Soft Tissue Sarcomas Flashcards
Withrow 2019 - Chapter 22
What tissues do STS arise from?
Mesenchymal
What have sarcomas been associated with in dogs?
Radiation, trauma, foreign bodies, orthopedic implants, and the parasite Spirocerca lupi
Age, breed, sex, and size predilection for STS (dogs)
Middle-aged to older
No breed
No sex
Large-breed dogs
Biologic behavior of cutaneous and subcutaneous STS
Locally expansive mass growing between fascial planes, but also can be infiltrative. Often surrounded by a pseudocapsule.
Cutaneous and subcutaneous STS recurrence rate and metastatic rate
Low to moderate recurrence rate after surgical excision with or without adjuvant RT
Low metastatic rate
Likelihood of local recurrence of STS depends on what?
Tumor size, degree of infiltration, completeness of histologic excision, histologic grade
Likelihood of metastasis of STS depends on what?
Primarily on histologic grade
Describe the STS grading system
- Differentiation
- Mitosis
- Necrosis
Grade 1
- Differentiation: resembles normal adult mesenchymal tissue
- Mitosis: 0-9
- Necrosis: None
Grade 2
- Differentiation: Specific histologic subtype
- Mitosis: 10-19
- Necrosis: <50%
Grade 3
- Differentiation: undifferentiated
- Mitosis: >20
- Necrosis: >50%
Name STS tumors of fibrous tissues (4)
Nodular fasciitis (fibromatosis, pseudosarcomatous, fibromatosis), fibrosarcoma, pleomorphic sarcoma (malignant fibrous histiocytoma), myxosarcoma
Benign non-neoplastic lesion arising from the subcutaneous fascia or superficial portions of the deep fascia in dogs
Nodular fasciitis (fibromatosis, pseudosarcomatous, fibromatosis)
Appearance of nodular fasciitis
- Grossly
- Histologically
Grossly - nodular, poorly circumscribed, and very invasive
Histologically - large plump or spindle-shaped fibroblasts in a stromal network of variable amounts of collagen and reticular fibers with scattered lymphocytes, plasma cells, and macrophages
Variant of nodular fasciitis characterized by fibroblast proliferation with a dense reticular fiber network and mucoid material
Infantile desmoid-type fibromatosis
Nodular fasciitis
- Treatment
- Recurrence
- Metastasis
- Treatment: wide excision usually curative
- Recurrence: local recurrence possible with incomplete resection
- Metastasis: do not metastasis
Tumor arising from malignant fibroblasts
Fibrosarcoma (FSA)
Age, breed, sex, and size predilection for FSA
Older dogs and cats (Dogs with FSAs were significantly younger than dogs with other histologic subtypes of STS in one study)
No breed or sex predilection (higher predilection for Goldens and Dobermans in one study)
Fibrosarcoma
- Recurrence
- Grade
- More likely to recur after incomplete histologic excision
- Have higher mitotic rates than other histologic subtypes but are more likely to be low grade
Age, breed, sex, and site predilection for pleomorphic sarcoma (malignant fibrous histiocytoma)
Middle-aged to older dogs
Flat-coated retrievers, Rottweilers, Goldens
No sex predilection
SQ tissues of the trunk and pelvic limbs and spleen
Histologic subtypes of pleomorphic sarcoma (4)
Storiform-pleomorphic
Myxoid
Giant cell
Inflammatory
IHC staining for pleomorphic sarcoma
Definitive IHC staining patterns have not been established; typically vimentin positive and CD18 negative
Pleomorphic sarcoma
- Grade
- Metastasis
- More likely to be high grade
- More likely to have metastasis at time of diagnosis compared with other subtypes
Neoplasms of fibroblast origin with an abundant myxoid matrix composed of mucopolysaccharides
Myxosarcoma
Age and site predilection for myxosarcoma
Rare tumor
- Middle-aged to older dogs and cats
- SQ tumors of the trunk and limbs, heart, eye, and brain
- Tend to be infiltrative growths with ill-defined margins
Tumors derived of the different cellular components of vascular wall, excluding the endothelial lining
Perivascular wall tumor (PWT)
PWT
- Biologic behavior
- Recurrence
- Less aggressive biologic behavior
- Significantly lower rates of local recurrence than other histologic subtypes
Tumors of nerve sheath origin, arising from Schwann cells, perineural cells, or perineural or endoneural fibroblasts.
Peripheral nerve sheath tumors
Most common benign PNST (2)
Schwannomas and neurofibromas
How can malignant PNST be differentiated from PWTs based on IHC staining?
Malignant PNSTs stain positive with S-100, vimentin, glial fibrillary acidic protein (GFAP), nerve growth factor receptor, and neuron-specific enolase.
PNSTs have significantly higher Ki67 index than PWTs.
PNST
- Location and biologic behavior
- Recurrence
- Metastasis
- Often subcutaneous,
poorly circumscribed, adherent to deeper tissues and may infiltrate underlying fascia, muscle, and skin. Tend to be slow growing (often confused with lipomas on PE) - Local recurrence common after conservative surgery
- Modest metastatic rate
Types of PNST of macroscopic nerves (3)
Peripheral
Root
Plexus
Clinical signs of plexus PNST
unilateral lameness, muscle atrophy, paralysis, and pain.
Treatment for PNST
surgery, surgery with adjuvant RT, or RT alone
Life-limiting factor for PNST
Regardless of histologic grade, local disease usually limits survival before metastasis occurs.
Benign tumors of adipose tissue
Lipoma
Three morphologic types of lipomas
Regular
Intermuscular lipomas
Infiltrative lipomas
Lipoma
- Age
- Clinical signs
- Location
- Treatment
- Recurrence
- Older dogs
- Rarely symptomatic, if so are secondary to compression or strangulation
- Mostly subcutaneous but have been reported in thoracic cavity, abdominal cavity, spinal canal, and vulva/vagina of dogs
- marginal excision recommended for those that interfere with normal function but majority do not need surgery
- Surgery usually curative but local recurrence has been noted
Most common location of intermuscular lipomas
Caudal thigh of dogs, particularly between the semitendinosus and semimembranosus muscles; also reported in axilla
Uncommon tumors composed of well-differentiated adipose cells without evidence of anaplasia
Infiltrative lipoma
Biologic behavior of infiltrative lipomas
Considered benign and do not metastasize but are locally aggressive and commonly invade adjacent muscle, fascia, nerve, myocardium, joint capsule, and bone
Treatment options for infiltrative lipomas
Aggressive treatment, including amputation, may be necessary for local control. RT can be considered either alone or in combination with surgical excision.
What is the prevalence of FISS?
AH
1-4/10K cases
but can be as high as 13-16/10K cases!
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
How did the ratio of FISS to non-ISS changed between 1984 and 1994?
AH
Increased from 0.5 to 4.3
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
How long after vaccination, FISS can occur?
AH
4 weeks - 10 years
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
Are non-adjuvanted vaccines associated with a lower risk of causing FISS compared to adjuvanted vaccines
AH
Unclear!
This theory has been proposed but 3 large epidemiologic studies did not provide evidence that aluminum-containing vaccines pose a greater risk of FISS.
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
What are the local recurrence rates with surgery + radiation therapy for STS?
Overall: 20 - 40%
1 year: 70 - 85%
2 year: 60 - 80%
3 year: 57 - 80%
4 year: up to 80%
What is the median time to recurrence?
14 - 27 mos (412 - >798d)
Grade 1 & 2: >47 mos (>1416d)
Grade 3: 2.5 mos (78d)
MST for incomplete surgical excision + fRT?
Overall: 76 mos (2270d)
1 year: 80-87%
2 year: 72-87%
3 year: 92%
5 year: 76%
At what mitotic count is a soft tissue sarcoma treated with sx + RT more likely to recur with a shorter OST?
MC >9/10 hpf
What is the rate of local recurrence following sx + hypofractionated RT?
~20%
What is the progression free interval following sx + hRT?
greater than or equal to 23 mos (698d)
What percentage of patients are free of local recurrence following sx + hRT at 1 year? 2 & 3 years?
1 - 80%
2 & 3 - 73%
What should the timing of hRT post-operatively be to improve outcome?
> 4 weeks
What is the progression free survival following hRT by grade?
Grade 1: 63.5 mos (1904d)
Grade 2: 19 mos (582d)
Grade 3: 10 mos (292d)
What is the OST following hRT by grade?
Grade 1 & 2: not reached
Grade 3: 31 mos (940d)
What is the metastatic rate of STS by grade?
Grade 1: 0 - 15%
Grade 2: 5 - 25%
Grade 3: 20 - 45%
How to differentiate FISS from non-ISS by IHC?
AH
ISS: positive for PDGFR, EGFR, TGF-β
Non-ISS: negative or faintly positive for these.
Lymphocytes, regional macrophages and ISS neoplastic cells are all positive for PDGFR.
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
Which gene is expressed more in FISS vs non-ISS?
AH
tive in ISSs and not expressed in non–injection-site FSAs.205,206
FeLV and the feline sarcoma virus are not involved in the patho-
genesis of feline ISSs.207
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
There are many similarities between histologic subtypes and
biologic behavior of STSs in cats and dogs.
What are the 3 main exceptions in cats?
AH
- FISS
- Virally induced multicentric FSA
- The relative rarity of PNST, SCS, and HS
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
How FISS and non-ISS are different clinically?
AH
FISSs are usually large with a rapid growth rate and typically arise from the subcutis at sites consistent with the administration of vaccines and other injections, such as the interscapular region, body wall, and pelvic limbs, whereas non-ISSs are smaller, slower growing, and will often arise from the skin rather thansubcutaneous tissue
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas
How to differentiate FISS from non-ISS histologically (other than IHC)?
AH
ISSs have histologic features consistent with a more aggressive biologic behavior than non–ISSs, such as:
marked nuclear and cellular pleomorphism
increased tumor necrosis,
high mitotic activity,
multinucleate giant cells
+
the presence of a peripheral inflammatory cell infiltrate consisting of lymphocytes and macrophages
Withrow 2019 - Ch 22 - Soft Tissue Sarcomas