Hemangiosarcoma

Question 1

describe the etiology and tumor biology of hemangiosarcoma

Answer 1

cell of origin: endothelial cells

etiology: not completely understood
-dermal HSA: strong link to UV exposure

biology:
-approx 50% have mutations in PTEN (a tumor suppressor)
-high expression of VEGF (pro-angiogenic peptide

Question 2

describe the anatomic sites where HSA is found

Answer 2

1. spleen: COMMON
2. skin, right atrium/auricle, and liver: less common
3. bone, retroperitoneal: rare
   -but IS one of the ddx for a primary bone tumor

Question 3

describe the biological behavior of HSA

Answer 3

1. highly locally invasive
2. highly metastatic: origin is endothelial cells that have direct access to blood vessels (hematogenous route)

-exception: stage 1 cutaneous HSA

-target organs of metastasis: lungs, liver, regional lymph nodes, omentum, mesentery (when a splenic mass ruptures, now HSA has access to entire abdomen)

-most common secondary/metastatic brain tumor in dogs!

3. rapid growth!

Question 4

describe the signalment of dogs affected by HSA

Answer 4

1. older dogs
2. breeds:
   -germa shepherds
   -goldens
   -labradors
3. cutaneous location: lightly haired, lightly pigmented dogs that like to sunbathe (pitties)

Question 5

describe the common presenting history of HSA

Answer 5

1. vary from mild lethargy/inappetance to collapse and hypovolemic shock

2 +/- intermittent periods (over days to weeks) of lethargy or collapse with recovery

3. cutaneous HSA often red, ulcerated, and may bleed frequently

Question 6

describe physical exam of HSA

Answer 6

1. can be normal!
2. cranial organomegaly +/- palpable mass possible
3. acute to chronic blood loss
   -pale MM
   -weak to bounding pulses
   -tachycardia
   -low body temp
4. muffled heart sounds secondary to pericardial effusion
5. cutaneous/SQ mass

Question 7

describe what to do in the case of hemoabdomen/splenic mass

Answer 7

1. stabilize the patient!
2. bloodwork:
   -CBC: thrombocytopenia, anemia (regen v. nonregen), schistocytes possible
   -chem: liver value elevations (poor perfusion v. metastatic disease)
   -clotting profile: PT/PTT often prolonged; approx 50% have signs consistent with DIC
3. abdominocentesis or pericardiocentesis
   -ultrasound guided (pericardio, but abdomino can be done blind)
   -non-clotting hemorrhagic effusion: PCV fluid = PCV peripheral blood
   -fluid cytology usually not helpful
4. imaging: site dependent
   -rads: important for staging (r/o metastasis)
   –AXR: peritoneal effusion, cranial abdominal mass effect
   –CXR: globoid heart, less likely to help with dx

-abdominal ultrasound
-echocardiography
-cross-sectional imaging (CT/MRI)

Question 8

describe differential diagnoses for splenic mass

Answer 8

1. benign: hematoma, hemangioma
2. malignant: HSA vs others

ruptured splenic mass:
-double 2/3s rule is an okay estimate
-step 1: 2/3 malignant, 1/3 benign
-step 2: 2/3 of malignancies are HSA
-may be as high as 65-70% of all are HSA

incidentally noted splenic nodules: 70% benign

only way to know for sure: histopathology

bigger masses may be high % benign (not reliably though)
-higher mass to splenic volume ratio: if whole spleen is a mass, is more likely benign bc has been growing so long and hasn’t killed dog yet
-higher splenic weight as a % of bodyweight: same thought as above

Question 9

describe clinical staging of HSA

Answer 9

TNM

T: primary tumor
T0: no evidence of tumor
T1: tumor less than 5cm diameter and confined to primary site
T2: tumor 5cm or greater or RUPTURED, invading SQ tissues
T3: tumor invading adjacent structures, including muscle

regional lymph nodes: N
N0: no regional LN involvement
N1: regional LN involvement
N2: distant LN involvement

distant metastasis: M
M0: no evidence of distance metastasis
M1: distant metastasis

stages:
I: T0 ot T1, N0, M0
II: T1 or T2, N0 or N1, M0
III: T2 or T3, N0, N1, or N3, M1

splenic HSA: most have a ruptured mass at initial presentation (T2), making them at least stage II!

important staging distinction in cutaneous HSA: T1 v T2
-T1: isolated to dermis, not invading below basement membrane = stage 1 = good prognosis
-T2: invading into SQ = stage 2 = more guarded prognosis

Question 10

how do you stage HSA?

Answer 10

1. chest rads/CT
   -3-view chest rads or thoracic CT
   -CXR: can look diffuse interstitial/miliary, harder to interpret in the lungs of older dogs so may make sense to send out for review
2. abdominal ultrasound (or CT)
   -part of complete staging
   -key organs: spleen, liver (nodules in older dogs aren’t always metastasis), LNs, omentum and mesentery, kidney, retroperitoneum
3. echocardiography: up to 24% of splenic HSA have concurrent cardiac mass

Question 11

describe HSA treatment

Answer 11

1. surgery:
   -full abdominal explore at time of surgery and biopsy of abnormalities (also part of staging)
   -splenic massa: splenectomy
   -cutaneous: STS margins (2-3cm, 1 fascial plane deep)
   -cardiac: very rarely right auricle mass might be resectable
   –pericardectomy: to prevent tamponade, resulting from bleeding events, may prevent acute death but does not extend survival
2. radiation therapy: if nonsurgical
   -palliative protocols for cardiac HSA
   -impact relatively unknown
   -difficult to treat with high doses due to movement of heart
3. chemotherapy:
   -best outcome: surgery + chemo (exception is stage I cutaneous HSA)
   -agent of choice: doxorubicin IV q2-3 weeks 5 times
   -chemo alone: no benefit to splenic HSA, but doxorubicin extends survival time in cardiac HSA

Question 12

describe complementary and alternative therapies for HSA

Answer 12

1. yunan baiyao:
   -herbal remedy
   -mechanism: enhanced surface glycoprotein expression on on platelets, might be mildly cytotoxic to HSA cells
   -controversies regarding manufacturing: inclusion of pangolins in product, consistency of product
2. aminocaproic acid: prevents fibrinolysos
3. tranexamic acid: prevents fibrinolysis

might help with small bleeding events but aren’t likely to prevent/stop large bleeds

4. polysaccharopeptide (mostly FYI)
   -bioactive component of cariolus versicolor (turkey tail) mushroom
   -commercial product: I’m Yunity; antitumor activity in vitro
   -small double blind clinical trial showed very little toxicity, delayed progression of metastases, improved survival times
   -INTERPRET WITH CAUTION (small trial, very expensive product)

Question 13

describe follow-up for HSA

Answer 13

1. splenic HSA: AUS and CXR q2-3 months
2. cutaneous: q3m PE and re-staging (AUS/CXR)
   -patients with stage I UV-induced lesions: high risk for more lesions (regular PE very important), low risk for metastasis (so +/- on AUS/CXR)
   -high risk of local recurrence

Question 14

describe HSA prognosis

Answer 14

1. bleeding splenic mass:
   -stage 2:
   –surgery alone 2-3 months
   –surgery + chemo: 4-6 months

-stage 3: short (usually weeks), may elect euth prior to sx

2. cutaneous (completely excised)
   -stage 1 (not invasive into SQ): good prognosis (>2 years) but high recurrence rate/new lesion rate

stage 2 (invasive into SQ): good with aggressive tx (surgery + adjuvant chemo) up to 18 months

3. cardiac:
   -surgery (rare) + chemo: approx 6 months
   -chemo alone: 3-6 months
   RT: TBD

Question 15

describe feline HSA

Answer 15

1. most commonly skin/SQ and abdominal
2. skin/SQ behaves similar to other STS (soft tissue sarcoma)
3. spleen (and other abdominal sites): behave similar to dog splenic HSA