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Onco boards 2024 > Tumor Specific AB Part II 25% > Flashcards

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

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1
Q

What % of adrenal carcinomas invade vasculature? Met rate?

A
  • 20% invasion
  • 50% metastatic rate
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2
Q

MST SRT adrenocortical tumors?

A

~ 35 mo

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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
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4
Q

Pheochromocytoma cell of origin? Vascular invasion rate? Met Rate?

A
  • Chromaffin cells of the medulla
  • 85% invasion
  • 40% metastasis
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5
Q

IHC to distinguish pheo from adrenal carcinoma?

A

chromogranin A

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6
Q

Urine metanephrine [ ] with pheo?

A

> 2x ULN

Sens 62%, spec 97%

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7
Q

Prognostic factors for pheos?

A

size, metastasis, invasion

  • MST ~ 1-3 years
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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
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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

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10
Q

Complication rate of adrenal FNA?

A

8% - similar to FNA of other major organ
1% mortality

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11
Q

Molecular markers associated with survival adrenocortical carcinoma?

A

Steroidogenic factor 1, PPTG1, TOP2A - decreased survival

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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
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13
Q

What is phenoxybenzamine?

A

Alpha adrenergic antagonist, irreversible

  • used preop/RT for pheos
  • some papers say improves survival others say no difference
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14
Q

Are most adrenal tumors benign or malignant?

A

Most benign incidental; Ferret 2/3 benign; Cat mostly LSA

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15
Q

Prognostic factors for cats w primary hyperaldosteronism (Conns syndrome) undergoing adrenalectomy?

A

Prognostic factor anesthesia time >4 hr

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16
Q

Most common thyroid panel with thyroid carcinoma?

A

euthyroid > hypothyroid > hyperthyroid

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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)
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18
Q

Common finding after bilateral thyroidectomy?

A

hypocalcemia - parathyroids often removed too

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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

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20
Q

Prognosis thyroid carcinoma with resection?

A

unilateral, mobile MST 36 mo, 1 yr 72%

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21
Q

Prognostic variables for thyroid carcinoma?

A

Tumor diameter and volume, bilateral location, metastatic disease, VASCULAR INVASION

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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
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23
Q

True or false: Hyperthyroid cats typically have carcinoma?

A

false; nodular hyperplasia

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24
Q

% of pets with primary hyperparathyroidism with thyroid mass?

A

90% - most common adenoma, dx d/t hypercalcemia

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25
Q

Breed disposition parathyroid tumor?

A

Keeshond - autosomal dominant inheritance

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26
Q

Prognosis parathyroid tumors?

A

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

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27
Q

Over represented breeds for functional thyroid carcinoma?

A
  • Labs, goldens
  • CS pu/pd, wt loss
  • MST 1,072D, 35 mo with surgery, chemo does not help
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28
Q

RR thyroid carcinoma SRT?

A

70%, 81% CB
- OST 1 year
- minimal AE
- mets not prognostic

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29
Q

Complication rate thyroidectomy when invasion present?

A
  • intra op ~7%
  • post op 16%
  • 10% local recurrence
  • OST 621d ~2 yr
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30
Q

MST parathyroid CARCINOMA with surgery?

A

~2 years
- 1 yr 84%m 2 yr 65%, 3 yr 51%
- 92% hypercalcemia resolved
- 3 euth d/t hypocalcemia post op

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31
Q

Insulinoma cell of origin? Hallmark?

A

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
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32
Q

Hormones produced by insulinoma?

A

insulin, glycogen, somatostatin, pancreatic polypeptide, GH, IGF1, gastrin

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33
Q

CS of insulinoma?

A

neuroglyopenia = weakness, collapse, disorientation, behavior changes, seizures, tremors, shaking, anxiety, hunger

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34
Q

US for insulinoma

A

not helpful <50% identification of pancreatic masses when present, low specificity and sensitivity for mets

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35
Q

Best TX for insulinoma? Complications?

A
  • sx best
  • persistent hypoglycemia, pancreatitis, hyperglycemia 33% may be persistent DM, GI (risk higher if preop CS, lack of liver mets, and high TP)
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36
Q

Medical TX hypoglycemia for insulinoma?

A

-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)

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37
Q

Response rate to diazoxide insulinoma? Octreotide?

A

70% - not cytotoxic, BG control

50% - same, become refractory

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38
Q

Streptozoocin MOA, use, AE?

A
  • 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)
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39
Q

Insulinoma prognosis?

A
  • 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
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40
Q

What is unique about ferret insulinoma vs. dog?

A
  • 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
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41
Q

What are the IHC for insulinoma?

A

ChromograninA+, insulin+

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42
Q

What is the met rate and location for insulinoma in dogs?

A

50% to liver, rare to lung

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43
Q

What other diseases can ferrets have with adrenocortical tumors?

A

25% insulinoma, 10% cardiomyopathy

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44
Q

How is streptozocin transported into cells?

A

GLUT2

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45
Q

When can laparoscopic pancreatectomy be considered?

A

small tumor in the distal aspect of the pancreatic lobe

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46
Q

Report glycemic control with pred and palladia after partial pancreatectomy?

A

24 mo

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47
Q

median OST in dogs with metastatic or recurrence insulinoma treated with Palladia+palliative therapy (pred)?

A
  • 399d (13 mo) to 656d (21 mo) vs 2 mo with pred alone
  • PFI 561d (18 mo)
  • RR 67%
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48
Q

What is the best imaging modality for insulinoma?

A

3phase CT - most notable on late arterial phase

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49
Q

Insulinoma MRI appearance?

A

T2 hyperintesine
T1 isointense

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50
Q

What can be useful intraop to assess for complete insulinoma excision?

A

BG

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51
Q

Cat insulinoma prognosis?

A
  • 863d = 28 mo (similar to dog)
  • 1 yr 75%, 2 yr 51%, 3 yr 10%
  • 18/20 immediately euglycemic
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52
Q

Gastrinoma Zollinger-Ellison syndrome.

A

triad of non-beta cell neuroendocrine tumor in pancreas, hypergastrinemia, and GI ulceration

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53
Q

Gastroninoma prognosis?

A
  • 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
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54
Q

Omeprazole for gastrinoma

A

Omeprazole will increase circulating gastrin levels (but decrease HCl secretion due to inhibition of PP)

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55
Q

Tumor associated with necrolytic migratory erythema?

A

glucagonoma - v. rare arise fro alpha cells, mets common, prognosis poor

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56
Q

Risk factors mammary tumors in dogs?

A
  • 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
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57
Q

Risk factors mammary tumors in cats?

A
  • 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)
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58
Q

Cat mammary tumor expression?

A

COX2, EGFR, low HR, RON

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59
Q

English Springer Spaniel mammary carcinoma mutation?

A

Germline polymorphisms in BRCA 1 & 2

+/- Shih Tzu

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60
Q

Which tumors are more likely to retain estrogen and progesterone receptor expression, benign or malignant?

A

Benign - loss is correlated with increasing size and undifferentiated tumors

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61
Q

Staging k9 mammary tumors?

A
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62
Q

Most common mesenchymal tumor of the canine mammary gland?

A

OSA

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63
Q

What is Paget-like syndrome?

A

mammary carcinoma present within the MG and carcinoma cells also in the epidermis of the nipple - seen in dogs and women

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64
Q

Criteria for grading mammary tumors is based on?

A

Elston and Ellis used mostly: tubule formation, nuclear pleomorphism, and mitosis/10 hpf

  • applies only to epithelial origin
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65
Q

Clinical prognostic factors for mammary tumors in dogs?

A
  • size >5cm
  • LN involvement: multiple studies have shown as v. important prognostic indicator
  • Stage
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66
Q

Recommended surgical dose for canine mammary tumors?

A
  • lupectomy (50/50 benign/malignant)
  • ~60% develop tumors in contralateral chain, 77% complication rate with radical mastectomy

recent review 2023 says that not lit as made a definitive conclusion about surgery dose

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67
Q

Is there benefit to spay at time of mastectomy for dogs with mammary tumors?

A

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

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68
Q

Do margins matter for mammary gland tumors in dogs?

A

Yes
- MST 2-15.5 mo for incomplete vs 22.8-30 mo for complete (grade dependent)

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69
Q

Situations to consider chemotherapy for dog mammary tumors?

A
  • > 3cm, neg LN, carcinoma
  • any size, pos LN, carcinoma
  • inflammatory carcinoma
  • OSA
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70
Q

Which medical treatment has been shown to be beneficial for mammary carcinoma?

A
  • 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
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71
Q

What % of cats have more than 1 mammary tumor?

A

60%

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72
Q

Staging for feline mammary tumors

A

Differs from dog with tumor size and nodal involvement

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73
Q

% of feline mammary tumors that are malignant?

A

85-95%

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74
Q

Histopathologic/clinical prognostic indicators feline mammary tumors?

A
  • grade,
  • lymphovascular invasion
  • size (<2cm w/ rad mastectomy MST 3+ yr, >2cm MST 6 mo)
  • LN mets
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75
Q

Prognosis feline mammary tumors based on grading?

A

I: 31-36 mo
II: 14-18 mo
III: 6-8 mo

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76
Q

Recommended surgical dose for cat mammary gland tumor?

A

bilateral mastectomy

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77
Q

Blue dye lymph node mapping is best for cats with mammary gland tumors?

A

False - Heinz body anemia and methemoglobinemia

idk if this is correct

lots of papers saying with repeated dosing maybe cause HBHA but with one does no cats had complications

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78
Q

Chemotherapy for cats with mammary gland tumors?

A
  • 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)
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79
Q

Situations to consider chemotherapy for cats mammary gland tumors?

A
  • <2cm-3, neg LN, carcinoma, vascular invasion/high grade
  • > 3cm, neg LN, carcinoma
  • any size, pos LN, carcinoma
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80
Q

Which tumors express PD-L1?

A

melanoma, OSA, mammary, prostatic adenocarcinoma, TCC, HSA

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81
Q

Pathways involved in mammary carcinogenesis?

A
  • 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
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82
Q

TLR4 mRNA is expressed in which k9 mammary carcinoma subtypes?

A

complex carcinoma grade I, ductal carcinoma grade II, and anaplastic carcinoma

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83
Q

PDL-1 and CTLA-4 k9 mammary carcinoma associated with?

A
  • metastasis
  • blockade could be therapeutic
  • dogs with malignant metastatic MGT MST 16 mo vs malignant non metastasizing MST 4 years

ctla4 is an immune checkpoint - CTLA4 on t cells down regulates immune response
PDL1 on cancer cells - down regulates immune response

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84
Q

Heat shock proteins are associated with tumorigenesis in which cancer type?

A

k9 mammary gland carcinomas (HSP110)

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85
Q

CD204 is an M2 type tumor associated macrophage is higher in grade I vs grade III mammary carcinomas?

A

grade III - associated with other aggressive features (vascular invasion, HR negative)

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86
Q

Mammary epethiliosis (ME) is premalignant dysplasia present in what % of canine mammary tumors?

A

52% - associated with older dogs, malignant tumors, higher stage, LN mets, higher grade, and short OST

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87
Q

Complication rate canine mastectomy?

A
  • 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
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88
Q

Which autoAbs have been shown to be elevated in canine mammary cancer patient serum?

A

TYMS, HAPLN1, IGFBP5

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89
Q

Chemokine and chemokine receptor expression associated with metastasis in canine mammary carcinoma?

A
  • chemokine: CCL5, independently prognostic of ST
  • receptors: CXCR3, 4, 7, CCR9
  • CXCR4 independently prognostic of ST

cxc= chemokine receptor

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

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90
Q

Ki67 cut off associated with higher grade mammary carcinoma?

A

33.3%
- also had higher p53 expression
- ER+ tumors associated with low ki67

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91
Q

What may be a cause for resistance in inflammatory mammary carcinomas?

A

P-Gp and BCRP/ABG2 - one or other expressed in 87%

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92
Q

What multi-agent protocol has been shown to improve survival in dogs with inflammatory mammary carcinoma?

A
  • 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
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93
Q

Which medical treatment is best for metastatic feline mammary carcinoma?

A
  • 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%
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94
Q

Neutrophil to lymphocyte ratio associated with worse outcome feline mammary carcinoma?

A

2.46

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95
Q

CDK 4/6 inhibitor with anti-tumor effects on mammary carcinoma?

A

Palbociclib

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96
Q

Which ovarian tumors are found in young dogs?

A

teratomas <6 yr

most others >6yr

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97
Q

Types of ovarian tumors?

A

Epithelial
Sex cord stromal
Germ cell
Mesenchymal - HSA, leiomyoma/sarcoma

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98
Q

Ovarian carcinoma: metastatic rate, presentation, IHC?

A
  • 48% - LN, momentum, liver, carcinomatosis
  • unilateral > bilateral; cysts/hyperplasia in contralateral common
  • Cytokeratin AE1/3, vimentin, desmin
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99
Q

Sex cord stromal tumors: types, metastatic rate, presentation, IHC?

A
  • 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
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100
Q

Germ cell tumors: types, metastatic rate, presentation, IHC?

A
  • 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
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101
Q

Which ovarian tumor type is most common in cats?

A

sex cord stromal cell tumors - granulosa-theca cell tumors that are up to 50% malignant

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102
Q

CS of estrogen producing ovarian tumor?

A

vulvar enlargement, sanguineous vulvar discharge, persistent estrus, alopecia, aplastic pancytopenia

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103
Q

CS of progesterone producing ovarian tumor?

A

cystic endometrial hyperplasia and pyometra

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104
Q

What is considered high risk with ovarian tumors?

A

Seeding- caution with FNA and SX (tx OHE)

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105
Q

Most common uterine tumor - dog? Cat?

A
  • leiomyoma - cured with SX
  • adenocarcinoma - guarded prognosis, highly metastatic
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106
Q

German Shepherd dog with multiple uterine tumor, bilateral cystic kidney masses, and cutaneous nodules. What is mutated?

A

Birt-Hogg-Dube gene

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107
Q

Most common vaginal/vulvar tumor in small animals?

A

Leiomyoma - hormone dependent, intact dogs, OHE prevents recurrence

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108
Q

Ovarian cancer defect people?

A

BRCA 1/2

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109
Q

What 2 cancers cause hyperestrogenism that can lead to bone marrow hypoplasia?

A

Male sertoli cell tumors & female granulosa cell tumor

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110
Q

What part of the vulva/vagina do leiomyomas arise?

A

Vestibule of vulva

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111
Q

Most common repro tumor in rabbits? TX? Prognosis?

A
  • 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
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112
Q

What can improve outcome in dogs with malignant ovarian tumor (adenocarcinoma) carcinomatosis?

A
  • 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)
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113
Q

Complications associated with vaginectomy/vulvoveginectomy for vaginal/vulvar tumors?

A
  • incontinence may resolve (~50%)
  • malignant tumor MST 20 mo
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114
Q

Paraneoplastic syndrome associated with clitoral tumors? Cytologic appearance? Histo patterns?

A
  • Hypercalcemia
  • Appear neuroendocrine like AGASACA
  • Tubular, solid, rosette
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115
Q

Feline ocular SCC predilection?

A

eyelid, 3rd eyelid, and medial canthus of white cats

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116
Q

Predisposing factors to ocular SCC?

A

Solar, lack of adnexal pigmentation, chronic ocular surface irriation

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117
Q

Predisposed breeds to vascular endothelial tumors of the lateral limbus?

A

Bassett hounds, springer spaniels, beagles

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118
Q

Most common tumor of k9 conjunctiva?

A

melanoma

  • others: HSA, MCT, adenocarcinoma
  • all seem to have good prognosis with complete excision but may rarely recur
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119
Q

% of eyelid and conjunctival tumors which are benign?

A

80% - sebaceous or meibomian gland adenomas, epitheliumas, papilolomas, and melanomas

  • even malignant tumors rarely spread and have low recurrence rates (10-15%)
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120
Q

Corneal SCC predispotions?

A

Brachycephalic breeds, chronic keratitis, immunosuppressive therapy

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121
Q

Indications for removal of eyelid tumors?

A
  • any in cat, rapid growth ,ocular surface irritation, impaired eyelid function, owner concern, appearance
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122
Q

Alternative treatment to surgery for eyelid tumors?

A

cryosurgery

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123
Q

How is benign canine anterior uveal melanoma differentiated from malignant?

A

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
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124
Q

When should surgery be considered for canine anterior uveal tumors?

A
  • glaucoma, inflammation, lack of vision
  • enucleation not shown to improve outcome
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125
Q

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?

A

extrascleral extension, necrosis, MI >7/10 hpf, choroidal invasion, increased E-cadherin and MelanA

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126
Q

When to enucleate and prognosis feline diffuse iris melanoma?

A
  • 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

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127
Q

Subtypes of post traumatic ocular sarcomas in cats?

A

spindle cell sarcoma - most common
round cell sarcoma - LSA CD79a b cell
osteosarcoma/chondrosarcoma

  • no evidence for tx beyond enucleation
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128
Q

Dogs with blue eyes at risk for?

A

spindle cell sarcomas of the uvea aka Uveal Scwannoma
- low metastatic rate

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129
Q

Rate of metastatic tumors to the eye? Location?

A

5%, highly vascularized Uveal tract

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130
Q

What percentage of patients with ocular lymphoma DO NOT have systemic disease?

A

60%
- no systemic involvement MST 769d 25 mo vs with systemic 103d

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131
Q

Most common tumor of the orbit?

A

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
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132
Q

Image of RT port films of dog receiving tx to distal nose. What are the side effects?

A

dental disease, oronasal fistula, ocular, ect

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133
Q

RT histogram showed higher dose to the left eye than left lens. SE?

A

OS blind, cataract, etc

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134
Q

What chemo drugs have ocular side effects?

A

Cyclophosphamide, cisplatin, doxorubicin, 5-FU, vincristine

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135
Q

ST ocular LSA vs conjunctival?

A

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
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136
Q

T or F: conjunctival squamous papillomas are not virally associated?

A

T

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137
Q

Most common iridociliary tumor dog?

A

Melanocytic neopalsms > epithelial tumors (adenomas/carcinomas)

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138
Q

Incidence of canine LSA?

A
  • 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
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139
Q

Chromosome alterations associated with developing LSA?

A

gain of 13 and 31
loss of 14

  • trisomy of chromosome 13 may result in improved outcomes
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140
Q

Immunophenotype GI LSA? Breed?

A

T-cell with epitheliotropism; Boxer, Shar Pei

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141
Q

% of mediastinal LSA that are hyerCA?

A

10-40%; T cell

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142
Q

Hepatosplenic LSA immunophenotype?

A

gamma-delta T cell

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143
Q

Breed predispositions based on immunophenotype?

A

B = Doberman Pinscher, cocker spaniel
T = Boxers
Equal = Goldens

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144
Q

% of dogs with multi centric LSA with thoracic abnormalities? Abdominal?

A
  • 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
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145
Q

Nervous system LSA immunophenotype based on location?

A

B cell: meningeal, perivascular, periventricular
T cell: peripheral nerves

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146
Q

% of dogs with multicentric LSA with ocular involvement?

A

~30-50%

37% specifically written in Withrow

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147
Q

Most common paraneoplastic syndrome with LSA?

A

anemia; normo, normo, non regen

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148
Q

MOA of LSA paraneoplastic HyperCa?

A
  • PTHrp most common
  • Humoral factors: IL-1, TNF-a, TGF-b, vit D analagous
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149
Q

DDX for peripheral lymphadenopathy?

A

bacteria, virus, protozoa (Toxo, leishmania), rickettsial (salmon poising, ehrlichia), fungal (blasto, histo), immune mediated (pemphigus, SLE, IMPA)

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150
Q

% of LSA with monoclonogammopathy?

A

6%

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151
Q

T cell markers

A

CD3 - panT
CD4 - helper
CD8 - cytotoxic

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152
Q

B cell markers

A

CD79a, CD20, CD21

  • some TZL express CD21* (cd 5 cd21 cd45-)
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153
Q

PARR amplifies which regions?

A
  • 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
Q

Sn, FP of PARR?

A

Sn 70-90%
FP 5%

155
Q

PARR false negative DDX

A
  • 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
Q

PARR false positive DDX

A

ehrlichia, leishmania

157
Q

DLBCL location, histo architecture, cell size, immunophenotype

A
  • multicentric
  • diffuse
  • large
  • CD1, CD20, CD21, CD45, CD79A, PAX5, MCHII positive, low CD18
158
Q

Peripheral T cell LSA location, histo architecture, cell size, immunophenotype

A
  • multicentric
  • diffuse
  • variable small to large
  • CD3, CD45, CD5 positive, +/- CD4, CD8, CD18 high, TCRa/b
159
Q

MZL location, histo architecture, cell size, immunophenotype

A
  • 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
Q

TZL location, histo architecture, cell size, immunophenotype

A
  • multicentric
  • nodular, paracortical progressing to diffuse
  • small- intermediate
  • CD45-, CD3+, CD21+,CD4 +/-, CD8 +/-
161
Q

Flow marker to help detect precursor cells?

162
Q

Mantle cell LSA (MCL) location, histo architecture, cell size, immunophenotype

A
  • splenic white pulp
  • nodular/follicular
  • small to intermediate
  • CD20, CD21, CD45, CD79A, MHCII positive
163
Q

Follicular LSA location, histo architecture, cell size, immunophenotype

A
  • nodes solitary or multiple
  • nodular, follicular
  • mixed mostly small
  • CD20, CD21, CD45. CD79A, MHCII positive
164
Q

Discrepancy between circulating LSA cells and bone marrow involvement on BM examination?

A

28% circulating
57% with BMA

  • BMA not necessary if the client is willing to treat regardless of stage
165
Q

Prognosis LSA no tx?

166
Q

CHOP remission rate, MST, 2 yr survival

A
  • 80-95%
  • 10-12 mo B, 6-9 mo T
  • 20-25%
167
Q

Fundamental goals of chemotherapy for LSA?

A
  • 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
Q

Is maintenance therapy beneficial for LSA?

169
Q

If CHOP not pursued, which protocol has similar remission?

A

DOX, Tanovea alternating

170
Q

CR rate and MST Dox alone tx naive?

A
  • 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
Q

CCNU alone response duration tx naive?

A

one study reports only 40 days

172
Q

MST pred alone LSA?

A
  • 1-2 mo (50d)
  • T cells 90 d vs B cell 39d
  • substage a 64 d vs b 36d
  • 7% 6 mo survival
173
Q

Why does starting pred prior to chemotherapy result in negative outcomes?

A

development of MDR mutation

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
Q

What is the increase in plasma PK/AUC estimated for MDR mutant patients receiving DOX?

A

25%

dec by 25% for +/- and 50% for +/+

175
Q

MDR1 breed and frequency of mutations (mut/norm)

A

70%: Collie
50%: Aussies, Long-haired Whippet
30%: McNab, Silken Windhound
25%: Chinook
15%: English Shepherd, Shelties
10%: GSD, Herding Breed X
</=5%: Border Collie, MBD, Old English Sheep dog
Maybe but not enough tested: Black Mouth Cur, Carolina Dog

This is from UW

176
Q

MDR1 mut/mut breed and frequency

A

Collie 35%
Aussies 10%
mini Aussie 3%
GSD 2%
Shelties, herding 1

from AG

177
Q

MDR1 mut/mut dose recommandation?

A

40-50% reduction; start non MDRI drug (cytoxan) while pending per Withrow

178
Q

Overall response rate to rescue chemotherapy LSA? Median duration?

A
  • 40-90%
  • 1.5-2.5 mo
179
Q

Rituximab MOA

A
  • 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
Q

When should splenectomy be performed for LSA?

A
  • not in other sites with complete staging
  • indolent disease
  • hemoabdomen
  • if indolent MST >1 year to many years
181
Q

Indications for RT LSA?

A
  • 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
Q

Colorectal LSA - phenotype, CS, PFS, OST with chemo?

A
  • B-cell, high grade
  • most substage b with hematochezia
  • PFS and OST >3 years with CHOP suggesting more favorable prognosis (Desmas 2017)
183
Q

RR and duration CCNU +/- Lspar for epitheliotropic LSA?

A
  • 40-80%
  • 3-6 mo
184
Q

Negative prognostic factors for LSA?

A
  • 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
Q

Favorable prognostic factors for LSA?

A
  • 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
Q

B cell expression associated with worse outcome?

A

low B5 and low MHCII

187
Q

3 primary CLL subtypes

A

1) T CLL = most common (2/3), CD3+/CD8+ granular lyphs

2) B CLL = CD21+, second most common

3) Atypical CLL = various expression

188
Q

B vs T ALL expression

A

B ALL = CD21+, CD3-, CD4-, CD8-, most common

T ALL = CD3+, CD4-, CD8-, CD21-

variable CD34 = stem cell

189
Q

Paraneoplastic syndromes with CLL?

A
  • hyerglobulinemic 80% B-CLL
  • monoclonal gammopathy (IgM or IgA) 68% B-CLL
  • hypercalcemia 13% B-CLLL
  • IMHA
  • Pure red cell aplasia
190
Q

Lymphocyte disruption normal dog blood

did you mean to say distribution?

A

80% T cell CD4 helper>CD8 cytotoxic
15% B cell
rest NK or double - lymphs

191
Q

DDX lymphocytosis in dogs?

A

infectious disease (chronic ehrlichia), post vaccine response in young dogs, IL-2 administration, transient physiologic or epinephrine induced

192
Q

Minimal % of bone marrow affected to call leukemia

193
Q

TX CLL, RR and ST

A

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
Q

What is Richter’s syndrome?

A
  • 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
Q

MST between CLL subtypes and prognostic indicators?

A

TCLL 930d (31 mo)
BCLL 480d (16 mo)
atypical 22d

  • neg young age and anemia
196
Q

MST ALL

A

guarder 16-130d reported with CHOP
- 29% (CR/PR) rate to vinc and pred

197
Q

Dog with Cushing’s has LSA - does not including pred in TX effect outcome?

198
Q

Environmental risk factors for LSA

A
  • Residency in industrial areas
  • Use of chemicals by owners
  • Illegal waste dumping
199
Q

What proteins/molecules are upregulated in large B cell LSA?

A
  • JAK1/2 – STAT3 and p-STAT3 – higher in DLBCL
  • Higher nuclear exp
  • Mitogen activated kinase ERK1/2 upregulated
200
Q

Signaling pathways associated w B cell LSA in dogs and humans?

A
  • NF-kB canonical pathway activation
  • NF-kB family of inducible transcription factors
  • Re1A(p65), Re1B, c-Re1, NFkB1 (p50), and NFkB2 (p52)
201
Q

Common mutation in TSG in LSA in people and in dogs?

A
  • 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
Q

Which morph can be confused with lymphoid hyperplasia on cytology- pick 2?

A

T zone, follicular

could be any that are nodular, not diffuse

203
Q

Most common LSA phenotype in Boxers?

A

T CD4+ large cell LSA in Boxers, aggressive clinical course (MST 159 d)

204
Q

Prognostic factors for CD21+ LSA?

A
  • Low MHC II – higher risk of death, relapse
  • Large cell – higher risk of death
  • Age – higher risk of death in younger dogs
205
Q

CCNU as a first line treatment for canine LSA?

A
  • 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
Q

DTIC response rate in relapsed LSA?

A
  • ORR 35%
  • PFS 43 days
  • Toxicity – thrombocytopenia 7-14 d post
207
Q

Immunophenotype for LSA treated w single agent doxorubicin?

A
  • 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
Q

Doxo + pred + L-spar as first line therapy for B-cell LSA ?

A
  • ORR 84%
  • Median PFS 147 d, OST 182 d
  • 1-yr survival 23%
209
Q

Half body irradiation w CHOP ?

A

(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
Q

What is a unique about rabbit LSA?

A

Cutaneous LSA more common in Europe than N. America

211
Q

What is the most common equine intestinal neoplasia?

A

LSA then adenoCA then smooth muscle

212
Q

What is the most common bovine neoplasia?

213
Q

What are the 2 different forms of LSA in cows and how do they develop it?

A

Sporadic-in young(1-3yr) juvenile, thymic, cutaneous;
Viral-enzootic BLV retrovirsus seen in older cow, cows persistent leukocytosis & minority develop LSA

214
Q

What kind of LSA do ferrets develop and where?

A

T cell, abdominal MC

215
Q

What type of LSA is common in both rabbits and horses?

A

T cell rich B cell LSA

216
Q

What is the diagnostic accuracy of US to detect hepatic and splenic LSA infiltration>

A
  • 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
Q

Sn, Sp, accuracy, and PPV US detection of LSA in spleen?

this is if you already KNOW the patient has lsa and confirming st4

A

~ 70% sn
~ 90% sp
~80% acc
~ 95% PPV
~75% NPV

218
Q

Sn, Sp, accuracy, and PPV US detection of LSA in Liver?

A

~ 15% sn
~ 90% sp
~55% acc
~ 60% PPV
~55% NPV

219
Q

Anemia characteristics differentiation between dogs with LSA (multi centric or GI) vs IBD?

A
  • 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

careful bc echinocytes = hsa

220
Q

Coagulation parameter sig associated with decreased PFS if elevated prior to tx in LSA?

A
  • D-dimers >0.5 ug/L
  • 54 vs 104d
  • tx was etoposide and F14152?
221
Q

Is ki67 a good marker for LSA?

A

No - wide confidence intervals between IHC and FC
- variability in predicting outcome in various studies

222
Q

Diffuse small cell B cell LSA OST?

A
  • 140d
  • considered aggressive small cell disease
  • required histo for DX same flow as DLBCL
223
Q

RR cytoxan/pred as first line treatment for DLBCL?

A

ORR 84%
- 9%CR
- 62% PR
- 12% SD
- 15% PD

  • 250 mg/m2 q7d
  • some dogs heavily pre-treated with pred - all SD
224
Q

PFS L-CHOP vs MOPP for T cell or hypercalcemic LSAs?

A

L-CHOP 133d
MOPP 97d

  • No sig dif
225
Q

Mitoxantrone and DTIC rescue protocol and response rate?

A
  • 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
Q

Bleomycin + cytosar rescue protocol and response rate?

A
  • 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
Q

What % of LSA has PDL1 expression?

A

50% - potential target, not associated with PFS

228
Q

OST high vs low CD44 expression LSA?

A

high 5 mo
low 9-10 mo

229
Q

miRNA markers that may differentiate DLBCL?

A

Let-7f (97% from control)

230
Q

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?

A

GI
- young dogs <4 yr
- B cell 70% +/- Mott differentiation

231
Q

List 6 genes associated with DLBCL specific survival

A

IL2RB, BCL6, TXK, C2, CDKN2B, ITK

232
Q

Which serum biomarker may be used to monitor response to chemo for LSA?

A

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
Q

Neutrophi:lymph ratio is not shown to be predictive of LSA survival in dogs receiving chop, but what parameter is?

A

neutrophilia at DX

234
Q

Is there a difference in RR, PFST, and OST in CHOP vs CMOP?

A

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
Q

Do elderly dog have a worse response to chemotherapy LSA?

A

No >14 yr had improved survival with chemo compared to pred

236
Q

Outcomes of dogs with nodal, non TZL, CD8+ vs CD4-CD8- LSA?

A
  • 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
Q

Is serum clusterin a good marker for LSA?

238
Q

For multi centric T-cell LSA addition of which chemo have resulted in improved outcome at induction?

A
  • 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
Q

What are B symptoms of LSA?

A

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
Q

What degree of weight changes has been associated with decreased PFS in LSA?

A

5%
- PFS decrease 129d vs increase 226 vs 256d stable
- initial HIGH body weight associated with worse PFS and OST

241
Q

Best on response-based CHOP protocols, which factor is associated with survival?

A

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
Q

Cure rate allogenic vs autologous bone marrow transplant B cell LSA?

A

allogenic 89%
autoglous 33-40%

243
Q

Is 12 week CHOP an acceptable alternative to 19 week?

A

no

PFS 141 d (4 mo) vs 245d (8 mo)
OST 229d (9 mo) vs 347d (11.5 mo)

244
Q

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?

A
  • 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
Q

Does dose intensity matter for CHOP and T-cell LSA?

246
Q

Clinical benefit rate of melphalan in LSA rescue setting?

A

19.4 mg/m2 - high dose protocol

31.6% CB for 14-34 days

247
Q

TMZ alone vs TMZ with DOX RR, TTP, MST, and toxicity in rescue setting

A

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
Q

Nodal small cell B cell LSA is thought to be an aggressive subtype. What is associated with poor OS in this disease?

A
  • 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
Q

What factor has been associated with improved overall survival in dogs with mediastinal LSA?

A
  • 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
Q

MST primary intestinal LSA in dogs? Best chemotherapy?

A
  • 64 days
  • no difference between CHOP or CCNU first line
251
Q

miRNA profile intestinal LSA not seen with IBD?

A

down regulated tumor suppressing: miR-194, 192, 141, 203
up regulated oncogenic: miR106a

252
Q

RR continuous L-spar administration dogs with presumed GI LSA?

A
  • 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
Q

What has a worse ST epitheliotropic or non epitheliotropic LSA?

A

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
Q

TZL parasite association

A

demodex in adults

  • in goldens hypthyroidism, omega 3 supplentation associated
255
Q

Laboratory findings associated with renal LSA dogs?

A
  • 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
Q

ORR Tanovea tx naive? phenotype?

A

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
Q

Can you combine L-spar and Tanovea in the relapse setting?

A

Yes
- safe and efficacious
- given first 2 tx
- 67% ORR, 41% CR
- PFS 63d, 144d if CR~ 5 MTH

258
Q

What has been shown to be a positive prog indicator in dogs with T LSA receiving LOPP?

A

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
Q

What is theory behind T cells responding more favorably to alkylating agents?

A
  • 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
Q

Which drug is most likely to cause GI toxicity in LOPP?

261
Q

MVPP vs MOPP relapsed LSA outcomes?

A

MVPP (vinblast): ORR 25%, PFS 15d - less toxicity
- MV day 0 & 7, procarb/pred 0-14

MOPP: ORR 65%, PFS 63d

262
Q

DMAC protocol. Response rates relapsed LSA?

A

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
Q

PPC protocol? RR?

A

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
Q

At which location and phenotype is currently most strongly associated with FeLV?

A

mediastinal/thymic, T cell

  • also more common with peripheral nodal non-Hodgkins B cell as opposed to any other location
  • common with LEUKEMIAS
265
Q

FIV risk of LSA?

A

5 fold risk compared to FIV -
- B cell phenotype more common
- indirect d/t immunosuppression

266
Q

Which other virus has been associated with a poor prognosis for feline LSA but not a risk factor?

A

herpes virus 1

267
Q

Helicobacter has been associated with?

A

gastric mucosa associated lymphoid tissue in cats but not direct to LSA

268
Q

T/F: LSA is the most common malignancy through the cat GI tract?

A

T; adenocarcinoma most common in the colon

269
Q

Characteristics low grade GI LSA cat?

A
  • 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
Q

Characteristics high grade GI LSA cat?

A
  • ~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
Q

Characteristics LGL cat? Prognosis

A

-~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
Q

Does GI perforation result from robust chemotherapy response in cats?

A

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
Q

RT for GI LSA

A
  • 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
Q

Characteristics Hodgkin’s like LSA cat?

A
  • 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

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
Q

T/F: hypercalcemia is uncommon with feline mediastinal lsa?

276
Q

Which breed is predisposed to mediastinal LSA FeLV/FIV-?

A

Siamese; also male and young <3 years

277
Q

Prognosis mediastinal LSA tx CHOP/COP?

A
  • FeLV -: RR 95% MST 1 year up to 3 years if CR achieved
  • FeLV+, young: MST 2-3 mo
278
Q

Protein aberrations with extra nodal LSA in cats?

A

low alb and high B globulins when compared to control population

279
Q

Sn of PARR feline LSA?

280
Q

% of cats with nasal LSA that have local extension or distant mets at necropsy?

281
Q

Cat Nasal LSA characteristics?

A
  • 9-10 yrs
    -FeLV/FIV neg
  • 75% B cell
  • Siamese
    75% intermediate to high grade, epithiotropism
282
Q

Cat nasal LSA RR to RT alone?

A
  • CR 75-95%
  • MST 1.5-3 years
  • No CR MST 4.5 mo
  • dose affects response >32Gy recommended
283
Q

Cat nasal LSA RR to chemo alone?

A
  • CR 75%
  • MST 2 yr
284
Q

Cat Renal LSA characteristics?

A
  • ~ 9 yr
  • FeLV -/ up to 50% FIV + in one study
  • high grade B cell
  • often have GI involvment
285
Q

Cat MST renal LSA CHOP/COP?

A

4-7 mo

pred alone 50 d

286
Q

Cat CNS LSA characteristics?

A
  • 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
Q

Forms of cutaneous LSA in cats

A
  • most epitheliotropic T cell
  • cutaneous lymphocytosis
  • response to CCNu reported, sx for solitary lesion, generally indolent course, little info
288
Q

FeLV proteins

A

gp70, gp27

289
Q

Behavior of SQ or deeper structure LSA in cats?

A
  • 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
Q

Characteristics & Prognosis laryngeal LSA?

A
  • 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
Q

ALL vs CLL diagnosis BMA in cats? Prognosis?

A

15% - CLL, 90% RR chlorambucil for DFI 6 mo
30% - ALL, most T cell, poor 27% RR to CHOP/COP

292
Q

Cats w/ LSA receiving vinblastine other than vincristine will experience?

A

less GI SE and similar response

293
Q

Overall response rate for Elspar in cats w LSA ?

A
  • ORR 30%
  • Ammonia and aspartic acid increased from baseline at day 2 and 7
  • Asparagine decreased at day 2
294
Q

Biopsy risks for GI LSA in cats ?

A
  • 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
Q

MST and CR with intracavitary COP in cats w LSA ?

A
  • CR 76%
  • MST 388 d (13mth)w 54.1% alive at 1yr and 46.9% alive at 2yr
  • various forms (laryngeal, mediastinal, etc)
296
Q

Which of the following is true of bovine leukemia virus?

A

30% develop persistent lymphocytosis, NOT associated with juvenile LSA, less than 5 % get LSA

297
Q

Bull dog CLL

A
  • B-cell
  • Lower MHC II, CD25
  • splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM
  • Polyclonal
298
Q

What form of CLL is there circulating increased lymphocytes but no BM involved?

A

Tcell LGL, blast arise from spleen

CD11d+ CD8+ CD34-

299
Q

Is epirubicin an appropriate alternative to DOX in CHOP?

A

Yes
- CR 96%, TTP 7 mo, OST 11.5 mo
- Tcell and substageb do worse

300
Q

RR cytoxan rescue following chlorambucil cat low grade GI LSA?

A
  • 90% CR
  • DFI 239 d (~8 mo)
  • OST 1,065 d (35 mo)
  • achieving a CR associated with survival
301
Q

Peak [ ] and half life oral chlorambucil cats SCGI LSA?

A

peak 15 mins, 1/2 1.8 hour

  • secondary small peak 4 hours
  • no accumulation btw doses
302
Q

MST surgical resection intermediate to large GI LSA masses in cats?

A
  • 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
Q

Serum amyloid A (SAA) correlates with LSA stage in cats?

A

No but is higher in non-nasal vs nasal forms
- not ass. with outcome
- low hct neg prognosis

304
Q

RR and ST Pegylated L-spar sole therapy cat high grade LSA?

A
  • 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
Q

Protocol developed in FeLV endemic area (Brasil) that showed survival benefit in cats?

A

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
Q

Feline intermed-large GI LSA tx with CCNU and RT, protocol and outcome?

A

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
Q

MOPP rescue cat LSA RR?

A
  • 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
Q

What % of cats with SCGI LSA develop LCGI LSA?

A
  • 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
Q

CCNU, methotrexate, and cytosar protocol for relapsed high grade cat LSA, RR and outcomes?

A

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
Q

DMAC RR relapsed cat LSA?

A
  • 26% CB
  • TTP 14d, OST 17d
  • GR IV neutropenia and thrombocytopenia
311
Q

Cat nasal LSA tx with pRT (35 GY) alone vs pRT followed by chemo (CHOP/COP)

A
  • 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
Q

What are negative prognostic factors for cats with nasal LSA tx with SRT?

A
  • 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
Q

Failure patterns and frequency of cats with nasal LSA tx with RT alone?

A
  • 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
Q

Which prostaglandin has shown to be unregulated in B and T cell LSA compared to reactive LN in vitro?

315
Q

Immunophenotype of aggressive T cell leukemia in young English Bull Dogs?

A

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
Q

Which is more common, primary or metastatic cardiac tumors?

A

literature conflicting 84% primary, 16-86% secondary

  • HSA> aortic body tumors most common
  • Cat LSA
317
Q

Breeds at risk for cardiac HSA? Aortic body tumors?

A

HSA - Golden, GSD
ABT - brachycephalic bulldogs, bostons, boxer 2nd to chronic hypoxia

318
Q

Sn of x-rays for daignosis of cardiac HSA?

319
Q

Sn and sp of detecting cardiac mass with pericardial effusion via echo?

A

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
Q

What is the most important factors leading to false neg when detecting cardiac mass via echo?

A

location (extra pericardial, non cavitary pericardial, auricular) and size

R atrial detection rate 95% r auricular 60%

321
Q

What % of dogs with cardiac tumors have pericardial effusion?

A

42% - most common with HSA 82% of cases

322
Q

Is cytology of pericardial effusion helpful in dx cardiac tumors?

A

No - 8% dx

  • improves if hct <10% to 20% dx rate
323
Q

Cardiac troponin I (cTnI) is higher in dogs with effusion secondary to HSA, what is the cut off value?

A

0.25 ng/mL - marker of myocardial ischemia and necrosis

324
Q

% of dogs with suspected primary HSA with mets?

A
  • spleen 29%
  • liver, mesentery, etc 42%
  • 8.7-24% of dogs with splenic HSA have concurrent R atrial mass
325
Q

Which tumors types does subtotal pericardectomy improve outcome?

A

Heartbase mass and mesothelioma regardless of whether effusion is present at time of DX

  • Not for HSA
326
Q

T/F: single 12 Gy RT to right atrial masses improves survival?

A

F - safe and decreased frequency of palliative pericardiocentesis only

327
Q

Prognosis cardiac HSA tx with surgery and chemo vs surgery alone?

A
  • SX 16d - 4 mo
    + chemo ~6 mo
328
Q

Prognosis heart HSA DOX alone?

A
  • 41% PFS time of 66 days
  • MST ~3.5-4.5 mo
329
Q

Prognosis aortic body tumors with pericardectomy?

A
  • 22 - 24 mo
  • no pericardectomy ~1-4mo
330
Q

What tumors arise from the paraganaglia?

A

Pheo, aortic body tumors, carotid body tumors; Pheo-secrete norepi/epi & aortic/carotid-PSNS-neg chromaffin cells

331
Q

Risk factor associated with death during pericardectomy?

A

ventricular fibrillation - may be associated with electrosurgical devices and cardiac manipulation but not definitievly

332
Q

Response aortic body tumors treated with fractionated RT? SRT?

A
  • 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
Q

Palliative surgical option for ventricular obstruction secondary to intracardiac masses?

A

translatorial stenting
- successful in 3 dogs 2 unobstructed at 14 mo

334
Q

Palladia for aortic body tumors?

A

10% ORR
- MST if mets 17 mo, no mets 25 mo (not different)
- 90% showed CB with 81% complete resolution of clinical signs

335
Q

What is the most potent APC for the induction of naive T cells?

A

Dendritic cells
- CD11b drives CD4+
- interdigititating DC DC8+: LN/spleen
- interstitial DC CD103: perivascular
- costimulation necessary for activation of naive T cells

336
Q

Where do histiocytes differentiate from?

A

CD34+ stem cell precursors into several dendritic cell lineages

337
Q

Which cytokines and GF influence dendritic cell development?

A

FLT3, GM-CSF, TNFa, IL4, TGFb

338
Q

CD expression of histiocytes

A

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
Q

Histiocytoma - species, cell of origin, key features, immunophenotype?

A
  • Dog
  • Langerhans
  • epidermal focus “top heavy” lesions
  • CD1a, CD11c, CD18, E-cadherin, Iba-1 positive
  • CD204 neg
340
Q

Cutaneous Langerhans cell histiocytosis - species, cell of origin, key features, immunophenotype?

A
  • Dog
  • Langerhans
  • multiple cutaneous lesion, LN and internal mets possible
  • CD1a, CD11c, CD18, E-cadherin, Iba-1 positive
  • CD204 neg
341
Q

Pulmonary Langerhans cell histiocytosis- species, cell of origin, key features, immunophenotype?

A
  • Cat
  • Langerhans
  • multinodular, diffuse involvement of lung lobes
  • Birbeck’s granules on TEM
  • CD1a, CD4, CD11c/CD18, E-cadherin, Iba-1, CD204
  • V aggressive!

look like tennis racket if shown an image

342
Q

Cutaneous histiocytosis- species, cell of origin, key features, immunophenotype?

A
  • 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
Q

Systemic histiocytosis- species, cell of origin, key features, immunophenotype?

A
  • 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
Q

Histiocytic sarcoma- species, cell of origin, key features, immunophenotype?

A
  • Dog, cat
  • interstitial (perivascular) dendritic cell
  • masses on spleen, lung, liver, LN
  • CD1a, CD11c/CD18, Iba-1, CD204 (variable)
345
Q

Hemophagacytic histolytic sarcoma- species, cell of origin, key features, immunophenotype?

A
  • 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
Q

Feline progressive histiocytosis - species, cell of origin, key features, immunophenotype?

A
  • cat
  • interstitial DC
  • skin nodules and plaques
  • CD1a, CD11c/CD18/CD5 (50%), Iba-1, CD204 (variable)
347
Q

Dendritic cell leukemia - species, cell of origin, key features, immunophenotype?

A
  • dog
  • interstitial dc
  • blood/bm
  • CD1a, CD11c/CD18, IBA1- CD204
348
Q

2.5 year old dog with rapidly growing solitary raised pink mass on shoulder - primary differential, tx, how to confirm dx?

A
  • histiocytoma
  • benign, typically regress 1-2 mo
  • E-cadherin UNIQUE to histiocytomas but rarely needed
349
Q

How do histiocytomas regress?

A

CD8+ alpha-betaT lymph infiltration - cytotoxic
- never immunosuppress a p while trying to regress

350
Q

TX options and prognosis cutaneous langerhans cell histiocytosis?

A
  • 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
Q

Breed with familial systemic histiocytosis?

352
Q

How is systemic histiocytosis and cutaneous histiocytosis treated?

A
  • these are the reactive histiocytosis types
  • immunosuppressive therapy typically with pred
  • long term survival, various maintenance therapies
353
Q

Genetic alterations shared between Bernese mt dog and flat coated retrievers? Types of HS in each breed?

A
  • deletions of CDKN2A/B, RB1, and PTEN (chromosome 10)
  • p53 46% in various breeds
  • BMD diffuse
  • FCR localized esp limbs
354
Q

IHC to differentiate periarticular HS from synovial cell tumor?

A

CD18, cytokeratin, SMA

355
Q

SN and Spec of CADET HS assay?

A

Sn 78%, spec 95%

356
Q

Lung lobe most commonly affected by HS?

A

right middle

357
Q

What may be a blood parameter used as screening for Berners predisposed to HS?

A
  • ferritin - higher in dogs with HS or pre development
  • also dogs with HS have higher fibrinogen,C-RP, and monocytes chemotactic protein 1
358
Q

Prognosis periarticular HS?

A
  • ~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
Q

CCNU ORR gross dz HS?

A
  • 46% for 2.8 mo
  • MST responders 5.7 mo vs 2 mo non responders
  • steroids do noti mprove response to therapy
360
Q

Lab abnormalities associated with hemophagocytic HS subtype?

A

severe anemia, thrombocytopenia, hypocholesterolemia, hypoalbuminemia

361
Q

MST localized HS tx with SX, RT, and CCNU?

362
Q

CCNU + DOX ORR HS?

A

-alternating q 2 week
- 58% TTP 6 mo

363
Q

Rescue drugs for HS and response rates?

A

Dacarbazine 18%
Epirubicin 29%

  • Case reports/series of liposomal DOX + paclitaxel, metronomic, clodronate, etc
364
Q

Anatomic sites of localized HS in cats?

A

tarsus, nasal planum, stomach

  • also get diffuse and hemophagocytic forms
  • all HS thought to be agressive
365
Q

Clinical course feline progressive histiocytosis?

A
  • skin lesions that typically spread internally late in the disease median 13.4 mo
  • no known therapy =, steroids dont seem to help
366
Q

Breeds for HS?

A

Berner, flat coated reliever, Rotties, mini- schnauzers

367
Q

Possible predisposition for periarticular HS in Berner?

A

prior joint disease ~88% of dogs
- CCL most common

368
Q

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?

A

benign neglect

369
Q

Common location for HS in mini schnauzer? Outcome with various treatments?

A
  • 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
Q

Alternative drug to CCNU with similar activity for HS?

A

Nimustine 25 mg/m2 q3-5 week
- OST gross disease 4mo, adjuvant setting 13 mo
- neutropenia

371
Q

ORR DOX first line for HS (localized or disseminated)?

A

26% ORR, 43% localized, 21% disseminated
TTP 42d, MST 5.6 mo

372
Q

Gain of function pathway in Bernese HS?

A

PTPN11e76k in ~37% via ERK/AKT

373
Q

Intracellular expression of CD5(AIM) apoptosis inhibitor of macrophages may be a marker for?

374
Q

mRNA sequence analysis of HS?

A
  • 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
Q

MST localized splenic HS treated with splenectomy and CCNU?

376
Q

MST of dogs undergoing curative intent lung lobectomy + CCNu for localized HS?

A

9- 14 mo
- LN mets NOT significant or sx margins

  • chemo only MST ~ 4mo-6 mo
377
Q

Is RT an appropriate alternative tx option for periarticular HS to sx?

A
  • 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
Q

CD206 Langehans cells expression from bottom of tumor to epidermis correlate with?

A
  • tumor regression phase and intratumoral T lymphocyte infiltrate
  • CD206 change in cells = change to mature phenotype with tumor regression
379
Q

Other cell line HS stuff

A
  • 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
Q

Corgi with disseminated CNS HS, what to TX with?

A
  • 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
Q

Differences in cell markers CNS vs periarticular HS?

A
  • 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
Q

HS prognostic factors associated w <1 mo survival?

A

palliative tx, disseminated HS, and concurrent use of corticosteroids

Onco boards 2024 (17 decks)

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