Melanoma Flashcards
In a recent histopathological study what kind of cells and pattern were found in dogs with oral melanoma that had less aggressive tumors?
(Yasumaru, VCO, 2021)
They had higher number of TILs (tumor infiltrating lymphocytes), brisk or non-brisk pattern and higher number of CD8+ T lymphocytes.
Brisk tumors had higher number of CD8+ cells when compared to Tregs.
TIL evaluation may aid in the prediction of tumor aggressivnes.
Which phases of the cell cycle did the administartion pf oral paclitaxel inhibit in a mouse model?
(Yang, VCO, 2020)
G1-through Cyclin D1 inhibition
G2/M- trough microtubule polymerisation and stabilisation
Did the administration of oral formation of paclitaxel have any adverse effects in the mice?
Did it have any effect on melanomas?
(Yang, VCO, 2020)
There were no adverse effects seen
There was a 30% tumor shrinkage after 3 weeks of administartion
It showed antiangiogenic and anti-proliferative effects, induced apoptosis
In which tumors does pevenedistat have an effect?
What is its mechanism of action?
(Wood, VCO, 2019)
DLBCL
Oral melanoma-reduced viability of cells in dose- and time-dependent manner; promotes apoptosis and inhibits cell growth
It is a NAE inhibitor, NAE regulates the degradation of proteins with important cellular function in cancer cells
What is the sensitivity and specificity of PET/CT for the evaluation of lymph node metastasis in canine oral melanomas?
(Willcox, VCO, 2020)
Sensitivity is 100%
but specificity can be increased from 73 to 94% if primary tumors site and standardized uptake value (SUV) are added
PET/CT performed better than contrast CT (sens 83%, spec 94%)
What was the most common presenting complain of dogs with anal sac melanoma?
What is the prognosis for these dogs?
(Vinayak, JSAP, 2017)
The most common presentation was bloody dicharge from the anal sac
The prognosis is poor to guarded, PFI 92 days, MST 107 days
Only 1 dog lived up to 1 year after the diagnosis
What is the potential of JARID-1 (histone demethylase inhibitor) in chemoresistant oral melanomas?
(Tobin, VCO, 2021)
The antiproliferative effect of JARID-1 is preserved in cell lines resistant to platinum based chemotherapeutics; could be used in chemoresistant patients
What was the expression of PD-1, PDL-1 and PDL2 mRNA dogs with melanoma?
(Stevenson, Ve Pathol, 2021)
Sig. higher in melanomas compared to melanocytomas
in the PD-1 expressiong subgroup CD3+ cells were markedly increased
Recently a chimeric PDL-1 checkpoint mAb (C4G12) has been successfully developed in administered in a clinical trial involving dogs with stage IV melanoma. What was the outcome of that study?
(Maekawa, Prec Onc, 2021)
MST 143 days vs 52 days (historical), 1 dog with gross tumor had CR
Adverse events in 50% of cases, similiar what has been described in humans
Does KIT-labeling correlate with c-KIT expression in canine oral melanoma?
(Smedley, Vet pathol, 2021)
No
most of the samples showed a strong labeling of intraepithelial nests, but just 30% had c-KIT expression
Is the use of TKI in canine oral melanomas justified according to the c-KIT expression?
(Smedley, Vet pathol, 2021)
No.
c-Kit was expressed in 30% of malignant melanomas and 8% of well. diff melanocytic tumors.
(None was on exon 11)
Masitinib was evaluated in a prospective trial involving stage III and IV melanomas (digit, anal, oral) . What was the hypothesis behind the trial? What was the outcome?
(Guliano, JSAP, 2020)
Masitinib inhibits: c-kit, PDGFR alpha, beta, Lyn (lymphocyte spec. protein kinase) and lesser extent FAK (focal adhesion kinase)
- -> some melanomas showed c-KIT expression, or KIT labeling (50% of the cases in 1 study)
- –> PDGFR alpha, beta expression was detected in 50% cases and correlated with poorer survival
- -> FAK has been found in humans (10%), but not investigated in dogs
The effects were mild, 2 PR, 7 SD (also got melanoma vaccine)–> MST 3,5 months, no difference in comparison to other studies
—-> NOT recommended as sole agent
Was COX-2 expression demonstrated in oral and cuatenous melanomas?
With which M1/M2 profile was the expression correlated?
(Silveira, VCO, 2020)
In cutabeous 42% and oral 34%
low COX-2 expression was associated with M1 profile
high COX-2 expression with M1/M2 hybrid pattern
How was EMT demonstrated in metastatic melanoma cell lines? What did the primary tumor cell lines show?
Which marker has maybe a prognostic value?
(Schmid, VCO, 2018)
Expression of Vimetin and MMP-2
all primary cell lines showed phagocytosis
100% showed (derived from amelanotic melanomas) expression of CD146 , but this was not in correlation with migration/invasion
What is essential for the diagnosis of feline oral melanomas?
(Saverino, Vet pathol, 2021)
IHC
only 2/22 origninally thought to be melanomas were confirmed by IHC, most were reclassified for STS, but a lot could not be defined (poor prognsis was demonstrated in all of them)
Melan-A, PLN-2 and S100 are usually used
(laminin, CD34 for STS, pancytokeratin for carcinomas)
Can be circulating free DNA extracted from the plasma of cats with presumtive diffuse iris melanoma be of diagnostic value?
(Rushton, JFSM, 2019)
No.
There was no sig. difference in the level of free DNA between cats with benign naevi, iris cysts and diffuse melanoma.
With what melanoma phenotype was CFA 30 (focal somatic amplification) on chromosome 30 Canis familiaris linked to?
(Protueau, VCO, 2019)
With amelanotic
Also higher MI and poorer prognosis was noted with the amplification CFA30–> it could be a new prognostic factor
Which lymphocyte population was associted with proorer outcome in a recent study evaluating lymphocytic infiltration of melanomas?
(Porcellato, VCO, 2019)
high CD20 infiltration was associated with death, metastasis and recurrence–> could be a new negative prognostic factor
How does the new grading system for cats with non-ocular melanocytic tumors look like?
(Pittaway, Vet Pathol, 2019)
MI > 4/10 Hpf or intratumoral necrosis + tumor located on lips, oral cavity or nose–> high grade
MI > 4/10 Hpf + intratumoral necrosis + non high grade location–> high grade
High grade tumors <90 days MST
Low grade not reached
Sens. 80%, spec. 92%
COX-2 was expressed on a lot of tumor–> potential use of COX-2 inhibitors
Where do feline non-ocular melanocytic tumors most commonly occur?
(Chamel, JFSM, 2017)
On the auricula (these cats are usually younger <10 years), head, oral cavity
According to which histological tumor sizes could we confindently rule out and rule in lymphatic invasion in canine oral melanomas?
(Carroll, JAVMA, 2020)
Rule out <6.5 mm
Rule in >24.5mm
Prognostic significance was not investigated
Can be lymph node metastasis be predicted according to enhancement pattern in sentinel lymph node mapping of dogs with melanoma and MCT?
(Grimes, VCO, 2020)
No, sentinel lymph nodes should be removed with histo
How was the CSPG4 vaccine most efficient, when lookig at the surgical technique?
(Giacombino, VCO, 2021)
It was more efficient with wide excision surgery (1,5-2cm) than marginal
MST 3 years vs. 15 months, DFI 11months vs 6 months –> the vaccine showes delayed occurance of mets!
Overall there was no difference between wide and marginal excision in the MST (20 months vs 15 months), but there was a difference between DFI (8 vs 6 months)
Are the neutrophil:lymphocyte and monocyte:lymphocyte ratios prognostic in oral melanoma?
(Camerino, VCO, 2021)
Seem not be
