A Clinicopathologic Study of Malignant Tumor in Dogs

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http://vet.sagepub.com/Veterinary Pathology Online

http://vet.sagepub.com/content/23/2/170The online version of this article can be found at:

DOI: 10.1177/030098588602300210

1986 23: 170Vet PatholA. K. Patnaik, P. H. Lieberman, R. A. Erlandson, E. G. Macewen and A. I. HurvitzDogs

Clinicopathologic and Ultrastructural Study of Undifferentiated Malignant Tumors of the Oral Cavity in

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Vet. Pathol. 23:170-175 (1986 )

A Clinicopathologic and Ultrastructural Study of UndifferentiatedMalignant Tumors of the Oral Cavity in Dogs

A. K. PATNAIK,. H. LIEBERMAN,. A. ERLANDSON,E. G. MACEWEN,ND A. I. HURVITZDepa rtment of Pathology and Do naldson-Atwood Cancer Clinic;The A nimal Medical Center, New Y ork, Ny, ndDep artment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, N Y

Abstract. Undifferentiated malignant tumors of the ora l cavity were diagnosed in six dogs under 2 years ofage. The dogs were examined because of pain an d swelling of the upper molar or prem olar areas. In all six dogs,the tumors were initially misdiagnosed as infections or carnasal abscesses. The differential diagnosis includedmalignant lymphom a, osteosarcoma, mesenchymal chondrosarcoma, embryonal rhabdomyosarcoma, and ma-lignant melanoma. Electron microscopy of three neoplasms showed th at the re were no specific features char-acteristic of carcinoma or sarcoma. Immun operoxidase studies for cytokeratins, epithelial membran e antigen,actin, myosin, desmin, and v imen tin were also negative. We conclude that these tumo rs be designated undif-ferentiated malignant tumors of the oral cavity until histogenesis is established.

Benign a nd mal ignant neoplasms in dogs unde r 2years o f age a re r a ~ e . ~ , ~ , ~n o ne s tudy of neoplasms inthe dog, malignant tu mo rs acco unted for only 3.2% ofthe tum ors in dogs under two years old.s Lymph oma,leukemia, and osteosarcoma were among the neo-plasms repo rted in the young dogs.5The purpose of this repo rt is to describe six cases ofundifferentiated neoplasm of the oral cavity in dogsunder 2 years of age.Materials and Methods

The case records of six dogs under two years old withundifferentiated tumors of the oral cavity diagnosed over a15-year period were reviewed. Only those cases with com-plete case records and follow-up information were chosenfor the study. D iagnosis was based on histologic examinationof tissue specimens. Specimens were processed routinely, fixedin 10% buffered formalin, and stained with hem atoxylin andeosin. Selected slides were stained with Mayers mucicar-mine, Schmorls fem c fem cyanide reduction stain for mel-anin, and Gridleys reticulum stains. Tissues for electronmicroscopy were fixed in K arnovskys fixative (parafo rma l-dehyde and glu taraldehyde), buffered with s-collidine, postfixed in osmium tetroxide, and em bedded in Maraglas epoxyresin. Immuno peroxidase procedures were used according tothe methods of SternbergerI4and further modification byErlandson et al. Antibodies against three hum an ep iderma lkeratins d esignated AE1, AE2 and AE3 were generously sup-plied by Dr. T ung-Tien Sien, Dep artmen t of Derma tology,New York University School of Medicine. Antibodies againstactin and myosin were from Miles-Yeda, Ltd. Antibodiesagainst epithelial membrane antigen (EMA) and desmin werefrom DAK O, Inc. Antibodies against vimentin were supplied

privately by DAKO, Inc. Three of the cases were examinedimmunohistologically

ResultsUndifferentiated, malignant neoplasm of the oral

cavity was diagnosed in six young dogs (Table 1).Th e average age of the dogs was 12.5 mo nth s (range,6 to 22 m onths) . Three dogs were 12 mo nths old oryounger. Fou r dogs were m ales an d two were females.Three dogs were German shepherds, and five werelarge-breed dogs.Mo st dogs were exam ined because of pain an d swell-ing of th e upper molar orprem olar areas. As t he tumorsgrew, subo rbita l swelling, facial ede ma , an d difficultyeating were observed. Other clinical findings includedexophthalmos , loose molar a nd premolar teeth , nasalan d ocular discharge, an d ulceration and bleeding fromthe mouth. Radiographs showed soft t issue swellingand bony eros ion. T he only a bnorm al f inding on he-matologic and biochemical testing was high WBCcounts (range, 13,000 to 33,0 00 WBC/mm3).In five dogs, the pr imary neoplasm, located in theright side of the oral cavity, was an ill-defined, soft,gray-tan, hemorrhagic tumor involving the upper pre-molar an d molar areas . The tum or extended into max-illary, nasal, a nd orbital t issues, an d som etimes int obrain t issue. In the sixth dog (dog 2), the neoplasminvolved the soft palate and surrounding tissue. Thesalivary glands were not invo lved in any dog.Five dogs were necropsied. Diffuse metastases w ere

170

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Undifferentiated Tumors of the Oral Cavity in Six Dogs 17 1Table 1 . Clinical and pathologic findings in six dogs with undifferentiated malignant neoplasm of the oral cavity.

Survi-valSites of Metastasis (days)(microscopic) After

Diag-nosisGross Pathologylinical Signs onSex Age(mo) Physical Examinationo. Breed

1 Germanshepherd

2 Giantschnauzer

3

6

Germanshepherd

Germanshepherd

Mixed breed

Dobermanpinscher

M 9 Firm, fluctuating swell-ing R* side of facewith exophthalmos,R nasal disease, &enlarged R mandibu-lar & pharyngeallymph nodes; lungmetastasis on X-ray

F 14 Mass in back of mouth& soft palate; anorex-ia & lethargy; sub-mandibular swelling1 months duration;lung metastasis onX-ray

M 6 Swelling under R eye;loose molars (1 st &2nd) extracted 1week before exami-nation

M 12 Swelling of R nasal &buccal areas; no boneinvolvement

F 22 Mass behind eye of 2/2months duration; nobone involvementinitially (surgery twotimes before exami-nation)

M 13 Bleeding from nose &mouth; swellingon Rside of face & mandi-ble

Mass with deformity Brain, lungs, lymphinvolving R maxilla nodes, liver, heart,& nasal passage; ul- kidneys, adrenalceration of gum & glands, mesentery,palate intestines, gastric

mucosa, testes

Grayish, friable mass Brain, lungs, lymphinvolving soft palate nodes, liver, heart,& nasal cavity bilat- kidneys, adrenalerally glands, mesentery,intestines, pancreas,

ovaries, mammaryglands

Mass involving R max-illa extending to tur- nodes, liver, heart,binates, palate & kidneys, adrenalgum glands, mesentery,

pleura, gastric mu-cosa, skeletal muscle

Brain, lungs, lymph

Mass involving buccal Lungs, pleura& nasal cavities &intraorbital tissue

Mass involving R eye,nose, frontal sinuses adrenal glands& cranial cavity; nooral lesion

Liver, lymph nodes,

Ulcerated mass involv- Lymph nodesing R molar arcade &surrounding tissue

20

42

6

2

60

2

present in all but dog 5 in which only liver metastasiswas seen.

The primary and metastatic tumors were character-ized by groups of small to medium-sized cells withscant stroma (Figs. 1-3). The cells were round or ovoidto spindle-shaped with round to elongated nuclei con-taining small amounts of chromatin and granular cy-toplasm. There were large areas of necrosis often co-agulative. The number of mitotic cells per high powerfield ranged from 23 to 30 . There was little morpho-logic variation among the neoplasms and the meta-static sites.

In all cases there was histologic evidence of tumorextension into the maxillary and frontal sinuses, tur-

binates, and adjoining bones, and, in three cases, thecranial cavity. The most common sites of metastasiswere lymph nodes (five), lungs (four), liver (four), heart(three), kidneys (three), and brain (three).

Because of rapid progression of disease and poorprognosis, all dogs were killed. The average time fromdiagnosis to death was 22 days (range, 2 to 60 days).The two dogs that lived for 42 to 60 days had multiplesurgical resections.

In three cases (dogs 1, 2, 5 ) , tissue specimens wereexamined by transmission electron microscopy; theyhad remarkably similar ultrastructural features. Thetumors consisted of patternless sheets of loosely-or-ganized, polygonal and spindle-shaped cells in stroma

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17 2 Patnaik et al.

Fig. 1. Highly cellular neoplasm; small to medium-sized cells, little stroma, and many mitotic cells. HE.Fig. 2. Small to medium-sized, spindle and round pleomorphic cells. HE.

Fig. 3. Higher magnification of Fig. 2. Pleomorphic cellswith many mitotic figures invading the mucosa.

containing scattered collagen fibrils (Figs. 4-6, 8,000 xand Figs. 7,8, 12,000 x) . The irreguIarly-shaped nucleidisplayed clumped chromatin and one to three nucleoli(Fig. 4). The relatively scanty cytoplasm containedscattered cisternae of rough endoplasmic reticulum,inconspicuous mitochondria, and a small Golgi ap-paratus (Figs.7,8) . Polysomes were prominent in manyof the neoplastic cells (Fig. 8) . Except for scattered,rudimentary cell junctions (Figs. 7, 8) , no structuresindicating tumor cell differentiation were seen. Im-munoperoxidase studies for AE1, AE2, AE3, EMA,actin, myosin, desmin, and vimentin were negative.

DiscussionBecause of the age and clinical signs of the dogs of

this report, their lesions were diagnosed as infectionsor carnasal abscesss, and thus accurate diagnoses weredelayed. Neoplasms were suspected when there was noresponse to antibiotics and when evidence of metas-tasis was observed.The differential diagnosis in young dogs with clinical

--tFig. 4. Lo w magnification electron micrograph of tumor in dog 1. Haphazardly arranged, undifferentiated cells withFig. 5. Low magnification electron micrograph of tumor in dog 2. Loosely organized neoplastic cells surroundingFig. 6. Low magnification electron micrograph of tumor in dog 5. Undifferentiated neoplastic cells. Nuclei are less

scanty cytoplasm. Irregularly-shaped nuclei, coarsely clumped chromatin, and multiple nucleoli.lymphocytes.atypical than in dog 1.

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Undifferentiated Tumors of the Oral Cavity in Six Dogs 173

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174 Patnaik et al.

Fig. 7.Fig. 8.

Electron micrograph of tumor in dog 1. Tumor cells joined by two rudimentary cell junctions. There are noElectron micrograph of tumor in dog 1. Two polygonal tumor cells joined by rudimentary cell junction adjacent

diagnostic structures.to a spindle-shaped cell. Polysomes are prominent.signs similar to those of our dogs includes malignantlymphoma, osteosarcoma, mesenchymal chondrosar-coma, embryonal rhabdomyosarcoma, and malignantmelanoma. The light microscopic features of the tu-mors in our dogs excluded all of t h e~e .~s~ - l~lso, mel-anomas usually develop in older dog^.^,^^Ultrastructural examinationof tissue specimens fromthree tumors confirmed results of light microscopy thatthese tumors were undifferentiated neoplasms. Nu-merous polysomes often were found in rapidly-growinganaplastic tumor cells.6 Features of epithelial differ-entiation, i.e., tonofilaments, lumens, microvilli, andbasement membrane were not evident making a di-agnosis of carcinoma untenable. The presence of celljunctions ruled out lymphoma, and the absence of pre-melanosomal organelles is not compatible with malig-nant melanoma. Rudimetary cell junctions have beenseen in poorly-differentiated carcinomas and, occa-sionally, sarcomas.6 The cells of embryonal rhabdo-myosarcoma usually are partially surrounded by base-ment membrane and contain arrays of actin and myosin

filaments in the cytoplasm. The fine structural findingsindicate an undifferentiated tumor and do not permitfurther subclassification. Immunocytochemical stud-ies further support the truly undifferentiated nature ofthis neoplasm. In humans also, there are neoplasmswhich are not possible to subclassify with presentlyavailable techniques.

AcknowledgementsAuthors thank the Bodman Foundation for support, A.Christine MacMurray for editorial assistance, Dr. T.-T. Sien

and DAKO, Inc. for supplying antibodies for immunocy-tochemistry, and Maryann D. Gangi and Daisy Jimenez-Joseph for the immunocytochemical procedures.

ReferencesAzar HA, Espinoza CG, Richman AV, Saba SR, WangT: Undifferentiated large cell malignancies: an ultra-structural and immunocytochemical study. Hum Pathol13:323, 1982Brodey RS: Canine and feline neoplasia. Adv Vet SciComp Med 14:309, 1970Cohen D, Brodey RS, Chen SM : Epidemiologic aspects

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Undifferentiated Tumors of the Oral Cavity in Six Dogs 175of oral and pharyngeal neoplasms of the dog. Am J VetRes 251776, 1964

4 Cohen D, Reif JS, Brodey RS, Keiser H: Epidemiologicalanalysis of the most prevalent sites and types of canineneoplasia observed in a veterinary hospital. Cancer Res34:2859, 19745 Dorn CR, Taylor DO, Schneider R, Hibbard HH, Klau-ber MR: Survey of animal neoplasms in Alameda andContra Costa counties, California. 11. Cancer morbidityin dogs and cats from Alameda County. J Natl CancerInst 40:307, 1968

6 Erlandson RA : Diagnostic Transmission Electron Mi-croscopy of Human Tumors: The Interpretation of Sub-microscopic Structures in Human Neoplastic Cells, pp.33, 107. Masson Publishing USA, Inc., New York, 1981

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8 Hulland TJ: Tumors of muscle. In : Tumors in Domestic

Animals, 2nd ed., ed. Moulton JE, p. 75. University ofCalifornia Press, Berkeley, 1978

9 Moulton JE, Dungworth D L Tumors of the lymphoidand hemopoietic tissues. In : Tumors in Domestic Ani-mals, 2nd ed., ed. Moulton JE, p. 156. University ofCalifornia Press, Berkeley, 197810 Patnaik AK, Lieberman PH, Erlandson RA, Liu S-K:Canine sinonasal skeletal neoplasms: chondrosarcomasand osteosarcomas. Vet Pathol 21:475, 1984

11 Pool RR: Tumors of bone and cartilage. In : Tumors inDomestic Animals, 2nd ed., ed. Moulton JE, p. 111 .University of California Press, Berkeley, 1978

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13 Stannard AA, Pulley LT: Tumors of the skin and softtissue. In : Tumors in Domestic Animals, 2nd ed., ed.Moulton JE, p. 62. University of California Press, Berke-ley, 1978

14 Sternberger LA: Immunocytochemistry, 2nd ed., p. 82.John Wiley and Sons, New York, 1979

Request reprints from Dr. A. K. Patnaik, Department of Pathology, Donaldson-Atwood Cancer Clinic, Animal MedicalCenter, New York, N Y 10021 (USA).

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