al. 2018.* Quantification and prognostic value of programmed cell death ligand-1 expression in dogs with DLBCL** How many dogs with DLBCL had PD-L1 fold change \>1? Median PFST? Was PFST associated with PD-L1 expression?

Answer 126

50% 249 days (8.3 months) NO, but was assosciated with thrombocytopenia PD-L1 overexpressed in half the study population - anti-PDL1 therapies may be beneficial in some dogs

Question 127

**Miniscalco et al. 2018. Flow cytometric characterization of S-phase fraction and ploidy in LN aspirate** Describe DNA content analysis uaing LN aspirated from 112 dogs with LSA S-phase fraction accurately descriminated between low- and high-grade LSA with ___ being the best cutoff value No significant results was obstained with regards to survival and SPF

Answer 127

3.15%

Question 128

***Hartlet et al. 2018.* Cancer stem cell population in LSA in dogs and impact of cytotoxic chemotherapy** Quantitated CSC in dogs with BCL and TCL uring tumor aspirates and FC with a panel of CSC markers The percentage of tumor cells expressing CSC marekrs were ___ in dogs with BCL, compared with B cells from normal LNs? TCL? In vitro studies revealed that LSA cells selected for resistance to CHOP had significantly ___ expression of CSC markers, and expressed greater \_\_\_, compared to chemotherapy sensitive cells

Answer 128

Significantly increased, similar in TCL Significantly greater, aldehyde dehydorgenase activity Similar results in relapsed BCL Cytotoxic chemotherapy can lead to enrichment of CSC properties and may be associated with relapse

Question 129

***Morgan et al. 2018.* Canine TCL treated with lomustine, vincristine, procarbazine and prednisolone chemotherapy in 35 dogs** Used a modified protocol Median PFS? 6-month, 1-year, 2-year, and 3-year PFS? MST? How many dogs had AEs?

Answer 129

431 days (14.4 mo) 69%, 54%, 29%, 12% 507 days (17 mo) 30 dogs (85%) with 73% being grase 1 or 2

Question 130

Assumpcao et al. 2018. Targeting NEDD8-activating enzyme is a new approach to treat canine DLBCL

Question 131

***Harding et al. 2018.* Response rate to a single dose of vinblastine administered to dogs with treatment-naive multicentric LSA** 22 dogs How many of the 14 dogs receiving vinblastine at 2 mg/m2 had response? How many of the 5 dogs receiving vinblastine at 2.5 mg/m2 had response? GI toxicity? How many dogs developed neutropenia at 2.5 mg/m2?

Answer 131

1/14 PR 3/5 PR Low in both groups 80% at 1 week post-administration **Treatment at 2.0 mg/m2 is not recommended. Higher does may have improved efficacy**

Question 132

***Sato et al. 2018.* Prognostic significance of hypermethylation of death-associated protein kinase (DAPK) gene CpG island with high-grade BCL** DAPK is a serine/threonine tumor suppressor genes 47 dogs Hypermethylation of DAPK was detected in how many dogs? PFS and OS with hypermethylation? In the multivariable analysis, what was prognostic factor indicating shorter PFS?

Answer 132

20/47 (42.5%) 220 and 266 days and shorter than without hypermethylation (301 vs. 412) Hypermethylation of DAPK

Question 133

***Tanis et al. 2018.* Evaluation of a multiagent chemotherapy protocol combining lomustine, procarbazine and prednisolone (LPP) for treatment of relapsed canine non-Hodgkin high-grade LSA** 41 dogs How may dogs responded? What was the time from initiation to discontinuation (TTD) in responders? How common was neutropenia? How many had elevated ALT? Treatment discontinued in how may?

Answer 133

61% - 12 CR and 13 PR 84 days for CR and 58 days for PR 57% - 12 grade I to II, 8 grade III to IV 59% - 9 grade I to II, 10 grade III to IV 19% 8 dogs

Question 134

***Hartley et al. 2018.* Checkpoint molecule expression by B and T cell LSA in dogs** FC used to analyze expression of PD-1 and PD-L1 from 34 BCL, 6 TCL, 11 relapsed Expression of PD-L1 B cells? Expression of PD-L1 and PD-1 T cells? Expression on tumor infiltrating lymphocytes? In-vitro chemotherapy resistant BCL and TCL had ___ PD1 and PD-L1?

Answer 134

Increased expression by malignant B cells compared to normal B cells Low to normal expression on tumor cells and normal T cells Increased expression of PD-L1 and PD-1 on TCL and BCL Increased expression **Canine LSA upregulate checkpount molecule expression**

Question 135

***Ku et al. 2017.* Cytologic-histologic concordance in the diagnosis of neoplasia in canine and feline LNs: a retropsective study of 367 cases** Determine the accuracy of cytologic diagnosis in LNs using histology as gold standard Cytology sensitivity? specificity? Accuracy? Likelihood of malignancy with positive cytologic diagnosis of neoplasia? High proportions of false negative found in? Factors contributing to discrepancy?

Answer 135

66.6%, 91.5%, 77% 93% mesenteric TCL (63%, mainly cats), metastatic sarcoma (57%), metastatic MCT (31%, mainly dogs) well differentiated lymphocyte morphology, focal distribution of metastases and poorly defined criteria for metastatic MCT

Question 136

Pawlak etl al. 2017. A novel B-cell leukemia cell lines. Establishment

Question 137

***Noland et al. 2018.* Subcutaneous Panniculitis-Like TCL in dogs: Morphologic and Immunohistochemical Classification** Canine nonepitheliotropic cutaneous T-cell lymphoma (NECTCL) are poorly characterized. 5 dogs with Subcutaneous Panniculitis-Like TCL (SPTCL) Median age Breed and sex predilection? Location? Treatment with CCNU? Histologically? Cloncal TCR rearrgement in 5 cases

Answer 137

8.5 years None Shoulder, neck, ventral abdomen 7 months post-diagnosis Proliferation of small to intermediate or large sized, CD3+ T cells infiltrated the subcutis in a lace like pattern and frequently rimmed adipocyts - No epitheliotropism was observed Noted in 4/5 cases

Question 138

***Chimura et al. 2013.* Transcription profile of chemokine receptors, cytokines and cytotoxic markers in peripheral blood of dogs with epitheliotropic cutaneous LSA** 10 dogs with MF and 10 healthy dogs What was the expression of CCR4, epitheliotropism (CXCR3), LN homing (CCR7), and type-1 cytokine (LT-a) and cytotoxic markers (perforin and granzyme) in circulation?

Answer 138

Lower in dogs with MF compared to healthy dogs ## Footnote **Peripheral cytotoxic T cells with skin-homing phenotype could be decreased in peripheral blood because of sequestration in lesional skin**

Question 139

***Holtermann et al. 2016.* Masitinib monotherapy in canine epitheliotropic lymphoma** CR occured in how many of the 10 dogs? Median? PR? Median? IHC available in 8 dogs - KIT expression?

Answer 139

2/10, 85 days 5, 60.5 days KIT-, 6/8 positive for SCF, PDGF-AA weakly positive in 2, PDGF-BB negative 4, weakly positive 1, strong positive 3. Strongly positive for PDGFR-B in 1, 7 negative Strongly positive for PDGFR-a in 5, 2 weak, 1 negative **Effects of masitinib are not through KIT.**

Question 140

***Morges et al. 2014.* Phase II evaluation of VDC-1101 in canine cutaneous TCL** 12 dogs received drug as 30min IV infusion every 21 days, prednisone 1 mg/kg q48 given concurrently Responses? ORR? BRR? Median PFS? How may dogs developed dematopathy?

Answer 140

1CR, 4PR, 2SD, 4PD 45% and 64% 37.5 days 3 and 1 of these was removed from the study

Question 141

***van Stee et al. 2015.* Outcome and prognostic factors for canine splenic LSA treated by splenectomy (1195-2011)** 28 dogs 1 year survival rate? Which immunphenotype had better prognosis? Most common subtypes of BCL? What were 4 poor prognostic indicators? Positive prognostic indicator? Adjuvant chemotherapy?

Answer 141

58.8% BCL than other variants of splenic LSA Marginal zone LSA and mantle cell LSA Hemoabdomen, abdominal distension, lethargy, anorexia Disease confined to the spleen No survival benefit

Question 142

***O'Brien et al. 2013.* Clinical characteristics and outcome in dogs with splenic marginal zone LSA** 34 dogs, 29 splenectomy and 5 necropsy Immunophenotype? How may had cloncal rearragemnet of Ig gene of 33 dogs? MST for 29 dogs that underwent splenectomy? MST for 14 dogs that were asymptomatic?

Answer 142

All BCL 24, 3 pseudocloncal, and 6 polyclonal 383 days 1153 days (3 years) compated to 309 with CS

Question 143

***Albonico et al. 2013.* The expression ratio of miR-15-5p and miR-155 correlates with grading in canine splenic LSA** The molar ratio between miR-15-5p and miR-155 correlated with?

Answer 143

WHO grading New molecular tool for grading canine splenic LSA

Question 144

***Wiggans et al. 2014.* Presumed solitary intraocular or conjunctival LSA in dogs and cats: 9 cases** Animals with introcular LSA represented \_\_\_% of patients with \_\_\_ Animals with conjunctival LSA represented \_\_\_% of patients with \_\_\_ Tumors included B-cell (2 IO and 1 conj), non-B cell, non Tcell (1 IO), and T cell (3 conj) Treatments? All dogs with IO developed? LN mets? Median PFS and OST for PSOL Median PFS and OST conj LSA

Answer 144

0. 19, uveitis 0. 16, conjunctivits enucleation (4 IO) and chemotherapy (3 IO and 2 conj) Neurologic signs 2 patients with conjunctival LSA 178 days for IO 221 and 549 days **Prongnosis better for conjunctival LSA than IO LSA**

Question 145

***George et al. 2016.* Outcome of dogs with intranasal LSA treated with various radiation and chemotherapy protocol: 24 cases** 18 cases were intermediate to high grade and 6 were low-grade Overall MST for high-grade? Cases treated with RT +/- chemo? Chemotherapy alone? MST for low grade group?

Answer 145

375 days (1 year) 455 days (15 months) 157 days (5 months) 823 days (2.25 years) Support the use of RT for intranasal LSA. Role of chemo requires further investigation

Question 146

***Nemec et al. 2012.* Erythema multiformer and epitheliotropic TCL in the oral cavity of dogs: 1989-2009** 14 dogs with erythema multiforme or epitheliotropic TCL What was common? Histologic features diagnostic in how many cases? IHC? What was also used to determine clonality?

Answer 146

Ulcerative stomatitis 7 cases (50%) 3 cases (21%) PARR - 1 case **Histologic features are not always diagnostic. IHC and clonality testing may assist between the two disease**

Question 147

***Hiyoshi et al. 2015.* Association between lymphocyte antigen receptor gene rearrangement and histopathological canine chronic enteropathy** Investigate the relationship between PARR and histopath diagnosis Endoscopic biopsies form 96 dogs with chronic enteritis and 21 GI LSA Clonality observed in how many chronic enteritis? mild enteritis? Dogs with marked enteritis, rate of PARR was ___ than those with lymphocyte epitheliotropism than without epitheliotropism Sensitivity of PARR with GI LSA? Who had shorter survival?

Answer 147

51%, 29% of those with mild enteritis Higher 76% Dogs with marked enteritis those with mild or moderate enteritis

Question 148

***Ohmura et al. 2017.* Detecttion of monoclonality in intestinal LSA with PCR for antigen receptor gene rearrangement analysis to differentiate from enteritis in dogs** Assessed clonality of 29 canine intestinal LSA, 14 enteritis, and 15 healthy controls Detect monoclonal rearragements in how many of intestinal LSA? Polycloncal rearragements? Immunophenotype?

Answer 148

76% (22/29) 100% enteritis and healthy controls T cell was 85% vs. B cell

Question 149

***Desmas et al. 2017.* Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal LSA (2001-2013)** What were the predominant features? Substage? 1 dog had surgery and 30 received chemotherapy (13 had surgery or RT) PFS and MST? Which dogs had longer survival? Presence of hematochezia corresponded with? Addition of local treatment to chemotherapy did not significantly improve the outcome

Answer 149

high grade (18) and B cell immunophenotype (24) b (25) with hematochezia (20) 1318 days (3.6 y) and 1845 days (5 years) Younger dogs Longer PFS

Question 150

***Flood-Knapik et al. 2013.* Clinical, histopathological and immunohistochemical characterization of canine indolent LSA** Indolent LSA comprise 29% of all canine LSA What was the most common histopathological subtype? The addition of IHC resulted in? Did the use of systemic chemotherapy influence survival? Dogs treated with CHB and pred MST? Dogs treated with CHOP?

Answer 150

T-zone (61.7% (MST 33.5 months), then marginal zone 25% (MST 21.2 months) Revised diagnosis 20% No Not reached 21.6 months

Question 151

***Seelig et al. 2014.* Canine T-zone LSA: unique immunophenotypic features, outcome, and population characteristics** Hypothesis - Loss of expression of CD45 is specific feature for TZL All 20 CD45- cases were classified as? The 15 CD45+ were classified as? MST of TZL? Immunophenotyping demonstarted most cases are in what breed and median age? Presented with what 2 signs?

Answer 151

TZL Aggressive TZL 637 days (1.7 years) Golden retrivers and 10 years and have lymphadenopathy and lymphocytosis

Question 152

***Harris et al. 2017.* Clinicopathologic features of lingual canine T-zone LSA** 12 dogs with tongue masses were diagnosed with lingual TZL 11 dogs had? 3 cases were initially diagnosed as? How many achieved clinical remission

Answer 152

lymphocytosis and/or LN enlargement Plasma cell tumors 7 dogs (58%) and 4 achieved SD 1 case had PD and failed to respond to treatment - had histologic features of high grade neoplasm

Question 153

***Martini et al. 2016.* Canine small clear cell/T-zone LSA: clinical presentation and outcome in a retrospective case series** Most dogs had what stage of disease? Was blood or BM more infiltrated? Prognosis?

Answer 153

Stage V Blood Favourable in most cases but few dogs died in a short time

Question 154

***Martini et al. 2015.* Flow-cytometric detection of phenotypic abberancies in canine small clear cell LSA** All cases showed antigen abberancies and neoplasia was always confirmed Combined use of cytology and FC allows solving the differential diagnosis between small clear cell LSA and non-neoplastic reactive conditions

Question 156

***Bromberek et al. 2016.* Breed distribution and clinical characteristics of B cell chronic lymphocytic leukemia in dogs** Median age of dogs? Clinical signs? What breeds had increased risk? What single breed had increased risk and possible unique features?

Answer 156

11 years 50% peripheral lymphadenopathy or splenomegaly, 26% anemia Small breeds English Bulldogs - median age 6 years and lower MHC II and CD25

Question 157

***Giantin et al. 2013.* Evaluation of tyrosine-kinase receptos c-KIT mutation, mRNA, and protein expression in canine leukemias: might c-KIT represent a therapeutic target?** 11 ALL and AUL and 12 CLL Higher c-KIT mRNA was found in?

Answer 157

ALL/AUL (acute undifferentiated leukemia) compared to CLL ## Footnote **Might represent rationale for using TKIs**

Question 158

***Stokol et al. 2015.* Alkaline phosphatase is a useful cytochemical marker for the diagnosis of acute myelomonocytic and monocytic leukemia in the dog** ALP is expressed in immature canine monocytes - possible marker for AML ALP activity in LSA and CLL? ALP activity in ALL? ALP activity in AML? How many of the AML were CD34+? MHCII-

Answer 158

None 31% had weak ALP activity 100% 80% and 100% MHCII- ALP activity may useful to confirm AML if neoplastic cells only express CD34+ on immunophenotyping

Question 159

***Moore et al. 2017.* Patient characteristice, prognostic factors and outcome of dogs with high-grade mediastinal LSA** Common clinical signs? 2 other common findings? Phenotype? Overall PFS and OS? Treatment with CHOP improved PFS in comparison to other medical therapies? OS? Absence of pleural effusion was associated with?

Answer 159

Lethargy, anorexia, PU/PD Hypercalcemia and pleural effusion T-cell 133 days (4.4 mo) and 183 days (6 months) 144 days (5 months) and 194 days (6.5 months) Increased OS but not PFS

Question 160

***Hughes et al. 2017.* Increased frequency of CD45 negative T cells (T zone cells) in older Golden Retrievers** TZL is characterized by T cells lacking expression pan-leukocyte antigen CD45 (TZ) Gene expression analysis on confirmed TZL showed what compared to normal dogs? Peripheral blood from senior dogs, 242 GRs and 42 non-GR were assessed for TZ cells by FC What % of GR had TZ cells? How many of these had clonal rearragement? How may GR without TZ cells had clonal rearragement?

Answer 160

Decrease in CD45 expression compared 31% vs. 14% non-GR 34% for TCR 20% GR have increased risk due to increased frequency of TZ cells

Question 161

***Thamm et al. 2013.* DNA repair deficiency as a susceptibility marker for spontaneous LSA in goldn retriever dogs: a case-control study** Evaluate DNA repair capability after exposure to ionizing radiation or bleomycin GR with LSA demonstrated elevated sensitivity to induction of chromosome damage compared to healthy GR or mixed breed dogs (MBD) Findigns suggest individual (rather than breed) susceptibility and suggest deficiencies in heirtable factors related to DNA repair capabilites may be invovled in development of LSA

Question 162

***Patterson et al. 2014.* Sonographic characteristics of thymoma compared with mediatinal LSA** Appearance of thymomas sonographically compared to LSA? Lymphomatous LNs were more like to be?

Answer 162

Cystic (57%) and heterogeneous (94%) in echogenicity Solid (80%) and divided between hypoechoic (47%) and heterogeneous (53%)

Question 163

**Taylor et al. 2014. Ultrasonographic characteristics of canine renal lymphnoma** All dogs with renal LSA had what feature? Other US findings? Bilateral lesions seen in? FNA performed in 9 dgos and yielded a diagnosis in 7 dogs on first attempt (78%)

Answer 163

Pyelectasia Loss of corticomedllary distinction (9/10), renomegaly (8/10), renal deformity (6/10), hypoehoic lesion (6/10), hyperechoic lesions (2/10) 90%

Question 164

**Linta et al. 2017. The feasibility of contrast enhanced ultrasonography in the diagnosis of non-cardiac thoracic disorders of dogs and cats** Majority of neoplastic lesions showed? Inflammatory lesions showed? Mediastinal malignant lesions showed? Lung and mediastinal abscesses?

Answer 164

Inhomogenoeus distribution of contrast medium Homogenoeus distribution Inhomogeneous distribution pattern Peripheral enhancement of the wall with an avascular center

Question 165

***Watton et al. 2017.* Can malignant and inflammatory pleural effusion in dogs be distinguished using CT?** 20 dogs with malignant pleural effusion (13 mesothelioma, 6 carcinoma, 1 LSA) and 32 pleuritis (18 pyothorax and 14 chylothorax) Age of dogs with malignant pleural effusion? CT findings with malignant pleural effusion? Signs of thoracic wall invasion were seen in?

Answer 165

Older (median 8.5 years vs. 4.9 years) Pleural thickening (65% vs. 34%), tended to have thickening of the parietal pleural only (45% vs. 3%) and more marked pleural thickening (3mm vs. 0 mm) Only with malignant pleural effusion No difference in pleural fluid volume, attenuation, contrast enhancement, amount of pannus, prevalence of mediastinal adenopathy **Marked thickening of the parietal pleural and signs of thoracic wasll invasion support malignant neplasia**

Question 166

***Allett et al. 2016.* MRI findings in the spine of 6 dogs diagnosed with LSA** Common findings included multifocal disease (4/6), vertebral invovlement (5/6), spinal cord compression (4/6), involvement of more than one spinal compartment (medullary cavity, vertebral canal, paraspinal soft tissues) (6/6) All spinal and paraspinal lesions identified were T2-W isointense to hyperintense, STIR hyperintense, T1-W hypointense to isointense, showed variable moderate to strong enhancement The STIR and T1-W postcontrast sequences were subjectively most useful to identify spinal and paraspinal lesions.

Question 167

***Feeney et al. 2013.* Applicability of 3T body MRI in assessemnof nonfocal BM invovlement of hematopoeitic neoplasia in dogs** Out-of-phase MR pulse sequence was useful in distinguising diffuse bone marrow infiltrate from minimally or unaffected marrow using skeletal muscle for signal intensity comparison on whole body MRI

Question 168

***Tater et al. 2017.* Assessment of cardiac troponin I and tissue velocity imaging in 14 dogs with malignant lymphooma undergoing chemotherapy treatment with doxorubicin.** Did the standard echocardiographic parametgers, tissue doppler indices or cTnI concentrations differ at any time point in 12-week cycle?

Answer 168

No ## Footnote **Use of doxorubicin at standard doses for LSA may not be associated with significant myocardial damage.**

Question 169

***Mizutani et al. 2016* Evaluation of CD25 positive cells in relation to the subtypes and pronoses in various lymphoid tumors in dogs** IHC of DLBCL, TZL, follicular lymphoma CD25 positive cells for consistently detected in? CD-25 positivity in LN was higher in? PFS with relation to CD25-high and CD25-low group?

Answer 169

TZL and FL, variable in DLBCL High grade BCL or TZL than healthy dogs Shorter in CD25-high group than CD25-low group

Question 170

***Fujiwara et al. 2015.* Expression profile of corculating serum micRNA in dogs with LSA** The expression levels of 4 miRNA were reduced in LSA group- let-7b, miR-223, miR-25, miT-92a miR-423a was significantly increased to the controls

Question 171

***Johnston et al. 2014.* The immunosignature of canine LSA: characterization and diagnostic application** An individual immunosignature and a generalized immunosignature was observed. General LSA immunosignature was able to predict disease status in independent set of dogs (97% accuracy) A seperate immunosignature was eblt to distinguish LSA based on immunophenotype (88% accuracy) Individual immunosignature was capable of confimring remission 3 months following diagnosis. Was able to predict which dogs with BCL would relapse in \<120 days (accuracy 97%)

Question 172

***Rutgen et al. 2015.* Composition of lymphocyte subpopulation in normal canine LNs** CD11a(+) 92.2 ± 12.3%, CD3(+) 55.0 ± 14.1%, CD3-12(+) 57.3 ± 14%, CD5(+) 52.3 ± 12.7%, CD21(+) 33.9 ± 11.8%, CD79αcγ(+) 46.9 ± 14.8%, CD56(+) 4.9 ± 5.9%, and CD14(+) 5.5 ± 6.8%. There were 58.7 ± 9% CD4(+) and 21.3 ± 7.8% CD8(+) cells inside the gate of CD3(+) cells. Cytology revealed a mixed population of mostly lymphoid cells in all samples. The absence of a monoclonal or oligoclonal neoplastic population was confirmed by PARR.

Question 173

***Deravi et al. 2017.* Specific immunotypes of canine T cell lymphoma are associated with different outcomes** Compared to multicentric T cell lymphoma, gastrointestinal lymphoma had shorter survival and progression free interval, and hepatosplenic lymphoma had shorter survival. Among dogs with multicentric T cell lymphoma, immunotypes of CD4+/CD8-/MHCII+, CD4-/CD8+/MHCII+ and CD4-/CD8+/MHCII- were associated with longer survival times than the immunotype of CD4+/CD8-/MHCII-, and immunotypes of CD4+/CD8-/MHCII+, CD4-/CD8+/MHCII-, and CD4-/CD8-/MHCII+ were associated with longer progression free intervals. Dogs with multicentric T cell lymphoma and concurrent leukemia had shorter survival but similar progression free interval compared to those without leukemia. Body weight, sex, hypercalcemia, cell size, expression of CD3 and use of combination or single agent chemotherapy did not significantly affect outcome of multicentric TCL.

Question 174

**Flesner et al. 2014. 6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells** 6-TG is epigenetically active as a demethylating agent casuing downregulation of DNA methyltransferase 1(DNMT1) through ubiquiting targeted degradation Zebularine a cytidine analog also has demethylating activity as oral bioavilability Cell line were treated with each agent, DNMT1 protein and global DNA methylatinn was significantly \_\_?

Answer 174

Decreased Dose-dependednt decrease in cel survival with apoptosis being the main cause of death

Question 175

***de Mello Souza et al. 2014.* Detection of retinoid receptors in non-neoplastic canine lymph nodes and in lymphoma** Non-neoplastic lymphocytes were ___ for all retinoid receptors? Retinoic acid receptor-g was detected in __ BCL and __ TCL Retinoid X receptor-g was positive in \_\_?

Answer 175

Negative 100%, 78% 78% of TCL

Question 176

**Fujiwara et al. 2014. Inhibition of p16 tumor suppressor gene expression via promoter hypermethylation in canine lymphoid tumor cells** Methylation status was examined in 4 cell lines In 3 cell lines with low level p16 mRNA expression, ___ CpG sites in promoter region wee methylated but not in 1 cell line Expression of p16 mRNA was restroed after cultivation with methylation inhibitor, 5-Aza-2'deoxycytidine **Inactivation of p16 gene by hypermethylation of its CpG island in a fraction of canine lymphoid tumor cells**

Answer 176

20

Question 177

***Asproni et al. 2014.* Immunohistochemical expression of COX-2 in normal, hyperplastic, and neoplastic lymphoid tissues** **24 hyperplastic samples and 44 lymphoma samples (22 BCL and 22 TCL)** How many were positive in hyperplastic LN? How many LSAs were positive?

Answer 177

Few macrophages were COX-2 positive Six of 44 LSA (13.6% - 3B and 3 T) overexpressed COX-2

Question 178

***Axiak-Bechtel et al. 2014.* Chemotherapy and remission status do not alter pre-existing innate immune dysfunction in dogs with LSA** Dogs had ___ production following LPS stimuation and ___ following peptidoglycan stimuation - did this imrpove following remission of LSA? Dogs had ___ E.coli induced respiratory burst function after chemotherapy induced complete or partial remission

Answer 178

decreased TNF, increased IL-10, did not improve Reduced

Question 179

***Poggi et al. 2015.* Flow cytometric evaluation of Ki67 for the determination of malignancy grade in canine lymphoma** High grade showed compared to low grade LSA? Was there a difference between B and T immunophenotype?

Answer 179

higher ki67 compared to low grade LSA Significant difference was detected Cut-off value of 12.2% with sensitivity 96.3% and specificity 100%

Question 180

Tomiyasu et al. 2014. The regulation of the expression of ABCG2 gene through mitogen-activated protein kinase pathways in canine lymphoid cell lines

Question 181

***Tomiyasu et al. 2014.* Epigenetic regulation of the ABCB1 gene in drug-sensitiveand drug-resiatnt lymphoid tumor cell lines obtained from canine patients** In 2 drug sensitive cell lines, GL-1 and CLBL-1, ABCB1 mRNA was lower than drug resistant cell line, UL-1, Ema CpG island present in the upstream regions of exon 2 was hypermethylated in GL-1 and CLBL-1, but hypomethylated in UL-1 and Ema Histone H3 was increased in UL-1 and Ema compared to GL-1 and CLBL-1 Treatment with inbhitor increased ABCB1 mRNA expression in GL-1 and CLBL-1

Question 182

***Thalheim et al. 2013.* Lymphoma immunophenotype of dogs determined by IHC, FC, and PCR for antigen receptor rearragements** Sensitivity of FC vs. PARR for B cell Sensitivity of FC vs. PARR for T cell Percent agreement between FC and IHC? Between PARR and IHC? FC and PARR? Among all 3

Answer 182

91% vs. 67% 100% vs. 75% 94% 69% 63% 63% FC is superior to PARR for immunophenotyong

Question 183

***Avery et al. 2014.* Flow cytometric characterization and clincial outcome of CD4+ TCL: 67 cases** The majority of CD4+ TCL were? Median survival? Histologically classified as either? What had an effect on PFI and survival? Which had a more indolent course?

Answer 183

CD45+, low MHCII and aggressive clinical course, 159 days lymphoblastic or peripheral T cell Size of the neoplastic lymphocytes CD45- and MHCII high

Question 184

**Woldemeskel et al. 2014. Tumor microvessel density-associated mast cells in canine nodal LSA** Mast cells are associated with angiogenesis What was the mast cell count in LSA compared to control? Was mast cell count correlated with tumor microvessel density? Was there a difference in mast cell count and tumor microvessel density among different grade of LSA?

Answer 184

Higher Yes No

Question 185

**Giantin et al. 2013. Evaluation of tyrosine-kinase receptor c-kit mutations, mRNA, and protein expression in canine LSA: might c-KIT represent a therapeutic target?** **25 BCL and 21 TCL** KIT mRNA was amplifiable but low limit in? Which showed higher expression of KIT? Gain of function mutations?

Answer 185

76% BCL and 33% TCL High grade TCL - higher mRNA observed None **Potential use in HG TCL**

Question 186

***Gramer et al. 2015.* Determination of MDR1 gene expression for prediction of chemotherapy tolerance and treatment outcome in dogs with LSA** MDR1 expression analyzed in 27 dogs with malignant LSA receiving chemotherapy Dog developing severe AEs under treatment had? In longitudinal MDR1 expression analysis, 4 dogs showed greater than 2-fold MDR1 upregulation - all 4 of these had disease progression but none of the other dogs

Answer 186

Signifcantly lower basal levels compared to those who tolerated the drugs well

Question 187

***Ginn et al. 2014.* Positive association between a glutathione-S-transferase polymorphism and LSA in dogs** Plays a role in detoxification of carcinogens Low activity of GSTT1 are risk factors for NHL in people 93 LSA and 86 age-matched controls Of the 27 canine GSTT1 variants the 12+28 G?A was assocaited with LSA with the AA genotype found in 18.3% but only 3.5% controls

Question 188

***Elliot et al. 2013.* Thymidne kinase assay in canine LSA** TK correlated with duration of first remission or survival in dogs with LSA How may had TK above the reference interval at initial? Difference between BCL and TCL? TK and higher stage of disease? TK activity prior to treatment and DFR and survival? TK at remission?

Answer 188

47% BCL had higher than TCL Not higher No association Fell into normal range at remission if elevated

Question 189

***Seiser et al. 2013.* Reading between the lines: molecular characterization of 5 widely used canine LSA tumor cell lines** Aberrant gains of what genes were noted? Deletions of what genes?

Answer 189

MYC, KIT, FLT3 PTEN and CDKN2

Question 190

***Aresu et al. 2014.* VEGF and MMP-9: biomarkers for canine LSA** TGF-B stimulates VEGF and MMP production (useful biomarkes in human LSA) Expression of MMP-9 and VEGF and TGF in dogs with LSA? Act-MMP9 and VEGF were higher in? VEGF in high grade vs. low grade TCL During chemotherapy, what happend to MMP-9 and VEGF?

Answer 190

MMP9 and VEGF were higher and TGF-B was lower than control dogs TCL, stage V compared to stage III-IV regardless of immunophenotype Higher in HG TCL No correlation between cytokines and outcome Decreased in BCL

Question 191

***Kiser et al. 2017.* Lymphoma classification in goats** Age and breed? Sexes? How many had TCL? BCL? Which distribution was common? TCL invovlved? TCL were further classified as? BCL were classified as?

Answer 191

You (median 3 years) and dwarf breeds (pygmy) Similar 73% amd 27% Multicentric Thoracic cavity and neck - thymic origin lymphoblastic (27%), LGL (9%), diffuse small lymphocytic LSA (27%), pripheral/mature TCL not otherwise specified (36%) DLBCL (50%), B-cell lymphocytic lymphoma intermediate type (50%) Goats get TCL!!!

Question 192

***Sogame et al. 2018* Intestinal lymphoma in dogs: 84 cases** Overall MST Factors associated with shorter survival times? Most common changes noted in intestinal tract? Protocols used? MST with treatments used?

Answer 192

62 days Anorexia, septic peritonitis and tumor location (intestinal tract only, intestinal tract and abdominal LN, or intestinal tract and extraintestinal organs) Altered wall thickening with loss of layering (41) and presence of \>1 discrete mass (24) L-CHOP or CHOP (48) and CCNU (14) 60 days vs. 144 days - but did not differ significantly **Anorexia and septic peritonitis are associated with poor prognosis**

Question 193

***Sadowski et al. 2018.* Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with LSA** Verdinexor is a orally bioavailable selective inhibitor of SINE 58 dogs with naive or progressive B or TCL - 1.5 mg/kg 3x/weekly Treatment with single agent resulted in ORR of? TCL had ORR? Toxicity?

Answer 193

37%, 71% Well tolerated with grade 1 or 2 anorexia

Question 194

***Comazzi et al. 2018.* Breed-associated risks for developing canine LSA differ among countried: an European canine LSA network study** Which breeds had significant predisposition to LSA? Which breed developed TCL? Which breed developed BCL? Were labradors predisposed to LSA? How about Golden Retriever?

Answer 194

Boxers, Rottie, Doberman, and Bernese mountain dog Boxers Rottie Nope b ut developed high grade TCL No predisposition to LSA to TZL

Question 195

***Yamazaki et al. 2018.* Dynamic changes in DNA methylation patterns in canine LSA cell lines demonstrated nu genome-wide quantitatice DNA methylation analysis**

Question 196

***Bonemblante et al. 2018.* Cytomorphological description and intraobserver agreement in whole slide imaging for canine LSA** ## Footnote The overall intra-observer agreement for cytomorphological features was fair to moderate (κ=0.34-0.52) for the three observers and moderate (κ=0.44-0.53) for the evaluation of grade of malignancy. The diagnostic agreement between FC and digital slides was slight (κ=0.16) for the inexperienced observer, fair (κ=0.32) for the mildly experienced observer and moderate (κ=0.50) for the very experienced observer. The diagnostic agreement between FC and glass slides was fair (κ=0.37) for the inexperienced observer, substantial (κ=0.63) for the mildly experienced observer and moderate (κ=0.50) for the very experienced observer. These findings underline the importance of observer experience in determining the grade of malignancy, especially if digital slides are used. The study also identifies some technical limitations of the WSI scanner used in this study, mainly linked to image quality, which might affect the morphological evaluation of neoplastic cells.

Question 197

***Couto et al. 2018.* Clinical characteristics and outcome on dogs with small cell T-cell intestinal LSA** Most common clinical sign? US abnormalities were present in? 14 dogs received the same tx MST for all dogs? for those that got tx? Which dogs had short survival?

Answer 197

Diarrhea (13) 8/13 dogs (61%) - abnormal wall layering (7), hyperechoic mucosal strictions (7) representing the most common findings 279 days (9.3 months) and 628 days (1.7 years) Anemia and weight loss **Dog that received alkylating agent and steroids had long survival time**

Question 198

***Tomiyasu et al. 2018.* Clinical and clinicopathological characteristics of acute lymphoblastic leukemia in cats** Clinical signs? Lymphoblasts orignated from what? 5/6 cats were treated with chemotherapy, MST?

Answer 198

lethargy and anorexia common and anemia and thrombocytopenia B-cell lineage in 4 cats and T-cell lineage in 1, and 1 was positive for both B-cell markers (CD21) and T cell marker (CD8) 55 days

Question 199

***LaRue et al. 2018.* CNS lymphoma in 18 dogs (2001-2015)** 15/18 received treatment other than prednisone 3 dogs chemo + RT after surgical decompression 5 dogs chemo 2 dogs RT after surgical decompression 2 dog RT and chemo Overall MST?

Answer 199

171 days Dogs receiving any tx lived longer than cases in historical reports

Question 200

***Noland et al. 2018.* Coexpression of CD3 and CD20 in Canine enteropathy-associated TCL** Increasing evidence some canine and human TCL express the B cell marker CD20 Describe 3 cases of CD3+, CD20+ Pax5-, EATL type 1 in dogs 3 cases had clonal rearrgament? Inital CS? Mean age? Survival?

Answer 200

TCR gene Weight loss, inappetance, diarrhea, and/or vomiting 9 years variable - 20 days to 1.6 years **Prognostic significance of T cells expressing CD20 is unclear**

Question 201

***Matsumoto et al. 2018.* Immunohistochemical profiling of canine intestinal TCL**

Question 202

***Degl'Innocenti et al. 2018.* Canine cerebral intravscular LSA: neuropahtological and immunohistochemical findgins** IVL is a rare angiotropic larger-cell LSA where neoplastic cells proliferate in the lumina of the small blood vessels in the absence of mass or leukemia 10 cases of IVL Average age? CS? Phenotype? Marked expression of? CD29?

Answer 202

8 years Depression, seizres, ambulatory deficits 3 Tcell, 3 B-cell, 4 non-T non-B Marked expression of CD44, CD29 positive cells seen in 4 IVL CD44 expression is as seen in humans but CD29 was variable confirming partial pathogenic mechanism CD44 and CD29 are needed for intravascular aggregation of neoplastic lymphocytes

Question 203

***Coy et al. 2017.* PD-1 expression by canine T cells and functional effects of PD-1 blockade** What % of CD4 T cells and CD8 T cells expressed PD-1 in healthy dogs? Expression in dogs with cancer? Levels of IFN-g?

Answer 203

5-10% and 20-25% Upregulated PD-1 enhanced T cell activation as assessed by proliferation and IFN-g production PD-1 Abs also reversed T cell suppression

Question 204

***Kumar et al. 2017.* Programmed death ligand 1 is expressed in canine B cell LSA and downregulated by MEK inhibitors** PD-L1 is expressed in canine B cell LSA

Question 205

***Gareasu et al. 2018.* In vitro efficacy of a first-generation valosin-containing protein inhibitor (CB-5083) against canine LSA** Plays a role in protein homeostatis. Exerts cytotoxicity through induction of irreversible proteotoxic stress CD-508 treatment resulted in preferential cytotoxicity in canine LSA cell lines Disrupted the ubiquitin-dependent protein degradation system, by inducing ER stress as indicated by increase in DDIT3 Activation of the unfolded protein response occured through the increase eIF2a phosphorylation and increased transciption of ATF4 Cells underwent apoptosis through caspase cascade

Question 206

***Matsumoto et al. 2018.* Pathological features of intestinal TCL in Shiba dogs in Japan** 7 breeds had increased risk of developing intestinal TCL? Phenotye? CD20 expression? Age? Survival difference between Shiba and Miniature Daschund?

Answer 206

Shiba dogs, GSD, Cairn terriers, Boston terriers, Papillions, Pugs, Maltese IHC revealed ubiquitous cyctotoxic immunophenotype CD20 co-expression noted in 11% Shiba were younger than Miniature Daschund None