Miscellaneous Tumours Flashcards
What’s the prevalence of thymoma in cats and dogs?
- uncommon
- but it’s the 2nd most common tumour in the cranial mediastinum
- usually in older patients (9,10 years old)
What’s the most common type of thymoma in the cat?
cystic thymoma
What’s the metastatic rate of thymoma in general?
low
What’s the metastatic rate feline cystic thymoma?
up to 20%
What are some differentials for cranial mediastinal mass?
- lymphoma
- thymoma
- ectopic thyroid
- brachial cysts
- rarely, sarcoma or metastatic disease
Are thymomas benign of malignant?
they are considered carcinomas
What are the most common signs of thymoma?
- regurgitation
- vomiting
- anorexia
- weight loss
- cough
- dyspnea
- tachypnea
What are the most common paraneoplastic syndromes for thymoma in dogs? in cats?
Overall prevalence is up to 67% of dogs and cats.
Dogs:
- myasthenia gravis (40%)
- not as commonly found in cats
- up to 40% will have megaesophagus with concurrent aspiration pneumonia
Cats:
- exfoliative dermatitis
When can paraneoplastic signs be present for thymoma?
- at the time of diagnosis
- some time later in the course of disease progression
- after tumour removal
What % of dogs with thymoma will have a concurrent 2nd tumour?
up to 27%
How common is hypercalcemia in patients with thymoma?
34% of dogs, and it’s also common in cats
- ddx: lymphoma
How does thymoma cause hypercalcemia?
via PTHrP
What ultrasound appearance would make thymoma significantly more likely?
cystic, heterogenous echogenicity
What other cell types are commonly found in FNA of thymoma?
small mature lymphocytes
mast cells
How often is neoplastic cells present on thymoma FNAs?
only in 61% of the time
What’s an unique cytological features of thymoma?
Hassal’s corpuscles, but they are not usually seen with Wright’s Giemsa compare to biopsy samples
How does flow cytometry help with thymoma diagnosis?
> 10% of cells will be CD4/CD8 double positive
(vs <2% for lymphoma)
What’s the outcome of thymoma treated with surgery alone in dogs? in cats?
Dogs, MST = 635 - 790d (1.7-2.1y)
Cats, MST = 1825d (5y)
What’s the outcome of canine thymoma without surgery/ treatment?
76 days
What’s the outcome of dogs with thymoma treated with weekly hypofractionated RT?
RR = 50%
1y survival rate = 75%
What’s the general outcome of RT for dogs and cats with thymoma?
RR = 75% (11/20 PR, 4/20 CR)
MST: dogs = 248d (8m)
MST: cats = 720d (~2y)
What’s the role of chemotherapy in thymoma?
undefined
may end up targeting the non-neoplastic lymphocytes…
What’s the general outcome of thymoma?
Good if non-invasive/ amendable for surgery
What’s the mortality rate in dogs and cats undergoing surgical removal of the thymoma?
Dogs: 20-27%
Cats: 11-22%
What are some prognostic factors for thymoma?
- Amount of lymphocyte infiltration (higher = longer ST)
- dogs with Masaoka-koga stage I or II = significantly longer MST compared to >II
- age, invasiveness, and MC = NOT prognostic for ST
- in cats, cystic thymoma = better prognosis
Describe the Masaoka staging system.
Stage I: Tumor is grossly encapsulated and no capsular invasion is noted microscopically.
Stage II: Gross invasion occurs to surrounding fatty tissue or mediastinal pleura. Microscopic invasion of the capsule is noted.
Stage III: Gross invasion into neighboring organs (pericardium, great vessels, lungs)
Stage IVa: Pleural or pericardial dissemination
Stage IVb: Lymphatic or hematogenous metastasis
What’s the natural behavioral of TVT?
- develop within 2-6m of mating
- can be grow slowly and unpredictably for years, or
- grow invasively and become malignant and metastasize
What’s the metastatic rate of TVT?
5-17%
What’s a unique arrangement of TVT that’s used as a primer for PCR?
LINE-c-myc gene sequence
What are the 3 phases of TVT?
- progressive: grow for the first 3-6m
- stationary phase: last months to years!
- regression phase: usually starts within 3m, but rarely if the tumour is present for >9m –> need immunocompetent host
What does TVT do in the progressive phase to allow for growth?
mostly due to immunoavoidance
- down regulates MHC class I and II expression –> evade T cell cytotoxicity
- secretion TGF-beta –> inhibits MHC antigen expression and NK cell activity (inhibits IFN-gamma)
- can also target and damage dendritic cells
What’s a major determine factor for a switch into the regression phase?
IL-6 concentration
- IL-6 = pro-inflammatory
- acts synergestic with host IFN-gamma, and will overcome the tumour TGF-beta effects, and restores NK cell activity and MHC expression up to 40% of tumour cells
What other hose immune defense is available for TVT?
humoral immune response –> antibody production
What’s the treatment of choice for TVT?
chemotherapy
- vincristine single agent weekly for 3-6 treatments = 90-95% CR
- combination protocol not as good
- can use doxorubicin in vincristine resistant cases
What’s the outcome of TVT treated with RT?
can have up to 100% durable CR
What’s the outcome of TVT treated with surgery?
recurrence rate is 30-75%
What’s the overall general prognosis of TVT?
very good to excellent
What are the 2 most common primary cardiac tumour in the dog?
- hemangiosarcoma
- aortic body tumour (chemodectomas, paragangliomas)
What’s the most common cardiac tumour in the cat?
- Lymphoma (both primary and metastatic)
- aortic body tumour can occur, with hemangiosarcoma = rare
How common is cardiac tumour in dogs and cats?
rare
What’s the predominant location for malignant cardiac tumours in the dog?
Right auricle/ right atrium
What’s are clinical signs of cats with cardiac tumours?
- tachypnea
- dyspnea
- anorexia
- weight loss
- lethargy
- acute collapse = less common than dogs
How good is chest radiographs at identifying cardiac tumours?
Sensitivity = 47% (of cardiac hemangiosarcoma)
- but can often see the secondary changes such as cardiac tamponade and effusions
What’s the sensitivity/ specificity of diagnosing cardiac tumours with echocardiogram?
Specificity = 100%
Sensitivity = 82%
- higher for right atrium/auricle masses (99% spec, 82% sensitivity) vs
- heart base tumours (98% spec, 74% sensitivity)
How common is pericardial effusion in dogs with echo diagnosed cardiac tumours?
42%
(it’s 84% for those with hemangiosarcoma)
What’s the diagnostic yield of cytology of the pericardial effusion?
8%, it’s better (~20%) if the PCV is < 10%
How is cardiac troponin I used in diagnosis of cardiac tumours in dogs?
It can help with hemnagiosarcoma diagnosis.
- can use the pericardial effusion (>0.25ng/mL) or peripheral blood (2.45 ng/mL)
- can help with false-positive on echocardiogram
What’s the % of dogs with cardiac hemangiosarcoma having splenic involvement?
What’s the % of dogs with splenic hemangiosarcoma with cardiac involvment?
- 29% of cardiac hemangiosarcoma has splenic involvement,
- but only 8% of splenic hemangiosarcoma has cardiac involvement (older literature = 24%)
- 42% of cardiac hemangiosarcoma has metastasis elsewhere than spleen
What’s the benefit of pericardial window in the treatment of cardiac tumours?
- can improve survival time in aortic body tumours and mesothelioma
- didn’t show to improve outcome in dogs with hemangiosarcoma
What chemotherapy can be considered with cardiac tumours?
- doxorubicin based, mono or combination therapy for hemangiosarcoma
- Palladia for aortic body tumours in dogs (not proven in cats)
- feline lymphoma = CHOP/ COP
What’s the outcome of RT for aortic body tumours?
- in a small study (8 dogs) using 3D-CRT (weekly), all dogs have gradual reduction of tumour size
- SRT: (23 dogs) - MST = 404 days (1.1y), with 25% PR and 60% SD for median of 333d (10m)
- in the SRT study, arrhythmia, clinical signs, locoregional LN enlargement = reduced ST
What’s the outcome of Palladia for canine chemodectoma?
RR = 89%
MST = 478 days, which was not significantly different than dogs treated with additional therapy (521 days)
What’s the outcome of IMRT with adjuvant vinblastine and propranolol for canine right atrial tumours?
- MST = 326d (~10m)
- 1/7 (14%) CR, 4/7 (57%) PR, 2 (28%) SD
- weekly vinblastine (2.6 mg/m2 IV) and daily propranolol (0.5 mg/kg PO TID, increased to 1 mg/kg PO TID after 1 week).
What’s the outcome of surgery vs surgery + adjuvant doxorubicin for dogs with cardiac hemangiosarcoma?
Surgery only: MST = 16d to 4m
With doxorubicin post-op: MST = 175d (~6m)
What’s the outcome of doxorubicin alone for canine cardiac hemangiosarcoma?
Response rate = 41%
median PFS = 66 days
MST = 116-140d (3-4.5m)
What’s the outcome of canine aortic body tumour with pericardiectomy vs no pericardiectomy?
Pericardiectomy MST = 661 -730d (22-24m)
No pericardiectomy MST = 42-129d (1-4m)
What’s the outcome of cats with cardiac tumours?
generally poor
What’s the most common presenting sign of mesothelioma?
effusion (pericardial, thoracic, abdominal) due to impaired lymphatic drainage
Vomiting and urinary signs could be a symptoms of which type of tumour?
Sclerosing mesothelioma
- more so in males, German Shepherds
- thick fibrous linings
- restrictions around organs
What’s the sensitivity of detecting cardiac mesothelioma with echocardiogram for dogs with pericardial effusion?
5/15 dogs
What tests can be run with effusions to rule out malignancy?
fibronectin
- mesothelioma can be ruled out if fibronectin is not increased
What’s the MST of cardiac mesothelioma treated with pericardiectomy?
MST = 4-9m
if followed up with chemo, MST = 10-27m
Is there a difference in out in dogs with pericardial effusion due to mesothelioma treated with pericardial window vs subtotal pericardiectomy?
no, MST 3-4m
What’s a chemotherapy option for intracavity infusion due to mesothelioma?
intracavity chemo! but only penetrates 2-3mm
What are histiocytes?
They are dendritic or macrophage lineage
Which stem cells do histiocyte differentiate from?
CD34+
Define intraepithelial, interstitial, interdigitating, and migratory dendritic cells.
- Intrepithelial = Langerhans cells
- Interstitial = those in perivascular location. Ex. dermal DCs
- Interdigitating = found in LNs, spleen
- migratory = part of interdigitating DCs
Which cytokines/ growth factors can influence blood monocyte differentiation into macrophage vs dendritic cells?
Monocyte –> macrophage = M-CSF
Monocyte –> DC = granulocyte-macrophage-CSF and IL-4
Which cells are the most potent antigen presenting cells?
dendritic cells
In cutaneous and systemic histiocytosis, which type of dendric cells are predominately responsible?
interstitial DCs
In histiocytic sarcoma, which type of dendric cells are predominately responsible?
it’s due to the migratory potential of the interstitial DCs –> rapidly disseminate
Which IHCs are important for differentiating the different dendritic diseases?
- Iba-1: macrophages and dendritic cells
- CD163 & CD 204: class A scavenger receptors –> expressed on macrophages and normal tissues
- CD18: CD11/CD18 = beta-integrins (adhesion molecules), expression is highly regulated in normal macrophages and DCs
- CD11b = macrophages
- CD 11c = Langerhans cells and interstitial cells
- CD80/CD86: expressed on antigen presenting cells –> ligand for T cell co-stimulation
What is reactive histiocytosis?
these include the cutaneous histiocytosis and systemic histiocytosis
Describe the pathophysiology of cutaneous histiocytoma.
- usually solitary, pink, raised mass in the a young dog/ cranial portion of the body
- rapid onset (1-4 weeks), regresses in 1-2 months
- CD8+ infiltration thought to help with regression
- will express E-cadherin = unique to cutaneous histiocytoma (can be used to differentiate from reactive histiocytosis)
Describe the pathophysiology of cutaneous Langerhans cell histiocytosis
- very similar to cutaneous histiocytoma but involve multiple masses or diffuse skin involvement
- can also spread to LNs and internal organs
- spontaneous regression may happen in about 50% of dogs, may be delayed up to 10m
- prognosis is poor with diffuse presentation
- can try CCNU or Griseofulvin
- if solitary with LN mets, surgery can have good outcome (1-4 y)
What’s the typical signalment for dogs with cutaneous histiocytosis?
- tend to be young dogs
- Golden, Great Dane, Bouvier may be predisposed
- most dogs have previous derm issues
What’s the distribution pattern for cutaneous histiocytosis?
- restricted to skin, subcutis
- head, ear, nose, limbs, scrotum
- benign condition
Which IHC markers are helpful for cutaneous histiocytosis?
- E-cadherin negative (positive with cutaneous histiocytoma)
- Thy-4 and CD4 = activated interstitial dendritic cells
- CD1a, CD1b, CD11c, MHC II
What’s the treatment for cutaneous histiocytosis?
- spontaneous regression is still possible
- usually with prednisone (partial response in most dogs)/ immuno-suppressants
- long term maintenance may be required
How can one distinguish between cutaneous histiocytosis and systemic histiocytosis?
- the IHC markers are the same
- will have same distribution patterns for the peripheral lesions
- but, will also involve other sites like LN, internal organs, eyes, bone marrow, etc
Which breeds are over-represented in systemic histiocytosis?
- Bernese mountain dogs (may be familial)
- Golden, Rottie and Irish Wolfhound
What are some common clinical signs of systemic histiocytosis?
- depression
- weight loss/ anorexia
- conjunctivitis
- harsh respiration
What are some common CBC abnormalities for dogs with systemic histiocytosis?
- monocytosis
- lymphopenia
- anemia
occasionally see hypercalcemia
What’s the treatment for systemic histiocytosis?
- tend not to spontaneous regress
- steroids alone may not be enough
- immunosuppressants: azathioprine, cyclosporine A, leflunomide
What’s the prognosis of systemic histiocytosis?
- treatment can often have episodes of response then recrudescence
- euthanasia generally due to repeated relapses or failure to respond to tx
Which breeds are predisposed to histiocytic sarcoma?
- Bernese mountain dog
- Flat coated retriever
- Rottie, mini Schnauzer
- Corgis in Japan
Which gene mutations have been identified for dogs with histiocytic sarcoma?
- CDKN2A/B, RB1, PTEN
- PTPN11
What could be a predisposing factor for periarticular histiocytic sarcoma in Berners?
previous injury to the joints
What are some differences in the histiocytic sarcoma in Berners vs. flat-coated retrivers?
- location: Berners = systemic, Flat-coated = periarticular (7x more likely to have localized HS)
- age: Berners are younger than Flat-coated retrievers at diagnosis
- histological differences also reported
Which IHC can be used to differentiate between periarticular histiocytic sarcoma and synovial cell sarcoma?
- CD18, cytokeratin, smooth muscle actin
What are some useful markers for diagnosing histiocytic sarcoma?
CD204, IBA-1
There is a CADET histiocytic malignancy assay –> sensitivity = 78%, specificity = 98%
What CBC abnormalities are common in dogs with histiocytic sarcoma?
- anemia, often regenerative
- thrombocytopenia
- leukocytosis
it’s this 2nd most common cause of pancytopenia
What biochem abnormalities are common in dogs with histiocytic sarcoma?
- hypocholesteremia
- hypoalbuminemia
- increased liver values
- hypercalcemia has been reported
How does ferritin level play a role in diagnosis of histiocytic sarcoma?
- Hyperferritinemia is common in dogs with HS (89%)
- but not so good as a screening tool
What diagnostic test can be used to differentiate between neoplastic and non-neoplastic cause of hemophagocytosis?
based on the scatter plot of flow cytometry
What type of lung pattern can be noted on CXR for histiocytic sarcoma?
- diffuse/ infiltrative
- patchy consolidated area
- focal/ multifocal masses
Right middle lung lobe!
What’s the general outcome of histiocytic sarcoma?
- poor
- localized/ periarticular have significantly better MST (391d vs 128d [1y vs 4m])
- even metastatic PAHS can do well, but if no mets on presentation, MST = 980d (2.7y) vs 253d (8m)
What’s the outcome of histiocytic sarcoma treated with CCNU?
- RR = 46% in gross disease setting
- median remission duration = 85d (3m)
- if responded, MST = 175d (8m), if not response, MST = 60d (2m)
What’s the response rate of doxorubicin alternating with CCNU very 2 weeks?
RR = 58%, median time to progrsesion = 185d (6m)
What are some rescue protocols reported for histiocytic sarscoma?
- dacarbazine, RR = 18%, event-free survival = 70d (2m)
- Epirubicin, RR = 29%
What are some outcome of metronomic chemotherapy for histiocytic sarcoma?
Lomustine: 2 cases, PR
Chlorambucil: 2 cases, 1 PR 1 SD
What’s the role of RT in histiocytic saromca?
HS = radioresponsive
- mostly used for periarticular histiocytic sarcoma
- MST 182d (6m)
- with CCNU = 208d (7m)
What cytological features can increase suspicion of hemophagocytic histiocytic sarcoma?
- atypical macrophages in the spleen with phagocytosis
What’s the outcome of hemophagocytic histiocytic sarcoma?
there is no effective therapy - euthanasia in 1-2 days
What bloodwork abnormalities are common in hemophagocytic histiocytic sarcoma?
- regenerative anemia (94%)
- thrombocytopenia (88%)
- hypoalbuminemia (94%)
- hypocholesterolemia (69%)
What are the 3 distinct forms of feline histiocytic disease?
- feline progression histiocytosis
- feline histiocytic sarcoma
- pulmonary Langerhans cell histiocytosis
Describe feline histiocytic sarcoma.
- both dendritic and macrophage origin have been described
- solitary lesions = rare; mostly multifocal or disseminated
- bone marrow involvement is common
- no effective treatment; use of CCNU. masitinib, and RT has been reported
Describe feline progressive histiocytosis.
- dendritic cell
- multifocal to coalescing skin nodules
- predilection to head, feet, and legs
- indolent, but progressive –> eventually go to LNs, lungs, and abdominal viscera
- doesn’t respond to steroids
- may spontaneously regress
- may respond to CCNU, masitinib
Describe pulmonary Langerhans cell histiocytosis.
Small case series of 3 cats
- all presented from respiratory compromise/ distress
- CXR: diffuse, severe broncho interstitial lung pattern with diffuse/ miliary nodules in all lung lobes
- needed extensive IHC for diagnosis (necropsy)
- all had metastasis to pancreas, kidneys, liver, LNs
What % of splenic tumours = hemangiosarcoma in dogs?
45-51%;
Which breeds are overrepresented for hemangiosarcoma?
Goldens, Labs, German Shepherds
-large breeds
Which mutation is commonly found in canine hemangiosarcoma?
PTEN
- also dysregulation of angiogenic pathways
What’s the likelihood of splenic hemangiosarcoma for dogs presenting with nontraumatic hemoabdomen?
63-70%
On necropsy, what % of canine splenic tumours are malignant and what % are hemangiosarcoma?
50% are malignant
50-74% are hemangiosarcoma
What’s the most common cardiac tumour in dogs?
hemangiosarcoma (the 2nd most common site in dogs = heart)
Which tumour is the most common secondary tumour to the brain in dogs?
hemangiosarcoma
Where are the most common sites for feline hemangiosarcoma?
skin, and visceral (spleen, liver, and intestines)
What are some common metastatic sites for feline hemangiosarcoma?
liver, omentum, lungs
Which IHC can be used for hemangiosarcoma?
- factor VIII, (von Willebrand’s factor)
- CD31/ platelet endothelial cell-adhesion molecule
How often is thrombocytopenia in dogs with visceral hemangiosarcoma?
75-97%
What coagulation parameters can be abnormal in dogs with visceral hemangiosarcoma?
seen in 50% of affected patients
- secondary coagulation parameters
- prolonged PT, PTT
- increased fibrin degradation product, fibrinogen, D-dimers
DIC!
What paraneoplastic syndrome can be noted on CBC of dogs with hemangiosarcoma?
- neutrophilia!
can also be due to tumour necrosis
What bio chem abnormalities can be found in cats with visceral hemangiosarcoma?
50% will have elevated AST
Describe the staging scheme for canine hemangiosarcoma.
What are some biomarkers used for diagnosis of hemangiosarcoma?
- cardiac tropnin 1
- VEGF, urine bFGF
- thymidine kinase
- serum collagen XXVII –> can be used for monitoring!
How often are multiple and/or dark red/ black lesions in the liver actually been benign in dogs with visceral hemangiosarcoima?
- 50%!
- almost 60% of histologically benign lesions were obtained from grossly abnormal livers
What are some single agent chemo that has shown effectiveness in hemangiosarcoma?
1 = doxorubicin
- ifosfamide
- epirubicin
- liposomal-encapsulated DOX
What’s the outcome of metronomic chemotherapy for hemangiosarcoma?
- can be used in post-op or as maintenance after MTD
- likely no survival advantage
- one study had thalidomide and that significantly increased the ST
How responsive is immunotherapy for canine hemangiosarcoma?
- mixed killed bacteria vaccine + doxorubicin had some improvement (no significant difference)
- allergenic cell lysate vaccine didn’t show difference
- adjuvant chemo + liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) had MST of 9.1m - but not commercially available
What’s the role of RT in hemangiosarcoma?
- can palliate cardiac hemangiosarcoma –> reduces the incidence of pericardial effusion
- they are radioresponsive, but not shown to have a significant improvement
What’s the outcome of RT for retroperitoneal hemangiosasrcoma?
~ 400d (1y)
How effective is tyrosine kinase inhibitors for hemangiosarcoma?
imatinib, masitinib, dasatinib:
- they have demonstrated in vitro effectiveness, but the concentration needed for in vivo benefit would be too high (too toxic)
Toceranib
- tried in combi with doxorubicin and had no difference
Which targeted therapy for hemangiosarcoma shown improvement in ST?
eBAT
MST = 8.5m with 70% survival rate @ 6m
What are some alternative therapies for hemangiosarcoma and how effective are they?
- Yunnan Baiyao –> maybe in vitro effectiveness, no in vivo changes noted
- Polysaccharopeptide (PSP) –> modest improvement in MST
What’s the overall prognosis of dogs with splenic hemangiosarcoma treated with splenectomy only?
19-86d ( <3m)
What’s the MST for splenic hemangiosarcoma treated with splenectomy and chemo based on stage?
- Stage 1: MST = 239-355d (8-12m)
- Stage 2: MST 120-148d (4-5m)
What’s the general outcome of splenic hemangiosarcoma treated with splenectomy and chemo?
with doxorubicin based chemo, MST = 5-7m
What’s the MST of primary renal hemangiosarcoma treated with nephrectomy +/- chemo?
MST ~ 9m
What’s the MST of primary retroperitoneal hemangiosarcoma treated with nephrectomy +/- chemo?
MST = 37.5d
What’s the outcome of true cutaneous canine hemangiosarcoma treated with surgery?
overall MST = 780-987d ; 1570d (2-2.7y; 4.3y)
- ventral tumour location MST = 1085d (~3y)
- solar induced MST = 1549d (4.2y)
What’s the outcome of cutaneous canine hemangiosarcoma with SQ infiltration or SQ/IM HSA treated with surgery?
- Cutaneous with SQ invasion, MST = 539d (~1.5y)
- SQ/ IM MST = 9m - 3y (with chemo)
What’s the outcome for cardiac hemangiosarcoma?
- no treatment = 2 weeks
- with surgery, MST = 1-3m
- surgery + chemo MST = 2.7 - 4m
What’s the responsive rate and MST of doxorubicin for cardiac hemangiosarcoma in dogs?
RR = 41%
MST = 4m
What’s the outcome of stage III splenic hemangiosarcoma treated with doxorubicin and deracoxib?
MST = 149d, similar to MST of 150d for all stages combined (5m)
What’s the outcome of stage III splenic hemangiosarcoma treated with the DAV protocol or the VAC protocol?
-DAV: RR = 47%, MST - 101d (3.5m)
- VAC: MST = 195d (6.5m), similar to stage I/II (MST = 189d)
What’s the outcome of feline visceral hemangiosarcoma?
poor, due to high metastatic rate
MST = 77-197d (2-6.5m)
What’s the outcome of feline cutaneous hemangiosarcoma?
MST 9m-4y
What’s the outcome of feline cutaneous with SQ invovlement hemangiosarcoma?
- with surgery, 50-94% will be incompletely removed
- 50-80% recurrence
