Primary Pigmented Intraocular Tumors in Animals

L. Z. SAUNDERSANDC. N. BARRON

(Brookhaven National Laboratory, Upton, N.Y., and Armed Forces Institute of Pathology, Washington, D.O.)

Intraocular melanomas, among the most com mented intraocular tumors together as "melano mon eye tumors in man, have seldom been reported mas." However, medullo-epitheliomas and uveal in animals. This is particularly surprising in regard melanomas are distinct from each other and from to the dog, a species that usually lives well into the adenomas and carcinomas in histogenesis, which "tumor age" and is affected by diverse neoplasms. makes such combining scientifically untenable. In his "Pathology of Tumours" (1953) Willis (48) Medullo-epitheliomas are not known to metasta- stated : ' 'I have not read of an intraocular melano size, whereas carcinomas can and uveal melano ma in an animal." While reported cases are not as mas often do; hence, there are also practical rea rare as this statement might imply, those that we sons for distinguishing among them. have found do not make an imposing total, attest In classifying human intraocular melanomas for ing to the apparent rarity of intraocular melano prognostic purposes, Wilder and Paul (47) applied mas in animals. In addition to melanomas, this two diagnostic criteria. The first is the histologie report embraces the tumors arising from the epi type, of which six are recognized: spindle A, thelium of the iris and ciliary body. spindle B, fascicular, necrotic, mixed, and epi- Reports of intraocular tumors of any kind in theliod, in order of increasing malignancy. This animals, whether primary or metastatic, number order was determined through a 10-year follow-up less than 50. The metastatic tumors (five), leio- on 585 cases and a 5-year follow-up on an addi myomas (one), hemangiomas (one), and retino- tional 226 cases from a series of 2535. blastomas (seven) have been omitted, but reports The second criterion is the argyrophil fiber con of all primary tumors that might come under the tent as revealed by the Wilder reticulum stain. heading of this paper are summarized in Table 1. The reticulum of a tumor may be heavy, medium, Of the cases listed there, only those reported in light, or absent in order of increasing malignancy, adequate detail are discussed in the text that as has been determined by following up the same follows. series of cases. The rationale of this classification The study of Case 1 of our series in 1951 was as proposed by Wilder and Paul is: "If the tumor hampered by the lack of any general discussion of is slow-growing, fiber production keeps pace with intraocular tumors of animals in the literature, tumor growth and fibers are able to encompass and to this day the only sources of information are individual tumor cells, forming a barrier to their widely scattered case reports. Since a number of escape from the globe and particularly into blood other cases of intraocular tumors have become vessels." available for study it is now feasible to compile the information gained from this material and from MATERIALS AND METHODS the literature into a single report. It is hoped that Fifteen cases of intraocular tumor in dogs were this report will dispel the prevalent opinion that available for study, eleven at the Armed Forces pigmented intraocular tumors do not occur in ani Institute of Pathology, and three contributed by mals and will stimulate recognition and further Drs. C. P. Zepp, Jr., H. A. Smith, and H. Veenen- study of them. daal. The eye in Case 1, studied clinically by one According to the literature, pigmented tumors of us (L.Z.S.) at Cornell University, was obtained in the eye may be melanomas of the uveal tract, after enucleation. Additional canine material was medullo-epitheliomas, adenomas, and carcinomas. studied from the cases of Bloom (6), Hopper (26), The kst two listed are derived from the mature and Cotchin (12), previously published, and from pigmented or nonpigmented epithelium of the an unpublished case of Dr. R. M. Mulligan. Ma ciliary body and from the pigment epithelium of terial from several human intraocular tumors at the iris. In the older literature, both medical and the Armed Forces Institute of Pathology was veterinary, the tendency was to combine all pig- studied for comparison. The materials were embedded in either paraffin Received for publication September 30, 1957. or celloidin, and sections were stained with hema- 234

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. TABLE1 SUMMARYOFPREVIOUSLYREPORTEDCASESOFPOSSIBLEPRIMARYINTRAOCULARTUMORSINANIMALS* AUTHOBANDYEAB SEX AOE DESCRIPTION Dogs Peut: 1919 F 6 years Melanotic sarcoma of the choroid which penetrated the cornea at the liubus of the right eye. Leone: 1926 M Pigmented sarcoma of left eye resulting in increased intraocular tension. Euthana sia, followed by necropsy; no visceral mÃ©tastasesfound, opposite eye normal. Tumor involved iris and ciliary body but not the choroid. Histologically, the cells were in alveolar and glandlike formations. Chaillous and Robin: 8 years "Melanotic sarcoma" in anterior chamber. Tumor, primary in ciliary body, 1930 pierced the upper half of the iris and extended into cornea. Tonometry indi cated intraocular pressure was increased. Enucleation of eyeball. No extension to the orbit. Buckler: 1933 18 months Bilateral pigmented tumor of the iris, histologically a "round-celled sarcoma." Darraspen: 1939 Tumor of the choroid, no details. McClelland: 19411 M 10 years Melanoma of choroid, causing blindness, increased intraocular tension, and pain. Eye enucleated, dog alive and well 1 year later. Aged Similar symptoms, euthanasia decided upon. No mÃ©tastasesfound at necropsy. Epithelioid type of melanoma in choroid. Bloom: 1942 M 11 years Tumor of iris seen at 9 months of age; disappeared following two x-ray treat ments. Recurred several months later and was no longer radiosensitive. Dog remained well following enucleation, no tumor present in orbit. Histologically, a pigmented epithelial tumor with gland formation. Fedrigo: 1942 M 14 years Left eye involved by pannus for 1 year and buphthalmus for 5 months. Enuclea tion. Round-celled melanoma of choroid invading the retina, sclera, and cornea, without penetrating the globe. Hopper: 1945 F 6 years Unilateral keratitis and glaucoma. Enucleation. Malignant melanoma of choroid, epithelioid-cell type. Death 16 days following enucleation. MÃ©tastasesfound in lungs, kidneys, and brain. Nordmann and Hoer- M Neuroepithelioma of the ciliary body. ner: 1946 Michael: 1947 F 5 years Eye enucleated because of inflammation, exophthalmos, and pain; healing un eventful. Posterior chamber contained a thick black mass. Death 6 months later; melanotic tumors found in kidneys, ovaries, and uterus. No histologie examination of growths in eye or other organs. Cotchin: 1954 11 years Intraocular epithelial tumor of unknown type. 8 years Adenoma of ciliary body. Aged Intraocular melanoma, no recurrence or metastasis 3 years after enucleation. 13 years Intraocular melanoma. Veenendaal: 1954 Young Tumor arising from the pars ciliaris retinae. Smythe: 1956 Melanotic sarcoma of choroid with extension along optic nerve to thalamus. CatÂ» Petit: 1902 M Sarcoma filling the left globe. Kraus: 1908 Grayish-black uveal sarcoma ("Pigmentsarkom") believed to be primary in the iris or ciliary body. Tumor became extrabulbar at the corneo-scleral junction. Iris greatly thickened; intraocular pressure increased. Eye enucleated. No his tologie description or mention of metastasis or follow-up. Burgi: 1920 Binocular metastatic rarcoma to the uvea, primary supposedly in the lymph nodes and lungs. Freese: 1929 F 7 years Bilateral sarcoma of the choroid which grew through the sclera into the orbit. Mediastinal lymph nodes contained pigmented cells with histologie appearance similar to those of the ocular growths. Leger: 1931 M 5 years Swelling of eye, 8 months' duration. Nonpigmented sarcoma of choroid in right eye with penetration of sclera and cornea. Eye enucleated. No follow-up. Darraspen: 1939 F 11 years Pigmented tumor of iris and ciliary body, arising from the pigmented epithelium of the iris, and encroaching on the pupillary margin. Petisca: 1947 M Intraocular sarcoma, no details. Cotchin: 1957 M 7 years Carcinoma of the ciliary body. HornÂ» Born: 1876 M 18 years Intraocular sarcoma invading choroid, retina, and optic nerve with mÃ©tastases to orbit and submaxillary nodes. KonhÃ¤user:1884 Whole eye included in a tumorous mass. No histologie details, but referred to as a sarcoma. Bayer: 1887 F 16 years Melanoma of choroid, 3 years' duration. Swelling and protrusion of the bulb. Terminally, abnormally high gait ("goose step") and ataxia. Euthanasia be cause of nervous symptoms. Tumor had pierced the cornea and also invaded the brain. Kitt: 1895 Sarcoma of the iris; no details except illustration. Eberlein: 1902 Melanoma of the iris, listed in statistical compilation of clinic cases, no details. Houdemer and 8 years Spindle-cell sarcoma with many pigmented cells, primary in the ciliary body. Guyonnet: 1907 Eye enucleated. No mention of extension to the orbit. Hartog and Loran: F 8 years Adenocarcinoma of cylindrical and polygonal cell type, with tendency to rosette 1924 formation in posterior chamber, optic nerve, and orbit. Kelly: 1940 "Melanosarcoma" of choroid, eye enucleated, no details. * Note: Where the sex and age are not given after the authors, this information was omitted in the original description, t Material from these cases and some additional information were subsequently submitted to the Armed Forces Institute of Pathology. The cases are reported in detail herein as cases six and fourteen, respectively.

TABLE \â€”Continued AUTHORANDYEAR SEX AGE DESCRIPTION Cattle Hess: 1884 F 1 year Sarcoma of the iris which impinged on the cornea and lens. Eye enucleated, heal ing uneventful. Richter: 1907 F 5-6 years Round-celled sarcoma of right eye following a horn injury by another cow. Exen- teration of orbit. No further details. Ball and Zaessinger: Epithelioma of the nonpigmented cells of the ciliary body which grew through the 1929 the iris causing keratoconus, staphyloma, and rupture of the cornea. Eye enu cleated. Histologically, the tumor cells had a glandular arrangement resembling thyroid. Craig and Da vies: F 11 years Tumor of iris and ciliary body of right eye; enucleated. Cow became emaciated 1937 after surgery and was killed 2 months later. Necropsy revealed similar tumor in left eye and in the parotid lymph nodes, lungs, liver, and kidneys. Sheep Bland-Sutton: 1885 "Melanotic sarcoma," intraocular.

Rabbit Brown and Pearce: M 18 months Melanoma arising from either the iris or the ciliary body. No extension present 1926 at necropsy to the orbit or to other organs. Chicken Ball: 1946 F 2 years Melanoma of iris, loss of pupillary reflexes. Preceded by small dark bleblike patches on the iris. No lesions elsewhere in the body. Fish Levine and Gordon: Malignant melanoma of the choroid, bilateral, conditioned by a genetic factor. 1946

toxylin and eosin, Masson's trichrome stain, Upon dissection of the eye, the tumor was found Wilder's reticulum stain, toluidine blue for mucin, to be adherent to the internal periphery of the and melanin bleach followed by hematoxylin and cornea over a segment of about 60Â°ofits circum eosm. ference in the lower outer quadrant. In addition, CASE REPORTS a round nodule of tumor tissue about 1 mm. in diameter was found on the anterior surface of the Case I.1â€”A12-year-old male cocker spaniel was iris at a point opposite the large tumor. admitted to the small animal clinic at Cornell Histologically, the tumor consisted of cuboidal University with symptoms of glaucoma in the epithelial cells with scanty cytoplasm and large, right eye. The intraocular tension was increased round or ovoid nuclei. Only a few mitotic figures over that of the left eye, and the dog evinced pain were seen. Many of the cells were arranged in the on palpation of the right eyeball. A light gray form of alveoli (Fig. 2), but in some areas they growth with a smooth surface could be seen on the were packed solidly enough to obliterate the alveo anterior surface of the right iris, involving about lar architecture. Homogenous eosinophilic materi one-fourth of its circumference (Fig. 1). It had first al in some of these closely packed areas did not been noted by the owner 1 month previously. The stain as mucin with toluidine blue nor as collagen base of the growth was at the periphery of the iris, with Masson's trichrome stain. where it had grown into the cornea. Its apex ex The tumor seemed to arise from the root of the tended somewhat beyond the pupillary margin. iris and did not involve the ciliary body. The fil The pupil was fixed in dilation, and no pupillary tration angle was obliterated by tumor cells which reflex could be elicited. The refracting media were had grown forward from the iris to the cornea and clear, and cupping of the optic disc was not seen then extended along, but did not invade, Desce- ophthalmoscopically. The right eye appeared nor met's membrane. The melanin content of the tu mal; its pupillary reflexes were present. mor was slight; a few melanin-containing cells were The growth had obliterated the filtration angle scattered through it or appeared in a clump near the on the temporal side, the glaucoma being second pupillary margin of the iris. In bleached sections, ary to impaired drainage of intraocular fluid. these appeared as plump, rounded cells (2-3 times Enucleation was performed, since the tumor did not meet Duke-Elder's criteria for iridectomy. the size of those forming the bulk of the tumor) with round nuclei; mitosis was not seen in them. Neoplastic tissue was not found in the orbit. Two The histologie appearance of the isolated iris nod years later the dog was reported to be alive and ule was similar to that of the larger tumor. Both well. were classified as adenoma of the iris originating i AFIP Ace. 766652. from its pigment epithelium.

Case 2?â€”An 8-year-old female cocker spaniel eye section taken for a survey of senile changes in was brought to the veterinary clinic at Iowa State the canine retina, a nodule about 1X2 mm. was College for euthanasia, because it had bitten a man. found, attached to one of the ciliary processes At necropsy (by Dr. H. A. Smith) it was noted (Fig. 4). It had not been noted when the eye was that the refractive media of the left eye were not incised for embedding, so that its extent in the as transparent as the right. The eye was removed gross specimen is not known. The nodule seemed and incised, revealing a mass of white tissue with to have arisen from the base of a ciliary process black borders, 1.5 cm. in diameter and 0.5 cm. but did not involve its tip at the anterior pole of thick in the region of the ciliary body on the the tumor (Fig. 4). medial side. The lens was rotated and displaced Histologically, the tumor appeared to be com laterally. A lesion was not found elsewhere in the posed of compressed ciliary processes sectioned in body. various planes. Many had central vascular cores Histologically, the tumor extended anterolat- (some containing blood), each surrounded by a erally from the root of the iris on the medial side double layer of epithelial cells, thus recapitulating to involve approximately four-fifths of the cornea. the structure of a ciliary process. Although they The sclera at the root of the iris was deeply infil were densely packed, there were discernible spaces trated and thickened by tumor cells which had between these pseudo-ciliary processes. The epi almost, but not quite, penetrated it (Fig. 3). The thelial cells were mature and well differentiated, tumor was in close apposition to the posterior sur and hyperchromatic nuclei or mitotic figures were face of Descemet's membrane and invaded the not seen. The only melanin observed in the tumor corneal substantia propria along its anterior sur consisted of a few trapped particles in its peripher face. The anterior lens capsule was adherent to a al portions. A small area of amorphous basophilic portion of the tumor and to that portion of the material was seen near the central margin of the cornea not covered by tumor. tumor; its nature was not determined. The tumor The tumor was composed of large, round and was diagnosed as an adenoma of the ciliary body. cuboidal cells with pale cytoplasm and dark, round Case 4-*â€”A4|-year-old female fox terrier was to ovoid nuclei. These cells were devoid of pig presented for examination (to Dr. H. Veenendaal) ment, and mitoses were rare. The cells were packed 3 weeks after the owner noted a swelling of her in solid masses in most areas, but in a few their right eye. Clinically, the cornea was found to be arrangement simulated alveolar formation. In clear, and there was no apparent increase of intra parts of the tumor a heavy stroma had formed, ocular tension. A reddish, "pea-sized" growth was and in some of the stroma and at the edges of the visible behind the temporal margin of the pupil; it tumor large plump, melanin-containing cells with appeared to be arising from the ciliary body. The round nuclei were seen. The reticular content of clinical suspicion was malignant tumor of the the tumor was fairly heavy. ciliary body, and the eye was therefore enucleated. The retina had lost its layer organization and A follow-up could not be made. appeared as a thin sclerotic membrane adherent The material available to us consisted of two to the choroid. Both structures were infiltrated paraffin sections through the whole globe, including with plump, melanin-containing cells; similar cells the tumor. In the sections, the tumor appeared as were present in the sclera, ciliary body, iris, and an ovoid mass about 3 mm. long and 1 mm. wide, cornea. attached to one of the ciliary processes by a nar The tumor apparently arose from the epitheli row stalk. The mass had almost no stroma, and um of the iris or ciliary body. In spite of a heavy consisted chiefly of epithelial cells, with a few reticular fiber content, it was evident that the neo- round, but mostly ovoid, nuclei and prominent plastic cells would shortly have penetrated the round nucleoli. The cells were densely packed in sclera and spread to the orbit. Therefore, the some areas and arranged in alveolar formation in tumor was interpreted as an adenocarcinoma of others. A few cells with nuclei 3-4 times the size the iris or ciliary body. The retinal degeneration of the majority were seen; some of these contained was of the type usually seen in canine glaucoma, two nucleoli. Mitotic figures were not seen, and which had probably resulted from blocking of the the only pigment present was a few trapped par filtration angle by the tumor. ticles, mostly at the periphery of the growth. A Case 3.3â€”Anaged cocker spaniel dog was de few blood vessels were scattered throughout the stroyed because of a metastatic seminoma. In an tumor. The growth was bounded by recognizable 'AFIP ace. 766651. and orderly ciliary body epithelium on part of its 3AFIP ace. 786191. ' AFIP ace. 821996.

posterior periphery, but elsewhere the involved uvea. Because of extensive involvement of the eye, ciliary process had been obliterated. It was diag it was impossible to determine the portion of the nosed as an adenoma of the ciliary body. uveal tract in which the tumor had arisen. The Case 5.6â€”A14-year-oldmale mongrel terrier was symptoms of circling may have been due to meta brought to Dr. C. P. Zepp, Jr., because of swelling static invasion of the brain, also a sequel in Hop of the left eye and corneal opacity of unspecified per's case. The obesity and genital atrophy were duration. Profuse hemorrhage in the eye prompted probably related to destruction of the hypothala the owner to seek veterinary advice. He reported mus; the adiposogenital syndrome had been seen the dog in good health, its appetite and activity in several other dogs with hypothalamic le normal, and no evidence of pain until the day be sions (43). fore, when hemorrhage occurred. The terrier was Case 6.6â€”A10-year-old male Boston terrier senile but lively and alert and in good condition. with a history of blindness and pain in the right The left eye was greatly enlarged, and the cornea eye of 2 months' duration was presented for treat had ruptured, but the globe had not collapsed and ment. The intraocular pressure was increased. The was abnormally firm. Shreds of black tissue were eye was enucleated. A black raised area was pres seen at the margins of the ruptured cornea. ent under the bulbar conjunctiva. Further gross The eye was enucleated; evidence of extension description of the specimen was not available. to the orbit was not seen at operation. A trans Histologically, the choroid was diffusely but not verse section through the eyeball revealed that uniformly thickened by round cells containing both chambers were filled with firm, dense, black heavy melanin deposits. In bleached sections the tissue (Fig. 5). The lens was displaced posteriorly, tumor cells were of fairly uniform size and shape, shrunken, and dark brown. Impression smears of corresponding to the epithelioid type. Most of the the tumor showed it to be a melanoma. There was sclera was infiltrated, and invasion of the cornea no evidence of perforation of the sclera. had begun. The argyrophil fiber content was Six months later the owner requested euthana heavy. The tumor had apparently penetrated the sia for the dog because of complete anorexia, a sclera to the conjunctiva, as seen at enucleation, harsh paroxysmal cough, moderate dyspnea, and but this area was not included in the sections. It a circling gait. At necropsy, the carcass was found was classified as a malignant melanoma, epitheli to be obese. Discrete pigmented tumors, from sev oid type, of the choroid. The dog was reported to eral millimeters to several centimeters in diameter, be alive and well 1 year later. were seen on the parietal pleura and pericardium, Case 7.7â€”Theowner of an 8-month-old female in the bronchial lymph nodes, in all lobes of the German shepherd dog had noted a progressively lungs, and in the liver. The pituitary gland was enlarging growth in the eye for a month prior to replaced by black tumor tissue. It also invaded the the examination. Clinically, a blackish, discoid pro brain from the optic chiasm caudad to the pons tuberance approximately 0.5 cm. in diameter was (Fig. 6). There was extensive infiltration of the seen in the lower border of the left iris. In gross hypothalamus and the third ventricle, causing section of the eye, the iris appeared locally massive destruction of the ventricular floor. thickened. The testes were small, firm, and atrophie, and a Histologically, the filtration angle was being Sertoli-cell tumor was present in the left. The pros invaded by tumor cells from a nodule at the pe tate was small and flaccid. riphery of the iris. It was made up of large polyg Histologically, the intraocular tumor consisted onal pigment-laden cells with round or ovoid of polyhedral cells with large round nuclei and nuclei (Fig. 8). The reticular fiber content was lightly pigmented cytoplasm (Fig. 7). Mitotic fig light. The tumor was classified as a malignant ures were fairly numerous. The globe was almost melanoma, epithelioid type, of the iris. Follow-up filled with neoplastic tissue which also invaded the was not available. sclera and cornea. Several areas of necrosis were This case is of interest, because neoplasia is not present deep in the tumor. Tumor cells were seen common in immature dogs. However, among the in the scierai blood vessels. The epithelium of the cases of iridai tumor in Table 1 are two others in which young animals were affected. In Bloom's cornea was hyperkeratotic. The histologie struc ture of the metastatic tumors was similar to that (6) case the dog was 9 months old when the iridai of the ocular one, and the reticular fiber content growth was first seen. In Buckler's (9) case the dog was light in all. The tumor was classified as a â€¢Thisisa detailed description of McClelland's Case 1 (35). malignant melanoma, epithelioid type, of the AFIP ace. 177030. 5AFIP ace. 766650. 7AFIP ace. 200395.

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. SAUNDERSANDBARRONâ€”PigmentedIntraocular Tumors 239 was 15 months old when presented for examina This tumor was classified as a malignant melano tion, but it is evident from his report that the ma, fascicular type, of the uvea. growth was already well established at that time. The neoplastic tissue filled the globe to an ex Case 8.*â€”Thespecimen from an 8-year-old fe tent that obliterated its individual structures. It male Boston terrier dog was not accompanied by was thus impossible to determine the portion of a clinical history. A pigmented mass was present the uveal tract from which the tumor had arisen. in the region of the ciliary body, subjacent to the Its reticular fiber content was medium, and this, scierai bulge, and also involved the whole of the along with the necrosis, would indicate a poor ciliary body and formed a small mass on the oppo prognosis. In the absence of a necropsy, the cause site side (Fig. 9). of the convulsions and death of the dog cannot be Histologically, a large tumor in the ciliary body determined. The symptoms suggest the possibility and root of the iris filled the anterior chamber at that the tumor metastasized to the brain, as oc the filtration angle. The overlying sclera was ele curred in Case 5, and in two published cases vated and thin. The neoplasm was closely ad (3, 26). herent to the corneal endothelium but did not Case JO.10â€”An8-year-old female St. Charles- penetrate the cornea. The iris and ciliary body on cocker spaniel cross-bred dog was presented for the opposite side were also infiltrated with tumor euthanasia. She had been ill for a week and, when cells. The neoplastic cells varied somewhat in size examined, was too weak to stand. The cervical and shape; the majority were large and round, lymph nodes were enlarged. with ballooned cytoplasm distended with melanin Post mortem findings consisted of a pigmented granules. The small hyperchromatic nuclei were subretinal mass in one eye, a mass on the buccal usually obscured by the melanin and could be seen mucosa, nodules from 1.5 to 2 cm. in diameter in only in bleached sections. In several places, the the lungs, bronchial nodes, pancreas, and kidneys, tumor cells tended to be spindle-shaped. The cen and enlargement of the right adrenal. tral portions of the tumor were necrotic. Numer Histologically, a highly cellular neoplastic mass ous cells laden with melanin were present in the was present near the ciliary body (Fig. 14). It con anterior and posterior chambers. Because of the tained considerable melanin pigment and several presence of epithelioid and spindle cells, the tumor areas of necrosis. The cells were spindle-shaped, was classified as a malignant melanoma, mixed with large elongate nuclei, prominent nucleoli, and type, of the iris and ciliary body. scanty cytoplasm. Mitotic figures were numerous. Case 9.9â€”A7-year-old male shepherd dog was The stroma was scanty, and reticular fibers were presented with one eye completely destroyed by a almost lacking. Tumor cells were present in the tumor. There was no history of neurologic involve scierai veins (Fig. 13), but not in the retinal or ment, and the mass was movable, so that surgical choroidal arteries. Neoplastic masses similar in removal was attempted, but could not be com cellular structure to the ocular tumor were seen in pleted. The pigmented tumor tissue that was vis the lungs, kidney, ovary, pancreas, right adrenal, ible was curetted until the orbit appeared free of and buccal mucosa; melanin, however, was pres it. The would healed readily; however, the dog had ent only in the buccal nodules. A diagnosis of convulsions and died 6 weeks later. A post mortem malignant melanoma, spindle-type B, of the cili examination could not be obtained. ary body with metastasis was considered. A description of the gross specimen was not The buccal mucosa of the dog is frequently pig available. Histologically, the tumor was composed mented; hence, it can and often does give rise to of oval to spindle-shaped cells which were usually melanotic tumors. Since in this case a malignant compact and arranged as irregular whorls in a tumor (possibly a melanoma, though lightly pig connective tissue stroma (Fig. 10). The nuclei of mented) was also present in the buccal mucosa, the tumor cells were large and vesicular with a one cannot state with certainty that the visceral prominent nucleolus. Mitotic figures were infre mÃ©tastases came from the intraocular tumor. quent, and only a few nuclei were hyperchromatic. Against this possibility is the propensity of ocular The cytoplasm of a few cells contained brown pig melanomas to metastasize first to the liver; yet no ment, and there were scattered deposits of this metastasis was seen in the liver sections, while nu pigment in areas of necrosis. Plasma cells and merous other organs were infiltrated. In support neutrophils were scattered in the conjunctival tis of a primary uveal origin with metastasis are the sue. Neoplastic cells had infiltrated the optic nerve. facts that (a) tumor cells were present in the 8AFIP ace. 204264. scierai veins, (6) the tumor was necrotic, and (c) it â€¢AFIPace. 261416. 10AFIP ace. 507824.

had almost no reticular fibers. The two latter fea lignant melanomas by the examining pathologist, tures place it among the most malignant of intra but we have not studied them personally. Whether ocular melanomas in the Callender-Wilder classi they are similar morphologically to the intraocular fication. With the concurrent buccal tumor the re tumor has not been established. Thus it cannot be lationship of the ocular melanoma to the growths stated with certainty that the intraocukr tumor elsewhere in the body cannot be determined, nor metastasized. should the possibility of multicentric origin be Case 12.lÃ¯â€”A3-year-old male Irish terrier had overlooked. In our opinion the least likely possi sustained an injury to the right eye 4 months be bility is that the intraocular tumor was meta- fore he was examined. The veterinarian suspected static from an extraocular primary site; an opinion a neoplasm, and the eye was enucleated. Grossly, bolstered by the absence of tumor cells in the the specimen was a dark, irregular mass, approxi arteries of the choroid and retina. mately 5 X 3 X 3.5 cm., without distinguishing Case ll.nâ€”The owner noted an abnormal ap features; its anatomic position in relation to the pearance of the left eye in an 8-year-old male ocular structures could not be established. Upon cocker spaniel dog shortly before presenting him incision of the specimen it was seen that a mass of for examination. A growth on the left iris extended dark tissue surrounded the sclera throughout the from 6 to 10 o'clock. It extended posteriorly to the greater portion of its circumference and had invad ciliary body, and anteriorly to the cornea. The eye ed it posteriorly and extended to the adjacent was enucleated. Upon incision, two-thirds of the extraocular muscles. iris was found to be infiltrated by a white mass Histologically, the mass was composed of neo measuring 13 X 5 X 2 mm.; it occluded the filtra plastic tissue which had apparently originated in tion angle on one side (Fig. 12). the choroid and extended extraocularly by pene Histologically, the growth involved the iris and trating the posterior sclera. Some remnants of ciliary body, which were extensively infiltrated atrophie ciliary processes were recognized, but and thickened. In addition, it extended forward lens, iris, retina, or choroidal tissue could not be and came in contact with the limbus. The tumor distinguished. The tumor was vascular and con consisted of large anaplastic cells with fused cyto tained several necrotic areas. It was composed of plasm and round or ovoid nuclei showing varying both spindle-shaped and polyhedral cells, with the degrees of hyperchromatism. There were numerous former predominating. The nuclei of the spindle- mitotic figures throughout the growth, and some shaped cells were hyperchromatic, vesicular, and of the cells contained melanin pigment. The reticu usually elongated; the nucleoli were prominent. lar content varied ; in some areas it could be clas Numerous mitotic figures were present. Most of sified as medium to heavy, but in adjacent ones the cells contained melanin that often obscured all there was no reticulum at all. Deposits of melanin internal detail. The reticular content varied from but no neoplastic cells were seen in some of the light in most areas to none in a few. It was diag scierai veins. The tumor was classified as a malig nosed as a malignant melanoma, spindle-type B, nant melanoma, epithelioid type, of the iris, and of the uvea. because of the active mitosis and the presence of Because of the extensive destruction of intra areas devoid of reticulum it was considered to be ocular structures, the portion of the uvea from highly malignant. which the tumor arose could not be determined; it On follow-up it was learned that the dog was re is presumed that it arose from the choroid. This is turned to the surgeon 4 months after enucleation the only tumor in the series that exhibited posteri with a tumorous enlargement of the upper gum ex or extraocular extension. The subsequent course is ternally. A month later the dog was destroyed be unknown, but, because of the extensive extraocu cause of the rapidly growing gingival tumor and lar involvement, recurrence and metastasis were noisy respirations, the latter of 4 days' duration. predicted. The left orbital region was grossly free of tumor. Case IS.13â€”A9-year-old male English setter dog A black, firm, oval growth, 3 mm. in diameter, was was presented for treatment of an inflammation of present on the right lower eyelid. The gingival tu one eye which had been noted 2 weeks previously. mor extended inward through the nasal cavity to The eye was enucleated and submitted for histo destroy the sinuses and turbinÃ¢tes.The medulla of logie study without additional clinical data. A both adrenals was involved by similar grayish to mass of tissue about 11 mm. thick was present out black tumor tissue. The gingival and adrenal tu side the globe, extending from the limbus along the mors were reported on histologie study to be ma- u AFIP ace. 480817. 11AFIP ace. 659308. Â»AFIP ace. 263491.

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. SAUNDERSAND BARRONâ€”Pigmented Intraocular Tumors 241 sclera for about one-fifth its circumference. The consisted of a paraffin block of the ocular tumor retina was detached. and of one of the pulmonary lesion. Histologically, the corneal tunica propria on the Histologically, the intraocular structures were involved side was infiltrated by tumor cells. The largely destroyed by neoplastic tissue which occu iris and ciliary body on this side had been largely pied most of the globe. Recognizable lens and cor destroyed by the neoplasm, which infiltrated and neal tissue were not present in the sections, and penetrated the adjacent sclera to reach the extra- only the root of the iris could be identified. Several ocular muscles (Fig. 13). Neoplastic tissue extend ciliary processes were infiltrated by neoplastic ed anteriorly and posteriorly to the lens. Tumor cells which had destroyed adjacent processes and cells infiltrated the iris, ciliary body, and retina of most of the iris. The posterior choroid was free of the side opposite the main tumor and were also neoplasm, but the peripheral portions were invad found in an eosinophilic exÃºdate in the anterior ed. The retina was not invaded by the tumor, but chamber, vitreous humor, and subretinal space. was in close apposition to it and showed changes The retina may have been loosened by the sub- attributed to pressure atrophy, viz., thinning, retinal infiltration of tumor cells, but its detach complete loss of layer organization, sclerosis, and ment was considered to be an artefact, since the only a few remaining cells from one of the nuclear degenerative changes usual in detached retinas layers. The tumor had penetrated the sclera over were not seen. Excavation of the optic disc was a wide area and had raised but not penetrated the deeper (Fig. 13) than the cupping normal in some bulbar conjunctiva. canine discs. It was interpreted as a glaucomatous The tumor consisted of densely packed poly change occasioned by partial blocking of the filtra hedral cells of different sizes, with ovoid nuclei and tion angle by the tumor. scanty cytoplasm; a few areas consisted predomi The neoplasm was composed of polyhedral nantly of spindle-shaped cells. Hyperchromatic epithelioid cells with an abundant cytoplasm and nuclei were few in epithelioid cells but more nu large, usually oval, vesicular, hyperchromatic merous in spindle cells. Mitoses, although rela nuclei. Mitotic figures were numerous. The size of tively few in number, were seen in all parts of the the cells varied, and, in addition, numerous multi- tumor. The pigment content of the tumor cells was nucleated giant cells were observed (Fig. 14). The light, many of them containing a few pigment tumor grew in diffuse sheets and infiltrated the granules, others none. The bulk of the pigment adjacent tissues extensively. Pigment cells were was concentrated in phagocytic cells which were scattered through the neoplasm, probably as a seen in the vicinity of necrotic areas. The diagnosis result of dispersal of such cells normally present was malignant melanoma, mixed type, of the cili in the eye. The reticular fiber content was light in ary body and iris, although spindle cells were not most areas of the tumor and absent in some. The numerous. tumor was diagnosed as a malignant melanoma, Two tumor nodules were found in the lung sec epithelioid type, of the iris and ciliary body. The tions. The larger was an adenocarcinoma, and was extension to the orbit correlated well with its his presumed to be primary in the lung. The other was tologie appearance and light reticular content, a tiny metastatic melanoma, morphologically suggesting eventual metastasis. Follow-up was not similar to the intraocular tumor. available. Case -Z5.15â€”A12-year-oldfemale German shep Case 14-liâ€”A15-year-old spayed female Boston herd guide dog was presented for examination 2 terrier dog was presented for treatment with a his weeks after a growth was noticed in her left eye. tory of blindness of the left eye of several years' The clinician found a tumor that involved the duration. The intraocular pressure was increased. lateral half of the iris and extended forward to the She was destroyed because of a painful bulging of cornea, occluding half of the pupillary area. Small the left eye. Grossly, soft gray masses were at "mÃ©tastases"were evident from 9 to 11 and 6 to tached peripherally to the sclera beneath the bui- 9 o'clock. Some iridai pigment was observed in the bar conjunctiva. Both chambers contained black, nonoccluded pupillary area. The growth was about friable material. The lens was opaque. A yellow the same color as the iris. Several weeks later the necrotic mass 2.5 cm. in diameter was present in eye was enucleated because of pain from increased the right lung. The patient reportedly had "fibro- intraocular pressure. papillomas" all over the skin. The material sub The enucleated eye could not be transilluminat- mitted to the Armed Forces Institute of Pathology ed, although a few flecks of light came through 14This is a detailed description of McClelland's Case 2 (35). half of the cornea, which was pigmented at the AFIP ace. 785978. Â»AFIP ace. 713975.

limbus, opaque, and streaked with white areas of ed detection of the primary site, and two filled the denser opacity. A horizontal section through the globe completely and could only be classified as globe revealed a black mass 6.5 X 4.0 X 14.0 uveal in origin. Considering the three tumors mm. attached to the iris. It protruded anteriorly which involved the iris alone and the three that and was in contact with the corneal endothelium involved the ciliary body in addition to the iris, at the lateral corneal margin. The lens was in this is a very high proportion of iridai tumorsâ€”six pkce. out of eleven. Reese's series of 421 human uveal Histologically, a cellular pigmented neoplasm melanomas contained only 23 iridai tumors, ap diffusely infiltrated and expanded the bulk of the proximately 5 per cent. The frequent occurrence iris, replacing pre-existing elements and extending of tumors of the iris in canine material other than to its periphery and into the filtration angle over ours and in other species of animals is shown in a considerable area. It consisted predominantly of Table 1. This apparent frequency may be real or large polyhedral cells with abundant eosinophilic merely a function of the greater ease of clinical cytoplasm containing golden-brown melanin gran detection of iridai tumors in animals. ules that were so abundant in some as to obscure The representation of the various cell types was cytoplasmic features. The large, round to oval, as follows: five epithelioid, three mixed, one vesicular nuclei had prominent nuclear mem fascicular, and two spindle-type B. In five cases in branes and large nucleoli. Mitoses were not recog which a follow-up was available, the correlation nized. Occasional areas were made up of cells that between the histologie classification and expected were similar but spindle-shaped. Very large cells, prognosis was good. In four (Cases 11-14) out of densely packed with melanin granules, were dis the six cases with extraocular extension, the reticu persed irregularly through the tumor. The reticu lar fiber structure was absent in part or all of the lar fiber content was medium. The tumor was in tumor. In Case 5, the epithelioid cells, necrosis, terpreted as a malignant melanoma, mixed type, and paucity of reticular fibers were all indicative of the iris. It was considered capable of recurring of a poor prognosis; fatal mÃ©tastasesdeveloped and metastasizing, but because of the cell type and within 6 months of enucleation. In Case 6, the reticular fiber content was believed to be less marked reticular fiber content indicated a favor malignant than melanomas of the epithelioid type able prognosis, and the dog was alive and well 1 with less reticulum. The absence of evident scierai year later. In Case 11, the epithelioid type and al invasion and extraocular extension, coupled with most absent reticular content suggested a poor predominant limitation to the iris, were regarded prognosis. On follow-up it was learned that the dog as indicative of a less grave prognosis. The dog was sacrificed 5 months following enucleation with was reported alive and well without recurrence or a rapidly growing gingival tumor that extended to metastasis 21 months after enucleation. involve the nasal cavity and paranasal sinuses. Bilateral adrenal mÃ©tastaseswerefound at necrop DISCUSSION sy. The gingival and adrenal tumors were identi fied as malignant melanomas. Whether they were Fifteen canine cases of pigmented intraocular mÃ©tastasesfrom the intraocular melanoma was tumors form the basis of this study. Four cases not established. In Case 14, the slight reticular were tumors of epithelium of iris or ciliary body fiber content suggested a poor prognosis, which and eleven were malignant melanomas. The was borne out by the pulmonary metastasis. The adenomatous epithelial tumors were in three aged 21-month post-enucleation in Case 15 without evi cocker spaniels and in one mature fox terrier. A dent recurrence or metastasis does not appear un histologie diagnosis of adenocarcinoma was made expected in view of the mixed type, medium retic in one case, but metastasis was not demonstrated. ular content, and predominant iridai confinement. The size of the series is inadequate to establish It is likely that the Callender-Wilder classification breed trends for intraocular malignant melano will also prove useful in the prognosis of intraocu mas, although three of eleven cases were Boston lar melanomas in dogs, but this will have to be de terriers and two were German shepherds. A differ ence in incidence as to sex is not indicated. Twelve termined in a much larger series of cases. Although of the dogs were 7 years old or older, the other some of the cases in the literature cited herein have three were 4f years, 3 years, and 8 months old. good descriptions of cellular components, none has With respect to site, three of the melanomas in any mention of reticular fiber content, so that they the present series involved the iris, one the ciliary cannot be studied from this standpoint of the Cal body, and two the choroid. Three involved both lender-Wilder classification. the ciliary body and iris to an extent that preclud In five of the cases (Nos. 1, 5, 6,14, and 15) there

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. SAUNDERSANDBARRONâ€”PigmentedIntraocular Tumors 243 was clinical evidence of glaucoma, secondary to in the ciliary body, the cases of Hess, Kitt, Houde- blocking of the filtration angle by neoplastic mer and Guyonnet, Brown and Pearce, Chaillous growth, and in two additional instances (Cases 2 and Robin, Buckler, Craig and Davies, Ball, and and 13) with inadequate histories we found histo Cotchin. On the basis of tissues available for our logie evidence of glaucoma. study, we interpret Case 2 of McClelland (our In several instances, the cases reported in the Case 14) to be primary in the iris or ciliary body literature appeared to be epithelial tumors. Ball and not the choroid. With so few available cases, and Zaessinger (2) reported a carcinoma of the both in our own series and in the literature, there nonpigmented epithelium of the ciliary body in a is as yet no basis on which to determine the rela cow, and Darraspen et al. (16) an epithelioma of tive frequency of involvement of the three uveal the pigment epithelium of the iris in a cat. Nei sites. ther of these reports was illustrated. In Bloom's Although four of the uveal melanomas reported (6) case, the glandular structure and epithelial in the literature were in horses, this is a rather appearance were well illustrated and described and small number in view of the great frequency with are consistent with a diagnosis of medullo-epitheli- which this species is affected by cutaneous mela oma. The youth of this patient (8 months) sug nomas. Bland-Sutton (5) commented on this in gests that this was a medullo-epithelioma of the 1922, when after many years of interest in both embryonal type which occurs in children, the so- melanomas and comparative oncology he was un called diktyoma. able to cite a single cases of intraocular melanoma The tumor described by Leone (33) as a pig- in a horse. Cutaneous melanomas occur almost in mented sarcoma in the eye of a dog is probably variably in grey horses, those with other coat also epithelial in nature. He noted that the growth colors being much less frequently affected. Al involved the iris and ciliary body, but not the though these tumors usually metastasize widely choroid. His illustrations are good but depict an to the thoracic and abdominal viscera, there is only epithelial tumor rather than a sarcoma, and many one case on record where intraocular metastasis of the cells are arranged in distinct alveolar forma may have occurred. Darraspen and associates (16) tions. We believe the tumor he described was an reported a sarcoma mÃªlaniquewhich was primary adenoma; his descriptions and illustrations are in in the left eye of a nine-year-old grey mare. Metas consistent with a diagnosis of sarcoma or a pres tasis was present in the submaxillary lymph nodes ent-day diagnosis of malignant melanoma. and in the perineum. The latter region is a rather Nordmann and Hoerner (37) reported a neuro- unlikely site for metastasis from an intraocular tu epithelioma from the ciliary body of a dog, but morâ€”on the other hand, it is the region where a without histologie details or illustrations. It is as large proportion of melanomas in grey horses first sumed that they chose their term to distinguish appear. We consider it more likely that the tumor the tumor from a melanoma. they reported metastasized to the globe from the Cotchin (12) reported two intraocular tumors in perineum than the reverse. dogs, an adenoma of the ciliary body and an intra The iris of the horse normally bears some small ocular epithelial tumor of unknown type. The tu dorsal projections into the pupil, the corpora nigra, mors were not described in detail, but were distin and these occasionally undergo hyperplasia. Sev guished from two other intraocular tumors which eral cases of such hyperplasia are in the literature were classified as malignant melanomas. It would (17, 18, 21) but there is no unequivocal record of thus appear that epithelial tumors of the iris and the hyperplasia's ever assuming a neoplastic char ciliary body are not uncommon in dogs, since four acter. Hyperplasia of the retinal pigment epitheli of the fifteen cases in this series were so classified um in a cow has been reported (45), but we have and five possible cases were found in the literature. not found any report of a neoplasm arising from In addition, two cases were reported in cats (14, these cells. 16) and one in a cow (2). Such tumors appear to Most of the authors of the reports cited here, be somewhat rare among human intraocular including the recent ones, believed that the tu neoplasms. mors they were reporting were very rare, or indeed Of the cases recorded in Table 1 there were had not previously been reported. By bringing the eighteen with sufficient details to permit a diagno various reports together in one place (Table 1), we sis of uveal melanoma. Of these, seven cases have shown that pigmented intraocular tumors do (Bland-Sutton, Bayer, BÃ¼rgi,Freese, McClelland, occur in animals, even though the published re Fedrigo, and Hopper) were melanomas of the ports, like our own data, are as yet too few for choroid. Ten melanomas arose either in the iris or their true incidence to be disclosed.

SUMMARY 8. BROWN,W. H., and PEARCE,L. Melanoma (Sarcoma) in the Eye in a Syphilitic Rabbit. J. Exper. Med., 43:807-13, Primary pigmented intraocular tumors, which 1926. may be diktyomas, adenomas, adenocarcinomas, or 9. BUCKLER,G.K. An Uncommon Condition of the Eye in a uveal melanomas, have been reported for horses, Dog. Vet. Ree., 45:1361, 1933. cattle, sheep, cats, dogs, fish, a rabbit, and a hen. 10. BÃœBGI,O.ÃœberAugengeschwUlste.Schweiz. Arch. f. Tier We have studied a series of fifteen intraocular tu heilk., 62:489-505, 1920. 11. CHAILLOTTS,J.,and ROBIN,V. Sarcome mÃ©laniqueirido- mors from dogs, of which three were adenomas, ciliaire chez le chien. Bull. Soc. opht. France, 5:312-16, one an adenocarcinoma of the iris and ciliary body, 1930. and eleven were malignant melanomas of the uveal 12. COTCHIN,E.Further Observations on Neoplasms in Dogs, tract. Histologically, the melanomas resembled with Particular Reference to Site of Origin and Malig those of man. The biologic behavior was also com nancy. Brit. Vet. J., 110:274-86, 1954. 13. . Melanotic Tumours of Dogs. J. Comp. Path. & parable, inasmuch as some of the melanomas in the Therap., 65:115-29, 1955. dogs extended to the orbit, to the cranial cavity, or 14. . Neoplasia in the Cat. Vet. Ree., 69:425-34, 1957. metastasized to distant organs. The prognostic 15. CRAIG,J. F., and DAVIES,G. O. Sarcomata in both Eye criteria of Callender and Wilder, viz., histologie balls of a Cow. Vet. Ree., 49:84-85, 1937. type and reticular fiber content, were applied to 16. DARRASPEN,E.; FLORIO,R.; and MEYMANDI,M.H. Des our cases. In two instances of metastasis in which modifications humorales dans certaines varieties de tu a necropsy was available, and in six cases with meurs oculaires, cÃ©rÃ©bralesetviscÃ©rales,chezles Ã©quidÃ©s, et les carnivores domestiques. Rev. mÃ©d.vÃªt.,Toulouse, extraocular extension, there was good correlation 91:65-92, 1939. between the histologie expectation and the bio 17. DAWSON,E. K.; INNES, J. R. M.; and HARVEY,W. F. logic behavior. Debatable Tumours in Human and Animal Pathology. VIII. Melanoma. Edinburgh M. J., 46:695-716, 1939. 18. DELBRETJVB.Uncas d'hyperplasie bilatÃ©raledel'Ã©pithÃ©li- ACKNOWLEDGMENTS um pigmentaire de l'iris (grains de suie), avec amaurose This study was commenced in the Department of Pathol consÃ©cutive,chezun jument. Ree. mÃ©d.vÃªt.,95:461-63, ogy, New York State Veterinary College, and thanks are due 1920. to Dr. P. Olafson, head of the department, for permission to 19. DUKE-ELDER,S. Textbook of Ophthalmology, Vol. 3. St. report the data on Case 1. Thanks are due to Drs. C. P. Zepp, Jr., H. A. Smith, and H. Veenendaal for providing the mate Louis: C. V. Mosby, 1941. rials and data for Cases 5, 2, and 4, respectively. We are in 20. EBEHLEIN. Bericht Ã¼berdie kÃ¶nigliche ThierÃ¤rztliche Hochschule, Berlin 1900-1901. Poliklinik f. grÃ¶ssereHaus- debted to Drs. F. Bloom, R. M. Mulligan, and E. Cotchin, who thiere. Arch. f. wissench. prakt. Tierheilk., 28:219-28, kindly provided sections of intraocular tumors from dogs for study and comparison with our material. The portion of this 1902. study carried out at Brookhaven National Laboratory was 21. EVERSBUSCH,O.Hochgradige SehstÃ¶rungbei einem Pfer under the auspices of the U.S. Atomic Energy Commission. de, veranlasst durch eine sehr starke Hypertrophie bezw. Hyperplasie der TraubenkÃ¶rner auf beiden Augen. Ztschr. f. vergi. Augenh., 3:68-74, 1885. REFERENCES 22. FEDHIGO,G.Di un raro caso di melanosarcoma dell'occhio 1. BALL,R. F. Two Unusual Neoplasms in the Chicken Iris. di un cane. Riv. mil. med. vet., Rome, 5:307-13, 1942. Cornell Vet., 36:383-86, 1945. 23. FREESE, W. Beidseitiges primÃ¤resUveasarkom bei der 2. BALL,V., and ZAESSINGER,J.Cancer des procÃ¨sciliaires. Katze, ein Beitrag zur Kasuistik der Augentumoren bei Bull. Soc. se. Vet., Lyon, 32:220-22, 1929. Tieren. Deutsche tierÃ¤rztl.Wchnschr., 37:769-72, 1929. 3. BATER, J. Kleinzelliges Sarcom des Bulbus, Caries der Knochen und der SchÃ¤delbasis.Ztschr. f. vergi. Augenh., 24. HARTOG,J. H., and LORAN,G. J. Carcinoom in de Orbita 5:45-55, 1887. en Bulbus oculi bij het Paard. Tijdschr. v. diergeneesk., 4. BLAND-SUTTON,J.Tumours in Animals. J. Anat. & Physi- 51:556-59, 1924. 25. HESS, E. Rundzellen-Sarkom des Iris bei einem Rinde. ol., 19:415-75, 1885. Schweiz. Arch. f. Tierheilk., 26:239-44, 1884. "Abstr.," 5. . Tumours, Innocent and Malignant, p. 129. 7th ed. London: Cassell, 1922. Ztschr. f. vergi. Augenh., 3:141, 1885. 6. BLOOM,F. Melanocarcinoma of the Iris in a Dog. J. Am. 26. HOPPER,H. D. Some Dog Neoplasms. Cornell Vet., 36: Vet. M. A., 100:439-40, 1942. 137-47, 1945. 7. BORN.Rundzellen-Sarcom vom Auge eines Pferdes. Arch, 27. HOUDEMERandGUYONNET.Tumeur de la choroÃ¯de.Rev. f. Tierheilk., 2:405-13, 1876. gÃ©n.demÃ©d.vÃªt.,10:474-76, 1907.

FIG. 1.â€”Tumorof the iris encroaching on the pupil. Case 1. FIG. 2.â€”Tumor of the iris with epithelial cells in alveolar arrangement. Case 1. H & E, X200. FIG. 3.â€”Adenocarcinoma of iridai and ciliary epithelium with invasion of the sclera (arrow). Case 2. H & E, X2.5. FIG. 4.â€”Section through a small adenoma of the ciliary body. Case 3. H & E, X50.

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. FIG. 5.â€”Cross section of eye completely filled with dark neoplastic tissue. The central depression contained the lens. Case 5. FIG. 6.â€”Coronal sections of brain showing invasion of basal region by dark neoplastic tissue. Case 5. FIG. 7.â€”Histologie details of intraocular malignant mela noma. Case 5. H & E, X350. FIG. 8.â€”Malignant melanoma, epithelioid type, of iris. Case 7. H & E, X425.

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. Fio. 9.â€”Section through entire eye with a malignant mela noma of the ciliary body and iris. Case S. II & K, X-. FIG. 10.â€”Malignant melanoma of uvea showing fascicular arrangement of cells. Case 9. H & E, X168. FIG. 11.â€”Malignant melanoma of ciliary body showing areas of necrosis. The arrow points to a scierai vein packed with neoplastic cells. Case 10. H & E, X14.

Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. Downloaded from cancerres.aacrjournals.org on October 3, 2021. © 1958 American Association for Cancer Research. Pio. 12.â€”Malignant melanoma diffusely infiltrating the iris and ciliary body. Case 11. FIG. 13.â€”Malignant melanoma of iris and ciliary body showing infiltration and penetration of the adjacent sclera to reach the extraocular muscles, and glaucomatous excavation of the optic disc. Case 13. H & E, XÃÂ». FIG. 14.â€”Malignant melanoma of iris and ciliary body, epithelioid type, showing multinucleated giant cells. Case 13. H & K, XÂ«X>.

28. KELLT,A. J. Melano-sarcoma in the Horse. J. Royal Army 38. PETIBCA,J.N. Blastemas dos animales domÃ©sticos.Repos. Vet. Corps, 12:81, 1940. Lab. Cent. Pat. VÃªt.,Lisboa, 6:361-72, 1947. 29. KITT, T. Lehrbuch der pathologisch-anatomischen Diag 39. PETIT, G. La mÃ©canismedela pigmentation dans le sar nostik ftlr ThierÃ¤rzteund Studierende der Thiermedizin, come mÃ©lanique.Ree.mÃ©d.vÃªt.,95:121-25, 1919. 2:647, Stuttgart: Ferdinand Enke, 1895. 40. PETIT,G., and BRETON.Sarcomedu globe oculaire chez un 30. KONHÃ„USER,F.Sarcom am rechten Auge bei einem Pferde. chat. Bull. Soc. Centr. mÃ©d.vÃªt.,66:38, 1902. Oesterr. Vierteljahrschr. f. wissensch. VeterinÃ¤rk.,61:55- 41. REESE, A. B. Tumors of the Eye. New York: Paul B. 56, 1884. Hoeber, 1951. 81. KRAUS.NÃ¼rnbergermedizinische Gesellschaft und Polikli 42. RICHTER.Kleinzelliges Rundzellensarkom des Auges beim nik: Offizielles Protokol. MÃ¼nchen,med. Wchnschr., 56: Rinde. Beri, tierÃ¤rztl.Wchnschr., 23:945, 1907. 305, 1908. 43. SAUNDERS,L.Z.; STEPHENSON,H.C.; and McEnrEE, K. 32. LÃ‰GER,A.D. Le Cancer du globe oculaire chez les ani Diabetes Insipidus and Adiposogenital Syndrome in a Dog maux. Lyon: ThÃ¨se,1931. due to an Infundibuloma. Cornell Vet., 41:445-58,1951. 33. LEONE,P. Sarcoma dell'occhio nel cane. Ann. ottal. e clin, 44. SMTTHE,R.H. Veterinary Ophthalmology, p. 821. London: ocul., 64:230-34,1926. Bailliere, Tindall, and Cox, 1956. 34. LEVINE,M., and GORDON,M.Ocular Tumors with Exoph- thalmia in Xiphorin Fishes. Cancer Research., 6:197-204, 45. STMMEHS,W. ST. C. Melanosis Derived from the Eye. Brit. M. J., 2:898, 1923. 1946. 35. MCCLELLAND,R.B. Melanosis and Melanomas in Dogs. 46. VEENENDAAL,H.Dictaat VÃ©tÃ©rinaireOogheelkunde,p. 85. J. Am. Vet. M.A., 98:504-7, 1941. Utrecht: the Author, 1954. 36. MICHAEL,S.J. Melanosarcoma of the Eye with Metastasis 47. WILDER,H. C., and PAUL,E. V. Malignant Melanoma of to the Kidneys and Ovaries. J. Am. Vet. M.A., 113:253-54, the Choroid and Ciliary Body. A Study of 2535 Cases. Mil. 1948. Surgeon, 109:370-78, 1951. 37. NORDMANN,J., and HOERNER,G. NeuroÃ©pithÃ©liomadu 48. WILLIS,R. A. Pathology of Tumours. 2d ed. St. Louis: corps ciliare chez un chien. Arch. Opht., 6:472, 1946. C. V. Mosby, 1953.

L. Z. Saunders and C. N. Barron

Cancer Res 1958;18:234-245.

Updated version Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/18/2/234

E-mail alerts Sign up to receive free email-alerts related to this article or journal.

Reprints and To order reprints of this article or to subscribe to the journal, contact the AACR Publications Subscriptions Department at [email protected].

Permissions To request permission to re-use all or part of this article, use this link http://cancerres.aacrjournals.org/content/18/2/234. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC) Rightslink site.