Tumor Specific 25% AB Flashcards
Skin/Sq, STS, FISS, GI, endocrine
What percentage of cutaneous tumors are malignant?
20-40%
List the top 4 most common skin tumors in cats.
basal cell tumor (~25%) > MST > SCC ? fibrosarcoma
Predisposing factors for SCC of the nasal planum, pinna, head and neck in cats?
white fur, UV light
Human syndrome xeroderma pigmentosum (XP) results in UV-induced skin cancer because it is deficient in what type of DNA repair?
nucleotide excision repair
How does papillomavirus result in neoplastic transformation?
- interaction of papilloma viral proteins with cellular proteins
- destabilization of p53 by viral protein E6 and inhibition of pRB by viral protein E7
How is disruption of p53 with E6 characterized on IHC?
increased levels of p16 protein
E6 protein of HPV types 16 and 18 interacts with the E3 ubiquitin protein ligase, resulting in ubiquitination and proteolysis of tumor protein p53. E7 inactivates retinoblastoma protein (Rb) by phosphorylation followed by an increase of free eukaryotic transcription factor E2F (E2F) in the cell. This leads to an increase of cyclin-dependent kinase inhibitor p16, that is used as an immunohistochemical marker of HPV-associated OSCC
What percentage of cutaneous SCC in cats in “UV-protected” (unexposed) areas are positive for papilloma virus via PCR DNA amplification?
76%
vs 42% in UV exposed areas
(no correlation in cats between virus and UV exposure; different in people)
What is the most common skin tumor in dogs?
MCT (~17%)
Which mutation is most common in human SCC?
p53
30% dogs
feline actinic keratosis 79%
feline Bowen’s in situ carcinoma 18%
Which gene is affected by a loss of function mutation in GSD resulting in nodular dermatofibrosis? Which cancer is this associated with?
- Birt-Hogg-Dube (BHD) have to be heterozygous or will die
- renal cystadenocarcinoma
Which RAF sand VEGF/PDGFR TKI is associated with rapid development of actinic keratosis and invasive SCC in people?
sorafenib
Which epithelial membrane glycoprotein is specific for BCC?
BerEP4
Incidence of BCC in dogs? At risk breeds?
- 6%
- Cocker Spaniel, Poodle
Histologic subtypes of BCC?
solid, keratinizing, clear cell
Behavior of BCC in dogs?
- low grade malignancy
- local recurrence possible
- no mets reported
Incidence of BCC in cats? Breeds?
- 10-26%
- Siamese, Himalayans, DLH, Persain
BCC behavior in cats?
- ~10% may be malignant based on stroll invasion, vascular invasion, high MI, LN mets
- pulmonary mets have been reproted
Recommended margins for BCC removal?
5-10 mm surgical
Growth pattern of papillomas?
exophytic
Surgical excision is often curative for papillomas that do not spontaneously regress. Which drug can be used for patients with multiple lesions?
azithromycin
Define SCC in situ.
carcinoma that has not penetrated the basement membrane of the epithelium
Causative agent of carcinoma in situ in cats?
Felis catus PV type 1
- when multiple present termed Bowen’s carcinoma or multicentric Papilloma virus induced carcinoma
What is identified on histopathology for UV induced SCC?
actinic keratosis
DFI and MST for cats with solitary SCC in situ of the nasal planum/pinna treated with surgery alone?
DFI 594d (19.8 mo)
MST 675d (22.5 mo)
Alternative treatment for solitary SCC in situ in cat nose/face?
Strontium-90 plesiotherapy
14/14 CR, >3000d OST
Cat breeds at decreased risk for cutaneous SCC?
- Siamese, Himalayan, and Persian
Dog breeds at risk for cutaneous SCC?
Labs and goldens - nasal planum SCC
blood hounds, Basset hounds, standard poodles
Paraneoplastic syndrome associated with cutaneous SCC in cats?
hypercalcemia
Metastatic rate of cutaneous SCC in cats?
5.3% ; primarily LN in 66%
(VCO 2023; reported higher if nasal planum in Withrow ~40%)
Metastatic rate of cutaneous SCC in dogs?
4.39% all LN
Response rate to electrochemotherapy for cats with cutaneous SCC?
82% CR for 2 mo to 3 yr
List the tumors arising from the hair follicle (most are benign).
Infundibular keratinizing Acanthoma
Tricholemmoma
Trichoblastoma
Trichoepithelioma
malignant trichoepithelioma
Pilomatircoma
Malignant pilomatricoma
Treatment for infundibular keratinizing acanthoma when surgery is not possible?
isotretinoin (1.7-3.7 mg/kg/d)
How is malignant trichoepithelioma differentiated from benign?
- invasion into surrounding tissues
- LN involvement
- high MI
- highly metastatic, need wide excision
- AKA matrical carcinoma
How is malignant pilomatricoma differentiated from benign?
- Can be difficult but invasion primarily into bone
- highly metastatic to lungs, LN, bone, mammary gland, and skin
Which breeds are predisposed to sebaceous gland tumors?
Mini schnauzers, beagles, poodles, and cocker spaniels
Which signalment characteristic is common in dogs with sebaceous gland carcinomas?
Intact male
Which proteins have been shown to be expressed in canine cutaneous neuroendocrine carcinoma?
B-catenin and E-cadherin
How do patients with ear canal tumors present?
Mass effect, chronic otitis, partial deafness, pain on opening, mouth, neuro signs
Differentials for tumors of the ear canal.
Ceruminous gland adenocarcinoma (most common in dogs & cats)»_space; SCC, undifferentiated carcinoma, BCC, HSA, MCT, melanoma, and benign fibroma, papilloma, polyps, etc
Predisposed breeds for ceruminous gland adenocarcinoma?
cocker spaniel, GSD
Are benign or maligner ceruminous gland adenocarcinoma more common?
malignant in cat (~70%), unknown in dog
- staging always recommended
Staging scheme for ear canal tumors?
T1 = confined to the external or horizontal canal
T2 = extending beyond the tympanic membrane
T3 = extending beyond the middle ear/bone
Most common surgical procedure for ear canal tumors?
TECA-LBO
cat MST = 42 - 50.3 mo (~4 yr)
dog MST = not reached at 36 mo
PFS for dogs (5) and cats (6) with ear canal tumors treated with 12 x 4 Gy = 48 Gy?
39.5 mo
56% 1 year PFS
Mitosis per 10 hpf associated with more favorable outcome for cats with ear canal tumors?
</=2 MST 180 mo
>/= 3 MST 24 mo
Dog presents with head tilt to the left, bilateral ventral strabismus, OS no menace, elevated 3rd eyelids bilaterally – where is ear tumor?
left middle ear
Dog presents with falling to the left when shaking head, positional nystagmus fast phase to the left and a miotic pupil OD – where is ear tumor?
left brain stem
MST for a cat with ear canal tumor presenting with neurologic signs?
1.5 mo
vs 15.5 mo if not neurologic
List the 3 histologic subtypes described for cats with ear canal tumors and their associated MST.
1) ceruminous gland adenocarcinoma 49 mo
2) SCC 3.8 mo
3) carcinoma of unknown origin 5.7 mo
MST for a cat with an ear canal tumor presenting with extension beyond the ear canal?
4 mo
vs 21.7 mo if no extension
Which factor has been shown to prognostic in dogs with ear canal tumors?
extension beyond the ear canal (T3)
if present MST 6 mo vs 30 mo if not
List the most common malignant digit tumors in dogs?
SCC 47% > melanoma 24% > STS 13% > MCT 8% > OSA 3%
others: round cell sarcoma, adenocarcinoma, malignant adnexal tumor, HSA, LSA, chondrosarcoma, giant cell tumor of bone, synovial cell
What percentage of dogs with digital SCC have multiple digits involved?
3%
Predisposed breeds: standard poodle, black labs, giant schnauzers, setters, rotties
THINK BIG AND BLACK
except doxins and flat coated retrievers
Which limbs are more commonly affected by digit tumors?
thoracic
Predisposed breed to digital melanoma?
Scottish Terrier
Rate of disagreement amongst pathologist when diagnosing digital tumors?
20%
75% doesn’t matter except SCC and IKA
Most common digital tumors in cats?
SCC 25% > fibrosarcoma 23% > adenocarcinoma 22% > OSA 8% > HSA 8% > MCT 7%
others: giant cell of bone, fibrous histiocytoma, sarcoma, melanoma
Which tumor types have been reported to affected multiple digits in cats?
fibrosarcoma, adenocarcinoma, SCC
Acrometastatsis AKA
lung digit syndrome
occurs in cats with lung tumors. Case series 88% of cats had acrometastsis and only 13% primary SCC of the digit
MST cats with acrometastasis?
5 weeks
MST cats with digital SCC treated with surgery?
30 weeks
~7 months
Frequency of bone lysis in dogs with digital SCC? Melanoma?
80% - SCC
5-100% - melanoma
Metastatic rate canine digital SCC?
6%-13% at time of diagnosis
9%-17% later
Subungual may be a BETTER prognosis
Metastatic rate canine digital melanoma?
32%-40% at time of diagnosis
additional 10%-26% after definitive treatment
Recommended treatment for most digital tumors?
partial foot amputation
Cytology of SCC + lysis of P3 – what is the metastatic rate?
20-30%
1 year and 2 year survival rate k9 SCC of the digit treated with surgery alone?
1 year = 50-80%
2 year = 18-62%
better if subungual
1 year = 95%
2 year = 74%
1 and 2 year survival rate K9 digital melanoma treated with surgery alone?
mst 12 mths
1 year = 42% - 57%
2 year = 13-36%
- other study added carbo with no difference in survival: 1 year 89%, 2 year 67%, MST 1350d (45 mo)
MST, 1 year, and 2 year survival rate for dogs with melanoma treated with digit amputation and murine xenogeneic vaccine +/- chemo and RT?
JVIM 2011 (Manley et al)
MST 476 days (15.8 mo)
1 year 63%
2 year 32%
Metastasis poor prognosis (distant>local)
Prognostic factors for digital melanoma?
- Distant mets – poor
- Lymphatic invasion – poor
- MI ≥3 in 10 random hpf – poor
- ≥20% nuclear atypia – poor
- Presence of ulceration – poor
- ≥15% Ki67 index – poor
- Extension beyond the dermis – poor
- tumor thickness >0.95 cm - poor
MSU panel from dog with digital melanoma:
- Ki67 10%
- >30% nuclear atypia
- MC >4/10hpf
What is the prognosis and which factor is swaying that?
Poor - both MC and nuclear atypia
ki67 okay >/= 15% assocaited with poor prognosis
Most common location for cutaneous SCC in dogs? Cats?
abdominal skin - dogs
nasal planum - cats
Rate of histologic changes suggestive of solar radiation in cat and dog SCC?
57%
Which histopathologic changes of cutaneous SCC are more likely to be associated with aggressive behavior?
presence of myofibroblasts, desk-plastic reaction, and incomplete margins
(suggest metastasis and poorly differentiated disease)
Which histologic factor has been shown the be associated with a more favorable survival in dogs with cutaneous SCC?
actinic change (solar) MST 1359d (45.3 mo, ~4 yr)
vs no solar changes 608d (20.2 mo, ~1.5 yr)
Which procedure can be used in cats with nasal planum SCC following curative intent surgery (nasal planectomy) to maintain aesthetics?
Lip to nose flap - minimal SE
OST for cats receiving SRT for facial SCC? AE?
118-991 days
Acute: alopecia, epilation, erythema
Late: alopecia, pigmentation, leukotrichia
4 mths to .2.5 year?
Cats with nasal planum SCC treated with strontium 90 have a favorable prognosis with DFI reported of ~2 years. Which protocol has been shown to result in a significantly longer DFI?
fractionated better than single dose protocol
Response rate of nasal planum SCC to Sr90? Local recurrence rate?
~75%
17%
Prognostic factors associated with response to Sr90 in cats with nasal planum SCC?
early stage disease, absence of concurrent problem, CR - favorable
Response rate of feline SCC of the head and neck to photodynamic therapy?
84% RR (61% CR, 22% PR)
PFS mean 35 mo
Does oclacitinib predispose to cancer?
no
Which pathway has been found to be persistently activated in cutaneous papillomas in dogs?
PI3k/akt/mTOR
True or false: Felis catus papillomaryvirus type 2 virus-like particle vaccine reduces FcaPV-2 viral loads?
False
- but is safe
What is the DFI for cats with incompletely excised sarcoids of the face?
250 d (~8.5 mo)
What is the recurrence rate of feline facial sarcoids following surgery?
40.5%
11.1% even with complete margins
Incidence of STS in dog? Cat?
Dog - 15% all skin/sq tumor
Cat 5%
What are predisposing factors to STS in dogs?
- RT
- Trauma
- foreign body
- orothopedic implatns
- Spirocerca lupi
Subclassifications of STS
fibrosarcoma
perivascular wall tumor
peripheral nerve sheath tumor (non-brachial plexus)
liposarcoma
myxosarcoma
pleomorphic carcoma
malignant mesenchymoma
undifferentiated sarcoma
Biologic behavior of STS
locally aggressive with low to moderate risk of distant metastasis
What is nodular fascitits?
AKA fibrzomatosis, pseuodsarcomatous, fibromatosis
- benign non-neoplastic lesions arising fromt he SQ fascia and superficial portions of the deep fascia in dogs
- Histo: large plump or spindle shaped fibroblast in a stroll network of variable amounts of collagen/reticular fibers
- can be misdiagnosed as fibrosarcomas
- Do not met, local recurrence possible following wide resection
STS grade I
- Differentiation: resembles normal adult mesenchymal tissue
- Mitosis: 0-9/10hpf
- Necrosis: none
cumaltive score </=4 for 3 categories
What is assessed when grading STS?
differentiation, mitosis, necrosis
STS grade II
- Differentiation: specific histologic subtype
- Mitosis: 10-19/10 hpf
- Necrosis: <50%
cumulative score 5-6
STS grade III
- Differentiation: undifferentiated
- Mitosis: >20/10 hpf
- Necrosis: >50%
cumulative score >/=7
Fibrosarcoma: cell type, histo features, IHC
- fibroblast/fibrocyte
- interwoven bundles, herring bone pattern, pronounced collagen stroma
- no IHC
Myxosarcoma: cell type, histo features, IHC
- fibroblast/fibrocyte
- stallate or spindle shaped cells in mucinous stroma
- no IHC
Pleomorphic sarcoma (malignant fibrous histiocytoma): cell type, histo features, IHC
- primitive mesenchymal cells (fibroblasts or myofibroblast)
- mix of fibroblastic cell and karyomegalic, multinucleate historic cells
- IHC +: lysozyme 29-100%, MCH II 70%, desmin 86%, viment
- IHC - : S-100, CD18
Perivascular wall tumo: cell type, histo features, IHC
- pericyte, myopericye, smooth myocyte
- vascular growth pattern
- IHC+: calponis, pan actin, smooth muscle actin 50%
-IHC-: S-100, NSE, GFAP, myoglobin
Peripheral nerve sheath tumor: cell type, histo features, IHC
- Schwann cell, neurofibroblast
- bundles and whorls around collagen bundles, Antoni A and B
- IHC+: NSE 45-82%, S-100 50-100%, neuofilament 82%, NGFR 47%, myoglobin 64%, GFAP 0-35%
Liposarcoma: cell type, histo features, IHC
- lipoblast, lipocyte
- polygonal cells with vacuolated cytoplasm
- IHC+: MDM2 67-75%. CDK4 (variable)
Rhabdomyosarcoma: cell type, histo features, IHC
- skeletal muscle myoblast, skeletal myocyte
- cytoplasmic striation, racket and strap cells
- IHC+: desmin, S-100 75%, NSE 50%, GFAP 50%
Lymphangiosarcoma: cell type, histo features, IHC
- lymph tissue no cell type given
- irregular vascular channels with single layer of plump spine cells and no RBCs
- IHC+ PROX-1 80-88%, Factor VIII related Ag 100%, LYVE-1 80%
Mesenchymoma: cell type, histo features, IHC
- multiple cell types
- multiple soft tissue mesenchyme components
- no IHC
Differentials for S-100 positive STS?
peripheral nerve sheath tumor, rhabomysoarcoma
Signalment differences for fibrosarcomas?
- Younger dogs than any other subtype
- oral location possible
Behavior of fibrosarcomas?
- very likely to recur after incomplete excision
- can have high MC but be low grade (HiLo)
Breeds pleomorphic sarcomas or malignant fibrous histiocytoma?
Flat coated retrievers, Rotties, goldens
Characteristic IHC for malignant fibrous histiocytomas?
vimentin +, CD18 -
Aggressive subtype malignant fibrous histiocytoma?
Giant cell pleomorphic tumors
- highly metastatic to SQ, LN, liver, lungs
- MST 61 days
Most common location of myxosarcomas?
- SQ of trunk and limbs but reports from heart, eye, and brain
Perivascular wall tumors can comprise various components of the vascular wall EXCEPT?
endothelial lining - this is HSA
How are perivascular wall tumors diagnosed/differentiated?
vascular growth patters (e.g. staghorn, planetoid, perivascular whirling, bundles of media)
Behavior of perivascular wall tumors?
less aggressive with low rates of local recurrence
Peripheral nerve sheath tumors of macroscopic nerves classification?
- peripheral, root, or plexus
- not considered part of STS of microscopic nerves
- neuro signs
- root or plexus worse prognosis since less ammenable to SX
MST dogs with brachial plexus peripheral nerve sheet tumor treated with limb sparing compartmental resection?
- MST 1303 d (43 mo, ~3.5 yr)
- completeness of excision prognostic: incomplete 487 d (16 mo) vs 2227d (74 mo)
PFS and OST dogs with brachial plexus tumors treated with SRT?
- PFS 240d (8 mo)
- OST 371d (12 mo)
- local progression reported 90% eventually
- dogs die of local disease before mets
Morphologic subtypes of lipomas?
- regular
- infiltrative
- intermuscular
Histo differentiation of lipoma vs liposarcoma?
lipoma- indistinct nuclei and cytoplasm resembling normal fat
liposarcoma- increased cellularity, distinct nuclei, abundant cytoplasm with one or more droplets of fat
Most common location for inter muscular lipomas?
caudal thigh of dogs between semitendinosus and semembranosus
Biologic behavior of inter muscular lipomas?
slow growing, firm, fixed, local recurrence rare after resection
Composition of infiltrative lipomas?
- well differentiated adipose cells without evidence of anaplasia
- cannot be differentiated by cytology or histo from lipomas
- distinguished only by invasiveness to other tissues - CLINICAL DIAGNOSIS
Signalment predisposition infiltrative lipomas?
4:1 female to male ratio
Treatment infiltrative lipomas?
Aggressive surge usually with amputation +/- RT
Biologic behavior of liposarcomas
- locally aggressive with low metastatic rates
- reports to lungs, liver, spleen, and bone
- bone, spleen, and abdominal cavity can also be PRIMARY
How are liposarcomas differentiated from lipomas?
- morphologic appearance
- cyto: OIL RED O to stain lipid
- CT: mixed-attenuating, heterogenous, multi nodular, contrast enhancing masses on PREcontrast CT
Prognosis liposarcoma with surgery?
- wide resection: 1188d (40 mo)
- sig different from marginal 649d (21 mo) or incisional BX (183d)
Histologic subtypes of liposarcomas in people?
- well differentiated, myxoid, round cell, pleomorphic, dedifferentiated
- pleomorphic highly metastatic
*not prognostic in dogs but one study showed metastasis more common with pleomorphic
Revised classification scheme for liposarcomas?
- based on IHC expression MDM2 and CDK4
- Ki67 higher in dedifferentiated than well differentiated
locations of rhabdomyosarcomas?
urinary bladder, retrobulbar musculature, larynx, tongue, myocardium
- locally invasive with low to moderate metastasis to lungs, liver, spleen, kidneys, and adrenals
How are rhabdomyosarcomas classified?
Histologically: embryonic, botryoid, alveolar, and pleomorphic
Rhambomyosarcoma IHC markers?
vimentin, skeletal muscle actin, myoglobin, myogenic, myogenic differfentiation
desmin s-100
Common location of embryonic rhabdo?
head and neck
Common location of botryoid rhabdo?
- urinary bladder of young, female, large breed dogs with St. Bernards over represented
- grape like appearance
Rhabdo metastatic rate based on subtype?
- botyroid 27%
- embryonal and alveolar 50%
- mets more common in dogs < 2 years of age
- in one study all dogs under 4 died of mets or local disease MST 2.5 mo
- no dogs over 4 died d/t tumor
Clinical signs of lymphangiosarcoma?
Usually soft, cystic like, and edematous.
Extensive edema and drainage of lymph through the skin or mass, non healing, discharging wounds
How can you differentiated lyphangiosarcoma from HSA with IHC?
- both CD31 and factor VIII ag +
- lymph LYVE-1 and PROX-1 positive
Prognosis lymphangiosarcomas?
- 3 dogs no treatment MST 168 (range 60-876; 2 - 30 mo)
- 5 dogs with alone MST 487d (range 240-941d; 8-31 mo)
- 2 SX, RT, and chemo MST 574d
- all dogs eventually died d/t tumor (recurrent or PD locally)
Splenic mesenchymoma reported - MST
- better than other types of splenic sarcomas
- MST 12 mo with 50% 1 year survival
Cytologic accuracy of correctly diagnosing STS?
63-97%
- always submit! disproportionate number of FALSE-NEGATIVE cytologic results associated with in-house assessment
Biopsy methods for STS?
- Can do core, punch, incisional or excisional BUT 41% not excision will differ in grade from definitive sample
- histologic grade UNDERESTIMATED in 29%
- OVERESTIMATED in 12%
Why is excisional biopsy not preferred for STS?
- may not be curative increasing morbidity and cost
- multiple attempts at resection before definitive therapy have negative effect on survival time
REFER
When should LN assessment be performed when staging STS?
- if enlarged, known to be grade III, or suspect nonconlvential type
Minimum recommended surgical margins STS?
2-3 cm lateral and 1 fascial plane deep
Alternative margin system for STS?
- proportional similar to MCT
- larger tumors significantly more likely to recur
Likelihood of STS recurrence with incomplete margins compared to wide resection?
10.5x higher
When might marginal excision be okay for STS?
- well circumscribed, non-infiltrative, <5 cm in diameter, located on limbs below the elbow/stifly
STS recurrence rates following incomplete excision based on grade?
I: 7% - 11%
II: 34%
III: 75% (3 of 4 dogs)
Peripheral nerve sheath tumor recurrence rates?
18-20%
- even with 60% being incompletely excised
- size associated with recurrence, 7x more likely if >5 cm diameter
- increasing risk 1.3x for every 1 cm
Recurrence risk STS based on grade?
5.8 fold if grade III compared to grade I & II
When might active surveillance be an appropriate treatment for incompletely excised STS?
grade I +/- II, well circumscribed, <5cm, distal limbs
further treatment may be unnecessary in up to 93% of dogs with incomplete excised grade I tumors
STS surgical scar revised with 0.5 o 3.5 cm lateral margins - frequency of residual disease identified?
22%
Local recurrence rate for intralesional bleomycin electrochemotherapy for incompletely excised STS?
- 36%
- mean time 730d (~24 mo)
- wound dehiscence in 14%
Local recurrence rate, DFI, 1- 2- 3- year disease free rate STS treated with surgery alone?
RR: wide 0-5%, marginal 11-29%
DFI: 368d to not reached
1 yr: 89-93%
2 yr: 78-82%
3 yr: 66-76%
Local recurrence rate, DFI, 1- 2- 3- year disease free rate STS treated with surgery and fractionated RT?
RR: 17-39%
DFI: 421d to not reached
1 yr: 71-84%
2 yr: 60-81%
3 yr: 57-81%
Local recurrence rate, DFI, 1- 2- 3- year disease free rate STS treated with surgery and hypo fractionated RT?
RR: 18-21%
DFI: 698d to not reached
1 yr: 81%
2 yr: 73%
3 yr: 73%
Local recurrence rate, DFI, 1- 2- 3- year disease free rate STS treated with marginal excision and electrochemotherapy?
RR: 17-31% (higher for grade III)
DFI: 264d to not reached
1 yr: 81-100%
2 yr:69-89%
3 yr: 69-84%
What is the earliest RT should be considered follow STS resection?
7 days to limit AE
- other weird study found that waiting at least 4 weeks to start hypo fractionated RT improved survival
Recommended RT for STS?
- full course, fractionated schedule
- optimal not defined but should be >50 Gy total
- better local control associated with higher cumulative doses
MST for incompletely excised STS (non oral) treated with fractionated RT?
MST 2270 d (75 mo)
1 yr 80-87%
2 yr 72-87%
3 yr 92%
5 yr 76%
What histologic findings in STS has been associated with recurrence when treated with RT?
MC > 9/10 hpf
Recurrence rate of STS to hypo fractionated RT (24-36 Gy) following incomplete or close resection?
18-21% - majority small ~ 3-4 cm, and low grade I -II (83%)
What should you consider when treating STS with hypo fractionated protocols?
patient age/expected survival time - risk of late toxicity increases if living long
PSF and likelihood to be tumor free following hypoRT for incompletely resected STS?
PFS: 698d (23 mo) - not reached
1 yr - 81%
2 yr -73%
3 yr - 73%
Prognosis for STS incompletely excised treated with hypofractionated RT to scar based on grade?
I:
- PFS 1904 d (63 mo)
- OST not reached
II:
- PFS 582d (~20 mo)
- OST not reached
III:
- PFS 292d (~10 mo)
- OST 940d (31 mo)
RT for gross STS tumor control rates?
- dose >50 Gy
- 1 yr 50%
- 2 yr 33%
Hypofractionated RT for gross STS
- 20-36 Gy
- ORR 46-50% (many SD)
- PFI 155-419 d (5-14 mo)
- prognostic factors: tumor location (better for limb 466d vs 110d) and previous surgery (more than 1 did worse 105d vs 420d)
- MST 206-513 d (~7-17 mo)
- MC used in this study did not improve PFI but did MST (757d vs 518d)
When can RT be considered preop for STS?
1) radiation field is smaller because, after surgery, the entire surgical site must be included in the field plus normal tissue margin
2) a larger number of peripheral tumor cells are inactivated with reduced contamination at surgery site
3) tumor volume reduction may make surgical resection less difficult
- lower doses recommended <50 Gy, wound healing may be harder (is in human med)
Metastatic rates for STS based on grade?
I: 0-13%
II: 7-27%
III 22-44%
Median time for metastasis STS?
365 d
MTD chemo protocols for STS?
- DOX
- DOX alternating ifosfamide
- neither shown to improve survival in dogs with grade III STS
How does MC work for STS? Dose?
- inhibiting tumor angiogenesis and suppressing regulatory T cells
- shown at 15 mg/m2/d but NOT 12.5 mg/m2/d
cyclophosphamide
Wound complication rate following intralesional chemotherapy for STS?
47-84%
Poor prognostic factors for local tumor control for STS?
large tumor >5 cm, infiltrative tumors. tumor in locations other than distal limbs, high grade, incomplete margins
What is the median post STS recurrence for dogs who are euthanized due to their tumors?
- 256 days (8.5 mo) vs 945 days (31 mo) median post recurrence for those who died of other caused
- importance of wide resection
Proliferative markers associated with STS survival?
AgNOR - increased 77 times more likely to die as a result of disease
ki 67- increased 12 times more likely to die from disease
You perform an FNA of a mass that is consistent with STS what are the next steps?
biopsy, chest rads, +/- referral
Incompletely excised STS grade II and owner cannot afford definitive RT. What is the recurrence rate? Alternative treatment options?
- recurrence <10%
- MC, hypo fractionated RT, electrochemotherapy, monitor
What is the survival time STS with >20MI, 10-19MI, <10MI in STS?
> 20 MST 236days (8 mo)
10-19 MST532 (18 mo)
<10 MST 1444 (48 mo)
Incompletely excised gr2 STS tx with hypoRT - what is 3 yr DFI?
70%
Recurrence with close margins (<3 mm) for STS based on grade?
I: 7-20%
II: 35%
III: 75%
Incompletely excised STS DFI to cytoxan 10 mg/m2 EOD and piroxicam 0.3 mg/m2 daily?
- 410+ days or ~14 mo (most still alive)
- untreated 210d was significant
With MC using cytoxan 15 mg/m2 daily + piroxicam what as found to be decreased in samples, time period?
28 days - microvessel density and Tregs
Frequency of sterile hemorrhagic cystitis for MC in dogs with SRS?
10%
RR of STS to chlorambucil 4 mg/m2 daily?
- 20% CR and 80% SD
- PFI 1-20 weeks
Treatment outcomes with 5 x 6 Gy RT with MC (thalidomide 1-2 mg/kg/d + piroxicam 0.3 mg/kg/d + cytoxan 7 mg/m2 EOD)?
- MC group sig longer OST 757 d (25 mo) vs 286d (9.5 mo) RT alone
- all PFI 419 d (14 mo), MC vs RT alone did not influence
- all OST 513 (17 mo)
- increased tumor burden decreased survival and location other than limbs
What is concordance between excision and pre-treatment biopsy of STS?
59%
Outcome fractionated RT for incompletely excised high grade STS +/- chemotherapy?
- OST 891d (29.7 mo)
- 1 yr 85%
- 2 yr 43%
- 5 yr 18%
- TTP 1581day, 52 mo (mean)
- 24% developed mets to nodes or lungs
- 20% local recurrence
- increased risk of death associated with not adhering to RT schedule and prolonging RT
JVIM Cronshaw 2020
Sensitivity and specificity of optical coherence tomography for STS margin assessment?
In vivo = SN 88%, SP 93%
Ex vivo = SN 83%, SP 93%
What is in-transit metastasis?
- type of metastasis in which skin cancer spreads through lymph vessel and begins to grow more than 2 cm away from primary tumor before it reaches LN
- Reported in metastatic STS in 6 yr Staffy
What cytologic parameter may correlate with increasing grade for STS?
MC >/=3
What percentage of rhabdomyosarcomas can be diagnosed on histology with IHC withOUT use of electronmicroscopy? IHC markers?
- 81% do no require EM
- myogenin and MyoD1
MST rhabdomyosarcoma?
47d - 1480d (~1.5-50 mo)
Vet path 2021
Are platinum containing biodegradable impregmentated beads a reasonable TX for canine STS?
- AE 37% (seroma, crusting, discharge, erythema)
- concern for manufacturing inconsistencies
STS gross response rate to SBRT (3 x 9-16Gy) or (2 x 16Gy)?
- ORR 46% (36% PR, 11% CR)
- PFS 521d (17 mo)
- TTP 705d (~24 mo)
- OST 713d (~23 mo)
- disease specific OST 1,149d (38 mo)
- location other than limbs poor prognostic indicator
- low grade = favorable
How prevalent are pulmonary nodules suggestive of metastasis at the time of STS diagnosis?
- 11.7%
- more likely if grade III 38%
- 6% in both grade II and I
- more likely if tumor present >3 mo
DFI and OST for 20 Gy SRT to microscopic STS scar with liquid fiducial markers?
- not reached >1,500 days at time of writing
- 80% acute skin AE, 36% late
Rhabdomyosarcomas occur in young dogs and may be confused with round cell tumors in 32% of cases. Which cytoskeleton linker protein can be used to differentiate?
Ezrin (membranous and cytoplasmic staining)
In the case of SQ STS can the skin be left intact rather than resected during surgery?
No - 51.7% infiltrated with tumor cells
- 100% grade III, 36% grade I
Is there a difference in RR and DFI between intraoperative ECT with bled and adjuvant for STS?
No, similar
Intra op- RR 23%, DFI 81.5d
Adjuvant - RR 25%, DFI 243d
What is the overall relative risk of tumor recurrence with complete margins vs incomplete margins for STS?
0.396
- 9.8% of complete excised recur
- 33.3% of incompletely excised recurred in this population
- microscopically complete margins confer sig. reduced risk
Immunotherapy for STS?
IL-2/agonist anti-CD40 Ab - induces long term curative responses in mice
- 3+3 phase 1 dose finding in dogs induced tumor regression with minimal SE at 3 dosing levels
What physical factors of perivascular wall tumors are associated with increased recurrence? Histo?
- ulcerated appearance and distal extremity tumors
- Grade, necrosis, MC, margins
- Grade II, >50% necrosis, and high MC decreased survival
OST for fractionated RT for infiltrative lipomas in gross and microscopic setting?
- 4.8 years with no dogs thought to die from tumor
- no difference between disease setting
What percentage of gastric tumors are sarcomas?
10-13% GIST>leiomyosarcoma
What is the metastatic rate of GIST? leiomyosarcoma?
32.1%, 15.3%
Which histologic factors are associated with improved survival for GIST?
MC <9
strong c-Kit staining
What is the most common visceral sarcoma?
leimyosarcoma 38.1%
- spleen & SI
- low local recurrence 4/7%
- Mets 40.4%
Which vaccines have been associated with FISS?
inactivated rabies and FeLV most common
Frequency of FISS?
1/10,000 vaccinated to 1/1,000 vacinated
Other injections associated with FISS?
steroids, NSAIDs, ABX, lufenuron, microchip, suture material
Time to tumor development FISS follow vax?
4 weeks to 10 years
Are non-adjuvant vaccines safer?
unclear - 3 epidemiological studies did not provide evidence
How are ISS hypothesized to develop?
inflammatory reaction induced by injectable leads to uncontrolled fibroblast and myofibroblast proliferation
- supported by histo: central areas of necrosis, inflammatory cells (lymphs, Macs), multinucleate giant cells
Immunoreactivity of ISS?
PDGF
EGF
TGF-b
- non ISS are not usually positive for these growth factors
- lymphocytes in ISS + for PDGF and may secrete to recruit Macs and lead to fibroblast proliferation
How does ISS differ from non ISS sarcomas on histo?
- FISS show increased inflammatory cells with transition area, MC, and cellular pleomorphism
- can sometimes see AlOH adjuvant with electron probe X-ray microanalysis
- 59% grade III
Which photo-oncogene has been found associated with FISS?
c-jun
*not on other sarcomas
Does FeLV/FIV status predispose to FISS?
no
What are the exceptions in cats in regards to similar biologic behavior between STS?
- ISS - large, rapid growth, arise from SQ
- virally induced multi centric fibrosarcoma
- rarity of peripheral nerve sheath tumors and hemangio
- “normal sarcomas” - small, slow growing, arise from skin
What subtypes of ISS have been described?
fibrosarcomas, rhabdo, undifferentiated sarcomas, extraskeletal OSAs and chonrosarcomas
How should ISS be staged?
CT and/or MRI local lesion, lungs
What CT finding has been associated with a worse prognosis for ISS?
presence of skip metastasis
What % of ISS peritumoral lesions identified on CT end up being non-neoplastic on histo?
59%
Minimal and preferred surgical margins for ISS?
Min - 2 cm lateral and deep
preferred- 5 cm lateral and 2 fascial planes deep (can go down to 3 and 1 if CT directed)
What % of ISS are completely excised based on surgical margins?
- 50% when 2 or 3 cm lateral margin
95-97% when 4 or 5 cm lateral margins used
What is contraindicated when ISS is suspected?
marginal resection or excisional biopsy
- marginal resection, more than 1 attempt, and non boarded surgeons associated with sig decreased DFI and MST
Median time to recurrence after marginal vs wide resection ISS?
marginal 79d vs 325-419d (1+ year)
- 66d non surgeon vs 274d with surgeon
DFI at 1 and 2 yr for ISS treated with 2, 3 cm resection vs 4, 5 cm?
2/3: 1 yr 35%, 2 yr 9%
4/5: 14% recurrence rate at 3 years
Median follow up time ISS treated with compartmental resection and epirubicin?
1072d (35 mo)
14% recurrence
Complication rate iSS treated with aggressive compartmental resections?
11-17%
- wound dehiscence more common after wide resection of inter scapular ISS over other locations
- overweight cats, larger tumors, ISS that require longer sx times, and defects closed in X-shape also associated with dehiscence
Does DOX improve ISS ST?
no difference in one study with 49 cats treated with DOX and sx compared to sx alone
Local recurrence rate and DFI preoperative RT and SX?
RR: 40-45% (398-584d post op)
DFI: 700-986d (23-32 mo) complete excision vs 112-292d (3.7-9.7 mo) incomplete
Local recurrence still reported in 42% with complete excision and 32% without
Local recurrence in ISS treated with SX then post op RT?
RR: 41% mean 405d
- one study showed that post op better than pre op RT but they treated larger tumors pre op so selection bias
When should RT start post sx for ISS?
10-14 days, longer interval associated with decreased DFI and ST
Compare definitive inent RT to hypofractionnated RT ISS
-dRT: PFI 37 mo
1 yr PF 63%
2 yr 60%
-hypoRT: PFI 10 mo
mST 24 mo
Summary RT MST and 1, 2, 3 yr survival rates following surgery?
MST 600-1307d
1 yr 86%
2 yr 44%
3 yr 28%
pRT for gross ISS?
- not really effective
- 7 PR and 2 CR reported after liposomal dox and 5 x 4Gy –> PFI 117d (4 mo) so not durable
- similar for 4 x 8 Gy with no DOX PFI 4 mo, MST 7 mo
SRT for gross ISS?
- most 3 x 20 Gy
- 3 CR, 5 PR = ORR 72%
- PFI 242 d (8 mo)
Metastatic rate of ISS?
0-26%
time to mets 265-309d (8 - 10 mo)
ISS cell lines show sensitivity to which drugs?
DOX, mito, vino, CCNU, paclitaxel
Gross ISS responses to chemotherapy?
ifosofamide 3% CR, 37% PR
doxo + cytoxan 50% PR
CCNU 3% CR, 21% PR
median 2.5-4 mo
carbo and Palladia ineffective in treating gross tumors
What is a prognostic factor for using chemo to treat ISS?
responders 242d vs non responders 83d
Alternative treatments for ISS?
IL-2: combined with surgery and iridium based brachytherapy 1 yr control rate 61%.
- When compared to sx/brachy alone IL2 increased time to relapse
Electrochemotherapy: cisplatin in tumor bed, bleo IV - improved survival compared to historic controls. mST 985d (32 mo)
RR FISS doxo and cytoxan?
50% for ~125 d (4 mo)
RR FISS to liposomal dox?
39% for 84 d
- no difference between liposomal or typical DOX*
CCNU dose cats FISS? RR?
38-60 mg/m2 q3 weeks
25%, 60-80d
cumulative neutropenia and lots of treatment delays
Prognosis for cats with FISS?
generally considered good
- wide resection 25-30 mo (2-3 yr)
- marginal ~1 yr
Which hematologic factors have been associated with decreased survival in cats with ISS?
- PCV <25%
- neutrophil:lymph, total WBC, and neutrophil count for recurrence (WBC >NLR and NC)
Efforts to prevent FISS?
low limb/tail vaccination, nonadjuvanted vaccines, avoid Al based adjuvants, increase vax intervals
3-2-1 rule
- mass evident for 3 or more months
- larger than 2 cm
- increasing in size for 1 mo
IHC of FISS?
Positive:
- vimentin 100%
- S-100 95%
- C kit 19%
- COX 2 62%
- FeLV particles 43%
Negative:
- desmin 81%
What is the disease specific survival and local recurrence rate for cats with ISS treated with surgery and brachytherapy (post op iridium 192 interstitial implants)?
ST 1242d = 42 mo
54.5% local failure
multiple surgeries prior ass. with poor prongisis
Cat presents for microscopic ISS following first surgery. Should you recommend fractionated or hypofractionated RT?
- fractionated
- 2018 paper compared the two and found for first occurrence cases benefit of fractionated RT (PFI 1430d 47 mo vs 540d 18mo pRT)
- significance was lost when comparing recurrent ISS so can consider pRT as an alternative in these cases
Which hormone receptor expression may be associated with worse prognosis for FISS?
estrogen - 64% of cases and higher MC
What are the mechanisms of AlOH vaccines inducing FISS?
- inflammation
- double strand DNA breaks w/o inflammation
Local recurrence rate of non-FISS sarcomas to RT?
37.5% hypofractionated protocol
50% fractionated
PFS hypo 164 d (5.4 mo)
PFS fractionated 2,748d (91 mo)
- not sig likely because under powered (18 cats)
Which drug has been shown to inhibit proteasome leading to cell death via apoptosis in vitro for FISS?
bortezomib
leiomyosarcoma markers?
Postive:
- SMA
- Desmin +/-
Negative:
- KIT
-CD117
- S-100
- Dog1
Desmin confirms myogenic origin but does not differentiate between smooth, striated, or cardiac muscle
What test is used to differentiate FISS from feline sarcoma virus?
FeLV DNA provirus+oncogene, Rapidly growing rare sarcoma in young cats, FeLV+ unlike FISS
What growth factor does FISS express and what drug may have activity against it in vitro?
PDGFRβ, Masitinib
What are some molecular mutations in FISS?
cJUN, p53, TGFB, PDGF, KIT
What has resulted from changing the vaccination locations recommended for cats?
Increase in right limb and right flank tumors
rabies = rHL
Sex predisposition oral tumors dog?
Male - OMM, tonsil SCC, odontogenic fibromas
Female - axial OSA
Dog breed oral tumor predispostions?
cocker, GSD, Gordon setter, German pointers, Weimaraner, Goldens, Poodle, chow chow, boxer
*OMM more common in smaller dogs
Most common oral tumor dog? Cat?
OMM > SCC > fibrosarcoma
SCC
% of amelanotic OMM?
38%
OMM IHC cocktail with 100% specificity and 94% sensitivity?
PNL-2, Melan A, TRP-1. TRP-2
Rate of OMM metastasis?
80%
Histologic subtypes of SCC?
conventional, papillary, busload, ademosquamous, spindle cell
Pappillary SCC behavior
- young dogs <9 mo
- rostral oral cavity
Metastatic rate non-tonsil SCC dog?
5-29%
site dependent rostral low caudal/tongue higher
Metastatic rate of tonsil SCC dog?
73%
% of oral tumors with bone involvement based on type?
OMM 57%
SCC 77%
FSA 60-72%
acan ameloblastoma 80-100%
common for SCC and FSA in cats
OMM SX response, recurrence rate, MST, 1 yr survival?
- fair to good
- 0-59%
- 5-17 mo
- 21-35%
OMM RT response, recurrence rate, MST, 1 yr survival?
- good, 83-94%
- 11-27%
- 4-12 mo
Overall prognosis OMM, MST, cause of death?
- guarded
- <36 mo
- distant metastasis (if tumor removed obvi)
SCC (dog) SX response, recurrence rate, MST, 1 yr survival?
- good
- 0-50%
- 9-26 mo
- 57-91%
SCC (dog) RT response, recurrence rate, MST, 1 yr survival?
- good
- 31-42%
- 16-36 mo
- 72%
Overall prognosis SCC (dog), MST, cause of death?
- good to excellent
- 26-36 mo
- local or distant disease
FSA (dog) SX response, recurrence rate, MST, 1 yr survival?
- fair to good
- 31-60%
- 10-12 mo
- 21-50%
FSA (dog) RT response, recurrence rate, MST, 1 yr survival?
- poor to fair
- 32%
- 7-26 mo
- 76%
Overall prognosis FSA (dog), MST, cause of death?
- gaurded
- 18-26 mo
- local disease
Acanthomatous ameloblastoma SX response, recurrence rate, MST, 1 yr survival?
- excellent
- 0-11%
- > 28-64%
- 72- 100%
Acanthomatous ameloblastoma RT response, recurrence rate, MST, 1 yr survival?
- excellent
- 9-18%
- 37 mo
- > 85%
death rarely tumor related
SCC (Cat) SX response, MST, 1 yr survival?
- poor
- 45 days
- <10%
SCC (cat) RT response and MST?
- poor
- 90d
Overall prognosis SCC (cat), MST, cause of death?
- poor to fair
- 14 mo
- local disease
predisposing facts to SCC cats?
- flea collars - 4 fold increase
- canned food esp. tuna
- smoke - 2 fold, associated with sig increase in p53 expression
- urban environment
- outdoor access
- Above have been ID with no overlap in studies
- new VCO 2023 found clay litter and flea collars to be significant
Clinical staging oral tumors
A 8 yr MN Golden presents for a tumor of his hard palate. Histopathology (large incisional) is consistent with a fibroma. How should you treat?
aggressively likely histologically low grade but biologically high grade FSA
Accuracy of FNA for dx oral tumors?
92% dogs
96% cats
In which oral tumor types is size associated with prognosis?
MM, SCC, tongue tumors
What percentage of head rads will miss bony lysis?
~60%
30% noted on rads 90% on CT
% of dogs with OMM with large LN that were not mets?
49%
% of dogs with OMM with normal LN that were mets?
40%
Accuracy of FNA for the detection of mets to LN in oral tumors?
77%
Favorable prognostic factors for oral tumors?
complete resection, small diameter, rostral locations
MST SCC cats treated with mandibulectomy and RT?
- 14 mo, 1 yr survival 57%
- non tonsil/tongues location more favorable
- Highly location specific - other study shows MST 921 (30 mo) if rostral mandibulectomy vs 192 d if >50% of manbdible removed
RR accelerated RT (14 fx 3.5 Gy twice daily 9 days) + carbo radio sens - cats SCC oral?
85% MST 163d, 5.4 mo
*similar with gemcitabine 75% MST 112d
Which combination of treatment for oral SCC cats has resulted in CR of 73%
mitoxantrone and RT
MST 184d
RR to hypofractionated RT cat SCC?
81% MST 174d
RR palliative SRT cat SCC?
- 39%
- PFI 87d
- MST 106d
- high complication rate: mandibular fx, fibrosis, fistula
- Higher microvessel density or more keratinzed SCC had sig shorter ST or PFI than patients w lower MVD or less keratinized SCC
What is bmi-1? Tumor type association?
- oncogene responsible for suppression of cell cycle inhibitors
- confers resistance to chemo and RT
- high expression associated with outcome in cats with oral SCC doing worse
Which systemic therapies have been shown to improve outcomes in cats with gross oral SCC?
- Palladia + NSAID
- 57% RR
- 4% CR, 9% PR, 43% SD
- MST 123 sig. longer than cats with no Palladia 45 d
- NSAID alone also improves survival 169d vs no NSAID 55d
Which drug has been shown to reduce feline SCC cells in vitro and provide palliation in vivo pilot study?
Pamidronate
- zoledronate has also been described with 8 Gyx4 with 44% RR and minimal AE (only decreased serum c-telopeptide which measures bone turnover)
Prognosis for axial OSA of the head?
better than appendicular
- 4% met at dx
- 32-46% following definitve tx
- MST 14-18 mo
Urban living is associated with which cancer?
tonsillar SCC, LSA, nasal adenocarcinoma
Metastatic rate of tonsilar SCC at dx?
20% - even when confined to the tonsil micrometastasis likely in 90% of cases
Does cervical lymphadenectomy improve outcome for tonsilar SCC?
No but tx with RT achieves local control for 75% cases though 1 yr survival still 10%
What is the most common equine gastric tumor?
SCC
What is the MST with tongue melanoma?
551d (18 mo)
What is the survival with tongue SCC with grade?
Grade1 MST 16months, grd2 4months, grd3 3months; Feline 1yr survival <25%
What is prognostic for tongue tumors?
size, grade, type
- <2-4 cm improved survival
What is undifferentiated malignancy of young dogs?
- disease of young, large breed dogs
- rapid growing cancer of palate, molars, maxilla, orbit
- highly metastatic
- no TX
- 30d ST
Where does MLO arise from?
mandible, maxilla, hard palate, orbit, calvarium
Histo of MLO?
multiple lobules with central cartilaginous or bone matrix surrounded by a thin layer of spindle cells
MLO imaging appearance?
Popcorn
MLO rate of recurrence after sx?
47-58% - depends on margins and grade
- DFI complete = 1,332d (44mo)
incomplete = 330d (11 mo) - recurrence:
grade III 78%
II 47%
I 30%
MLO metastatic rate?
-up to 58% late in the course of disease to lungs
- time to mets 465-542 d (15-18 mo)
- worsens if incompletely excised 75% vs 25% if complete
Which of the following has been associated with development of gastric SCC in scottish cows with papiloma virus?
Bracken fern ingestion
- 30% cattle that had SCC of upper GIT had concurrent bladder tumors
Prognosis for dogs <2 year of age with oral SCC?
great - surgery curative (wide)
Paraneoplastic syndrome associated with disseminated tonsillar SCC reported in dog?
hypoglycemia secondary to insulin like GF1 production
Which has a better prognosis following excision +/- RT in dogs, oral SCC or FSA?
SCC
- MST not reached SCC, 557d (~19mo) FSA
- RT protective in incomplete margins for SCC (MST 2,000+d) vs 181d for FSA
- RT not protective for FSA
Non-tonsilar oral SCC response to ECT?
27.3% - low toxicity
RT for papillary SCC in dog
- 10-16 daily x 3.2 Gy total >36
- 9/10 CR - PFS/OST not reached
- dog with PR PD at 228d
Which mutation has been reported in up to 85% of k9 oral papillary SCC?
V595E
What induced epithelial to mesenchymal transition in k9 oral SCC?
SLUG
What is the effect of combining piroxicam and cisplatinum? Tumor types it may be effective against?
- moderate to severe renal AE
- OMM, SCC
Marker of epithelial to mesenchymal transitions identified in feline SCC?
P-cadherin, Twist, HIF-a, and PDL1
- Ncadherin which is classically associated with EMT not expressed
- production of VEGF regulated by HIF-a was inhibited by dasatanib in vitro
Protocol NOT recommended for cats with oral FSS d/t high morbidity and low RR?
- bleomycin, piroxicam, thalidomide + RT (48Gy in 10 fx)
- 30% grade III toxicity
What mutation has been shown to be higher in feline oral SCC than inflammatory tissue?
p53
- oral brushing may be an early detection method with 69% sensitivity and 97% specificity, accuracy 86% (pilot)
Can mRNA detection of felus catus be used to dx oral SCC?
No- also elevate din ulcerative non cancer lesions with no sig difference between groups
Fatty acid synthase expression has been shown in oSCC cell lines. What is an inhibitor?
Orlistat
Which breeds are predisposed to peripheral odontogenic fibromas?
Boxer, Border terrier, Bassett hound
males
In dogs with oral tumors who undergo full body staging (chest, abd) prior to surgery what is the frequency of IDing mets?
- thx 4.9%, abd 2% (OMM in most)
- incidental findings more common than mets.
- thx 53%, and 81%, most common other tumors
Is radical mandibulectomy a viable tx option for cats with oral tumors?
Yes
- MST 712 (~24mo) with 3 long term survivors dying of other causes
- 6/8 ate on their own
What types of osteomas have been described in dogs? What do they look like?
- peripheral and central
- no evidence of bone lysis
Most common salivary gland tumor?
adenocarcinoma
DDX for tumor primary location in area of mandibular ramus on CT?
salivary, thyroid, ceruminous gland, laryngeal, tonsils
What are prognostic factors for salivary carcinoma?
Stage; grade NOT prognostic
MST dog salivary carcinoma treated with sialoadenectomy?
- 1886d, 63 mo, 5 yr
- local recurrence in 42%
- DFI 299d
Metastatic rate salivary carcinoma dog?
~30%
- 29% of dogs may have local LN mets at time of surgery - removal encouraged but sstill associated with poor prognosis compared to no mets 98d vs 248d
OST dogs with tonsillar carcinoma (various tx - Sx, RT, chemo, NSAIDs or comp)?
- MST 126 d
- PFI 91d
- OST longer without overt mets
Positive prognostic indicators associated with tonsil carcinoma?
absence of clinical signs, surgery, use of adjuvant chemo, and NSAIDs
What percentage of malignant tonsil histo samples are metastatic?
~8% - some with unknown primary
-hematogenous route based on CT
Survival range for cats with salivary carincoma treated with surgery (5) or RT (4)?
55-570d
Most common laryngeal mass in cats?
LSA
Can cats tolerate partial laryngectomy?
Yes - but often require temporary trach
Which parasite is associated with esophageal tumors?
Spirocerca lupi
- OSA, fibrosarcoma, undiffentiated sarcoma
- can use fecal float to dx but not sens
- TX partial esophagectomy and dox MST 276d
Esophageal tumor that may have a heredity component?
Leiomyomas
- so not invade the mucosa but sarcomas will
Most common esophageal tumor of cat?
SCC occurring in the middle 3rd of the esophagus
Who is at higher risk for exocrine pancreas cancer?
older, female dogs, Spaniels
Most common type of exocrine pancreatic cancner?
adenocarcinomas of ductular or acinar origin
-overall exceedingly rare <0.5% of all cancers
What might be used on IHC to differentiate well differentiated and undifferentiated exocrine pancreatic carcinomas?
cluadin4
- loss in undifferentiated
General prognosis for exocrine pancreatic carcinoma?
Poor - often metastatic at time of dx to local LN
What is a paraneoplastic syndrome for exocrine pancreatic cancer?
Alopecia on the ventrum of cats
MST dogs diagnosed with exocrine pancreatic carcinoma?
-1 day, euth at dx
- 78% metastatic
- 1 dog diabetic
Post surgical MST for cats with exocrine pancreatic carcinoma?
316d
- may be a viable tx for cats w/o mets
Most common non-hematopeotic gastric cancer in dogs?
Gastric carcinoma
DDX: leiomyoma/sarcoma, GIST, MST. HS, plasmayctoma, undifferentiated sarcoma
Most common gastric tumor in cats?
LSA > carcinoma
- gastritic and H.pylori may be predisposing factor
Metastatic rate gastric carcinoma in dogs?
32% at dx, 77% post mortem to LN > liver/lungs
Dog presents with gastric tumor and hypoglycemia- what’s your top differential?
leiomyoma/sarcoma
- excessive release of IGF-2
IHC to differentiate GIST from leiomyosarcoma?
GIST express c-kit (CD117, exon 11) and CD34, vimentin+, DOG1+, weak SMA (smooth muscle actin)
leio express sma+, desmin+, kit-, dog1-
Agreement between cytology and histo for gastric masses in cats and dogs?
poor ~50%
ST following sx (Billroth, gastrectomy, gastronomy) for gastric carcinomas in dogs?
- gaurded- 4-6 mo
- persistent vomiting and anorexia common
- 20% major complication rate (dehiscence)
- adding chemo may improve survival (various: palladia, carbo, 5fu, etc)
MST gastric tumors dogs
Carcinoma < 6 mo
GIST 37.4 mo
Leiomyosarcoma 8-12 mo
undifferentiated sarcoma 3 mo
MCT 1 mo
leiomyoma cured with surgery
MST cats with gastric MCT?
~18 mo
Cecal tumors are often?
GIST
25-32% may perf and cause acute abdomen
Frequency of exon 11 mutations in GIST?
35%- conventional PCR
74%- RT-PCR
prior Q be careful
- exon 9 5-10%
Owner declines surgery for GIST - TX and MST?
- Palladia
- clear benefit in the gross disease setting
- PFI 110d
- less clear in microscopic disease setting (dogs with NED many months after stopping drug)
- PFI 61d
- Mets at dx and high MC associated with survival –> some are aggressive
IHC prognostic for gastric carcinoma?
- Vimentin expressed in 30%
- higher in undifferentiated, emboli 82%, and mets 50%
- associated with high Ki-67
- high ki-67 associated with decreased ST
Stem cell markers increased in intestinal adenomas/carcinomas compared to normal mucosa?
Sox9, DCLK1, survivin, Hopx
MST SI adenocarcinoma tx with surgery?
- 18 mo
- 1 yr 60%, 2 yr 36%
- chemo did not affect survival
- dogs <8 yr did better
Complication rate for submucosal resection via transanal approach for epithelial rectal tumors?
- 29%
- recurrence 215d (7mo)
Categories of primary hepatic tumors ?
- hepatocellular
- bile duct
- neuroendocrine (carcinoid)
- mesenchymal
mets 2.5x more frequent than primary in liver
HCC morphology and frequency? Met rate?
massive 50-80%, met 0-37%
nodular 16-25%
diffuse 19%
- both nodular and diffuse met 93-100%
- most common liver tumor in dogs
- > 2/3 left sided
Most common hepatic tumor in cats?
HCC 42.5%, Bile duct carcinoma 32.5% (VCO 2022 paper)
Withrow says bile duct more common
Metastatic rate bile duct carcinoma?
dog 88% LN, lungs
cat 67-80% carcinomatosis
How do you differentiate neuroendocrine tumors from other hepatic tumors?
silver stain
Behavior of non HCC hepatic tumors?
Most aggressive (sarcomas, neuroendocrine) met rates 80-100%
bile duct carcinoma MST < 6 mo after surgery
True or false: degree of hepatocellular enzyme elevation can predict likelihood for cancer?
false
Most common clin path abnormality in cats with liver tumors?
azotemia
- also Tbili and ALT
Paraneoplastic syndrome reported with hepatic adenoma?
hypoglycemia
What may be helpful in differentiating HCC from other causes of liver disease?
hyperferritinemia
- must r/o IMHA first (most common cause)
Accuracy of FNA for HCC?
22.9% agreement to histo only 18.9% of cancer correctly diagnosed
Most effective imaging technique to differentiate benign from malignant HCC?
3-phase CT; 2 phase not effective
Which virus is associated with HCC in people?
hepatitis B AND woodchucks
What factor is associated with better ST for sx for HCC?
- completeness of excision
- can be assessed intra op with flourescent imaging
Intra op mortality rate HCC?
4.8%
- 28.6% complication rate: hemorrhage, devascularization, transeint hypoglycemia and liver failure
- transfusion needed in 17% of dogs and 44% of cats
Local recurrence HCC dogs? Prognosis?
Complete margins
- 12% recurrence
- PFI 1000d (33 mo)
- MST 1836d (62 mo)
incomplete
- 58% recurrence
- PFI 521d (17 mo)
- MST 765 (25 mo)
- nodular or diffuse = poor prognosis
MST cats with HCC treated with liver lobectomy?
2.4 yr
MST dogs HCC who do not undergo sx?
270 d (9 mo)
- 15.4x more likely to die from their rutmor
Prognostic factors HCC dogs?
surgical tx, side of tumor (R bad), high ALT, AST, ALT:AST ratio, margins
RT for HCC?
- must be 3D IMRT, in tradition liver cannot tolerate doses above 30 Gy
- 18-42 Gy deliver 6-10 gY at a time
- MST 567d (18mo); PRs mostly
- SRT described in case report with on-going shrinkage at 10 mo
Why is HCC chemo resistant?
- role of hepatocytes in detoxification OR expression of P-gp
Chemo with some reported responses for HCC?
Gemcitabine
- MST massive 44 mo
- nodule 32 mo
- diffuse 3 mo
Case report: dog with primary hepatic neuroendocrine carcinoma treated with dox/cytoxan, ST?
465 d, 15mo
When might the ST for bile duct carcinoma be improved in dogs?
If localized and tx with liver lobectomy
- MST 894d 30 mo
- PFI 16 mo
Response rate to Palladia for massive HCC?
50% (3/6 with PR and reduced liver enzymes)
- increased VEGFR2 and ELE in non responders
Alternative local tx for HCC?
chemoembolization
-with drug eluting bead CB 8, 2 dogs died from tx
- w/o beads MST 419d 14 mo, hemmorhage and tumor volume poor prog
Combined hepatocellular-cholangiocarcinoma dog outcomes?
- massive tumors in all (14)
- 14% intrahepatic mets at dx
- MST 700d 23 mo post op
Most common tumor type and prognosis for hemoabdomen secondary to liver tumor?
- hCC 36% MST 897d 30 mo
- benign 37% cured
- HSA 45d
- pre op ALT elevated + prog
- anemia and transfusion -
What can aid in detecting recurrence of HCC?
- routine follow up with monitoring liver enzymes
- no risk factors for recurrence in newer paper including margins
- no difference in OST in those with occurrence than those without or if more tx is pursued
Most common causes of non-islet cell hypoglycemia?
HCC, leiomyosarcoma
- IGF2 over expression
Cat breed predisposed to intestinal tumors?
Siamese 1.8x more likely to get intesitnal cancer and 8x more likely for adenocarcinoma specifically
Sites of intestinal tumor metastasis in decreasing frequency
LN (adenocarcinoma esp)> liver (leiomyosarcoma esp) > mesentery, spleen omentum, kidney, bone, peritoneum, lung
Common sites of adenocarcinoma GI based on species?
Cat - SI
Dog - colorectal
Breed predisposition inflammatory colorectal polyp?
doxin
Paraneoplastic clinpath finding intestinal Tcell LSA?
hypereosinophilia secondary to IL5 secretion
Perioperative mortality for intestinal tumors?
30-50% d/t sepsis
1 year survival dogs with solid intestinal tumors?
40%
80% for GIST/leiomyosarcoma
Chemotherapy shown to be effective for cats with colonic adenocarcinoma following subtotal colectomy?
Dox
MST 246d with 56d w/o
Dog SI adenocarcinoma prognosis?
- Guarded
- ST 12 d no treatment
- 4-10mo after sx
- 5-FU used in ppl little info in dog
Perianal gland tumor cytologic appearance?
hepatoid
Perinal tumors in cats?
dont happen bc they dont have the same glands, AGASCA rare
Signalment predisposition perianal adenomas?
intact male - growth stimulated by androgenic hormones and suppressed by estrogenic hormones
- this is NOT true for adenocarcinomas which are rare but occur in castrated animals
What might have led to perianal gland tumors formation in a female dog?
- spay = lack of estrogen
- can develop rarely secondary to Cushing’s
Metastatic rate perianal adenocarcinoma at DX?
<15%
- occurs later to LN
TX perianal adenoma? Carcinoma?
- SX 1 cm margin only needed, castrate –> cure
- ECT 90% ORR, 65% CR
- SX 1+cm
- can remove ~1/2 anal sphincter with minimal incontinence
Prognosis perianal adenocarcinoma?
- stage dependent
-if <5cm T2 –> 2 yr control rate >60% - if mets 7 mo MST (ln excision may improve outcome
Dog with hx of anal sac tumor removed, now hyperca with enlarged miln. Started ivf , next step?
FNA LN
Histo findings in 95% of AGASACA?
solid and tables/rosette/pseudorossette patterns
Frequency of hyperCA with AGASACA?
16-53%
Metastatic rate AGASACA at time of dx?
- overall 26-96%
- 26-89% LN (can skip sacral to others in 75%)
- 0-42% distant
- tumor size not predictive but presence of CS may be
E-cadherin is a cellular protein involved in adhesion and cell to cell communication. Loss of this protein is associated with decreased survival in which cancer?
AGASACA
Prognosis non AGASACA anal sac tumors?
melanoma - poor, 50 MI/10hpf often metastatic
SCC- not metastatic often recurrence
Complication rate after local AGASACA excision?
5-24% - dehiscence,, rectal perf, fistula, infection, transient incontinence
Does lymphadenectomy improve survival for AGASACA?
Yes
- 0-12% complication rate - hemorrhage, inability to resect
Chemos with gross disease AGASACA response?
carbo
cisplatin
actinomycinD
post op use: mito, melphalan
- NO SURVIVAL BENEFIT IN MULTIPLE STUDIES and even negative for DFI
AGASACA Palladia response gross disease?
- 69-88% CB
- ~25% PR, 40-63% SD
- duration 2.5-12 mo
- resolution of hyperca reported
AGASACA RT overall response gross disease?
- 38% -75% hypofractionated or fractionated protocols
- not shown to improve survival in microscopic disease
AE AGASACA fractionated protocols
- 15 x 3.2 Gy = 48 Gy
- MST 956 days
- 50% complications (late): rectal stricture, perf, chronic colitis
- late AE more common if dose >3 / fx
- acute AE: severe desquamination of perinal area and colitis lasting 1-4 weeks
- image guided improves with 3.8 Gy x 12 showing no late and 73% acute grade I-II
Clinical benefit rate hypofractionated RT AGASACA?
- 63% including resolution of obstipation
- 31% resolution of hyperCA with RT alone up to 77% when combined with pred and bisphosonate
- PFI 10-11 mo
-MST 8-15 mo - AE acute mild/infrequent, late rare
Local recurrence rate AGASACA?
5-44% not dependent on completeness of margins
DFI AGASACA tx with surgery +/- adjuvant chemo?
- LN mets 134-197d, 4-7 mo
- no mets 529-760d, 17-25 mo
- When recurrence further surgery can improve ST, additional 12 mo reported with vs 47d w/o
MST overall dogs AGASACA?
1-3 years
1 yr ST 65%
2 yr 29%
tumor related death range from 41-81%
Favorable prognostic indicators AGASACA?
tumor < 2.5 cm, no mets
- MST not reached only 9% died d/t tumor
Negative prognostic indicators AGASACA?
size >2.5 cm, CS, LN mets, 4+ metastatic LN, distant mets, not doing sx, tx with chemo alone, e-cadherin loss, hyperCA
Can sx still be considered for massive AGASACA (>5cm)?
Yes
- 18% intraop complication, 36% post op
- none permanent
- 37% local recurrence rate
- PFI 204d ~6mo
- OST 671d ~ 22 mo
What % of post op analsacullectomy complications are high grade - requiring intervention?
68%
- infection and recurrence most common
- also intraop complication (anal rectal wall perforation) post op sig more likely
RR and poor histo features cats with AGASACA?
- 36% recurrent with median 96d
- high nuclear pleomorphism
Pituitary tumors most likely to excrete which hormone based on species?
dog: ACTH –> increased cortisol –> Cushings
cat: GH –> hyersomatotropism –> acromegaly
- both adenoma, carcinomas rare
MOA mitotane? Trilostane?
Mitotane - o,p’-DDD-lysodren, potent adrenocorticolytic that causes direct cytotoxicity to the adrenal
Trilostane - Vetoryl, synthetic corticosteroid analog that inhibits 3-B-hydroxysteroid dehydrogenase
Blood test to dx acromegaly?
IGF1 - sens 84%, spec 92%
MST SRT acromegaly cats?
- 1,072d, 35 mo
- 32% diabetic remission
- 14% with previously elevated t4 became hypothyroid
Does hormonal activity influence survival for pituitary dependent hyperadrenocrticism in dogs undergoing RT?
- NO
- DOse of RT does
- fractioanted ST 605d (20 mo) vs 262d (8 mo) pRT
- use fractionated
What is recommended for SRT planning in pituitary macroadenomas?
CT + MRI
- single 17 Gy fx
- ~70% neuro improvement followed by decline 1.5-18 mo post SRT
- OST 1 year with 15% alive at 18 mo
Dog MRI with pituitary mass (T1 hyper intense) what is the ST with definitive RT?
> 2 years
Radiographic finding associated with adrenal tumor?
mineralization