Papilloma Flashcards
What is a koilocyte (Welle, Maulidn, JPC)
swollen keratinocytes with eosinophilic to lightly basophilic cytoplasm and perinuclear halo
-can have multiple nuceli
Name viral cytopathic effects papilloma (JPC)
- Koilocytes
- Intranuclear inclusion bodies
- Large, irregular keratohyalin granules (in exophytic types)
- Variable degress of ortho/para HK
- Degenerating KC with eosinophilic cytoplasmic inclusions (represent aggregates of keratin)- may be confused with POX!
How are papillomaviruses sperad
- Transplacental (FcPV-a in almost all cats from early in life)
- Fomites (direct and indirect contact)
- Skin abrasions
- bovine- arthropod, vertical, blood
- horse-flies, miking machines + co factors: malnutrition, hormonal imbalance, mutations, long term exposure to sunlight
Name 3 genera
- Lambda
- Tau
- Chi
What are the predispositions /predilections
- IgA deficiency- oral papillomatosis
- GC, chemotherapy
Predilection in old animals (accumulations of spontaneous mutations throughout life)
Which proteins are involved in malignant transformation
- p53
- p16
How does the infection occur
- Microtrauma allows PV to intreact with BM
- PV enters cells after binding to alpha 6 integrin - infects KRT in SB
- Basal cell replication- episomal DNA spread through basal cell population and maintain infection, during this phase normal epithelial regulation not altered, infection is asymptomatic, non-infective
- PV to complete the life cycle - in a basal cell that undergoes terminal differentiation
- Replication of PV DNA dependent on host nucelus
-key feature: ability to prevent cells from leaving the S phase (where DNA replicate , ensure that KC keep dividing, amplifies infection because every divided KC will be infected - genome replication in SS and SG
- release new infection in keratinized squames - achantosis, HK, koilocytes in SS, giant KH granules in SG
PV- induced cancer. What is the critical step
integration od E6 and E7 genes (proteins- oncogenes) in host DNA
Where are early genes expressed
in basal and suprabasal layers
Where are late genes expressed
in SS and SG
Where are virions expressed
-upper SG and SC
How are infective viruses spread
-released due to normal cell death
What are the methods of evading immune system (ch infections)
- infection of immune privileged site (epidermis, HF)
- no idnuction of type I IFN of infected KC by CPV-2
Name 3 components of genes
- Early genes (E7)
- Late genes (L2)
- LCR - long control region
What are the oncogens
E5,E6,E7
What is the function of E1, E2
-regulation of viral DNA replication
Function of E3
modulates immune response of infected cells
Function of E4
disrupt cytokeratins facilitating viral release (viral replication)
Function of E5
BPV-1, BPV-2
-inhibits intercellular communication through gap junctions
-activates PDGF receptor
-down regulates MCH-1
-interactions with growth factors
functions of E6 and E7
= cell proliferation and immortalization
E6-disrupts focal adhesions, degrade p53 (accumulate various mutations)
E7-cell growth, chromosomal instability, , inhibit retinoblastoma (Rb): important tumor suppressor protein
What is function of late genes
=coded in SS and SG
L1, L2- genes encode for viral capid protein
L1- major capsid protein highly immunogenic, used to classify PV in genera
What are LCR (long control region)
-does not code proteins
-regulates viral gene transcription (when and which genes are necessary in the process of infections)
How can dg be made
- PCR
- In situ hybridization
- EM
- Rolling circle amplification
- IHC
- Histo
- Clinical examination
- Blot: southern, dot, reverse
How is IHC used for dg PV
-SG: Ab detect L1 protein or increased p16
-L1 protein forms the capsid- largely produced in late process of viral repilcation
-rarely present in advanced BISC or in PV + SCC
DDX in dogs
- IKA
- trichofolliculoma
- cutaneous horn
- lentigo
- melanocytic neoplasms
DDX in cats
- MCT
- cutaneous horn
- dilated pore of Winer
- melanocytic neoplasms
How can you differentiate pathogenic PV and asymptomatic infection in lesions of other etiology
p 16 protein expression
+ in PV induced skin lesions
In bovine which animals usually develop disease
-young cattle
-usually regress, may lead to neoplasia + environmnetal cofactors
ch ingestion of bracken fern ( Pteris aquilina)
ch immunosupressed animals
infection with BVDV
Which PV cause oral papilomas in dogs
CPV-1 (SCC) , 3, 13
What are associations for development of oral papilomas in dogs
- IgA deficiency (beagle)
- GC: severe oral + generalized cutaneous in young Shar Pei
- CsA- anecdotal
- chemotherapy
- Imunosupressive th?
- UV radiation?
Which PV cause exophtic papilloma in dogs
CPV-1, 2, 7, 14
Which breeds are predisposed to exophtic PV and age ?
- Kerry blue
- Cocker
- CsA
+ OLDER DOGS
+ can udergo sponatenous remission
What are recommedned treatments for exophytic PV in dogs
- 4-fluorouracil topical
- imiquimod
- oral etretinate
Which PV are associated with generalised verrucosis PV
CPV-2, 9
Which PV are associated with inverted papiloma and which is associated with SCC
CPV-1, 2, 6
CPV-2 SCC
Which PV are associted with feline cutaneous papilloma
FcPV-1
-melanocytic macules-> HK pigmnted plaques, greasy
-2 Persian cats /immunosompromised
How are caprine cutaneous PV manifested
- First form: no predilection, self cure, multiple animals
- Second form
- white females that lactated at least once
-udder, teats
-no self cure
-may transform to SCC
How are ovine cutaneous PV manifested
- FILIFORM SQUAMOUS PAPILLOMAS
-legs young,
- scrotum rams
- face , pinnae, legs, teats adults
-facial can transform to SCC - FIBROPAPILLOMA
-adults
-facial into SCC
-Merinos may be at risk
Are cutaneous papilomas reported in pigs
yes
-congenital
-face and genitalia
In birds, where are papillomas most commonly reported
-cloaca
-feet, head, mm
-often proliferative,
-th: autogenous vaccines, laser
Have PV been reported in snakes
yes
Which are unique camelid PV
- viral papillomas
- fibropapillomas
Name other PV in camelids
1,5-cauliflower like on penis
2,6-typical papillomas
2,7-congenital probable epidermal nevus
8- frond like
3, 9
5- finger like or rice grain on teat
What does PV in rabbits cauase
ā Shope PVā
Cotton tail rabbit PV
What PV cause in primates
-warts
-epidermal hyperplasia
-oral plaques
Which PV are associated with pigmented plaques in dogs
CHI
CPV-4 + 3,5, 8, 9, 16
CPV-4 pugs, viszla
-can progres to SCC (not in pugs)
What are predilections for canine pigmented plaques
- young
- min Schnautzer
- pug - autosomal mode if inheritance
- Boston terrier
- French bulldog
- Viszla (genetic pred in Australia?)
- Chinese Shar pei
What is recommended for canine viral plaques
-usually not effective
1. Tigilanol tigilate - 2 times 9 days apart
2. imiquimod
Which PV are assocaited with viral plaques in cats?
FcPV-2 (BISC)
+3,5
What are predispositions for feline pigmented plaques
- early age- Sphinx, Devon rex: highly metastatic SCC
- underlying immunosupersion- FIV, FeLV, Ch GCs
- usually middle age, old
Feline sarcoid/feline cutaneous fibropapilloma
BPV-14, 1
Equine sarcoid
BPV1,2, 13
Which PV is associted with cutaneous horn
CPV-1
What are other causes of cutaneous horns
- solar dermatitis
- skin carcinoma
- IKA
- intracutaneous epithelioma
- keratin cysts
- viral papilloma
- FeLV
Name treatment options for PV
- Azytrhomicin
- Surgery
- Laser, cryosurgery, electrosurgery, CO2 laser ablation
- Cryotherapy ( 2 sessions)
- Freezing or crusing (Ag stimulation)
- IFN-alpha (low dose po, high dose intralesional, INF-omega)
- Topical 4-fluorouracil, 5-fluorouracil (no CATS- neurotoxic)
- Imiquimod
- Photodynamic th
- Retinoids
- Tatantula venom
+ VACCINE
In wich species horn have been seen
-bovine, goat, ovine, rabbit
Which vaccines have been developed for PV
- Live autologous- protective, associted with injection site SCC
- Modified (formalin inactivated or replication deficient)- no SCC
- recombinant- induce regression, may be prophylactic
