Tumor Specific AB Part II 25% Flashcards
Endocrine, mammary, female repro, LSA, misc
1
Q
SX for Adrenocortical carcinoma?
A
SX
- MST 230-778d, 8 -26 mo carcinoma
- MST similar for adenoma ~ 600d
- prognosis excellent if survive 4 weeks pos top
- 20% intra op/post op death
1
Q
What % of adrenal carcinomas invade vasculature? Met rate?
A
- 20% invasion
- 50% metastatic rate
2
Q
MST SRT adrenocortical tumors?
A
~ 35 mo
3
Q
When using mitotane in leu of sx for adrenocortical tumor what needs to be considered?
A
- dose is higher than using for PDH
- using as true cytotoxic agent
- mean ST 14-16 mo
- trilostane not cytotoxic but has been compared for to mito for ADH with no difference in ST
- can use PRE OP to reduce thromboembolic risk
4
Q
Pheochromocytoma cell of origin? Vascular invasion rate? Met Rate?
A
- Chromaffin cells of the medulla
- 85% invasion
- 40% metastasis
5
Q
IHC to distinguish pheo from adrenal carcinoma?
A
chromogranin A
6
Q
Urine metanephrine [ ] with pheo?
A
> 2x ULN
Sens 62%, spec 97%
7
Q
Prognostic factors for pheos?
A
size, metastasis, invasion
- MST ~ 1-3 years
8
Q
Prognostic factors adrenal tumors general?
A
presence and size of tumor thrombus, if nephrectomy is needed, need for transfusion, tumor type (pheo worse), tumor size >5cm
- laparoscopic procedures described for small tumors with great outcome
9
Q
Histologic scoring system for cortisol secreting adrenocortical carcinoma?
A
Utrecht score = Ki67+, >/= 33% clear/vacuolated cytoplasm, presence of necrosis
Score < 6 - survival not reached
>/= 6 MST 50 mo
>/= 11 MST 14 mo
10
Q
Complication rate of adrenal FNA?
A
8% - similar to FNA of other major organ
1% mortality
11
Q
Molecular markers associated with survival adrenocortical carcinoma?
A
Steroidogenic factor 1, PPTG1, TOP2A - decreased survival
12
Q
SRT pheos
A
- 8 dogs with CS
- all had resolution of CS and reduced urine metanephrin
- MST 26 mo
- all pre-treated with phenoxybenzamine
13
Q
What is phenoxybenzamine?
A
Alpha adrenergic antagonist, irreversible
- used preop/RT for pheos
- some papers say improves survival others say no difference
14
Q
Are most adrenal tumors benign or malignant?
A
Most benign incidental; Ferret 2/3 benign; Cat mostly LSA
15
Q
Prognostic factors for cats w primary hyperaldosteronism (Conns syndrome) undergoing adrenalectomy?
A
Prognostic factor anesthesia time >4 hr
16
Q
Most common thyroid panel with thyroid carcinoma?
A
euthyroid > hypothyroid > hyperthyroid
17
Q
How should thyroid masses be sampled?
A
US guided FNA only - low diagnostics yield almost all thyroid masses carcinoma
- can also BX with US guidance (8/9 minimal hemorrhage in new paper)
18
Q
Common finding after bilateral thyroidectomy?
A
hypocalcemia - parathyroids often removed too
19
Q
TX for invasive thyroid carcinomas that cannot undergo sx?
A
RT:
- pRT MST 24 mo (pulm mets at dx not prognostic)
- dRT MST 24 mo
- hypothyroidism after both ~50%
Radioactive iodine:
- 35% RR but CB in 76%
-MST 30-34 mo
- good for metastatic lesions
20
Q
Prognosis thyroid carcinoma with resection?
A
unilateral, mobile MST 36 mo, 1 yr 72%
21
Q
Prognostic variables for thyroid carcinoma?
A
Tumor diameter and volume, bilateral location, metastatic disease, VASCULAR INVASION
22
Q
RR gross thyroid carcinoma to Palladia?
A
80%-90%
- PFI first tx 206d, 6 mo
- prior tx (sx, rt, MTD chemo) PFI 1015d, 33 mo
23
Q
True or false: Hyperthyroid cats typically have carcinoma?
A
false; nodular hyperplasia
24
% of pets with primary hyperparathyroidism with thyroid mass?
90% - most common adenoma, dx d/t hypercalcemia
25
Breed disposition parathyroid tumor?
Keeshond - autosomal dominant inheritance
26
Prognosis parathyroid tumors?
Excellent with surgery or ablation
- rare metastasis
- often hypocalcemia post op tx if <8-9 mg/dL or clinical
- rare persistent hypercalemia, look for ectopic tissue
27
Over represented breeds for functional thyroid carcinoma?
- Labs, goldens
- CS pu/pd, wt loss
- MST 1,072D, 35 mo with surgery, chemo does not help
28
RR thyroid carcinoma SRT?
70%, 81% CB
- OST 1 year
- minimal AE
- mets not prognostic
29
Complication rate thyroidectomy when invasion present?
- intra op ~7%
- post op 16%
- 10% local recurrence
- OST 621d ~2 yr
30
MST parathyroid CARCINOMA with surgery?
~2 years
- 1 yr 84%m 2 yr 65%, 3 yr 51%
- 92% hypercalcemia resolved
- 3 euth d/t hypocalcemia post op
31
Insulinoma cell of origin? Hallmark?
Pancreatic Beta cell
- paired normal/increased blood insulin with low BG (<60 mg/dL) --> confirms DX
- insulin [ ] alone not useful to detect mets vs no mets
32
Hormones produced by insulinoma?
insulin, glycogen, somatostatin, pancreatic polypeptide, GH, IGF1, gastrin
33
CS of insulinoma?
neuroglyopenia = weakness, collapse, disorientation, behavior changes, seizures, tremors, shaking, anxiety, hunger
34
US for insulinoma
not helpful <50% identification of pancreatic masses when present, low specificity and sensitivity for mets
35
Best TX for insulinoma? Complications?
- sx best
- persistent hypoglycemia, pancreatitis, hyperglycemia 33% may be persistent DM, GI (risk higher if preop CS, lack of liver mets, and high TP)
36
Medical TX hypoglycemia for insulinoma?
-mostly aimed at stabilizing BG:
- steroids (insulin antagonism, gluconeogenic, glycogenolytic)
- dextrose/glucagon (ER setting)
- diet (high fat/protein/CHO, small, frequent meals)
- diazoxide (non-diuretic benzodthiadiasine that suppresses insulin)
- octreotide (somatosatin inhibitor, stops insulin secretion)
37
Response rate to diazoxide insulinoma? Octreotide?
70% - not cytotoxic, BG control
50% - same, become refractory
38
Streptozoocin MOA, use, AE?
- DNA alkylation (mono functional alkylation) and ROS generation --> beta cell necrosis (selective)
- insulinoma but DOES NOT increase length of euglycemia following sx
- liver injury, diabetes mellitus (may result in euthanasia), GI, nephrotoxic (give with diuresis)
39
Insulinoma prognosis?
- partial pancreatectomy alone 12-24 mo vs ~ 8 mo if medical
- stage dependent:
50% with stage I euglycemic at 14 mo vs <20% stage II or III
- sx + medical management with pred post op MST 46 mo
- 50% with mets dead at 6 mo
40
What is unique about ferret insulinoma vs. dog?
- Rarely mets but 75% have multi nodules so after sx many still hypoglycemic
- 25% have adrenocorticol tumors also, Pytalism
- sx MST 15-22months, medical 1-9months
41
What are the IHC for insulinoma?
ChromograninA+, insulin+
42
What is the met rate and location for insulinoma in dogs?
50% to liver, rare to lung
43
What other diseases can ferrets have with adrenocortical tumors?
25% insulinoma, 10% cardiomyopathy
44
How is streptozocin transported into cells?
GLUT2
45
When can laparoscopic pancreatectomy be considered?
small tumor in the distal aspect of the pancreatic lobe
46
Report glycemic control with pred and palladia after partial pancreatectomy?
24 mo
47
median OST in dogs with metastatic or recurrence insulinoma treated with Palladia+palliative therapy (pred)?
- 399d (13 mo) to 656d (21 mo) vs 2 mo with pred alone
- PFI 561d (18 mo)
- RR 67%
48
What is the best imaging modality for insulinoma?
3phase CT - most notable on late arterial phase
49
Insulinoma MRI appearance?
T2 hyperintesine
T1 isointense
50
What can be useful intraop to assess for complete insulinoma excision?
BG
51
Cat insulinoma prognosis?
- 863d = 28 mo (similar to dog)
- 1 yr 75%, 2 yr 51%, 3 yr 10%
- 18/20 immediately euglycemic
52
Gastrinoma Zollinger-Ellison syndrome.
triad of non-beta cell neuroendocrine tumor in pancreas, hypergastrinemia, and GI ulceration
53
Gastroninoma prognosis?
- 85% met at time of diagnosis
- sx debulking can still be considered to reduce gastrin secretory capacity and improve medical therapy (PPIs)
- Octreodtie has been used in 3 dogs
- ST 1 week to 26 mo dogs & cats
54
Omeprazole for gastrinoma
Omeprazole will increase circulating gastrin levels (but decrease HCl secretion due to inhibition of PP)
55
Tumor associated with necrolytic migratory erythema?
glucagonoma - v. rare arise fro alpha cells, mets common, prognosis poor
56
Risk factors mammary tumors in dogs?
- Dogs spayed prior to first estrus – 0.05% risk
- Dogs spayed prior to second estrus – 8% risk
- Dogs spayed after 2nd estrus – 26% risk
- Progestins – 2.3x higher risk
- Obesity – increased risk
- Breeds – Shih tzus, English springer spaniels
- Age – older dogs higher risk
57
Risk factors mammary tumors in cats?
- Sig assoc w increasing age after 7-9 yrs
- Breed – Siamese
- Hormonal – cats OHE prior to 6 mo have reduced risk by 91%, prior to 12 mo reduced risk by 86%, and prior to 24 mo reduced risk by 11%
- Cats w oral progestins – increased risk (usually of benign tumors)
58
Cat mammary tumor expression?
COX2, EGFR, low HR, RON
59
English Springer Spaniel mammary carcinoma mutation?
Germline polymorphisms in BRCA 1 & 2
+/- Shih Tzu
60
Which tumors are more likely to retain estrogen and progesterone receptor expression, benign or malignant?
Benign - loss is correlated with increasing size and undifferentiated tumors
61
Staging k9 mammary tumors?
62
Most common mesenchymal tumor of the canine mammary gland?
OSA
63
What is Paget-like syndrome?
mammary carcinoma present within the MG and carcinoma cells also in the epidermis of the nipple - seen in dogs and women
64
Criteria for grading mammary tumors is based on?
Elston and Ellis used mostly: tubule formation, nuclear pleomorphism, and mitosis/10 hpf
- applies only to epithelial origin
65
Clinical prognostic factors for mammary tumors in dogs?
- size >5cm
- LN involvement: multiple studies have shown as v. important prognostic indicator
- Stage
66
Recommended surgical dose for canine mammary tumors?
- lupectomy (50/50 benign/malignant)
- ~60% develop tumors in contralateral chain, 77% complication rate with radical mastectomy
## Footnote
recent review 2023 says that not lit as made a definitive conclusion about surgery dose
67
Is there benefit to spay at time of mastectomy for dogs with mammary tumors?
Unknown - conflicting literature
- likely benefit if HR positive
- if doing should spay first then remove tumor to pv seeding
- ALSO unknown if spayed or intact animals are more likely to have malignant phenotype
68
Do margins matter for mammary gland tumors in dogs?
Yes
- MST 2-15.5 mo for incomplete vs 22.8-30 mo for complete (grade dependent)
69
Situations to consider chemotherapy for dog mammary tumors?
- >3cm, neg LN, carcinoma
- any size, pos LN, carcinoma
- inflammatory carcinoma
- OSA
70
Which medical treatment has been shown to be beneficial for mammary carcinoma?
- NSAIDs with or without adjuvant chemotherapy for high grade III, advanced stage, and inflammatory carcinomas
- desmospressin preop improves survival, newer paper shows this is not true, also not true in cats
71
What % of cats have more than 1 mammary tumor?
60%
72
Staging for feline mammary tumors
Differs from dog with tumor size and nodal involvement
73
% of feline mammary tumors that are malignant?
85-95%
74
Histopathologic/clinical prognostic indicators feline mammary tumors?
- grade,
- lymphovascular invasion
- size (<2cm w/ rad mastectomy MST 3+ yr, >2cm MST 6 mo)
- LN mets
75
Prognosis feline mammary tumors based on grading?
I: 31-36 mo
II: 14-18 mo
III: 6-8 mo
76
Recommended surgical dose for cat mammary gland tumor?
bilateral mastectomy
77
Blue dye lymph node mapping is best for cats with mammary gland tumors?
False - Heinz body anemia and methemoglobinemia
| idk if this is correct
## Footnote
lots of papers saying with repeated dosing maybe cause HBHA but with one does no cats had complications
78
Chemotherapy for cats with mammary gland tumors?
- generally recommended
- 40-50% RR to DOX/cytoxan in gross disease setting
- DOX based protocols in microscopic disease setting have shown improvement in survival in multiple retrospectives (30-60 mo)
- Newer retrospective showed no Dif between radical mastectomy (RM) alone vs RM + DOX vs RM + MC (DFI 270d)
79
Situations to consider chemotherapy for cats mammary gland tumors?
- <2cm-3, neg LN, carcinoma, vascular invasion/high grade
- >3cm, neg LN, carcinoma
- any size, pos LN, carcinoma
80
Which tumors express PD-L1?
melanoma, OSA, mammary, prostatic adenocarcinoma, TCC, HSA
81
Pathways involved in mammary carcinogenesis?
- WNT/B-catenin, hippo
- B-catenin higher in tumors than normal tissue (strong neg correlation)
- YAP/TAZ higher in triple - human/cats
- Dasatinib and Statins may inhibit those with WNT signaling
82
TLR4 mRNA is expressed in which k9 mammary carcinoma subtypes?
complex carcinoma grade I, ductal carcinoma grade II, and anaplastic carcinoma
83
PDL-1 and CTLA-4 k9 mammary carcinoma associated with?
- metastasis
- blockade could be therapeutic
- dogs with malignant metastatic MGT MST 16 mo vs malignant non metastasizing MST 4 years
## Footnote
ctla4 is an immune checkpoint - CTLA4 on t cells down regulates immune response
PDL1 on cancer cells - down regulates immune response
84
Heat shock proteins are associated with tumorigenesis in which cancer type?
k9 mammary gland carcinomas (HSP110)
85
CD204 is an M2 type tumor associated macrophage is higher in grade I vs grade III mammary carcinomas?
grade III - associated with other aggressive features (vascular invasion, HR negative)
86
Mammary epethiliosis (ME) is premalignant dysplasia present in what % of canine mammary tumors?
52% - associated with older dogs, malignant tumors, higher stage, LN mets, higher grade, and short OST
87
Complication rate canine mastectomy?
- 16.9% of these ~35% need to be hospitalized
- complications highest in dogs with chain mastectomy who did not receive ABX
- other factors ass. with complication: increasing body weight, undergoing bilateral mastectomy, and post op ABX
- concurrent OHC reduced complication rate
88
Which autoAbs have been shown to be elevated in canine mammary cancer patient serum?
TYMS, HAPLN1, IGFBP5
89
Chemokine and chemokine receptor expression associated with metastasis in canine mammary carcinoma?
- chemokine: CCL5, independently prognostic of ST
- receptors: CXCR3, 4, 7, CCR9
- CXCR4 independently prognostic of ST
| cxc= chemokine receptor
## Footnote
The CXCR4/CXCL12 axis plays a critical role in therapeutic resistance by (i) directly promoting cancer cell survival, invasion, and cancer stem (or tumor-initiating) cell phenotype; - ras/pi3k/jakstat (ii) recruiting myeloid bone marrow-derived cells to indirectly facilitate tumor recurrence and metastasis; and (iii) promoting angiogenesis directly or in a paracrine manner
90
Ki67 cut off associated with higher grade mammary carcinoma?
33.3%
- also had higher p53 expression
- ER+ tumors associated with low ki67
91
What may be a cause for resistance in inflammatory mammary carcinomas?
P-Gp and BCRP/ABG2 - one or other expressed in 87%
92
What multi-agent protocol has been shown to improve survival in dogs with inflammatory mammary carcinoma?
- NSAID, palladia, and cytoxan combo resulted in longer OST compared to NSAID alone 96 vs 37d
- ability to have surgery improved survival
- absence of disease progression at day 3 associated with longer survival
93
Which medical treatment is best for metastatic feline mammary carcinoma?
- No difference in ST between MTD chemo (various), Palladia, and metronomic
- overall TTP 23d, tumor specific survival 44d
- CS at time of dx neg indicator (14d vs 128d)
- toxicity highest with MTD ~66% > Palladia 30% > MC 20%
94
Neutrophil to lymphocyte ratio associated with worse outcome feline mammary carcinoma?
2.46
95
CDK 4/6 inhibitor with anti-tumor effects on mammary carcinoma?
Palbociclib
96
Which ovarian tumors are found in young dogs?
teratomas <6 yr
most others >6yr
97
Types of ovarian tumors?
Epithelial
Sex cord stromal
Germ cell
Mesenchymal - HSA, leiomyoma/sarcoma
98
Ovarian carcinoma: metastatic rate, presentation, IHC?
- 48% - LN, momentum, liver, carcinomatosis
- unilateral > bilateral; cysts/hyperplasia in contralateral common
- Cytokeratin AE1/3, vimentin, desmin
99
Sex cord stromal tumors: types, metastatic rate, presentation, IHC?
- Granulosa-theca cell tumors (GCTC), Sertoli-Leydig (SLT) tumors, {thecomas, luteomas-benign}
- <20%
- can secrete steroid hormones; uni>bilateral with contralateral hyperplasia
- vimentin, S-100, INHa
100
Germ cell tumors: types, metastatic rate, presentation, IHC?
- dysgerminomas, teratomas, malignant teratomas
- 10-30% (up to 50% for malignant teratomas)
- uterine abnormalities (pyo, cystic endometrial hyperplasia), uni>bilateral contralateral cyst/hyperplasia
- vimentin positive
- PLAP, CK7, desmin, S-100, CK AEi/3, INHa negative
101
Which ovarian tumor type is most common in cats?
sex cord stromal cell tumors - granulosa-theca cell tumors that are up to 50% malignant
102
CS of estrogen producing ovarian tumor?
vulvar enlargement, sanguineous vulvar discharge, persistent estrus, alopecia, aplastic pancytopenia
103
CS of progesterone producing ovarian tumor?
cystic endometrial hyperplasia and pyometra
104
What is considered high risk with ovarian tumors?
Seeding- caution with FNA and SX (tx OHE)
105
Most common uterine tumor - dog? Cat?
- leiomyoma - cured with SX
- adenocarcinoma - guarded prognosis, highly metastatic
106
German Shepherd dog with multiple uterine tumor, bilateral cystic kidney masses, and cutaneous nodules. What is mutated?
Birt-Hogg-Dube gene
107
Most common vaginal/vulvar tumor in small animals?
Leiomyoma - hormone dependent, intact dogs, OHE prevents recurrence
108
Ovarian cancer defect people?
BRCA 1/2
109
What 2 cancers cause hyperestrogenism that can lead to bone marrow hypoplasia?
Male sertoli cell tumors & female granulosa cell tumor
110
What part of the vulva/vagina do leiomyomas arise?
Vestibule of vulva
111
Most common repro tumor in rabbits? TX? Prognosis?
- Uterine adenocarcinoma
- Treatment of choice consists of OHE with periodic follow-up to monitor for mets
- If no mets – prognosis good with >80% OHE rabbits reported to be alive 6 mo following surgery
- Chemotherapy – unknown
- LSA second most common
112
What can improve outcome in dogs with malignant ovarian tumor (adenocarcinoma) carcinomatosis?
- OVH and intracavitary chemotherapy
- DFI following OVH 171-584d (6-19 mo) then received intracavitary carbo or cisplatin --> additional DFI 155- 368d (5-12 mo)
- GCT also included who did not have effusion OST 822-1840d (27 mo - 5 yr)
- OST carcinoma 20-28 mo
- good prognosis
- JAHAA 2021 paper
- other VCO 2020 paper found MST ~30 mo for various tumor types with 1/2 of dogs with mets are diagnosis living >1 year (slow growing tumors)
113
Complications associated with vaginectomy/vulvoveginectomy for vaginal/vulvar tumors?
- incontinence may resolve (~50%)
- malignant tumor MST 20 mo
114
Paraneoplastic syndrome associated with clitoral tumors? Cytologic appearance? Histo patterns?
- Hypercalcemia
- Appear neuroendocrine like AGASACA
- Tubular, solid, rosette
115
Feline ocular SCC predilection?
eyelid, 3rd eyelid, and medial canthus of white cats
116
Predisposing factors to ocular SCC?
Solar, lack of adnexal pigmentation, chronic ocular surface irriation
117
Predisposed breeds to vascular endothelial tumors of the lateral limbus?
Bassett hounds, springer spaniels, beagles
118
Most common tumor of k9 conjunctiva?
melanoma
- others: HSA, MCT, adenocarcinoma
- all seem to have good prognosis with complete excision but may rarely recur
119
% of eyelid and conjunctival tumors which are benign?
80% - sebaceous or meibomian gland adenomas, epitheliumas, papilolomas, and melanomas
- even malignant tumors rarely spread and have low recurrence rates (10-15%)
120
Corneal SCC predispotions?
Brachycephalic breeds, chronic keratitis, immunosuppressive therapy
121
Indications for removal of eyelid tumors?
- any in cat, rapid growth ,ocular surface irritation, impaired eyelid function, owner concern, appearance
122
Alternative treatment to surgery for eyelid tumors?
cryosurgery
123
How is benign canine anterior uveal melanoma differentiated from malignant?
MC
benign - <2-4 MF/10 hpf
malignant >4
- still overall metastatic rate low ~4%
- difference in prognosis varies older literature suggests <6 mo newer suggest not much different form benign tumors
124
When should surgery be considered for canine anterior uveal tumors?
- glaucoma, inflammation, lack of vision
- enucleation not shown to improve outcome
125
Feline diffuse iris melanoma is typically a benign, slowly progressive disease. However, malignant behavior has been rarely reported with metastasis as high as 66%. What has been associated with an increased risk of metastasis?
extrascleral extension, necrosis, MI >7/10 hpf, choroidal invasion, increased E-cadherin and MelanA
126
When to enucleate and prognosis feline diffuse iris melanoma?
- ideal before malignant transformation- not clinically realistic so typically happens if iridal changes progress to the entire surface being involved or if the pupil is distorted
Enucleation at degree of invasion:
- confined to the stroma/trabecula - cured
- invasion to ciliary body - 5 yr
- scleral invasion - 1.5 yr
127
Subtypes of post traumatic ocular sarcomas in cats?
spindle cell sarcoma - most common
round cell sarcoma - LSA CD79a b cell
osteosarcoma/chondrosarcoma
- no evidence for tx beyond enucleation
128
Dogs with blue eyes at risk for?
spindle cell sarcomas of the uvea aka Uveal Scwannoma
- low metastatic rate
129
Rate of metastatic tumors to the eye? Location?
5%, highly vascularized Uveal tract
130
What percentage of patients with ocular lymphoma DO NOT have systemic disease?
60%
- no systemic involvement MST 769d 25 mo vs with systemic 103d
131
Most common tumor of the orbit?
Canine meningioma, feline secondary tumors
- others: feline posttraumatic sarcomas, feline SCC, and canine cordial melanoma, OSA, MCT, HS, sarcomas
- Orbital rhabdomyosarcoma in young dogs
- Most locally and distantly aggressive- 90% malignant; except meningiomas
- Can attempt RT/SX with 50% disease free at 1 year
132
Image of RT port films of dog receiving tx to distal nose. What are the side effects?
dental disease, oronasal fistula, ocular, ect
133
RT histogram showed higher dose to the left eye than left lens. SE?
OS blind, cataract, etc
134
What chemo drugs have ocular side effects?
Cyclophosphamide, cisplatin, doxorubicin, 5-FU, vincristine
135
ST ocular LSA vs conjunctival?
PFST and OST – 178 d for all animals w ocular LSA
PFST and OST – 221 and 549 d for conjunctival LSA
- most end up developing neuro signs
136
T or F: conjunctival squamous papillomas are not virally associated?
T
137
Most common iridociliary tumor dog?
Melanocytic neopalsms > epithelial tumors (adenomas/carcinomas)
138
Incidence of canine LSA?
- 7-24% of all neoplasms
- 83% of all hematopoietic malignancy
- 80% of LSA multi centric, nodal, DLBCL
- 60-80% B Cell
- 10-38% T cell
- 22% mixed
- 5% null
139
Chromosome alterations associated with developing LSA?
gain of 13 and 31
loss of 14
- trisomy of chromosome 13 may result in improved outcomes
140
Immunophenotype GI LSA? Breed?
T-cell with epitheliotropism; Boxer, Shar Pei
141
% of mediastinal LSA that are hyerCA?
10-40%; T cell
142
Hepatosplenic LSA immunophenotype?
gamma-delta T cell
143
Breed predispositions based on immunophenotype?
B = Doberman Pinscher, cocker spaniel
T = Boxers
Equal = Goldens
144
% of dogs with multi centric LSA with thoracic abnormalities? Abdominal?
- 60-75% intrathoacic abnormalities
- 30% diffuse infiltrate
- 70% lymphadenopathy sternal, tracheobronchial
- 20% cranial mediastinal lymphadenopahty - prognostic
- 50% abdominal changes (LN, liver, spleen); authors only stage abd if GI signs since no difference btw stage III/IV disease
145
Nervous system LSA immunophenotype based on location?
B cell: meningeal, perivascular, periventricular
T cell: peripheral nerves
146
% of dogs with multicentric LSA with ocular involvement?
~30-50%
37% specifically written in Withrow
147
Most common paraneoplastic syndrome with LSA?
anemia; normo, normo, non regen
148
MOA of LSA paraneoplastic HyperCa?
- PTHrp most common
- Humoral factors: IL-1, TNF-a, TGF-b, vit D analagous
149
DDX for peripheral lymphadenopathy?
bacteria, virus, protozoa (Toxo, leishmania), rickettsial (salmon poising, ehrlichia), fungal (blasto, histo), immune mediated (pemphigus, SLE, IMPA)
150
% of LSA with monoclonogammopathy?
6%
151
T cell markers
CD3 - panT
CD4 - helper
CD8 - cytotoxic
152
B cell markers
CD79a, CD20, CD21
* some TZL express CD21* (cd 5 cd21 cd45-)
153
PARR amplifies which regions?
- variable T cell receptor
- Immunoglobulin receptor B cell
- AG binding portion is what varies in size and sequence with nucleotides added between V,D,J
154
Sn, FP of PARR?
Sn 70-90%
FP 5%
155
PARR false negative DDX
- clonal segment not detect with PCR primer used, mutation of primer site hasn't occurred, background non-neoplastic lymphs, NK cell LSA, too low DNA of clinical population
156
PARR false positive DDX
ehrlichia, leishmania
157
DLBCL location, histo architecture, cell size, immunophenotype
- multicentric
- diffuse
- large
- CD1, CD20, CD21, CD45, CD79A, PAX5, MCHII positive, low CD18
158
Peripheral T cell LSA location, histo architecture, cell size, immunophenotype
- multicentric
- diffuse
- variable small to large
- CD3, CD45, CD5 positive, +/- CD4, CD8, CD18 high, TCRa/b
159
MZL location, histo architecture, cell size, immunophenotype
- node, spleen, extra nodal mucosa
- nodular, follicular
- intermediate
- CD1, CD20, CD21. CD45. CD79A, MCDII positive, CD18 intermediate
- nodal aggressive PFI 5 mo, PST 8.5 mo vs splenic CURED with splenectomy
160
TZL location, histo architecture, cell size, immunophenotype
- multicentric
- nodular, paracortical progressing to diffuse
- small- intermediate
- CD45-, CD3+, CD21+,CD4 +/-, CD8 +/-
161
Flow marker to help detect precursor cells?
CD34
162
Mantle cell LSA (MCL) location, histo architecture, cell size, immunophenotype
- splenic white pulp
- nodular/follicular
- small to intermediate
- CD20, CD21, CD45, CD79A, MHCII positive
163
Follicular LSA location, histo architecture, cell size, immunophenotype
- nodes solitary or multiple
- nodular, follicular
- mixed mostly small
- CD20, CD21, CD45. CD79A, MHCII positive
164
Discrepancy between circulating LSA cells and bone marrow involvement on BM examination?
28% circulating
57% with BMA
- BMA not necessary if the client is willing to treat regardless of stage
165
Prognosis LSA no tx?
4-6 weeks
166
CHOP remission rate, MST, 2 yr survival
- 80-95%
- 10-12 mo B, 6-9 mo T
- 20-25%
167
Fundamental goals of chemotherapy for LSA?
- induce durable CR >6 mo first remission
- re-induce remission when relapse (reinduction)
- induce remissions when cancer fails to respond to induction or reinduction using other drugs (rescue)
168
Is maintenance therapy beneficial for LSA?
no
169
If CHOP not pursued, which protocol has similar remission?
DOX, Tanovea alternating
170
CR rate and MST Dox alone tx naive?
- 50-75%
- 6-8 mo
- one study combined with cytoxan given first 3 days of each cycle, improved numeric PFI BUT NOT STATISTICALLY
-nT-cell 50% vs B cell 100%- poss due to increased ABCG2 expression on T cell
171
CCNU alone response duration tx naive?
one study reports only 40 days
172
MST pred alone LSA?
- 1-2 mo (50d)
- T cells 90 d vs B cell 39d
- substage a 64 d vs b 36d
- 7% 6 mo survival
173
Why does starting pred prior to chemotherapy result in negative outcomes?
development of MDR mutation
## Footnote
Clinical resistance to prednisone was observed after a median of 68 days
Resistance was not consistently associated with changes in ABCB1
Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma
2020 paper from WSU Jvet pharm/therapeutic
174
What is the increase in plasma PK/AUC estimated for MDR mutant patients receiving DOX?
25%
## Footnote
dec by 25% for +/- and 50% for +/+
175
MDR1 breed and frequency of mutations (mut/norm)
70%: Collie
50%: Aussies, Long-haired Whippet
30%: McNab, Silken Windhound
25%: Chinook
15%: English Shepherd, Shelties
10%: GSD, Herding Breed X
176
MDR1 mut/mut breed and frequency
Collie 35%
Aussies 10%
mini Aussie 3%
GSD 2%
Shelties, herding 1
from AG
177
MDR1 mut/mut dose recommandation?
40-50% reduction; start non MDRI drug (cytoxan) while pending per Withrow
178
Overall response rate to rescue chemotherapy LSA? Median duration?
- 40-90%
- 1.5-2.5 mo
179
Rituximab MOA
- recombinant chimeric murine/human AB against CD20 Ag (hydrophobic transmembrane protein located on normal pre-B and mature B lymphs)
- Binds --> triggers host cytotoxic immune response against CD20+ cells
- Standard of care in people R-CHOP
- DOES NOT WORK IN DOGS d/t lack of external recognition of CD20- AG on canine LSA cells
- Blontuvetmab (B cell) and tramtuvetmayn (T cell) caninized MoAb that were once approved but didn't work and no longer in use
- CD19 moAB B cell similar no efficacy
180
When should splenectomy be performed for LSA?
- not in other sites with complete staging
- indolent disease
- hemoabdomen
- if indolent MST >1 year to many years
181
Indications for RT LSA?
- curative intent for Stage I and solitary extra nodal disease (nasal, cutaneous, spinal)
- Palliation of local dz (bone involvement, huge mandibular, etc)
- Total body for bone marrow
- Whole or staged half RT after chemo induced remission
182
Colorectal LSA - phenotype, CS, PFS, OST with chemo?
- B-cell, high grade
- most substage b with hematochezia
- PFS and OST >3 years with CHOP suggesting more favorable prognosis (Desmas 2017)
183
RR and duration CCNU +/- Lspar for epitheliotropic LSA?
- 40-80%
- 3-6 mo
184
Negative prognostic factors for LSA?
- high/intermediate grade
- T-cell (except TZL)
- Stage V (sig bone marrow infiltrate; weak association)
- substage
- male (more like T cell; weak)
- anatomic location (CNS, GI, leukemia, etc)
- anemia at dx
- steroid pre treatment
- cranial mediastinal lymphadenopathy
- increased: LDH, thymidine kinase, haptoglobin, VEGF, glutathione S transferase, CRP
- decreased: cobalamin, albumin
- hyperCA
185
Favorable prognostic factors for LSA?
- indolent/low grade
- B cell
- Stage I/II (weak)
- substage a
- neutered female (weak)
- location (solitary, B cell multi centric)
- grade III/IV neutropenia with tx (weak)
186
B cell expression associated with worse outcome?
low B5 and low MHCII
187
3 primary CLL subtypes
1) T CLL = most common (2/3), CD3+/CD8+ granular lyphs
2) B CLL = CD21+, second most common
3) Atypical CLL = various expression
188
B vs T ALL expression
B ALL = CD21+, CD3-, CD4-, CD8-, most common
T ALL = CD3+, CD4-, CD8-, CD21-
variable CD34 = stem cell
189
Paraneoplastic syndromes with CLL?
- hyerglobulinemic 80% B-CLL
- monoclonal gammopathy (IgM or IgA) 68% B-CLL
- hypercalcemia 13% B-CLLL
- IMHA
- Pure red cell aplasia
190
Lymphocyte disruption normal dog blood
| did you mean to say distribution?
80% T cell CD4 helper>CD8 cytotoxic
15% B cell
rest NK or double - lymphs
191
DDX lymphocytosis in dogs?
infectious disease (chronic ehrlichia), post vaccine response in young dogs, IL-2 administration, transient physiologic or epinephrine induced
192
Minimal % of bone marrow affected to call leukemia
30%
193
TX CLL, RR and ST
chlorambucil 0.2 mg/kg or 6 mg/m2 PO daily q 7-14d then can be reduced to 0.1 mg/kg or 3 mg/m2 daily
or 2 mg/m2 EOD
RR 70% have normalization of lymphs - mostly going to SD
ST 1-3 years indolent but uniformly fatal
194
What is Richter's syndrome?
- CLL evolves to aggressive phenotype characterized by pleomorphic large lymphocytes with multi centric presentation
- occurs in 2% TCLL and 10% BCLL
- can occur btw 2-16 mo
- MST CHOP 41 days
195
MST between CLL subtypes and prognostic indicators?
TCLL 930d (31 mo)
BCLL 480d (16 mo)
atypical 22d
- neg young age and anemia
196
MST ALL
guarder 16-130d reported with CHOP
- 29% (CR/PR) rate to vinc and pred
197
Dog with Cushing's has LSA - does not including pred in TX effect outcome?
No
198
Environmental risk factors for LSA
- Residency in industrial areas
- Use of chemicals by owners
- Illegal waste dumping
199
What proteins/molecules are upregulated in large B cell LSA?
- JAK1/2 – STAT3 and p-STAT3 – higher in DLBCL
- Higher nuclear exp
- Mitogen activated kinase ERK1/2 upregulated
200
Signaling pathways associated w B cell LSA in dogs and humans?
- NF-kB canonical pathway activation
- NF-kB family of inducible transcription factors
- Re1A(p65), Re1B, c-Re1, NFkB1 (p50), and NFkB2 (p52)
201
Common mutation in TSG in LSA in people and in dogs?
- P53 mutations in p53 noted in human tumors and assoc w poor prognosis; mutated in 16% of dogs w LSA at diagnosis and 84% devoid mutation
- P16 CpG islands methylated in dogs w LSA
202
Which morph can be confused with lymphoid hyperplasia on cytology- pick 2?
T zone, follicular
could be any that are nodular, not diffuse
203
Most common LSA phenotype in Boxers?
T CD4+ large cell LSA in Boxers, aggressive clinical course (MST 159 d)
204
Prognostic factors for CD21+ LSA?
- Low MHC II – higher risk of death, relapse
- Large cell – higher risk of death
- Age – higher risk of death in younger dogs
205
CCNU as a first line treatment for canine LSA?
- CCNU med dosage of 67 mg/m2 q21d until 5 doses or dz prog
- Pred tapered over first mo
- 35% CR 18% PR
- Med duration of response 39.5d, MST 111.2 d
- Female sex and higher total CCNU dose sig assoc w longer DFI
- Neutropenia DLT
206
DTIC response rate in relapsed LSA?
- ORR 35%
- PFS 43 days
- Toxicity – thrombocytopenia 7-14 d post
207
Immunophenotype for LSA treated w single agent doxorubicin?
- Single dose – 100% response for B cell, 50% response for T cell
- B-cell CR 85%, T-cell CR 16%
- Single-agent doxo for B cell LSA CR 78% , Total remission time – 80.5 d , MST 169.5 d
- Affected by stage, substage
208
Doxo + pred + L-spar as first line therapy for B-cell LSA ?
- ORR 84%
- Median PFS 147 d, OST 182 d
- 1-yr survival 23%
209
Half body irradiation w CHOP ?
(Lurie et al 2009)
- CHOP + 6 Gy HBI (2 weeks in btwn doses of RT)
- Median first remission – 410d
- MST 684 d
(newer papers with similar outcomes)
210
What is a unique about rabbit LSA?
Cutaneous LSA more common in Europe than N. America
211
What is the most common equine intestinal neoplasia?
LSA then adenoCA then smooth muscle
212
What is the most common bovine neoplasia?
LSA
213
What are the 2 different forms of LSA in cows and how do they develop it?
Sporadic-in young(1-3yr) juvenile, thymic, cutaneous;
Viral-enzootic BLV retrovirsus seen in older cow, cows persistent leukocytosis & minority develop LSA
214
What kind of LSA do ferrets develop and where?
T cell, abdominal MC
215
What type of LSA is common in both rabbits and horses?
T cell rich B cell LSA
216
What is the diagnostic accuracy of US to detect hepatic and splenic LSA infiltration>
- 23x more likely to be B cell if leopard pattern
- splenomegaly also associated
- US normal liver associated with NOT having lsa
- is specific but NOT sensitive for both
217
Sn, Sp, accuracy, and PPV US detection of LSA in spleen?
| this is if you already KNOW the patient has lsa and confirming st4
~ 70% sn
~ 90% sp
~80% acc
~ 95% PPV
~75% NPV
218
Sn, Sp, accuracy, and PPV US detection of LSA in Liver?
~ 15% sn
~ 90% sp
~55% acc
~ 60% PPV
~55% NPV
219
Anemia characteristics differentiation between dogs with LSA (multi centric or GI) vs IBD?
- anemia more common with LSA 53 vs 22%
- Eccentrocytes more common with LSA
- >3 RBC morphologic anomalies with LSA (71% sn, 20% sp)
NOT GOOD AT DIFFERENTIATING
## Footnote
careful bc echinocytes = hsa
220
Coagulation parameter sig associated with decreased PFS if elevated prior to tx in LSA?
- D-dimers >0.5 ug/L
- 54 vs 104d
- tx was etoposide and F14152?
221
Is ki67 a good marker for LSA?
No - wide confidence intervals between IHC and FC
- variability in predicting outcome in various studies
222
Diffuse small cell B cell LSA OST?
- 140d
- considered aggressive small cell disease
- required histo for DX same flow as DLBCL
223
RR cytoxan/pred as first line treatment for DLBCL?
ORR 84%
- 9%CR
- 62% PR
- 12% SD
- 15% PD
- 250 mg/m2 q7d
- some dogs heavily pre-treated with pred - all SD
224
PFS L-CHOP vs MOPP for T cell or hypercalcemic LSAs?
L-CHOP 133d
MOPP 97d
- No sig dif
225
Mitoxantrone and DTIC rescue protocol and response rate?
- Mito 5 mg/m2 IV over 10 min then DTIC 600 mg/m2 IV over 5 hours q3 week
- ORR 34% for 97 days TTP
- more likely to respond if prev. achieved CR with CHOP
- 18% Gr IV neutropenia, 5% hospitalized
- minimal GI toxicity
226
Bleomycin + cytosar rescue protocol and response rate?
- Bleo SQ day 1-8, cytosar SQ day 1-5 of 21 days cycle
- ORR 36% for 15 days TTP
- myelosuppression grade II/IV in ~25%
227
What % of LSA has PDL1 expression?
50% - potential target, not associated with PFS
228
OST high vs low CD44 expression LSA?
high 5 mo
low 9-10 mo
229
miRNA markers that may differentiate DLBCL?
Let-7f (97% from control)
230
Doxins are generally considered low risk breeds for LSA; Although, a new study out of Japan showed they may be at risk for which anatomic location?
GI
- young dogs <4 yr
- B cell 70% +/- Mott differentiation
231
List 6 genes associated with DLBCL specific survival
IL2RB, BCL6, TXK, C2, CDKN2B, ITK
232
Which serum biomarker may be used to monitor response to chemo for LSA?
serum thymidine kinase 1 activity
- sn 76%, spec 100% for detecting non fully responders
- 5 fold increase in activity at 4 week interval predicted relapse at next 4 week interval Sn 50%, spec 94%
- increase >2.7 fold predict relapse at next 4 week interval sn 61%, spec 88%
233
Neutrophi:lymph ratio is not shown to be predictive of LSA survival in dogs receiving chop, but what parameter is?
neutrophilia at DX
234
Is there a difference in RR, PFST, and OST in CHOP vs CMOP?
No
But
- CHOP: 97% RR, PFS 208d (7 mo), OST 348d (11 mo)
- CMOP: 100% RR, PFS 165d (5 mo), OST 234d (8 mo)
- not statistically sig
- 20% of AE to mito
235
Do elderly dog have a worse response to chemotherapy LSA?
No >14 yr had improved survival with chemo compared to pred
236
Outcomes of dogs with nodal, non TZL, CD8+ vs CD4-CD8- LSA?
- both aggressive clinical course MST ~5-6 mo
- CD8+ associated with skin lesions
- CD4-/CD8- associated with mediastinal mass or hypercalcemia
- large cell size associated with survival 2 mo large vs 8.5 mo small
237
Is serum clusterin a good marker for LSA?
no
238
For multi centric T-cell LSA addition of which chemo have resulted in improved outcome at induction?
- with CCNU 70% RR vs non CCNU based tx 30%
- ORR 80% at induction
- Dogs receiving procarbazine at induction associated with improved survival
- other factors associated with improved response: neuts <8.7l, MC<10/5hpf
- PFS 105d - 3.5 mths
- Lack of CD3 and pretx with pred assocaited with poor PFS
- Lack of CD3, anemia, and monocytpenia ass with poor OST
- MST 136d - 4.5 mth
239
What are B symptoms of LSA?
fever, weight loss, and night sweats (in dogs unexplained tachypnea at night)
- B symptoms may be more prognostic than substage b
- PFS 95 d vs 330d
240
What degree of weight changes has been associated with decreased PFS in LSA?
5%
- PFS decrease 129d vs increase 226 vs 256d stable
- initial HIGH body weight associated with worse PFS and OST
241
Best on response-based CHOP protocols, which factor is associated with survival?
response to treatment is mot important factor
- RBCHOP1 responders at week 3 received typical CHOP
- RBCHOP2 responded after DOX with SD initially received 4 consecutive doses of DOX then vinc/cytoxan
- RBCHOP3 were non responders and received recue
only RBCHOP3 had worse PFS 34 d and OST 80d
242
Cure rate allogenic vs autologous bone marrow transplant B cell LSA?
allogenic 89%
autoglous 33-40%
243
Is 12 week CHOP an acceptable alternative to 19 week?
no
PFS 141 d (4 mo) vs 245d (8 mo)
OST 229d (9 mo) vs 347d (11.5 mo)
244
Cell block method is where FNA samples are concentrated, fixed, and embedded in paraffin for histological processing/staining. How does this method compare to typical cyto for LSA?
- 65% diagnostic vs 95% cytology
- can use IHC to improve accuracy of B cell to 96% but only 17% for TCELL
- agreement overall 86% if you combine probably LSA and LSA
245
Does dose intensity matter for CHOP and T-cell LSA?
No
246
Clinical benefit rate of melphalan in LSA rescue setting?
19.4 mg/m2 - high dose protocol
31.6% CB for 14-34 days
247
TMZ alone vs TMZ with DOX RR, TTP, MST, and toxicity in rescue setting
TMZ: 32%, 15d TTP, MST 40 d, 46% tox
DOX/TMZ: 60%, 19d TTP, MST 24d, 63% tax
- no statistically sig differences so TMZ alone recommended by authors d/t decreased toxicity
248
Nodal small cell B cell LSA is thought to be an aggressive subtype. What is associated with poor OS in this disease?
- increasing age, substageB, high B-cell CD25, low B-cell CD21, low MHC class II
- low ki67 <11% associated with improved survival on uni
249
What factor has been associated with improved overall survival in dogs with mediastinal LSA?
- absence of pleural effusion
- TX with CHOP opposed to other therapies (MOPP, Lspar pred, pred alone) mst 6 mths
- 1 case was B cell
250
MST primary intestinal LSA in dogs? Best chemotherapy?
- 64 days
- no difference between CHOP or CCNU first line
251
miRNA profile intestinal LSA not seen with IBD?
down regulated tumor suppressing: miR-194, 192, 141, 203
up regulated oncogenic: miR106a
252
RR continuous L-spar administration dogs with presumed GI LSA?
- Weekly L-spar median 7 doses (up to 30)
- no hypersensitvity
- 56% RR on AUS, 94% CB
- not on pred
- PFS 50d OST 147d - 5mth
253
What has a worse ST epitheliotropic or non epitheliotropic LSA?
epitheliotropic 141d ~5 mth vs non 364d - 12 mth
- presence of circulating cancer cell (sezary), thrombocytopenia <91k and initial response to therapy associated with prog
254
TZL parasite association
demodex in adults
- in goldens hypthyroidism, omega 3 supplentation associated
255
Laboratory findings associated with renal LSA dogs?
- azotemia 86%m erythrocytosis 51%
- bilateral but hypoechoic subcapsular ring less common
- PFS 10d, OST 21d
- usually T cell CD3/CD8+
- case report diagnosed using PARR and flow of urine
256
ORR Tanovea tx naive? phenotype?
ORR 87% (52% CR, 35% PR)
- 97% B cell, 50% T Cell
- PFI 122d - 4 mth
- T cell and steroid pre neg prog indicator
- 3/63 pulmonary fibrosis, grade V
- GI most common AE
- okay to dose reduce 0.82 mg/kg showed no diff btw 1 mg/kg in another study
257
Can you combine L-spar and Tanovea in the relapse setting?
Yes
- safe and efficacious
- given first 2 tx
- 67% ORR, 41% CR
- PFS 63d, 144d if CR~ 5 MTH
258
What has been shown to be a positive prog indicator in dogs with T LSA receiving LOPP?
# of cycles - OST (suggests favorable response to tx since staying on therapy)
hypercalcemia - PFS
- PFS 118d (~4 mo)
- OST ~6-7 mo
- other study did not ID hypercalcemia as favorable
- RR 97%, PFS 176d (5.8 mo)
- other study 2018 Morgan et al had crazy ST: PFS 282d (9 mo) OST 13 mo
- Boxers did worse
259
What is theory behind T cells responding more favorably to alkylating agents?
- contain low levels of AGT (O6-alkylguanine-DNA alkyltransferase ) and MGMT (o7-methylguanine-DNA methyltransferase). who mediate reactions caused by alkylation by removing the lesion and keeping guanine intact
- T cell do not have the repair mechanism that fixes alkylated guanine or methylation
- Alkylating agents are resistant to ABC transporter protein - favorable for relapsed disease or highly resistant dz
- t cells will readily export doxorubicin via the ABC transporter
260
Which drug is most likely to cause GI toxicity in LOPP?
Vinc
261
MVPP vs MOPP relapsed LSA outcomes?
MVPP (vinblast): ORR 25%, PFS 15d - less toxicity
- MV day 0 & 7, procarb/pred 0-14
MOPP: ORR 65%, PFS 63d
262
DMAC protocol. Response rates relapsed LSA?
Day 1
- actinomycin D 0.75 mg/mg2 IV
- cytosar 300 mg/m2 SQ or IV
- DexSP 1 mg/kg IV or PO
Day 8
- DexSP 1 mg/kg IV/PO
- Melphalan 20 mg/m2 PO
- ORR 35%
- high toxicity 6 hospitalized 5 stopped
263
PPC protocol? RR?
procarb 50 mg/m2 PO q24 + pred 30 g/m2 tapered to 10 mg/m2 q24 over 3 weeks + cytoxan 12.5-15. mg/m2 PO q24
- 50 dogs relapsed or did not tolerate MTD
- ORR 70%, 46% CR, 24% PR
- minimal SE
- PFI if CB 87d (3 mo) CR 115d (4mth), PR 61d, SD 31d
264
At which location and phenotype is currently most strongly associated with FeLV?
mediastinal/thymic, T cell
- also more common with peripheral nodal non-Hodgkins B cell as opposed to any other location
- common with LEUKEMIAS
265
FIV risk of LSA?
5 fold risk compared to FIV -
- B cell phenotype more common
- indirect d/t immunosuppression
266
Which other virus has been associated with a poor prognosis for feline LSA but not a risk factor?
herpes virus 1
267
Helicobacter has been associated with?
gastric mucosa associated lymphoid tissue in cats but not direct to LSA
268
T/F: LSA is the most common malignancy through the cat GI tract?
T; adenocarcinoma most common in the colon
269
Characteristics low grade GI LSA cat?
- 50-80% of all GI cases
- indolent
- mucosa, epitheliotropic, T cell CD3+, >80% small cell
- TX: chlorambucil/pred
- >80% RR, MST 1.5-3 years
- usually response to rescue (alkylating vs vinb) for additional 9-29 mo
270
Characteristics high grade GI LSA cat?
- ~20% GI cases
- acute
- mass, >90% intermediate to large lymphs, Cell CD70a+
- CHOP/COP
- 50-60% RR, 30% CR
- MST 3-10 mo (response based)
271
Characteristics LGL cat? Prognosis
-~10% GI cases
- Acute
- mass
- cytotoxic T cell (CD3+/CD8+/CD79a-) or NK cell (CD3-/CD79a-); often CD103+ and granzyme B+
- CHOP/COP
- ~30% RR
- MST 21-90d
- MST sig shorter for substage b, circulating neoplastic cells, lack of chemo, lack of response
- 7.3% survived 6 or more mo
- MST CHOP 60d, CCNU 90d **CCNU MAY BE BETTER**
272
Does GI perforation result from robust chemotherapy response in cats?
No
- GI perf reported in 17% of HG GI LSA tx with chemo along but occurred after the acute post chemo period and more likely represent PD
273
RT for GI LSA
- 11 cats (6 SC, 4 LC, 1 LGL) received rescue 8 Gy x 2 abdominal RT. MST 7 mo
- 8 cats w/ LC following CHOP 10 Gy x 1.5 abdomen 3 died in 3 weeks, 5 durable remission
- well tolerated, GI stricture, improved ST, chemo more effective
274
Characteristics Hodgkin's like LSA cat?
- solitary or regional ln
- T cell rich B cell LSA, nodlar or diffuse small to large lymphs with REED-STERNBERG cells. back ground of normal lymphs
- indolent
## Footnote
when you see lymphoma, but there are also scattered chunky histiocyte-looking cells that are actually binucleate lymphocytes with a single huge nucleolus in each nucleus. Looks like eye balls looking at you. :)
These are called "Reed-Sternberg cells" - from cytopath resident
275
T/F: hypercalcemia is uncommon with feline mediastinal lsa?
T
276
Which breed is predisposed to mediastinal LSA FeLV/FIV-?
Siamese; also male and young <3 years
277
Prognosis mediastinal LSA tx CHOP/COP?
- FeLV -: RR 95% MST 1 year up to 3 years if CR achieved
- FeLV+, young: MST 2-3 mo
278
Protein aberrations with extra nodal LSA in cats?
low alb and high B globulins when compared to control population
279
Sn of PARR feline LSA?
80%
280
% of cats with nasal LSA that have local extension or distant mets at necropsy?
20%
281
Cat Nasal LSA characteristics?
- 9-10 yrs
-FeLV/FIV neg
- 75% B cell
- Siamese
75% intermediate to high grade, epithiotropism
282
Cat nasal LSA RR to RT alone?
- CR 75-95%
- MST 1.5-3 years
- No CR MST 4.5 mo
- dose affects response >32Gy recommended
283
Cat nasal LSA RR to chemo alone?
- CR 75%
- MST 2 yr
284
Cat Renal LSA characteristics?
- ~ 9 yr
- FeLV -/ up to 50% FIV + in one study
- high grade B cell
- often have GI involvment
285
Cat MST renal LSA CHOP/COP?
4-7 mo
pred alone 50 d
286
Cat CNS LSA characteristics?
- young 4-10 yr
- 17-50% FeLV +
- ~60-80% multicentric
- diffuse brain, extra and intradural spine
- <50% RR to chemo, MST 1-4 mo
287
Forms of cutaneous LSA in cats
- most epitheliotropic T cell
- cutaneous lymphocytosis
- response to CCNu reported, sx for solitary lesion, generally indolent course, little info
288
FeLV proteins
gp70, gp27
289
Behavior of SQ or deeper structure LSA in cats?
- SQ considered aggressive, may be injection related, go on to develop distant, 75% die d/t LSA, MST ~3-5 mo with surgery
- tarsal SQ DFI with amp alone ~16 mo (3 cats), chemo and RT ~6 mo
290
Characteristics & Prognosis laryngeal LSA?
- 48% B cell
- 100% RR to chemo +/- SX (65% CR, 35% PR)
- PSF/OST 909d (30 mo); older reports say 5-9 mo
- response to tx and pretax with steroids ass. with longer PFI and survival
291
ALL vs CLL diagnosis BMA in cats? Prognosis?
15% - CLL, 90% RR chlorambucil for DFI 6 mo
30% - ALL, most T cell, poor 27% RR to CHOP/COP
292
Cats w/ LSA receiving vinblastine other than vincristine will experience?
less GI SE and similar response
293
Overall response rate for Elspar in cats w LSA ?
- ORR 30%
- Ammonia and aspartic acid increased from baseline at day 2 and 7
- Asparagine decreased at day 2
294
Biopsy risks for GI LSA in cats ?
- Full thickness GI sx
- No difference even w albumin <2.5
- No evidence leakage
- Post-op complications – anorexia/decreased appetite, hyperthermia, panc, constipation
- NOT at higher risk for dehiscence
295
MST and CR with intracavitary COP in cats w LSA ?
- CR 76%
- MST 388 d (13mth)w 54.1% alive at 1yr and 46.9% alive at 2yr
- various forms (laryngeal, mediastinal, etc)
296
Which of the following is true of bovine leukemia virus?
30% develop persistent lymphocytosis, NOT associated with juvenile LSA, less than 5 % get LSA
297
Bull dog CLL
- B-cell
- Lower MHC II, CD25
- splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM
- Polyclonal
298
What form of CLL is there circulating increased lymphocytes but no BM involved?
Tcell LGL, blast arise from spleen
| CD11d+ CD8+ CD34-
299
Is epirubicin an appropriate alternative to DOX in CHOP?
Yes
- CR 96%, TTP 7 mo, OST 11.5 mo
- Tcell and substageb do worse
300
RR cytoxan rescue following chlorambucil cat low grade GI LSA?
- 90% CR
- DFI 239 d (~8 mo)
- OST 1,065 d (35 mo)
- achieving a CR associated with survival
301
Peak [ ] and half life oral chlorambucil cats SCGI LSA?
peak 15 mins, 1/2 1.8 hour
- secondary small peak 4 hours
- no accumulation btw doses
302
MST surgical resection intermediate to large GI LSA masses in cats?
- gastric, large intestine, and small included
- 4 cats died in hosp
- MST 185d (6 mo)
- LI had better outcome MST 675d (22 mo) >Gastric 3 mo> SI 2 mo
- complete resection + indicator
- went onto to various chemo - not ass. with outcome
303
Serum amyloid A (SAA) correlates with LSA stage in cats?
No but is higher in non-nasal vs nasal forms
- not ass. with outcome
- low hct neg prognosis
304
RR and ST Pegylated L-spar sole therapy cat high grade LSA?
- ORR 74% -82%
- 38% CR
- DFI 70d, OST 79d
- pred did not affect survival
- when followed by COP 92% CR, if CR DFI 841d (28 mo)
- OST 181d (6 mo)
- Gastric LSA did better than SI
305
Protocol developed in FeLV endemic area (Brasil) that showed survival benefit in cats?
LOPH- CCNU, Vinc, pred, DOX
- 90% FeLV + with mediastinal or multicentric forms
- 81% CR, 14% PR, 4 % PD
- tumor spc. MST 214d (7 mo) for mediastinal not reached for multicentric
306
Feline intermed-large GI LSA tx with CCNU and RT, protocol and outcome?
8 GY in two 4 Gy fx 21 days apart + CCNu 40 mg/m2 q21d
- 50% ORR
- 3 cats euth d/t PD or toxicity prior to 2nd tx
- 3 live >244d
- PFS 77d
- bottom lined as similar to chop, tolerated, and cost effective
307
MOPP rescue cat LSA RR?
- 70% for 166d (~5-6 mo)
- 18.4% AE low grade neutropenia/GI
- ~30% of responders DF at 6 mo, ~15% at 1 yr
308
What % of cats with SCGI LSA develop LCGI LSA?
- 7-14%
- time btw dx 543d (18 mo)
-MST 20 mo from SC dx, 55d from LC dx
- HCT, alb, and total protein sig decreased when cats developed LC LSA and may be markers of transformation
309
CCNU, methotrexate, and cytosar protocol for relapsed high grade cat LSA, RR and outcomes?
CCNU 45 mg/m2 PO days 1
methotrexate 0.5-0.6 mg/kg IV d14 or 21
cytosar 300 mg/m2 SQ 2 weeks post methotrexate
- 46% RR
- grade III myelosuppression
- OFI 61d
310
DMAC RR relapsed cat LSA?
- 26% CB
- TTP 14d, OST 17d
- GR IV neutropenia and thrombocytopenia
311
Cat nasal LSA tx with pRT (35 GY) alone vs pRT followed by chemo (CHOP/COP)
- pRT + chemo had sig longer PFS (677d (22 mo) vs 104d (4 mo)) and OST (983d (32 mo) vs 263d (9 mo)) than those in pRT group
- cats in pRT alone group went on to receive chemo at relapse and had poorer outcomes than those immediately after
- suggests we should be treating simultaneously but older studies have long ST (up to 3 yrs) with RT alone
312
What are negative prognostic factors for cats with nasal LSA tx with SRT?
- cribriform lysis 121d (4 mo) vs 876d (30 mo) w/o
- intracalvarial involvment 100d (3 mo) vs 438d (14 mo) w/o
- no acute SE, ~50% developed late KCS, alopecia, and leukotrichia
- 75% chronic rhinitis
- PFS 225d (7.5 mo)
- MST 1 year
313
Failure patterns and frequency of cats with nasal LSA tx with RT alone?
- Local 10%
- local regional 4%
- Local & local regional 6%
- SYSTEMIC ~17%
- systemic and local ~12%
- prophylactic nodal RT protective
- TTP 2.7 yr
- MST 2.5 yr
- 50% relapsed in 6 mo of tx
314
Which prostaglandin has shown to be unregulated in B and T cell LSA compared to reactive LN in vitro?
EP4
315
Immunophenotype of aggressive T cell leukemia in young English Bull Dogs?
small to intermediate cell
CD45+, CD4-, CD8-, CD5+, CD3+, low MHCII
- liver/spleen commonly involved, LN NOT
- OST w/ chemo 83d, w/o 1 week
- other breeds with similar outcomes but low #
316
Which is more common, primary or metastatic cardiac tumors?
literature conflicting 84% primary, 16-86% secondary
- HSA> aortic body tumors most common
- Cat LSA
317
Breeds at risk for cardiac HSA? Aortic body tumors?
HSA - Golden, GSD
ABT - brachycephalic bulldogs, bostons, boxer 2nd to chronic hypoxia
318
Sn of x-rays for daignosis of cardiac HSA?
47%
319
Sn and sp of detecting cardiac mass with pericardial effusion via echo?
Sn 82%, sp 100%
- higher if R auricular 82% sn, 99% sp
- lower if heart base 74% sn, 98% sp
PPV 100% NPV 75%
320
What is the most important factors leading to false neg when detecting cardiac mass via echo?
location (extra pericardial, non cavitary pericardial, auricular) and size
R atrial detection rate 95% r auricular 60%
321
What % of dogs with cardiac tumors have pericardial effusion?
42% - most common with HSA 82% of cases
322
Is cytology of pericardial effusion helpful in dx cardiac tumors?
No - 8% dx
- improves if hct <10% to 20% dx rate
323
Cardiac troponin I (cTnI) is higher in dogs with effusion secondary to HSA, what is the cut off value?
0.25 ng/mL - marker of myocardial ischemia and necrosis
324
% of dogs with suspected primary HSA with mets?
- spleen 29%
- liver, mesentery, etc 42%
- 8.7-24% of dogs with splenic HSA have concurrent R atrial mass
325
Which tumors types does subtotal pericardectomy improve outcome?
Heartbase mass and mesothelioma regardless of whether effusion is present at time of DX
- Not for HSA
326
T/F: single 12 Gy RT to right atrial masses improves survival?
F - safe and decreased frequency of palliative pericardiocentesis only
327
Prognosis cardiac HSA tx with surgery and chemo vs surgery alone?
- SX 16d - 4 mo
+ chemo ~6 mo
328
Prognosis heart HSA DOX alone?
- 41% PFS time of 66 days
- MST ~3.5-4.5 mo
329
Prognosis aortic body tumors with pericardectomy?
- 22 - 24 mo
- no pericardectomy ~1-4mo
330
What tumors arise from the paraganaglia?
Pheo, aortic body tumors, carotid body tumors; Pheo-secrete norepi/epi & aortic/carotid-PSNS-neg chromaffin cells
331
Risk factor associated with death during pericardectomy?
ventricular fibrillation - may be associated with electrosurgical devices and cardiac manipulation but not definitievly
332
Response aortic body tumors treated with fractionated RT? SRT?
- 42 GY - Median follow up 17 mo with gradual reduction and no regrowth in all dogs (6)
- 50 Gy - MST 27 mo
- 24-39 GY SRT - MST 13 mo
- in most cases symptoms improve gradually and tumors reduce in size
333
Palliative surgical option for ventricular obstruction secondary to intracardiac masses?
translatorial stenting
- successful in 3 dogs 2 unobstructed at 14 mo
334
Palladia for aortic body tumors?
10% ORR
- MST if mets 17 mo, no mets 25 mo (not different)
- 90% showed CB with 81% complete resolution of clinical signs
335
What is the most potent APC for the induction of naive T cells?
Dendritic cells
- CD11b drives CD4+
- interdigititating DC DC8+: LN/spleen
- interstitial DC CD103: perivascular
- costimulation necessary for activation of naive T cells
336
Where do histiocytes differentiate from?
CD34+ stem cell precursors into several dendritic cell lineages
337
Which cytokines and GF influence dendritic cell development?
FLT3, GM-CSF, TNFa, IL4, TGFb
338
CD expression of histiocytes
CD1 - skin dendritic cells (DC)
CD11/CD18 - all leuks
CD11c - Langerhans cells, interstitial DC
CD11b - Macs
CD11d- Macs in splenic pulp or BM +/- dermal subset
CD80/86 - co stimulatory molecules on DCs
339
Histiocytoma - species, cell of origin, key features, immunophenotype?
- Dog
- Langerhans
- epidermal focus "top heavy" lesions
- CD1a, CD11c, CD18, E-cadherin, Iba-1 positive
- CD204 neg
340
Cutaneous Langerhans cell histiocytosis - species, cell of origin, key features, immunophenotype?
- Dog
- Langerhans
- multiple cutaneous lesion, LN and internal mets possible
- CD1a, CD11c, CD18, E-cadherin, Iba-1 positive
- CD204 neg
341
Pulmonary Langerhans cell histiocytosis- species, cell of origin, key features, immunophenotype?
- Cat
- Langerhans
- multinodular, diffuse involvement of lung lobes
- Birbeck's granules on TEM
- CD1a, CD4, CD11c/CD18, E-cadherin, Iba-1, CD204
- V aggressive!
## Footnote
look like tennis racket if shown an image
342
Cutaneous histiocytosis- species, cell of origin, key features, immunophenotype?
- Dog
- interstitial (perivascular) dendritic cell- activated
- Vasocentric lesions on mid dermis to SQ "bottom heavy", vasculitis
- CD1a, CD4, CD11c/CD18, CD90, Iba-1, CD204
343
Systemic histiocytosis- species, cell of origin, key features, immunophenotype?
- DOg
- interstitial (perivascular) dendritic cell - activated
- lesions identical to cutaneous histiocytosis except extend to LN, ocular, nasal mucosa, and internal
- CD1a, CD11c/CD18, Iba-1, CD204
344
Histiocytic sarcoma- species, cell of origin, key features, immunophenotype?
- Dog, cat
- interstitial (perivascular) dendritic cell
- masses on spleen, lung, liver, LN
- CD1a, CD11c/CD18, Iba-1, CD204 (variable)
345
Hemophagacytic histolytic sarcoma- species, cell of origin, key features, immunophenotype?
- Dog, cat
- macrophage
- no masses, diffuse splenomegaly with insidious infiltration of liber, lung, BM. Splenic pulp expanded by erythrophagocytic histiocytes
- CD1a (low), CD11d/CD18 (dog), iba-1, CD204
346
Feline progressive histiocytosis - species, cell of origin, key features, immunophenotype?
- cat
- interstitial DC
- skin nodules and plaques
- CD1a, CD11c/CD18/CD5 (50%), Iba-1, CD204 (variable)
347
Dendritic cell leukemia - species, cell of origin, key features, immunophenotype?
- dog
- interstitial dc
- blood/bm
- CD1a, CD11c/CD18, IBA1- CD204
348
2.5 year old dog with rapidly growing solitary raised pink mass on shoulder - primary differential, tx, how to confirm dx?
- histiocytoma
- benign, typically regress 1-2 mo
- E-cadherin UNIQUE to histiocytomas but rarely needed
349
How do histiocytomas regress?
CD8+ alpha-betaT lymph infiltration - cytotoxic
- never immunosuppress a p while trying to regress
350
TX options and prognosis cutaneous langerhans cell histiocytosis?
- may have delayed regression up to 10 mo
- ~50% will not regress and dogs euth d/t ulcerative lesions
- CCNU and griseofulvin temporary CR reported
- Solitary lesion +/- LN tx with surgery alone 1-4 yr
351
Breed with familial systemic histiocytosis?
Bernese
352
How is systemic histiocytosis and cutaneous histiocytosis treated?
- these are the reactive histiocytosis types
- immunosuppressive therapy typically with pred
- long term survival, various maintenance therapies
353
Genetic alterations shared between Bernese mt dog and flat coated retrievers? Types of HS in each breed?
- deletions of CDKN2A/B, RB1, and PTEN (chromosome 10)
- p53 46% in various breeds
- BMD diffuse
- FCR localized esp limbs
354
IHC to differentiate periarticular HS from synovial cell tumor?
CD18, cytokeratin, SMA
355
SN and Spec of CADET HS assay?
Sn 78%, spec 95%
356
Lung lobe most commonly affected by HS?
right middle
357
What may be a blood parameter used as screening for Berners predisposed to HS?
- ferritin - higher in dogs with HS or pre development
- also dogs with HS have higher fibrinogen,C-RP, and monocytes chemotactic protein 1
358
Prognosis periarticular HS?
- ~6 mo-1 yr with amputation, 91% metastatic rate
- no mets do better MST 30 mo vs 8 mo if mets
- appears better than any other site
359
CCNU ORR gross dz HS?
- 46% for 2.8 mo
- MST responders 5.7 mo vs 2 mo non responders
- steroids do noti mprove response to therapy
360
Lab abnormalities associated with hemophagocytic HS subtype?
severe anemia, thrombocytopenia, hypocholesterolemia, hypoalbuminemia
361
MST localized HS tx with SX, RT, and CCNU?
19 mo
362
CCNU + DOX ORR HS?
-alternating q 2 week
- 58% TTP 6 mo
363
Rescue drugs for HS and response rates?
Dacarbazine 18%
Epirubicin 29%
- Case reports/series of liposomal DOX + paclitaxel, metronomic, clodronate, etc
364
Anatomic sites of localized HS in cats?
tarsus, nasal planum, stomach
- also get diffuse and hemophagocytic forms
- all HS thought to be agressive
365
Clinical course feline progressive histiocytosis?
- skin lesions that typically spread internally late in the disease median 13.4 mo
- no known therapy =, steroids dont seem to help
366
Breeds for HS?
Berner, flat coated reliever, Rotties, mini- schnauzers
367
Possible predisposition for periarticular HS in Berner?
prior joint disease ~88% of dogs
- CCL most common
368
Dog with CCL is tx and then develops skin mass cytology is a round cell tumor (plasma cell vs histiocytoma) do you remove, change chemo, or benign neglect?
benign neglect
369
Common location for HS in mini schnauzer? Outcome with various treatments?
- lung 24/29
- 83% PR to CCNU alone, PFS 117d-4 mth, OST 130d- 4.3mths
- SX alone (2 dogs) 45d, 157d - 5mth
- SX + CCNU 16 mo in one dog
370
Alternative drug to CCNU with similar activity for HS?
Nimustine 25 mg/m2 q3-5 week
- OST gross disease 4mo, adjuvant setting 13 mo
- neutropenia
371
ORR DOX first line for HS (localized or disseminated)?
26% ORR, 43% localized, 21% disseminated
TTP 42d, MST 5.6 mo
372
Gain of function pathway in Bernese HS?
PTPN11e76k in ~37% via ERK/AKT
373
Intracellular expression of CD5(AIM) apoptosis inhibitor of macrophages may be a marker for?
HS
374
mRNA sequence analysis of HS?
- MAPK activated in localized and Langerhans
- PI3K in disseminated and localized
- ALL cell lines downregulated tp53, CDKN2A, CDKN1A
- Palbociclib CDK 4/6 inhibior may be therapeutic
375
MST localized splenic HS treated with splenectomy and CCNU?
14 mo
376
MST of dogs undergoing curative intent lung lobectomy + CCNu for localized HS?
9- 14 mo
- LN mets NOT significant or sx margins
- chemo only MST ~ 4mo-6 mo
377
Is RT an appropriate alternative tx option for periarticular HS to sx?
- most dogs tx with palliative intent hypofx RT <36 Gy
- No diff between TTP or OST
- TTP 11 mo SX vs 7 mo RT
- OST 13 mo SX vs 8 mo RT
378
CD206 Langehans cells expression from bottom of tumor to epidermis correlate with?
- tumor regression phase and intratumoral T lymphocyte infiltrate
- CD206 change in cells = change to mature phenotype with tumor regression
379
Other cell line HS stuff
- MMPs expression assocaited with tumor progression and invasion
- TAMs play a role in microenvironment and angiogenesis
- HS expresses TBGb and PDL1
- increase FOXP3 and TGFb associated with worse prognosis
380
Corgi with disseminated CNS HS, what to TX with?
- CCNU
CNS - Mariani et al 2015
- Retrievers and Pembroke Welsh Corgis overrepresented
- Tumors involved brain in 14 dogs and spinal cord in 5
- 4 dogs – HS part of disseminated process whereas confined to CNS in 15 dogs
- Extracranial masses predominated in brain; brain herniation, profound meningeal enhancement, and pleocytosis in combo w 1+ mass lesions
- Meningeal enhancement in all dogs – often profound and remote from the primary mass lesion
- Pleocytosis was present in all dogs w CSF eval
- MST 3 d
381
Differences in cell markers CNS vs periarticular HS?
- IHC of the brain HS cells – S100/CD208/CD1/CD4 (DC markers) and CD68/CD163/CD204 (macrophage markers) both expressed
- IHC of articular – negative for CD204 and CD68 (mac markers) but consistently positive for DC markers
- Suggests HS from CNS may have tendency to be more undifferentiated compared w other organs
382
HS prognostic factors associated w <1 mo survival?
palliative tx, disseminated HS, and concurrent use of corticosteroids
