odontogenic and non-odontogenic oral tumours in non ... · in contrast with domestic carnivores,...

Odontogenic and non-odontogenic oral

tumours in non-domesticated members

of the order carnivora

Word count: 20 179

Sam Boulanger Student number: 01206557

Supervisor: Prof. dr. Lieven Vlaminck

Co-Supervisors: Dr. Gerhard Steenkamp

Prof. dr. Sonja Boy

Elke Pollaris, DVM

A dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of

Master of Veterinary Medicine

Academic year: 2017 - 2018

Ghent University, its employees and/or students, give no warranty that the information provided in this

thesis is accurate or exhaustive, nor that the content of this thesis will not constitute or result in any

infringement of third-party rights.

Ghent University, its employees and/or students do not accept any liability or responsibility for any use

which may be made of the content or information given in the thesis, nor for any reliance which may

be placed on any advice or information provided in this thesis.

Preface

Writing this dissertation felt challenging and wouldn't be possible without the help of many. Therefore, I

would like to express a word of gratitude to a few people in particular. Firstly, I would like to thank my

two head supervisors, Dr. Gerhard Steenkamp and Prof. dr. Lieven Vlaminck, for all their support and

feedback I got since the beginning of this little project. I consider myself very lucky being able to call

them my supervisors. Their great experience in the field of veterinary dentistry and oral health gave

me a lot of motivation to finish this project in a good way and I have big admiration for the work they

deliver, projecting them as lead examples of my own personal professional ambition.

I'm also very thankful to Elke Pollaris for the numerous hours she invested in correcting my work and

for all her advice I got when I was in doubt. For the histopathological part of the project, I would like to

thank Prof. dr. Sonja Boy and Prof. dr. Koen Chiers. Their help in the composition of survey questions

about tumour characteristics is very much appreciated.

All of these opportunities wouldn't be able without the great support of my beloved parents. As well my

brother as myself always got every support to study whatever we wanted to, something which I realize

isn't the case for everyone. They supported me in every possible way to fulfil my dreams and were the

first to encourage me during hard moments.

Last but certainly not least, a word of thank is necessary for my friend group 'Les Flutes'. Thank you

for the unforgettable memories and tremendous feelings of deep friendship I experienced during six

years of study. You are and always will be in the deepest of my heart.

Table of contents

Preface .................................................................................................................................................... 3

Table of contents ..................................................................................................................................... 4

Abstract .................................................................................................................................................... 6

Samenvatting ........................................................................................................................................... 6

Introduction .............................................................................................................................................. 7

Situation ................................................................................................................................................... 8

1.1 Order Carnivora ......................................................................................................................... 8

1.2 Anatomy of oral structures ......................................................................................................... 9

1.3 Oral neoplasia.......................................................................................................................... 13

Strategy ................................................................................................................................................. 13

Literature review .................................................................................................................................... 14

Oral tumours in domesticated carnivores .............................................................................................. 14

1. Prevalence, differentiation and classification ................................................................................ 14

1.1 Odontogenic tumours .............................................................................................................. 14

1.2 Non-odontogenic tumours ....................................................................................................... 15

2. Pathological behaviour .................................................................................................................. 15

2.1 Squamous cell carcinoma ....................................................................................................... 15

2.2 Malignant melanoma ............................................................................................................... 15

2.3 Fibrosarcoma ........................................................................................................................... 16

2.4 Papilloma ................................................................................................................................. 16

2.5 Adenocarcinoma ...................................................................................................................... 16

2.6 Mucoepidermoid carcinoma .................................................................................................... 16

2.7 Osteoma .................................................................................................................................. 16

2.8 Haemangioma ......................................................................................................................... 16

2.9 Anaplastic carcinoma .............................................................................................................. 17

2.10 Fibromatous epulis of periodontal origin ............................................................................... 17

2.11 Amyloid-producing odontogenic tumour ................................................................................ 17

2.12 Gingival hyperplasia .............................................................................................................. 17

3. Symptoms and history ................................................................................................................... 17

4. Diagnostic approach ...................................................................................................................... 17

5. Histological features ...................................................................................................................... 18



5.3 Fibrosarcoma ........................................................................................................................... 18

5.4 Papilloma ................................................................................................................................. 19

5.5 Adenocarcinoma ...................................................................................................................... 19


5.7 Osteoma .................................................................................................................................. 19

5.8 Haemangioma ......................................................................................................................... 20


5.10 Fibromatous epulis of periodontal origin ............................................................................... 20

5.11 Amyloid-producing odontogenic tumour ................................................................................ 20

5.12 Gingival hyperplasia .............................................................................................................. 20

6. Therapy .......................................................................................................................................... 21

6.1 Surgery .................................................................................................................................... 21

6.2 Radiation therapy .................................................................................................................... 21

6.3 Chemotherapy ......................................................................................................................... 22

7. Prognosis ....................................................................................................................................... 22

Materials and methods .......................................................................................................................... 24

1. Survey outline ................................................................................................................................ 24

2. Response....................................................................................................................................... 24

Results ................................................................................................................................................... 25

Discussion ............................................................................................................................................. 27

Conclusion ............................................................................................................................................. 30

References ............................................................................................................................................ 31

Appendix A: Taxonomy chart of the Carnivora order (ITIS, 2018) ........................................................ 39

Appendix B: Reported cases of oral tumours in non-domesticated carnivorans described in literature,

classified per tumour type ...................................................................................................................... 40

1. Odontogenic tumours .................................................................................................................... 40

1.1 Amyloid-producing Odontogenic Tumour ................................................................................ 40

1.2 Calcifying epithelial odontogenic tumour ................................................................................. 40

1.3 Fibromatous epulis of periodontal origin ................................................................................. 40

2. Non-odontogenic tumours ............................................................................................................. 40

2.1 Papillomatosis.......................................................................................................................... 40


2.3 Adenocarcinoma ...................................................................................................................... 43



2.6 Secondary carcinoma .............................................................................................................. 44


2.8 Haemangioma ......................................................................................................................... 44

2.9 Fibrosarcoma ........................................................................................................................... 44

Appendix C: Reported cases of oral tumours in non-domesticated carnivorans retrieved through

survey .................................................................................................................................................... 45

6

Abstract

In this comprehensive literature review, an attempt was made to enlist all reported cases of oral

tumours, as well from odontogenic as non-odontogenic origin, in members of the order Carnivora and

classify them regarding different tumour types. Only cases supported by histopathological evidence

were included in the study. To add up the number of collected case reports, surveys were send out to

professionals, organisations and institutions experienced with carnivorans and/or (oral) tumours. A

total number of 75 cases were included in the study, and consisting of multiple tumour types.

Symptomatology, diagnostic approach, treatment therapy and outcome were investigated in

comparison to the current knowledge of oral tumours in domestic cats and dogs. Only a slight minority

of animals were reported to undergo curative treatment (21%) and successful outcome was noticed in

only one third of the treated individuals. The use of multimodality therapy may be a valuable option,

but comprises financial and technical restraints. In a large number of cases (22 out of 75 cases), oral

tumours were only identified at necropsy. In 9 cases the decision for euthanasia or palliative treatment

was made based on poor prognosis or expected complications of treatment. Detection of oral tumours

and their associated symptoms in an early stage should be strived for and could be achieved by solid

retraining of staff members and regular examination of the oral cavity.

Samenvatting

In deze literatuurstudie werd getracht alle gerapporteerde gevallen van orale tumoren, van zowel

odontogene als niet-odontogene oorsprong, in dieren behorend tot de orde Carnivora in kaart te

brengen en in te delen volgens type tumor. Enkel gevallen ondersteund door histopathologisch

onderzoek werden ingebrepen in de studie. Om bijkomende cases te verzamelen werd een

zelfgecreeërde enquête opgestuurd naar professionelen en organisaties ervaren met Carnivora en/of

orale tumoren. In totaal werden 75 cases verzameld met tumoren behorende tot verschillende types.

Symptomatologie, diagnostische aanpak, behandeling en uitkomst werden onderzocht en vergeleken

met de huidige kennis in orale tumoren van de gedomesticeerde hond en kat. Enkel in een kleine

minderheid van de gevallen werd curatieve behandeling beschreven (21%) en succesvolle

behandeling werd in acht genomen in een derde van de gevallen. Het gebruik van combinatietherapie

kan een waardevolle optie betekenen, maar gaat gepaard met de nodige financiële en technische

beperkingen. In een groot aantal cases (22 van 75 cases) werd een orale tumor pas geïdentificeerd

na autopsie. In 9 gevallen werd geopteerd voor euthanasie of palliatieve behandeling ingesteld

gebaseerd op slechte prognose of verwachte complicaties bij behandeling. Er moet gestreefd worden

naar detectie van orale tumoren en bijhorende symptomen in een vroeg stadium, wat zou kunnen

verwezenlijkt worden door middel van doelgerichte bijscholing van personeel en door regelmatig

onderzoek van de mondholte.

7

Introduction

A great diversity of neoplasms has been reported in captive wild carnivores (Effron et al., 1977;

Lombard and Witte, 1959; Owston et al., 2008) but only few of them originate from the oral cavity. This

in contrast with domestic carnivores, where oral tumours represent 3-12% of the tumours in cats

(Stebbins et al., 1989) and 5-7% in dogs (Frew and Dobson, 1992).

Odontogenic tumours in the oral cavity of the small domestic animals are rare (Fiani et al., 2011;

Gardner, 1992; Walsh et al., 1987) and infrequently observed in wild Carnivora. Although odontogenic

tumours are considered rare, various cases have been reported in animals throughout the last couple

of decades. Further on, different histological types have been identified and classified. (Walsh et al.,

1987)

For a long time, neoplasia was not regarded as a major threat concerning wildlife conservation.

Recent discoveries about a certain number of neoplastic diseases with the ability to severely decrease

population numbers have raised the awareness of the impact of cancer on conservation outcomes.

(Curry et al., 2000; Gulland et al., 1996; Hawkins et al., 2006; Maccubbin et al., 1985; Martineau et al.,

2002; McAloose and Newton, 2009)

A good example of the impact of certain neoplastic diseases on population numbers is devil facial

tumour disease (DFTD), a contagious cancer in Tasmanian devils (Sarcophilus harrisii). This

transmissible allograft cancer can spread through direct contact with diseased cells and behaves as a

focal or multicentric neuroendocrine tumour. It can cause severe soft tissue malformations with a

predisposition for the head and neck area. Metastasis, mostly in local lymph nodes and lungs, is found

in up to 65% of affected animals. (Loh et al., 2006) Affected animals have a mortality rate of 100% due

to complications caused by tumor growth or metastasis. Since the first observation of the disease in

1996, Tasmanian devil populations have declined by 53%. (McCallum et al., 2007) Mathematical

modeling of this disease estimates a population decline of 90% in 60% of territories with affected

animals and a reduction of the entire Tasmanian devil population by 70% over the next ten years.

(Hawkins et al., 2006; Lachish et al., 2007; Pyecroft, 2007) The International Union for the

Conservation of Nature and Natural Resources (IUCN) has enlisted the Tasmanian devil as

endangered in 2008, while extinction of the Tasmanian devil is a possibility in the near future.

Disappearance of this animal could interfere with Tasmania's ecosystem and would make DFTD as

the first contagious cancer causing the extinction of a species. (Hollings et al., 2015)

In two studies, captive wildlife and domestic animals show similar rates of neoplasia. (Effron et al.,

1977; Lombard and Witte, 1959) A variety of tumour cases have been described for captive wildlife

and even less frequent tumour types have been detected in these animals. (McAloose and Newton,

2009) Occasionally, management practices in zoos, aquariums or sanctuaries can play a role in

neoplasia development. The former use of megestrol acetate for contraception in exotic felids is linked

with an increased risk of mammary carcinoma. (McAloose et al., 2007) Subcutaneous microchip

implementation in zoo animals has been associated with soft tissue sarcomas in a few species.

(Pessier, 1999; Siegal-Willott et al., 2007)

Although quite some studies have been done on oral neoplasia in domestic carnivores, odontogenic

and non-odontogenic tumours in wildlife carnivores are slightly documented. A limited number of

cases have been published since the major development of veterinary dentistry in 1970’s. (Bernstein

and Schelling, 1999; Bossart, 1990; Broughton et al., 1970; Dadone et al., 2014; Dorso et al., 2008;

Fecchio et al., 2015; Joslin et al., 2000; Kang et al., 2006; Lam et al., 2013; McNulty et al., 2000;

Mylniczenko et al., 2005; Nelson et al., 2013; Samuel et al., 1978; Sato et al., 2002; Sladakovic et al.,

2016; Sundberg et al., 2000; Wolfe and Spraker, 2007; Yanai et al., 2003) Due to their familiarity with

humans, oral diseases of domestic carnivores are detected in an earlier stage. Oral problems of

captive wild carnivores are mostly not detected by a clinician until the oral disease is so aggravated or

chronically evaluated to a point of oral inability and depletion of strength. (Fagan et al., 1998) Almost

8

all oral tumours that have been seen in exotic carnivores are described in their domestic relatives.

(Wiggs and Bloom, 2003) As such, the clinical approach of oral tumours in non-domesticated

carnivores could be based on the current knowledge in domestic animals. An increased knowledge of

the presentation, diagnosis and treatment options of oral neoplasm in exotic carnivores would benefit

anyone who’s involved in their management or health care. (Fagan et al., 1998)

To date no study has attempted to classify and compare oral tumours described within members of the

order Carnivora. Considering the limited number of reported cases, the primary aim of this study

project is to create a comprehensive literature review where collected cases are analysed by their

classification.

This literature review could serve as a reference for wildlife practitioners when dealing with oral

neoplasia. Treatment options and prognosis could be reviewed or considered based on their clinical

descriptions in the literature.

A second objective of this study is to add extra cases through mining of University of Pretoria’s

database as well as questionnaires to wildlife facilities/veterinarians.

Situation

1.1 Order Carnivora The order Carnivora (from Latin carō "flesh" and vorāre "to devour"), belonging to the Class of

Mammalia within the animal kingdom, includes 12 families and over 280 species. Members of this

group are referred as carnivorans, not to be confused with the general term “carnivores” which

comprises any meat-eating organism. Most animals belonging to the order Carnivora are strictly meat

eaters, although a substantial number of them also feed on vegetation and are thus omnivorous (f.ex.

Ursus arctos ssp.) or herbivorous (f.ex. Ailuropoda melanoleuca). Due to evolutional specialization

concentrating on the functionality of devouring meat, carnivorans have developed characteristic skull

structures and dentition, which are further on described in “Anatomy of oral structures”.

Members of the order Carnivora are split into two suborders: Feliformia (cat-like) and Caniformia (dog-

like). Extinct animals are not included in the following description. Feliformia are divided into six

families: Eupleridae, Felidae, Herpestidae, Hyaenidae, Viverridae and Nandiniidae. Eupleridae are a

group of carnivorans endemic to Madagascar and strongly related to the Herpestidae. Herpestidae

are mainly consisting out of moongooses (f.ex. Cynictis penicillata, Herpestes edwardsii), meerkats

(f.ex. Suricata suricatta), and dwarf mongooses (f.ex. Crossarchus obscurus). Felidae is the best

known family within Feliformia and animals belonging to this family are the strictest carnivores of all

terrestrial families in the order Carnivora. They can be split up in Pantherinae and Felinae.

Pantherinae are often referred in popular language as "big cats" and comprise amongst other species

the famous lion (Panthera leo), tiger (Panthera tigris), jaguar (Panthera onca), leopard (Panthera

pardus) and snow leopard (Panthera uncia). The other subfamily of Felidae is Felinae or non-

pantherine cats, in which the lynx (f.ex. Lynx lynx), ocelot (Leopardus pardalis), serval (Leptailurus

serval), cheetah (Acinonyx jubatus) or domestic cat (Felis silvestris catus) can be found. Hyaenidae

has three genera: Crocuta (Spotted Hyaena or Crocuta crocuta), Hyaena (f.ex. Hyaena brunnea) and

Proteles (aardwolf or Proteles cristatus). Although behaviour and morphology are similar to

Caniformia, Hyaenidae are phylogenetically closer to Viverridae and Felidae. This is represented in

grooming, defecating habits, parental behaviour, scent marking and mating, but for their hunting

methods and feeding habits they are more similar to Caniformia. Of all the families of the Feliformia,

Viverridae are the most primitive and are obviously less specialised in comparison to Felidae. Best

known animals in this family are civets (f.ex. Civettictis civetta) and genets (f.ex. Genetta genetta).

Nandiniidae consist of only one living species, the African palm civet (Nandinia binotata).

The suborder Caniformia counts nine suborders: Ailuridae, Canidae, Mephitidae, Mustelidae,

Odobenidae, Otariidae, Phocidae, Procyonidae and Ursidae. Contrary to Feliformia, Caniformia also

comprise semi-aquatic members within the suborder (Odobenidae, Otariidae, Phocidae, Lutrinae,

Mustela lutreola, Neovison vison). Ailuridae only comprise the red panda, the sole living representative

of this family. Canidae can further on be grouped into thirteen genera with a certain number of

9

monotypic genera (Atelocynus, Cerdocyon, Chrysocyon, Cuon, Dusicyon, Lycaon, Nyctereutes,

Otocyon, Speothos). The genus Canis consists out of some well-known species such as the grey wolf

(Canis lupus), golden jackal (Canis aureus), coyote (Canis latrans) and domesticated dog (Canis lupus

familiaris). Another large genus is Vulpes (true foxes, f.ex. Vulpes vulpes, Vulpes zerda). The Ursidae

family or bears is divided into four monotypic genus (Ailuropoda, Helarctos, Melursus and Tremarctos)

and the genus Ursus, in which can be found the American black bear (Ursus americanus), brown bear

(Ursus arctos), polar bear (Ursus maritimus) and Asian black bear (Ursus thibetanus). Phocidae, also

known as earless seals or true seals, counts thirteen genera. Well known members of this family are

the harbour or common seal (Phoca vitulina), elephant seal (f.ex. Mirounga angustirostris) and

bearded seal (Erignathus barbatus). Phocidae has to be distinguished from Otariidae, also called

eared seals referring to the small external ear flaps visible on the head. Seven genera are identified in

the Otariidae family which includes for example the California sea lion (Zalophus californianus) and

brown fur seal (Arctocephalus pusillus). The Odobenidae family has only one living species:

Odobenus rosmarus. Mustelidae is a diverse family and the largest one in the order Carnivora. It is

divided into two subfamilies: Lutrinae; basically grouping otter-like carnivorans such as the Eurasian

otter (Lutra lutra), North American river otter (Lontra canadensis) and sea otter (Enhydra lutris) and

Mustelinae. This subfamily contains further on a variety of fifteen genera. The biggest genera are

Martes (f.ex. Martes americana, Martes martes) and Mustela. Mustela contains seventeen species

including polecats (f.ex. Mustela putorius), ermines (f.ex Mustela erminea), weasels (f.ex Mustela

nivalis) and minks (f.ex. Mustela lutreola). Other notable genera are Meles (f.ex. Meles meles),

Mellivora (Mellivora capensis), Neovison (f.ex. Neovison vison) and Taxidea (Taxidea taxus). The last

two families are Mephitidae -often referred as skunks (f.ex. Mephitis mephitis) - and Procyonidae, a

new world family generally omnivorous and including raccoons (f.ex. Procyon lotor), kinkajous (Potos

flavus), ringtails (Bassariscus astutus), olinguitos (Bassaricyon neblina), olingos (Bassaricyon gabbii),

coatis (Nasua narica) and cacomistles (Bassariscus sumichrasti).

1.2 Anatomy of oral structures

1.2.1 Oral cavity

The oral cavity stretches out from the lips to the palatoglossal arch and is enclosed dorsally and

ventrally by mucosal lining inside the lips and cheeks. The cavity's outer vestibule is limited by lips and

cheeks and forms a small separated space from the teeth and gingiva. (Barnes et al., 2005) It includes

the lips, hard palate (the bony front portion of the roof of the mouth), soft palate (the muscular back

portion of the roof of the mouth), front two-thirds of the tongue, gingiva (gums), buccal mucosa (the

inner lining of the lips and cheeks), and floor of the mouth under the tongue. (NCI, 2018)

1.2.2 Dentition

Carnivoran teeth are divided into incisors, canines, premolars and molars. The characteristic sharp

canines are used for the apprehension, killing and butchering of their prey. They have another

important role in the retainment of the tongue and the positioning of the lips. The incisors are relatively

small in comparison to the canines, premolars and molar. The main functions of these teeth are

grooming, nibbling, biting and cutting. Incisors are single rooted teeth normally aligned in a scissor

occlusion. Very prominent teeth in a carnivoran dentition are the carnassials, which are the upper

fourth premolars and the lower fourth molars. They act as a pair of scissors when the jaw is closing

due to their knife-like edges and are essential to cut off slices of meat. Other premolars are generally

used for shearing, cutting and holding and contain one to three roots depending on their anatomical

localisation and inter-species differences.(Harvey et al., 1990; Hillson, 2005)

10

Figure 1: skull of a wolf (Canis lupus): characteristic for carnivore dentition are the well-developed carnassials

and canine teeth (Matthews and Preston, 2004)

The basic dental formula of carnivores is I 3/3, C 1/1, PM 4/4, M 3/3, but adaptations in the diverse

diets of carnivorans have led to many variations on this formula. Some few species have adapted to

highly specialised diets: panda bears (Ailuropoda melanoleuca) feed on bamboo, aardwolves

(Proteles cristata) on termites, walruses (Odobenus rosmarus) on molluscs and crab-eating seals

(Lobodon carcinophaga) on krill. Omnivores such as bears have carnassials with a slightly different

morphology from strict carnivores. (Hillson, 2005) They are also used to, but not perfectly suited for,

the devouring of solid plant material. This results in the swallowing of large, bit-sized pieces or crushed

food that is not chewed carefully. (Feldhamer, 2007) An example of dentition adaptation within the

same genus can be found in polar bears (Ursos arctos). Polar bears are, in comparison to other bears

strictly carnivore with feeding habits based on seal flesh and blubber. This results in reduced molars

and premolars, since vegetable food don't have to be grinded. (Sacco and Van Valkenburgh, 2004)

Figure 2: skull of a bear (Ursidae): Adaptations include undeveloped carnassial teeth and broad flat molars

(Matthews and Preston, 2004)

1.2.3 Anatomy of the tooth and periodontium

The tooth contains a crown which can be detected visually because of its exposition above the

gingival margin and a root covered by periodontal tissues and situated below the gum level. The crown

is coated in enamel, while the embedded root is covered by cement. The borderline between cement

and enamel is at the cementoenamel junction. (Harvey et al., 1990) Enamel formation is initiated by

ameloblasts before dental eruption. After eruption tooth damage can only be restored by

remineralisation of the tooth (Nanci and Ten Cate, 2008), a process interaction between phosphorus,

calcium and fluoride ions which finally results in ion deposition into crystal voids in the non-cavitated

lesion.(Featherstone, 2004) The cement is formed by cementoblasts that are present in the parodontal

ligament, which is the connective tissue between cement and alveolar bone.

11

Beneath this tooth surface lays the dentine which is the greater and main part of the tooth. Dentine is

produced (primary dentine) and provided lifelong (secundary dentine) by odontoblasts. These cells are

of neural crest origin and are lining the pulp chamber as well as a connexion with numerous

microtubules that are being part of the dentine (70 000 per mm² in average). The pulp chamber

contains dental pulp, which is composed of blood vessels, nerves and lymphatic tissue in a

mesenchymal tissue matrix. The pulp chamber is large while the dentine layer is rather thin in juvenile

animals, and due to continuously remodelling of dentine by odontoblasts it results in narrowing of the

pulp chamber and widening of the dentine particularly during the first 24 months of age. The dental

apex receiving the nerves, blood vessels and lymphatics will gradually close in a similar period of

time.(Harvey et al., 1990)

The base of the dental crown forms a bulge just above the dental cervix and just above the gingival

attachment. This bulge allows a good adaptation and protection of the gingiva during mastication;

alimentary particles are deviated from the gingival sulcus. This gingival sulcus consists of a fine and

shallow space separating the free gingival margin of the tooth. The epithelial attachment is situated at

the end of this margin and inserts the gingiva on the tooth. (Hennet and Boutoille, 2013)

Enamel

Dentine

Dental pulp

Gingival sulcus

Parodontal ligament

Gingiva

Dentine

Radicular cement

Lamina cribriforme

Alveolar bone

Apical delta

Crown

Neck

Root

Figure 3: Anatomical representation of at tooth (first mandibular molar) and adjacent tissues in the dog (Hennet and Boutoille, 2013)

Figure 4: Anatomical representation of the periodontium (Hennet and Boutoille, 2013)

Enamel

Dentine

Gingival sulcus

Epithelium of the sulcus

Epithelial attachment

Gingival epithelium

Alveolar bone

Parodontal ligament

Muco-gingival junction

12

The periodontium consists of gingiva, periodontal ligament, cement and alveolar bone. Its primary

function is to assure attachment and support of the tooth. The gingiva surrounds the alveolar bone and

the teeth. Two parts can be distinguished: the free gingival margin and the attached gingiva that is

bound to the cement at the level of the dental cervix and to alveolar bone.

The gingiva is separated from alveolar mucus by the mucogingival junction. The gingival sulcus is

aligned internally by non-keratinised epithelium which allows the diffusion of sulcus fluid. This fluid is

rich with immunoglobulins (Ig G in majority, Ig G and Ig M), plasma proteins (albumine, fibrinogen ...),

antibacterial substances (protease, lysosym ...), antioxidants (ascorbic acid, α-Tocopherol ...) and

cellular elements (neutrophils, lymphocytes, granulocytes, monocytes, desquamated epithelial cells

and bacteria). It protects the periodontal ligament and epithelial attachment against bacterial infection

and generated oxidative reactions.

The periodontal ligament plays a key role in the periodontium and has several functions: fixation of the

tooth in the alveolar bone, shock absorber of moving teeth, sensory mechanisms, formation and

resorption of cement and adjacent bone. It consists of collagen fibres and elastic fibres that connect

cement and lamina dura (internal cortex) of alveolar bone. Aside from fibres, the periodontal ligament

also contains lymphatic and blood vessels, nerves, fibroblasts, mesenchymal cells capable of forming

clastic or blast cells (fibroblasts, osteoblasts, cementoblasts, osteoclasts, cementoclasts).

Alveolar bone is the part of maxilla or mandibula that forms and supports dental alveoli. The alveolar

process is composed simultaneously with dental development and eruption and is resorbed

progressively when the tooth disappears. It consists of compact bone situated in the periphery and

spongy bone in the centre. It possesses two cortices: an external cortex covered with periosteum

connecting with the mandibular or maxillary cortex, and an internal cortex forming the osseous margin

of the alveolus where fibres of the periodontal ligament are attaching. (Hennet and Boutoille, 2013)

1.2.4 Anatomy of the skull

Carnivorans have varied skull forms. The transverse glenoid fossa is mostly well developed and the

jaw is orientated in dorso-ventral direction. Jaws in carnivorans are unequal: the maxillar molar

occlusal zone is wider than the mandibular counterpart, and the mandibula is shorter than the upper

jaw. This phenomenon is described as anisognathism and is also present in bovine and equine

species. (Wiggs and Bloom, 2003) Well-developed temporomandibular joints allowing high occlusive

forces, wide vertical excursion but limited lateral excursion are required with the aim of entrapping pray

and applying shearing forces. (Wiggs and Bloom, 2003) The temporal muscle enforces the jaw as the

primary force and an obvious part of the surface of the skull is the sagittal crest, which is connected to

the temporal muscle. Characteristic for carnivorans is the strong zygomatic arch and relatively large

cranium. Carnivorans are considered to be intelligent animals. Most have brains of larger size; the

turbinals and auditory bullae are large, while the ear structure contains a higher complexity than most

other animals. (Stains, 1984; Vaughan et al., 2000)

Figure 5: Skull of an African lion (Panthera leo): a/ temporomandibular joint b/ sagittal crest c/ zygomatic arch

(Matthews and Preston, 2004)

a b

c

13

1.3 Oral neoplasia

1.3.1 Definitions

Neoplasia of the oral cavity can be separated into two groups depending on the origin of the

tumour: odontogenic and non-odontogenic tumours.(Theodorou et al., 2003) Neoplastic lesions

developed from mesenchymal, ectomesenchymal and/or epithelial origin that still are, or have been,

part of the tooth forming structures are categorised as odontogenic tumours. Consequently, these

tumours are mainly observed in the soft tissue overlying tooth-bearing areas or alveolar mucosae in

teeth-lacking region, or within the maxillofacial skeleton. Odontogenic tumours can develop at any age

of an individual. (Barnes et al., 2005)

The term non-odontogenic indicates that the tumour is composed of cellular constituents whose

primary purpose is to form structures in the oral cavity with the exception of teeth or 6 tooth-related

structures during odontogenesis, or the remnants of these structures after odontogenesis.

1.3.2 'Epulis'

The term ‘epulis’ must be considered as a pure clinical descriptive term and mustn’t be associated with

odontogenic or non-odontogenic origin alone. A histological review of 129 dogs appearing with

epulides done by Verstraete et al. (1992) suggested that the majority of these cases can be classified

as focal fibrous hyperplasia (43,5%), peripheral ameloblastoma (17,5%), peripheral odontogenic

fibroma (16,9%) and pyogenic granuloma (1,95%). Further on, some of other odontogenic tumours

(1,95%) and non-odontogenic tumours (18,2%) such as fibrosarcoma and squamous cell carcinoma

which are not traditionally associated with the clinical appearance of an epulis, were diagnosed.

(Verstraete et al., 1992) Therefore, the appearance of epulis-like lesions is advised to be accompanied

by histopathological examination.

For many years the nomination of benign gingival masses has been a point of discussion. A

classification scheme created by Dubielzig et al. (1979) divided them into three categories:

fibromatous epulis, ossifying epulis and acanthomatous epulis. Fibromatous and ossifying epulis were

grouped under the human peripheral odontogenic fibroma (POF) by another group of authors because

of similarities between the two veterinary tumours and the human POF. (Gardner, 1982, 1996;

Verstraete et al., 1992) This nomination also led to the separation of reactive lesions provoked by

plaque and calculus which were classified as focal fibrous hyperplasia (FFH). (Fiani et al., 2011b) This

distinction between reactive lesions (FFH) and neoplastic lesions (POF) is important. Although POF is

considered as the current term for the neoplastic lesions, fibromatous epulis of periodontal ligament

origin is preferred by other authors. It is reported to reflect the stroma as having features of the

periodontal ligament, while this would not be the case for the cellular fibrous stroma of POF. (Dubielzig

et al., 1979; Head et al., 2002) To avoid further confusion in this classification scheme, fibromatous

epulis of periodontal ligament mentioned by Head et al. (2003) is used in this dissertation to classify

lesions formerly known as 'fibromatous epulis' or 'ossifying epulis'. The formerly known acanthomatous

epulis is now named as canine acanthomatous ameloblastoma (CAA) because of the microscopic and

clinical similarities with human ameloblastoma without specifying a subtype. (Fiani et al., 2011b)

Strategy

Research was primarily conducted using online databases specialised in medical or veterinary topics.

The following search engines were used: PubMed, Embase, Elsevier sciencedirect, Web of Science

and the AAZV & EAZA annual meeting databases. Some journals were also hand-searched for

relevant articles. These journals were Journal of Zoo and Wildlife Medicine, Journal of Veterinary

Dentistry, Journal of Comparative Pathology and Journal of Wildlife Diseases. The content of articles

was looked after the presence of oral tumours supported by histopathology in non-domesticated

carnivorans. Bibliographies of those papers that match the inclusion criteria were evaluated to identify

any further, relevant references.

Until today, 64 cases of oral tumours in non-domesticated members of the order Carnivora have been

retrieved from literature. A detailed list with description of species name, age and sex of the animal,

histopathological diagnosis, oral localisation, author(s), journal name and year of publication can be

14

found under 'Appendix A'. To collect additional cases, self-created surveys were drafted and send to

several organisations/institutions frequently dealing with non-domesticated carnivorans or examination

of oral tumours in animals.

Literature review

Oral tumours in domesticated carnivores

1. Prevalence, differentiation and classification

1.1 Odontogenic tumours Figures about the prevalence of odontogenic tumours are generally rare and few retrospective studies

exist. (Boehm et al., 2011; Fiani et al., 2011b; Schmidt et al., 2010; Verstraete et al., 1992) A

retrospective case study of 1390 canine and 317 feline oral tumours by Boehm et al. (2011) revealed

that 18% of the canine and 3,2% of the feline oral neoplasia turned out to be of odontogenic origin.

The most common odontogenic tumour in dogs (67%) and cats (40%) was odontogenic fibroma.

Ameloblastoma was the second most frequent observed odontogenic tumour in dogs (30%), while for

cats this was ameloblastic fibroma (20%). In this study, all discovered odontogenic tumours in cats

were of benign origin, while in dogs only 3 cases representing 1,2 % of odontogenic tumours were

malignant.

Another retrospective study by Schmidt et al. (2010) in 112 dogs up to the age of 12 months reported

a prevalence of 38% for tumours of odontogenic origin within discovered oral tumours. 50% of the

tumours of odontogenic origin were classified as fibromatous epulis of periodontal ligament origin (or

peripheral odontogenic fibroma), followed by, in descending order, unspecified epulis/odontogenic

tumours (24%), acanthomatous ameloblastoma (14%), ameloblastoma (7%) and odontoma (5%). No

specific figures about prevalence in malignity were mentioned.

No differentiation is made between benign and malignant odontogenic tumours according to the

veterinary WHO-classification of 2003. The differentiation of malignancy is therefore classified

following the latest human WHO-classification. (Barnes et al., 2005) Benign neoplasms are divided

into epithelial, epithelial and ectomesenchymal, and ectomesenchymal. Malignant neoplasms consist

of two categories: odontogenic carcinomas and sarcomas. According to a retrospective study of 250

domestic dogs and 10 domestic cats, only 1,2% of the odontogenic tumours were defined as

malignant after histopathological examination. (Boehm et al., 2011)

The classification of odontogenic tumours has been largely discussed throughout the last decades.

(Gardner, 1992; Poulet et al., 1992; Walsh et al., 1987) A broad classification is one which divides

tumours into three groups depending on whether the tumours are able to induce a stromal reaction –

inductive and non-inductive – and depending on the origin of the tumour cells – epithelial or

mesenchymal. (Gorlin et al., 1961; Walsh et al., 1987) Critics stated that this classification was tending

to be confusing and was leading to such paradoxes as tumours that have large or even predominant

mesenchymal components could still be classified as epithelial tumours. (Gardner, 1992) An

alternative was suggested by separating epithelial, mesenchymal and mixed types of odontogenic

tumours. (Gardner, 1992; Thoma and Goldman, 1946)

Since 1976 the World Health Organisation (WHO) is publishing its own classification for odontogenic

tumours of domestic animals. Their first classifications were very similar to the human-ones presented

in 1971. (Boehm et al., 2011; Pindborg et al., 1971) In 2003, a new WHO-classification was presented

for veterinary use only. (Boehm et al., 2011; Head et al., 2003) In this classification, odontogenic

tumours are divided into 6 groups: tumours of odontogenic epithelium without odontogenic

mesenchyme, tumours of odontogenic epithelium with odontogenic mesenchyme, tumours composed

primarily of odontogenic ectomesenchyme, tumours derived from the tissues of the periodontal

ligament, cysts of the jaw and finally tumour-like lesions. In this paper, the WHO-classification will be

used as a reference to classify all collected cases.

15

1.2 Non-odontogenic tumours Oral tumours account for approximately 10% of all tumours in domestic cats, and approximately 90%

of these oral tumours are malignant. Squamous cell carcinoma (SCC) is the most commonly

encountered malignant oral tumour in domestic cats, making 60-70% of malignant oral tumours.

Fibrosarcomas are the second most frequent oral neoplasia’s and are considered to represent 10-15%

of oral tumours. Other notable non-odontogenic tumours encountered in the same survey are

adenocarcinoma, osteosarcoma and salivary adenocarcinoma. (Stebbins et al., 1989)

Benign tumours are mostly at least as common as malignant tumours in the dog. (Lascelles et al.,

2011)

The most common malignant non-odontogenic tumours of the mandible and maxilla in dogs are, in

descending order, malignant melanoma, squamous cell carcinoma and fibrosarcoma. Other malignant

oral tumours include osteosarcoma, chondrosarcoma, anaplastic sarcoma, multilobular

osteochondrosarcoma, intraosseus carcinoma, myxosarcoma, haemangiosarcoma, lymphoma, mast

cell tumour, and transmissible venereal tumour. (Lascelles et al., 2011)

Following the classification proposed by Head et al. (2003) tumours of the upper alimentary tract are

divided into eight histological types: epithelial tumours, neuroendocrine tumours, melanocytic tumours,

mesenchymal tumours, granular cell tumours, tumours of bone, tumours of hematopoietic and related

tissues and tumourlike lesions.

2. Pathological behaviour

2.1 Squamous cell carcinoma Squamous cell carcinoma (SCC) can appear anywhere in the oral cavity and shows a particular local

invasiveness in bone tissue, with severe and extensive invasion in the cat. Even if precise causes of

the disease have not been determined yet, a number of environmental or contributing factors have

been described such as flea collars, high intake of canned food or canned tuna and exposure to

household tobacco smoke. (Bertone et al., 2003; Snyder et al., 2004)

Their metastatic rate in cats at diagnosis is rather low, but there is still some discussion about the true

metastatic potential because long-term follow-up for metastasis is complicated by the difficult control of

local disease. Results of few studies on metastasis in cats with oral SCC support the belief that the

metastatic rate is low and that local disease is rather the cause of death than metastatic effects.

(Hutson et al., 1992; Northrup N .C. et al., 2006; Postorino Reeves et al., 1993; Withrow and

MacEwan, 2001) In dogs, non-tonsillar SCC was reported to have a metastatic rate of approximately

20% with rates depending on localisation in the oral cavity: rostral located oral tumours had lower

metastatic rate than the caudal tongue and tonsil. (Theon et al., 1997b)

2.2 Malignant melanoma Although malignant melanoma is the most frequent oral tumour in dogs, it is uncommon in cats.

(Farrelly et al., 2004) Oral melanoma is known to be a highly malignant tumour with high metastatic

rate to the lymph nodes and lungs. (Kudnig et al., 2003; Overley et al., 2001; Williams and Packer,

2003) Reported in up to 80% of dogs, metastasis is depending on site, size and stage. Use of the

clinical staging system composed by the World’s Health Organization (WHO) may benefit in prognostic

interpretation of oral melanoma. (Blackwood and Dobson, 1996; Hahn et al., 1994; Kudnig et al.,

2003; Overley et al., 2001; Owen, 1980; Proulx et al., 2003) Histopathological diagnosis of malignant

melanoma can be challenging: in one third of all melanoma cases amelanotic melanoma is present. If

dealing with undifferentiated or anaplastic sarcoma or epithelial cancer, underlying presence of

malignant melanoma should be checked. (Liptak and Withrow, 2007) Malignant melanoma shows high

immunoreactivity and therefore active research in the molecular approaches of treatment, especially in

genetic immunotherapy, is intensively conducted. (Alexander et al., 2005; Bergman et al., 2004;

Bergman et al., 2006; Bergman et al., 2003; Dow et al., 1998; Elmslie et al., 1994; Elmslie et al., 1995;

Hogge et al., 1998; MacEwen et al., 1999; Macewen et al., 1986; Moore et al., 1991; QuintinColonna

et al., 1996)

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2.3 Fibrosarcoma On histology fibrosarcoma tends to have a benign appearance and histological diagnosis provided by

pathologists often includes “fibroma” and “low-grade fibrosarcoma” due to doubt. This appearance

frequently involves the hard palate and dental arcade between the canine and carnassial teeth of

large-breed dogs and has been described as “histologically low-grade but biologically high-grade”

fibrosarcoma. (Ciekot et al., 1994) Fibrosarcoma requires an aggressive treatment, particularly when

fast tumour growth, recurrence or bone invasion is present. Despite its high local invasion, metastasis

to the lungs and regional lymph nodes in dogs was reported in less than 30% of cases. (Hahn et al.,

1994; Kosovsky et al., 1991; Schwarz et al., 1991a, b; Todoroff and Brodey, 1979; Wallace et al.,

1992)

2.4 Papilloma Papilloma is caused by a viral agent (papovavirus) and transmitted horizontally by direct contact;

however indirect spread is possible because of their ability to survive in the environment. (Roden et

al., 1997) Papillomatosis mostly affects young animals. Spontaneous regression of the lesions within 4

to 8 weeks is seen in most affected animals. Significant side effects are uncommon, but occasionally

marked involvement of the lesions can cause dysphagia or respiration problems. (Liptak and Withrow,

2007) Because of their self-limiting nature and easy visual detection, prevalence records may vary

and are difficult to determine. The influence of papillomavirus in the development of cancer has been

reported multiple times in cats and dogs, but the precise role of papillomavirus in cancer processes is

still unclear. (Altamura et al., 2016; Luff et al., 2016; Munday, 2014; Munday and Kiupel, 2010;

Munday et al., 2011; Thomson et al., 2016) A predisposition for oral SCC in individuals affected longer

than 18 months has been suggested. (Regalado, 2016)

2.5 Adenocarcinoma Adenocarcinoma is an uncommon malignant tumour usually originating from palate and salivary gland.

It has local invasive growth and metastasis to regional lymph nodes is common.

2.6 Mucoepidermoid carcinoma Mucoepidermoid carcinoma can be defined as a combination of squamous epidermoid cells, mucus-

producing cells and intermediate type cells. Due to this characteristic several sections of the tumour

have to be closely examined until all three components are observed. Pathological behaviour of this

tumour varies from low grade (well differentiated) to high grade (poorly differentiated). The degree of

malignancy depends on the degree of differentiation of the mucous cells, the number of well-

differentiated epidermoid cells, anaplasia and the growth pattern. This growth pattern may vary from

broad “pushing” invasion to infiltrative growth, while all cells are poorly encapsulated. (Head et al.,

2002)

2.7 Osteoma Osteoma is a benign tumour and consists of normal mature compact bone and/or trabecular bone on

histological appearance. (Fiani et al., 2011a; Goldschmidt and Thrall, 1985; Goudar et al., 2011;

Misdorp and Vanderheul, 1976) It is a progressively slow growing mass and no clinical signs occur

until it interferes with occlusal functioning of the jaw or nearby structures and tissues. (Dalambiras et

al., 2005; Ogbureke et al., 2007) Predisposed localisations of oral osteoma are skull and maxillofacial

bones. (Goldschmidt and Thrall, 1985) Osteoma has not been reported with metastasis, malignant

transformation, bone destruction or bone lysis. (Baba and Catoi, 2007; Gassel and Huber, 2002;

Woldenberg et al., 2005)

2.8 Haemangioma Haemangioma is a benign tumour of vascular endothelial origin occurring in a variety of sites. Despite

their benign character, they can induce severe anaemia due to heavy blood loss. (Schoofs, 1997;

Widmer and Carlton, 1990)

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2.9 Anaplastic carcinoma Anaplastic carcinoma is a malignant epithelial tumour without further squamous or glandular

differentiation. (Head et al., 2003) It is a very malignant, diffusely infiltrating and extensively

metastasizing cancer causing death in a short period. Anaplastic carcinoma is not only highly invasive

but also predominantly scirrhous which is not the usual feature in human anaplastic carcinoma.

(Misdorp et al., 1973)

2.10 Fibromatous epulis of periodontal origin Fibromatous epulis of periodontal origin is a benign gingival proliferation appearing similar on

macroscopical appearance to gingival hyperplasia. They are slow-growing and firm masses usually

covered by intact epithelium and having a predilection for maxillary premolar teeth. (Yoshida et al.,

1999)

2.11 Amyloid-producing odontogenic tumour Amyloid-producing odontogenic tumor (APOT) is distinguished by the proliferation of odontogenic

epithelium along with intercellular deposition of amyloid materials. APOTs usually are reported with

expansile growth, form solid or cystic masses, and typically behave as a benign tumour. They may

show local invasion, incorporate teeth, and may progressively destroy the jaw and facial bones.

Recurrence occasionally occurs following excision. (Dubielzig, 2002)

2.12 Gingival hyperplasia Gingival hyperplasia is a reactive proliferation of epithelium and may appear focal, multiple focal or

generalized. Generalized hyperplasia may be induced by plaque accumulation, but also certain drugs

(diphenylhydantoine, cyclosporine, amlodipine) can be the cause of these gingival enlargements.

Treatment consists of removing the underlying cause or surgical excision in more developed cases.

(Verhaert, 2001)

3. Symptoms and history In domestic cats and dogs, the presence of a mass in the mouth is usually noticed by the owner. Other

symptoms that may occur in animals with an oral tumour are increased salivation, dysphagia or pain

when opening the mouth, bloody oral discharge, facial swelling or exopthalmos, swollen lymph nodes

in the cervical region and epistaxis. The combination of loose teeth and a general good dentition has

to raise the clinician's attention for possible neoplastic bony processes. (Liptak and Withrow, 2007)

Paraneoplastic syndromes are quite rare for tumours, although hypercalcemia and hyperglycemia

have been reported. (Hutson et al., 1992; Padgett et al., 1997)

4. Diagnostic approach When an oral tumour is suspected to be in connection with bone tissue, radiographic examination

under general anaesthesia is recommended. Useful projections are intra-oral, open mouth, lateral and

ventrodorsal or dorsoventral. Bone lysis can be evaluated, keeping in mind that cortical destruction

has to be 40% or more before being radiographically visible. However, bone invasion can’t be

excluded by normal radiographs. Radiographs will facilitate clinical staging of the tumour and resection

width when surgery is recommended. Involvement and dislocation of associated teeth can be revealed

through intraoral radiographs. Possible secondary pathological jaw fractures can also be identified.

The use of computer tomography (CT) can be a helpful indicator to determine more detailed

information for staging or tumour extension into bone, nasal cavity, orbit or caudal pharynx because of

its higher sensitivity. (Liptak and Withrow, 2007)

Palpation of the regional lymph nodes for enlargement or asymmetry is advised as a possible predictor

of metastasis; however it isn’t an accurate predictor. (Williams and Packer, 2003) These regional

lymph nodes consist of the mandibular, parotid and medial retropharyngeal lymph node. Aspiration of

the lymph nodes should be undertaken in all suspected cases of oral cancer, regardless of size or

mobility. (Herring et al., 2002; Williams and Packer, 2003) Valuable staging information can be

18

obtained by en bloc resection of the lymph nodes, even though therapeutic effects are uncertain.

(Herring et al., 2002; Smith, 1995)

Golden standard in the diagnostic approach of oral tumours is biopsy. Incisional biopsies include large

samples of healthy tissue at the edge and deeper areas of the lesion. It is recommended to biopsy

through an intraoral incision, skin biopsies should never be undertaken because of the risk of tumour

spreading. Excisional biopsies can be performed when dealing with smaller lesions, but awaiting

biopsy results is strongly advised due to the possibility of an additional treatment plan. Aspiration or

cytological touch of the tumour mass was believed not to provide useful information considering

necrosis and inflammation of tissue. (Liptak and Withrow, 2007) Nevertheless, a recent study in 85

dogs and 29 cats reported a great agreement in diagnostic accuracy between cytological (fine needle

aspiration, fine-needle insertion and impression smear) and histopathological diagnosis. It was

suggested that cytological examination of oral tumours is an appropriate and a reliable diagnostic tool.

(Bonfanti et al., 2015)

5. Histological features

5.1 Squamous cell carcinoma The typical histologic characteristics of SCC in cats consist of irregular cords and islands of

pleomorphic squamous epithelial cells with abundant eosinophilic cytoplasm, prominent intercellular

bridges and occasional formation of keratin pearls. (Bilgic et al., 2015; Stebbins et al., 1989) Extensive

squamous differentiation is seen in many squamous cell carcinomas, even though only few foci are

present in some tumours. Variable degrees of inflammation (neutrophils, plasma cells, lymphocytes),

necrosis, ulceration and desmoplasia are featured on regular basis. (Bilgic et al., 2015) Invasion in

nearby connective tissue, skeletal muscle or bone, with possibility of osteolysis or bone resorption, is

common. (Martin et al., 2011) Canine oral SCC has a similar histological appearance, but can further

on be differentiated in various histological subtypes comparable with human oral SCC. (Nemec et al.,

2012) Histological differentiation can be difficult between canine oral SCC and canine acanthomatous

ameloblastoma which may result in inadequate treatment therapy. Using expression profiles of

cytokeratins and calretinin can help to distinguish between these two epithelial-derived neoplasms.

(Fulton et al., 2014)

5.2 Malignant melanoma Small foci of up to 20 heavily pigmented cells may be observed in the basal levels of the epithelium of

adjacent mucosae. Intraepithelial cells and cells situated in this junctional change have a different

appearance. Intraepithelial cells may vary in size and shape of both cytoplasma and nuclei, while cells

of the second type have a uniformly round or polygonal appearance with uniformly round or oval

central nuclei. Infiltration into submucosa is common with possible further migration to the epithelium.

A malignant melanoma is divided into lobules, and the cells are supported by a minimum of

collagenous stroma. In tumours and between tumours the mitotic index and melanin content can differ.

Sections can be bleached with 1 percent potassium permanganate if the nucleus is masked by

pigment granules. Poorly pigmented and amelanotic tumours can make diagnosis complicated, but

respectively the detection of melanophages and the use of Masson Fontana silver stain may help in

revealing their true nature. (Head et al., 2002) Other helpful tools in the visualization of these tumours

are electron microscopy and monoclonal antibodies for melanoma. (Berrington et al., 1994; Carpenter

et al., 1980; Turk and Leathers, 1981) A general agreement has been made that basically all canine

oral melanomas are malignant, but benign forms have been reported as well. (Bostock, 1979) Feline

oral melanoma has comparable histological features to dogs, but highly pigmented and pleomorphic

tumours are uncommon. (Patnaik and Mooney, 1988)

5.3 Fibrosarcoma Fibrosarcomas show numerous uniform to pleomorphic spindle cells separated by small amounts of

collagen or surrounded by reticulin fibers in silver stained sections. The tumour consists of interlacing

19

bundles, of which some are cut longitudinally forming elongated cells and others are cut tangentially or

at right angles forming round cells. Highly malignant tumours are characterized with numerous mitotic

figures, infiltrative borders, pleomorphic cells, and even multinucleate giant cells. Histopathological

features of feline fibrosarcoma resemble the canine form comprising densely packed pleomorphic

fibroblasts in interwoven fascicles with variable amounts of collagen. (Head et al., 2002) Feline

melanoma has up to five mitoses per high power field, and in two studies including 43 cases 3

tumours revealed a few multinucleated cells. (Kemp et al., 1976; Stebbins et al., 1989)

5.4 Papilloma Papillomatosis is determined on histology by thickening of the epithelium due to the promotion of

epithelial cell proliferation by papillomaviruses (PV). If a marked proliferation is present, it can result in

folding of the thickened epithelium and a papilloma. Viral replication in papillomas can appear on

histology as PV-induced changes with the possibility of enlarged cells with a shrunken nucleus

surrounded by a clear cytoplasmic halo (koilocytes), cells with increased quantities of grey or blue

fibrillary cytoplasm, cells with intracytoplasmic inclusions or cells with enlarged vesicular nuclei.

Observation of intranuclear inclusions can be made, even though these inclusions can be difficult to

differentiate from nucleoli due to its transient appearance. PV-induced lesions frequently include

clumping of keratohyalin granules in the granular cell layer.

In general, lesions with more marked epithelial proliferation, such as papillomas, are in favor of greater

viral replication and are more likely to exhibit PV-induced cell changes. This contrasts lesions with

more modest epithelial proliferation (such as a viral plaque) involve less viral replication and

occasionally exhibit PV-induced cell changes. PV-induced cell changes present within a lesion do not

support automatically PV infection as cause for the lesion. Nevertheless, the presence of PV-induced

cell changes does prove viral replication in this lesion and consequently suggests the fact that PV may

have influenced normal cell behavior. (Munday et al., 2017)

5.5 Adenocarcinoma In adenocarcinoma, the acinar aspect is structurally dominant, although papilliferous proliferations may

also be seen. Cells have a round to polygonal appearance, with basophilic cytoplasm and small oval

nuclei. Clear cells have been identified in small salivary glands tumours related to the dog tongue. A

great variation in degree of cellular atypia, mitotic activity and infiltrative growth has been observed,

even within the same tumor, but in particular from one case to another. (Head et al., 2003)

5.6 Mucoepidermoid carcinoma Mucoepidermoid carcinoma can be defined as a malignant tumour distinguished by the presence of

mucous cells and the formation of cysts. The tumour is bordered by occasionally keratinized

squamous cells and intermediate cells with one of the structures having a dominant presentation.

Malignancy is revealed trough the grouping of mucoid cells into nests, numerous atypical mitoses,

large polymorphic nuclei and infiltrative growth. The predominance of the epidermoid component is

characterized by stratification of squamous cells and their arrangements in cords. These squamous

cells are seen with large vesicular nuclei and prominent nucleoli, while the presence of keratin is easy

to detect. The cell cytoplasm may reveal PAS-positive mucopolysaccharide drops and contain smaller

cysts than low-grade tumours. Rupture of these cysts may be possible, provoking a granulomatous

reaction with giant cells and cholesterol clefts. (Head et al., 2003)

5.7 Osteoma Osteoma consists of growing bone tissue, initially cancellous bone and progressively becoming

compact. In soft tissue spaces between bony trabeculae one or more centrally located small caliber

blood vessel, a sparse population of spindle cells, and a moderately fibrillary connective tissue matrix

are present. Hematopoietic elements and adipose tissue may be present as well in this area. Actively

growing osteomas are characterized with a border of connective tissue layer resembling the

periosteum, while newly formed trabeculae are slender and oriented perpendicular to the surface of

the osteoma. Older and less superficial trabeculae have a thicker appearance and may show no

orientation. Usually osteomas are organized in an orderly zonal pattern. In an active growing osteoma,

20

the periosteum is well differentiated and consists of both fibrous and osteogenic layers. A layer of

peripheral trabeculae is formed by a border of typical osteoblasts depositing woven bone. Due to

normal remodeling activity woven bone is replaced partially or complete by finely fibered lamellar bone

forming deeper trabeculae. Osteomas with minor organization may also be seen. This type of osteoma

includes poorly differentiated periosteal covering, absence of osteoblasts in the periosteum, irregular

shaped and disoriented trabeculae, and infrequent remodeling and replacement by lamellar bone.

(Thompson and Pool, 2002)

5.8 Haemangioma On histological appearance haemangioma comprises proliferating, vasoformative mesenchymal tissue

forming capillary and cavernous vessels and, less frequent, arterial and venous structures. Pericytes

and fibroblasts were described to encircle endothelial cells. (Calonje and Fletcher, 2007; Gross et al.,

2007) Haemangiomas may be divided histologically as capillary, cavernous, arteriovenous, lobular,

spindle cell or epithelioid subtypes. (Calonje and Fletcher, 2007; Gross et al., 2007; Vos et al., 1986;

Warren and Summers, 2007)

5.9 Anaplastic carcinoma Anaplastic carcinoma is primarily characterized by irregular masses of pleomorphic cells ranging from

polyhedral to spindle-shaped and showing anisocytosis. Nuclei comprise anisokaryosis and are

sometimes found hyperchromatic, while the prominent nucleoli exhibit many mitoses. Multinucleate

giant cells may be exposed, and areas of necrosis and hemorrhage are common. (Head et al., 2003)

5.10 Fibromatous epulis of periodontal origin The main histological characteristic is the presence of a mesenchyme suggesting the periodontal

ligament. This mesenchyme consists of a dense cellularity composed of small stellate to spindle

fibroblast cells regularly positioned in a dense fibrillar collagen background. Localized deposition of

collagen matrix is observed regularly, and the matrix consistency varies from bone to cementum and

dentin. The stroma is filled with evenly spaced large empty blood vessels. A secondary feature is the

presence of a frequently seen odontogenic epithelium. Long fronds can sometimes be found attaching

to the surface epithelium; although the surface gingiva is not always attended meaning these epithelial

cords can also originate from the cell rests of Malassez within the periodontal ligament. (Head et al.,

2003)

5.11 Amyloid-producing odontogenic tumour The two basic histological features of an amyloid-producing odontogenic tumour (APOT) are

irregularly shaped islands or strands of squamous epithelium within a fibrous connective tissue stroma

and deposits of amyloid associated with the epithelium; with some of the amyloid calcified. In some

areas of the epithelium palisading of the basal cells may be exposed. Occasionally stellate reticulum

occurs in the centre. Next to the epithelium, a collagenous matrix with the appearance of dentine is

present focally. (Gardner et al., 1994) APOT is often related in veterinary literature to calcifying

epithelial odontogenic tumour (CEOT) (Abbott et al., 1986; Stebbins et al., 1989; Walsh et al., 1987),

but has specific microscopical differences with the human CEOT (Pindborg tumour) of man. The main

difference on histological aspect is the appearance of the epithelium, which in the CEOT comprises

sheets of eosinophilic epithelial cells that often show considerable nuclear pleormorphism. Epithelial

cells can vary from small and resembling reduced enamel epithelium to hyperchromatic and palisaded

basal cells occasionally found in APOT, do not occur in CEOT. Another difference is the presence of

focal areas of stellate reticulum in APOT, but not exhibited in CEOT. Amyloid can be found in both

tumours, sometimes calcified. (Gardner et al., 1994)

5.12 Gingival hyperplasia Excessive amounts of nearly normal-looking gingival collagen and an intact epithelium are seen in

gingival hyperplasia. Oedema, vascular dilation, and/or perivascular lymphocytes can be present. In

the case of proliferative gingivitis, a profuse infiltrate of lymphocytes and plasma cells are observed.

21

Frequently, complex folds that extend both inward and outward are formed by the epithelium

(pseudoepitheliomatous hyperplasia). (Head et al., 2003)

6. Therapy Surgery and radiation therapy are the most used methods in the local control of oral tumours. They are

the only treatment options with the opportunity of achieving curative effects.

6.1 Surgery Surgical resection is the fastest, most economical and most curative treatment method. Due to the

frequent adherence of tumour tissue on bone, bony margins should be included when determining

surgical resection width. Maxillectomy (segmental), mandibulectomy (hemi or segmental) and

orbitectomy are advised for most oral tumours, especially in tumours non-reactive to radiation therapy

or with extended bone invasion. Malignant oral tumours such as fibrosarcomas, squamous cell

carcinomas or malignant melanoma’s require margins of at least 2 cm. For oral squamous cell

carcinoma in cats, margins greater than 2 cm are strongly indicated due to the high rate of local

recurrence. This wide size of margins is usually not possible in domestic carnivores because of

significant morbidity effects. Therefore, margins of 1 cm are encouraged by some clinicians if broad

margins are technically not possible. (Lascelles et al., 2011) Logically, results of oral surgery will be

affected by more narrow margins. Benign lesions and rostral SCC in dogs can be treated successfully

with segmental or rostral resections. More aggressive tumours such as fibrosarcomas or tumours with

pronounced caudal localisation demand large resections such as orbitectomy, hemimandubulectomy,

hemimaxillectomy or radical maxillectomy. These procedures imply some morbidity, but are usually

well accepted by cats and dogs. Most common peroperative complications are blood loss and

hypotension and are mostly found during caudal mandibulectomy. (Lascelles et al., 2003)

Owner satisfaction with the remaining life quality and cosmetic appearance of their pet can exceed

80%. (Lascelles et al., 2003; Northrup et al., 2006) Post-operative care has to be discussed with the

owner because of possible temporary or permanent complications. Malocclusions and mandibular drift

can cause trauma to the hard palate. Filling down of the damaging tooth in combination with root canal

treatment is a possible resolution for this complication. In a situation of inability to eat or drink, feeding

tubes have to be administered, but are usually not required after oral surgery in dogs. (Garrett et al.,

2007)

For tongue tumours, surgical resection is advised starting from the mobile rostral part. It is required to

remove unilateral tumours not crossing the midline of the tongue with partial glossectomy of up to 60%

of the tongue surface. Tumours located caudal to the midline or bilateral tumours necessitate larger

resection, however this could interfere with basic functions of the tongue such as thermoregulations in

dogs and grooming in cats. Case reports of resection or avulsion of the tongue varying from 50 - 100%

in 5 dogs suggest more aggressive resections may be in favour of minimal postoperative

complications and a decent life quality. (Dvorak et al., 2004) Short-term complications of glossectomy

consist of ptyalism and dehiscence, while minor changes in drinking and eating habits are reported as

long-term complications. (Lascelles et al., 2011)

In patients with tonsillar SCC, bilateral tonsillectomy is advised due to the high frequency of bilateral

disease.

Cryosurgery can be used for lesions less than 2 cm in diameter with bony fixation or minimal invasion.

However, serious side effects can be caused in more extensive lesions. Mandibular fractures or

maxillary oronasal fistulas may be the result using too aggressive cryosurgery. In general, cryosurgery

may not be used in tumours only involving soft tissues. (Liptak and Withrow, 2007)

6.2 Radiation therapy Radiation therapy can be used as primary treatment method or in addition to surgical resection. Sole

therapy can be used for tumours that are radio responsive such as malignant melanoma, canine oral

SCC and fibromatous epulis of periodontal ligament. In these tumours, tumour control is better with

radiation therapy alone in the T1 and T2 stage. (Blackwood and Dobson, 1996; Theon et al., 1997a;

Theon et al., 1997b) Adjunct radiation therapy is usually required for incomplete resected tumours or

tumours with an aggressive local behaviour, since radiation therapy has specific locoregional

22

effectiveness. When treating resistant tumours, radiation therapy can be assisted by surgery,

chemotherapy and radiation sensitizers such as gemcitabine and etanidazole in order to improve local

tumour control and survival time (Evans et al., 1991; Hutson et al., 1992; Jones et al., 2003; LaRue et

al., 1991; Ogilvie et al., 1993; Thrall et al., 1981) Fraction dose is in positive correlation with response

rates, although one study didn't find any differences in survival time or local recurrence rate between

two hypofractionated protocols and a conventional protocol. (Overgaard et al., 1986; Proulx et al.,

2003)

Tonsillar SCC can be controlled locally by regional radiation of the pharyngeal region and cervical

lymph nodes in over 75% of cases, even though survival time of more than a year is only seen in 10%

of the irradiated patients. (Brooks et al., 1988; Macmillan et al., 1982) A combination of radiation

therapy and a variety of different chemotherapy drugs was reported to significantly improve the

survival time and local tumour control of 22 dogs in one study. (Brooks et al., 1988)

Acute effects can occur but are usually self-limiting. Depending on the irradiated region, side effects

can consist of oral mucositis, dysphagia, alopecia, moist desquamation and ocular changes such as

keraititis, uveitis, conjunctivitis and blepharitis. (Jamieson et al., 1991; Larue and Gillette, 2001;

Roberts et al., 1987; Theon et al., 1997a; Theon et al., 1997b) Coarse fractionation results in less

acute effects than full course protocols and generally disappears quickly. (Blackwood and Dobson,

1996) In general late complications are very uncommon (less than 5% of cases) but can include skin

fibrosis; permanent alopecia; formation of oronasal fistula and bone necrosis; development of

secondary malignancy within the radiation field and ocular changes such as keratoconjunctivitis sicca,

ocular atrophy and cataract formation. (Theon et al., 1997a; Theon et al., 1997b; Thrall, 1984; Thrall et

al., 1981)

6.3 Chemotherapy Although local tumour control is the biggest challenge in the treatment of oral tumours, some oral

tumours such as oral melanoma or tonsillar SCC are linked with high metastatic potential. In these

cases, chemotherapy could be a valuable tool in treatment management, but chemosensitivity is low in

these tumours. Tonsillar SCC has been linked with significant increase in COX-2 expression but the

use of nonsteroidal anti-inflammatory drugs has not proven any clinical results. For oral SCC in dogs,

piroxicam may have some effect in combination with cisplatin, but cisplatin at standard dosage can

cause renal toxicity. (Boria et al., 2004; de Vos et al., 2005) In cats, mitoxantrone in combination with

radiation therapy has shown promising results against oral SCC in a small number of animals. (LaRue

et al., 1991; Ogilvie et al., 1993) Although oral melanoma is considered chemoresistant, platinum

drugs consisting of intralesional cisplatin and systemic carboplatin would achieve favourable but minor

effects on treatment in dogs. (Rassnick et al., 2001) A promising pathway in the treatment of oral

melanomas is the use of immunotherapy agents and biologic response modifiers. Preliminary studies

including amongst others Corynebacterium parvum, liposome-muramyl tripeptide-

phosphatidylethanolamine (L-MTP-PE), interleukin-2 (IL-2), tumour necrosis factor, pro-inflammatory

cytokines, etc. have suggested improvements in survival time and local tumour control, but clinical

trials on large scale are lacking. (Alexander et al., 2005; Bergman et al., 2004; Bergman et al., 2006;

Bergman et al., 2003; Dow et al., 1998; Elmslie et al., 1994; Elmslie et al., 1995; Hogge et al., 1998;

MacEwen et al., 1999; Macewen et al., 1986; Moore et al., 1991; QuintinColonna et al., 1996) This

emerging approach is considered promising as a complementary method to surgery and radiation

therapy.

7. Prognosis

Various case series covering a broad variety of oral tumour types, the majority surgically treated, have

been published. In general, acanthomatous epulis and SCC have the best results in survival time and

local tumour recurrence in dogs, while the highest rates are found in fibrosarcoma and malignant

23

melanoma. (Liptak and Withrow, 2007) Fibrosarcoma still has very high local recurrence rates;

excessive resections and or the addition of adjuvant therapies are necessary. (Forrest et al., 2000) In

melanoma's, high metastatic rate demands other adjuvant therapies, even though in 75% of cases the

disease is controlled locally. (Liptak and Withrow, 2007) Oral SCC in cats has a poor prognosis mainly

due to difficult achievement of complete surgical resection, high recurrence rates and unfavourable

results using radiation therapy and/or chemotherapy. (Bilgic et al., 2015)

For oral tumours in general, rostral localisation and histological complete resection are considered as

favourable in terms of prognosis. Rostral located oral tumours are usually discovered earlier than

caudal ones, which permits the increased probability of complete resection of the tumour in an earlier

stage. Local recurrence rate has a positive correlation with incomplete resection (Schwarz et al.,

1991a, b) and therefore a negative effect on survival time: consecutive treatments tend to be less

successful and the effect on tumour response decreases. (Harvey et al., 1981; Overley et al., 2001) In

two studies led by the same author, tumour related deaths were found multiple times more likely with

malignant tumours, tumours located caudal to the canine teeth and incomplete resections. (Schwarz et

al., 1991a, b)

In dogs treated with megavoltage radiation the size of the tumour has an impact on local tumour

control for malignant as well as benign tumours. Local recurrence as encountered in 30% of the cases

is three and up to eight times more likely in respectively T2 (2-4 cm diameter) and T3 (>4 cm

diameter) tumours compared to T1 tumours (< 2 cm diameter). Survival rates in dogs with malignant

oral neoplasia are also influenced by tumour size with 3-year progression-free survival rates of 55%,

32% and 20% for T1, T2 and T3 tumours respectively. (Theon et al., 1997b)

For tumours of the tongue, the prognosis depends on the type, grade and localisation of the tumour.

(Carpenter 1993) Rostral localisation has better prognosis due to earlier tumour detection and easier

resections widths. Cancer in the caudal tongue may have richer lymphatic and vascular vessels what

is in favour of metastasis. (Liptak and Withrow, 2007)

24

Materials and methods

1. Survey outline

A questionnaire was drafted on www.enquetesmaken.be with the purpose of reaching as many

veterinarians and veterinary pathologists dealing with wildlife carnivorans as possible. To reach this

target audience, organisations or societies frequently dealing with these kinds of animals were

contacted by email to send the questionnaire to their affiliated zoos or animal parks and veterinarians.

In this questionnaire, wildlife facilities/veterinarians were being asked about characteristics of their

encountered oral tumour(s). Questions of the survey were created to retrieve following data topics:

Species of the animal (Latin name)

Sex of the animal

Age of the animal at moment of diagnosis

Geographical region of tumour occurrence

Symptoms and clinical history of the animal

Presence of histopathological examination

(Histological) diagnosis of the tumour

Location of the tumour in the oral cavity

Shape of the tumour

Delineation of the tumour

Invasiveness of the tumour

Distribution

Cut surface appearance

Lymph node involvement

Presence of metastasis

Biopsy method

Treatment

Recurrence of the tumour after treatment

Survival time

Participants of this questionnaire were briefed about the possibility of the data being used in a peer

reviewed paper later on and were asked for their permission to use this data before proceeding to

further questioning.

The survey can be found on the following internet link: https://www.enquetesmaken.com/s/84df898

2. Response

Thirty one survey participations were received until May 2018. In total, eleven additional cases were

collected and considered as complete contributions to the study. These cases can be found under

‘Appendix B’.

25

Results

In total, 75 case reports of oral tumours in non-domesticated carnivorans with histopathological

evidence were retrieved. 64 case reports were described in literature, while 11 useful case reports

were gathered by sending out an online survey. 67 case reports (89%) were diagnosed as non-

odontogenic oral tumours and 8 case reports (11%) as odontogenic oral tumours. In the group of non-

odontogenic tumours, oral papilloma’s had the highest incidence with 37 described cases, followed by

squamous cell carcinomas (17 cases) and melanomas (5 cases). Other less commonly retrieved non-

odontogenic tumours were carcinoma (3 cases), muco-epidermoïd carcinoma, fibrosarcoma, osteoma

and hemangioma (1 case each). Of the 8 reported odontogenic tumours, 4 were classified as

fibromatous epulis of periodontal ligament, in some papers referred to as peripheral odontogenic

fibroma (POF). Gingival hyperplasia was reported twice, while amyloid-producing odontogenic tumour

(APOT) and calcifying epithelial odontogenic tumour (CEOT) both had one representative.

41 cases of oral tumours (54%) were reported in animals belonging to the suborder Feliformia and 34

cases (46%) were caniform species. In 42 out of 75 cases, the animal's sex was mentioned resulting

in an equal representation of 21 male and 21 female species. Only 4 animals were neutered: one male

and three females. Due to differences in species' physiology and life expectancy, it's very difficult to

evaluate and compare the age of affected animals. A variety of different age groups was represented,

from juvenile to (sub) adult and aged animals. In a group of 46 animals where age was mentioned or

perceived, most of them were belonging to the group of adult to aged animals and only 2 out of 46

animals were categorized as non-adult animals. 30 cases of oral tumours were reported in free-

ranging animals and all of them were diagnosed as oral papillomatosis.

Symptoms or a description of oral mass discovery were reported in 54 out of 75 cases. With 22

observations facial swellings were frequently reported. These swellings included swollen jawbones (6

observations), lingual masses (5 observations), swollen lips (6 observations), swollen gingiva (4

observations) and swollen skin under the eye (1 observation). Other more frequently mentioned

symptoms were anorexia (10 observations), hypersalivation (4 observations), blood-tinged saliva (4

observations), presence of ulceration/hemorrhage/erythema in the region of lip or gingiva (4

observations), depression (3 observations) and weight loss (3 observations). Alopecia and staggering

were both seen twice. Only one observation was reported for unilateral chewing, scratching, irregular

adjacent mucosae, polydipsia, waning and waxing facial lesions, increased coughing and ataxia. In 3

papilloma cases in coyotes (Canis latrans) a good body condition despite the discovery of (severe)

papilloma-like lesions was reported. In 22 cases, an oral mass was observed during a physical

examination without a specific oral tumour check-up purpose. Oral tumours were thus discovered 12

times during translocation examination, 5 times during general physical examination, twice during

dental treatment and once during behavioral/ecologic studies, surgical intervention and feeding time.

Treatment of an oral tumour was undertaken in 16 cases, divided in 7 odontogenic and 9 non-

odontogenic cases. 6 out of 9 non-odontogenic cases were SCC, all of them appearing in Malayan

sun bears (Helarctos malayanus). The 3 remaining non-odontogenic tumour treatments were applied

in a malignant melanoma, fibrosarcoma and osteoma respectively. The odontogenic group consisted

of 2 gingival hyperplasia cases, 1 calcifying epithelial odontogenic tumour and 4 fibromatous epulis of

periodontal ligament.

Treatment was considered successful in 5 out of 16 cases. Unsuccessful outcome was registered in 7

cases, while 4 cases were unclear about clearance or recurrence of the tumour. 3 of the 5 successful

treatments were accomplished by local excision of the tumour: 2 gingival hyperplasia cases in

cheetah’s (Acinonyx jubatus) and an osteoma in a female striped skunk (Mephitis mephitis). The

remaining 2 successfully treated tumours were the result of a multimodality therapy: malignant

melanoma in a African lion (Panthera leo) and SCC in a Malayan sun bear (Helarctos malayanus).

The African lion underwent a series of hypofractionated radiation therapies and immunotherapies

followed by surgical excision of the tumour. In the case of the Malayan sun bear, bilateral rostral

mandibulectomy and subsequent intra- and perilesional cisplatin injections were firstly performed, after

26

which radiation therapy and one additional cisplatin treatment were started due to histopathological

incomplete resected margins. 5 of the 7 unsuccessful tumour treatments were cases of oral SCC, all

of them appearing in adult to aged Malayan sun bears (Helarctos malayanus). 4 cases were found

Gammaherpesvirus positive, while one case was Herpesvirus negative. Surgical excision of the oral

tumour was undertaken in all of the 5 cases, but recurrence of an oral mass appeared in a time lapse

of months to years depending from case to case. Another attempt of surgical resection was

undertaken in 3 out of 5 cases, all of them herpesvirus positive. In one case, additional sub-lesional

injections of carboplatin were administered following a second excision of the tumour. Another therapy

that was started after tumour recurrence was the combination of intralesional injections of fluorouracil

and cisplatin and oral administration of piroxicam and L-lysin. The 2 non-SCC that failed to achieve

favorable results were fibrosarcoma in a maned wolf (Chrysocyon brachyurus) and fibromatous epulis

of periodontal ligament in an African lion (Panthera leo). Rostral maxillectomy was performed in the

maned wolf, but recurrence and distant metastasis occurred after 7 months. In the case of the African

lion, a histologically similar mass reappeared on the same location 6 months following excision. Of the

4 cases where tumour recurrence was unknown; 3 cases comprised fibromatous epulis of periodontal

ligament, all appearing in cheetah’s (Acinonyx jubatus). The remaining case was CEOT in a Siberian

tiger (Panthera leo altaica). All of these 4 tumours underwent local excision as only treatment method.

No curative treatment was attempted or treatment was unknown in 59 out of 75 cases (79%). In 22

cases, the oral mass was only observed at necropsy and obviously treatment couldn't be initiated. The

affected animals and their diagnosed oral tumour can be found in Table 1. 24 cases were left

untreated, all of them had papilloma. This papilloma group consisted of 2 coyotes (Canis latrans), 2

puma's (Felis concolor), 2 bobcats (Felis rufus), 4 Asiatic lions (Panthera leo persica), a snow leopard

(Panthera uncia), a clouded leopard (Neofelis nebulosa), 11 Canadian lynx (Felis lynx canadensis)

and one spotted hyena (Crocuta crocuta). Euthanasia was performed in 9 cases, divided in 3 groups

depending on the moment between histopathological diagnosis and euthanasia. A first group,

consisting of 4 cases was euthanized shortly following the biopsy diagnosis: a tiger with gingival

melanoma and both a meerkat (Suricata suricatta), a Californian sea lion (Zalophus californianus) and

a coyote (Canis latrans) with SCC. In a second group animals diagnosed by histopathological proof

were kept on palliative treatment until the decision was made to euthanize the patient because of a

(severe) decrease in life quality. This palliative treatment was used in a bobcat (Felis rufus) and coyote

(Canis latrans) both diagnosed with SCC. A third group of patients was euthanized before

histopathological diagnosis of the oral mass was made and biopsy was therefore taken at necropsy.

This group comprised three individuals: a lion (Panthera leo) with muco-epidermoïd carcinoma, a

meerkat (Suricata suricatta) with anaplastic carcinoma and a wolf (Canis lupus) diagnosed with

tonsillar SCC. In another case, a Bengal tiger (Panthera tigris tigris) was diagnosed with a mandibular

Amyloid-producing Odontogenic Tumour (APOT) at necropsy after he was treated with antibiotics and

was put on adapted nutrition (minced meat) for two months. Finally, 4 cases of diagnosed oral tumours

were retrieved without further clarifications about possible attempted treatments. These comprise SCC

in a red wolf (Canis rufus) and 2 papilloma cases in snow leopards (Panthera uncia).

Metastasis was mentioned in eight cases: 4 SCC, of which 2 were tonsillar SCC; one adenocarcinoma

in a Syrian golden Jackal (Canis aureus syriacus), one muco-epidermoïd carcinoma in an African lion

(Panthera leo), one malignant melanoma in a tiger (Panthera tigris), and one fibrosarcoma in a maned

wolf (Chrysocyon brachyurus). The two tonsillar SCC were found in a polar wolf (Canis lupus arctos)

and captive wolf (Canis lupus) while a mandibular SCC was reported in a meerkat (Suricata suricatta)

and a lingual SCC in a Californian sea lion (Zalophus californianus). Nine times metastasis was found

in the regional lymph nodes: Twice in a submandibular lymph node, both three times in a

submandibular and retropharyngeal lymph node and once in a deep cervical lymph node. The lungs

were reported metastasized six times. Other thoracic organs where metastasis was observed were

mediastinum, heart and mediastinal lymph node with respectively two, one and one observation(s).

Esophagus, diaphragm and kidney all were found metastasized each once. Only in the Syrian golden

Jackall diagnosed with adenocarcinoma the metastasis localizations were not reported.

27

Species name

(English)

Species name (Latin) Histopathological

diagnosis

Localisation

Coyote Canis latrans Papillomatosis

Lips, tongue and

adjacent tissue

Wolves Canis lupus Papillomatosis Oral cavity

Wolves Canis lupus Papillomatosis Oral cavity

Coyote Canis latrans Papillomatosis

Lips, tongue and

adjacent tissue

Coyote Canis latrans Papillomatosis Unknown

Coyote Canis latrans Papillomatosis Oral cavity






California sea lion Zalophus californianus

Squamous cell

carcinoma Tongue

Ocelot Leopardus pardalis

Squamous cell

carcinoma Tongue

Syrian Golden

Jackal C. aureus syriacus Adenocarcinoma

Cheetah Acinonyx jubatus Hemangioma Tongue

Black bear Ursus americanus Carcinoma Tongue

Japanese brown

bear Ursus arctos lasiotus Malignant melanoma Tongue

Amercan badger Taxidea taxus Carcinoma Oral cavity

Mexican Grey Wolf Canis lupus baileyi Amelanotic melanoma Gingiva mandibula left

Mexican Grey Wolf Canis lupus baileyi Amelanotic melanoma

Buccal side left lower

lip

Polar wolf Canis lupus arctos

Squamous cell

carcinoma Tonsilla

Canadian lynx Lynx canadensis

Squamous cell

carcinoma Oral cavity

Table 1: List of animals with discovered and diagnosed oral tumours at moment of necropsy

Discussion

In this literature review, a large number of cases without curative treatment were reported: 59 cases or

almost 8 cases out of 10. Under curative treatment, treatment methods with the purpose of improving

the length of the patient's life are meant. For oral tumours, these methods can include surgical

excision, radiation therapy, chemotherapy or more recently introduced immunologic approaches. It's

clear that a curative treatment is not advised for every patient. This largely depends on the tumour

type, stage, malignancy and presence of metastasis; all elements influencing the patient's prognosis.

Other external factors also have to be taken into consideration. Firstly, financial responsibility of the

treatment has to be taken, while medical curative cancer treatment comes with high costs. In

companion animals, costs of tumour treatment are of less importance than it once was due to their

newly perceived role as 'members of the household'. In wildlife species, this interacting bond with

humans is less present, especially in wild-ranging animals. Captive animals are usually held in zoos or

sanctuaries, while these facilities may be limited by available finances. Treatment of an individual wild-

ranging animal is of less importance than the health of the entire group or even ecosystem. Secondly,

technical equipment must be available. Some facilities may be located in rural areas with high distance

to veterinary practices/hospitals or may not be equipped to provide proper intervention by external

practitioners. The additional costs and clinical consequences of anesthesia necessary for

28

transportation and treatment of these non-domesticated patients neither may be neglected. It is

recommended to trust an experienced team with the monitoring of anesthesia, considering the broad

range of species variation in physiology and metabolism and of course guaranteed safety of the staff.

A large portion of the cases (24 out of 75 cases) were simply left untreated even after

histopathological diagnosis. It has to be mentioned that all of these cases were diagnosed as

papillomatosis which are considered to be self-limiting without further (major) clinical consequences.

Papillomatosis was the most reported oral tumour in this study with an additional 13 cases diagnosed

at necropsy. A total number of 37 case reports were classified as papillomatosis, but the actual

number is estimated higher as a result of case restrictions in this study. For this literature review the

amount of counted cases appearing in spotted hyenas (Nelson et al., 2013) was reduced to one

report. The reason for this lays in the uncertainty in case numbers distinguishing oral and genital

masses. The large representation of papillomatosis may be explainable through multiple reasons.

Papillomatosis has a characteristic macroscopical appearance and thus is more easily to be

suspected and examined further on. The tumour has been subject to large publications held by

multidisciplinary, international scientific teams. In this study, the papilloma lesions were examined

through advanced techniques such as immunohistochemistry, electron microscopy and molecular

genomic sequencing in order to investigate the coevolution and migration of cat species and their

pathogens. (Sundberg et al., 1996; Sundberg et al., 2000) Two other articles included each more than

10 individual case reports. (Samuel et al., 1978; Wolfe and Spraker, 2007)

Oral tumours were frequently discovered at necropsy. Some necropsies revealed oral tumours which

were discovered incidentally and were not considered as the cause of death. In the other cases,

unfavorable clinical symptoms appeared before death of the animal without suspecting the presence

of an oral mass. Unfortunately the exposed symptoms in these cases didn’t lead clinicians to

examination of the oral cavity with consecutive diagnostic procedures and an eventual therapeutic

treatment plan.

Nine cases resulted in euthanasia, consisting of 3 cases where the patient was euthanized before

histopathological examination confirmed an oral tumour. (Dadone et al., 2014; Dorso et al., 2008;

Ryan and Nielsen, 1979) Specific reasons for not taking biopsies of the mass were not précised. In all

the three cases, variable (non-specific) symptoms developed for a couple of weeks before further

action was undertaken. Two animals went through oral examination under general anesthesia when in

both cases a sublingual mass was discovered. Instead of performing biopsies, other diagnostic

approaches were preferred (respectively cytological aspiration and radiographic imaging) to estimate

the nature of the mass. In a meerkat, an odontogenic tumour was suspected and due to the age of the

animal, presence of severe arthritis, and the stress associated with daily treatments further curative

treatment was not attempted and palliative treatment was initiated. At later necropsy, the sublingual

mass was diagnosed as a highly malignant anaplastic carcinoma. Waiting for the cytological results of

the sublingual mass of the lion, NSAIDS were given for two days before the animal showed signs of

dramatic dyspnea. Therefore, the lion was humanely euthanized and at necropsy the mass turned out

to be a histological mucoepidermoid carcinoma. For the third case there were no specifications about

attempted examinations or treatments but histopathological diagnosis of the tonsillar SCC was made

after the captive wolf was euthanized. Although it would result in just a marginal benefit in these cases,

histopathology is indispensable in the identification of oral tumours as this results in facilitating the

choice of the most appropriate treatment therapy.

Six other patients were euthanized, all of them after histological examination of the mass. Two of them

firstly had palliative treatment. The most common reason to perform euthanasia was because of poor

prognosis and aggressive nature of the tumour. The impossibility of wide surgical resection and

complications resulting in interference with eating were also mentioned. The six cases comprised 5

SCCs, all of them were non-tonsillar and occurred in 3 feliform and 2 caniform species, and one

malignant melanoma in a tiger. Although the prognosis for dogs with oral SCC is considered good, two

dog-like species (coyote and Californian sea lion) were amongst euthanized patients. Due to the

reported malignancy of SCC (Californian sea lion) and wide anatomic extent (coyote), euthanasia was

considered the most appropriate decision. Rostral tumour location is prognostic favorable, but wasn't

29

the case for these two cases: they both appeared on the gingiva of the mandibular molar region. In

domestic dogs, local recurrence rate and survival time achieve better results with mandibulectomy

than maxillectomy. (Kosovsky et al., 1991) For radiation therapy, smaller lesions, young age and

maxillary location were mentioned as favorable prognostic factors. (Evans and Shofer, 1988; Theon et

al., 1997b) In the coyote and sea lion, none of them were present. Results of chemotherapy in dogs

with oral SCC are regarded as unsuccessful. Renal toxicity as a mentioned side-effect for the use of

cisplatin and piroxicam could form an additional problem in a 19-year old coyote and 30-year old sea

lion.

Curative treatment was only applied in a minority of cases (16 cases out of 75), with only 5 cases

considered to result in a successful outcome. The specific description of a successful treatment is hard

to define. No recurrence or visual detection of the tumour during a variable time lapse was mentioned

in all of the cases. Two cases reported a time period of 4 months. One osteoma case in a skunk was

only recently subjected to surgical intervention and until survey participation no recurrence occurred;

while a cheetah with gingival hyperplasia had to be euthanized 4 months after surgical excision due to

an unrelated neutrophilic cholecystitis. In the remaining three treatments, no visible detection of the

tumour varied from 6 months to 6,5 years. Besides visual detection criteria such as blood and urine

analysis, signs of metastasis on thoracic radiographs, signs of bone lysis on mandibular radiographs,

survival time and lymph node cytology were used to assess successful outcome. Sole therapy

consisting of surgical resection was performed in considerably benign neoplasia: gingival hyperplasia

and osteoma. Malignant melanoma in a lion and SCC in a sun bear were treated by use of a

multimodality therapy. Due to external-beam radiation and administration of an immunotherapeutic

melanoma vaccine, the tumour size decreased by 50% which made surgical excision of the

mandibular melanoma possible.

The unsuccessfully treated tumours were primarily consisting of five oral SCC cases appearing in

Malayan sun bears. Four of these bears tested positive for the presence of gammaherpesvirus, even

though its pathogenicity and relationship to squamous cell carcinoma is unknown. In the same article,

periodontal disease and traumatic stereotype behaviour were reported as other suggested causes of

recurrence, but warranted further investigation. (Lam et al., 2013) Recurrence of the tumour could also

be explained by the difficulty of complete resection due to large transition between normal tissue and

malignant cells. The use of computer tomography in order to precisely determine tumour margins may

contribute to avoid incomplete resections, but comes with additional financial costs. In the successfuly

executed multimodality therapy, additional chemo- and radiation therapy was initiated because of

incomplete surgical excision. Some bears repeatedly underwent surgical resection of a new growing

mass, in two individuals intra- or sublesional administration of chemotherapy was performed after

recurrence. Radiation therapy was never used in the unsuccessfull treatments. It is tempting to

conclude that multimodality therapy use in tumours with associated malignancy is favorable in exotic

carnivorans, even though the number of reported treatments is insignificantly low. Keeping in mind that

the patients we are dealing with are of non-domesticated nature, the same considerations as being

mentioned in the start of this discussion have to be made.

Similar to domesticated carnivores, oral tumors are frequently diagnosed in a more advanced stage,

leading to a poorer prognosis. Contrary to their domestic relatives, examination of the oral cavity in

exotic carnivorans is only possible under general anesthesia or in circumstances where the animal is

trained to open the mouth. Even though exposure of the oral cavity is possible, it is still challenging to

perform a decent examination in safe conditions. The appearances of particular symptoms are thus a

paramount auxiliary method in the detection of oral neoplasia. Zookeepers or affiliated staff members

hold a key role in the visual detection of minor signs that could imply oral pathology. Careful

communication between these professionals and health practitioners are of extreme importance if

diagnosis in an early stage wants to be achieved. Continuous education of caretakers and even

veterinarians concerning oral discomfort signs is recommended as well in order to anticipate oral

diseases and neoplasia. A great variety in signs suggestive for oral pathologies are described, but

may include a decrease in appetite, external facial swelling, draining tracts, bleeding from the mouth,

excessive salivation, nasal discharge, increased or reduced activity, aggression, and indications of

pain or discomfort. More subtle signs mostly appearing in early oral disease comprise modification in

30

eating or chewing pattern, alterations from normal behaviour activity, a gradual weight loss, and

periodic upper respiratory–type infections. (Wiggs and Bloom, 2003) Additional symptoms as seen in

literature include irregular shaped mucosae and lips, alopecia, staggering, polydipsia, waning and

waxing facial lesions, increased coughing and ataxia.

The importance of general check-ups was accentuated by the number of tumours discovered during

such examinations: almost one third of the reported cases had almost incidental findings of an oral

mass. Even if the intention of a procedure isn't necessarily oral, it's always worth paying attention to

the oral cavity. If general anesthesia is undertaken for whatever reason, the opportunity has to be

seized to perform a solid oral examination and further approaches such as (dental) radiography, dental

scaling and other assessments or treatments can also be initiated if necessary.

Conclusion

Oral tumours have been described in a variation of carnivoran species, but the number of reported

cases is rather limited. All of the oral tumours reported in non-domesticated carnivorans have been

described in domestic carnivores. A majority of these cases were of non-odontogenic origin, while

papillomatosis, squamous cell carcinoma and melanoma represented the most frequently described

tumour types. Regarding the odontogenic tumour group fibromatous epulis of periodontal origin was

the most common tumour type.

Only a minority of animals diagnosed with an oral tumour were subjected to curative treatment. This

treatment therapy comprised in all of the cases surgical resection. Clinical outcome of tumour excision

was variable and tumour recurrence appeared in a slight minority of treated cases. Multimodality

treatment was attempted in two cases diagnosed with a malignant tumour type and resulted in

satisfying clinical outcome. Although highly dependent on tumour characteristics and external factors,

multimodality treatment may be regarded as a promising approach in the resolution of oral tumours

with distinct malignancy in non-domesticated carnivorans.

In a large number of cases, no cancer treatment approach was initiated. Frequently the presence of

oral tumours was only confirmed at necropsy, while particular animals suffered from oral symptoms

prior to death. In these cases, the presence of signs didn't lead to the suspicion of an oral neoplasia

and further workup. Diagnosis of an oral tumour led to euthanasia in several cases. Poor prognosis

and wide tumoral extent were commonly mentioned as the reason for this decision.

Due to various difficulties in treatment therapy of exotic carnivorans, special attention has to be paid

on the early recognition of symptoms or discrete signs caused by oral tumours. The role of caretakers

dealing with exotic carnivorans on daily basis is fundamental and it is advisable that animal keepers as

well as affiliated veterinarians are retrained in the detection of suggestive signs associated with the

presence of oral tumours. A second step in earlier detection of oral masses lays in more frequent

examination of the oral cavity. Any situation of an anesthetized animal forms an excellent opportunity

to achieve this goal.

This comprehensive enumeration can be considered not exhaustive in time and reality. Further

submission of case reports in both captive and free-ranging animals future needs to be undertaken in

order to evaluate tumour detection, diagnostic approach and treatment therapy; or in the case of free-

ranging carnivorans, the impact of oral tumours on population dynamics.

31

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39

Appendix A: Taxonomy chart of the Carnivora order (ITIS,

2018)

Carnivora

Feliformia

Eupleridae

Felidae

Pantherinae

Felinae

Herpestidae

Hyaenidae

Crocuta

Hyaena

Proteles Nandiiidae

Viverridae

Caniformia

Ailuridae

Canidae

Mephitidae

Mustelidae

Lutrinae

Mustelinae

Martes

Mustela

Meles

Mellivora

Neovison

Taxidea

Odobenidae

Otariidae

Phocidae

Procyonidae

Ursidae

Ailuropoda

Helarctos

Melursus

Tremarctos

Ursus

40

Appendix B: Reported cases of oral tumours in non-

domesticated carnivorans described in literature, classified per

tumour type

Abbreviations: M: Male intact

F: Female intact

MC: Male castrated

FC: Female castrated

1. Odontogenic tumours

1.1 Amyloid-producing odontogenic tumour

Species

name

(Latin)

Oral

localisation Sex

Age

(years) Author Journal Year

Panthera

tigris tigris Mandibula

(incisors)

M 13 Kang et al. Journal of Comparative

Pathology

2006

1.2 Calcifying epithelial odontogenic tumour

Species

name

(Latin)

Oral

localisation Sex

Age


Panthera

tigris altaica Gingiva at

right

maxillary

canine tooth

M Adult Fecchio et al. Journal of Veterinay

Dentistry

2015

1.3 Fibromatous epulis of periodontal origin

Species

name

(Latin)

Oral

localisation Sex

Age


Panthera leo Gingiva at

left maxillar

canine tooth

M Aged Castro et al. Brazilian Journal of

Veterinary Pathology

2011

2. Non-odontogenic tumours

2.1 Papillomatosis

Species

name

(Latin)

Oral

localisation Sex

Age


Canis latrans Lips, tongue,

adjacent

tissue

F ? Broughton et al. Journal of wildlife

diseases

1970

Canis lupus unknown ? puppy Samuel et al. Journal of wildlife

diseases

1978

41

Canis lupus unknown ? puppy Samuel et al. Journal of wildlife

diseases

1978

Canis latrans Lips, tongue,

adjacent

tissue

? ? Samuel et al. Journal of wildlife

diseases

1978

Canis latrans unknown ? ? Samuel et al. Journal of wildlife

diseases

1978


diseases

1978


diseases

1978


diseases

1978


diseases

1978


diseases

1978


diseases

1978


diseases

1978


diseases

1978

Panthera

uncia Sublingual ? ? Joslin et al. PROCEEDINGS AAZV AND

IAAAM JOINT

CONFERENCE

2000

Panthera

uncia Sublingual ? ? Joslin et al. PROCEEDINGS AAZV AND

IAAAM JOINT

CONFERENCE

2001

Felis

Concolor Tongue ? Adult Sundberg et al. Veterinary Pathology 2000

Felis

Concolor Tongue ? Adult Sundberg et al. Veterinary Pathology 2000

Felis rufus Tongue ? Adult Sundberg et al. Veterinary Pathology 2000

Felis rufus Tongue ? Adult Sundberg et al. Veterinary Pathology 2000

Panthera leo Tongue M Adult Sundberg et al. Journal of Zoo and

Wildlife Medicine

1996


Wildlife Medicine

1996


Wildlife Medicine

1996

Panthera leo Tongue F Adult Sundberg et al. Journal of Zoo and

Wildlife Medicine

1996

Panthera

uncia Tongue,

buccal

mucosae

? 5-16 y Sundberg et al. Veterinary Pathology 2000

Neofelis Tongue ? Adult Sundberg et al. Veterinary Pathology 2000

42

nebulosa

Felis lynx Tongue ? ? Wolfe and

Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007


Spraker

Journal of Wildlife

diseases

2007

Crocuta

crocuta Muzzle ? (Sub)-

adult

Nelson et al. Journal of wildlife

diseases

2013

2.2 Squamous cell carcinoma

Species

name

(Latin)

Oral

localisation Sex

Age


Lynx Rufus Right

mandibula

F 23 Sladakovic et al. Journal of Zoo and

Wildlife Medicine

2016

Canis latrans Maxilla right FC 19 Bernstein et al. Journal of Zoo and

Wildlife Medicine

1999

Zalophus

californianus Tongue F 28 Sato et al. Journal of Zoo and

Wildlife Medicine

2002

Leopardus

pardalis Tongue F 19 Yanai et al. The Veterinary record 2003

Zalophus

calif

ornianus

Left

Mandibula

F 30 Bossart Journal of Zoo and

Wildlife Medicine

1990

Lynx

canadensis unknown ? ? Effron et al. Journal of national cancer

institute

1978

Helarctos

malayanus Left lower lip F 19 Lam et al. Journal of Veterinary

Diagnostic Investigation

2013

43

Helarctos

malayanus Right lower

lip

M 18 Lam et al. Journal of Veterinary


2013

Helarctos

malayanus Left lower lip M 8 Lam et al. Journal of Veterinary


2013

Helarctos

malayanus Left lower lip F 17 Lam et al. Journal of Veterinary


2013

Helarctos

malayanus Right lower

lip

M 18 Lam et al. Journal of Veterinary


2013

Helarctos

malayanus Mandibula:

lingual

surface

incisors

F 6 Mylniczenko et

al.

Journal of Zoo and

Wildlife Medicine

2005

Canis lupus

arctos Tonsilla M 11 Teifke et al. Journal of Zoo and

Wildlife Medicine

2005

Canis lupus Tonsilla M 13 Ryan et al. Journal of wildlife

diseases

1979

Suricata

suricatta Mandibular

gingiva

M 10 Sladky et al. Veterinary Pathology 2000

2.3 Adenocarcinoma

Species

name

(Latin)

Oral

localisation Sex

Age


C. aureus

syriacus

oral cavity

glandular

epithelium

M ? Effron et al. Journal of national cancer

institute

1977

2.4 Mucoepidermoid carcinoma

Species

name

(Latin)

Oral

localisation Sex

Age


Panthera leo Left

mandibular

salivary

gland

MC 13 Dorso et al. Veterinary Pathology 2008

2.5 Anaplastic carcinoma

Species

name

(Latin)

Oral

localisation Sex

Age


Suricata

suricatta Tongue,

rostral

mandibula

F 8 Dadone et al. Journal of Zoo and

Wildlife Medicine

2014

44

2.6 Secondary carcinoma

Species

name

(Latin)

Oral

localisation Sex

Age


Ursus

americanus Tongue M ? Lombard and

Witte

Cancer research 1959

Taxidea

taxus Mouth M ? Lombard and

Witte


2.7 Malignant melanoma

Species

name

(Latin)

Oral

localisation Sex

Age


Panthera leo Left

maxillary lip

thv canine

F 13 Steeil et al. Journal of Zoo and

Wildlife Medicine

2013

Ursus arctos

lasiotus Tongue F ? Lombard and

Witte


2.8 Haemangioma

Species

name

(Latin)

Oral

localisation Sex

Age


Acinonyx

jubatus Tongue F ? Effron et al. Journal of national cancer

institute

1978

2.9 Fibrosarcoma

Species

name

(Latin)

Oral

localisation Sex

Age


Chrysocyon

brachyurus Left maxilla M 12 McNulty et al.

Journal of Zoo and

Wildlife Medicine 2000

45

Appendix C: Reported cases of oral tumours in non-

domesticated carnivorans retrieved through survey

Abbreviations: M: Male intact

F: Female intact

MC: Male castrated

FC: Female castrated

Species name

(Latin)

Histopathological diagnosis

Sex

Age

(years) Region

Acinonyx jubatus Fibromatous epulis of periodontal ligament

origin M 1,5 North America





Acinonyx jubatus Gingival hyperplasia M 6,5 North America

Acinonyx jubatus Chronic fibrosing gingival hyperplasia F 14 North America

Canis latrans Squamous cell carcinoma FC 8 North America

Canis rufus Squamous cell carcinoma FC 15 North America

Panthera tigris Malignant melanoma F 12 North America

Canis lupus baileyi Amelanotic melanoma F 12 North America

Canis lupus baileyi Amelanotic melanoma F 14 North America

Mephitis mephitis Osteoma F >4 North America

odontogenic and non-odontogenic oral tumours in non ... · in contrast with domestic carnivores,...

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