LSA Flashcards
In dogs with multicentric lymphoma how does the presence of peripheral neutrophilia or the N:L ratio associate with progression free survival time?
Neutrophilia is associated with significantly shorter progression free survival time ( 70 vs. 184 days) at the time of diagnosis, but N:L ratio does not.
(Veluvolu, JAVMA, 2021)
Recently different subsets if nodal T cell lymphoma were identified in a study combining flow cytometry, histopathology and gene expression. Which were these subsets characterized by flow cyto and were they identifiable on histology?
Which pathway was downregulated? Which breed is usually encountered?
(Harris, VCO, 2018)
The subsets were: CD4+ (most common, 82%), CD8+, CD4-CD8-
They were not distinguishable on histology, features were consistent with WHO PTCL.
(Usually CD3+, CD4+, CD45+, low MHCII, CD21-)
Downregulation of PTEN, consequent upregulation of PI3K/AKT/mTor pathway; Boxers are more commonly seen
Which were the patient characteristics in the study characterizing nodal T cell CD8+, CD4- CD8- lymphomas?
Which lymphomas had a better outcome
(Harris, VCO, 2020)
CD8+: mostly female, older, (Boxer, Goldie), cutaneous involvement, MST 7 months
CD4- CD8-: mostly male, older, (Boxer, Goldie), mediastinum, hypercalcemia, MST 5 months (this one similar to CD4+ lymphomas, possibly same origin
The cell size was variable, dogs with smaller sized lymphos did better approx. 9M (but still too little to be considerd indolent)
What is diffuse small B-cell lymphoma (DSBCL)? How can it be identified ? What is the prognosis?
(Hughes, Vet Pathol, 2021)
It was noticed on flow cytometry, smaller sized B-cells than with the usual DLBCL
Small B-cells: marginal zone or follicular lymphoma (mantle mostly spleen) and SLL/CLL
On flow cyto same as DLBCL: CD21+, MHCII+, CD25+ (activated B cells)
Prognosis poor: MST 140 days (<5 months)!!!
Only identifiable on histo: diffus small B -cells!
SLL/CLL-same entety in humans (in the dog 45% of cases with CLL have lymphadenopathy, but usually no LN biopsy is taken)–>in 27% of cases lymphocytosis was seen, which was higher than with DLBCL
What are the features of a newly identified syndrome of polyclonal B-cell expansion in english bulldogs?
(Rout, JVIM, 2020)
The english bulldogs are approx. 7 years (youngish)
mostly male (70%)
in 60% have splenomegly or splenic mass (lymphadenomegaly is rare (10%))
median 22 000/µl lymphos
77% hyperglobulinemia, IgA +/- IgM (polyclonal or restricted (1-5 peaks, >2000 amplitude, 2x height of polyclonal peaks) polyclonal)
low MCH II and CD25
–> splenectomy and treatment for hyperglobulinemia might be needed; malignant transformation is possible
Is B-CLL considered a heterogenous disease? Which dogs have a markedly worse prognosis and why?
What can be an indicator of worse prognosis?
(Rout, JVIM, 2021)
Yes (in people as well), Boxers have a worse outcome, approx. 6 months vs 14 months for non-boxers (small breeds also do better, 18 months)
Boxers do not have a mutation on the IGH gene (in people the mutation is associted with prolonged survival
>40% Ki67 and >60 000/µl associated with worse outcome
MST for the whole population 300 days
(dogs with splenomegaly and lymphadenomegaly included–> these dogs might have DSBCL)
Golden retrievers are overrepresented in T-zone lymphoma. Which factors have a possible protective role?
Which factors are associated with development on CD45-like diesease?
(Labadie, JVIM, 2019)
Hypothyroidism (Thyroid hormones might facilitate in the development)
Omega fatty acids-antiinflammatory role, in humans NHL associated with chronic inflammation
UTI/calculi and eye disease associated with development of T-zone lymphoma
In the case of GI localized high grade lymphoma, according to prognostic indicators either surgery or chemotherapy should be the preferred treatment. Which are these prognostic factors and in which therapy should be chosen accordingly?
(Yamazaki, VCO, 2020)
Ki67 (can inidcate relapse after surgery) prognostic for better outcome with chemotherapy
MGMT (maybe contributing to drug resistance) prognostic for surgery
What was the MST for dogs with high grade GI lymphoma in a recent study?
What contributed to poorer prognosis?
In which cases is surgery indicated?
(Sogame, JAVMA, 2018)
MST was 62 days
With and without surgrery no difference in survival
Anorexia and peritonitis -poorer survival
Perforation, peritonitis, obstruction or localized disease
(dogs purely intestinal tumors had a longer survival compared to when LN or extraintestinal sites were involved)
What is the prognosis for dogs with small cell GI lymphoma?
Which biochemical parametes were changed?
What had a negative effect on survival?
(Couto, VCO, 2018)
Good, approx. 2 years with treatment
Hypoalbuminemia
Hypocobalaminemia
(histo+IHC+ clonality is needed for diagnosis)
Anemia, weight loss, lack of therapy poorer prognosis
How was the efficacy of TMZ alone in comparison to TMZ/DOX for relapsed lymphoma?
(Treggiari, VCO, 2017)
Similar, short
TTP 15 vs 19 days
MST 40 vs 24 days
ORR 30% vs 60%
In a prospective study investigating B-cell subtypes with FC, histo+ IHC and CHOP-19, which conclusions were met?
It is possible to differentate B-cell subtypes by flow cytometry?
(Wolf-Ringwall, VCO, 2019)
B-cell lymphoma is a heterogenous disease
It is possible to differentiate by size between DLBCL and smaller cell lymphomas, but further classification is only possible via histology (nMZL, follicular, SBCL, Burkitt)
Some smaller cell lymphomas possibly have a poorer outcome eg. nMZL
DLBCL vs. non-DLBCL PFI 8m vs 5m, MST 11 m vs 4 m
Factors associated with better outcome >5.5 years, weight > 29 kg, lower level of CD25 expression, lack of lymphocytosis, completed CHOP
Can T-zone lymphoma be safely diagnosed through flow cytometry?
(Stein, Vet Pathol, 2021)
Mostly yes, but histopathology is still the gold standrad.
In the study 2 CD45+ T cell were indendified, which were characterized histopathologically as T-zone
What was the response rate and toxicity profile in the LPP protocol?
(Tanis, VCO, 2018)
The response rate was 61% (compatible with other alkylating based rescues, 34-65%)
For CR 84 days, PR 56 days (time to discontintinuation)
-Neutropenia 57%, Thrombocytopenia 20%, Gi tox 30% (Vinc not the reason for GI tox in LOPP), ALT (59%)
-discontinuation due to toxicity 20%
-more pulsatile dosage of procarbazine may be better (longer response)
Why had DMAC protocol lower response in a recent assessment?
Smallwood, VCO, 2020
Possible cross-resistance to DOX
Some patients recieved prior DMAC drugs
Alvarez excluded dogs that did not finish 2 weeks of the cycle (here 1 week )
Previous response 42 and 73%–> here 35%
What are B-symptoms? What is the association of B-symptoms with PFI and MST?
(Skor, VCO, 2020)
Weight loss, Fever, unexplained resting tachypnea
The occurance of B-symptoms had a sig. negative effect on survival
PFI 3M vs 11 M
MST 5M vs 15 M
In which phases of the cell cycle is Ki67 detectable?
Is it possible to measure Ki67 by flow cytometry? How does it compare to gold standard, IHC?
(Rigillo, VCO,2021)
Ki67 expressed in all active phases, except G0
It is possible, although further studies are needed to correlated it better to IHC
With both methods Ki67 expression was higher in intermediate/high garde lymphomas
There were discrepancies between the 2 methods–> it might be to early to use them in an alternative way
