Ch 82 STS Flashcards
Describe the TNM classification of STS
Stage I: G1-2, Any T, N0, M0
Stage II: G3, T1a/b, T2a, N0, M0
Stage III: G3, T2b, N0, M0
Stage IV: N1 or M1
tumor biology
- slow-growing, locally invasive tumors composed mainly of spindle-shaped cells
- low tendency for metastatic spread
- histologic diagnosis may be reached using immunohistochemistry
- exact histologic differentiation is not of major clinical importance because of the overall similar biologic behavior.
- often appear to be encapsulated but show an invasive growth pattern.
- pseudocapsule composed of compressed tumor cells and reactive fibrovascular tissue.
- The tumor can infiltrate along and through fascial plane (microextensions)
- Recurrence after marginal resection is therefore common
8% to 15% of all skin and subcutaneous tumors in dogs and 7% to 18% in cats.
fibrosarcomas;
peripheral nerve sheath tumors, (malignant schwannoma and neurofibrosarcoma)
perivascular wall tumors;
liposarcoma;
myxosarcoma
undifferentiated sarcomas
FNA
- many not be diagnosed by fine needle aspiration > do not exfoliate well
- A correct diagnosis via FNA in 63-69%
In what percentage of cases is pretreatment biopsy accurate?
- Accurate in 59%
- Overestimated grade in 12%,
- underestimated in 29%
STS grade
- predictive for both distant metastasis and local recurrence
- low (grade 1), intermediate (grade 2), and high (grade 3) grade
- based on the degree of tissue differentiation, cellular pleomorphism, cellularity and matrix formation, mitotic index, and amount of tumor necrosis
staging
- route of metastasis is mostly hematogenous
- most common site of distant metastasis is the lungs.
- Reported overall rate of metastasis in dogs is 6% to 17%
- depends on histologic grade (≤13% for grade 1 + 2, up to44% for grade 3)
- overall metastatic rate in cats is 14% to 20%
- distant metastasis is an important prognostic indicator
complete resection
- most important prognostic factor of local recurrence is clean surgical margins
- size, mobility, depth of invasion influence outcome
- Wide surgical excision is the preferred: 2-3cm with 1 x facial plane
- first surgery offers the best chance for cure
- incomplete resections increase patient morbidity, treatment costs, and recurrence
- CATS: MST after complete excisions (>16 months) was significantly longer compared with incomplete excisions (9 months)
incomplete excision Tx options
- radiation of the wound bed
- reexcision
- Recurrence rate after reexcision (15%) comparable to after radiation therapy
- complete exision vs incomplete + radiatin MST comparable (1500d)
- outcome grade dependent
Marginal Resection of distal limb STS
- marginal resection either as sole therapy or combined with radiation may result in a similar long-term outcome with less morbidity compared to amputation
- Grade I: marginal excision in 35 dogs, MST not reahced more than 1000 days
- Histologic margin status (34% “incomplete,” 34% close,” and 32% “complete”) did not affect survival time
- grade-dependent recurrence after marginal excision:
(7%) grade 1 tumors
(34%) grade 2 tumors
75% grade 3 tumors - Results suggest that marginal excision of low- and intermediate-grade soft tissue sarcomas may not influence survival time compared with wide or radical resection > most likely because of old age and slow growth
- Radical resection of extremity sarcoma > last resort treatment for recurrent and high-grade tumors
If primary wound closure is not possible after distal extremity tumor excision
- open wound treatment (wound contracture concerning the carpal area in 10% and bleeding form thin skin 16% of the cases, grade 1 and 2 DFI 980d)
- skin grafting (high “take rate” and minimal complications +/- NPWT)
outcome
- grade dependent
- margin dependedent
- Reported overall median survival after surgery for grade 3 soft tissue sarcoma ranges from 236 to 856 day
radiation
- after marginal excision or debulking resulted in good clinical outcomes
- no benefit for macroscopic dz (palliative, reduce pain and morbidity)
- preoperative radiation for downstaging local disease
chemo
- role for chemotherapy in preventing distant metastasis is unknown.
- Grade 3 tumors have a relatively high rate of metastasis (>40%), systemic adjuvant antitumor therapy would be preferred > only small response rates (doxorubicin)
- low-dose cyclophosphamide combined with piroxicam significantly prolonged disease-free intervals in 30 dogs
prognosis
- generally good, with complete resection resulting in long-term DFI and survival times.
- Marginal resection can also give favorable results for low-grade
- incomplete/marginal for igher grade benefot from radiation or recut
- median time for recurrence grade 1 and 2 tumors > 12 months (monitor q3-6mths)
Fibrosarcoma
- originating from fibroblasts
- histologically low grade and biologically high grade, arises in the oral cavity of dogs. It has an aggressive biologic behavior, but biopsies suggest a low histologic grade
Perivascular Wall Tumors
- diagnosis is based on specific immunohistochemical staining
- Perivascular wall tumors arise from cellular components of the vascular wall
- 20% had satellite nodules, and 30% were infiltrative
- despite marginal excision, recurrence rate low
- Distant metastasis was observed in only 0% to 2%
- perivascular wall tumors have a less aggressive biologic behavior compared to canine soft tissue sarcomas
Peripheral Nerve Sheath Tumors
- Schwann cells, perineural fibroblasts
- immunohistochemical differentiation by vimentin
- from peripheral nerves, resulting in tumors of the skin that infiltrate the subcutis locally or arise in a nerve plexus and in nerve roots
What is a myxosarcoma?
A neoplasm arising from fibroblasts or other primitive mesenchymal cells
- Produce an abundant extracellular matrix composed of mucin, rather than collagen
Feline Injection Site–Associated Sarcoma
- linked to tissue reaction associated with local inflammation and trauma.
- 0.63 sarcomas per 10,000 cats post vaccination
- ## usually occur at a younger age (median, 8 years) compared with non–injection site sarcomas
What have been associated with feline injection site sarcoma?
etiology
- Inactivated vaccines (Rabine, FeLV)
- Other multivalen vaccines
- Long actine pencillins inj
- Long acting corticosteroid inj
- nonabsorbable sutures
- Cisplatin inj
- Meloxicam inj
- Microchips
- Steel skin staples
- Retained surgical sponge
Tumor Behavior
Compared with other sarcomas
- more malignant biologic behavior and histologic features
- an inflammatory component
- chronic inflammation from a traumatic incident (injection or vaccination), can lead to local tumor formation in a host that is genetically tumor sensitive
- solid, raised, nonpainful, often cystic
- shoulder blades (84%), previously the most common site > recommended vaccinate distal hindlimbs (associated with change in tumor distribution)
- usually of a higher histologic grade than other soft tissue sarcomas i.e. 20% to 50% grade II, and 25% to 70% grade III.
- distant metastasis varies 0-24% (lungs)
- tumor tissue extend to underlying musculature or spinous processes.
Diagnosis
- cytology and clinical presentation and confirmed with histologic biopsy.
- Fibrosarcomas most common (79% to 93%)
- Other: osteosarcoma, chondrosarcoma, myxosarcoma,
- Marginal excision is the major reason that very high recurrence rates (up to 70%) have been reported > also common after wide excision
- palpation tends to underestimate the real tumor dimensions advanced imaging of the tumor is recommended
CT
- tumor dimensions and distant metastasis (good contrast uptake)
- scan with the front limbs positioned caudally to improved evaluation of the tumor in relation to surrounding tissues
Prognostic Factors
- recurrence, occurrence of distant metastasis, and number of surgeries
- most effective therapy is aggressive surgery with wide margins (i.e amputation do better)
- improved outcome with specialist surgeon
- most important prognostic factor for local recurrence, and thus survival time, is clean surgical margins
- Aberrant cytoplasmic p53 expression
- size
What are the recommended margins for injection site sarcoma?
5cm lateral marings, 2 fascial planes deep
surgery
- may involve resection of spinous processes, partial scapulectomy, lateral body wall resection, and hemipelvectomy to achieve margins
- latissimus dorsi or serratus ventralis muscle flaps may be required
- survival times 576 to 608 days with surgery alone, significantly higher with radical margins
- High recurrence rates > lead to larger margins
- 4- to 5-cm, complete resections 95% of the tumors; 5% had tumor cells in the margins. Local tumor recurrence developed in 39%, distant metastasis 21%, and 51% of the cats were alive at 1 yr
- 5cm/2 facial planes: overall median survival, 901 days
- complete anatomic muscle compartment involved, recurence 14%, surivial >1000d
Radiation
- In all cases of marginal excision,
- increase disease-free interval and survival times comparable in some studies, with reported recurrences of up to 42%
- complete excision + radioation also reported
chemo
A definitive role for chemotherapy in the treatment of feline injection site–associated sarcomas is still not established
- several retrospective studies reported no significant improvement of outcomes of combining surgery + chemo
- Doxorubicin possiby increase disease-free interval after surgery
- Electrochemotherapy: disease-free interval of 12 months (intraoperative electrochemotherapy) and 19 months (postoperative electrochemotherapy) + following recurence
Prevention and Monitoring
below the stifle or elbow, or on the tail if possible
- removal of masses at injection sites that exist for more than 3 months after injection, that increase significantly in size within 4 weeks, and that are larger than 2 cm in diameter.
Lipoma
- Liposuction has been reported as an effective treatment for lipomas
- Masses larger than 15 cm or in areas with increased movement had a higher risk for bruising and seroma formation.
infiltrative lipoma
- poorly defined, deep subcutaneous and intermuscular and intramuscular tumors composed of well-differentiated adipose cells
- Labrador Retrievers were overrepresented in two reports
- presence of infiltration of other tissues, typically muscle and fascia, and do not have a capsule.
- locally aggressive and infiltrate surrounding tissue
- Surgical resection is the main therapy, and aggressive treatment, including amputation, may be necessary
- (MRI) or CT, to investigate invasiveness
- nfiltration of important structures, including major nerves, often precludes complete excision.
- Multiple surgeries, including liposuction techniques, may prolong life expectancy for years
What is the reported recurrence rate after surgical resection of an infiltrative lipoma?
36-50%
Can follow with radiation therapy
Liposarcoma
neoplastic lipoblasts,266 is a rare tumor of older dogs
- usually located subcutaneously and secondarily involve the dermis
- 1% to 2% of feline injection site–associated sarcomas
- poorly circumscribed, are locally invasive, and rarely metastasize.
- FNA: lipid vacuoles that stain strongly with “oil red O”
- good prognosis with appropriate surgical management.
- Median survival times were 1188 days after wide excision, 649 days after marginal excision
Hemangiosarcoma of the Skin
DOGS
- dermal hemangiosarcoma may be associated with (ultraviolet) solar exposure (ventrum, medial thigh, and inguinal region) but subcutaneous hemangiosarcoma is more often observed
- staged according to tumor depth and invasion:
superficial tumors confined to the dermis (stage I),
tumors extending into subcutaneous tissues (stage II)
tumors invading muscle and fascia (stage III)
- stage I: Median survival was 780 days.
- Stage II and III guarded prognosis: 23% complete resections because of large size and poor circumscription, 60% metastasis to the lungs, and a median survival of 172 to 307 days.
- Other reported sites of metastasis include lymph nodes, spleen, liver, and heart
- Completeness of excision was the most important prognostic factor
- chemo may improve (high metastatic rate)
CATS
- more commonly in poorly pigmented skin, more often on the pinnae; nose and face; flank; and digits; and in the subcutis of the abdomen, inguinal region, and axilla.
- Tumor site (dermis or subcutis), clean margins, and mitotic rate were prognostic for survival.
- favorable disease-free intervals after complete resection and the relatively long survival after incomplete resection of hemangiosarcomas indicate that distant metastasis in cats is not as common
Long-term outcomes of dogs undergoing surgical resection
of mast cell tumors and soft tissue sarcomas: A prospective
2-year-long study
Milan Milovancev 2020
Prospective clinical study.
Sample population: Fifty-three dogs with 52 MCT (50 low grade, 2 high grade) and 19 STS (12 grade I, 6 grade II, 1 grade III). followed up to 24mths.
narrowest histologic tumor-free margins measured <1 mm in 21 of 52 (40%) MCT and 7 of 19 (37%) STS despite 2-3cm intraop margin
(4%) low-grade MCT local recurrence (6%) low-grade MCT developed visceral metastasis
One of 2 dogs with high-grade MCT developed local recurrence
No local recurrence or metastasis was diagnosed after excision of 19 STS
Local recurrence rates among predominantly low- to intermediategrade
MCT and STS were low, despite a high prevalence of histologic tumor-free
margins <1 mm.
limitations of histopathology in predicting outcomes
Diagnostic accuracy of optical coherence tomography
for assessing surgical margins of canine soft tissue
sarcomas in observers of different specialties
Dornbusch 2021
Blinded clinical prospective study.
Animals: Twenty-five dogs undergoing surgical excision of STS
sensitivity and specificity were 88.2% and 92.8%,
Use of OCT to accurately assess surgical margins after STS
excision was associated with a high sensitivity and specificity
potential utility for
real-time surgical margin assessment in dogs
Radial trimming methodology: surgical margin assessment
from as few as four sections representing the short axis
and long axis through the tumor specimen > represent assessment of <1% of the entire surgical margin
Optical coherence tomography is a high-resolution,
depth-resolved, cross-sectional, microscopic imaging
technique > comparable to a lowmagnification histology image
Prevalence of pulmonary nodules suggestive
of metastasis at presentation in dogs with cutaneous
or subcutaneous soft tissue sarcoma
Erika J. Villedieu 2021
146 client-owned dogs, retrospective
nodules present in 16 (11.7%)
dogs (5/77 [6%] with grade 1 STSs, 2/36 [6%] with grade 2 STSs, and 9/24
[38%] with grade 3 STSs).
Results indicated that pulmonary staging was a low-yield diagnostic procedure
for dogs with grade 1 or 2 cutaneous or subcutaneous STSs, especially when tumors
had been present for ≤ 3 months
Treatment of feline injection-site
sarcoma with surgery and iridium-192
brachytherapy: retrospective
evaluation of 22 cats
Jacqueline Bloch 2020
retrospective descriptive study
complications associated with postoperative brachytherapy were typically mild, although four cats developed more
severe complications. The median time to progression for all cats was 619 days and disease-specific survival time
for all cats was 1242 days
local failure rate was 54.5% and the distant failure rate was 13.6% due to lung metastasis
Carneiro 2019 – immunohistochemical characteristics of FISS
positive stains: desmin (19%), vimentin (100%), S-100 protein (95.2%), c-KIT (19%)
COX-2 (61.9%), FeLV viral particles (42.9%)
Curative-intent radical en bloc
resection using a minimum of a
3 cm margin in feline injection-site
sarcomas: a retrospective analysis
of 131 cases
Müller 2018
3cm lateral margins + full thickness body wall resection or minimum 2 fascial planes
- mDFI 21m, MST 24m
- operations for recurrent tumours more likely to result in tumour-related death
- local tumour recurrence 38.1%
- reoperation for recurrence associated with higher risk of another recurrence
(55% vs 33%)
- tumour bed biopsies negative for tumour → lower recurrence rate (30.5% vs 76.2%)
- 3.8% perioperative mortality
Non-injection-site soft tissue
sarcoma in cats: outcome following
adjuvant radiotherapy
Zajc 2022
adjuvant radiotherapy for non-injection-site STS in 18 cats
- tumour recurrence in 8/18 (44.4%)
- 3/8 (37.5%) hypofractionated, 5/10 (50%) conventional
- median PFI – overall 2748d, 164d in cats with recurrence
- hypofractionated 164d, conventional 2748d – not statistically significant
Incomplete histological margins following planned
narrow excision of canine appendicular soft tissue
sarcomas and mast cell tumors, using the residual
tumor classification scheme
David L. Haine 2022
assessment of histological margins for ‘planned narrow excision’ of MCT and STS
using the residual tumour classification scheme (R scheme)
- R scheme: R1 (tumour on ink) = incomplete, all other margins R0 (complete) – objective
- planned narrow excision = surgeon intention to resect outside gross visible tumour
<10mm lateral margins + deep fascial plane
- MCT: 6-10mm measured lateral margins → 7% R1, 0-5mm → 55% R1
- no association between histologic grade and R1 margins (no high grade in study)
- STS: 6-10mm measured lateral margins → 43% R1, 0-5mm → 41% R1
- wider lateral margins recommended for STS
- no association between histologic grade and R1 margins (1 high-grade in study)
- R scheme → greater %agreement
planned narrow excision (PNE): removing as much tissue
as possible within the constraints of the anatomical
location and the need for primary wound closure (as healing
by second intention would preclude/delay some
adjuvant therapies).
definition
of what entails an “incomplete histological excision” varies
between different studies (eg, tumor cells ≤1 mm,5,7,17
2 mm,23 or 3 mm,12 from the inked surgical margin),
meaning direct comparisons cannot be performed. The
residual tumor classification (“R”) scheme is an objective
measure of histopathological margin reporting, with a
definition of “tumor on ink” to define an incomplete histological
margin (R1), and all other margin lengths being
designated as complete (R0).
There is no clear consensus on approach; however, wide or proportional surgical margins (2 cm or proportional for grade I/II MCTs, 3 cm for high-grade MCTs, 3 cm for STSs) and a deep fascial plane are frequently
cited as necessary for complete surgical excision
limb tumors: One strategy to manage these tumors is marginal
excision (ME): removing macroscopic disease, followed by
active surveillance and/or adjunctive therapy, been shown to have good
long-term clinical outcomes in veterinary patients1
Conventionally fractionated radiation therapy is associated with long-term survival in dogs with infiltrative lipomas
Feng 2023
24 dogs, retrspec
for gross (18) or microscopic (8) infiltrative lipomas
he estimated median overall survival (OS) after completing radiotherapy was 4.8 years
This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas
Single high-dose radiation therapy and liquid fiducial markers can be used in dogs with incompletely resected soft tissue sarcomas
Timothy Ericksen 2023
single 20-Gy fraction of radiation in combination with a liquid fiducial marker to treat marginally or incompletely resected STS in the absence of gross disease resulted in similar OST and DFI compared to other previously reported radiation protocols.
Grade shifts in recurrent canine soft tissue sarcomas and mast cell tumors
Maureen A. Griffi 2023
15 dogs with recurrent cutaneous/subcutaneous STS and 5 dogs with recurrent cutaneous MCT
46.7%) dogs with recurrent STS had grade shift > 50% higher or lower
the heterogeneity of the tumor resulted in the assignment of a different grade. This has been demonstrated in studies comparing grade between incisional and excisional biopsies of the same tumors, where grade has been reported to be different in 41% of canine STS and up to 10% of canine MCT.
Mitotic activity and necrosis contribute significantly to grade and can be variable throughout the tumor.
Variability between pathologists in STS grading is common and should be considered as a potential source of alteration in tumor grades
Validated grading schemes that minimize the potential role of intra- and inter-observer variability and account for tumor heterogeneity are needed in companion animals.
need more study to dertermine prognostic significance of grade shift
Long-Term outcome following surgical excision of large, low to
intermediate grade soft tissue sarcomas in dogs
A Davis and G Hosgood 2023
AVJ
> 5cm, 39 dogs
Tumours were
removed by at least a narrow margin excision (≥1 cm) and deep
fascial plane in all cases. Histological margins were deemed complete
in 15/39, close (1–3 mm) in 8/39, incomplete in 4/39, and
unknown in 12/39.
Minor complications
occurred in 10/39 and major complications requiring surgical
intervention occurred in 5/39.
median 1064 days) reported good postoperative function, with
owner reported local recurrence in 2/39.
morbidity associated with skin flap
reconstruction,
case selection should be based on establishing a
preoperative diagnosis from incisional biopsy, supported by CT findings,
with important consideration given to reconstruction options
A retrospective comparison of carbon dioxide surgical laser and non-laser
excision for removal of cutaneous and subcutaneous soft-tissue sarcomas in
dogs
L Agulian
NZVJ
These data provide preliminary evidence that excision of cutaneous or
subcutaneous STS with CO2 surgical laser is comparable to non-laser methods for the
measured outcomes.
98% of the laser energy produced
by a CO2 laser is absorbed within 0.1 mm of its
target tissue, thermal damage to the surrounding
tissue is minimal, ranging from <0.1–0.5 mm
cut, coagulate, and seal
blood vessels up to 0.5 mm in diameter
Laser vaporisation seals small lymphatic vessels
and small nerve endings reducing postoperative swelling
and pain sensation
vaporises
bacterial organisms in the tissue, reducing intraoperative
wound contamination and risk of postoperative
infection (
Sanchez-Redondo 2020 – correlation between cytologic features and histologic grade in canine STS
- no significant correlation between cytologic features and grade
- increased mitotic figures (≥3 per 200 cells) may be associated but low sensitivity
Evaluation of the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcomas: An explorative study
Sara Del Magno 2021
VCO
subcutaneous STS infiltrated into the skin overlying the tumour
- incidence higher with higher grade sSTS (100% of Gr2 and 3) (36% of Gr1)
- consideration for lower surgical dose of cutaneous excision for low-grade sSTS
Electrochemotherapy
ECT associates the systemic administration of chemotherapy agents with the delivery of permeabilizing electric pulses with specific amplitude, duration, and waveforms
increase the efficacy of lipophobic drugs but minimizing patient toxicoses while maintaining adequate anticancer efficacy
in STSs, ECT used in an adjuvant modality since these neoplasms show a limited response to ECT alone
studies evidenced a clear clinical gain in terms of local control. In all these adjuvant studies, side effects were limited to local inflammation and occasional wound dehiscence
The overall response rate was 95% (21 out of 22 patients) with a mean time to recurrence of 730 days.
Electrochemical
Spuginini
