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Comparative pathology of oral neoplasms
COMPARATIVE
PATHOLOGY
OF ORAL NEOPLASMW
T
HE comparative method has been effectively used to investigat,e the normal anatomy and physiology of oral st ruc+urcs. Except for work with domestic animals very little has been done toward establishing a comparative pathology of diseases affecting the mouth. It is the j)urpose of this brief review to call attention to the spontaneous ol’ill neol)l;lsnls fountl in the tlifterent classes of vertebrates.
Fishes+ Benign
Epithelial
Tumors.-J’al)il
lolltas arc the nlost frequently observed oral neoplasms of fishes. A cursory inslwtioll of the fish in ;III~ large munici1~1 aquarium will usuallyrcvclal f;lirIy l;~r~g(~masses on the snouts of several specimens, particularly those that. have Iwen in caaptivity for several years. The tumors were probably initintc(1 1)~ rrl)eat4 trauma against the glass L\s pointctl out by Nigrelli,“” ulcerated front or concrete sides of the tanks. lesions often appear on 011~ or both lij)s of these fish. Although healing coltimanly occurs, repeated tl*i\Llilla ltatls to hyperplasia which 111ay cventuntc in the formation of a true neoplasm. Sigwll i rel)orts the owurrrnce of pupillomas in the climbing I)erch .~lnc~Oaswnntlens in which the epithelial elements of the tumors were mucous cells, and in the dwarf gourami Colisn 7aPi?L4”~4i A good example of a papillonm is that. on the rock bass A>&o#is ?,ul>estri~ shown in Fig. J. This fish was kept. as a pet in an Ohio hatchery for many years. The tumor grew slowly and (lid not interfere with the normal activitl\ of the animal. Histologically it was cwnposetl of f’usi form epithelial ~11s sup ported by a delicate connective tissue stronra. Benign epithelial tumors may owasionally be observed on the snout 01 than those large goldfish Cwussius nurcl2zcs where the>. appear less papillary Inore compics ant1 COIIof the rock bass (Fig. 2 1. The tuulor is histologically tains mucous as well as pavement. cpithclial c.ells; the fatter Inay form structures that resemble t,he epitheliitl pearls of marnmali;~n tumors. Careful search failed to reveal thr presence ol’ nryxosporidia which in some fishes may produce marked epithelial hyperpl:lsi;l t~csenlbling a I)enign neoplasm.“” In the Mosel River of C!ern~ntly, licyssclitz”” obscwed that many of the barbels Bcrrhs fhvintinlis bore pea-sized papillary tumors on their lips. The neoplastic epithelial cells were unusual in that many contained one or more cytoplasnlic inclusions that the author likened to those found in some virus
Fig.
Fig.
Fig
6, Section of the papilloma showi] wz Fig. 1.-A, Rock bass bearing a yayillurna on snout. ( Magniflc a.neoplastic stratIfled transitional cell epithelium suuuorted by a vascular stroma. tion, X 260.) Fig. 2.-A, Head of goldflsh with a. flattened 3 by 2 by 1 cm. papillama between WC? ~1nd ,1e Injury to the eye is commcm in the goldfish and in this case had no demonsWat :1y %?il&x to the tumor. B Section of the papilloma. On the left is the free surface immediate beneath which are two c&e&ions of concentrically arranged epithelial cells resembling “peal .,” formations. The bulk of the tumor is composed of pavement epithelium and mucous cells wi th (Magnification, x 12 0. ) a delicate vascular stroma. Another histologically similar tumor w as Fig. 3.-A, Neurilemoma on snout of goldlUsh. B, The nuclear palisading characteristic of this tumor is well shorn r”. present in the tail. (Magnification, X120.)
3.
1080
H$NS
G.
SCEILURIBERGER
diseases. Papillomas were reported on the lips of the stint &,zerus eperlalzus caught in the brackish waters of an ilrlct of the Baltic Sea. Breslauer” described them as cauliflower-likr growths that occasionally were as large as the head of the affected fish. Hist,ologically thry showed a typically papillomatous structurc with no tendency to invade. In 1912 Johnst.one:” found an irregrllar papillary growth on the snout of a 120-pound halibut Elil)lqAossr&s hippoglossus. Histologically the bulk of the tumor was made up of proliferat~in, 0’ connective tissne of the corium wit,11only slight hyperplasia of t,lle overlying epithclium. Thomas and Oxner”” report thr occinrcnce of a papilloma on the lower lip in each of 3 eels Anguilln vrclgnris.
Malignant Epithelial Tumors.--The lips and oral mucosa are the most common sites of carcinoma thus far recorded in fishes. The benign or malignant character of some (Jf the epithelinl tumors is diflicult to determine. The absence of met,astasis is not significant because this mode of spread is such an uncommon occurrence in fishts, even lvhere the histologic appearance and local invasion of the tumor indicate it,s malignant character. The first epidermoid carcinoma reported in a fish was observed on the lips of a catfish Ictalzmrs catm by McFarland in 1901.4” Many years later Dr. Balduin Luck6 and I”” collected nea.rlp 200 specimens of the catfish Anzeiurus nebulosus that bore tumors very similar to those in the fish described by MeFarland. The majority of the tumor-b,earing catfish were taken from the Schuylkill and Delaware Rivers near Philadelphia. The neoplasms were often multiplt~ and usually arose from tht: dental plates just inside the mouth behind the lips. Occasionally they formed large fleshy masses that int,erfered with clos~~re of the mouth, but metastasis was not observed. In the large neoplasms there was moderate cellular pleomorphism ; keratinization, which does not occur normally in the skin of this species, was absent. Histologic sections occasionally showed in\:asion 01’ thr underlying tissues. The degree of autonomy achieved by these tumors is indicntctl by their growth after transplantation to the cornea or ardel+ior chamber of the eye in other catfish. Frequently tumors developed on the oplmsitc dental plate, in apposition wit,h the first tumor. It was possible by direct microscopic observation of these appositional lesions to follow the early changes, particularly capillary ectasia, that occurred during the initial stages of t,amor growth. Epidermoid carcinomas have also been reported on the lips of 2 tenth Tinca tinca,1g a barbel Bclrhus ,~wlgwis,,~~a whiting Merlangus vlerlangus,33 a codfish Pollachius Gw~s,“7 and 2 croakers Pogonias chronGs.3 MazzarellF described a 4.5 by 3.5 cm. tumor that arose from the oral epithelium of the fish Chondrostonza soetta. Only two cases of adenocarcinoma of the oral tissues are on record. TakahashiG3described a t,umor that arose at the left angle of the mouth and extended onto the skin of the cheek in a coalfish, Theragra chakogranzma. The neoplastic cells formed alveoli ant1 invaded adjacent &sues. A tumor that arose from venom glands in the palate of a moray Muraena helena and showed extensive Of interest is the observation that local invasion was described by Ladreyt3*
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASM8
1081
the secretion of the neoplastic glands produced similar, though diminished, physiologic response. Jn fishes the thyroid gland is rather diffusely scattered over the floor of the mouth; enlargements of the gland form distinctive intraoral swellings. Goiter in fishes, with particular reference to the occurrence of adenocarcinoma, has been reviewed elsewhere.58 Neoplastic growth of the thyroid in an inbred laboratory strain of the small tropical swordtails Xiphophorus montezumae was recently reported by Berg and associates.4 The tumor cells destroyed the deeper musculature, gill filaments, cartilage, and bone. Death was possibly due to destruction of the visceral gill arches and the consequent interference with normal respiration. Tumors of Dental Tissues.-Only four examples of dental tumors in fishes have been reported; three are identified as odontomas, one as an ameloblastoma. In 1912 Plehns2 described multiple odontomas in two brook trout. The oral cavities were almost filled by partly confluent nodular massesthat arose from all the tooth-bearing surfaces, viz., both dental plates, the hyoid bones, and, in one case, the vomer. The tumors had become so large that they interfered with feeding. Histologically they were composed of atypically formed teeth. Roff o,~* one of the pioneers of cancer research in Argentina, made a careful study of an odontoma that occurred on the upper dental plate of a marine fish, the croaker Micropogon opercularis. The 3 by 2.5 by 2 cm., faintly lobulated, firm, gray-pink tumor arose from the mid-center of the maxilla and partly obstructed the mouth. A roentgenogram of the head showed numerous radiopaque masses scattered throughout the tumor. Histologic sections disclosed toothlike structures composed of dentine covered by a layer of enamel and embedded in a dense connective tissue stroma. An ameloblastoma was found in a haddock Melanogrammus neglifinus and measured 2.5 by 1 cm. ThomasG4observed that it had infiltrated the maxilla and protruded into the oral cavity. Although the figures are poor, its histologic appearance resembles that of the cystic ameloblastoma of man. Tumors of Mesenchymal Tissues.-Of the tissues usually placed in this category only the connective tissue proper, bone, cartilage, and blood vessels have been the source of oral neoplasms in fishes. The single reported case of an oral fibroma was described by Fiebigerlg as arising from the oral mucous membrane of a codfish Pollwchius virens. It was approximately 2 cm. in diameter and consisted of bundles of connective tissue covered by epithelium. Multiple tumor nodules identified by Johnstone3* as sarcomas of “mixed cell type” were present in the mouth and about the left orbit of a codfish. In another codfish the same autho?* found an 8 cm. fibrosarcoma that arose from the median aspect of the mandible and invaded the soft tissues of the mouth. Takahashis3 reported a 7.5 by 3 cm. fibrosarcoma in the pharynx of a Japanese bass Lateolabrax japonicus. Chondromas have been found twice in the mandible of fishes. In 1917 Surbecke2 found a bilobed tumor measuring 1.5 cm. in diameter, composed of cartilage, and arising from the posterior portion of the mandible of a barbel
1082
HANS
G. SCHLUMBERGER
Barbus fluviatialis. And&’ reported a minnow Phoxinus sp. that had a peduneulated mulberry-like mass attached LO the tip of the mandible ; the weight of the tumor bowed the head. IIistologically it consisted of hyaline cartilage. Recently Nigrelli and G ordon4” described an osteochondroma that involved the operculum as well as the inferior part of the cheekbone and maxilla of a jewelfish, Hemichromis bimuculn tus. although osteomas have been frequently reported in fishes, involvement of the jaws is uncommon. !)f the four on record Bland-Sutton” reported two in 1885. One occurred on the dental plate of a pike Esox lucius; the other was a disk-shaped tumor two inches in diameter and half an inch in thickness on the maxilla of a codfish Gadus ~zorhua. WilliamsC7 described a 5 by 2 cm. osteoma on the anterior portion of the left premaxilla of another codfish. Among 500 specimens of Pagrosomus major, a common food fish in Japan, KazamzQ” found one with a 1.5 cm. nodular ostcoma of the mandible. Marianne Plehn”’ reported an extensive hemangioma of the head in each of 3 sticklebacks Pungitius pungitiw. The dark red tumors spread from thcl ventral surface of the head to the angle of the mouth, involving the lateral margin of the lips and a portion ol‘ the operculum. Tumors of Neuroectoderm.---It is now fairly will established that t,he pigment cells of fishes have their or&ill in the neLu~oectodern1 that forms the ‘I’ntllors of pigment cells, particularly those madtl embryonic neural crests. up of melanophorcs, are cluite common in fisheP and hare been the subject of intensive study with sl)t~cial emphasis on theil genetics. However, except for the following report-, none has l)ten observed in th(l oral tissues. Recently Ronlet”” published an accaount of a ttisease that occurred in ~1 group of t,ropical aquarium fish G~))lnoco~1~))t6us t~~rtzi. Virst, to appear was a dark discoloration oi’ the lips, followctl by tmnefac+on. The dark color was due to large cells that coI~t:G~led melanin pigment and which the author COD siders are malignant. The cells invaded the soft tissues of the head, often producing an exophthalmus l)y the fortllation of tumor masses in the orbits. Roulet ground ~111 some of the tissue and was able to observe tumor formatiotl at the site of inoculation in healthy fish. E’nrthertnorc, normal fish of the same species, when placed in the tank with diseased fish, developed similar tumors. Hecause inflammation is often associat cd it1 fishes wit,h the local :~.~curnnlatior~ of pigment cells, the possibility t,hat this has occurred here atl(1 that the lesiotr is a chronic inflammatory response to an infections agent must be carefully ruled ont. IVeurogenic tumors involving oral structures have not been reportetl in fishes. However, while studying multiple nerve sheath tumors in goldfish.“7 I observed several instances in which one of the neoplasms involved th(I I’(‘The growths were lobulated, orange-yellow, gion of the snout (Fig. 3, A). IIistologically they soft in consistency, and bled profusely when injured. closely resembled the neurilernomas found in man. The loose aggregation of stellate cells characteristic of the Antoni type 1: neurilemoma was often associated with areas identified as type A, in which the cells were compactly arranged and the nuclei offered striking examples of palisading (Fig. 3, B j .
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1083
Amphibians Tumors in frogs, toads, and salamanders are rarely reported in the literature.58 In some measure this may be attributed to the fact that unlike the fishes they play a very minor role as a source of human food; furthermore, when compared with the other classes of vertebrates, their absolute number is small. Only a single oral neoplasm has been reported in an amphibian. In 1902 Vaillant and PettiF6 briefly described a tumor that they found in the EuroThe growth was a fibroma which arose in the pean edible frog Rana esculsnta. buccal cavity and protruded from the mouth.
Reptiles There are over 20 reports in the literature of tumors in turtles, crocodiles, lizards, and snakes.“* Oral structures were the primary site of the lesion in 4 instances.
Fig. 4.-A, Oral cavity of a lizard, the tegu. showing bilateral squamous cell carcinomas that arise from the gingiva and partly cover the teeth. 1.5 x natural size. (BY permission, Cancer Research.) B, Representative area of the carcinoma showing marked variation in size of the nuclei. A suggestion of “pearl” formation is seen at top center. (Magnification, X200.)
Bland-Sutton” observed multiple ene1~ondroma.sin a lizard, t.he Indian dracoena. Tumors were present in 2 vertebrae, both humeri, monitor Varanus and 2 metacarpals. The case is noted here because 4 enchondromas were also found in the hyoid hone. In the Philadelphia Zoological Garden, Dr. Herbert Ratcliffe observed a squamous cell carcinoma on the left upper gingiva of a large Mexican lizard,
1084
HAKS
G.
SCHLUMBERGER
the tegu Tupinambis nigr~opunctatus. When first seen the tumor measured 2.5 by 2 by 1 cm., but during the following year doubled in size. At that time a similar neoplasm appeared in the same location on the right side. (Fig. 4, 11.) Histologically the tumor was a fairly well differentiated squamous cell carcinoma showing occasional “pearl" formation and pronounced variation in size of the nuclei (Fig. 1, B). Dr. Ratcliffe and I made numerous transplant’s of the tumor to lizards, alligators, frogs, chicks, and even to rats, but, all failed to grow.5x The animal died as the result of an accidental injury. At autopsy the tumor was seen to invade locally, but no metastases mere found. Eall* report,s a remarkable instance of melanosarcoma arising in each of a mated pair of pine snakes Pituophis nzel~anoleucus. In t,he female the tumor arose on the trunk, but, in the ma.le it first appeared on t,he I.eft upper labia,1 fold. It grew rapidly and after eight months measured 4 by 2.5 cm. As ill the case of the lizard noted above, a second tumor appeared in the same location on the right gingiva and reached a diameter of 2 cm. before the animal was sacrificed eight months aft,er the first tumor was seen. ;Zt autopsy no metastases were found. I was privileged t,o examine the specimens and the histologic sections. The neoplastic cells are often arranged in bundles, and are of an c~longated spindle shape with large oval nuclei. Most of the cells contain melanin granules. A reticulated python Python reticulatus was observed by its keeper at the Philadelphia Zoological Garden to have a swelling in the right side of the upper jaw, and two black tumors on its body. When the animal was sacrificed a year later the tumor at the angle of the jaw measured 6 by 3 by 2 cm. and was only faintly pigmented; the overlying skin was intact. The two tumors on the trunk measured 2 cm. and 0.5 cm. in diameter, respectively, and were heavily pipmcnted. Attempts at transplantation were unsuccessful. I )rs. Tiucl~6 and Rreedis identified the t,umors as nonmalignant melanomas.“’
Birds ,211existing species of birds are toothless, but some fossil birds possessed well-developed teeth. Rudirnents of teeth have therefore been sought in the embl*yos of existing birds. An ectodermal ridge projecting slightly into the mesenchyme just inside the margin of the jaw is seen in the 6-day-old chick embryo. The same ridge, but better developed, has been found in the embryos of t,he tern and ostrich. T,illie3” believes that the ridge represents the \-~ry last vestige of the teeth. This complete absence of even rudimentary teeth or dent,al pa.pillae in birds accounts for the absence of tumors of dental origin in this class of vertebrates. The horny port,ion of the beak of birds has not been reported as the site of a neoplasm. Yet, overgrowth of the bill occurs frequently in some birds. Among parakeets the cause of the abnormality is not always due to a lack of That a neoplastic potential normal wear but rather to a dietary deficiency.” may reside in t,he bill is suggested by the nuptial wart horn that normally forms on the beak of the American white pelican and is cast when the bird
COMPARATIVE
PATHOLOGY
OF
OR$L
NEOPLASMS
1085
Few cases of oral neoplasm of any kind have been reported in birds despite the fact that thousands of chickens are examined by veterinary pathologists each year. In 7,408 autopsies on chickens Gossz2 found 1,332 cases of leukosis and 113 examples of other tumors, but none that involved the oral tissues. In their review of neoplastic diseases of the chicken, Feldman and Olson” mention the case of a pigeon with warty growths on the skin adjacent to the beak and around the eyes. Similar lesions have been observed in parakeets where some are due to the virus of bird pox, others to vitamin deficiency.18 The occurrence of nonriral papillomas on the combs and wattles of chickens has been reported.17
Fig. 5.--A, Ventral aspect of parakeet head. removed. A hemispherical tumor (arrow) arising the skull and invaded the oropharynx. Removal of adjacent to the first, lying in the orbital cavity mophobe cells of the pituitary comprise the bulk
The lower jaw and zygomata have been in the pituitary has penetrated the base of the soft tissues has revealed another tumor B, Neoplastic chrobehind the right eye. of the tumor. (Magnification, x500.)
Only 5 intraoral tumors were found in a cursory review of the literature; all were squamous cell carcinomas in chickens. PickSo reported an epidermoid carcinoma that arose in the floor of the mouth and destroyed the mandible. Joest and Ernest?O described a similar case in which the tumor had infiltrated the larynx. In an g-year-old Erahman hen, Koch3’ found a squamous cell carcinoma of the roof of the mouth. It had spread to the pharynx, completely filled the larynx, and deeply invaded the neighboring st.ructures. Jacksonzg observed a 5 by 4 cm. ulcerated tumor that invaded the full thicknes of the pharyngeal wall. Although some areas were histologically of squamous cell type, he prefers to classify the neoplasm as a transitional cell carcinoma. Another tumor of the pharynx, identified as a squamous cell carcinoma, was seen by Feldman and O1sonl’ in a 2-year-old hen. The carcinoma had infiltrated the adjacent tissues, but no metastases were found. In parakeets Melopsittacus undulatus I have recently seen two cases in which adenocarcinoma of the pituitary body had invaded the roof of the mouth and presented as a mass in the oropharynx (Fig. 5).
1086
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G.
Captive
SCHLUMBERGER
Wild
Mammals
D;Lt:l 011 tumors in Is ;I1’t’ \-et’). sc*;lIlt,y. l)ul the larger zoological gardens lmblish af~flilill 01’ i trl~~\.;~ I r(il)orts of tlis~asrls causing death itm0ng their captive xvil(l illlilllillS. Over a periotl of i11i11iy \cars af the I’hilaclc~lphia Zoological Gat*(lens, Of 1~‘os”” found only t,wo instances of or;11 trunors ilt the ma~nmals exhibited. these one was a squamous cell carcinoma of the tongue in a black bear Ursus antericanus; the other was an osteofibroma of the jaw in a gazelle, Gazelln iscrbella. During the following ten years at, the same institution (1923 to 1933) Ratcliffes3 encountered no additional instances of oral neoplasm, although many tumors were found at other sites. In a personal communication Dr. Ratcliffe stated that, he has seen two iristances of oral cancer in the period 1933 to 1953. A very old badger I’asid~cr tazus developed a S~L~II~OLIS cell carcinoma of the lip which also invaded the gingiva and mandible. ,\t, autopsy a Japanese bear T’I.SU.S,japonicxs that had been in the Philadelphia Zoo for over thirty years was found to have widespread metastases of melanosarcoma. Several metastases wcrc prescrit in the tongue; the primary site could not be identified. IIuring the years 19% to 1957. only four oral neoplasms were enconnter~tl I,- the pathologists at. the Zoological (hardens of Tdonclon. Of t,hese, two were fibrous epulides and two were squamous cell carcinomas. A pygmy mongoose Heloyale waGz4 died ol’ inanition resulting frorn several epulides that arose on the gingiva of both ;j:l\vs and prevented closure of the mouth. A Canadian heaver Custer cnnrrrrliensis'"" became markedly emaciated when 3!4 years old. A fibrous t,umor the size of a walnut was found growing from the periosteuni and periodontal membrane of the left ramus of the mandible. Of the t,wo squamous cell carcinomas, one was found by Scott?’ on the right t,onsil of a wolf (‘Ia11z’s 7ul)u.s. The tonsil was almost replaced by an ulcerating tumor that infiltrated t,hc nc+hboring tissues and had metastasized to the I’(‘gional lymph notlcs. The second instance of oral cancer seen at the London Zoo was a poorl) diffcrentiatcd squamous ccl1 carcinoma on t,he floor of the mouth in a rhesus monkey Macaca nlulatttr. A small ulcer was first noted beneath the tongue near the I’renulum. This grew rapidly in size and after four months involved the entire floor of the mouth in front of the tongue and extended into the gingiva about both canines. At, autopsy the mandible and salivary glands were infilt.rated by the tumor which had also metastasized to the regional lymph nodes. Zuckerman,Y’l reporting this case in 1930, observed that he had been unable to find a previous record of oral cancer in a rnonkey or ape. He added t,hat a dead orang-utang had been brought to the zoo with gross findings simiTJnfortunately, the absence of any history lar to those seen in the monkey. and preclusion of histologic study by t,he state of decomposition in which the material was received did not allow a definitive diagnosis. Squamous cell (~av.4~tc)tna of the tongue in each of two monkeys was deThe animals had been kept in a laborascribed by Steiner and associates.“’ tory color1y for many yraw. One IviIs a l&year-old male rhesus monkey that I'rl'il
liltltli
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1087
bore 2 lingual tumors. Of these, one was an ulcerated lesion measuring 2.3 by I..1 cm. on the lateral border of the tongue near the base; the other, on the ventral surface left of the frenulum, was a sessilepapilloma t,hat measured 9 by 7 mm. Histologically both were squamous cell carcinomas. No metastases were present. The second animal was a male Java monkey Macaca irus aged 14 years. It had an ulcerated carcinoma at the base of the tongue that extended posteriorly to the epiglottis and laterally over the pharyngeal walls and the adjacent hard and soft palates. Microscopically the lesion was classified as an undifferentiated squamous cell carcinoma. The authors also saw histologic sections of a lingual carcinoma in a macaque from another colony.
reflected mandible y;;logY).
Fig.
.
6.-A,, Head revealmg an and destroyed B, Section (Magnitlcation,
of a baboon. The angle of the mouth has been incised and the lips extensive carcinoma of the lower gingiva. The tumor has invaded the considerable alveolar bone (Courtesy Armed Forces Institute of of the poorly differentiated squamous cell carcinoma invading adjacent X 240.)
Together with Dr. Henry Goldman I examined a b.aboon at the National Zoological Garden in Washington, D. C. The keeper had not,ed that for several weeks the animal had experienced difficulty in eating. At the time of our visit the baboon appeared listless and was obviously in pain. Streams of ropy saliva drooled from its mouth. The animal was sacrificed and dissection carried out at the Armed Forces Institute of Pathology. An extensive carcinoma of the left gingiva was found. It had destroyed so much alveolar bone that several teeth were loosened (Fig. 6, a). The tumor invaded the mandible and the floor of the mouth and had metastasized to the regional lymph nodes. IIistc~logically ii, was a poorly differentiated squamous cell carcinoma (Fig. 6, B). Tumors of dental origin are occasionally reported. Dentigerous cysts, although not true neoplasms, may be mentioned; 3 were found at the London ualabatus, 26the Patagonian cavy DolichZoo, one in the black wallaby Macropus otis nzagellanica,25 and the viscacha, Lagostomus maxinl?Ls,2”a relative of the chinchilla. In every instance the cyst was found in the mandible. Bland-
1088
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SCHLUMBERGER
Sutton: states that odontomas have been observed in the marmot, porcupine, agouti, boar, and elephant. Moodie,“” on Plate 46 of his monograph on palcoI)at,hology, depicts a lesion that may be an odontoma in the basal portion ot an elephant’s tusk. Also illustrated on this plate is the tooth ol’ a c~achalot Lvhale with large “ csosl oses of dentine. ’ ’ Xot true neoplasms, such lesions are commonly seen on the 1.oot.s of Ihe teeth in these whales. They l,rolx~l~l,v represent hypcrcelncrltosis which occasionally reaches proportions comparabl(~ to that of the cementomas in man. Similar excrescences were noted by Moodir on the fossil tooth of a Pliocene camel from Nebraska. LZnother lesion that has been reported by I)aleopathologists4”j G’ is a remarkable overgrowth of the facial atltl jawbones of mummified baboons Papio hn??zndrlJas from Egyptian tombs. The lesion has been identified as Paget’s disease ; hov;cver, it closely t~cstmblcs the leontiasis ossea observed in monkeys on vitamin-deficiciit, tlicJts.28 It w:x also seen in a baboon from the colony kept. at the Idildon Zoological (lardens.
Domesticated
Mammals
Widely scattered throughout the literature of many countries are single case reports of oral neoplasms observed by the practicing veterinarian. Here only a representative sample of the tumors encountered will be given (Table I). The largest number of neoplasms have been found in the dog, a fact that, is explained in part by the longevity of the dog when contrasted with food animals such as cattle, swine, sheep, and goats. When compared with the horse t.he greater number of t,umors found in the dog may be attributed in part at least to its overwhelming numerical superiority. However, this factor cannot be so significant when the dog is compared with the cat. One of the most striking esamplcs of oral neoplasia encountered in an> animal is the viral papillomatosis of dogs (Fig. 7, A). The lesions are multiple and involrc any part of the oral mIIcosa and tongue, occasionally even estending onto the snout. Histologically the tumors arc composed of massed epithelial cells, showing progressive keratinization as the!. approach the free surface (F‘ig. 7, I: and C). The broad base is composed of vascular connective tissue. DeMonhreun and Goodpa,stnre’5 descril)ed basophilic intranuclear bodies, similar to the Tdipschtitz bodies of human warts, in a few of the large epithelial cells of the older lesions. These investigators I)roved t,he infectious nature of the disease and found that practically all puppies are susceptible. The average incubation period is from thirty to thirty-three days; pupljies that have recovered a.re immune to reinfection. The disease is easily transmitted by means of a Berkefeld filtrate obtained from the papillomas. The deep pigmentation frequently observed on the lips, oral mucosa, and tongue of (logs may account for the high incidence of melanosarcoma in these Tn the I)epartment of Veterinary Pathology of the Ohio State llnitissues. versity, I)r. C’larence (.‘olc found that the pigmented tumor was more frequently observed during the past ten years than was squamous cell carciCole also encountered melan0sarcoma twice in cats; in ofie instance llotna.l’
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1089
the tumor arose on the gingiva, in the other on t,he palate. Despite the prevalence of melanosareoma. in horses, the tumors are seldom primary on the oral mucosa. Although squamous cell carcinoma has been seen to arise from all free surfaces in the mouth of dogs, involvement of the tongue is comparatively less common than in other domestic animals, particularly the cat. On the other hand, recent work by Withers68 would show that squamous cell carciIt is of noma of the tonsil is one of the most common of canine oral tumors. interest that in 1928 when ScottGo reported a carcinoma of the tonsil in a wolf he was unable to find a recorded instance of another such tumor in any animal. Eleven years later Withers reported that during a five-year period in London he had collected 40 histologically proved cases in dogs, but believed that over twice that number had been seen and diagnosed at the Royal Veterinary College. In 16 months 24 cases were autopsied; the average age was 9 years; metastases were found in the regiona. lymph nodes and lungs.
gingiva, nance tumor
Fig.
7.-A, Dog with viral papillomatosis. hard palate, tongue, and even nose. of epithelial over connective tissue showing hyalinization and keratinization
Lesions Single elements. of epithelial B,
are seen on the lips, buccal mucosa, small papilloma; note the predomi(Magnification. x 10.) C, Detail of cells. (Magnification, X280.)
Adenomas and adenocarcinomas arising in the major and minor salivary glands have been reported in the dog (Table I) but are rare in other animals. A mixed tumor has been seen in the dog by Mulligan44 and a papilloma of the parotid duct by Goodpasture.*l Tumors of dental origin are uncommon in domestic animals. Mulligan44 described an ameloblastoma in the mandible of a dog; histologically it was similar to those of man. In a group of 79 mice with an hereditary tendency
Maxilla
&lIldS
Salivary
Palate
Tonsils
Tongue
Gingiva
Fibroma Fibroma Papilloma
Oral mucosa
(many)
Rq.
carcinoma
Sq. carcinoma Sq carcinoma Sq: carcinoma Melanosarcoma Xelanossrcomn Myxosarcoma ndcrloma hdenocarcinorna Sq. carcinoma Melanosarcomn HII:ll,~lom~yor;:~lcol~l~
Papil onra (2) Sq. carcinoma
Melanosarwm;l Aq. carcinoma .-\drnocarcinoma
SITE
Lips
---
(2)
(3 j
(2 ) (6)
and
(6 j *
DOG
BOUC&
COlC
Ruddick Wilis Withers Colt
Mulligan
and
Mulligan Jackson Cole Mulligan Cole Feldman Cole Mulligan Cadiot Cole Mulligan
Feldman Cole DcNonbreun Goodpasture Cole Cole
Colt
Colt!
Colt
---
I
Sq. Sq. Sq.
carcinoma carcinoma earcirwmn
Mclnnosarcoma
___-.CAT
(2;
Cole
Cadiol Feldman Cole
Cole
__._____~____
.~____~ 1
Sq. carcinoma Wq. carcinoma M~sosarcoma
Sq. carcinoma Fibrosareoma Fibrosarcoma Hcmangioma
Hemangiomn
(3)
(3)
HORSE
Cadiot IIenson Feldman
Cole Cole Feldman Feldman
Feldman
I
Sq. carcinoma Fihroma
cow
Cadiot Feldman
4
z $ u:
s
z
COMPARATIVE
PATHOLOGY
Fig.
Fig.
OF
ORAL
NEOPLASMS
1091
8.
9.
Fig. S.-Complex compound odontoma of a horse. Notable are the intertwining roots, of which (top, right) lies horizontally. The cross sections of many abnormally formed are visible on the occlusal surface. (Courtesy Armed Forces Institute of Pathology.) Fig. 9.-A, Muzzle of a pony. A flbrosarcoma is seen arising in the lower gingiva and involving the entire chin. B, Neoplastic connective tissue cells arranged in noorly formed bundles: a moderate number of capillaries are present. (MagniAcation, x 225 ; reduced $6.) one teeth
1092 to tumor
HANS
formation
Zegarelli””
G.
SCHLUMBERGER
found
LO3 lesions that he identified
as amelo-
idast~ornas. Some 01: these wre odontogenic cysts which he believes arc stage.3 in the development of the tumors.
In their rat colony Bullock and Curtis I” found two animals each bearing arr odontoma in the mandible. I:urn and associates” studied the development of odontomas in the incisor teeth of rats on a dirt low in vitamin A. The tumors consisted chiefly of spindle cells similar to those of embryonic pull) tissue ; odontoblasts and epithelial cells were scattered throughout the growtl1s. &hour and associateP have described pseudo-odontornas in t,ha r;rt. They regard the lesion as a dental hamart~oma. A large odontorna from a horse was described by I:land-Sutton.” I founcl another large complcs compound odontorna frorn a horse in the collection oi the Armed ~~‘OIWS Ittstitkrte of Pathology. The tumor weighed orer a pound irrld was made up 01’ rnalfornlcd cvmjoittetl teeth arranged at ha~haz;~rd (Fig. 8). M:rrly of the abnolnral teeth wew sufYiciently well orientecl to l)t*ovitlc ;I f;r irly ::;lti:;filctOl’~ O('(dlUSil I surface. 1Icman:;iornas of tlr(l lips and of the gingiva in horses have been sported by I~‘eldman.lG Other oral tumors of n~esenclrymal tissues are a rhabdomyosarcoma of the tongue”” and myxosarcoma of the gingival” in the dog. Myxosarcoma and fihrosarcoma have also been found in horses on the tongue and gingiva, respectivcl\- (Table I). Through the courtesy of Dr. Cole, T was able to examine a case of fil)IYWLYTOllliI in a pony. The tumor arose on the gingiva and prcscnted as a 6 cm. hrmispheric;~l mass at, the midpoint of the lower jaw (Ii’ig. 9, A). Rocntgenograms slrowed that the tumor had deeply invaded the r;lt:ndible. Histologically it was composed of large spindle-shaped cells loosel> artwrgcd in bundles (Fig, 9, E) ; occasional17 the cells were more nearly stellatc and the tissue assumeda myxomatons character. Benign and malignant tumors of bone have been found in the jaws of rnost domestic animals (Table I). The frequency of these lesions in the maxilla as Feldmanl” mentions an cont,rastcd with the nrarrdiblc in dogs is noteworthy. osteogenic sarcoma of the maxilla and one of the mandible in sheep. The sarnc irntlror* statcs that, ostconlas irr’c common in mules where they OCCUR ;IS project,ing or even pedunculat~cd rrrassesattached to the mandible.
Conclusion :I large variety of oral tumors, representing the majority of those ohserved in man, hare been found in fishes and domesticated mammals. A good 1)eginning has been rn:~tlc in the collection of cases among captive wild mammals, and here also the similarity to Ihe human neoplasms is striking. In alnphibians, wptiles, ant1 birds the numbrr of cases available for study is still very small.
References 1. Andrb,
IX.: 1927.
Sur un chondrome (Cited by Tomas,
du vairon. Bull. I>.:
Bull. Assoc.
Suisse franc.
and Rhabdomyoma 6: 134-138, 1946.
in
P&he et Pisciculture, p. 1’6tude du Cancer
28: 21:
177-178, 537-546,
1932.)
2. Ball,
H. A.: noleucus,
Melanosarcoma Cancer Research
Two
Pine
Snakes,
Pituophis
mela-
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1093
3. Beatti, 4. Berg, 5. 6. 7. 8. 9. 10. 1 I. 1%. 13. 1-l. I,?. 16. 17. 18. 19. 30. 21.
M.: Geschwiilste bei Tieren, Ztschr. f. Krebsforsch. 15: 452491, 1916. Olga, Edgar, Martha and Gordon, M.: Progressive Growth Stages in the Development of Spontaneous Thyroid Tumors in Inbred Swordtails Xiphophorzcs montezzLmae, Cancer Research 13: l-8, 1953. Bland-Sutton, J. : Tumours in Animals, J. Anat. & Physiol. 19: 415475, 1885. Bland-Sutton, J. : A Very Large Odontome From a Horse, Tr. Odont. Sot. Great Britain 23: 215, 1891. Bland-Sutton, J. : Tumours, Innocent and Malignant, Chicago, 1907, W. T. Keener and co. Boucek? Z.: Mittheilungen ueber 35 histologisch untersuchte Ticrgeschwiilste, Arch. wiss. u. prakt. Tierheilk. 32: 585-600, 1906. Zur Kenntnis der Epidermoidalgeschwiilste von Kaltbliitern, Arch. f. Breslauer, T.: mikroskp. Anat. 87: 200-264, 1916. Bullock, F. D., and Curtis, M. R. : Spontaneous Tumors of the Rat, J. Cancer Rcsc:trcl~ 14: l-115, 1930. Development of Tumors in Incisor Teeth Burn, C. G., &ten, A. W., and Smith, A. H.: of Rats on Diet Low in Vitamin A, J. D. Res. 16: 317-318, 1937. Cadiot, M. : Sur le cancer de la langue et celui des levres chez les animaux, Bull. Acad. de med., Paris 81: 218-223, 1919. Recherches Experimentales sur les Tumeurs Malignes, Paris, 1910. (Cited by Clunet, J.: Wolff, J.: Die Lehre von der Krebskrankheit 3: 283-316, Jena, 1913, Gustav Fisher.) Cole, C. R.: Personal communication, March, 1953. DeMonbreun, W. A., and Goodpasture, E. W.: Infectious Oral Papillomatosis of Dogs, Am. J. Path. 3: 43-55, 1932. Feldman, W. H.: Neoplasms of Domesticated Animals, Philadelphia, 1932, W. B. Saunders Company. Feldman, W. H., and Olson, C., Jr.: Neoplastic Diseases of the Chicken, in Diseasrs of Poultry, ed. by Biester, H. E., and Schwarte, L. H., Ames, Iowa, 1948, Iowa State College Press. Diseases of Budgerigars, All-Pets Magazine, Fond du Lac, Wis., 1951. Feyerabend, Cessa: Fiebiger, J.: Ueber Hautgeschwiilste bei Fischen nebst Bermerkungen iiber die Pockenkrankheit der Karpfen, Ztschr. f. Krebgforsch. 7: 165-179, 1909. Fox, H.: Disease in Captive Wild Mammals and Birds. Philadelphia,_, 1923, , J. B. Lippincott Company. An Anatomical Study of Senescence in Dogs, With Special ReferGoodpasture, E. W.: ence to Relation of Cellular Changes of Age to Tumors? J. M. Res. 38: 127-190, 1918.
22. Goss, 23. 23a. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35.
L. J.: The Incidence and Classification of Avian Tumors, Cornell Vet. 30: 75-88, 1940. Hamerton, A. E.: Report of Deaths Occurring in the Society’s Gardens During the Year 1932, Proc. Zool. Sot. Lond., pt. 1, 451-482, 1933. Hamerton, A. E.: Report on the Deaths Occurring in the Society’s Gardens During the Year 1934, Proc. Zool. Sot. Lond., pt. 1, pp. 443-474, 1935. Hamerton, A. E.: Report on the Deaths Occurring in the Society’s Gardens During the Year 1936, Proc. Zool. Sot. Lond., 107: series B., pp. 443-474, 1937-1938. Hamerton, A. E.: Report on the Deaths Occurring in the Society’s Gardens During the Year 1937, Proc. Zool. Sot. Lond., 108: series B., pp. 489-526, 1938. Hamerton, A. E.: Review of Mortality Rates and Report on Deaths Occurring in the Society’s Gardens During the Year 1938, Proc. Zool. Sot. Lond., 109: series B, pp. 281-327, 1939-1940. Henson. W. R.: Carcinoma of the Tonaue in a Horse. J. Am. Vet. M. A. 94: 124. 1939. ---I --.-Howe, P. R.: Cited by Thoma, K. H.7 Oral Pathology, ed. 3, See esp. Figs. 12G and 127. St. Louis, 1950, The C. V. Mosby Company. Jackson, C.: The Incidence and Pathology of Tumours of Domesticated Animals in South Africa, Pretoria, 1936, Govt. Printer. Untersuchungen ueber spontane Geschwiilste bei VGgeln, Joest, E., and Ernesti, S.: mit besonderer Beriicksichtigung des Haushuhns, Ztschr. f. Krebsforsch. 15: l-75, 1916. Johnstone, J.: Internal Parasites and Diseased Conditions in Fishes, Proc. and Tr. Liverpool Biol. Sot. 26: 103-104, 1912. Johnstone, J.: On Certain Parasites, Diseased and Abnormal Conditions in Fishes, Proc. and Tr. Liverpool Biol. Sot. 34: 120-129, 1920. Johnstone, J.: Diseased Conditions in Fishes, Proc. and Tr. Liverpool Biol. Sot. 38: 183-213, 1924. Malignant and Other Tumours in Marine Fishes, Proc. and Tr. LiverJohnstone, J.: ~001 Biol. Sot. 40: 75-98. 1926. Kazama, Y.: Einige Gcschwiilste bei Fischen (Pagrus major et Paraliohthys olivaceus), Gann 18: 35-37, 1924.
109-C 36. 37. 38. 39. 40.
41. 42. 4::. 44. 45.
46.
HASS
G.
SCHLUMBERGER
Keysselitz, G.: Ueber clin Epithelioma dclr Barben, Arcll. f. l’rotistenkuotlo 11: :izt;-3:;::, 1908. Koch, W. : Demonstration einigcl (~c’srIl\VCIste lwi Ti~~wn, vc~rll:rntll. rlontsvll. [‘:l’ll. Gesellsch. 7: 136-14;. 190-i. Ladreyt, F. : Sur un epithelioma rltx Ia llluyu~ww l)alatir~c~ cII(~/ ull murew / .If?o~cc, ,,(, helena), Bull. de l’lnst. Ocean (Monaco) 677: l-16, 1935. Lillie, F. R.: The Development of the Chick, ed 2, New lTork, 1930, .H(~lry Holt K; (:OIII. pany, Inc. Luck6, B., and Schlumberger, H.: Transplantable Epithr~liomns 01 the Lip and Jloutli of Catfish. I. Pathology. Transplantation to Anterior Ch:\ml~~~r of E:yl> anll I111 0 Cornea, J. Exper. Mrcl. 74: 397.408, 1941. Mnzzarelli : Epithelioma of the Mouth of f‘lzondwstnwa soctta (cittxl by ‘l’ho~nas, I,.: Bull Assoc. franC 1’. 1 ‘etude clu Cancer 20: iO3-760, 1931). McFarland, J. : Epithelioma of the Mouth and Skin of :I Catfish, l’roc. I’ath. S:oc,. Philadrlphia 4: 79-81, 1901. Moodi?, R. L.: Paleopathology. An lnirotluct ion to tlw Study of ~\urii~ut ~;vi~lr~rw~ IIE Dw,case, Urbana, 1923, University of Illinois Press. Mulligan, R. M.: Neoplssms of the Dog, Baltimore, 1949, \Villiam k \Vilkius (‘oml)an~, Nigrelli, R. F.: Prickle 011 Hyperplnsia in the Snout of the Redhorse Sucker, Xolostoma aurtolum, Associated JVith an Infection by the ,Mysosporidi:in Xyzoholsr:: mozostomi, Zoologica 33: 43-46, 194X. Nigrrlli, R. F.: Lip Tumors in Fishes Kcxpt iu Cal)ti\-ity, i’ancer Research .\lwt. 11: i'iL', 1951.
47. 48. 49. 50.
Nigrelli, It. F.: Virus and Tumors iu I<‘ishes, Ann. New Tork Acad. SC. 54: JO?&1092, 1952. Nigrelli, R. F., and Gordon, M.: Spontaneous Neoplasms in Fishes. I. Osteoc.lloll(lro111:l in the Jcwelfish, IIemichromis bimaculatw, Zoologica 31: 89-92, 1946. Pales, L.: Paleopathologie et Pathologie Comparative, Paris, 1930. Masson & <:icl. Pick, L.: Zur Frage vom Vorkommen des Carcinomas bei Viigeln: grosser Platteri. epithelkrebs des Mundhiihlenbodens bei einem Huhn, Berl. klin. \Vrlrnschr. 40: (i69670,
1903.
Ueber Geschwiilste bei Kaltbltitern, Ztsehr. f. Krebsforsch. 4: 525-564, 1906. Ueber Geschwiilste bei Kaltbliitern, Wicn. klin. Wchnschr. 25: 691-697, 191% H. L.: Incidence and Nature of Tumors in Captive Wild Mammals and Birds. J. Cancer 17: 116-135, 1933. 54. H.: Sobre un Tumor Paradwllario cn la Corvina, Bol. de1 Inst. de Xcd. Espw. 2: 28-42, 1925. 55. Roulet, F. : Eine uebertragbare Gcscl~w~1st beim Traucrrr~antel~alnrl~~r Gy?n?toc~o~~~mb~f.? tclnetzi, Schweiz. Ztschr. f. Path. u. Bakt. 12: l&15?, 1949. 56. Ruddick, H. B., and Willis, R.. A.: Malignant Tumours in Dogs. A Description of 9 Cases. Am. J. Cancer 33: 205217. 1938. Nerve Sheath’ Tumors in an Isolated Goldfish I’opulation, (::tnwr 57. Schlumberger, H. G.: Reseawh 12: 890-899. 1952. Tumors of E’ishw , .Imphibians, and Rel,tilr*. 58. Rchlumberncr. H. CT., and Luck& B.: Can& %search’8: 657-754, i948. Otlont.orne-like Forma. 59. Sohour. I.. Bhaskar. S. N.. Green. R. 0.. and 1Ycinmann. J. P.: tions’in a M&nt Striin of-kats, ,irn. J. hnat. 85: ?3-112, 1949. Carcinoma of the Tonsil in a Common Wolf Canis Zup2ts, Proc. Zool. Sw. 60. Scott, H. H.: Lond., pt. 1, pp. 43-47, 1928. Three Carcinomas of the Toncrue ill 61. Steiner. P. E.. Kliiver. H.. and Brunschwie. A.: ~, Ti.0 Monkeys, Caicer &search 2: 704%. 1942. 62. Surbeck, G. : Bull. Suissc P&&e ct Pisciculture, rol. 18, 1917 (cited by Thomas! 1,. : Bull. Assoc. franc. p. l’btude dn (‘anwr 21: 537-546. 1932). Studie iibrr die Fischgeschlsiilstc,, Ztschr. f. Kwbsforscll. 29: 1-Y::. 63, Takahashi, K. : 1929. L. : Epithelioma odontoblastiqw &Y mnxillaiws chez une Xoruc, Bull. *lssor,. 64. Thomas, franf. p. 1’Gtude du Cancer 15: 464-470, 1926. Papillomes do la lerre inferieure clwx .f~/l
Plehn, M. Plehn, M.: Ratcliffe, Am. Roffo, A.
:
68.
Withers, F. W.: Squamous-celled Bact. 49: 429-432, 1939. Zegarelli, E. V.: Adamantoblastomas
1929.
69.
87, 70.
Zuckerman, Proc.
i944.
S.: Zool.
A Rhesus Sot. Lond.,
Macaque pp. 59-61,
Carcinoma in the
(Macaca 1930.
af Slye
the Stock
nmlatta)
Tonsil
in
of Mice, With
the
Dog,
J.
Path.
Am.
J. Paih.
20:
Carcirroma
of
tile
Mouth
X; 23
PATHOLOGY
OF ORAL NEOPLASMW
T
HE comparative method has been effectively used to investigat,e the normal anatomy and physiology of oral st ruc+urcs. Except for work with domestic animals very little has been done toward establishing a comparative pathology of diseases affecting the mouth. It is the j)urpose of this brief review to call attention to the spontaneous ol’ill neol)l;lsnls fountl in the tlifterent classes of vertebrates.
Fishes+ Benign
Epithelial
Tumors.-J’al)il
lolltas arc the nlost frequently observed oral neoplasms of fishes. A cursory inslwtioll of the fish in ;III~ large munici1~1 aquarium will usuallyrcvclal f;lirIy l;~r~g(~masses on the snouts of several specimens, particularly those that. have Iwen in caaptivity for several years. The tumors were probably initintc(1 1)~ rrl)eat4 trauma against the glass L\s pointctl out by Nigrelli,“” ulcerated front or concrete sides of the tanks. lesions often appear on 011~ or both lij)s of these fish. Although healing coltimanly occurs, repeated tl*i\Llilla ltatls to hyperplasia which 111ay cventuntc in the formation of a true neoplasm. Sigwll i rel)orts the owurrrnce of pupillomas in the climbing I)erch .~lnc~Oaswnntlens in which the epithelial elements of the tumors were mucous cells, and in the dwarf gourami Colisn 7aPi?L4”~4i A good example of a papillonm is that. on the rock bass A>&o#is ?,ul>estri~ shown in Fig. J. This fish was kept. as a pet in an Ohio hatchery for many years. The tumor grew slowly and (lid not interfere with the normal activitl\ of the animal. Histologically it was cwnposetl of f’usi form epithelial ~11s sup ported by a delicate connective tissue stronra. Benign epithelial tumors may owasionally be observed on the snout 01 than those large goldfish Cwussius nurcl2zcs where the>. appear less papillary Inore compics ant1 COIIof the rock bass (Fig. 2 1. The tuulor is histologically tains mucous as well as pavement. cpithclial c.ells; the fatter Inay form structures that resemble t,he epitheliitl pearls of marnmali;~n tumors. Careful search failed to reveal thr presence ol’ nryxosporidia which in some fishes may produce marked epithelial hyperpl:lsi;l t~csenlbling a I)enign neoplasm.“” In the Mosel River of C!ern~ntly, licyssclitz”” obscwed that many of the barbels Bcrrhs fhvintinlis bore pea-sized papillary tumors on their lips. The neoplastic epithelial cells were unusual in that many contained one or more cytoplasnlic inclusions that the author likened to those found in some virus
Fig.
Fig.
Fig
6, Section of the papilloma showi] wz Fig. 1.-A, Rock bass bearing a yayillurna on snout. ( Magniflc a.neoplastic stratIfled transitional cell epithelium suuuorted by a vascular stroma. tion, X 260.) Fig. 2.-A, Head of goldflsh with a. flattened 3 by 2 by 1 cm. papillama between WC? ~1nd ,1e Injury to the eye is commcm in the goldfish and in this case had no demonsWat :1y %?il&x to the tumor. B Section of the papilloma. On the left is the free surface immediate beneath which are two c&e&ions of concentrically arranged epithelial cells resembling “peal .,” formations. The bulk of the tumor is composed of pavement epithelium and mucous cells wi th (Magnification, x 12 0. ) a delicate vascular stroma. Another histologically similar tumor w as Fig. 3.-A, Neurilemoma on snout of goldlUsh. B, The nuclear palisading characteristic of this tumor is well shorn r”. present in the tail. (Magnification, X120.)
3.
1080
H$NS
G.
SCEILURIBERGER
diseases. Papillomas were reported on the lips of the stint &,zerus eperlalzus caught in the brackish waters of an ilrlct of the Baltic Sea. Breslauer” described them as cauliflower-likr growths that occasionally were as large as the head of the affected fish. Hist,ologically thry showed a typically papillomatous structurc with no tendency to invade. In 1912 Johnst.one:” found an irregrllar papillary growth on the snout of a 120-pound halibut Elil)lqAossr&s hippoglossus. Histologically the bulk of the tumor was made up of proliferat~in, 0’ connective tissne of the corium wit,11only slight hyperplasia of t,lle overlying epithclium. Thomas and Oxner”” report thr occinrcnce of a papilloma on the lower lip in each of 3 eels Anguilln vrclgnris.
Malignant Epithelial Tumors.--The lips and oral mucosa are the most common sites of carcinoma thus far recorded in fishes. The benign or malignant character of some (Jf the epithelinl tumors is diflicult to determine. The absence of met,astasis is not significant because this mode of spread is such an uncommon occurrence in fishts, even lvhere the histologic appearance and local invasion of the tumor indicate it,s malignant character. The first epidermoid carcinoma reported in a fish was observed on the lips of a catfish Ictalzmrs catm by McFarland in 1901.4” Many years later Dr. Balduin Luck6 and I”” collected nea.rlp 200 specimens of the catfish Anzeiurus nebulosus that bore tumors very similar to those in the fish described by MeFarland. The majority of the tumor-b,earing catfish were taken from the Schuylkill and Delaware Rivers near Philadelphia. The neoplasms were often multiplt~ and usually arose from tht: dental plates just inside the mouth behind the lips. Occasionally they formed large fleshy masses that int,erfered with clos~~re of the mouth, but metastasis was not observed. In the large neoplasms there was moderate cellular pleomorphism ; keratinization, which does not occur normally in the skin of this species, was absent. Histologic sections occasionally showed in\:asion 01’ thr underlying tissues. The degree of autonomy achieved by these tumors is indicntctl by their growth after transplantation to the cornea or ardel+ior chamber of the eye in other catfish. Frequently tumors developed on the oplmsitc dental plate, in apposition wit,h the first tumor. It was possible by direct microscopic observation of these appositional lesions to follow the early changes, particularly capillary ectasia, that occurred during the initial stages of t,amor growth. Epidermoid carcinomas have also been reported on the lips of 2 tenth Tinca tinca,1g a barbel Bclrhus ,~wlgwis,,~~a whiting Merlangus vlerlangus,33 a codfish Pollachius Gw~s,“7 and 2 croakers Pogonias chronGs.3 MazzarellF described a 4.5 by 3.5 cm. tumor that arose from the oral epithelium of the fish Chondrostonza soetta. Only two cases of adenocarcinoma of the oral tissues are on record. TakahashiG3described a t,umor that arose at the left angle of the mouth and extended onto the skin of the cheek in a coalfish, Theragra chakogranzma. The neoplastic cells formed alveoli ant1 invaded adjacent &sues. A tumor that arose from venom glands in the palate of a moray Muraena helena and showed extensive Of interest is the observation that local invasion was described by Ladreyt3*
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASM8
1081
the secretion of the neoplastic glands produced similar, though diminished, physiologic response. Jn fishes the thyroid gland is rather diffusely scattered over the floor of the mouth; enlargements of the gland form distinctive intraoral swellings. Goiter in fishes, with particular reference to the occurrence of adenocarcinoma, has been reviewed elsewhere.58 Neoplastic growth of the thyroid in an inbred laboratory strain of the small tropical swordtails Xiphophorus montezumae was recently reported by Berg and associates.4 The tumor cells destroyed the deeper musculature, gill filaments, cartilage, and bone. Death was possibly due to destruction of the visceral gill arches and the consequent interference with normal respiration. Tumors of Dental Tissues.-Only four examples of dental tumors in fishes have been reported; three are identified as odontomas, one as an ameloblastoma. In 1912 Plehns2 described multiple odontomas in two brook trout. The oral cavities were almost filled by partly confluent nodular massesthat arose from all the tooth-bearing surfaces, viz., both dental plates, the hyoid bones, and, in one case, the vomer. The tumors had become so large that they interfered with feeding. Histologically they were composed of atypically formed teeth. Roff o,~* one of the pioneers of cancer research in Argentina, made a careful study of an odontoma that occurred on the upper dental plate of a marine fish, the croaker Micropogon opercularis. The 3 by 2.5 by 2 cm., faintly lobulated, firm, gray-pink tumor arose from the mid-center of the maxilla and partly obstructed the mouth. A roentgenogram of the head showed numerous radiopaque masses scattered throughout the tumor. Histologic sections disclosed toothlike structures composed of dentine covered by a layer of enamel and embedded in a dense connective tissue stroma. An ameloblastoma was found in a haddock Melanogrammus neglifinus and measured 2.5 by 1 cm. ThomasG4observed that it had infiltrated the maxilla and protruded into the oral cavity. Although the figures are poor, its histologic appearance resembles that of the cystic ameloblastoma of man. Tumors of Mesenchymal Tissues.-Of the tissues usually placed in this category only the connective tissue proper, bone, cartilage, and blood vessels have been the source of oral neoplasms in fishes. The single reported case of an oral fibroma was described by Fiebigerlg as arising from the oral mucous membrane of a codfish Pollwchius virens. It was approximately 2 cm. in diameter and consisted of bundles of connective tissue covered by epithelium. Multiple tumor nodules identified by Johnstone3* as sarcomas of “mixed cell type” were present in the mouth and about the left orbit of a codfish. In another codfish the same autho?* found an 8 cm. fibrosarcoma that arose from the median aspect of the mandible and invaded the soft tissues of the mouth. Takahashis3 reported a 7.5 by 3 cm. fibrosarcoma in the pharynx of a Japanese bass Lateolabrax japonicus. Chondromas have been found twice in the mandible of fishes. In 1917 Surbecke2 found a bilobed tumor measuring 1.5 cm. in diameter, composed of cartilage, and arising from the posterior portion of the mandible of a barbel
1082
HANS
G. SCHLUMBERGER
Barbus fluviatialis. And&’ reported a minnow Phoxinus sp. that had a peduneulated mulberry-like mass attached LO the tip of the mandible ; the weight of the tumor bowed the head. IIistologically it consisted of hyaline cartilage. Recently Nigrelli and G ordon4” described an osteochondroma that involved the operculum as well as the inferior part of the cheekbone and maxilla of a jewelfish, Hemichromis bimuculn tus. although osteomas have been frequently reported in fishes, involvement of the jaws is uncommon. !)f the four on record Bland-Sutton” reported two in 1885. One occurred on the dental plate of a pike Esox lucius; the other was a disk-shaped tumor two inches in diameter and half an inch in thickness on the maxilla of a codfish Gadus ~zorhua. WilliamsC7 described a 5 by 2 cm. osteoma on the anterior portion of the left premaxilla of another codfish. Among 500 specimens of Pagrosomus major, a common food fish in Japan, KazamzQ” found one with a 1.5 cm. nodular ostcoma of the mandible. Marianne Plehn”’ reported an extensive hemangioma of the head in each of 3 sticklebacks Pungitius pungitiw. The dark red tumors spread from thcl ventral surface of the head to the angle of the mouth, involving the lateral margin of the lips and a portion ol‘ the operculum. Tumors of Neuroectoderm.---It is now fairly will established that t,he pigment cells of fishes have their or&ill in the neLu~oectodern1 that forms the ‘I’ntllors of pigment cells, particularly those madtl embryonic neural crests. up of melanophorcs, are cluite common in fisheP and hare been the subject of intensive study with sl)t~cial emphasis on theil genetics. However, except for the following report-, none has l)ten observed in th(l oral tissues. Recently Ronlet”” published an accaount of a ttisease that occurred in ~1 group of t,ropical aquarium fish G~))lnoco~1~))t6us t~~rtzi. Virst, to appear was a dark discoloration oi’ the lips, followctl by tmnefac+on. The dark color was due to large cells that coI~t:G~led melanin pigment and which the author COD siders are malignant. The cells invaded the soft tissues of the head, often producing an exophthalmus l)y the fortllation of tumor masses in the orbits. Roulet ground ~111 some of the tissue and was able to observe tumor formatiotl at the site of inoculation in healthy fish. E’nrthertnorc, normal fish of the same species, when placed in the tank with diseased fish, developed similar tumors. Hecause inflammation is often associat cd it1 fishes wit,h the local :~.~curnnlatior~ of pigment cells, the possibility t,hat this has occurred here atl(1 that the lesiotr is a chronic inflammatory response to an infections agent must be carefully ruled ont. IVeurogenic tumors involving oral structures have not been reportetl in fishes. However, while studying multiple nerve sheath tumors in goldfish.“7 I observed several instances in which one of the neoplasms involved th(I I’(‘The growths were lobulated, orange-yellow, gion of the snout (Fig. 3, A). IIistologically they soft in consistency, and bled profusely when injured. closely resembled the neurilernomas found in man. The loose aggregation of stellate cells characteristic of the Antoni type 1: neurilemoma was often associated with areas identified as type A, in which the cells were compactly arranged and the nuclei offered striking examples of palisading (Fig. 3, B j .
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1083
Amphibians Tumors in frogs, toads, and salamanders are rarely reported in the literature.58 In some measure this may be attributed to the fact that unlike the fishes they play a very minor role as a source of human food; furthermore, when compared with the other classes of vertebrates, their absolute number is small. Only a single oral neoplasm has been reported in an amphibian. In 1902 Vaillant and PettiF6 briefly described a tumor that they found in the EuroThe growth was a fibroma which arose in the pean edible frog Rana esculsnta. buccal cavity and protruded from the mouth.
Reptiles There are over 20 reports in the literature of tumors in turtles, crocodiles, lizards, and snakes.“* Oral structures were the primary site of the lesion in 4 instances.
Fig. 4.-A, Oral cavity of a lizard, the tegu. showing bilateral squamous cell carcinomas that arise from the gingiva and partly cover the teeth. 1.5 x natural size. (BY permission, Cancer Research.) B, Representative area of the carcinoma showing marked variation in size of the nuclei. A suggestion of “pearl” formation is seen at top center. (Magnification, X200.)
Bland-Sutton” observed multiple ene1~ondroma.sin a lizard, t.he Indian dracoena. Tumors were present in 2 vertebrae, both humeri, monitor Varanus and 2 metacarpals. The case is noted here because 4 enchondromas were also found in the hyoid hone. In the Philadelphia Zoological Garden, Dr. Herbert Ratcliffe observed a squamous cell carcinoma on the left upper gingiva of a large Mexican lizard,
1084
HAKS
G.
SCHLUMBERGER
the tegu Tupinambis nigr~opunctatus. When first seen the tumor measured 2.5 by 2 by 1 cm., but during the following year doubled in size. At that time a similar neoplasm appeared in the same location on the right side. (Fig. 4, 11.) Histologically the tumor was a fairly well differentiated squamous cell carcinoma showing occasional “pearl" formation and pronounced variation in size of the nuclei (Fig. 1, B). Dr. Ratcliffe and I made numerous transplant’s of the tumor to lizards, alligators, frogs, chicks, and even to rats, but, all failed to grow.5x The animal died as the result of an accidental injury. At autopsy the tumor was seen to invade locally, but no metastases mere found. Eall* report,s a remarkable instance of melanosarcoma arising in each of a mated pair of pine snakes Pituophis nzel~anoleucus. In t,he female the tumor arose on the trunk, but, in the ma.le it first appeared on t,he I.eft upper labia,1 fold. It grew rapidly and after eight months measured 4 by 2.5 cm. As ill the case of the lizard noted above, a second tumor appeared in the same location on the right gingiva and reached a diameter of 2 cm. before the animal was sacrificed eight months aft,er the first tumor was seen. ;Zt autopsy no metastases were found. I was privileged t,o examine the specimens and the histologic sections. The neoplastic cells are often arranged in bundles, and are of an c~longated spindle shape with large oval nuclei. Most of the cells contain melanin granules. A reticulated python Python reticulatus was observed by its keeper at the Philadelphia Zoological Garden to have a swelling in the right side of the upper jaw, and two black tumors on its body. When the animal was sacrificed a year later the tumor at the angle of the jaw measured 6 by 3 by 2 cm. and was only faintly pigmented; the overlying skin was intact. The two tumors on the trunk measured 2 cm. and 0.5 cm. in diameter, respectively, and were heavily pipmcnted. Attempts at transplantation were unsuccessful. I )rs. Tiucl~6 and Rreedis identified the t,umors as nonmalignant melanomas.“’
Birds ,211existing species of birds are toothless, but some fossil birds possessed well-developed teeth. Rudirnents of teeth have therefore been sought in the embl*yos of existing birds. An ectodermal ridge projecting slightly into the mesenchyme just inside the margin of the jaw is seen in the 6-day-old chick embryo. The same ridge, but better developed, has been found in the embryos of t,he tern and ostrich. T,illie3” believes that the ridge represents the \-~ry last vestige of the teeth. This complete absence of even rudimentary teeth or dent,al pa.pillae in birds accounts for the absence of tumors of dental origin in this class of vertebrates. The horny port,ion of the beak of birds has not been reported as the site of a neoplasm. Yet, overgrowth of the bill occurs frequently in some birds. Among parakeets the cause of the abnormality is not always due to a lack of That a neoplastic potential normal wear but rather to a dietary deficiency.” may reside in t,he bill is suggested by the nuptial wart horn that normally forms on the beak of the American white pelican and is cast when the bird
COMPARATIVE
PATHOLOGY
OF
OR$L
NEOPLASMS
1085
Few cases of oral neoplasm of any kind have been reported in birds despite the fact that thousands of chickens are examined by veterinary pathologists each year. In 7,408 autopsies on chickens Gossz2 found 1,332 cases of leukosis and 113 examples of other tumors, but none that involved the oral tissues. In their review of neoplastic diseases of the chicken, Feldman and Olson” mention the case of a pigeon with warty growths on the skin adjacent to the beak and around the eyes. Similar lesions have been observed in parakeets where some are due to the virus of bird pox, others to vitamin deficiency.18 The occurrence of nonriral papillomas on the combs and wattles of chickens has been reported.17
Fig. 5.--A, Ventral aspect of parakeet head. removed. A hemispherical tumor (arrow) arising the skull and invaded the oropharynx. Removal of adjacent to the first, lying in the orbital cavity mophobe cells of the pituitary comprise the bulk
The lower jaw and zygomata have been in the pituitary has penetrated the base of the soft tissues has revealed another tumor B, Neoplastic chrobehind the right eye. of the tumor. (Magnification, x500.)
Only 5 intraoral tumors were found in a cursory review of the literature; all were squamous cell carcinomas in chickens. PickSo reported an epidermoid carcinoma that arose in the floor of the mouth and destroyed the mandible. Joest and Ernest?O described a similar case in which the tumor had infiltrated the larynx. In an g-year-old Erahman hen, Koch3’ found a squamous cell carcinoma of the roof of the mouth. It had spread to the pharynx, completely filled the larynx, and deeply invaded the neighboring st.ructures. Jacksonzg observed a 5 by 4 cm. ulcerated tumor that invaded the full thicknes of the pharyngeal wall. Although some areas were histologically of squamous cell type, he prefers to classify the neoplasm as a transitional cell carcinoma. Another tumor of the pharynx, identified as a squamous cell carcinoma, was seen by Feldman and O1sonl’ in a 2-year-old hen. The carcinoma had infiltrated the adjacent tissues, but no metastases were found. In parakeets Melopsittacus undulatus I have recently seen two cases in which adenocarcinoma of the pituitary body had invaded the roof of the mouth and presented as a mass in the oropharynx (Fig. 5).
1086
HANS
G.
Captive
SCHLUMBERGER
Wild
Mammals
D;Lt:l 011 tumors in Is ;I1’t’ \-et’). sc*;lIlt,y. l)ul the larger zoological gardens lmblish af~flilill 01’ i trl~~\.;~ I r(il)orts of tlis~asrls causing death itm0ng their captive xvil(l illlilllillS. Over a periotl of i11i11iy \cars af the I’hilaclc~lphia Zoological Gat*(lens, Of 1~‘os”” found only t,wo instances of or;11 trunors ilt the ma~nmals exhibited. these one was a squamous cell carcinoma of the tongue in a black bear Ursus antericanus; the other was an osteofibroma of the jaw in a gazelle, Gazelln iscrbella. During the following ten years at, the same institution (1923 to 1933) Ratcliffes3 encountered no additional instances of oral neoplasm, although many tumors were found at other sites. In a personal communication Dr. Ratcliffe stated that, he has seen two iristances of oral cancer in the period 1933 to 1953. A very old badger I’asid~cr tazus developed a S~L~II~OLIS cell carcinoma of the lip which also invaded the gingiva and mandible. ,\t, autopsy a Japanese bear T’I.SU.S,japonicxs that had been in the Philadelphia Zoo for over thirty years was found to have widespread metastases of melanosarcoma. Several metastases wcrc prescrit in the tongue; the primary site could not be identified. IIuring the years 19% to 1957. only four oral neoplasms were enconnter~tl I,- the pathologists at. the Zoological (hardens of Tdonclon. Of t,hese, two were fibrous epulides and two were squamous cell carcinomas. A pygmy mongoose Heloyale waGz4 died ol’ inanition resulting frorn several epulides that arose on the gingiva of both ;j:l\vs and prevented closure of the mouth. A Canadian heaver Custer cnnrrrrliensis'"" became markedly emaciated when 3!4 years old. A fibrous t,umor the size of a walnut was found growing from the periosteuni and periodontal membrane of the left ramus of the mandible. Of the t,wo squamous cell carcinomas, one was found by Scott?’ on the right t,onsil of a wolf (‘Ia11z’s 7ul)u.s. The tonsil was almost replaced by an ulcerating tumor that infiltrated t,hc nc+hboring tissues and had metastasized to the I’(‘gional lymph notlcs. The second instance of oral cancer seen at the London Zoo was a poorl) diffcrentiatcd squamous ccl1 carcinoma on t,he floor of the mouth in a rhesus monkey Macaca nlulatttr. A small ulcer was first noted beneath the tongue near the I’renulum. This grew rapidly in size and after four months involved the entire floor of the mouth in front of the tongue and extended into the gingiva about both canines. At, autopsy the mandible and salivary glands were infilt.rated by the tumor which had also metastasized to the regional lymph nodes. Zuckerman,Y’l reporting this case in 1930, observed that he had been unable to find a previous record of oral cancer in a rnonkey or ape. He added t,hat a dead orang-utang had been brought to the zoo with gross findings simiTJnfortunately, the absence of any history lar to those seen in the monkey. and preclusion of histologic study by t,he state of decomposition in which the material was received did not allow a definitive diagnosis. Squamous cell (~av.4~tc)tna of the tongue in each of two monkeys was deThe animals had been kept in a laborascribed by Steiner and associates.“’ tory color1y for many yraw. One IviIs a l&year-old male rhesus monkey that I'rl'il
liltltli
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1087
bore 2 lingual tumors. Of these, one was an ulcerated lesion measuring 2.3 by I..1 cm. on the lateral border of the tongue near the base; the other, on the ventral surface left of the frenulum, was a sessilepapilloma t,hat measured 9 by 7 mm. Histologically both were squamous cell carcinomas. No metastases were present. The second animal was a male Java monkey Macaca irus aged 14 years. It had an ulcerated carcinoma at the base of the tongue that extended posteriorly to the epiglottis and laterally over the pharyngeal walls and the adjacent hard and soft palates. Microscopically the lesion was classified as an undifferentiated squamous cell carcinoma. The authors also saw histologic sections of a lingual carcinoma in a macaque from another colony.
reflected mandible y;;logY).
Fig.
.
6.-A,, Head revealmg an and destroyed B, Section (Magnitlcation,
of a baboon. The angle of the mouth has been incised and the lips extensive carcinoma of the lower gingiva. The tumor has invaded the considerable alveolar bone (Courtesy Armed Forces Institute of of the poorly differentiated squamous cell carcinoma invading adjacent X 240.)
Together with Dr. Henry Goldman I examined a b.aboon at the National Zoological Garden in Washington, D. C. The keeper had not,ed that for several weeks the animal had experienced difficulty in eating. At the time of our visit the baboon appeared listless and was obviously in pain. Streams of ropy saliva drooled from its mouth. The animal was sacrificed and dissection carried out at the Armed Forces Institute of Pathology. An extensive carcinoma of the left gingiva was found. It had destroyed so much alveolar bone that several teeth were loosened (Fig. 6, a). The tumor invaded the mandible and the floor of the mouth and had metastasized to the regional lymph nodes. IIistc~logically ii, was a poorly differentiated squamous cell carcinoma (Fig. 6, B). Tumors of dental origin are occasionally reported. Dentigerous cysts, although not true neoplasms, may be mentioned; 3 were found at the London ualabatus, 26the Patagonian cavy DolichZoo, one in the black wallaby Macropus otis nzagellanica,25 and the viscacha, Lagostomus maxinl?Ls,2”a relative of the chinchilla. In every instance the cyst was found in the mandible. Bland-
1088
HANS
G.
SCHLUMBERGER
Sutton: states that odontomas have been observed in the marmot, porcupine, agouti, boar, and elephant. Moodie,“” on Plate 46 of his monograph on palcoI)at,hology, depicts a lesion that may be an odontoma in the basal portion ot an elephant’s tusk. Also illustrated on this plate is the tooth ol’ a c~achalot Lvhale with large “ csosl oses of dentine. ’ ’ Xot true neoplasms, such lesions are commonly seen on the 1.oot.s of Ihe teeth in these whales. They l,rolx~l~l,v represent hypcrcelncrltosis which occasionally reaches proportions comparabl(~ to that of the cementomas in man. Similar excrescences were noted by Moodir on the fossil tooth of a Pliocene camel from Nebraska. LZnother lesion that has been reported by I)aleopathologists4”j G’ is a remarkable overgrowth of the facial atltl jawbones of mummified baboons Papio hn??zndrlJas from Egyptian tombs. The lesion has been identified as Paget’s disease ; hov;cver, it closely t~cstmblcs the leontiasis ossea observed in monkeys on vitamin-deficiciit, tlicJts.28 It w:x also seen in a baboon from the colony kept. at the Idildon Zoological (lardens.
Domesticated
Mammals
Widely scattered throughout the literature of many countries are single case reports of oral neoplasms observed by the practicing veterinarian. Here only a representative sample of the tumors encountered will be given (Table I). The largest number of neoplasms have been found in the dog, a fact that, is explained in part by the longevity of the dog when contrasted with food animals such as cattle, swine, sheep, and goats. When compared with the horse t.he greater number of t,umors found in the dog may be attributed in part at least to its overwhelming numerical superiority. However, this factor cannot be so significant when the dog is compared with the cat. One of the most striking esamplcs of oral neoplasia encountered in an> animal is the viral papillomatosis of dogs (Fig. 7, A). The lesions are multiple and involrc any part of the oral mIIcosa and tongue, occasionally even estending onto the snout. Histologically the tumors arc composed of massed epithelial cells, showing progressive keratinization as the!. approach the free surface (F‘ig. 7, I: and C). The broad base is composed of vascular connective tissue. DeMonhreun and Goodpa,stnre’5 descril)ed basophilic intranuclear bodies, similar to the Tdipschtitz bodies of human warts, in a few of the large epithelial cells of the older lesions. These investigators I)roved t,he infectious nature of the disease and found that practically all puppies are susceptible. The average incubation period is from thirty to thirty-three days; pupljies that have recovered a.re immune to reinfection. The disease is easily transmitted by means of a Berkefeld filtrate obtained from the papillomas. The deep pigmentation frequently observed on the lips, oral mucosa, and tongue of (logs may account for the high incidence of melanosarcoma in these Tn the I)epartment of Veterinary Pathology of the Ohio State llnitissues. versity, I)r. C’larence (.‘olc found that the pigmented tumor was more frequently observed during the past ten years than was squamous cell carciCole also encountered melan0sarcoma twice in cats; in ofie instance llotna.l’
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1089
the tumor arose on the gingiva, in the other on t,he palate. Despite the prevalence of melanosareoma. in horses, the tumors are seldom primary on the oral mucosa. Although squamous cell carcinoma has been seen to arise from all free surfaces in the mouth of dogs, involvement of the tongue is comparatively less common than in other domestic animals, particularly the cat. On the other hand, recent work by Withers68 would show that squamous cell carciIt is of noma of the tonsil is one of the most common of canine oral tumors. interest that in 1928 when ScottGo reported a carcinoma of the tonsil in a wolf he was unable to find a recorded instance of another such tumor in any animal. Eleven years later Withers reported that during a five-year period in London he had collected 40 histologically proved cases in dogs, but believed that over twice that number had been seen and diagnosed at the Royal Veterinary College. In 16 months 24 cases were autopsied; the average age was 9 years; metastases were found in the regiona. lymph nodes and lungs.
gingiva, nance tumor
Fig.
7.-A, Dog with viral papillomatosis. hard palate, tongue, and even nose. of epithelial over connective tissue showing hyalinization and keratinization
Lesions Single elements. of epithelial B,
are seen on the lips, buccal mucosa, small papilloma; note the predomi(Magnification. x 10.) C, Detail of cells. (Magnification, X280.)
Adenomas and adenocarcinomas arising in the major and minor salivary glands have been reported in the dog (Table I) but are rare in other animals. A mixed tumor has been seen in the dog by Mulligan44 and a papilloma of the parotid duct by Goodpasture.*l Tumors of dental origin are uncommon in domestic animals. Mulligan44 described an ameloblastoma in the mandible of a dog; histologically it was similar to those of man. In a group of 79 mice with an hereditary tendency
Maxilla
&lIldS
Salivary
Palate
Tonsils
Tongue
Gingiva
Fibroma Fibroma Papilloma
Oral mucosa
(many)
Rq.
carcinoma
Sq. carcinoma Sq carcinoma Sq: carcinoma Melanosarcoma Xelanossrcomn Myxosarcoma ndcrloma hdenocarcinorna Sq. carcinoma Melanosarcomn HII:ll,~lom~yor;:~lcol~l~
Papil onra (2) Sq. carcinoma
Melanosarwm;l Aq. carcinoma .-\drnocarcinoma
SITE
Lips
---
(2)
(3 j
(2 ) (6)
and
(6 j *
DOG
BOUC&
COlC
Ruddick Wilis Withers Colt
Mulligan
and
Mulligan Jackson Cole Mulligan Cole Feldman Cole Mulligan Cadiot Cole Mulligan
Feldman Cole DcNonbreun Goodpasture Cole Cole
Colt
Colt!
Colt
---
I
Sq. Sq. Sq.
carcinoma carcinoma earcirwmn
Mclnnosarcoma
___-.CAT
(2;
Cole
Cadiol Feldman Cole
Cole
__._____~____
.~____~ 1
Sq. carcinoma Wq. carcinoma M~sosarcoma
Sq. carcinoma Fibrosareoma Fibrosarcoma Hcmangioma
Hemangiomn
(3)
(3)
HORSE
Cadiot IIenson Feldman
Cole Cole Feldman Feldman
Feldman
I
Sq. carcinoma Fihroma
cow
Cadiot Feldman
4
z $ u:
s
z
COMPARATIVE
PATHOLOGY
Fig.
Fig.
OF
ORAL
NEOPLASMS
1091
8.
9.
Fig. S.-Complex compound odontoma of a horse. Notable are the intertwining roots, of which (top, right) lies horizontally. The cross sections of many abnormally formed are visible on the occlusal surface. (Courtesy Armed Forces Institute of Pathology.) Fig. 9.-A, Muzzle of a pony. A flbrosarcoma is seen arising in the lower gingiva and involving the entire chin. B, Neoplastic connective tissue cells arranged in noorly formed bundles: a moderate number of capillaries are present. (MagniAcation, x 225 ; reduced $6.) one teeth
1092 to tumor
HANS
formation
Zegarelli””
G.
SCHLUMBERGER
found
LO3 lesions that he identified
as amelo-
idast~ornas. Some 01: these wre odontogenic cysts which he believes arc stage.3 in the development of the tumors.
In their rat colony Bullock and Curtis I” found two animals each bearing arr odontoma in the mandible. I:urn and associates” studied the development of odontomas in the incisor teeth of rats on a dirt low in vitamin A. The tumors consisted chiefly of spindle cells similar to those of embryonic pull) tissue ; odontoblasts and epithelial cells were scattered throughout the growtl1s. &hour and associateP have described pseudo-odontornas in t,ha r;rt. They regard the lesion as a dental hamart~oma. A large odontorna from a horse was described by I:land-Sutton.” I founcl another large complcs compound odontorna frorn a horse in the collection oi the Armed ~~‘OIWS Ittstitkrte of Pathology. The tumor weighed orer a pound irrld was made up 01’ rnalfornlcd cvmjoittetl teeth arranged at ha~haz;~rd (Fig. 8). M:rrly of the abnolnral teeth wew sufYiciently well orientecl to l)t*ovitlc ;I f;r irly ::;lti:;filctOl’~ O('(dlUSil I surface. 1Icman:;iornas of tlr(l lips and of the gingiva in horses have been sported by I~‘eldman.lG Other oral tumors of n~esenclrymal tissues are a rhabdomyosarcoma of the tongue”” and myxosarcoma of the gingival” in the dog. Myxosarcoma and fihrosarcoma have also been found in horses on the tongue and gingiva, respectivcl\- (Table I). Through the courtesy of Dr. Cole, T was able to examine a case of fil)IYWLYTOllliI in a pony. The tumor arose on the gingiva and prcscnted as a 6 cm. hrmispheric;~l mass at, the midpoint of the lower jaw (Ii’ig. 9, A). Rocntgenograms slrowed that the tumor had deeply invaded the r;lt:ndible. Histologically it was composed of large spindle-shaped cells loosel> artwrgcd in bundles (Fig, 9, E) ; occasional17 the cells were more nearly stellatc and the tissue assumeda myxomatons character. Benign and malignant tumors of bone have been found in the jaws of rnost domestic animals (Table I). The frequency of these lesions in the maxilla as Feldmanl” mentions an cont,rastcd with the nrarrdiblc in dogs is noteworthy. osteogenic sarcoma of the maxilla and one of the mandible in sheep. The sarnc irntlror* statcs that, ostconlas irr’c common in mules where they OCCUR ;IS project,ing or even pedunculat~cd rrrassesattached to the mandible.
Conclusion :I large variety of oral tumors, representing the majority of those ohserved in man, hare been found in fishes and domesticated mammals. A good 1)eginning has been rn:~tlc in the collection of cases among captive wild mammals, and here also the similarity to Ihe human neoplasms is striking. In alnphibians, wptiles, ant1 birds the numbrr of cases available for study is still very small.
References 1. Andrb,
IX.: 1927.
Sur un chondrome (Cited by Tomas,
du vairon. Bull. I>.:
Bull. Assoc.
Suisse franc.
and Rhabdomyoma 6: 134-138, 1946.
in
P&he et Pisciculture, p. 1’6tude du Cancer
28: 21:
177-178, 537-546,
1932.)
2. Ball,
H. A.: noleucus,
Melanosarcoma Cancer Research
Two
Pine
Snakes,
Pituophis
mela-
COMPARATIVE
PATHOLOGY
OF
ORAL
NEOPLASMS
1093
3. Beatti, 4. Berg, 5. 6. 7. 8. 9. 10. 1 I. 1%. 13. 1-l. I,?. 16. 17. 18. 19. 30. 21.
M.: Geschwiilste bei Tieren, Ztschr. f. Krebsforsch. 15: 452491, 1916. Olga, Edgar, Martha and Gordon, M.: Progressive Growth Stages in the Development of Spontaneous Thyroid Tumors in Inbred Swordtails Xiphophorzcs montezzLmae, Cancer Research 13: l-8, 1953. Bland-Sutton, J. : Tumours in Animals, J. Anat. & Physiol. 19: 415475, 1885. Bland-Sutton, J. : A Very Large Odontome From a Horse, Tr. Odont. Sot. Great Britain 23: 215, 1891. Bland-Sutton, J. : Tumours, Innocent and Malignant, Chicago, 1907, W. T. Keener and co. Boucek? Z.: Mittheilungen ueber 35 histologisch untersuchte Ticrgeschwiilste, Arch. wiss. u. prakt. Tierheilk. 32: 585-600, 1906. Zur Kenntnis der Epidermoidalgeschwiilste von Kaltbliitern, Arch. f. Breslauer, T.: mikroskp. Anat. 87: 200-264, 1916. Bullock, F. D., and Curtis, M. R. : Spontaneous Tumors of the Rat, J. Cancer Rcsc:trcl~ 14: l-115, 1930. Development of Tumors in Incisor Teeth Burn, C. G., &ten, A. W., and Smith, A. H.: of Rats on Diet Low in Vitamin A, J. D. Res. 16: 317-318, 1937. Cadiot, M. : Sur le cancer de la langue et celui des levres chez les animaux, Bull. Acad. de med., Paris 81: 218-223, 1919. Recherches Experimentales sur les Tumeurs Malignes, Paris, 1910. (Cited by Clunet, J.: Wolff, J.: Die Lehre von der Krebskrankheit 3: 283-316, Jena, 1913, Gustav Fisher.) Cole, C. R.: Personal communication, March, 1953. DeMonbreun, W. A., and Goodpasture, E. W.: Infectious Oral Papillomatosis of Dogs, Am. J. Path. 3: 43-55, 1932. Feldman, W. H.: Neoplasms of Domesticated Animals, Philadelphia, 1932, W. B. Saunders Company. Feldman, W. H., and Olson, C., Jr.: Neoplastic Diseases of the Chicken, in Diseasrs of Poultry, ed. by Biester, H. E., and Schwarte, L. H., Ames, Iowa, 1948, Iowa State College Press. Diseases of Budgerigars, All-Pets Magazine, Fond du Lac, Wis., 1951. Feyerabend, Cessa: Fiebiger, J.: Ueber Hautgeschwiilste bei Fischen nebst Bermerkungen iiber die Pockenkrankheit der Karpfen, Ztschr. f. Krebgforsch. 7: 165-179, 1909. Fox, H.: Disease in Captive Wild Mammals and Birds. Philadelphia,_, 1923, , J. B. Lippincott Company. An Anatomical Study of Senescence in Dogs, With Special ReferGoodpasture, E. W.: ence to Relation of Cellular Changes of Age to Tumors? J. M. Res. 38: 127-190, 1918.
22. Goss, 23. 23a. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35.
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20:
Carcirroma
of
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Mouth
X; 23