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Sarah - Equine > Chapter 16 - Neoplasia > Flashcards

Chapter 16 - Neoplasia Flashcards

1
Q

Classical equine viral papillomatosus occurs in young horses at which body site?

A

Most commonly on the muzzle and lips

Less commonly the eyelid, genitalia and distal legs

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2
Q

How long does spontaneous remission of classical equine viral papillomatosus in young horses take?

A

2-3 months

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3
Q

Equine ear papillomas

a) spontaneously resolve rarely
b) spontaneously resolve commonly

A

rarely

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4
Q

Which insect may help transmit equine ear papillomas?

A

Black flies (Simulium)

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5
Q

At what age do equine genital papillomas occur?

A

Older (13-28 years)

Can be precursor for SCC

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6
Q

Which type of immunity is key in papilloma regression, humoral or cellular?

A

Cellular

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7
Q

In equine papillomatosis, are viral inclusion bodies intracytoplasmic or intranuclear?

A

Intranuclear

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8
Q

How is epidermal pigmentation affected in equine papillomatosis?

A

It is hypopigmented

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9
Q

Which topical treatment may help resolve equine ear papillomas?

A

Imiquimod

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10
Q

What is the most common neoplasm of the eyelid and genitalia in horses?

A

Squamous cell carcinoma

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11
Q

Which enzyme is thought to aid neoplasm growth and invasion by increasing angiogenesis, invasiveness, and metastasis; inducing resistance to apoptosis?

A

COX-2

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12
Q

Is UV light exposure important in the development of basal cell tumours in horses as it is in people?

A

No - they develop in haired, dark-skinned areas in horses

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13
Q

Which are more commonly reported in horses, basal cell tumours or trichoepitheliomas?

A

Basal cell tumours

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14
Q

Which bovine papilloma viruses are associated with equine sarcoids?

A

BPV-1 and BPV-2

BPV-13 also reported

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15
Q

What are the predilection sites for occult sarcoids in horses?

A

Predilection sites include the perioral and periorbital areas, neck, other relatively hairless areas (e.g., medial surface of forearm and thigh; axilla; groin), sheath, and shoulder.

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16
Q

Which type of sarcoids can occult sarcoids progress to?

A

They usually progress to verrucous sarcoids or, particularly if traumatised, may rapidly develop into fibroblastic sarcoids.

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17
Q

What is a differential for a papillomatous lesion in an adult or older horse?

A

Verrucous sarcoid

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18
Q

What are the predilection sites for nodular sarcoids in horses?

A

Predilection sites include periorbital region, groin, and sheath.

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19
Q

Which type of sarcoid resembles exuberant granulation tissue?

A

Fibroblastic sarcoid

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20
Q

What are two differentials, other than exuberant granulation tissue, for fibroblastic sarcoids?

A

Infectious (bacterial, fungal) granulomas, habronemiasis, and squamous cell carcinomas

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21
Q

Which type of equine sarcoid is best described as below:
A history of repeated trauma (e.g., surgery) is commonly described. Lesions are aggressive and deeply invasive. One or more “cords” of tumor (lymphatic involvement) are commonly palpated, and numerous ulcerated nodules may be present.

A

Malevolent (malignant) sarcoid

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22
Q

Name the six types of sarcoids in horses

A 
Occult
Verrucous
Nodular
Fibroblastic
Malevolent (malignant)
Mixed
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23
Q

True or false?

On histopathology, distinct borders separating neoplasm (sarcoid) and normal tissue are often absent.

A

True

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24
Q

Are mitoses typically high or low on histopathology of equine sarcoids?

A

Typically low (1/HPF)

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25
Q

What causes the ‘picket-fence’ pattern on histopathology of equine sarcoids?

A

Fibroblasts at the dermo-epidermal junction are frequently oriented perpendicularly to the basement membrane zone in a so-called “picket fence” patter

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26
Q

In equine sarcoids, has BPV been demonstrated in keratinocytes or dermal spindle cells?

A

Dermal spindle cells

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27
Q

Weibel-Palade bodies, which can be seen on electron microscopy, are a specific cytoplasmic marker for which cells?

A

Endothelial cells

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28
Q

Haemangiomas and haemangiosarcomas can be congenital in horses, true or false?

A

True

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29
Q

Which type of melanocyte tumours occur in young horses (<2 years), are usually solitary and occur most commonly on the legs or trunk?

A

Melanocytomas

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30
Q

What % of grey horses over 15 years of age are estimated to have melanomas?

A

80%

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31
Q

What are the histopathological findings of melanomas in horses?

A

Histopathologically, melanomas are characterized by atypical melanocytes in sheets, packets (nests or theques), and cords. The melanocytes may be predominantly epithelioid, spindle, or a combination of these

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32
Q

Has aberrant KIT expression been demonstrated in horses with cMCTs?

A

Yes, the majority are benign with KIT pattern 1 however, in Ressel et al. (2015), in ~1/3rd there was more infiltrative growth, anisokaryosis and proliferation with KIT 2 and 3 patterns – there is a subgroup of poorly differentiated equine cMCTs

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33
Q

What are the histopathological differentials for cMCTs in horses?

A

Eosinophilic granulomas (older lesions contain variable degrees of fibrosis and palisading granuloma formation)

Calcinosis circumscripta (dystrophic mineralisation is frequently seen in areas of collagen degeneration and necrosis)

34
Q

What are the subgroups of fibroblastic sarcoids?

A

Type 1 Fibroblastic sarcoid with a narrow pedicle (stem attaching the sarcoid to the body)
- Type 1a Fibroblastic Sarcoids have no root extension beyond the pedicle or stem
- Type 1b Fibroblastic Sarcoids have a narrow pedicle or stem but a root that extends into the body beyond the pedicle.
Type 2 Fibroblastic Sarcoid with no pedicle

35
Q

What are the differential diagnoses for occult sarcoids?

A

Infectious folliculitis (bacterial, dermatophytosis) and alopecia areata

36
Q

What are the differential diagnoses for malignant sarcoids?

A

Other invasive neoplasms and infections granulomas with lymphangitis

37
Q

What are the major oncoproteins of BPV associated with sarcoid development?

A

E2, E5, E6 and E7

38
Q

Has BPV been detected in equine skin not associated with sarcoids?

A

Yes, normal skin and some cases of dermatitis and some reports of schwannomas and fibroscarcomas
Not specific test for sarcoid

39
Q

Have BPV protein levels been associated with severity of disease in equine sarcoids?

A

Yes, E2, E5, L1 and L2 DNA levels and E2, E5, E6 and E7 mRNA abundance have been positively correlated with severity of disease

Highest expression was observed in the aggressive fibroblastic variant and nodular sarcoids

40
Q

Studies looking at immunotherapy for equine sarcoids have shown that the use of which proteins can induce protection against BPV infection or enhance tumour regression and reduce progression?

A

BPV-1 L1 and E7

41
Q

The invasiveness of sarcoids is associated with dysregulation in the functioning of which enzymes?

A

Matrix metalloproteinases (MMPs)

42
Q

How is MMP expression increased in equine sarcoids?

A

Expression of MMP-1 can be increased by BPV-1 oncoproteins E6 and E7 through the activator protein 1 (AP-1) and by E5 via an indirect mechanism.

MMP production is also stimulated by vascular endothelial growth factor (VEGF), which is strongly expressed in equine sarcoid.

43
Q

Decreased expression of TLR4 in equine sarcoids is due to expression of which BPV-1 oncoproteins?

A

E2 and E7

44
Q

Which BPV-1 oncoprotein downregulates MHC I expression?

A

E5

45
Q

Which proteins, other than BPV oncoproteins, may be involved in the pathogenesis of equine sarcoids?

A
  • platelet-derived growth factor b receptor (PDGFb)
  • p38 mitogen-activated protein kinase (MAPK)
  • Role of p53 (regulates DNA repair, cell cycle, apoptosis, cellular metabolism and initiation of cell death) unclear in equine sarcoids
  • S100 calcium-binding protein A14 (S100A14), which inhibits proliferation and cancer cell metastasis
  • Fragile histidine triad (FHIT)100, a tumour suppressor gene, is reduced or absent in sarcoid tissues
46
Q

Increased transcription of FOXP3 (fork 3 protein) and interleukin 10 (IL10) has been demonstrated in equine sarcoids associated with BPV-1 E5 mRNA; FOXP3 is a marker for what?

A

Treg cells – suggests local, Treg induced immune suppression

47
Q

Which insect is the proposed vector for BPV spread in horses?

A

Stable flies (Stomoxys calcitrans)

48
Q

Are the BPV-1 strains found in horses the same as those found in cattle?

A

Yes – they are a common host and viral transfer between species is common

49
Q

Which body sites are most often affected with sarcoids?

A

Head, ventral abdomen, limbs (ventrum and limbs are feeding sites for stable flies)

50
Q

Has metastatic disease been reported with sarcoids?

A

No, including no spread to local LNs

51
Q

Can sarcoids spontaneously regress?

A

Yes – studies report variable proportions - can be up to ~1/3 of cases (usually milder forms e.g. occult or verrucous)

52
Q

What are the typical histopathological changes on histopathology of equine sarcoids?

A

Increased density of dermal fibroblasts - proliferation of interlacing bundles and whorls of spindle-shaped fibroblasts

Epidermis is hyperplastic (54-67%) and hyperkeratotic with long rete peg-like extensions (46-88%) into the dermal mass

At the dermoepidermal junction there is a characteristic perpendicular orientation of fibroblasts toward the basement membrane, reminiscent of a picket fence (48-91%)

53
Q

What are histopathological differentials for equine sarcoids?

A

Fibroma, fibrosarcoma or neurofibroma

No reliable IHC marker for sarcoids

54
Q

What are the surgical treatment options for equine sarcoids?

A

Traditional, electro-, cryo- and laser

55
Q

What are the chemotherapy treatment options for equine sarcoids?

A
  • Topical: Acyclovir (has little or no effect), 5-fluorouracil (5%) ointment, AW5 (combination of fluorouracil, thiouracil, heavy metal salts and steroid), Imiquimod 5%
  • Intralesional: cisplatin
  • Systemic rarely used
  • Electrochemotherapy and calcium electroporation - alone or as an adjunct to surgery
56
Q

What are the immunotherapy treatment options for equine sarcoids?

A

bacillus Calmette-Gue ́rin (BCG)
Autogenous vaccines and BPV-1 L1
BPV-1 E6 and E7 (with influenza vector)
recombinant canarypox virus expressing feline IL-2

57
Q

What are the radiotherapy treatment options for equine sarcoids?

A

Brachytherapy using radon, iridium and gold

Plesiotherapy using decaying strontium (limited evidence)

58
Q

What are the phytotherapy treatment options for equine sarcoids?

A

Sanguinaria canadensis (blood root plant) + zinc chloride

59
Q

In the paper by Loschelder-Ostrowsk et al. (2021), what % of horses improved with the use of intralesional recombinant canarypox virus expressing feline IL-2?

A

Complete regression was achieved in eight horses (40%) and partial regression in two horses (10%)

60
Q

In the paper by Petterson et al. (2020), what % of horses improved with either topical imiquimod or Sanguinaria canadensis (blood root plant) + zinc chloride?

A 
Imiquimod: complete remission was recorded in 84.4% and replapse in 7.3%
Sanguinaria canadensis (blood root plant) + zinc chloride: complete remission was recorded in 75% of the tumours and relapse in 21.4%

Spontaneous remission was observed in 1.9% of untreated tumours.

61
Q

Which breeds of horse are predisposed to SCC?

A

Lightly pigmented draft breeds (Belgian, Clydesdale, Shire)

Appaloosas, Pintos, Quarter horses, Thoroughbreds

62
Q

SCC is most commonly found at which body sites in the horse?

A

Eyelid, prepuce, vulva, penis

63
Q

Which type of equine papilloma virus has been associated with genital SCC?

A

EcPV-2 (not associated with other SCC!)

64
Q

Which medications have reportedly been used to treat equine SCC?

A 
Cisplatin in sesame oil intratumorally
5-fluorouracil cream
Bleomycin intratumorally
Doxorubicin IV
Piroxicam
Tigilanol tiglate
65
Q

Have vaccine-associated fibrosarcomas been reported in the horse?

A

Yes, a myofibroblastic fibrosarcoma with multifocal osseous metaplasia associated with influenza vaccination

66
Q

Fibromas in horses are most common at which body sites?

A

Can occur anywhere but most common on the periocular skin, neck and leg

67
Q

How do fibromas differ from fibrosarcomas clinically?

A

Both are firm to fleshy nodules; fibrosarcomas are poorly demarcated, have subcutaneous infiltration and are frequently ulcerated and infected

68
Q

Equine genital SCC may be associated with activation of which pathways?

A
  • RANKL/RANK and IL17 (receptor activator of nuclear factor-kappa B ligand)
  • canonical and non-canonical Wnt signaling pathway that could be critical for carcinogenesis and tumor progression
69
Q

What are the strongest negative predictors of overall survival time in equine SCC?

A
  • Lack of treatment

- Recurrence post-treatment

70
Q

How common are these skin tumours, arising from structural cells, in the horse?

A
71
Q

What are predilection sites for melanomas in horses?

A

Eyelid, parotid, perianal or perigenital, lips, sheath

72
Q

How long can it take for SCC metastases to become apparent?

A

Can take several years!

73
Q

Which other tumour do basal cell carcinomas look like?

A

Sarcoids (nodular/fibroblastic)

74
Q

Name a molecular marker of malignancy in melanomas in horses

A

RACK1 (receptor for activated C kinase 1)

75
Q

All gray horses inherited a single gene mutation, ____, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma.

A

STX17

Horses of any base color (black, bay, chestnut) with STX17 G at one or both alleles (i.e. G/g or G/G) will become gray

76
Q

Apart from STX17, the coat color genes ____ and ____ add risk such that relative likelihood of melanoma based on pre-graying coat color is black > bay > chestnut.

A

ASIP (encodes agouti signaling protein)

MC1R (encodes melanocortin-1 receptor)

77
Q

Melanomas begin at 4 years. Each year thereafter, prevalence increases by what %?

A

4% to 8%

78
Q

Which ASIP phenotype carries the lowest risk of melanoma?

A

AA

79
Q

Which MCR1 phenotype carries the highest risk of melanoma?

A

EE

80
Q

Which ASIP/MCR1 phenotype carries the highest risk of melanoma?

A

aa/EE

81
Q

What are the treatment options for melanomas in horses?

A
  1. Surgery (including CO2 and cryo)
  2. Intralesional cisplatin or carboplatin beads or slow-release emulsions
  3. Electrochemotherapy
  4. Hyperthermia (adjunctive)
  5. Radiation (brachytherapy)
  6. Oncept vaccine (tyrosinase - licensed for dogs)?

Sarah - Equine (13 decks)

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