The oral pathology of domesticated animals

Oral THE

ORAL

Pathology

PATHOLOGY

OF DOMESTICATED

ANIMALS

R’. J. GORLIN, D.D.S., M.S.,” ,J. J. CLARK, D.V.M.,“*** AND A. P. CHAUDHRY, B.D.S., M.S., PH.D.,* MINNEAPOLIS,

MINN.

T

HIM study was undertaken to ascertain the various types of oral lesions seen in domesticated animals and their frequency. The material for this study has been collected from the files of the Surgical Pathology Division of the School of Veterinary Medicine, University of Minnesota, and includes the neoplastic and nonncoplastic diseases limited to the oral cavity, The material represents 104 successive biopsied oral lesions obtained from ninety dogs, six cows, five cats, one sheep, and one horse. Autopsy specimens have been cxclnded from this series. All biopsy specimens were rediagnosed by us indclwndeltt~ly. ‘l’hero is abundant literature available in the form of case reports of oral Icsions of domestic animals, but no general survey of both oral neoplastic and It is doubtful whether vital conclusions nonneoplastic pathology is available. can be drawn from the computation of case reports, as there is a tendency to report the unusual and ignore the common or self-limiting lesions, such as viral papillomatosis. Moreover, a survey tnade in one part of the country may differ from that made in another part ; the difference between surveys made in different parts of the world is even greater. Perhaps this is due to differences in species distribution; perhaps other factors are responsible. It is logical, therefore, to expect the results of this survey to be different from any made in the past. Moreover, there seems to be little justification for comparing the data obtained from animals with data pertaining to human beings. A glance at samples of human oral pathology cited by Woodbridge,l Boyle,’ INcCarthy,“’ and Gorlin” will show the wide disparity between the frequency of lesions in man and in animals. The veterinary pathologist deals with different populations. Clinical or pathologic follow-up is far more difficult in animals than in human beings and, finally, the specimens sent to the veterinarian pathologists From the School of Dentistry and the School of Veterinary Medicine, University of Minnesota. This study was made possible through grants from the Graduate School, University of ~Iinncsota. and the IJnited States Public Health Service. Presked at the American Academy of Oral Pathology, Washington, D. C., April 7, 1957. *Division of Oral Pathology, School of Dentistry. **Division of Pathology. School of Veterinary Medicine. 500

goIll,: ”

y

ORAL

PATHOLOGY

TABLE

I.

DOMESTICATED

OF

ORAL PATHOLOGY

BENIGNTUMORS

OF DOMESTICATED

DOG

I

Epulis Infectious papillomatosis Noninfectious papilloma Lipoma Neurofibroma Ameloblastic odontoma Sebaceous adenoma Fibroxanthoma Nt?VU9 Hemangiopericytoma Total

ANIMALS ANIMALS CAT

I

OTHER

I

-

28 9 1 1 1 1 1 1 43

501

1 cow 1 cow 2 cows

-i 1

suffer from all the inadequacies that we experience and, therefore, are frequently inadequate in size, improperly fixed, or not well documented with desirable information. TABLE

II.

ORAL

PATHOLOGY

OF DOMESTICATED

MALIGNANTTUMORS

DOG

Melanoma Squamous-cell carcinoma Mast-cell tumor Basal-cell carcinoma Lymphoblastoma Aclenocarcinoma Fibrosarcoma Chondrosareoma Total

18 5 4

ANIMALS CAT

I

-i -

i f 1 38

2

OTHER

1 sheep 1 sheep

For the sake of clarity, we have chosen to present this material under several headings : (1) nonneoplastic lesions, (2) benign neoplastic lesions, and (3) malignant neoplastic lesions (Tables I, II, and III). We have limited our discussion to only those pathologic lesions that were represented in our series. The reader should be made aware that many systemic diseases in animals have oral manifestations, just as in man, but many of these (such as black tongue in dogs, blue tongue in sheep, or foot-and-mouth disease) are not ordinarily biopsied and hence would not come under our purview. TAEZLE III.

ORAL

MISCELLANEOUSLESIONS

Pyogenic granuloma A~t&omy~sis Bovine hyperkeratosis Fibrous dysplasia or osteoma Eosinophilic granuloma Foreign body granuloma Total

PATHOLOGY I

DOG

-

OF DOMESTICATED I

CAT

9

-

Nonneoplastic

I

OTHER

1

4 COW8 1 cow 1 horse -

2

6 (5 cows) (1 horse)

-i -

-i 10

ANIMALS

Lesions

Pyogenic Granuloma.-There were ten cases of pyogenic granuloma in our series. The gingiva was a common site. Nine occurred in dogs and the remaining one was noted in a cat. Age and breed did not seem to be factors.

X2

GOR~T,lX,

CLARK,

AND

(‘H~\I!l)HRY

0. S.. 0. M.. & 0. I’ May.

195%

Jn Irticroscopicd ;11)1)(2ran(7’, llit~ lesion was idantical to those observc4 in 111;111 and similarly rcprc~sc~nted I)rolif(lratiou ot’ granulation tissue in rclsponxc~ 10 low-grade chronic inflamnlatory and/or hormonal stimuli. Although our series was too small to reflect the true incidence, t,his lesion is especially common 011 the oral mucosa of catC 34 and has been erroneously called “rodent ulcer.” Several bacteria (Bacillus protez~s. It has been shown to be nonr-iral in origin. Xtaphylococcus aweus, and Streptococcus hemolyticus) have been implicated in its etiology.“” In an overwhelming majority of cases the disease is spantaneous, although occasionally two or more animals in the same household arc affected and sometimes “kissing” lesions are observed involving two approsimating surfaces. There seems to be no special predilection for any particular site in the mouth. The clinical appearance of these lesions varies with the age of the lesion As in the lesions found in and the dcbgree of ulceration and/or epithelization. man, the pyogenic granuloma is generally brownish red with a granulnl surface. In older, well-epithelized lesions, the color is less red and the surface is rather smooth. The histology of the pyogenic granuloma in both man and animals is th(> same. The lesion is composed 01 dilated blood capillaries, fibroblasts, and a. variable number of inflammatory cells. The epithelial surface may be ulcerated or intact.

Actinomycosis and Actinobacillosis.--Four cases of actinomycosis occurrrtl in our series. All were found in cattle. Although it is reported occasionnll~ in the mouths of animals other than cattle, the disease is rarely found in other the disease systemically, seldom hnrc species. Swine, although manifesting oral involvement. Actinomycosis is caused by a ray fungus, Acti?zomyces bol*is. The organism enters the jaws by way of abrasions of th(> oral or pharyngeal mucosn caused by the rough nature of the diet. It produces an enlargement of the affected maxilla or mandible called “lumpy jaw.” The infection may spreatl to the deeper structures of the neck or even the cranial fossa, but it does not involve lymph nodes. Viscera are seldom involved, as they are in man. In the older literature, involvement of the tongue, with subsequent induration called “wooden tongue,” was attributed to this same organism. However, more recent investigation has shown that this condition is caused by a different, though similar organism, Actinobacillus lignieresi. In actinobacillosis, lymph nodes (especially about the head and neck) are commonly involved, as arc the skin, mucosa, and internal organs. In contrast to actinomycosis, bone is never attacked. Both diseases, however, are characterized by abscesses in which are found small grayish white or yellowish granules. Microscopically, these consist of rosettes of radiating clublike structures. In actinomycosis the central area of the ro$ctte consists of gram-positive filamentous mycelia, whereas the central zone of an actinobacillosis colony is composed of minute gram-negative bacilli. The club-shaped terminal ends of both organisms arc gram negative, The

Volume I I Number 5

ORAT, PATHOLOGY

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503

$NIMAJ,S

In contrast to most inflammatory response to both organisms is quite similar. other granulomatous diseases, the cellular response consists chiefly of polymorphonuclear leukocytes. Because both organisms are easily stained with aniline dyes, especially carbolfuchsin, Gram’s stain should always be employed for differentiation (Fig. 1).

Eosinophilic Uranuloma.-To the best of our knowledge, this lesion herctofore has not been reported in animals. We noted a single case in the upper lip of a 3-year-old female cat. Bone lesions were not observed. The microscopic picture was identical to that seen in man. LeveP, G3has pointed out Fig.

1.

Fig.

2.

Fig. l.-Actinomycosis. The ray fungus, ActCnonayces bow&s, is surrounded morphonuclear leukocytes, fibrin, and cell debris. Fig. Z.-Eosinophilic granuloma. Note large numbers of eosinophilic leukocytes ing markedly granular cytoplasm, Intermixed are numerous histiocytes.

by

poly-

exhibit-

504

GORLTN, CLABK,

AND C'FI.4UDHRl'

0. S..0. M., &0. I' May.

1938

that in marl several tlistinct types of eosinophilic granuloma occur. There is the “lruc ~osinophilic granuloma of t,he skin,” which is simply a dermal manifcstativn c)t’ t bc mildest form of osseous cholrsterol histiocytosis. A second type is no1 associated with bone involvement and is designated “eosinophilic granuloma of the skin, erythema elevatum diutinum type.” IJesions are frequently manifest on the face. The microscopic picture is quite characteristic. There is a dense granulomstous infiltrate, especially around capillaries, consisting largely of eosinophilic Icukocytes and histiocytes (Fig. 2). In older lesions, increased numbers of fibroblasts are noted. Bovine Hyperkeratosis.-Bovine hyperkeratosis is a most peculiar disease originally described in detail by 01afson53 in 1947. Its etiology being originally unknown, it was called X disease. It seemed to be widespread in the United States. Nurnerous attempts were made to identify an infectious agent, a nutritional disturbance, or a toxic substance.54, 55 These probings have been reviewed by Olson and Cook.55 Attempts either failed or resulted in conditions unlike the spontaneously occurring disease. McEntee, Hansel, and Olafsoq5” in 1951, did succeed in producing the disease experimentally in cattle with the free fatty acid fraction of a processed food concentrate, and in the satnc year Wagener,57 in Germany also produced the disease in cattle by contact, Ieicding, or inhalation of a wood preservative. This indicated that the disease was caused by a toxic substance. In 1952, Be1158,jQ also produced the disease by the use of a lubricant administered in gelatin capsules. Wagener57 reported that cats also had the cliseasc. A year later, Hansel, Olafson, and McEntceGo confirmed that the offending agents were highly chlorinated naphthalene compounds used in the tarring of roads and in the preservation of wood (such as telephone poles, fences, barns, etc.) Oil-based insecticides have also been implicated.71 The clisease has bt:cn produced experimentally by the use of these purified chemicals.7*-77 Recent investigation seems to implicate a virus in the production of the oral lesion. The disease is manifest especially by younger animals. Initial signs are lacrimation and skin and mucous membrane thickenings. It is usually associated with a mild rise of temperature, salivation, a nasal discharge, and some Erythematous erosive areas appear on the lips, tongue, hard loss of appetite. palate, muzzle, and gingivae. These gradually change into papillomatous or warty growths. The skin becomes hard, dry, and thickened and is wrinkled and folded, especially around the neck. Autopsy reveals other gross systemic changes, such as ulcers in the intestinal tract and degenerative changes in the We had but a single case in our series. liver and kidneys. Microscopic changes in the skin are those of hyperkeratosis and plugging Parakeratosis is also noted (Figs. 3 to 7). of the hair follicles. Neoplasms.-There is rather abundant literature available in the form of case reports of neoplasia of domesticated aninlals.Z’ e, 12,I41‘8~21 Far less is available if one wishes to include only oral tumors.16, 63

Volume 11 Number 5

ORAL

PATHOLOGY

O-J? DOMESTICATED

505

ANIMALS

Fi

g.

3.

Fi

F ‘ig. S.-Bovine hyperkeratosis. Highly chlorinated naphthalene compounds Pro dt me char: 2c teristic changes in the skin and oral mucous membrane. Note rugose form ati n of region. (From Bell, W. B.: skin Of cervical Virginia J. SC. 3: 169, 1952.) F ‘ig. 4.-Bovine hyperkeratosis. Arrow points to raised hyperkeratotic plaque cm u PI ,er gingi vi a. (From Bell, W. B.: Virginia J. SC. 5: 71, 1952.) ‘ig. 5.-Bovine hyperkeratosis. Note numerous raised hyperkeratotic plaques on do) x41nn and I,”tteral surface of tongue.

X)6

GORLIN,

CLARK,

AND

CHAUDHRY

0. s.. 0. M., 8: 0. P.

May, 19SR

/n~~itlence (czget species, awl sex): Mulligan” found, in a survey 0 ,reral moplasms of the clog, that, about 45 per vcsnt W(‘I’C malignant. Ily thcl same incidence held true for ora. neoplasms in our srrk tht, of ninct,y (42 per cent) canine oral tumors wwc rrralignant~. Fig.

6.

Fig. 7. Fig. 6.-Bovine hyperkeratosis. This specimen taken from the skin surface of th e “upper lip” shows hyperkeratosis, plugging of hair follicles, and papillary formation of the surface epit :helium. marked Fig. ‘I.-Bovine hyperkeratosis. Photomicrograph of oral mucosal lesion exhibits acanthosis. and an occasional focus of quite benign-appearing dysker atosis. hn lerkeratosis.

Generally the age incitlcncr of neoplasms in animals follows the 1pattern ;er~cd in rnan.“~ lo Malignant tumors usually do not occur in youn, ger anils. Cohvs,*” in a series of autopsies on dogs less than 10 years of age , found

Volume Number

II 5

ORAL

PSTHOLOGY

OF DOMESTICATED

ANIMALS

507

a cancer incidence of about 3 per cent. Animals more than IO years of age yielded a result of 25 per cent. Cotchin14 reported recently that 68.5 per cent of cats with tumors were between 6 and 12 years old. These general observations were borne out by our study. One-half of the malignant tumors in our series occurred in animals past 10 years of age. A convenient conversion table of equivalent age between man and dog has recently been published.7” Many factors enter into species incidence. An overwhelming number of reflective of the relaspecimens in our series are from dogs. This is partially tive population of dogs as opposed to horses, for example. It also reflects the intimacy of daily contact where closer observation of deviation from the norm is possible. Another factor is the slaughtering of many domestic animals (cows, sheep, etc.) before they reach “cancer age.” It must also reflect species difference, for cats are more numerous than dogs.73 TrotterI reported no neoplasms in 5,300 slaughtered sheep from 6 to 12 months of age. Martin and HollandlO collected 122 case reports of cancer occurring in the mouth, throat, and nasopharynx of animals and thirty-five unreported cases from zoos, veterinary schools, and veterinarians. In their series, cancer of the oral cavity was as common in the horse as in the dog. This contention was certainly not demonstrated by a similar series collected by Schlumberger.‘G As has been pointed out previously, it is highly debatable whether any valid conclusions can be drawn from a series culled from select case reports. In our series collected from a single institution over a period of eight years, only a single oral neoplasm in the horse was encountered. Even if one does not take into consideration all of the above-mentioned factors, it seems highly unlikely that oral cancer in the horse and dog should have a similar percentage incidence. Martin and Holland’o found oral cancer to be about four times more common in dogs than in cats. The relatively greater incidence of dog neoplasm has been pointed out by others.4, By7 In our series the most common benign and malignant canine oral neoplasms were epulis and melanoma, respectively. Perhaps the number of cases of infectious papillomatosis (nine of fifty-three benign oral lesions) does not reflect its true incidence, for it is easily recognized and therefore not always biopsied. This is especially true since the veterinarian or professional dog breeder knows of its benign nature and short duration and hence will not bother to biopsy it. In our series, malignant melanoma was far more common than squamous-cell carcinoma. Cole, cited by Schlumberger,16 made similar observations in his series from the DepartOn the other hand, ment of Veterinary Pathology of Ohio State University. Withers” and Cotchin4* I2 in England, have found that squamous-cell carcinoma of the tonsil is the most common oral canine neoplasm. This difference between findings in England and in America appears to be most striking and requires further investigation. Squamous-cell carcinoma of the tongue is exceedingly rare in the dog, but in the cat thi.s tumor is not uncommon.14 As in man, the most predominant site in the cat is the ventrolateral surfa.ce. This neoplasm invades the deep tongue musculature with subsequent bilateral metastases to the regional lymph nodes.

r,OS

CORLlN,

CLARK,

AND

CH~4.I’l~lIRT

0 5.. 0. M.. & 0. P. May, 1958

SC?; seems to play a role in certain animal neoplasms but not in others. collt~ctccl I,- Mulligan” from 809 dogs, 407 were In the 1,000 goneral ~~eo~tlasu~s from males, 392 wcrc fro!t~ Irtti:l.lcs, and 10 wo~‘e from dogs of unknown sex. When these figures ~PI’C corr’ec~tc~tl for the greater incidence of male dogs in the general population, it appeared that neoplasia was slightly more common in bitches. Comparable figures on general neoplasia were given by Cotchin.2’ As for the cat, CotchinX4 reported tha.t 127 of 172 cats were males. Since this is an unadjusted figure, conclusions cannot be drawn. It is interesting to note that in his series all cats with squamous-cell carcinoma of the tongue were males. In dogs, about 10 per cent of all neoplasms occur in the oral cavity.“’ A similar figure can bc calculated for cats.4,14

Benign Tumors Epulis of Periodontal Origin.-The

Fibromatous term epuZis is used to designate fibromatous gingival tumors, irrespective of their inflammatory or neoplastic nature. Clinically, they are hard, firm, pedunculated fibrous growths exhibiting a smooth or somewhat nodular surface. They mayc be localized or generalized. When generalized, they may involve the whole arch and simulate the “idiopathic” variety of fibromatosis seen in human beings. These growths may be so extensive sometimes as to cover the teeth entirely. Mulligan5 and Riser I7 described gingival tumors in dogs, and the latter authoP st,atcd that they were more common in boxers and Boston bull terriers. In a series of 226 tumors involving the mouth and nose, Riser reported that 150 were epulides. In 1952, Burstone, Bond, and Littl” described a familial gingival hypertrophy in boxers of close ancestry. Microscopically, their lesions were characterized by central areas of mature lamellated bone and by nests and cords of cells suggestive of odontogenic epithelium. In the present series, 53 per cent (twenty-eight of fifty-five) of the nonmalignant oral neoplasms in dogs were classified as epulides. No epulides were observed in animals other than dogs. CotchirP found twenty-two of eightyfour canine oral tumors to bc epulidcs, corresponding to twenty-eight of ninety oral lesions in the present series. Information concerning sex was not available in seven cases in our series, but in the other twenty-one dogs this lesion was twice as common in females. The age range was 3 to 14, with an average of 7.5 years. Of twenty-four ascertained breeds, only seven were boxers. Microscopically, 60 per cent of the growths exhibited calcified tissue which ranged from osteoid to mature lamellated bone. This bony tissue was invariably associated with a cell-rich bone-forming matrix. A cementum-like material was present in two cases. In six cases, when the involvement was localized, no bone or osteoid tissue was found. Inflammatory cells were observed only in those cases in which the lesions were subjected to biting trauma. Epithelial proliferation similar to that observed by Burstone and colleaguesl” was seen in about GO per cent of the epulides. There was a high correlation

Volume

It

Number 5

ORAL

PATHOLOGY

OF

DOMESTICATED

ANIMALS

509

between epithelial proliferation and osteoid or bone formation. No cystic changes were observed in any of the epulides in this collection, whereas Burstone and associates1g reported that one in four of their cases had such changes. By virtue of the odontogenic epithelium, the bone, and the cementum that these lesions so frequently contain, it seems highly probable that this lesion is of periodontal membrane origin. Because of the pseudoepitheli-omatous hyperplasia and odontogenic epithelium, they are frequently mistaken for ameloblastoma. In view of our findings, therefore, it seems speculative to draw a parallel between a “familial multilocular cystic lesion” of man and this single case in the boxer (Figs. 8 to 11). Giant-cell reparative granuloma is exceedingly rare in animals. Olafsons2 cited a single case in a 6-year-old bulldog.

Fig. 8.-Fibromatous epulis of periodontal origin. Note enlargement of gingiva between two teeth. These growths may be focal or generalized resembling idiopathic flbromatosis in man. They seem to be especially common in boxers over 5 years of age.

Canine Oral Papillomatosis.-One of the more common types of benign oral neoplasms in the dog is viral papillomatosis. This lesion has its counterpart in human dermal warts. Their histopathology is quite similar, and both are caused by viruses. The infectious nature of canine oral papillomatosis was described before the turn of the century. Findlay, Goodlow, and De Monbreun and Goodpasture2” demonstrated the viral and immunologic aspects of this disease. The disease oceeurs most commonly in puppies or young adult dogs, the mode age in this series being 1.0 year. There was no sex preference. The incubation period varies from thirty to thirty-three days. Although they may occur anywhere in the mouth, most often the lesions are seen about the inner margin of the upper lip. They do not usually extend into the pharynx. They vary in appearance from whitish, flattened or smooth nodules a few millimeters in diameter to grayish, pedunculated, cauliflower-like growths. Other favorite

3. M.. R 0. I’ my, 195x

F’ig.

II

(Fov

legends,

see

opposite

page.)

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511

sites are the lower lip, tongue, palate, and even the nose. They regress in size within six weeks and become darker a.nd shriveled and finally disappear and within another week or two, leaving no scar. The virus is intracellular species specific for the oral and occasionally the nasal mucous membranes of the dog nor on the oral mucosa of other animals. The virus also produces a lifelong immunity to reinfection. There is marked similarity between the histologic appearance of canine The initial change is a simple oral papillomatosis and that of human warts. As acanthosis increases, small islands of prickle hyperplasia of the epithelium. cells seem to lose their intercellular bridges. The next change is an increase in the thickness of the cornified layer. The cells of the basal layer remain normal in size, but the cells of the outer stratum spinosum increase greatly in size

Fig.

1 %.-Canine

oral

papillomatosis. labial mucosa

Note numerous wartlike growths of this young golden retriever.

on

the

buccal

and

With this epithelial proliferation, the and exhibit intensely stained nuclei. surface is thrown up in folds containing connective tissue cores. In older lesions, keratohyaline-like eosinophilic cytoplasmic and basophilic nuclear inclusions are noted. There is frequently an abundance of mitotic figures in the Malpighian layer. The corium is usually richly vascular with variable numbers of lymphocytes and plasma cells (Figs. 12, 13, and 14).

Fig. 9.-Fibromatous epulis of periodontal foci of odontogenic epithelium. Note palisading ygvge2t;ssue stroma. (From Burstone, M., Bond,

Most of these lesions exhibit origin. of nuclei of peripheral cells, and loose E., and Litt, R.: A. M. A. Arch. Path.

several connec54: 208,

Fig. lO.-Fibromatous epulis of periodontal origin. This most common benign canine oral neoplasm frequently contains either bone or cementum. This. in addition to the odontogg:;; epithelium, has led the authors to the conclusion that this lesion is of periodontal origin. rich “bone-forming” matrix. Fig. Il.-Fibromatous epulis of periodontal origin. Note numerous strands of epithelium and lamellated bone. (From Burstone, M., Bond, E., and Litt. R. : A. M. A. Arch. Path. 54: 208, 1952.

5 1”Y

GORLIN,

CLARK,

AND

CHATJDHRY

0. S.. 0. M.. & 0. I’ Mar, 195s

It will be noted from ‘I’ablc JT t,hat, among Ilin(+y canine oral lesions, there, ~vcre nine cases of infectious papillomatosis and one ca,se of a noninfeetiou> .It is intvrcsting to note that this single case which was sc~parat(:(I papilloma. on microscopic criteria from the others occurred in an “old” dog.

Fig. 13.-Canine oral papillomatosis. duces PaPillomatous growths that superficially observed in the tonsiliar and uvular areas Fig. 14.-Canine oral papillomatosis. like projections showing swollen epithelial

Fig.

13.

Fig.

14.

This

virus-inrlnced disease resemble the arborescent in man. High-power photomicrograph cells with intracytosplasmic

It prois short lived. papillomas frequently of one of the inclusions.

Anger-

A single case was most unusual in that a single specimen from the mouth of a female dog of unknown breed manifest three distinct lesions. One was an

Volume I I Number 5

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513

unmistakable viral papilloma, the deeper portion of which had become dyskeratotic and was invading the co&m as a squamous-cell epithelioma. In addition, bits of osteoid and bone were scattered about the base of the lesion (Fig. 15). Sebaceous Adenoma.-Although “sebaceous adenoma” is reported commonly in dogs, there seems to be a rather marked difference in the rate of incidence as reported by various investigators. Perhaps this is due to a difference in nomenclature. For example, Mulligan5 in a series of 1,000 tumors, found forty-five examples of “sebaceous adenoma” and fifteen examples of “sebaceous gland carcinoma.” All of these apparently occurred in the skin. Willisz6 indicated four examples of “sebaceous adenoma of skin” in 204 specimens. Mulligan indicated a far higher incidence in male dogs. Cotchin12p 21 observed fourteen examples in 422 skin tumors or in 1,150 tumors of all systems in the dog. In his discussion of cat neoplasms no mention of sebaceous adenoma was noted.

In deeper portion Fig. I%-Canine oral papillomatosis and squamous-cell carcinoma. of one typical section, invasion of the connective tissue by neoplastic epithelium was noted. Associated with this squamous-cell carcinoma was metaplastic (see arrow) bone formation. See section on canine oral papillomatosis.

If one examines the photomicrographs employed by Mulligan5 it becomes apparent that he is talking about sebaceous nevus and not sebaceous adenoma. We are using the term adenoma to refer to incompletely differentiated sebaceous structures.45 It should be pointed out, however, that the term adenoma is frequently employed in the former sense in veterinary literature. We had only one example of this tumor from the mucocutaneous junction of the lower lip of a g-year-old German shepherd dog.44 Whether the origin was in skin or in mucous membrane could not be determined.

QORT,TN,

.-)I 1

cells both

CLAR ti, AiW

Fig.

16.

Fig.

17.

Fig. 16.--Sebaceous adenoma. This lip tumor and mature sebaceous cells. Fig. 17.-Sebaceous adenoma. Higher-power Cell Wpe and intermediate transitional forms.

was view

composed of

section

of a mixture shown

in

ative

of ge Fig.

1.6.

Note

stratum germiuativum or basal layer. The other resembles a ma,tuw iceous cell. The percentage of the two types varies with the lo1NIP I exami necl (Figs. 16 and 17).

of

Sebi

1;he

0. s.. 0. Al,. s 0. I’ May. I’lih

CHAUDHRY

Fig. 18.

Fig. 19. >ft tissu Fig. 18.- Ameloblastic odontoma. This tumor consisted of both ha1 and Lntine- s ! the tall c:olumnar ameloblastic cells, the loose stellate reticulum, an the g% entim e-like material. In the upper right-hand corner, observe dep rits E osteoid ceme?ntoid islands odontoma. In another section of the tumor, sever Fig. ‘19.- Ameloblastic odon togen tic epi thelium were observed in a sea of loose stellate stroma.

Tumors of Dental Origin.--‘l’ul~~ors of cl(~rltal origin itt animals arc not bar-c> tliscnsscd otlontomas in rats, and (aommon. I~3ullocl~ and CurW’ %cgarclli”” 1~s indicated the occurrence of ’ ’ adamantoblastomas ’ in a select tumor-prone stock of mice. Not all of th(lsc t,umors seem to us to 1x1 true’ ;I~~lcloblxstoI~las. This tumor has brcn described in the rat. by Ratcliffe”” ant1 Olafson5” cited a single cast of in thv cat a~lcl OS by Nicberlc ant1 Cohrs.“’ indicated no csamples in “ad;tnlantinotna” in the former species. Mulligan” his survc~y of 1,000 canine t~eoplasms ; yc%, ItiseP found five c~samples of “adalrlantino~~~~~ of c~namcl epithrlium” in his group of 1,147 specimens. (‘otchin,‘” in a similar number of specimens (1,150)) found no dent,al neoplasms in this species. Neither were any observed in his feline series.” Odontomas were discovcrtd in horses by Bland-Sutton”l and Schlumberger.‘”

Fig. epithelium. Consists

This lip tumor was covered 20.-Hemangiopericytoma. The subepithelial connective tissue was compressed of large numbers of minute vascular channels.

by normal parakeratinizecl The tumor by the tumol-.

We observed only one example of a tumor of dental origin in our seriesan ameloblastic odontoma’” in the mandibular incisor region of a 2-year-old Holstein bull. As in man, the tumor consists of two components: nest’s or ancl a ha,rd connective tisstrands of proliferating odontogenic cpitheliutn sue component resembling cemcntum or dentine. No normal tooth structure arrangement was observed (Figs. 18 and 19). Hemangiopericytoma.-In our series we had but one example of this most unusual tumor; that one csamplc o~currcd in the lip of a 6-year-old female

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ORAL

PATHOLOGY

cocker spaniel. It has been Chaudhry.37 As recently as dogs, none of which occurred nally described this tumor in

OF D6MESTICATED

.ANIMALk

517

reported in a separate paper by Gorlin and cases in 1955, Mulligan 38 described sixty-eight in the oral region. Stout and Murray3g origi1942, and Stout has published several excellent Fig.

21.

Fig.

22.

Note proliferation of cells about endothelial Fig. 2L -Hemangiopericytorrla. lined Jumina. Gorlin and Chaudhry: ORAL SURG., ORAL MED. & ORAL PATH. 10: 422. 1957.) Fig. 22.-Hemangiopericytoma. Silver-stained section seen in Fig. 21 shows position of reticulin sheath in relation to lumen of vessel. This Is done to differentiate hemangiopericytoma from hemangioendothelioma. (From Gorlin and Chaudhry : ORAL Sums., ORAL MED. & ORAL PATH. lo: 422, 195'1.) (From

reviews of this tumor.“‘, 42 In a recent paper’” he indicated that hc has twelve examples of this tumor in the oral cavity of man (three each in the tongue,

r\ND

(‘HrlCJI)H~T

0. s., 0. M., & 0. I’. May, 1958

lips, and palatch, anal one each in the alveolar p~~ocess, parotid gland, ant1 caheekj. \Ve are not aware of this tumor occurring in domestic animals other than dogs. The tumor consists of hug0 numbers of capillary-like structures linctl hy normal endothelium but surrounded by pa.cked contractile “cpithclioid described by Zimnlcrman as “perieytes.” The exact positioll VC?llS,”originally of these cells in relation to the rcticulin sheath cannot be well determined with routine hematosylin and eosin stain. A silver reticulin stain is employed tcr differentiate hemangiopericytoma from hemangioendothelioma, whose cells proliferate within the reticulum sheath (Figs. 20 to 22).

Fig. 23; -0steoma. (Courtes

sir 1”S Tumor mass of dense bony tissue occupying maxillary j of Dr. A. K. Fisher. University of Iowa. School of I 3enl :isti

Osteoma.-SchlumbergeP cited Cole’s finding of an osteoma and osteofibroma in the maxilla of a dog. In view of what we know about the frequency of bone in canine cpulides, it is possible that these tumors were examples of

Volume I1

Number S

OBAL

PATHOLOGY

OF DOME&TICATED

ANIMALS

519

this latter entity. Feldman* has noted several osteomas and osteofibromas in the jaws of horses and cows. We found one example of a fibro-osteoma in a horse in our series, and it would appear from perusal of the files of the Veterinary Section, Armed Forces Institute of Pathology, Washington, D. C., that this t,umor is not rare in horses (Fig. 23). Ma&pant

Tumors

Melanoma.-Melanoma was the most common malignant tumor ,of our series. All of these tumors occurred in dogs. Whether this is in some way related to the melanotic pigment,ation so often seen on the oral mucous membrane of dogs, as Schlumberge9 contends, is certainly open to question, for in man melanomas are relatively uncommon in Negroes.9 It is interesting to note that Cotchin14 did not observe any oral melanomas in a large series of cats, while Colez5 cited two cases in an unstated number of cats examined. The horse, although frequently subject to melanoma, does not commonly have primary lesions of the oral cavity.16T 78 One of the most perplexing problems is the apparent difference in this tumor’s incidence in England and in America. While melanoma appears to be the most common canine oral malignancy in this country, with squamous-cell carcinoma a poor second,25 the reverse seems to be true in Britain, Withers” and Cotchin12y 21 have presented good evidence that in their series squamous epithelioma of the tonsil is overwhelmingly more common than any other oral malignancy. Whether this is due to an environmental factor is yet to be determined. Willis26 has rightly pointed out that we have much to learn from a study of neoplasia in the lower animals. In still another report covering a rather large series of oral tumors, Rise+ has found an almost equal number of these two neoplasms in the oral cavities of dogs. This tumor does seem to be more common in certain breeds. Mulligan59 27 found that the airedale, Scotch and Boston bull terriers, and English springer spaniels were most frequently affected. He felt the dark-skinned animals were more prone to have this tumor. These breeds were also cited by Cotchin.z1 Our series of oral melanomas, although the species data were missing in large part, indicated that perhaps the black cocker spaniel had a higher incidence. Sex seemed to play a significant role in the genesis of this oral neoplasm, for in twelve of our cases in which sex was ascertained, ten were males. However, this does not seem to be borne out in the case of skin melanoma, for in Mulligan’s series of thirty-five cases; twenty occurred in males.5 This could easily have been a matter of chance. Age seems to play a significant role also, for twenty-six of his cases (about ‘75 per cent) occurred in dogs between 9 and 14 years of age. Our series provided thirteen dogs with ascertainable ages, the mean being 11.5 years. About 70 per cent of our dogs were over 9 years of age. The lips seem to be the most common site of origin, although the palate, The rarity buccal mucosa, cheek, and floor of the mouth were also involved. In fact, involvement of tongue involvement in the dog is perhaps significant. of the canine tongue with any lesion save that of infectious papillomatosis is

c~st~cdingly

rare.

C”otchin,”

oi

of the

tonguc~

Y~IWIII:I

I~ow~vt~r, did in his scrios of

c.itlzcl a casc~ 01 Inalignnni hl clanotna

usually

tumor

that

hcmorrhagc matter

not

weeks

the

separated

into

The

rpithelial

cells,

the

forms

granules are

common

the

has

to most

large

C’otchinZ1 first

divided

the

two

benign

of histologic t,hat

a

pattern.

are

supported

connective

tissue.

patterns,

nucleolus-containing Some are

and

within

of spread.

or alveolar

Areas of these

All

site

of collagenic

others

numerous.

or brownish ulceration

is usual

cells

whorls,

seen. while

melanomas cellular

types

~anccro~~s”

spulTcP”

seem

types.”

into

to

arc

nucleus.

cells will completely

of necrosis observations

exhibit fine amelanotic. and inflammaalso apply to

third

that

overlying

the

were

to

secondarily

Separation

into

the

following

is characterized

by

shaped.

cells

Many

visualization

I

arranged,

and

resembling

uniform

be the

the

bizarre

eyelid.27

benign

and

criteria cells

The

and

“non-

to have been described by which he considered to be by

a “sinking-in”

of pigment

have

single forms

and not

MALIGNANT -~ Loose Rare Two or more commonly seen Absent Present Present

processes may

have but seen.

is not

so hea.vily The take The

laden

cells

a bundle

with

cells

cytoplasm. site

Mitoses of

pigment compactly

or palisade

polyhedral

clear

or spindle

a.re usually

nucleolus.

A favorite

too

melanoma

be polyhedral

an acidophilic a single

always

or noncancerous may

is impossible. corpuscles.

a.ntl bears arc

JScnign They

types.

cells

Meissner’s

MELANOMA

I

melanomas

used :

dendritic

spindle-sha,pcd

MALIGNANT

Present Absent Absent

malignant werca

of several

in appearance

always

and

mel-

melanoma.

“cancerous”

BENIGN Compact Common Single

tumors

of the nucleus

somewhat

mon,

Mulligan’s

pigmented

ma,lignant

fibrous

epithrlium.

Areas resembling m~rve slwittlt Nuclear pleomorpl~ism Xizarrr mitoscs

is nearly

benign

type seems neurofibromas,”

CIIARAC’TERISTIC’S Arrangement of cells Pigmented dendritics forms ~‘iwlroli

quite

the

;\~ICROSCOI%: CHAI~AC’I’ERISTI(‘S OF RENIGN AND

‘l~.~UI.lS I I’.

but

categories-the

and

correspond

Cotchin’s

~~~11s from

three

melanoma,

iIS “spottily-pigm~ntcci

Ile~~t~c~fiGr~oluas

that

range

epithelial

a single

tumors.

chow.

metastases.

anomas,

cut,

a wide

nests,

occasionally quite

metastasis

1)~ bands

with

male

grayish

Marked

to be a common

of large

caytoplasnz

usually

firm

down.

seem

iu sheets,

ark

in

figures are

up

polymorphous

Multinuc~lcated

iion

lungs

lobules

arrangetl

breaks

widespread

mc~lanoma

indistinct

frcqurntly

Mitotic

and

is mado

of an g-year-old

in dogs.3Z

as a somewhat and

The

car&c growth

iIll<

melanin

rges

or months.

new

itself

c&j

unconunon,

Micl.oscopically, I-snally

produced

pr(tsents

rapidly

arc

of

quite

of t,hc t cmgue

has bec~ri cspcrimentally

Melanoma black

rt~c~l;r noma

find two cases of carcinoma and one (aanintl ncoplasms, and McClelland”’

occurrence

pattern

usually The arc

are

nucleus not

com-

seems

to

Volume 1I Number 5

ORAL

PATHOLOGY

OF DOMESTICATED

ANIMALS

521

In contrast, the malignant variety almost never exhibits dendritic forms. The cells are usually loosely arranged. Pigmentation to the degree exhibited by the benign variety is almost never seen. Mitotic activity is great, and bizarre forms are common. Nuclei are frequently quite large in relation to the amount of cytoplasm, and two or more nucleoli are quite common (Table IV). Both Mulliganj and Cotchin 21 have expressed the opinion that the majority of skin melanomas are benign. Exactly the opposite is true of oral melanomas. All but one in our oral series (and that one exception came from the mucocutaneous portion of the lip) were of the “cancerous type.” In view of the general absence of junctional changes in canine melanomas, their origin is still open to question. However, several sections of oral melanomas examined by us revealed junctional cha.nges adjacent to the tumor (Pigs. 24 to 29).

Fig. 24.-Benign is a densely pigmented merous dendritic forms

melanoma. Beneath a normal-appearing tumor. The pigment is so dense that are observed.

stratifled it obscures

squamous epithelium cellular detail. Nu-

Squamous-Cell Carcinoma.-Although squamous-cell epithelioma behaves clinically in dogs and cats much as it behaves in man, its incidence appears to be considerably smaller.25 In man, squamous-cell carcinoma comprises over 90 per cent of oral malignancies, the lip and tongue being the most common sites.*” In this country, such statistics as are available do not bear out the reports of WithersI and Cotchin12 that canine squamous-cell carcinoma of the tonsil is overwhelmingly the most common oral malignancy. Perhaps this reflects a difference in geographical incidence Large surveys in various centers in this country or in several countries are necessary to clarify this situation. Martin and Holland,10 having collected 122 case reports of oral and nasopharyngeal neoplasms from the literature and an additional 35 cases from

GORLLN,

CLARK,

AND

CHhUI)HR~Y

0. S.. 0. M., & 0. P. May, 1959

presented an interesting comLOOS, veterinary schools, and veterinarians, They were faced with the same parativc topographical incidence breakdown. problems that wc encountered, that is, the nonspecification of exact location that is so characteristic of submitted animal material. Because of this difficulty, the inclusion of data on other than domesticated animals, and their use of the general term cuncer rather than more specific nomenclature, their figures However, they did present several rather interestare not, especially helpful. ing points: that jaw cancer in “animals” is about four times more common than in man and that tongue cancer is about one and one-half times as common iii man as in animals. They believe D ‘Arty Power ‘s3” comments on the rarity of lingual cancer in animals to be somewhat exaggerated. In their grouped series it is interesting to note that “cancer of the tonsil” comprised only 5 per cent of oral cancer.lO

Fig. 25.-Malignant dible, especially about the uninvolved side.

melanoma, the teeth and

Tumor arose periodontium.

Another unusual phenomenon cancerous oral lesion, leukoplakia.

in floor of the mouth and The photograph contrasts

invaded the manthe involved with

is the absence in animals of man’s preIn our series we noted a single case of

Several investigators have inFig. 26.-Junctional changes near a malignant melanoma. that melanoma in dogs and horses does not arise from the junctiOna neVUS. The above does not bear out their contention. Note also the Fig. 27.-Malignant melanoma. Note the grouping of cells into units. The cells of a melanoma may be relatively uniform or moderate amount of pigment present. exceedingly pleomorphic. Arrow points to mitotic figure. Cells are quite pleomorphic and have not produced large Fig. 28.-Malignant melanoma. amounts of melanin. Typical cellular arrangment is suggestive but not definite. Note the marked uniformity of cell type and the way the Fig. 29.-Malignant melanoma. cell groups mimic Meissner’s corpuscles. dicated finding

Volume Number

fI 5

ORAL Fig.

Fig.

PATHOLOGY

OF DOMESTICATED

ANIMALS Fig.

26.

27.

Fig.

(For

legends,

see opposdte

page.)

523 28.

29.

}I)-perlrcl.atosis. I)nt no dyskeratosis WilS prc%Wlt, SO we did Ilot fW1 justifietl As fal. as WC know, Icukoplakia has nevclr IWCII in calling it leukoplakia. This single CRSCoccurrctl in a cow as part of a cliseascl t~c~l)orteclin anintals. ~:omplcs called bovine: hypcrk(*ratosis or S disease. This has been discuss4 in an earlier section of this article. As may bc seen frorrl the scrips by Cotchin” and this present study, the tongue is not commonly affectecl in the dog. In cats, on the other hand, s~~~oJno~ww11 carcinoma of the tongue is not uncommon.” Feldman belie~~etl it, to he the most common cat malignancy. It is quite unlikely that this is tlue to preening or fur-licking, for lingual cancer does not appear to be conJJJOIJ aJnong other felines exhibiting this habit’” ; perhaps it is merely a population siztl dfference. The predominant site in the cat is the left ventrolateral surface at about, the level of the frenum.‘” I)eep invasion of the tongue musc+ulature can occur with early metastasis to local lymph nodes. The averag(a agr of the affected animals in our series was 10.5 years, the range being 7 to I6 In years. 0f somewhat less importance in the cat is tonsillar carcinoma. Clotchin’s dog series this was by far the most important oral malignancy.

Islands of Fig. SO.--Squamous-cell carcinoma. cell keratinization. E’leomorghism is marked. Keratin observed at arrow.

squamous pearls,

epithelium shoxing individual although not numerous, van be

There were seven cases of squamous-cell el)ithclioma in our series. Five were in dogs and two were in cats. One of t,he cases (50-255) was odd in that it was associated with viral papillomatosis and osteoid deposits. The rcadel The esact may refer to the preceding section on infectious pa~pillomatosis. age could be ascertained in only three examples, with a single additional statement of “old” in the case of a cat. Within our limited series, no conclusions could bc drawn as to sex, site, or breed incidence. There is no difference in microscopic appearance between this tumor in animals ancl in man (Fig. 30).

c!:er7

ORAL

PATHOLOGY

OF DOMESTICATED

ANIMALS

525

Basal-Cell Carcinoma.-Basal-cell carcinoma in animals, as in man, is not an intraoral tumor. It is found in the skin. Three examples were observed in our series, all in dogs. Two were found in the upper lip and one was found in the skin of the submaxillary area. RiserI found sixteen examples of this tumor in his series of 613 canine skin neoplasms. CotchirP observed forty-seven examples of the same tumor in his similar group of 510 neoplasms, and in a later report he noted 210 cxamples of “basal-cell and glandular tumors” in a series of 932 canine skin Rig-

31.

Fig.

32.

Fig. 31.--Basal-cell carcinoma. Islands of basal cells tend to form glandlike Around each cell group is hyalinized connective tissue. Most basal-cell carcinomas skin appendages. As in man, this tumor is not found intraoral&. Fig. 32.--Basal-cell carcinoma. This high-power view of the section shown demonstrates the basal nature of these cells.

structures. arise from in

Fig.

31

5 L’6

GORI,IS,

CLARK,

z\SU

CII~~~.~l~IIR~

0. S., 0. M., 8; 0. I’.

May. 1958

nc~~l)las~~s.“~ 7ll a sorics nf forty fclinc skin tumors of c~pithclial origin, thirtpolli’ wcw of basal-cell 01’ ~1;1ntlula7~ oripin.‘~’ Malts xvrrc nffectcd at least fivt, C)I’sis tiititbs ltloi’(’ c~nu~rc,nly than females.“~ ‘Ii ITead;*I; in 1953, cited an incidence of fift.v-one of these tumors in his skin scrics 01’ -t‘)-’ -- in the dov Cotchin” noted, in reviewing these tumors, that fourtc~n i~pl)c’ar(~d to beY;f sebaceous origin and sixteen of sweat gland origin. The ;Igc ~.ariccl from 10 months to 14 years with an average of 8 years. The b(Jhavior (11 1his tumor seems to be quite similar to that of thn same tumor ill lllil11. It slo\\,l~- canlarges, ulccratex, and invades but does not metastasize. Mulligan” has subtlivided and subcategorized skin lesions much more than his IS~lglisll ccrll~~aguos. He found twent,y-five examples in his survey of 1,000 gcncr;il canine ncoplasms, 283 of these 1,000 being skin tumors of various types. Feldman reported the existence of this tumor in a horse. hgain as in man, one of the favorite sites of this tumor is the faccb, VSpcci:tll>- the ,ja,ws, cars, eyelids, and lips, although this point is disputed by Willis.“; The origin ma-y be in the epidermis, in glands, or in hair follicles. Willis believes that lnost basal-cell carcinomas in dogs arise from sweat glands. This tunlor may rcscmble the tumor commonly seen in ma,n, it may cshibit an atlenoid or reticular structure (suggesting origin from sweat glands), or it may consist of diffuse collections of closely packed uniform cells intermircstl with pipltlclnt-latlcn ~11s reminiscent of norma, hair matrix. Mitotic activit>is va viii l)lc~. (SC F’igs. 31 and 32.)

Neoplasms of the Major and Minor Salivary Glands.-We encountered no casrs of 111ajor salivary gland neopla.sms in our series. Schlumberger,16 in r(.\.i(l\viny. th(l litc~raturc~ ant1 through personal communication, cited cases of ;1&‘110111~1, ~tdcriocni~~ilioina, mised tumor , and duct papilloma in the dog. Mulligan” has noted a “ cancerous mpoepithelioma! ’ of the parotid gland ant1 has l)oilltcd out the marked similarity of these tumors to those of the canin(a lTl~llll?llil I’y fi’hllClS. Trottcr’j reported a cast of “mixed-ccl1 sarcoma” of th(L parotid in a survey of 305 malignant neoplasms in cattle. StickeP reported a. single (‘asc of carcinoma, of t,he parotid in a cow and two cases in dogs. Riser” found three cases of “adcnocarcinoma of salivary glands” in a series of 226 c*aniuc>ncoplasms of the mouth a.nd nose. Hc did not state which glands wert~ invol\-cd. A single neoplasm of canine salivary glands was cited hy C’otcdhin.“, “I Its precise pathologic nature was not specified. Although no true major salivary gland neoplasm was observed in OUI series, a pseudoparotid mass in a IO-year-old male I,abrador (not included in this series) prescbnted a diagnostic problem. It was reported by Qorlin and Clark’;” as a case of calcifying epithelioma of Malherbe. Two cases of adrnocarcinomn of minor salivary glands in dogs a11t1one ill a sheep werc~ observed in our series. In all cases the neoplasm arose in the palate (Figs. X3 and 34). Colt, cited by Schlumbergcr,l” saw a case of adenocwrcinomi-i of a dog lip, and Mulligan” noted one in a canine’s tongue. These also TV~W undoubtedly of minor saliva.ry gland origin. Cotchin,4* I2921 in his scrernl papers, did not mention th(A occurrence of this tumor in the oral rcgion.

V&me 11 Nomber 5

ORAL PATHOLOGY

33 .-Adenocarcinoma. th< 3 palate. 34 .-Adenocai-cinema.

This Note

OF DOMESTICATED

Fig.

33

Fig.

34.

mucus-producing both

glandlike

tumor and

ANIMALS

arose

sheetlike

from

527

the

arrangement

mil

sallvary of

cells.

528

GORLTN,

CLARK,

AXI)

CH;\I’J)HRY

0. S.. 0. M.. & 0. I’ May, 19:fi

Mast-Cell Tumor.-The mast-cell tumor, or mastocytoma, is chiefly a tn~nor of the skin. It was separated as an entity from other round-ccl1 neoplasrim h-y Bloot~~“” in 1942. The general and oral pathologist will find the older terminology employed somewhat confusing. In 1932, for example, Feldman,* in an at.tempt to simplify the myriad of names applied to various roundcell tumors, grouped them into two classes: (1) lymphomas, which wee “‘benign tumors, which arise within lymph nodes, and other lymphoid t,issnes.” and (2) lymphocytomas, which are ‘Yhe malignant types of neoplastic hyprt,plasias of which the immature lymphocyte or its forerunner is the cell type.” Mulligan,5 in 1949? divided canine round-cell tumors into three categories: mast-cell sarcoma, lymphosarcoma, and histiocytoma. Because this specific tumor is not seen in man, it might be worth while to discuss its salient features. The mast-cell tumor is quite malignant. Although it may remain rathe? dormant for several months or even years, it more frequently enlarges rapidly and may metastasize widely. Because of its marked similarity to other roundcell tumors, a special stain (such as Giemsa stain) is employed to stain the cytoplasmic granules which are not always evident in less differentiated, more clinically malignant tumors. These granules, which have been shown to contain heparin stain an intense blue with Giemsa stain. Although there is still debate on the subject, the mast cell has been considered by most pathologists to be distinct from the basophilic leukocyte seen in human blood.67-6s We have had good results staining with toluidine blue. Although this dye is not as permanent, the staining technique is easily performed. We found four examples of mast-cell tumor in this series, All were in dogs. Two were in the upper lip, one was in the skin of the chin, and one was on the hard palate. RiseP found three mastocytomas in his series of canine neoplasms of the nose and mouth. Mulligan5 has made no mention of any intraoral mast-cell tumors in his series, although he has indicated that occasionally they occur on the lip. Cotchin did not find any oral examples, although he did have twenty dermal examples in a series of 422 skin tumors. Males seem to be more commonly affected, possibly twice as often as females. Ages in various series ranged from 2 to 13 years, with an average of about 8 years. In both Cotchin’s and Mulligan’s series, boxers, bull terriers, and bulldogs were the breeds in which this tumor most commonly occurred (Figs. 35 to 37). I,ymphoblastoma.-Among some species, such as cattle and pigs and to a lesser extent dogs, cats, and horses, leukemic and nonleukemic lympho. blastomas are among the most common tumors, The latter term is used synonymously with “malignant lymphoma.” In dogs, it occurs in all ages, although it has a slight tendency to affect the younger dog. It is seen more comThe monly in the Scottish terrier.5r ‘l There appears to be no sex preference. enlargement of submaxillary initial sign is frequently bilateral, symmetrical and cervical lymph nodes. Cats have this neoplasm more commonly than dogs, although lymphosarcoma of the intestine in this species seems to be the most common site.*O Cervical adenopathy in the cat is quite unusual.

Volulrle I I Number 5

OItAL

PATHOLOGY

OF DOMESTlCATED

Fig. though specific ules.

ANIMALS

529

36.

AlThis malignant tumor consists of masses of round cells. Fi lg. 35.-Mastocytoma. granules may be observed in some sections stained with hematoxylin and eosin 1, a stain such as Giemsa or toluidine blue is best employed. Section stained with toluidine blue shows the cytoplasmic go.anFI ig. 36.-Mastocytoma.

x0

GORLIN,

CLARK,

AND

C.HAUDIIRY

0. S.. 0. M.. & 0. P. May, 19.55

Jt, should lx emphasizc4 that, because many of the less well-cliffet,elltiatctl Iosions show few granules, it should be standard procedure to stain all rountl~11 snrcvmatous ncoplasms of the skin and oral mucous membrane with

B‘ig.

37.-

Fig.

38.-Lymphoblastoma. tion revealed

Xast-cell

tumor.

High-power

photomicrograph with Giemsa stain.

Tumor consists of uniform that most of the cells were

showing

cytoplasmic

granules

masses of round cells. Closer of the lymphoblastic type.

stainc
examina-

Qiemsa stain or toluidine blue to separate the mastocytomas. Malignant lymphoma is a rapidly5 fatal illness, affected animals rarely la.sting Inore than seven months, Microscopically, it may be fymphoblast,ic or lymphocytic. Wc had three examples of this t,umor in our series. All were in females more than 8 years of age (Fig. 38).

Volume 1 I Number 5

ORAL

PATHOLOGY

OF DOMESTICATED

531

ANIMALS

Fibrosarcoma, Chondrosarcoma, and Osteosarcoma.-Fibrosarcoma was seen twice in our series (Fig. 39). One ease occurred in the mandible and the other in the hard palate. A search of the available literature for statistics

Fig. 39.-Fibrosarcoma. was of rather long duration Fi 40.-Chondrosarcoma. chondro %lasts and immature

Fig.

39.

Fig.

40.

This low-grade malignancy exhibited and had invaded only locally. Tumor is composed bf immature or poorly formed cartilage.

few

mitotic

cartilage-forming

Agures. cells

It or

seems to muddle rather than clarify the picture. Schlumberger,‘G in his review of animal oral neoplasms, cited two cases in horses but none in dogs. Cotchinl* found twelve examples of “sarcoma” in a series of ninety canine oral tumors, nine of which occurred on the gingiva or palate. However, he did

Ilot specify ihc~ type 0C sarcoma. Mulligan5 makes no mention of any intraoral fibrosareolllas, though Plate XXX111 shows one from the submental region. Whether this was of dermal origin or the skin extension of a mandibular site was not discussed. RiseP found three examples of this tumor in the mandibles of dogs. In another paper describing eighty-four canine neoplasms of the mouth exclusive of the tonsillar area, Cotchin found seventeen of them to bc sarcomas of undesignated type, all of the gingiva. Willis26 observed a Ilumber of fibrosarcomas in a.nimals, but none of them occurred about the rtrouth. If’ we may hazard an opinion based upon the reports available, the lower jaw and palate seem to be common sites. There was but a single example of chondrosarcoma in our series (Fig. 40). in the palate of a ii-year-old male pointer. If the various general It occ~t*retl surveys reflect the true incidence of this tumor, it is found quite uncommonly in animals. Perhaps in some surveys it has been included under the designation of osteogenic sarcoma. However, Schlumberger,16 in his review, noted none affecting oral structures. Mulligan5 observed that these tumors are more conman in the shepherd breed. It was his belief that they occur most commonly Feldman,* in reviewing the on t,he hard palate, nasal passages, and mandible. early European literature, failed to disclose any cases involving the oral structures of domestic animals. WilliszR described a case that he had seen in the nasal cavity of a 6-year-old cocker spaniel; this tumor did not metastasize. Osteosarcomas arc apparently much more common tumors than chondrosarcomas. 71( Cotchin found forty of fort,)--one bone tumors to be of this type. In his series t,herc were three involving the mandible and two in the maxilla. About half of the dogs were over S years of age. The tumor metastasizes early in the c*linical course of the disease, chiefly by way of the blood stream much as in man.” Bone tumors in general are not commonly benign in dogs and must bc removed carly.18 WilliP noted a ca.se in the palate of a Samoyed, ant1 Nielsen and associates’” reported one in the mandible of an U-year-old grey110urld. Feldman,* in reviewing the literature, has noted several cases in horses and cows. He stated that the tissues of the head are most prone to this tumor. Similar I(asions involving t,he masillac were reported in the dog, sheep, and cat.* In microscopic nppcarance, this tumor is virtually identical to those COPresponding tumors occurring in man.

Summary We have reviewed 103 successive14 biopsied oral lesions obtained fro111 ninety dogs, six cows, five cats, one sheep, and one horse. These lesions include both neoplastic and nonneoplastic diseases. Among the nonneoplastic group we encountered cases of pyogenic granuloma, actinomycosis, eosinophilic granThe benign neoplastic lesions found in uloma, ant1 bovine hyperkrratosis. t,liis series were fibromatous epulis of periodontal origin, canine oral papillomatosis, sebaceous adenoma, hemangiopericytoma, osteoma, and ameloblastic odontoma. The most common malignant neoplasm found in this series was

Volume Number

ORAL

II 5

melanoma

in

PATHOLOGY

dogs, in

OF DOMESTICATED

ANIMALS

533

contrast

to squamous-cell carcinoma observed by Other malignant neoplasms found in different animals were squamous-cell carcinoma, basal-cell carcinoma, adenocarcinoma of the minor salivary glands, mast-cell tumor, fibrosarcoma, chondrosarcoma, and lymphoblastoma. The incidence, clinical features, and the macro- and microscopic natures of all these lesions have been discussed in detail.

Withers and Cotchin in their surveys.

The authors are indebted to Dr. J. H. Sautter, Director of the Division of Veterinary Pathology, Dr. Donald H. Clifford of the School of Veterinary Medicine, and Dean William Crawford of the School of Dentistry for their invaluable help and advice, and to Drs. E. Bell, J. Dawson, and R. Hebbel for their encouragement and critical review of the paper. May we also extend our sincere thanks to Mrs. Helenmae Schauer, Miss Wilma Hayes, and Mr. James Rothenberger for their excellent technical help.

References H. McF.: Study of a Biopsy Service: Problems in Diagnosis of 1,283 1. Woodbridge, Cases, ORAL SURG., ORAL MED. & ORAL PATH. 7: 297,1954. 2. Boyle, P. E.: Differential Diagnosis of Soft Tissue Lesions of the Mouth With a Discussion of Biopsy Procedures, ORAL SURO., ORAL MED. & ORAL PATH. 7: 507, 1954. 3. Gorlin, R. 5.: Twenty-Five Years of Growth, Oral Pathology Division and Biopsy Service, University of Minnesota, School of Dentistry, North-West Dent. 35: 308, 1956. Cotchin, E.: Neoplasms in Small Animals, Vet. Rec. 63: 67, 1951. 2 Mulligan, R. W.: Neoplasms of the Dog, Baltimore, 1949, Williams & Wilkins Company. G. C., and Douglas, S. W.: The Incidence of Cancer in Dogs, Vet. Rec. 66: 6. Knight, 195, 1943. C., and Labatut, R.: Rec. Med. Vet. 90: 425, 1938. 7. Lassere, R., Lombard, Neoplasms of Domesticated Animals, Philadelphia, 1932, W. B. 8. Feldman, W. H.: Saunders Company. Disease in the American Negro. I. Melanoma, Surgery 9: 425, W. A. D.: 9. Anderson, 1941. H. E., and Holland, B. F.: JO. Martin, The Zoologic Distribution of Intraoral Cancer, Seient. Monthly 49: 262, 1939. F. W.: Squamous-Celled Carcinoma of the Tongue in the Dog, J. Path. & 11. Withers, Bact. 49: 429, 1939. 12. Cotchin, E.: Further Observations on Neoplasms in Dogs With Particular Reference to Site of Origin and Malignancy, Brit. Vet. J. 110: 218, 1954. Cohrs, P.: Multiple Tumours in Domesticated Animals, Cancer Rev. 2: 197, 1927. ii: Cotchin, E. : Neoplasms in Cats, Proc. Roy. Sot. Med. 45: 671, 1952. 15. Trotter, A. M.: Malignant Disease in Bovines, J. Comp. Path. & Therap. 24: 1, 1911. H. G. : Comparative 16. Rehlumberger, Pathology of Oral Neoplasms, ORAL SURG., ORAL MED. & ORAL PATH. 6: 1078, 1953. 17. Riser, W. H.: In Hoskins, H. P., and LaCroix, J. V. (editors): Canine Surgery, North American Veterinarian, Evanston, Ill., 1949. 18. Riser, W. H.: Treatment of Tumors in the Dog: Comparison of Surgery and Physiology, Proc. 91st Annual Meeting, A. V. M. A., pp. 279-285, 1954. 19. Burstone, M. S., Bond, E., and Litt, R.: Familial Gingival Hypertrophy in the Dog (Boxer Breed). Arch. Path. 64: 208. 1952. 20. Hughson, J. : Gum Tumors: Clinical-Pathological Conference, Angel1 Memorial Animal Hospital, August, 1952. 21. Cotchin, E. : Neoplasia in the Dog, Vet. Rec. 66: 879, 1954. 22. Findlay, G. M.: A System of Bacteriology, Lontlon, 1930, His Majesty’s Stationery Office. in Canine Oral Papillomatosis, J. Bact. 38: 111, 1939. 23. Goodlow, R. J.: Immunity 24. De Monbreun, W. A., and Goodpasture, E. W.: Infectious Oral Papillomatosis of Dogs, Am. J. Path. 8: 43, 1932. 25. Cole, C.: Cited by Schlumberger.rc of Tumors, ed. 2, St. Louis, 1953, The C. V. Mosby Company, 26. Willis, R. A.: Pathology Neoplastic Diseases of Dogs. 27. Mulligan, R. M.: I. Neoplasms of Melanin-Forming Cells, Am. J. Path. 25: 339, 1949. 28. Spurrell, W. R.: Six Cases of Canine Cancer, J. Comp. Path. 45: 172, 1932.

GORL I N, CLARK,

534 29. Bornicr,

J.

L.:

The 1\Lanagement

of Oral

AKD

C!lIAUI)HRY

J)iscasc,

St. J,ollis,

0. s.. 0. M., & 0. P. May, 19i4 1055, The C. V. Mosh,v

at. 2 1. 3”. 12. 13.: X-Ray Therapy in Labial &ti Cutaneous Granulomas’ in Cats, 33. McCl~llantl, North Am. Vet. 21: 296, 1940. 34. I\lcCarthy, F. P.: A Clinical and Pathological Study of Oral Disease, J. A. M. A. 116: 16. 3941. 35. Poppen$iek, (i.: Cited by McClelland.ss xi. Hutvra, F., Marek, J., ant1 Xlsnninger, R.: Special Pathology and Therapeutics of the ’ Diseases of Domestic Animals, e(l. 5, vol. I, Chicago, 1946, Alexander Eger, Inc. Benign Hemangioprricytoma of Dog Lip, ORAJ. 3i. (+orlin, ft. J., ancl Chaudhr,v, A. P.: SCRC.. ORAL M&D. & ORAl. PATH. 10: 422. 1%i7. :VL Mulligan, ‘R. N.: Hemangioperieytoma in ihe Dog, Am. J. Path. 31: 773, 1955. 39. Stout, A. P., and Nurray, M. K.: Hemangiopericytoma-a Vascular Tumor Featuring Zimmerruann’s Pericvtes. Ann. Sure. 116: 26. 1942. Caocer 2: l(i27, 194Q. 40. ,stolJt, A. P.: Hemangioieri-toma, Pericytes: 41. stout, A. P.: Tumors Featuring Glomus Tumor anti HemangiopericFtoma, I,ab. Invest, 5: 217, 1956. The Glomus Tumor; Investigation of Its Distribution 42. xllurray, M. R., and Stout, A. I’.: and Behavior and Identity of Its Epithelioitl Cell, Am. J. Path. 18: 183, 1942. Tumors of Soft Tissues, Mid-Year Symposium, TVashington, D. C., 1956, 43. Htout, A. P.: American Academy of Oral Pathology. Sebaceous Adenoma in a Dog, ORAL WRC., ORAL MED. & ORAL PATH. 44. (+orlin, R. J.: 10: 304, 1957. 4.5. Lever, IV. F.: Sebaceous Atlenoma-Review of the lAit,erature ant1 Report of a Case, Arch. 1)ermat. & S~ph. 57: 102, 1948. Ijiseases, Vet. Rec. 65: 926, 1953. 46. Head, I<. I\-.: Neoplastlc 47. Bullock, F. J)., and Curtis, 11. R.: Spontaneous Tumors of the Rat, J. Cancer Rex. 14: 1, 1930. 48. Zegarelli, +:. Y.: Adarrlantoblastorrlxs in the Slye Stock of Mice, Am. .T. Path. 20: 23, 1944. 49. Ratclifl’e, 1-I. I,.: Incitlence ant1 Nature of Tumors in Captive JViltl Mammals and Hirds,

Am.

.r. (Iancer

17:

llci,

1933.

Lehrbuah der Speziellen Path., Anat. der Haustiere, Jena, Ii., and Cohrs, J’.: 50. Nielrerle, lQ31. .I.: A \.‘er>- Large Odontome From a Horse, Tr. Odont. Sot. Great 51. Blantl-Sutton, Britain 23: 215, 18Ml. t52. Olafson, P.: Oral Tumors of Small Animals, Cornell Vet. 29: 222, 1939. R3. Olafson, P. : Hyperkeratoxis (X-Disease) of Cattle, Cornell Vet. 37: 195, 1947. The Relation of Feed to an Outbreak of 54. Olson, C.,, Cook, R. H., and Hrollse, E. K: Bovine Hyperkeratosisi, j4111..J. Vet. Res. 11: 355, 1950. Attempts to Produce liovine Hyperkeratosiu, Am. .T. Vet. 55. Olson, C., and Cook, R. H.: Res. 12: 261, lQ51. The Protluction of Hyperkeratosis (X5fi. McEntee, I<., Hansel, W., autl Olafson, P.: I)isaase) 1117Feeding a Processed Concentrate. (lornell Vet. 41: 107. 1951. !Hyperket%tosis of Cattle in Germariv, J. Am. Vet. M. A. ‘119: 133, 1951. 57. Wagener, K’: of Hyperkeratosii by the Administration of a Luhri58. Bell, IV. B.: The Administration cant, Virginia .J. SC. 3: 7J, 1952. Further Stutlies on the Production of Bovine Hyperkeratosis by the 59. Bell, W. B.: Administration of a Lubricant, Virginia J. SC. 3: 169, 1952. 60. Hansel, W., Olafson, P., and McEntee, I<.: Studies on a German Wood Preservative, Cornell Vet. 43: 311, 1953. Streptomycin in the Treatment of Actinomycosis, H. E., and Palen, J. S.: 61. Ringman, .T. Am. Vet. M. A. 118: 28. 1951. 6”d. Lever, W. F.: Eosinc&ilic Grknuloma of the Skin, Its Relation t,o Erythema Elevatum Dietinum and Eosinophilic Granuloma of Bone, Arch, Dermat. & @ph. _ _ 56: 194, 1947. 63. Lever, W. F., Lane, C. G., Downing, J. G., and Spangler, A. S.: Eosinophilic Granuloma of the Skin, Arch. Dermat. & Spph. 58: 430, 1948. 64. Sticker, A.: Cited by Feldman.8 6.5. Gorlin. R. J.. and Clark. .J. J.: Calcifying EDithelioma of Malherbe in a Doe.-1 ORAL &RG.. &AL MED. & URAL PATH. 10:'108~. 1957. (iii. Hloom, F. : Spontaneous Solitary and Multiple Mast Cell Tumors (“Mastocytoma in Dogs”), Arch. Path. 33: 661, 1942. 67. Bloom. F.: Effect of Cortisone on Mast Cell Tumors Chladncvtoma~ of the Doa. Proe. Sbo. Exper. Riol. & Med. 79: 651, 1952.

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68. Paff, G. H., Bloom, F., and Reilly, C.: J. Exper. Med. 86: 117,1947. 69. Oliver. J., Bloom. F.. and Mareieri. C.: J. ExDer. Med. 86: 107, 1947. 70. Nielseh. &. W.. ‘ani others: -The’ Patholoev*-v of Osteoeenic Barcoma in Dons. v , J. Am. V;t. M. A: 124: 28, 1954. 71. Hoekstra, W. G., and others: Production of Hyperkeratosis in Calves With a Topically ADDlied Oil-Based Insecticide Carrier. Am. J. Vet. Res. 15: 47, 1954. 72. Lebea;.&A.: Age Comnarison Between Man and Doe.-I J. Am. Vet. G. A. 124: 236,,. 1954. 73. J. Am. ‘Vet: M.-A. 1241 !%l, 1954. 74. Bell, W. B.: The Relative Toxicity of the Chlorinated Naphthalenes in Experimentally Produced Bovine HvDerkeratosis. Vet. Med. 48: 135, 1953. 75. Sikes, D., and Bridges, $: E.: Expekmental Productioi of Hyperkeratosis (X-Disease) of Cattle With a Chlorinated Naphthalene, Science 116: 506, 1952. 76. Bell, W. B.: The Production of Hyperkeratosis (X-Disease) by a Single Administration of Chlorinated Naphthalenes, J. Am. Vet. M. A. 124: 289, 1954. 77. Greeorv. R. P.. and others: ExDerimental Production of Bovine HvDerkeratosis With a -F%d Coicentrate Exposed to Vapors of a Highly Chlori&& Naphthalene, J. Am. Vet. M. A. 125: 244, 1954. 78. Mostafa. M. S. E.: A Case of Malignant Melanoma in a Bay Horse, Brit. Vet. J. 109: 201; 1953. 79. Cotchin, E.: Spontaneous Sarcomas of Bone of Dogs; 30 Cases, Brit. Vet. J. 109: 248, 1953. 80. Nielsen, 5. W., and Holzworth, J.: Visceral Lymphosarcoma of the Cat, J. Am. Vet. M. A. 122: 189, 1953.