LSA, Histiocytic, HSA, Melanoma Flashcards
How does Yunnan Baiyao induce cell death in HSA cells in vitro
Caspase-mediated apoptosis
Can serum VEGF aid in distinguishing hemangiosarcoma from splenic hematoma?
NO - elevated in both compared to normal dogs
Which IHC markers can help distinguish HSA?
c-kit, CD31 (PECAM-1), VEGFR-3, vWF, CD44
What % of nontraumatic hemoabdomen in cats is neoplastic in origin? What is the most common underlying neoplasia?
44% neoplastic
most common = hepatic neoplasia
What is the metastatic rate at diagnosis of feline visceral HSA?
33% mets to lungs @ dx
What conditions can result in acanthocytosis (spiculated RBCs)?
HSA (ie microangiopathic - also expect schistocytes)
liver disease
hypercholesterolemia
spherocytes –> zinc, IMHA
Name two positive prognostic indicators for cutaneous HSA?
Predisposed breed with ventral abdominal location
Histologic solar changes
In a whippet with multiple ventral cutaneous HSA, what is the prognosis?
Higher risk for recurrence – predisposed breed with multiple ventral masses
What clinical factors are associated with poor prognosis in cutaneous hemangiosarcoma?
Non-predisposed breed with invasive tumors
In dogs that received allogenic HSA tumor vaccines, which of the following were observed: antibody production, fever, vasculitis
Antibodies
Strong humoral response
Which of the following is higher in feline HSA: multicentric disease at diagnosis or mets to lungs at diagnosis?
Multicentric in 77%
Mets to lungs in 33%
What was the ORR and MST for dogs with presumptive cardiac HSA treated with DOX?
ORR=41%
MST = 120d
What is the response rate to DOX treatment in dogs with SQ HSA?
38.8%
What is the MST for dogs with B-ALL treated with multiagent chemotherapy?
120d
Flow cytometry from a dog with a mediastinal mass shows >10% CD4+CD8+ cells. What is the diagnosis?
Thymoma
What is the flow cytometric phenotype for LGL lymphoma? What is the survival time?
CD3+/CD8+
MST = 57d
What effect did CD40L vaccination have in dogs with lymphoma?
Improved SECOND remission duration and OST
What drug increases sensitivity of mast cells to chemotherapy but is limited by toxicity?
Calcitriol
What % of patients with digital melanoma have mets detected at diagnosis?
30-40%
What is the reported ORR of melanoma to RT?
82-94%
Which radiation protocol reported to date has resulted in the longest MST for dogs with oral melanoma?
6x6Gy
What is the recurrence rate reported by Proulx et al for dogs treated with RT for oral melanoma in the setting of microscopic disease? Macroscopic disease?
Microscopic - 26%
Macroscopic - 45%
MST 7mo
What is the reported ORR of melanoma to platinum-containing drugs?
18-28%
To which canine chromosome has p53 been mapped?
CFA 5
What is the function of p21/Waf-1?
universal CDK inhibitor
What is the function of p16?
CDK 4/6 inhibitor
What is L-MTP-PE? What was the conclusion of a randomized placebo-controlled trial using L-MTP-PE as an adjunct to surgery in patients with oral melanoma?
liposomal muramyl tripeptide phosphatidylethanilamine
–> induces proinflammatory cytokines
improved survival in canine OMM
For which types of melanoma is ulceration prognostic?
Digital, cutaneous
NOT oral
Name 5 factors that are prognostic for melanoma regardless of the site.
Distant mets Nuclear atypia Mitotic index Ki67 Degree of pigmentation
What is the prognostic Ki67 threshold for oral melanoma? For cutaneous/digital?
Oral - >19.5
Digital - >15%
Name two breeds in which melanocytic neoplasms are more likely to be benign.
Dobbies, mini Schnaz
What is the prognostic mitotic index threshold for oral melanoma? For cutaneous/digital?
Oral - >/= 4
Digital - >/=3
What effects did celecoxib have in COX-2 expressing melanoma cell lines?
Decreased PGE2
Decreased cell viability, increased activated caspase 3
Cell cycle arrest, decreased cyclin D1
In which melanocytic tumors was COX2 expression higher? Did COX2 expression correlate with survival?
Oral tumors, MI >3, high Ki67 –> higher COX2
Higher COX2 = decreased survival
What impact did KPT335, an XPO1 inhibitor, have on melanoma cell lines?
induced apoptosis and inhibited proliferation
Were CSCs (identified by CD133, CD24, CD34, CD44, and Oct3/4 expression) more common in melanoma tumors or cell lines?
Tumors
What are the most frequent chromosomal aberrations in melanocytic tumors?
gain of CFA 13 & 17
loss of CFA 22
Despite the rare presence of BRAF and NRAS mutations in canine melanoma, evidence of constitutive activation of which pathways was similar between human and canine cell lines?
MAPK
PI3K/AKT
What impact did decreased expression of miR-203 have on overall survival in dogs with melanoma? What impact did ectopic expression of miR-203 in melanoma cell lines?
Decreased survival
Ectopic expression –> inhibited cell growth
What % of melanoma cell lines investigated expressed alpha-3 integrin, a protein associated with increased motility and metastatic behavior?
100%
Mutations in kit exon 11 were detected in what % of canine melanoma? Did kit mutation/expression correlate with outcome?
0 - 10% mutation rate, 51 - 100% kit expression
NO correlation with outcome (2 studies)
What % of canine OMM showed co-expression of PDGFRa/B, and what impact did this have on prognosis?
37.5%
associated with poor prognosis
What were the staining patterns of canine melanoma and melanocytoma for receptor of activated c-kinase 1 (RACK1)?
melanomas - 100% homogenous staining
melanocytomas - 100% heterogenous staining
Increased expression of which genes was detected in metastatic canine uveal melanoma (compared to nonmetastatic)?
HTR2B, FXR1, LTA4H, CDH1
PNL2 is an antigen of unknown function identified on what two cell types?
Melanocytes, granulocytes
What is the sensitivity and specificity of an IHC cocktail of PLN2, Melan-A, and TRP-1/TRP-2 for diagnosis of canine oral amelanotic melanoma?
100% Sn, 94% specific
High tyrosinase expression (compared to normal tissue) has been documented in both canine and equine melanomas. Does tyrosinase expression correlate with degree of pigmentation?
No
What impact did the expression of actin-bundling protein fascin-1 have on survival in canine melanoma?
Associated with higher stage and decreased survival
Microvessel density and endothelial area were found to be higher in oral melanomas than cutaneous melanocytomas. Were these features prognostic for survival?
No- no correlation with survival
Which of the following markers is most sensitive for detection of melanocytic tumors?
PNL2, Melan-A, tyrosinase
PNL2
What % of melanoma stained + for VEGF?
95%
What correlation did plasma VEGF levels have with melanoma disease status and survival?
Higher plasma/serum VEGF in dogs with melanoma than controls
Higher VEGF correlated with higher stage and decreased survival
What was the sensitivity and specificity of ICC using cytokeratin, vimentin, and melan A for the cytologic diagnosis of amelanotic melanoma? How does this compare to routine cytology?
100% Sn/Sp
better than routine cyto (67% Sn, 85% Sp)
Which pathologic feature was prognostic for cats with non-ocular melanoma?
Lack of pigmentation
What were the ROC cutoff values identified for predicting death due to melanoma at 1 year for the following parameters: Ki67, nuclear atypia, MI
Ki67 > 19.4
Nuclear atypia score > 4
MI > 4
What was the mPFI and MST following curative-intent surgery for oral melanoma?
508d PFI
723d MST
Which factors were predictive of disease progression following curative-intent surgery for oral melanoma?
administration of adjuvant therapy
presence of mets at dx
higher tumor stage, increased size (>3cm)
sexually intact female dogs
What is the ORR of melanoma to carboplatin?
28%
What outcome parameters were significantly different in dogs receiving RT + temozolomide vs RT alone?
Temo group had longer TTP and lower failure rate (distant + local)
Met rate was not significantly different
What was the rate of AEs observed in cats recieving Oncept?
11.4%
What was the 1-year survival rate for dogs with digital melanoma treated with a murine tyrosinase DNA vaccine?
63%
MST =476d
What % of canine malignant melanoma express CSPG4?
57%
What was the affect of CSPG-4 electovaccination on MST and antibody formation in dogs with OMM?
significantly longer DFS
all dogs developed antibodies
What are the B2 integrins?
CD11(a-d) and CD18 – adhesion molecules differentially expressed by all leukocytes
Which cell types express CD11c and CD11d, respectively?
CD11c - LCs and interstitial DCs/most histiocytic diseases
CD11d - macrophages/hemophagocytic HS (also CD11b in some settings)
In which species are the characteristic Birbeck’s granules lacking from Langerhans cells?
dogs
Which breed is predisposed to multiple cutaneous histiocytomas?
Shar pei
Abnormalities in which tumor suppressor genes have been implicated in the formation of histiocytic sarcoma in BMD and flat-coated retrievers?
CDKN2A/B
Rb1
PTEN
In hemophagocytic HS, where is the primary tumor?
Spleen (splenic red pulp)
Which joints are most commonly affected by periarticular HS? Which breed is predisposed?
stifle and elbow
Rotties
Name 3 negative prognostic factors for canine histiocytic sarcoma identified by Dervisis et al (2016).
Use of corticosteroids
Disseminated disease
Palliative treatment
What is the odds ratio for development of PAHS in BMD with previous joint disease vs. those without?
5.4
Which diseases resulted in the highest levels of hyperferritinemia?
IMHA
Histiocytic sarcoma
Liver dz
Degree of elevation allowed differentiation from LSA and inflammatory disease
Name two factors associated with decreased survival in dogs with periarticular histiocytic sarcoma.
Use of prednisone
Mets at diagnosis
What was the ORR of histioctytic sarcoma to a combination protocol using DOX and CCNU?
58%
Copy number aberrations in histiocytic sarcoma were recently investigated in BMD and flat coats. Did identified CNAs differ between these breeds?
No, the CNAs were shared between the two breeds
Is CD204 more sensitive, specific, or both than CD18 or MHC II for detection of histiocytic sarcoma?
More specific
Sn = 100% for all 3, CD18/MHC II are much less specific
What % of histiocytic sarcoma are + for CD204 on IHC? on ICC?
100%
Which of the following is likely to be a therapeutic target in feline histiocytic disorders? PDGFR-B, Kit
PDGFR-B
Kit expression negative in all tumors investigated
What is the OR for development of histiocytic sarcoma in BMD and FCR compared to other breeds?
BMD - 45.0
FCR - 62.0
What is the ORR and duration of HS to CCNU?
ORR = 46% MPFI = 85d
Which gene locus has been identified as a germline susceptibility locus for histiocytic sarcoma in BMD?
MTAP
Which CD11 isoforms are expressed by macrophages?
CD11b; CD11d (BM and splenic mphages)
Which CD11 isoform is expressed by interstitial DCs?
CD11c
Which histiocytic cells express E-cadherin?
Langerhans cells
Which histiocytic cells express Thy-1 (CD90)?
Dendritic cells
What is the response rate of histiocytic sarcoma treated with CCNU at 70 and 90 mg/m2, respectively?
70mg/m2 - 46%
90mg/m2 - 29%
VEGF and MMP-9 were highest in dogs with which types of lymphoma?
T-cell > B-cell
High grade > Low grade
Stage 5 > other
What Ki67 cutoff value (determined by FC) distinguished high grade from low grade lymphoma?
12.2%
Was neutrophil/lymphocyte count prognostic for survival in dogs with lymphoma?
NO
Was VEGF expression or MVD prognostic for survival in dogs with lymphoma?
NO
MRD status at which timepoints has been shown to be prognostic in dogs with lymphoma?
CHOP week 11
completion of CHOP
Which of the following flow cytometric characteristics are associated with poor prognosis in canine lymphocytosis? CD34+, CD4-CD8-CD5+, large cell size, lymphocytosis >30K
CD34+
lymphocytosis >30K for CD8+ subset
large cell size for CD21+ subset
Which features were common to the 10% of canine lymphoma patients living >2years
BW >10kg B-cell centroblastic phenotype No hypercalcemia No BM involvement No steroids
In a study of lymphoma stage migration by Flory et al, what impact did stage have on remission rate and duration and overall survival?
None
“There was migration between all of the staging methods. However, the stage was not a predictor of remission rate, remission duration, or survival, regardless of staging method used.”
Human Burkitt lymphoma is characterized by a chromosome 8:14 translocation, juxtaposing which two genes? What is the corresponding recombination in dogs?
Myc-IgH
Dogs - CFA 8:13
What was the odds ratio for neutered male dogs to develop TCC of the bladder and prostate?
bladder - 3.6
prostate - 8.0 !!!
*** increased risk for TCC, prostate CA, any prostatic tumor. Hypothesis = increased estrogen efx on tissue, epigenetic changes due to loss of androgen-R signaling
What was the rate of high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic inflammatory atrophy (PIA) in prostatic samples from dogs?
HGPIN - 24%
PIA - 19%
Anti-Mullerian hormone is a useful IHC marker to detect what tumor?
Sertoli cell tumor
Which breeds have an increased incidence of BCL?
Cockers and Bassets
Which breeds have the highest incidence of TCL?
Irish wolfhounds
Huskies
Shih Tzus
Which IHC marker is useful in equine melanoma: S-100, PNL2, MelanA?
PNL2 - sensitive and specific
MelanA was not expressed in equine melanomas
What were the most common subtypes of lymphoma in horses?
T-cell–rich large B-cell lymphoma = most common
Peripheral T-cell lymphomas
diffuse large B-cell lymphomas
