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Soft tissue sarcomas Flashcards

1
Q

STS account for what percent of skin and SQ tumors in dogs and cats?

A

15% of skin and SQ tumors of dogs and 7% of cats

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2
Q

List 5 etilogies for STS?

A

radiation, trauma, foreign bodies, orthopedic implants and the parasite (Spirocerca lupi)

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3
Q

Age predisposition for STS?

Exception?

A

middle-aged to older dogs and cats

rhabdomyosarcoma occurs in young dogs

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4
Q

Breed and sex predilection for STS?

A

None

Large breeds are over-represented

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5
Q

Describe the 3 features of biologic behaivour of STS?

A

Local expansile mass growing between fascial planes – but also can be infiltrative

Often surrounded by a pseudocapsule

Low to moderate local recurrence after surgical excision and low metastatic rate

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6
Q

List 4 features associated with likelihood of local recurrence?

A

Tumor size, degree of infiltration, completeness of histologic excision, and histologic grade

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7
Q

The likihood of metastasis is dependent on?

A

Histologic grade

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8
Q

STS grading scheme?

A
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9
Q

What is nodular fasciitis?

Describe 3 features?

Can be misdiagnosed as?

Local recurrence and metastasis?

A

benign, non-neoplastic lesion of the subcutaneous and superficial deep fascia

nodular, poorly circumscribed, and very invasive

FSA

local recurrence is possible with incomplete resection, but they do not metastasize

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10
Q

FSA arises from what cells and 3 common locations?

Higher predilection seen in 2 breeds?

Local recurrence with what 2 features and metastasis?

A

Arises from malignant fibroblasts in any location/Skin, SQ, oral cavity

Golden retrievers and Doberman pinschers

more likely to recur after incomplete excision and higher mitotic rates than other type of STSs

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11
Q

Pleomorphic Sarcoma (malignant fibrous histiocytoma, MFH)

Resembles what cells?

Breeds predisposed?

2 most common locations?

List 4 histologic subtypes?

IHC staining pattern?

Metastasizes to what 4 organs?

MST?

A

Resembles histiocytes and fibrocytes

Flat-coated retrievers, Rottweilers and golden retrievers are overrepresented

Most common in SQ tissue of trunk and pelvic limbs and spleen

4 histologic subtypes?

Storiform-pleomorphic, myxoid, giant cell, and inflammatory

IHC staining pattern

vimentin (+) and CD18 (-)

Giant cell pleomorphic sarcomas in 10 dogs

highly metastatic to SQ, LNs, livers and lungs

MST: 61 days

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12
Q

What is the origin of myxosarcoma?

2 most common locations for myxosarcoma?

A

fibroblast origin with abundant myxoid matrix of mucopolysaccharides

majority are on trunk and limbs

tend to be infiltrative growths w/ ill-defined margins

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13
Q

Perivascular Wall Tumor (PWT) is derived from?

Pericytes express?

Myopericytes express?

Smonth mucles cells express?

Behaivour and local recurrence?

A

derived from different cellular components of vascular wall, excluding the endothelial lining

cytologic appearance w/ moderate to high cellularity, cohesion of spindle cells, presence of capillaries, and multinucleate cells

IHC: pericytes express vimentin and variable amount of pan and α-smooth muscle actin; myopericytes express desmin and calponin; smooth muscle cells express smoothelin and heavy caldesmon.

Less aggressive biologic behavior, significantly lower rates of local recurrence than other histologic subtypes

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14
Q

Peripheral Nerve Sheath Tumor (PNST)

Arises from what cells?

What are the benign PNSTs?

5 IHC markers?

A

nerve sheath origin, arising from Schwann cells, perineural or endoneural fibroblasts

Benign PNSTs are schwannomas and neurofibromas

Positive with vimentin and S-100, glial fibrillary protein (GFAP), nerve growth factor receptor, and neuron-specific enolase.

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15
Q

PNST can be classified as peripheral, root, or plexus

A

peripheral PNST involve macroscopic nerves distant to either brain or spinal cord- much amenable to treatment than either root or plexus PNSTs

plexus PNSTs can involve either the brachial or lumbrosacral plexus- show signs of unilateral lameness, muscle atrophy, paralysis and pain

invade the spinal cord, especially high-grade root and plexus PNST

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16
Q

Surgical excision typically involves forequarter amputation, although limb-sparing compartmental resection is occasionally possible16 dogs w/ brachial plexus PNST treated w/ limb-sparing compartmental resection

Overall MST: 1303 days (3.6 yr); complete excision: 2227 days (6 yr) and incomplete excision 487 days (1.3 yr)

SRT in 10 dogs w/ brachial plexus – partial or complete resolution of neurologic signs in all dogs

MPFS: 240 days (8 mo); MST: 371 days; progression reported in 90% of dogs

A
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17
Q

List 3 morphologic types of lipoma?

Clinical signs?

Problematic locations?

Treatment?

A

3 morphologic types: regular, infiltrative and intermuscular

usually asymptomatic unless causing compression or strangulation

Problematic location – thoracic cavity, spinal canal, abdominal cavity, vulva or vagina

Marginally excision is recommended if interfering with function

usually curative, but local recurrence has been reported

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18
Q

Intermuscular lipoma

Common location

Common clinical sign?

Treatment? What needs to be placed?

A

Usually located in the caudal thigh – notably between the semitendinosus and semimembranosus muscles

slow growing, firm, fixed

may cause lameness

surgical excision should be curative, but drains are typically necessary

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19
Q

Infiltrative lipoma

A

Well-differentiated adipose cells, cannot be differentiated by cytology or small biopsies

Do not metastasize, but invade muscle, fascia, nerve, myocardium, joint, and bone

CT is used to better delineate margins, but they do not contrast enhance

Aggressive surgery (amputation) or RT can be used for local control

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20
Q

Liposarcoma originates from what cells?

Stain useful to differentiate liposarcoma from other STSs?

Prognosis with complete, marginal, incisional?

A

Uncommon and originate from lipoblasts, NOT from malignant transformation of lipomas

Oil Red O is useful to differentiate liposarcomas from other STSs by cytologic staining lipid

Prognosis is good with surgery (MST 1188 or 3.2 yrwith adequate surgery) compared to 649 days (1.8 yr), and 183 days (6 mo) with marginal or incisional biopsy

Histologically classified as well-differentiated, myxoid, round cell (poorly differentiated), pleomorphic or dedifferentiated

Histologic subtype has clinical and prognostic importance in humans

pleomorphic has a high metastatic rate, myxoid is more likely to met to extra-pulmonary structures, and well-differentiated are unlikely to met.

Histologic subtype in dogs was not prognostic, but met disease was more common in

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21
Q

Rhabdomyosarcoma arises from what cells?

5 Common sites?

Common locations for metastasis (5)

5 IHC markers?

A

rare tumor of myoblasts or primitive mesenchymal cells differentiating into striated muscle cells

common sites: urinary bladder, retrobulbar musculature, larynx, tongue, and myocardium

locally invasive, low to moderate mets: lungs, liver, spleen, kidneys, and adrenal glands

difficult histologically and may require IHC for vimentin, skeletal muscle actin, myoglobin, myogenin, and myogenic differentiation (MyoD)

classifications: prognostic in humans, not in dogs

Embryonal – predilection for tongue, oral, larynx or retrobulbar musculature

Botryoid – grapelike appearance. Commonly in the bladder of younger female dogs (St. Bernard over-represented)

Alveolar and Pleomorphic

rare tumor, but reports of surgery +/- RT or chemo encouraging

22
Q

Lymphangiosarcoma arises from?

Clinical signs?

MST with no tx and surgery alone?

A

rare tumor from lymphatic endothelial cells

usually soft, cystic-like, and edematous, usually occurring in the subcutis

clinical signs: extensive edema and drainage of lymph through the skin or a cystic mass, or nonhealing, discharging wounds

12 dogs – MST of 168 days (5.6 mo) for dogs w/ no treatment; 487 days (1.3 yr) w/ Sx alone

23
Q

Malignant Mesenchymoma

A

rare STSs

fibrous component but has a variety of other sarcomas present as well.

slow rate of growth and can growth very large

metastasis reported

Splenic mesenchymoma (MST: 12 mo) is better prognosis than other splenic sarcomas.

24
Q

Surgery and RT

A

RT can be used for after planned marginal resection or unplanned incomplete histologic excision

local recurrence rates are similar in dogs treated w/ marginal resection alone, compared w/ recurrence rates occurring in dogs w/ incomplete excision treated w/ adjuvant RT (Table 22.3)

the results cannot be compared b/c different study population and methodologies

RT should be started a minimum of 7 days after Sx to minimize the risk of delayed healing wound and dehiscence

Full course of fractionated protocol is recommended

3 - 4.2 Gy fractions for total 42 - 63 Gy (M to F or M-W-F)

Recurrence rate: 16.7 - 36.8 %.

The median time to recurrence for is 412 to >798 days

the median of recurrence: grade III (78 days) << grade I and II (>1416 days or 4 yr)

MST was 2270 days (6 yr) for non-oral sites

Dogs with MI > 9/10HPF were more likely to have local recurrence and shorter ST

Hypofractionated RT after incomplete excision has also been reported

6-9 Gy weekly fx to total dose of 24-36 Gy

18-21 % local recurrence rate

PFI were 698 days (1.9 yr) or not reached

median PFS in grade I, II, and III were 1904 (5.2 yr), 582 (1.6 yr) and 292 days (10 mo)

25
Q

Response rate with hypofractionated RT for STS?

Median PFI

MST

A

hypofractionated RT (4-8 Gy x 3-6 fx, total of 20-36 Gy) has been reported

overall response rate was 46 - 50%

median PFI: 155 - 419 days

MST: 206 - 513 days

26
Q

Pre-operative RT for STS, list 3 advantages?

Disadvantage?

A

Pre-operative RT advantage:

Smaller radiation field

Peripheral tumor cells are killed

Tumor reduction – less difficult Sx

disadvantage:

Greater wound complications (35% vs 17% post-op RT in human) – so doses <50Gy used

27
Q

Chemotherapy for STS

A

Metastasis can occur >1year later, so it may minimize the benefits of post-op chemo

retrospective study – Sx alone (n=18) vs. Sx and Doxorubicin (n=21)

no significant difference in survival outcome b/w 2 groups

Metronomic chemo with cyclophosphamide and piroxicam prolongs DFI in dogs with incompletely excised tumors.

There may be a role for tyrosine kinase inhibitors

VEGF and VEGF receptor expression increase in peri- and intratumoral regions of canine STS

Intralesional chemo agents (Cisplatin and 5-FU) may decrease risk of local recurrence

local recurrence: 17-31 %

wound complications are common – 47-84%

28
Q

STS tumor recurrence is dependent on what 6 factors?

A

tumor size, local tumor characteristics (well-circumscribed or infiltrative), tumor location, histologic grade, completeness of excision, and Tx methods.

29
Q

Local recurrence for STS

Wide resection

Marginal resection

Incomplete resenstion and RT

sx and hypoFx RT

A

0-5% after wide resection,

11-29% after marginal resection,

17-37% after incomplete excision and fractionated RT

18-21% after Sx and hypoFx RT

30
Q

Prognosis

A

Median DFI: 368 – 798 days (similar b/w different Tx) or 1-2 yr

local recurrence rate after incomplete histologic excision was 28% and 11x more likely to recur than complete excision

grade III STS have 6x greater risk for local recurrence compared w/ low grade

grade I - 7%; II - 34%; III - 75%

Histologic subtype may be associated w/ local tumor recurrence

PWT - low risk; FSA – higher

Tumor size have a negative effect on local tumor control

7x more likely recurrence in >5 cm PWT

1.3x for every 1 cm increase in size

dogs w/ fixed or invasive STS have significantly decreased DFIs and STs

31
Q

Metastasis for STS?

A

Metastasis

overall met rate from 0-31% with median time of met of 230-365 days (8-12 mo)

met rate in grade I, II, and III are 0-13%, 7-27%, and 22-44%

metastasis is 5x more likely when MI>20/10 HPF than <20

one study – no dogs at or below elbow or stifle developed met

32
Q

MST for dogs with Sx alone or Sx and RT?

A

MST of dog w/ STS ranges from 1013 to 1796 days after Sx alone to 2270 days w/ Sx and RT (nonoral STS)

only 9-33% of dogs die of tumor-related causes after curative-intent Tx

clinical factors associated w/ decreased ST include tumor invasiveness, surgical approach, completeness of excision, and local tumor recurrence

incomplete resection (MST of 657d) ≪ complete resection (1306d)

Histologic and IHC features associated w/ ST include tumor necrosis, MI, grade, AgNOR and Ki67 scores

Mitotic rates >10, 10-20, >20 have MST 1444d or 4 years, 532d or 1.5 yr, 236d or 8 mo

Tumor related death 2.8x more likely with >10% necrosis, 2.6x with MI >20

33
Q

Feline injection site sarcomas have been associated with what risk factor?

A

Inactivated feline vaccines (rabies and FeLV)

Association of adjuvant in vaccines is unclear, but correlation appears higher in killed vaccines (rabies)

also seen at injection sites (lufenuron and microchips)

34
Q

When do injection site sarcomas develop?

A

develops 4 weeks – 10 years postvaccination

35
Q

What is a proposed hypothesis for feline injection site sarcomas?

What are the possible involved growth factors?

What proto-oncogene?

What two viruses are not associated?

A

Inflammatory reaction leads to uncontrolled fibroblast and myoblast proliferation +/- immunologic factors

platelet derived GF, epidermal GF, transforming GF-β, lymphocytes also stain for PDGF (possibly the source)

C-jun a proto-oncogene is also strongly expressed compared to other sarcomas

FeLV and feline sarcoma virus to not appear to be associated

36
Q

List 3 differences between feline ISS and non-ISS?

A
  1. ISSs are large with a rapid growth rate
  2. Typically arise from the subcutis at interscapular region, body wall and pelvic limbs
  3. ISSs are more aggressive biologic behavior and are more likely to be grade III (59%)

increased nuclear and cellular pleomorphism, increased tumor necrosis, high mitotic activity, peripheral inflammatory infiltrates of lymphocytes and macrophages (along with aluminum hydroxide – adjuvant in feline Vx)

37
Q

Treatment for feline ISS is surgery. What are the recommended margins?

A

Margins recommended from 5-cm lateral and 2 fascial layers for deep when based on gross palpation

3-cm lateral and 1 fascial layer for deep margins based on CT

38
Q

DFI and MST are affected by what 3 factors?

A

DFI and MST are decreased by marginal resection, increasing number of surgeries, and surgery performed by rDVM

Sx to first recurrence is 79d (2.6 mo) after marginal resection vs 325-419d (11-14 mo) for wide resection

Sx to first recurrence is 66d (2 mo) at rDVM vs 274d (9 mo) at referral

39
Q

Recurrence in up to __% of cats treated with only 2-3 cm margins with 1 fascial plane

Compared to __% recurrence at _____ with 5 cm and 2 fascial planes

A

50%

14%, 3 years

40
Q

Recurrence rate for feline ISS and RT

A

In studies using pre-op RT: recurrence rates 40-45% at median of 398 – 584 days

complete resection longer DFI (700-986d vs 112-292d), but not improve recurrence rate (42% vs 32%)

Post-op RT has similar outcomes

In 1 study: MST was longer in cats treated w/ post-op than pre-op RT, but may be due to selection bias

In 1 study of post-op RT (25 cats): 28% recurrence rates, but time to first recurrence not reached (vs 661d in cats also treated with doxorubicin)

In another study median PFI was 37mo with Sx + curative intent RT compared to 10mo for hypoFx RT

RT should start 10-14 days post-op as DFI and ST decreases as the interval b/w Sx and RT increases

MST 600-1307 days with Sx and RT (local recurrence does not affect survival time)

41
Q

RT for Gross Disease – palliative large and unresectable ISSs

A

In 10 cats - 2 had CR and 7 had PR with 4 Gy x 5 and liposomal doxorubicin, but median PFI 117 days

In 17 cats (8Gy x 4 weekly) - PFI was 4 mo and MST was 7 mo

SRT in 11 cats (most 10 Gy x 3 daily) – PFI was 242 days and MST was 301 days

42
Q

Metastatic rate for feline ISS and time to metastasis?

A

Met 0-26% with median time to met 265-309 days (9-10 mo)

43
Q

Feline ISS: Doxorubicin (+/- cyclophosphamide or CCNU) for gross tumors response (CR/PR ___%) for ____ days

MST prolonged in?

A

Doxorubicin (+/- cyclophosphamide or CCNU) for gross tumors response (CR/PR 25-50%) for 84-125 days

MST prolonged in cats who responded compared to non-responders

44
Q

MST improved in cats with gross residual disease followed by RT and doxorubicin (__mo vs __mo without chemo)

DOX (or liposome DOX) prolonged DFI in cats after Sx and RT (___d vs __d w/o chemo)

but the completeness of Sx margin may confound analysis (449d w/ complete margin vs 281d w/o)

A

MST improved in cats with gross residual disease followed by RT and doxorubicin (29mo vs 5mo without chemo)

DOX (or liposome DOX) prolonged DFI in cats after Sx and RT (393d vs 93d w/o chemo)

45
Q

Electrochemotherapy with bleomycin improved time to local occurrence from ___ for Sx only, ___ for intraoperatively, and __ for cats treated post-op

met rate only 1.7%

Immunotherapy, using recombinant viruses expressing IL-2, improved local tumor control rates

IL-2 vaccine after Sx and RT had 1-y recurrence rate of ____% compared to ___% w/o adjuvant Tx.

A

4 mo, 12 mo, 19 mo

28-39%, 61%

46
Q

The best results when after aggressive Sx w/ complete excision

the rate of complete excision <50% when ISS were excised w/ 2-3 cm margins, compared w/ 95-97% when 4-5 cm margins

local recurrence rate 14-22% after complete excision compared 58-69% after incomplete

Sx w/ RT (either pre or post-op) had local recurrence 28-45% w/ DFI 13-37 mo

A
47
Q

List 4 prognostic factors for feline ISS associated with local tumor recurrence?

A

tumor size, Sx dose or aggressiveness, completeness of histologic excision and histologic grade

48
Q

Metastatic rate with ISS?

Metastasis is more common with?

Metastatic rate with grade 1, 2, 3?

Most common site for metastasis?

A

met is uncommon in cats with ISS – from 0-24%

more likely in grade III

mets rate in grade I, II, and III are 0-17%, 15-19%, and 22-100%

lungs – most common site

49
Q

Feline ISS

MST with wide resection?

MST with less aggressive surgery?

MST with Sx and RT?

A

MST of 804-901d for wide resection (4-5 cm margins)

395-608d (1-1.7 yr) for less aggressive Sx

520-1307d (1.4-3.6 yr) for Sx +RT

50
Q

List 7 prognostic factors for survival in feline ISS?

A

Prognostic factor of survival: anemia, tumor size, Tx type, histologic subtype, mitotic rate, local tumor recurrence, and met disease.

PCV < 25% decreased ST (308d vs 760d)

tumor size associated w/ prognosis treated w/ Sx alone

<2 cm: 643 d (1.8 yr); 2-5 cm: 558d (1.5 y); >5 cm: 394d (13 mo)

>3.75 cm significantly decreased ST

In 1 study: post-op RT (705d) had longer MST than pre-op RT (310d)

2-y survival rate for cat w/o local recurrence was 75% vs 37% w/ recurrence

MST for cats w/o mets 929-1528d (2.5-4y) vs 165-388d (6-12 mo) w/ mets (20-21%)

51
Q

List 3 ways to prevent feline ISS?

A

Avoiding use of polyvalent vaccines, aluminum adjuvant or using non-adjuvanted vaccines and increasing intervals b/w vaccinations (> 3 years)

Vaccinating at distal extremities – R rear for RV, L rear for FeLV, R front for others

3-2-1 Rule: Indicated if mass is present 3 months after vaccination, >2cm, or increasing in size after 1 mo

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