Oral Papillomatosis in a Dog: Surgical Management and Histopathological Findings

Abstract

Canine oral papillomatosis is a viral disease that commonly affects young dogs. A six-month-old male German shepherd dog was presented with a history of progressively developed nodular growth in the lip, gingiva and tongue. All physical parameters were found to be normal. The animal was pre-medicated using atropine, butorphanol and diazepam as per the standard pre-anesthetic protocol. General anaesthesia was induced using ketamine hydrochloride. General maintenance was provided using Ketamine-diazepam mixture and the nodular masses were removed using a combination of surgical excision and electrocautery. Post-operatively, the animal was treated with antibiotics for five days and anti-inflammatory drugs for three days. Excised tissue samples were processed and subjected to standard histopathological examination. Histopathologic examination revealed a diffuse epidermal hyperplasia, marked neovascularization, koilocytes with clear perinuclear vacuolization and keratinocytes with keratohyalin granules.
The findings were suggestive of canine oral papilloma virus induced papillomatosis. The animal made an uneventful recovery without any recurrence. This paper describes the successful surgical management of canine oral papillomatosis without any recurrence and its peculiar histopathological findings

Full text

NE
US
Academic Publishers
Advances in Animal and Veterinary Sciences
April 2020 | Volume 8 | Issue 4 | Page 408
INTRODUCTION
Canine oral papillomatosis is a viral disease of dogs,
which is caused by the canine oral papillomavirus
(CPV ) that comes under the family Papovaviridae (Nicholls
and Stanley, 1999). Canine oral papillomavirus consists
of a group having eight viruses, which are represented
by CPV-1 to CPV-8. Among these viruses, CPV-1 is
responsible for causing canine oral papillomatosis in young
dogs (Lange and Favrot, 2011). e Papillomavirus is a
DNA virus that has special anity towards the cutaneous
squamous or mucosal epithelium (Gross et al., 2008).
Canine papillomatosis is commonly seen in mixed-breed
dogs of age in between 6 months to 10 years, and majority
of the lesions are seen in skin followed by lips (Bianchi et
al., 2012). Studies conducted by Sundberg et al., 1994 have
reported that dogs with immunosuppressive disorders are
highly predisposed to canine papillomatosis. Canine oral
papillomatosis is characterized by the presence of multiple
cauliower-like masses seen commonly on the tongue, lips,
palate gingiva, buccal mucosa and pharynx (Teifke et al.,
1998).
Canine oral papillomatosis has a specialized ability for
spontaneous regression due to development of cell-
mediated immune responses that may develop over a period
of up to 12 months in naturally infected animals (Sancak
et al., 2015). Hence surgical management is indicated in
most cases for the immediate removal of papillomas due
to its superior results when compared to other modes of
Case Report
Abstract | Canine oral papillomatosis is a viral disease that commonly aects young dogs. A six-month-old male
German shepherd dog was presented with a history of progressively developed nodular growth in the lip, gingiva and
tongue. All physical parameters were found to be normal. e animal was pre-medicated using atropine, butorphanol and
diazepam as per the standard pre-anesthetic protocol. General anaesthesia was induced using ketamine hydrochloride.
General maintenance was provided using Ketamine-diazepam mixture and the nodular masses were removed using a
combination of surgical excision and electrocautery. Post-operatively, the animal was treated with antibiotics for ve
days and anti-inammatory drugs for three days. Excised tissue samples were processed and subjected to standard
histopathological examination. Histopathologic examination revealed a diuse epidermal hyperplasia, marked
neovascularization, koilocytes with clear perinuclear vacuolization and keratinocytes with keratohyalin granules.
e ndings were suggestive of canine oral papilloma virus induced papillomatosis. e animal made an uneventful
recovery without any recurrence. is paper describes the successful surgical management of canine oral papillomatosis
without any recurrence and its peculiar histopathological ndings.
Keywords | Canine, Papillomatosis, Wart, Electrocautery, Surgical excision
Khan Sharun1*, KalaiSelvan e1, Sindhoora K2, FaSlu rahman aT2, azam Khan1, am Pawde1,
amarPal1
Oral Papillomatosis in a Dog: Surgical Management and
Histopathological Findings
Received | November 12, 2019; Accepted | March 12, 2020; Published | March 25, 2020
*Correspondence | Khan Sharun, Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India; Email: shar-
unkhansk@gmail.com
Citation | Sharun K, Kalaiselvan E, Sindhoora K, Faslu Rahman AT, Azam Khan, AM Pawde, Amarpal (2020). Oral papillomatosis in a dog: Surgical management
and histopathological ndings. Adv. Anim. Vet. Sci. 8(4): 408-411.
DOI | http://dx.doi.org/10.17582/journal.aavs/2020/8.4.408.411
ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331
Copyright © 2020 Sharun et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
1Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India; 2Division
of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.

NE
US
Academic Publishers
Advances in Animal and Veterinary Sciences
April 2020 | Volume 8 | Issue 4 | Page 409
therapy. Canine tumors can be treated using therapeutic
strategies involving dierent modes of treatments such
as surgical excision, chemotherapy, radiation therapy, and
immunotherapy (Sharun et al., 2019)
e present paper reports a case of canine oral papillomatosis
involving lips, gingiva and tongue that was managed by
surgical excision and electrocautery.
CaSe hiSTory and CliniCal examinaTion
A six month old male German shepherd dog was presented
with a history of nodular growth in the lip, gingiva and
tongue that developed progressively over a period of
one month. e owner reported that the animal had
progressive loss of appetite during this period. On physical
examination, the animal showed normal rectal temperature
(102.5 °F), respiratory rate (20/minute), and heart rate (90
bpm). Clinical examination revealed presence of multiple
nodular growth (>25) of 2-16 mm diameter, which was
dispersed over the oral mucocutaneous junction involving
the lips and the gingiva, which was visible externally.
Examination of the oral cavity further identied multiple
(>12) hard pale pink cauliower shaped nodules of 3-15
mm diameter in the tongue margin (Figure 1). Due to
the extensive nature of the nodular mass, it was decided
to surgically excise it using electrocautery under general
anaesthesia.
Figure 1: (a) Gross appearance of nodular masses having
dierent sizes present in the lips and gingiva. (b) Multiple
nodular mass present at the tongue margin.
SurgiCal managemenT
e surgical site was prepared aseptically and diluted
povidone iodine (1% w/v) was used to ush the oral cavity
prior to the surgery. Preoperative antibiotic therapy was
initiated using intravenous ceftriaxone at the dose rate of
25mg/kg bodyweight. e patient was premedicated using
atropine sulfate at the dose rate of 0.04mg/kg body weight
intramuscularly. After 10 minutes, butorphanol was given
at the dose rate of 0.2 mg/kg body weight intravenously
which was followed by diazepam at the dose rate of 0.5
mg/kg body weight intravenously. Induction of general
anaesthesia was achieved by using Ketamine at the dose
rate of 10 mg/ kg body weight. A cued endotracheal tube
was placed into the trachea to provide oxygen at the ow
rate of 1.5 L/minute. e anesthesia was maintained using
diazepam-ketamine mixture at a ratio of 1:1 to eect.
e nodular masses, present in the lips, gingiva and tongue,
were excised one after another carefully. Electrocautery
was used to control the bleeding and vicryl 2-0 was used to
ligate bigger bleeding points in cases where electrocautery
failed to control the bleeding. All of the nodular masses
were removed completely by surgical excisions (Figure 2).
e defects, produced secondary to excised nodular mass,
were sutured using vicryl (2-0). Post-operatively, animal
was treated with ceftriaxone at the dose rate of 25mg/
kg bodyweight intravenously for ve days along with
meloxicam at the dose rate of 0.2 mg/kg body weight
intramuscularly for three days. During the initial 48 hours,
enteric nutrition was withdrawn and the animal was
provided with parenteral uid therapy to facilitate healing.
e owner was advised to apply chlorhexidine gluconate
gel (1% w/w) at the surgical site. e surgical wound healed
within 7 days of performing surgery. e animal made an
uneventful recovery without any recurrence during the
surveillance period of one year.
Figure 2: Reconstructed tongue margins following the
surgical excision of nodular cauliower shaped nodules.
hiSToPaThology
e excised nodular mass was preserved in 10% buered
formalin which was later processed in routine manner.
Following processing and sectioning, the tissue sample was
stained using Haematoxylin and Eosin (H and E).
Histopathological examination of stained tissue sections
revealed diused epidermal hyperplasia with parakeratosis
and broad elongated rete pegs (epithelial extensions that
project into the underlying connective tissue). ere was a
marked neovascularization in supercial dermis underlying
the acanthotic epidermis. In stratum granulosum and

NE
US
Academic Publishers
Advances in Animal and Veterinary Sciences
April 2020 | Volume 8 | Issue 4 | Page 410
stratum spinosum, few numbers of koilocytes with
clear perinuclear vacuolization were noticed and many
keratinocytes contain clumps of giant keratohyalin
granules. ese characteristic histopathological ndings
indicate that this is a case of papillomatosis suggestive of
viral etiology (Figures 3 and 4). Based on gross appearance
and histopathological examination, it was diagnosed as a
case of canine oral papillomatosis.
Figure 3: Histomicrograph showing diuse epidermal
hyperplasia with parakeratosis (arrows), broad and
elongated rete pegs (arrowhead) and neovascularization of
supercial dermis (star). H and E, 10x.
Figure 4: Histomicrograph showing koilocyte with a
clear perinuclear cytoplasmic vacuolization (arrow) and
clumps of keratohyalin granules (arrow head) in stratum
granulosum of epidermis. H and E, 10x.
DISCUSSION
Canine oral papillomatosis is generally diagnosed based on
the histopathological ndings. Microscopic examination of
stained section is characterized by presence of prominent
epithelial proliferations with thickened epidermis. e
keratinocytes present in the stratum granulosum or
spinosum had prominent nucleus (Yhee et al., 2010).
Canine papillomatosis can also be eectively managed
medically using dierent drugs. Azithromycin is considered
as a safe and eective therapeutic agent for the management
of papillomatosis in canines. It is used at a dose rate of
10 mg/kg every 24 hour for a period of 10 days for the
management of oral and cutaneous canine papillomatosis
(Yaǧcı et al., 2008). Recombinant feline interferon-ω is a
good choice for the management of canine papillomatosis
cases, which are not responsive to other modes of therapy
(Fantini et al., 2015). Surgical excision is one of the
immediate technique that is used for managing canine oral
papillomatosis. But there is a possibility of recurrence. In
cases which are refractory to surgical excision, treatment
with a recombinant canine oral papillomavirus vaccine
gives good result. Humoral immune response is produced
when canine oral papillomavirus major coat protein L1
is systemically administered (Kuntsi-Vaattovaara et al.,
2003). Oral administration of the antiviral drug Acyclovir
is another option in managing canine oral papillomatosis.
A ten day treatment with oral Acyclovir was found to be
eective in managing papillomatosis resulting in complete
remission (Uwagie-Ero et al., 2017). But further studies
should be conducted in a larger population to evaluate its
ecacy.
Canine transmissible venereal tumor (CTVT) is another
tumor that produces friable, eshy, and cauliower like
mass in the oral cavity, and this tumor can be identied
histopathologically. CTVT responds well to the treatment
with chemotherapeutic agent known as vincristine
(Rezaei et al., 2016). Even though there are many well-
established treatment protocols for managing canine
oral papillomatosis, it is dicult to evaluate the ecacy
of dierent therapy due to the self-limiting nature of the
disease. is might be the reason why each case of canine
papillomatosis responds unpredictably to dierent modes
of treatment. In the present case, the dog had multiple oral
papillomas spread over lips, gingiva, and the tongue, which
were managed eectively by surgical excision alone with
the help of electrocautery. Post-operatively, no recurrences
were reported in the present case that indicated the
eectiveness of surgical excision in managing canine oral
papillomatosis. e histological ndings were conclusive
in diagnosing the case to be canine oral papilloma virus-
induced papillomatosis.
CONCLUSIONS
Histopathological examination revealed diuse epidermal
hyperplasia, marked neovascularization, and koilocytes
with clear perinuclear vacuolization and keratinocytes with

NE
US
Academic Publishers
Advances in Animal and Veterinary Sciences
April 2020 | Volume 8 | Issue 4 | Page 411
keratohyalin granules suggestive of papillomatosis. ese
characteristic histopathological ndings were suggestive
of canine oral papillomatosis due to viral etiology.
Selection of a single but superior method of managing oral
papillomatosis will be dicult. But surgical excision can
be always considered as the bare minimum requirement
in managing non-metastatic but contagious tumors like
canine oral papillomatosis due to its immediate results.
Other therapeutic agents can be used as an add-on to the
surgical excision for obtaining superior results either for
preventing the recurrence or in cases of incomplete surgical
excision.
AUTHORS CONTRIBUTION
KS collected clinical data, drafted and revised the man-
uscript. KE, SK, FRAT, AK interpreted the clinical and
histopathological data. AMP and A critically revised the
manuscript.
eThiCal aPProval
is article does not contain any studies with human or
animal participants performed by any of the authors. All
protocols followed were as per the guidelines from the
standard textbooks in Veterinary Medicine and Surgery
and were ethical.
CONFLICT OF INTEREST
e authors declare that they have no conict of interest.
REFERENCES
•Bianchi MV, Casagrande RA, Watanabe TT, Wouters AT,
Wouters F, Boos GS, Driemeier D (2012). Canine
papillomatosis: a retrospective study of 24 cases (2001-
2011) and immunohistochemical characterization. Pesqui.
Vet. Bras.,32(7): 653-657. https://doi.org/10.1590/S0100-
736X2012000700012
•Fantini O, Videmont E, Pin D (2015). Successful treatment
of orid papillomatosis in a dog using subcutaneous feline
recombinant interferon-ω.Rev. Méd. Vét.166(1-2): 25-29.
•Gross TL, Ihrke PJ, Walder EJ, Aolter VK (2008).Skin diseases
of the dog and cat: clinical and histopathologic diagnosis. John
Wiley and Sons, pp. 406-410.
•Kuntsi-Vaattovaara H, Verstraete FJM, Newsome JT, Yuan
H (2003). Resolution of persistent oral papillomatosis
in a dog after treatment with a recombinant canine oral
papillomavirus vaccine. Vet. Comp. Oncol., 1(1): 57-63.
https://doi.org/10.1046/j.1476-5829.2003.00005.x
•Lange CE, Favrot C (2011). Canine papillomaviruses.Vet. Clin.
North Am. Small Anim. Pract.,41(6): 1183-1195. https://
doi.org/10.1016/j.cvsm.2011.08.003
•Nicholls PK, Stanley MA (1999). Canine papillomavirus-A
centenary review.J. Comp. Pathol.,120(3): 219-233. https://
doi.org/10.1053/jcpa.1998.0278
•Rezaei M, Azizi S, Shahheidaripour S, Rostami S (2016).
Primary oral and nasal transmissible venereal tumor in a
mix-breed dog. Asian Pac. J. Trop. Biomed., 6(5): 443-445.
https://doi.org/10.1016/j.apjtb.2016.03.006
•Sancak A, Favrot C, Geisseler MD, Müller M, Lange CE
(2015). Antibody titres against canine papillomavirus 1
peak around clinical regression in naturally occurring oral
papillomatosis. Vet. Dermatol., 26(1): 57-e20. https://doi.
org/10.1111/vde.12189
•Sharun K, Basha MA, Shah MA, Kumar K, Kumar P, Shivaraju
S, Pawde AM (2019). Clinical management of cutaneous
hemangiosarcoma in canines: a review of ve cases. Comp.
Clin. Pathol., 28(6): 1815–1822. https://doi.org/10.1007/
s00580-019-03039-1
•Sundberg JP, Smith EK, Herron AJ, Jenson AB, Burk RD, Van
Ranst M (1994). Involvement of canine oral papillomavirus
in generalized oral and cutaneous verrucosis in a Chinese
Shar Pei dog. Vet. Pathol., 31(2): 183-187. https://doi.
org/10.1177/030098589403100204
•Teifke JP, Löhr CV, Shirasawa H (1998). Detection of canine
oral papillomavirus-DNA in canine oral squamous cell
carcinomas and p53 overexpressing skin papillomas of the
dog using the polymerase chain reaction and non-radioactive
in situ hybridization. Vet. Microbiol., 60(2-4): 119-130.
https://doi.org/10.1016/S0378-1135(98)00151-5
•Uwagie-Ero EA, Abiaezute CN, Odigie EA, O’kwu AJ (2017).
Management of canine papillomatosis using oral acyclovir-a
case report. Int. J. Vet. Sci., 6(4): 187-190.
•Yaǧcı BB, Ural K, Öcal N, Haydardedeoǧlu AE (2008).
Azithromycin therapy of papillomatosis in dogs: a
prospective, randomized, double-blinded, placebo-controlled
clinical trial. Vet. Dermatol., 19(4): 194-198. https://doi.
org/10.1111/j.1365-3164.2008.00674.x
•Yhee JY, Kwon BJ, Kim JH, Yu CH, Im KS, Lee SS, Sur JH
(2010). Characterization of canine oral papillomavirus
by histopathological and genetic analysis in Korea. J. Vet.
Sci.,11(1): 21-25. https://doi.org/10.4142/jvs.2010.11.1.21