LSA - General Flashcards
What chromosomal changes have been documented in canine LSA?
gains of canine chromosomes 13 and 31, loss of 14
Tisomy of what chromosome increased duration of first remission and OST in dogs with LSA?
chromosome 13
____ virus is a _____ type of virus that has been linked to some forms of LSA in humans but has not been linked to canine LSA
Epstein-Barr, gammaherpesvirus
Helicobacter infection in Beagles showed gastric lymphoid follicle formation that is considered a precursor of what lymphoma in humans?
mucosa-associated lymphoid tissue (MALT) LSA
What herbicide has been shown to increase the risk of LSA in dogs?
2,4-dichlorophenoxyacetic acid (2,4-D)
What % of cats undergoing renal transplant developed cancer while on cyclosporine immunosuppressive therapy?
36%
In what breed has a syndrome of immunoproliferative instestinal disease characterized by LP-IBD that can develop into GI LSA been recognized?
Basenjis
In what % of dogs is hypercalcemia found?
10-40%
Epitheliotropic cutaneous LSA typically originates from ____ cells in dogs vs. ____ cells in humans
Dogs: CD8+ T cells
Humans: CD4+ T cells
What is it called when a patient with cutaneous LSA develop peripherally circulating large malignant t cells?
Sezary syndrome
What is intravascular LSA?
akak angiotropic or angioendotheliomatosis
proliferations of neoplastic lymphs w/in lumen and wall of blood vessels in absence of primary extravascular mass or leukemia
What anatomic form of canine LSA has intravascular LSA been most commonly associated with
CNS or PNS LSA
What criteria does the REAL/WHO system for LSA incorporate
anatomic, morphologic (cyto and histo), and immunophenotype
What does the National Cancer Institue Working Formulation (WF) use to categorize LSA?
Pattern (diffuse or follicular)
cell type
does NOT include immunophenotype
What does the updated Kiel classifcation used to classify LSA?
architectural pattern
morphology (centroblastic, centrocytic or immunoblastic)
immunophenotype
Diffuse pulmonary infiltration on radiographs is present in what % of dogs with multicentric LSA?
27-34%
Actual incidence may be higher based on BAL data
What are the anatomic site categories used for WHO staging of LSA in domestic animals?
A. Generalized
B. Alimentary
C. Thymic
D. Skin
E. Leukemia
F. Others
What are the three clinical stages of epitheliotropic T-cell LSA?
- scaling, alopecia and pruritus
- progression to erythematous, thickened, ulcerated and exudative lesions
- progression to proliferative plaques and nodules with progressive ulceration
What was the ORR and MST for horses treated with chemo for LSA? (Luethy JVIM 2018)
ORR 93.3%, CR 33%, PR 60%, SD 7%
MST 8mo
What is the most common subtype of lymphoma in horses?
Multicentric
T cell rich Large B cell LSA
(peripheral T cell LSA and DLBCL also frequent)
Most canine LSA that involves the CNS is ____ (primary vs. secondary) and is ______ (T or B cell). LSA of the PNS is usually _____ (T or B cell)
CNS usually secondary and B cell
PNS usually T cell
What is the MST of dogs with presumed solitary ocular LSA (PSOL) treated with enuc?
if no systemic involvement 769d
if systemic involvement 103d
What is the most common paraneoplastic syndrome associated with LSA?
Anemia
Hypercalcemia associated with LSA is usually due to ____ but can be associated with what other factors?
PTHrp
Also production of IL-1, TNF-alpha, TGF-beta and vitamin D analogs
Monoclonal gammopathies occur in ~_____% of dogs with LSA
6%
What are the usual T cell flow markers
CD3 (pan T) CD4 (helper T) CD8 (cytotoxic T)
What are the usual flow B cell markers? Which one can also be expressed by TZL?
CD79a, CD20 and CD21
CD21 can also be expressed by TZL
T cell precursor LSA has what immunophenotype
CD45+, CD34+/-, CD5+/-, CD3+/-, CD4+/-, CD8-
B cell precursor lymphoma has what immunophenotype?
CD45+, CD18+, CD34+/-, CD79a+, CD21+/-, CD20+/-
Based on withrow, standard CHOP-based chemo induces remission in ____% of dogs with overall MSTs of _____ and ____% alive at 2years after initiation of chemo
remission in 80-95% of dogs
MST 10-12mo
20-25% of dogs alive at 2 yrs
Based on withrow, the CR rate fod gos with LSA treated with single-agent dox is ____% with an MST of ______
50-75%, MST 6-8mo
What is the most important outcome measure and preferred temporal outcome criterion for assessing LSA protocols?
PFS
What are the canine mAb drugs designed to target B-cell or T-cell LSA? Why aren’t these commercially available
B cell: blontuvetmab/Blontress (meant for CD20)
T cell: tamtuvetmab/Tactress (meant for CD52)
Specificity inadequate to effect clinical efficacy
What are the most consistently identified prognostic factors for peripheral nodal LSA in dogs?
immunophenotype
WHO substage (a vs. b)
indolent classification
Dogs with low expression of class II MHC and what other Ag have been shown to have shorter remissions and survival times
B5 antigen
What are the three primary subtypes of CLL in dogs?
- T-CLL (most common), usually CD3+/CD8+ granular lymphs
- B-CLL (next most common) CD21+
- Atypical CLL
What is the most distinguishing cyto feature of large lymphs in ALL
Large lymphs have a nuclear chromatin patter that is typically less condensed that chromatin in small lymphs but more condense than myeloblasts
What % of dogs with CLL had monoclonal gammopathies and what type were they usually?
68%, usually IgM or IgA
What is the term for CLL that evolves into an acute phase that is rapidly progressive and characterized by large lymphs?
Richter’s syndrome
happens in 2% of T-CLLs and 10% of B cell CLL
Siamese/oriental breeds are more likely to be what age and develop what form of LSA?
Younger (median 2yrs)
Mediastinal that is not related to FeLV
FIV associated LSA is more likely to be ______ phenotype. FeLV associated LSA is more likely to be ________ phenotype
FIV: B cell
FeLV: T cell
What environmental factor has been associated with an increased risk of LSA in cats?
environmental tobacco smoke (ETS) - risk increases with duration of exposure
THe majority of LGAL (low-grade alimentary LSA) in cats are what phenotype and are thought to arise from what?
T-cell
MALT
Most T-cell GI LSA in cats are mucosal and equivalent to what WHO type?
WHO enteropathy-associated T-Cell LSA (WHO EATCL) type II
The majority of feline intermediate or high grade alimentary LSAs are ____ phenotype and equivalent to what WHO classification?
B cell
WHO EATCL type I (even though that stands for enteropathy-associated T cell LSA…)
Large granular LSA stains for what with IHC and includes what cells? What other marker is commonly expressed?
IHC: granzyme B, also 60% expressed CD103 (integrin alpha E)
cytotoxic t cells (usually CD3+/CD8+/CD21-) but also includes NK cells
According to withrow, when treated with combination chemotherapy, cats with intermediate to high grade alimentary LSA have ____% response rates with ~_______ CR. Cats with CR have MSTs of _____
50-65% response rate
1/3 CR, MST 7-10mo
Cats with Hodgkin’s like LSA have what immunophenotype
T-cell-rich-B-cell LSA
PARR in cats is approximately ____% sensitive for the diagnosis of LSA
80%
According to withrow, ~____ of cats with renal LSA will benefit from COP or CHOP based protocols with MSTS reported to be ______
2/3’s of cats benefit
MSTs 4-7mo
~____% of cats with CNS LSA are FeLV antigenemic
50%
Most cats with ocular LSA are presented with what?
Uveitis or iridial masses + signs related to systemic involvement of LSA
~_____% of cats with ALL are FeLV positive and have ______ immunophenotype
60-80%, T cell
Serum thymidine kinase 1 is higher or lower in dogs with lymphoma compared to control dogs (Boye, JVIM 2019)
Higher (>20Du/L) Dogs that achieved CR sTK1 similar to controls; PR higher than controls
A ___ increase in serum thymidine kinase 1 predicted relapse at next recheck in dogs with LSA; sensitivity and specificity? (Boye, JVIM 2019)
5-fold increase; sensitivity 50%, specificity 94%
What forms of LSA less likely to have high serum thymidine kinase 1 at baseline
T cell Small or intermediate LSA
Rate of response for equine LSA (Luethy JVIM 2019)
CR 33.3% (5/15) PR 60% SD 6% ORR = 93.3%
AEs related to chemotherapy in horses treated for LSA (Luethy JVIM 2019)
Mostly mild, related to doxorubicin most commonly, 1 grade 5 hypersensitivity
Most common forms of LSA in horses (Luethy JVIM 2019)
T cell rich diffuse B cell LSA
MST for horses with LSA (Luethy JVIM 2019)
MST 8mo, best for epititheliotropic (34mo)
Did duodenal perfusion measured by contrast-enhanced ultrasound show differences in dogs with intestinal LSA compared to chronic inflammatory enteropathy or controls
No - differences between symptomatic CIE dogs and controls/asymptomatic CIE dogs, but no differences for LSA dogs
Factors associated with decreased odds of developing T-zone LSA (Labadie JVIM 2019)
Omega-3 supplementation Hypothyroidism
Factors associated with increased odds of developing T-zone LSA (Labadie JVIM 2019)
Historic or concurrent mange
Shared associations between t-zone lymphoma and T-zone-like cells of undetermined significance (TZUS)
UTI/calculi Eye disease
Progression free survival time and MST for dogs treated with mito instead of doxo (CMOP) compared to CHOP dogs? (JAVMA 2019, Marquardt)
CMOP (n=44) - 100% CR or PR (81.8%/18.2%) - PFS 165, MST 234 CHOP (n = 51) - 97.4% CR or PR (92.1%/5.3%) - PFS 208, MST 348d (not stat sig compared to CMOP)
Prevalence of anemia in dogs with LSA vs. IBD? (Parachini-Winter JAVMA 2019)
LSA 53% IBD 22%
Individual RBC anomaly more common in LSA vs. IBD? (Parachini-Winter JAVMA 2019)
Eccentrocytes
Incidence of large-cell LSA dx following previous treatment for small-cell GI LSA in cats (Wright, JFMS 2019)
9.9% (12/121)
Mean event-free survival time and MST from time of diagnosis of large cell LSA for cats previously treated for small cell GI-LSA? Wright JFMS 2019
Mean event-free survival = 55d
MST =24.5d
Hematologic changes significantly decreased in cats that developed large cell LSA after treatment of small cell GI-LSA? Wright JFMS 2019
HCT, albumin and total protein (compared to values at dx of small cell GI LSA)
