Hemangiosarcoma and Mast Cell Tumor Flashcards
What tissue types are sarcomas in general?
- Connective tissue/mesenchymal tumors
How do sarcomas spread?
By blood
Tissue origin for HSA
- Vascular endothelial cells (may be of bone marrow origin)
Signalment of HSA
- Large breed dogs - GSD, golden, and labrador retriever overrepresented
- Older dogs, but can be young
- Male predominance?
Where can HSA present?
- Anywhere there is blood
- Spleen, liver, right atrium are typical
- Kidney, SC tissues/muscle
- Oral cavity, urinary bladder, pericardium and peritoneum, bone
How does HSA usually present?
- Sudden collapse, weakness, pallor
- Sudden enlargement of a mass
- Sudden cardiac tamponade - weakness and arrhythmia
Biologic behavior of HSA
- EXTREMELY aggressive
- High rate of early development of metastasis
- Endothelial cells can go anywhere they want
- 25% have right atrial involvement at diagnosis
Splenic lesions and malignancy rule
2/3 are malignant, and of those 2/3 are HSA
- Evidence of splenic bleeding or rupture makes it a 75% chance of being a hemangiosarcoma
How do you officially make a diagnosis with HSA?
- Histopathology, but you can have a very high degree of suspicion dependent on the clinical picture
Other clinical suspicion for HSA
- Right atrial masses with pericardial hemorrhage
- Ultrasound appearance of cellular fluid-filled mass anywhere
- Aspirate for cytology or biopsy yielding only blood
- Evidence of DIC (elevated coags or D-dimers or FDPs)
- Plasma troponin 1 concentration high in the pericardial fluid
Plasma troponin 1
- High correlation with hemangiosarcoma
- Not sure if it’s just a correlation with blood
Staging of hemangiosarcoma
- CBC, Chem, UA
- Thoracic Rads are ESSENTIAL
CBC findings of HSA
- Normocytic, normochromic anemia
- NRBC
- Fragmented red cells (schistocytes that are HIGHLY suggestive)
- Neutrophilic leukocytosis, thrombocytopenia (but not horribly low unelss DIC)
Which cell type on blood smear is very suggestive of HSA?
- Schistocytes
Thoracic rad possible findings with HSA
- Chest mets in most cases
- 47% of cardic lesions present are identified
Additional findings for hSA
- Coagulation panel
- EKG
- Abdominal ultrasound
What is the best way to identify a cardiac lesion for HSA?
- Cardiac ultrasound
- About 1/4 will have right atrial involvement at outset
Treatment for HSA
- Surgical removal and systemic therapy
- Really only able to do with spleens and some SC masses
- Right atrial masses are quite difficult to remove
Chemotherapy - what’s best for HSA?
- Single agent doxorubicin once every 2-3 weeks
- Can do a combination therapy (Doxo + Vincristine + cyclophosphamide)
Biologic therapy for HSA
-Liposome encapsulated muramyl tripeptide
Anti-angiogenesis therapy and HSA
- Low dose chemotherapy is best (cyclophosphamide daily, lomustine daily, or chlorambucil daily)
Which anti-angiogenesis agents probably don’t work as well for HSA?
- NSAIDs and Tyrosine kinase inhibitors (although NSAIDs might not be that bad)
- Minocycline didn’t do anything
Prognosis for HSA in general
- Poor
Prognosis for HSA: surgery alone
2-3 months median survival
Prognosis for HSA: surgery + chemotherapy
- 4-6 months (NOT FOR METASTATIC DISEASE)
Prognosis for HSA: Right atrial
- With doxorubicin, surgery alone, surgery +doxorubicin, radiation
Doxorubicin alone: median survival about 4 months
- Surgery about 4 months with doxorubicin
- Surgery alone about 1 month
- Radiation about 2 months
Yunnan Baiyao evidence for helping HSA?
- Limited - seems like it doesn’t help
SC HSA mass treatment
- May benefit from local palliative radiation in addition to chemotherapy (and surgery?)
- Tend to live longer but the disease still USUALLY metastasizes
WSU Protocol for HSA
- Control local disease (surgery when possible + palliative radiation)
- Doxorubicin x 4 (chemo)
- Follow up with metronomic chemotherapy
Survival for WSU protocol
- ~6 months
Who gets cutaneous hemangiosarcoma?
- Light coat color, thinskin dog and cat disease
What likely causes cutaneous hemangiosarcoma?
- Sunlight induce
Prognosis for cutaneous hemangiosarcoma
- If it doesn’t invade into deeper tissues, this is a surgically curable disease
- 1 cm margins
What can Mast cell’s look like?
- ANYTHING!!!! I REPEAT, anything!
What is Darier’s sign?
- Tumor disappears
- possible mass that comes and goes could be a mast cell tumor
What do mast cell granules contain?
- Histamine
- Heparin,
- Other bioactive compounds which can cause systemic signs
Paraneoplastic syndromes associated with mast cell tumors
- GI ulceration (vomiting blood)
- Impaired LOCAL healing
- Coagulopathy (locally)
- Hypotensive shock (rare)
- Urticaria
- Eosinophilia, basophilia
Breeds who get MCT?
- Boxers!
- Boston Terrier
- Labrador Retrievers
- Schnauzers
- Beagles
- Pugs
- Siamese for cats
Age for MCT
- Any age in dog, tend to be older cats
- No gender predilection
Dog MCT presentation
- Most are external skin masses
- PRIMARY internal tumors are rare
Cat MCT presentation
- Equal numbers of external and internal tumors
- Primary symptom is not always a skin mass and MAY be vomiting in a cat
Cytology for MCT
- Round cell, often has granules
- Gives you a good idea it is a mast cell tumor so surgery and staging can be planned
Histopathology of MCT
- REQUIRED for grading the tumor
- Don’t forget to submit margins
- Often just take them out
Diagnosis of MCT
- Often start with cytology to give you an idea that it’s a mast cell tumor so that you can take it off with appropriate planning
Grading MCT: Pathologists vs Oncologists
- Pathologists prefer a 2 level grading scheme vs 3 levels
- Not truthful for lowest grade 1 tumors, so oncologists prefer having both systems used and then being able to split the grade 2 tumors additionally into high and low grade grade 2
Grade 1 MCT prognosis
- Good
Grade 2 MCT prognosis
Variable prognosis
Grade 3 MCT prognosis
- VERY POOR :(
Define a grade 1 MCT
- well differentiated and superficial
Define a grade 2 MCT
Well to medium differentiation, SQ involvement
Define a grade 3 MCT
- Poorly differentiated
Mitotic index of MCT - cut off for likelihood to recur or metastasize?
- <5 mitoses/10 HPF is less likely to recur or metastasize
- >5 mitoses/10hpf is more likely to recur or metastasize
What are the gold standards for determining prognosis for canine MCT?
- Grade and mitotic index**
- There are other helpful markers too (c-Kit, AgNOR’s, Ki-67)
Staging for a grade 1 and lower grade 2 MCT
- Lymph node check and possible imaging
- CBC/Chem
- Buffy coat smear
Staging for a higher grade 2 and grade 3 MCT
- Lymph node check and possible imaging
- CBC/Chem
- Buffy coat smear
- Abdominal ultrasound +/- spleen and liver aspiration (EVEN IF NORMAL APPEARING)
- Bone marrow aspirate
Staging MCTs
0 = one tumor, already excised
I = one tumor
II = one tumor with regional LN involvement
III = multiple dermal tumors, large infiltrating tumors, with or without lymph node involvement
IV = any tumor with distant metastasis or recurrence with metastasis
Is LN involvement really bad with MCT?
- No
Symptomatic therapy for MCT (not always needed)
- H1 blocker
(diphenhydramine) - H2 blocker (cimetidine, ranitidine, famotidine)
- Prednisone
H1 blocker function in MCT
- Prevent bronchoconstriction, vasodilation
H2 blocker function in MCT
- prevent gastric ulceration
- Could give omeprazole too
Prednisone function with MCT
- Shrink the tumor prior to surgery
General treatment for MCTs
- Surgery
- Electrochemotherapy
- Radiation
- Traditional chemotherapy
Surgery for MCTs
- 3 cm margins in ALL directions
Electrochemotherapy for MCT - when to use?
- Small low grade tumors
Radiation therapy for MCT - when to use?
- Local disease
- Best if minimal disease
Traditional chemotherapy for MCT - when to use?
- Used ONLY for high stage/systemic disease (all grade III)
- Minimally effective alone
Chemo for canine MCT
- Traditional
- Prednisone, vinblastine, lomustine (huge)
- Vinblastine, bred
- Vinblastine, cyclophosphamide, prednisone
- Hydroxyurea
WSU protocol for canine MCT?
- Vinblastine and lomustine
Tyrosine kinase inhibitors for MCTs
- Save for aggressive tumors; about 50% respond for about 2 months
- There are toxicities - NOT a benign tumor
- On it for life
RTK combination therapy either vinblastine/toceranib or palliative radiation and toceranib for MCT (all grades)?
- Not sure
- Might be helpful?
- Might not be helpful?
Grade 1 MCT prognosis
- Most cured with surgery
- Don’t use palladia or chemo with these!
- can irradiate or use electrochemotherapy when surgery not possible
Grade 2 MCT prognosis
- Surgery CAN be curative
- Often need radiation as follow up
- Low grade grade 2 electrochemo to follow up
- Some require systemic therapy (traditional chemo or TK inhibitor)
Grade 3 MCT prognosis
- Surgery rarely curative
- Can irradiate if no confirmed metastasis
- ALL require systemic therapy
- Slow progression, not curative
- In addition to local therapy
- Best case is surgery, irradiation, and chemotherapy
Feline MCT on skin - malignant or benign?
- Usually benign
- Cured with surgery often
Feline MCT internally - malignant or benign?
- More aggressive!
Two forms of internal feline MCT
- Lymphoreticular
- GI
How do cats with internal MCT present?
- Vomiting (often still eating)
- Mass in abdomen, aspirate yields mast cells (solid sheets or pretty normal mast cells)
Diagnosis of feline MCTs
- Aspirate of mass in abdomen yields mast cells
- Often circulating mast cells in blood (buffy coat smear on CBC)
Treatment for feline internal MCT
- Symptomatic treatment important
- Corticosteroids, H1, and H2 blockers
- Splenic form may stop therapy after surgery?
- Intestinal form may require therapy for life
- Remove tumor from spleen or intestine
TKI and feline internal MCT
- Beneficial but not often necessary
Prognosis for feline internal MCT
- Prolonged for splenic (>3 years)
- Less for GI (11 months)
- If you can take the spleen out, they often do quite well
