- Email: [email protected]
The Choroid
NOTES, CASES, INSTRUMENTS
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tachment appeared to have fluid under it. The pa tient was advised that further detachment surgery was not indicated. In January, 1957, the patient developed absolute glaucoma in the right eye with pain. Enucleation was done January 11, 1957. The sclera appeared intact and there was no gross evidence of tumor or scleral invasion. The pathologic report was lymphosarcoma, lymphocytic type, of the choroid with extension through the sclera. The slides were ex amined by several pathologists, including the Armed Forces Institute of Pathology, and the diagnosis was the same from each examiner (figs. 1, 2 and
3). While the patient was still in the hospital, a thorough physical examination was done by an internist, with lymphomatous disease in mind. No nodes were found and all blood and bone-marrow studies were normal. The right orbit was treated with 1,200 r of X-rays as measured in air, to each of two ports. The patient has had subsequent check-ups in the past three years and still there is no evidence of general lymphogenous disease, and no recurrence of the primary process in the orbit. 1201 West Presidio
Street.
REFERENCES
Benedict, W. L., and Martens. T. G.: Malignant lymphocytic tumors of orbit. S. Clin. North America, 26:871-875, 1946. Forrest, A. W.: Intraorbital tumors; Arch. Ophth., 41:198-232, 1949. Hartshorne, I.: Lymphosarcoma of the orbit: Probably arising in the choroid. Am. J. Ophth., 5:604608, 1922. McGavic, T. S.: Lymphomatoid disease involving the eye and its adnexa. Arch. Ophth., 30:179-189, 1943. Reese, A. B.: Tumors of the Eye. New York, Hoeber, 1951, pp. 453-469. Stout, A. P.: Results of treatment of lymphosarcoma. N.Y. State T. Med., 47:158-164, 1947. ■ : Is lymphosarcoma curable? I.A.M.A., 118:968-970, 1942.
T H E CHOROID A S SITE OF P R I M E MANIFESTATION OF SYSTEMIC INVOLVEMENT I N S K I N MELANOMA
is poor and radical and mutilating surgery is, therefore, not indicated. On the other hand, if the lesion is taken to be another pri mary or a different tumor,3 early surgery is, at present, the treatment of choice.
REPORT OF A CASE CLINICAL REPORT LESTER L. COVELL,
M.D.
Boston, Massachusetts AND H A R R I H . M A R K I E W I T Z , M.D.
Brookline, Massachusetts Ernst Fuchs 1 stated that a metatastic choroidal sarcoma was unknown. A review of the literature and personal communica tions with colleagues confirmed the rarity of a secondary involvement of the eye in malig nant melanoma. A description in detail of such a case therefore seems warranted. 2 Presently accepted views that malignant melanoma can arise from multiple origins adds a therapeutic problem as well as a diag nostic one. T h e assumption that the intra ocular manifestation represents a distant metastasis of a primary lesion elsewhere leads to the conclusion that the life prognosis
H. M., a 43-year-old white carpenter, was first seen by an ophthalmologist on February 11, 1960, with the chief complaint of blurred vision in the right eye. Family history was irrelevant. Past his tory revealed that the patient was originally re jected from military service because of an easily reducible inguinal hernia. Following reduction of this hernia in 1942, he was admitted to active duty and was discharged five months later because of a "nervous condition." The only other medical com plaint consisted of a persistent rash on both legs, diagnosed as lichen planus. The present lesions began over 20 years ago at which time he recalls a "birth-mark" on his left heel. The birth-mark was symptom-free until 1956 when he stated that a callus developed which was diagnosed as a plantar wart and treated by nitric acid, followed by curettage. In 1958, the lesion began draining clear fluid and was painful on wear ing a shoe. It gradually became more prominent and, early in 1959, a biopsy was taken under local anesthesia. At this time the left inguinal lymph nodes became easily palpable and the patient was hospitalized in June, 1959. Examination of the lesion at this time showed
NOTES, CASES, INSTRUMENTS an area about the size of a 10-cent piece, slightly elevated, white and not pigmented, over the left heel. There was a recurrence of the left inguinal hernia and the rash over the lower extremities. Chest X-ray films were reported negative. Urine contents: 5.0 WBC, + albumin; -f- bacteria, and three epithelial cells. BUN was 11 mg. percent. A wide margin excision of the lesion on the heel, with a primary closure of the wound, was performed under spinal anesthesia. After receiving the pathologic report, a radical left groin dissec tion was done and revealed grossly positive nodes present to within one cm. of the bifurcation of the internal and external iliac arteries. The patient made an uneventful recovery and was discharged on July 3, 1959. In the interval from July, 1959, until February, 1960, the patient gained 30 pounds in weight and appeared to be in good physical condition. He had returned to his regular employment and was symtom-free until his visual complaint of blurring of his right eye was noted. The patient consulted an optometrist who dis covered that his myopic astigmatism had changed in the right eye. The patient had been wearing a —2.25D. sph. Z 1.0D. cyl. ax. 180° and this lens was changed to a —1.0D. sph. C —1.0D. cyl. ax. 180°. The blur persisted with the new lens, where upon he consulted an ophthalmologist. At this time the visual acuity in the right eye was cor rected with a —1.0D. cyl. ax. 180° to 20/40. The left eye was corrected to 20/20 with a —3.25D. sph. C 1.0D. cyl. ax. 180°. External examination revealed both eyes to be completely within normal limits, the positive find ings being confined to the fundus of the right eye. Here a gray area was seen adjacent to the macular region, not definitely elevated but distinctively de marcated from the otherwise normal appearing retina. Corresponding to this lesion was an active scotoma superior temporally to the fixation point, measuring five degrees with a 3/1000 white ob ject. Two weeks later the refraction in the right eye had changed to a +2.5D. sph. C —1.0D. cyl. ax. 180° and the visual acuity was corrected to 20/50. The fundus lesion was then definitely ele vated and about two disc diameters in size. On March 12, 1960, the vision had dropped to hand motion. The lesion covered four diopters of elevation and included the entire macular area, spreading nasally over the temporal half of the optic disc. The patient was admitted to the Massachusetts Memorial Hospital on April 10, 1960. At this time both eyes appeared to be within normal limits ex ternally, and no engorged vessels could be seen. Ocular tension was 21 mm. Hg (Schi0tz, new scale) in each eye. The media were clear bi laterally,4 the pathologic findings being confined to the right, somewhat tessellated, fundus. Here, a large solid mass occupied the greater portion of the posterior field of view (fig. 1). The margins were well defined and no retinal breaks or folds were visible. The retina did not appear detached.
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Fig. 1 (Covell and Markiewitz). Topographic position and extent of intraocular mass as seen at time of enucleation two months after onset of visual symptoms. The highest elevation of the mass measured eight diopters. Visual acuity was restricted to perception of shadows in the temporal periphery. X-ray examination of the chest revealed a few discrete nodular densities in the right lung (fig. 2), suspicious of metastases. Urine contained 5.0 to 7.0 WBC and 2.0 or 3.0 RBC per high-power
Fig. 2 (Covell and Markiewitz). Roentgen film of right chest at time of enucleation. Indicated are four nodular densities compatible with metastatic disease.
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NOTES, CASES, INSTRUMENTS
Fig. 3 (Covell and Markiewitz). Normal epi dermis of heel with no definite junction activity (left). Pleomorphonuclear tumor cells, largely in alveolar formation and lacking continuous cohesiveness (right). field. Alkaline phosphatase was 4.1. Bodansky units and transaminase: 24 units. PSP excretion was: 0 in 15 min., 19 percent in 30 min., 20 percent in one hr. and 55 percent totally (two hr). The dif ferential blood picture was normal. The right eye was enucleated the day after admission. No extrabulbar extensions of the tu mor were seen in the orbit at the time of enucleation. Healing was uneventful and the patient went home on the third postoperative day.
tinct character and consisted of cell groups of varying size separated by a fibrous stroma. Some of these alveoli were more basophilic than others and also the cohesiveness of the cells within them varied greatly. The cell form was pleomorphic but pre dominately fusiform, the individual cells pointing in one direction in such manner as to leave the impression of flow. They most properly fitted the description of spindle cells subtype B, possessing, as they did, prominent nucleoli. Occasionally larger and more eosinophilic cells were seen, whose nucleus had a more rounded configuration, and which could therefore be typed as epitheloid cells. Cuboidal cells were rather num erous.5 The number of cells in all stages of mitosis was large, metaphase, anaphase or telophase. Atypical mitotic figures were not detectable with certainty. Blood vessels and hematogenous cells were most abundant at the vicinity of the ulcerated area. No pig ment was visible anywhere. Of the 22 superficial lymph nodes ob tained from the inguinal area one contained malignant cells; two deep lymph nodes were reported negative. The histologic picture
PATHOLOGIC REPORT
The erosive lesion of the skin, which was excised in June, 1959, appeared on crosssection to go down into the subcutaneous tissue and invade this supportive structure quite extensively. The cut surface was somewas gritty. Histologic slides were prepared with the usual hematoxylin-eosin stain (figs. 3 and 4 ) . Pronounced keratosis, as typical to the skin of the heel, was observed, but no junctional activity could be identified with cer tainty. The normal structure of the epider mis was, however, interrupted for about 10 mm. by an ulcer. Here areas of necrosis, in cluding cell debris, were prominent. Below this surface the structure had a more dis
Fig. 4 (Covell and Markiewitz). Fascicular arrangement of predominantly spindle cells with distinct nucleoli (skin).
NOTES, CASES, INSTRUMENTS
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Fig. 6 (Covell and Markiewitz). Intraocular lesion seen on section. Ciliary nerve in sclera (left), optic nerve and retina (right).
Fig. 5 (Covell and Markiewitz). Section from regional lymph node demonstrating fascicular (left) and alveolar (right) configurations. Fusiform cells are found mostly in fascicles, whereas cuboidal cells in alveoli. resembled that of the heel (fig. 5 ) . T h e structure was lobular, groups of cells being separated by a fibrous stroma. T h e cells themselves formed fascicular strands and possessed a well-defined nucleolus. In some groups the nuclei were more round than fusiform, giving the impression as though the spindles had been cross-sectioned. Pig ment was completely absent here too. T h e enucleated eye was fixed in formalin and the sections stained with hematoxylineosin. Grossly, the fundus lesion appeared of light brown color and measured IS mm. in diameter and 5.0 mm. in thickness (fig. 6 ) . T h e retina detached artificially on section. T h e report received from the pathologic laboratory of the hospital was: "Malignant melanoma compatible with primary origin in the eye." I n relation to the previous slides from the heel and lymph nodes it noted that "the tumor seen in these sections is histologically indistinguishable from that seen in the eye. It seems reasonable to consider the eye as the primary site of the tumor with metastases to the heel and inguinal lymph nodes."
O n microscopic examination the entire eye was not remarkable except for the posterior portion adjacent to the optic nerve entrance. At this site, a basophilic cellular mass was present in the choroid (fig. 7 ) , seemingly in filtrating this layer alone. Neither the sclera nor the optic nerve was observed to have been directly invaded by malignant cells (fig. 8 ) . The elongated cells were arranged in characteristic interwining bundles, fasciculi, whorls and palisadelike formations. The ap pearance (fig. 9 ) therefore suggested, at first, a neurogenic origin. 0 Indeed, spindle cells were seen inside a scleral emissary of a posterior ciliary nerve (fig. 10). In some areas in the canal it thus became exceed ingly difficult to distinguish between normal
Fig. 7 (Covell and Markiewitz). Invasive tumor edge (right) confined to the pigmented choroid. Bruch's membrane and retinal pigment layer are normal.
NOTES, CASES, INSTRUMENTS
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Fig. 8 (Covell and Markiewitz). No direct pene tration of tumor cells (top) into either sclera (right) or optic nerve (left).
Schwann's cells and malignant cells as seen inside the tumor. The alveolar structure, visible in the lymph nodes and skin, was al most inconspicuous in the ocular lesion. Blood vessels were rare, but areas of necro sis not infrequent. Many cells contained yellow-brown pigment granules, at times ar ranged like cups on both ends of the elon gated nucleus (fig. 11). Mitotic figures were numerous. Although the predominant cell type was, here too, of the spindle B category, cells to which the description of spindle A or epitheloid type would apply, were observed. No Wilder silver stain7 was obtained to demon strate the relative quantity of argyrophilic reticulum fibers as a presumptive indicator of malignancy. One nevertheless had the im pression that the fibrous stroma was more common in the skin and affected lymph nodes. Similarly, no branching, deeply pigmented cells, as described by Friedenwald8 and Reese,9 could be made out with any de gree of certainty.
in temporal sequences, little doubt would re main that the malignant skin lesion of the left heel preceded the systemic spread, and that therefore the tumor in the eye was only one manifestation of a generalized involve ment. As we know, clinically, trauma can be the exciting cause of change in normal cells to malignant ones. Typical of melanomas5 the tumor spread first by the lymphatics to the regional lymph nodes, and only at a later date did hematogenous metastases appear. The predominant cell type in the ocular lesion resembled the one in the skin and lymph nodes, thus leaving the matter of uniform cytogenesis beyond dispute. The over-all picture may differ some in each of the three sites, due probably to differences in the pre-existing anatomy. That the metastatic lesions are more com mon in the left eye is generally attributed to hemodynamic factors based on the different origin from the aorta of the left and right carotid arteries. However, the circle of Willis can also be reached by way of the symmetrically situated vertebral arteries.
DISCUSSION
The crux of the problem in this case is the inability of fixed histologic pictures to reflect the dynamics of cellular behavior. It is easily understood how the pathologist would state that the ocular lesion represents the original source of the tumor. If, how ever, the pathogenesis is viewed clinically
Fig. 9 (Covell and Markiewitz). Palisadelike arrangement of fusiform nuclei in ocular lesion. Areas of necrosis (top) and multiple mitoses.
NOTES, CASES, INSTRUMENTS
Fig. 10 (Covell and Markiewitz). Ciliary nerve protruding from scleral emissary into melanoma. Spindle cells and pigment are present, both in the canal and tumor. The ocular lesion here described some what defied the accepted appearance of uveal metastases 10 in that it was sharply circum scribed, showed a globular elevation into the vitreous cavity, and the retina was not detached. O n e puzzling phenomenon, over which opinions differ, is the problem of pigment. It is well documented 2 9 that the incidence of malignant melanomas is extremely low in Negroes. O n the other hand, it is said that, if a white horse lives long enough, it is al most certain to die of melanoma. 6 It would appear, therefore, that the frequency of the occurrence of melanoma is inversely pro portional to the degree of normal pigmenta tion. W h e r e a s it is common for liver metastases to contain large amounts of melanin, it has been stated that metastases almost never contain more pigment than the primary tu mor. 12 In our case the choroidal lesion was obviously the more pigmented one. T h e pig ment-forming power of normal choroidal cells is greater than epidermal ones, but whether it is the tumor cells which produce the pigment only the dopa reaction could have determined. Adequate consideration must be given to
1301
the question of multiple primary tumors. Could the choroidal melanoma be a coinci dental primary tumor not related to a hematogenous spread from the melanoma of the heel? The dilemma of whether uveal mela nomas arise from mesenchymal cells 8,9 or from neuro-ectodermal cells 13-15 cannot be elucidated here, although the latter view ap pears to apply better to our case. It is said that neurilemmoma of the eye may arise from Schwann cells around the ciliary nerves as they pass through the scleral canals or enter the uveal tract, 11 and that their nuclei show some degree of pali sading. F r o m Figures 9 and 10 one could be led to believe that we have here a neuri lemmoma, or at least a neurogenic giant growth. FROM THE
LITERATURE
A search for a similar case in the litera ture 16 " 18 reveals only one or two instances in which pigmented nevi of the skin became malignant and metastasized to the uvea. Bromser 1 6 was probably the first (1870) to report such a case, the metastatic nature of which was, however, denied by Fuchs (1882) and others, because the primarylesion on the cheek did not grow, the ocular
Fig. 11 (Covell and Markiewitz). Pigment granules in spindle cell (left) and mitosis (right), as seen in a typical field of the ocular lesion.
1302
NOTES, CASES, INSTRUMENTS
lesion grew extremely slowly (five years) and there were no other systemic metastases. 20 The case of Schiess-Gemuseus and Roth 2 2 involved the optic disc and neighboring retina, but not the choroid. The case reported by I'fluger 21 did not include a histologic examination and it was not decided where the lesion was, in the choroid or elsewhere. Wagenmann, 2 3 too, failed to present histologic documentation as to the site of the metastasis. The ciliary body was affected in Cordes and Horner's case, 24 as well as in that of Corrado. 2 5 In Adamiik's patient 2 ' 1 the primary lesion was in the conjunctiva only.
eludes a well-rounded account of the literature. SUMMARY A case of malignant melanoma of the skin with secondary metastasis to the choroid is presented with its clinical and pathologic aspects. T h e first manifestation of generalized involvement occurred in the choroid of the right eye. T h e ocular picture was histologically and grossly indistinguishable from a primary melanoma of the choroid. T h e possibility of more than one primary focus to explain the clinical and pathologic find; n g s must be considered. Some general aspects of the problem are
Eross 2 7 and Vannas 2 8 recently reported a large series of intraocular neoplasms and mention one or two instances of melanotic
discussed. 358 Commonwealth
,
Avenue.
ACKNOWLEDGMENT
metastases from the skin, without adequate ' ^ description. The most detailed account of such a metastatic lesion of the choroid (inVOlving epitheloid cells predominantly) is r J ° r , . . 1 furnished in F r y s paper, which also in-
„ . , , , , . . _. . Gratetul acknowledgment is made to Charles Snyder, librarian, Lncien Howe Library of Ophthalmology, Harvard Medical School, and to the Massachusetts Eye and Ear Infirmary, for friendly assistance in obtaining needed reference material.
REFERENCES
1. Fry, W. E.: Metastatic sarcoma of the choroid. Arch. Ophth., 9:248, 1933. 2. Verhoeff, F. H.: Personal communication. 3. Asbury, M. K., and Vail, D.: Multiple primary malignant neoplasms. Am. J. Ophth., 26:688, 1943. 4. Kirk, H., and Petty, R.: Malignant melanoma of the choroid. AMA Arch. Ophth., 56:843, 1956. 5. Lever, W. F.: Histopathology of the Skin. Philadelphia, Lippincott, 1954, pp. 458, 460. 6. Boyd, W.: Textbook of Pathology. Philadelphia, Lea, 1950, pp. 285, 296, 39. 7. Wilder, H. C, and Callender, G. R.: Melanoma of the choroid: The prognostic significance of argyrophil fibers. Am. J. Cancer, 25:251, 1935. 8. Friedenwald, J. S.: Melanoma of the choroid. In Penfield's: Cytology and Cellular Pathology of the Nervous System, New York, Hoeber, 1932, pp. 1063. 9. Reese, A. B.: Pigmented tumors. Am. J. Ophth., 27:217, 1944. 10. : Tumors of the Eye. New York, Hoeber, 1953, pp. 503, 507. 11. Armed Forces Institute Pathology: Ophthalmic Pathology: Atlas and Textbook. Philadelphia, Saunders, 1952, pp. 400, 452, 475. 12. Milares, T.: Structural differences in intraocular tumors and their metastases. Ophthalmologica, 98:271, 1940. 13. Theobald, G. D.: Neurogenic origin of choroidal sarcoma. AMA Arch. Ophth., 18:971, 1937. 14. Masson, P.: Les Naevi Pigmentaires. Ann. anat. Pat., 3:417, 657, 1926. 15. Gartner, S.: Malignant melanoma of the choroid and v. Recklinghausen disease. Am T Ophth 23:73, 1940. 16. Kreibig, W.: Zur Kenntnis Intraokularer Sarkommetastasen. Ztschr. f. Augenh., 87:265, 1935. 17. Elshnig, A.: Die Metastatischen Geschwiilste des Sehorgans. Arch. f. Augenh., 22:149, 1891. 18. Ten Doesschate, G.: Ueber Metastatisch Sarkoom in Het Oog. Nederl. Tijdschr. f Geneesk 21432, 1919. 19. Bromser, G.: Ueber ein Fall von Sekundareni Melanom der Chorioidea. Tuaug. Diss., Berlin, 1870. 20. Elschnig, H. H.: Metastatisches Aderhautsarkom. Arch. f. Ophth., 117:316, 1926. 21. Pfliiger, E.: Metastatisches Sarkom der Chorioidea. Arch. f. Augenh., 14:129, 1885. 22. Schiess-Gemuseus, R. M.: Metastatisches Sarcom der Papille u. Angrenzenden Retina Arch f Ophth., 25:177, 1879. 23. Wagenmann, D.: Ein Fall von Multiplen Melanosarkomen mit Eigenartigen Complicationen beiden Augen. Deutsch. Med. Wchnschr., 25:262, 1900.
NOTES, CASES, I N S T R U M E N T S 24. 25. 26. 27. 28. 29.
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Cordes, F. C : H o m e r , W. D.: Metastatic melanoma of both eyes. J.A.M.A., 95:655, 1930. Corrado, A.: Sul sarcoma metastatico del corpo ciliare. Arch. Ottal., 38:508, 1931. Adamiik, V.: Ein Fall v. Metastatischen Melanosarkom d. Uvea. Ztschr. f. Augenh., 21:505, 1909. Eross, S.: Intraokulare Karzinommetastasen. Klin. Monatsbl. f. Augenh., 135:417, 1959. Vannas, S.: Prognose der Malignen Geschwiilste, Klin. Monatsbl. f. Augenh., 135:686, 1959. Scruggs, J. H . : Malignant melanoma of the uvea. Am. J. Ophth., 49:594, 1960.
PAPILLOMA O F T H E LACRIMAL SAC J O H N S. CRAWFORD, Toronto, Ontario
M.D.
Tumors of the lacrimal sac are rare. Duke-Elder* has analyzed 117 of these cases, and found that the majority are granulomas and papillomatous polypi, carci nomas and sarcomas. Of the epithelial tumors, carcinomas are the most common, the occurrence of papillomas being about one third as common as carcinomas. From the clinical point of view, the ap pearances presented by the majority of these lesions are so alike that differential diag nosis is impossible until a biopsy has been done. The following case history is char acteristic. CASE HISTORY A 15-year-old boy ( D . S.) came to the eye clinic at the Toronto General Hospital on Septem ber 7, 1955, complaining of a swelling over the left lacrimal sac and extending into the nasal side of the upper lid. The lump measured approxi mately 8.0 by 8.0 mm. The lump was painless with no inflammation of the overlying skin. H e had come to the clinic because the swelling was affecting his appearance. The patient was not having any excessive tearing from this eye. On pressure over the lump nothing was expressed through the puncta. The patient was treated with antibiotic therapy and returned to clinic on October 5, 1955. At this visit he stated that on pressure over the mass, some pus was expressed through the puncta. Both puncta were dilated and irrigation of the sac was carried out; and saline passed freely into the nose. The local therapy was continued until November 23rd when the patient returned to clinic. At this visit a small curette was passed through the lower punctum and the sac curetted. The curettings were sent for smears and cultures. After this the mass * Duke-Elder, S.: Textbook of Ophthalmology. London, Kimpton, 1954, v. 5, pp. 5345-5358.
appeared to become somewhat smaller until about the end of December, 1955. During the first two weeks of January, 1956, the mass enlarged with the appearance of a mucopurulent discharge. The report on the curettings showed several pieces of stratified squamous epithelium, but no streptothrix were seen. There were many gram-positive bacilli. On February 13, 1956, the patient was taken to the operating room and, under a general anesthetic, an incision was made over the left lacrimal sac above the medial canthal ligament. The sac was identified and an incision made into it. A large mass of lobulated friable tissue presented itself and appeared to be on a pedunculated base. A photo graph was taken at this point showing the tumor in the sac (fig. 1). The tumor was clipped off with a polyp snare and sent for section. It had the appearance of a mulberry. The sac was examined and all traces of the tumor appeared to have been removed. The pathology report (figs. 2 and 3) was as follows: Vascular connective tissue cores are sur rounded by acanthotic squamous epithelium. The basal layers are intact and there is no evidence of malignancy. These tumors are likely to recur if not completely excised. Following the operation the wound healed up without any complications and all discharge dis appeared. During the summer of 1957, the patient noticed the gradual recurrence of the swelling over the tear sac. This increased to about the same size as when it first appeared in 1955. In October, 1957,
Fig. 1 (Crawford). Photograph, showing tumor in the sac.
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tachment appeared to have fluid under it. The pa tient was advised that further detachment surgery was not indicated. In January, 1957, the patient developed absolute glaucoma in the right eye with pain. Enucleation was done January 11, 1957. The sclera appeared intact and there was no gross evidence of tumor or scleral invasion. The pathologic report was lymphosarcoma, lymphocytic type, of the choroid with extension through the sclera. The slides were ex amined by several pathologists, including the Armed Forces Institute of Pathology, and the diagnosis was the same from each examiner (figs. 1, 2 and
3). While the patient was still in the hospital, a thorough physical examination was done by an internist, with lymphomatous disease in mind. No nodes were found and all blood and bone-marrow studies were normal. The right orbit was treated with 1,200 r of X-rays as measured in air, to each of two ports. The patient has had subsequent check-ups in the past three years and still there is no evidence of general lymphogenous disease, and no recurrence of the primary process in the orbit. 1201 West Presidio
Street.
REFERENCES
Benedict, W. L., and Martens. T. G.: Malignant lymphocytic tumors of orbit. S. Clin. North America, 26:871-875, 1946. Forrest, A. W.: Intraorbital tumors; Arch. Ophth., 41:198-232, 1949. Hartshorne, I.: Lymphosarcoma of the orbit: Probably arising in the choroid. Am. J. Ophth., 5:604608, 1922. McGavic, T. S.: Lymphomatoid disease involving the eye and its adnexa. Arch. Ophth., 30:179-189, 1943. Reese, A. B.: Tumors of the Eye. New York, Hoeber, 1951, pp. 453-469. Stout, A. P.: Results of treatment of lymphosarcoma. N.Y. State T. Med., 47:158-164, 1947. ■ : Is lymphosarcoma curable? I.A.M.A., 118:968-970, 1942.
T H E CHOROID A S SITE OF P R I M E MANIFESTATION OF SYSTEMIC INVOLVEMENT I N S K I N MELANOMA
is poor and radical and mutilating surgery is, therefore, not indicated. On the other hand, if the lesion is taken to be another pri mary or a different tumor,3 early surgery is, at present, the treatment of choice.
REPORT OF A CASE CLINICAL REPORT LESTER L. COVELL,
M.D.
Boston, Massachusetts AND H A R R I H . M A R K I E W I T Z , M.D.
Brookline, Massachusetts Ernst Fuchs 1 stated that a metatastic choroidal sarcoma was unknown. A review of the literature and personal communica tions with colleagues confirmed the rarity of a secondary involvement of the eye in malig nant melanoma. A description in detail of such a case therefore seems warranted. 2 Presently accepted views that malignant melanoma can arise from multiple origins adds a therapeutic problem as well as a diag nostic one. T h e assumption that the intra ocular manifestation represents a distant metastasis of a primary lesion elsewhere leads to the conclusion that the life prognosis
H. M., a 43-year-old white carpenter, was first seen by an ophthalmologist on February 11, 1960, with the chief complaint of blurred vision in the right eye. Family history was irrelevant. Past his tory revealed that the patient was originally re jected from military service because of an easily reducible inguinal hernia. Following reduction of this hernia in 1942, he was admitted to active duty and was discharged five months later because of a "nervous condition." The only other medical com plaint consisted of a persistent rash on both legs, diagnosed as lichen planus. The present lesions began over 20 years ago at which time he recalls a "birth-mark" on his left heel. The birth-mark was symptom-free until 1956 when he stated that a callus developed which was diagnosed as a plantar wart and treated by nitric acid, followed by curettage. In 1958, the lesion began draining clear fluid and was painful on wear ing a shoe. It gradually became more prominent and, early in 1959, a biopsy was taken under local anesthesia. At this time the left inguinal lymph nodes became easily palpable and the patient was hospitalized in June, 1959. Examination of the lesion at this time showed
NOTES, CASES, INSTRUMENTS an area about the size of a 10-cent piece, slightly elevated, white and not pigmented, over the left heel. There was a recurrence of the left inguinal hernia and the rash over the lower extremities. Chest X-ray films were reported negative. Urine contents: 5.0 WBC, + albumin; -f- bacteria, and three epithelial cells. BUN was 11 mg. percent. A wide margin excision of the lesion on the heel, with a primary closure of the wound, was performed under spinal anesthesia. After receiving the pathologic report, a radical left groin dissec tion was done and revealed grossly positive nodes present to within one cm. of the bifurcation of the internal and external iliac arteries. The patient made an uneventful recovery and was discharged on July 3, 1959. In the interval from July, 1959, until February, 1960, the patient gained 30 pounds in weight and appeared to be in good physical condition. He had returned to his regular employment and was symtom-free until his visual complaint of blurring of his right eye was noted. The patient consulted an optometrist who dis covered that his myopic astigmatism had changed in the right eye. The patient had been wearing a —2.25D. sph. Z 1.0D. cyl. ax. 180° and this lens was changed to a —1.0D. sph. C —1.0D. cyl. ax. 180°. The blur persisted with the new lens, where upon he consulted an ophthalmologist. At this time the visual acuity in the right eye was cor rected with a —1.0D. cyl. ax. 180° to 20/40. The left eye was corrected to 20/20 with a —3.25D. sph. C 1.0D. cyl. ax. 180°. External examination revealed both eyes to be completely within normal limits, the positive find ings being confined to the fundus of the right eye. Here a gray area was seen adjacent to the macular region, not definitely elevated but distinctively de marcated from the otherwise normal appearing retina. Corresponding to this lesion was an active scotoma superior temporally to the fixation point, measuring five degrees with a 3/1000 white ob ject. Two weeks later the refraction in the right eye had changed to a +2.5D. sph. C —1.0D. cyl. ax. 180° and the visual acuity was corrected to 20/50. The fundus lesion was then definitely ele vated and about two disc diameters in size. On March 12, 1960, the vision had dropped to hand motion. The lesion covered four diopters of elevation and included the entire macular area, spreading nasally over the temporal half of the optic disc. The patient was admitted to the Massachusetts Memorial Hospital on April 10, 1960. At this time both eyes appeared to be within normal limits ex ternally, and no engorged vessels could be seen. Ocular tension was 21 mm. Hg (Schi0tz, new scale) in each eye. The media were clear bi laterally,4 the pathologic findings being confined to the right, somewhat tessellated, fundus. Here, a large solid mass occupied the greater portion of the posterior field of view (fig. 1). The margins were well defined and no retinal breaks or folds were visible. The retina did not appear detached.
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Fig. 1 (Covell and Markiewitz). Topographic position and extent of intraocular mass as seen at time of enucleation two months after onset of visual symptoms. The highest elevation of the mass measured eight diopters. Visual acuity was restricted to perception of shadows in the temporal periphery. X-ray examination of the chest revealed a few discrete nodular densities in the right lung (fig. 2), suspicious of metastases. Urine contained 5.0 to 7.0 WBC and 2.0 or 3.0 RBC per high-power
Fig. 2 (Covell and Markiewitz). Roentgen film of right chest at time of enucleation. Indicated are four nodular densities compatible with metastatic disease.
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NOTES, CASES, INSTRUMENTS
Fig. 3 (Covell and Markiewitz). Normal epi dermis of heel with no definite junction activity (left). Pleomorphonuclear tumor cells, largely in alveolar formation and lacking continuous cohesiveness (right). field. Alkaline phosphatase was 4.1. Bodansky units and transaminase: 24 units. PSP excretion was: 0 in 15 min., 19 percent in 30 min., 20 percent in one hr. and 55 percent totally (two hr). The dif ferential blood picture was normal. The right eye was enucleated the day after admission. No extrabulbar extensions of the tu mor were seen in the orbit at the time of enucleation. Healing was uneventful and the patient went home on the third postoperative day.
tinct character and consisted of cell groups of varying size separated by a fibrous stroma. Some of these alveoli were more basophilic than others and also the cohesiveness of the cells within them varied greatly. The cell form was pleomorphic but pre dominately fusiform, the individual cells pointing in one direction in such manner as to leave the impression of flow. They most properly fitted the description of spindle cells subtype B, possessing, as they did, prominent nucleoli. Occasionally larger and more eosinophilic cells were seen, whose nucleus had a more rounded configuration, and which could therefore be typed as epitheloid cells. Cuboidal cells were rather num erous.5 The number of cells in all stages of mitosis was large, metaphase, anaphase or telophase. Atypical mitotic figures were not detectable with certainty. Blood vessels and hematogenous cells were most abundant at the vicinity of the ulcerated area. No pig ment was visible anywhere. Of the 22 superficial lymph nodes ob tained from the inguinal area one contained malignant cells; two deep lymph nodes were reported negative. The histologic picture
PATHOLOGIC REPORT
The erosive lesion of the skin, which was excised in June, 1959, appeared on crosssection to go down into the subcutaneous tissue and invade this supportive structure quite extensively. The cut surface was somewas gritty. Histologic slides were prepared with the usual hematoxylin-eosin stain (figs. 3 and 4 ) . Pronounced keratosis, as typical to the skin of the heel, was observed, but no junctional activity could be identified with cer tainty. The normal structure of the epider mis was, however, interrupted for about 10 mm. by an ulcer. Here areas of necrosis, in cluding cell debris, were prominent. Below this surface the structure had a more dis
Fig. 4 (Covell and Markiewitz). Fascicular arrangement of predominantly spindle cells with distinct nucleoli (skin).
NOTES, CASES, INSTRUMENTS
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Fig. 6 (Covell and Markiewitz). Intraocular lesion seen on section. Ciliary nerve in sclera (left), optic nerve and retina (right).
Fig. 5 (Covell and Markiewitz). Section from regional lymph node demonstrating fascicular (left) and alveolar (right) configurations. Fusiform cells are found mostly in fascicles, whereas cuboidal cells in alveoli. resembled that of the heel (fig. 5 ) . T h e structure was lobular, groups of cells being separated by a fibrous stroma. T h e cells themselves formed fascicular strands and possessed a well-defined nucleolus. In some groups the nuclei were more round than fusiform, giving the impression as though the spindles had been cross-sectioned. Pig ment was completely absent here too. T h e enucleated eye was fixed in formalin and the sections stained with hematoxylineosin. Grossly, the fundus lesion appeared of light brown color and measured IS mm. in diameter and 5.0 mm. in thickness (fig. 6 ) . T h e retina detached artificially on section. T h e report received from the pathologic laboratory of the hospital was: "Malignant melanoma compatible with primary origin in the eye." I n relation to the previous slides from the heel and lymph nodes it noted that "the tumor seen in these sections is histologically indistinguishable from that seen in the eye. It seems reasonable to consider the eye as the primary site of the tumor with metastases to the heel and inguinal lymph nodes."
O n microscopic examination the entire eye was not remarkable except for the posterior portion adjacent to the optic nerve entrance. At this site, a basophilic cellular mass was present in the choroid (fig. 7 ) , seemingly in filtrating this layer alone. Neither the sclera nor the optic nerve was observed to have been directly invaded by malignant cells (fig. 8 ) . The elongated cells were arranged in characteristic interwining bundles, fasciculi, whorls and palisadelike formations. The ap pearance (fig. 9 ) therefore suggested, at first, a neurogenic origin. 0 Indeed, spindle cells were seen inside a scleral emissary of a posterior ciliary nerve (fig. 10). In some areas in the canal it thus became exceed ingly difficult to distinguish between normal
Fig. 7 (Covell and Markiewitz). Invasive tumor edge (right) confined to the pigmented choroid. Bruch's membrane and retinal pigment layer are normal.
NOTES, CASES, INSTRUMENTS
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Fig. 8 (Covell and Markiewitz). No direct pene tration of tumor cells (top) into either sclera (right) or optic nerve (left).
Schwann's cells and malignant cells as seen inside the tumor. The alveolar structure, visible in the lymph nodes and skin, was al most inconspicuous in the ocular lesion. Blood vessels were rare, but areas of necro sis not infrequent. Many cells contained yellow-brown pigment granules, at times ar ranged like cups on both ends of the elon gated nucleus (fig. 11). Mitotic figures were numerous. Although the predominant cell type was, here too, of the spindle B category, cells to which the description of spindle A or epitheloid type would apply, were observed. No Wilder silver stain7 was obtained to demon strate the relative quantity of argyrophilic reticulum fibers as a presumptive indicator of malignancy. One nevertheless had the im pression that the fibrous stroma was more common in the skin and affected lymph nodes. Similarly, no branching, deeply pigmented cells, as described by Friedenwald8 and Reese,9 could be made out with any de gree of certainty.
in temporal sequences, little doubt would re main that the malignant skin lesion of the left heel preceded the systemic spread, and that therefore the tumor in the eye was only one manifestation of a generalized involve ment. As we know, clinically, trauma can be the exciting cause of change in normal cells to malignant ones. Typical of melanomas5 the tumor spread first by the lymphatics to the regional lymph nodes, and only at a later date did hematogenous metastases appear. The predominant cell type in the ocular lesion resembled the one in the skin and lymph nodes, thus leaving the matter of uniform cytogenesis beyond dispute. The over-all picture may differ some in each of the three sites, due probably to differences in the pre-existing anatomy. That the metastatic lesions are more com mon in the left eye is generally attributed to hemodynamic factors based on the different origin from the aorta of the left and right carotid arteries. However, the circle of Willis can also be reached by way of the symmetrically situated vertebral arteries.
DISCUSSION
The crux of the problem in this case is the inability of fixed histologic pictures to reflect the dynamics of cellular behavior. It is easily understood how the pathologist would state that the ocular lesion represents the original source of the tumor. If, how ever, the pathogenesis is viewed clinically
Fig. 9 (Covell and Markiewitz). Palisadelike arrangement of fusiform nuclei in ocular lesion. Areas of necrosis (top) and multiple mitoses.
NOTES, CASES, INSTRUMENTS
Fig. 10 (Covell and Markiewitz). Ciliary nerve protruding from scleral emissary into melanoma. Spindle cells and pigment are present, both in the canal and tumor. The ocular lesion here described some what defied the accepted appearance of uveal metastases 10 in that it was sharply circum scribed, showed a globular elevation into the vitreous cavity, and the retina was not detached. O n e puzzling phenomenon, over which opinions differ, is the problem of pigment. It is well documented 2 9 that the incidence of malignant melanomas is extremely low in Negroes. O n the other hand, it is said that, if a white horse lives long enough, it is al most certain to die of melanoma. 6 It would appear, therefore, that the frequency of the occurrence of melanoma is inversely pro portional to the degree of normal pigmenta tion. W h e r e a s it is common for liver metastases to contain large amounts of melanin, it has been stated that metastases almost never contain more pigment than the primary tu mor. 12 In our case the choroidal lesion was obviously the more pigmented one. T h e pig ment-forming power of normal choroidal cells is greater than epidermal ones, but whether it is the tumor cells which produce the pigment only the dopa reaction could have determined. Adequate consideration must be given to
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the question of multiple primary tumors. Could the choroidal melanoma be a coinci dental primary tumor not related to a hematogenous spread from the melanoma of the heel? The dilemma of whether uveal mela nomas arise from mesenchymal cells 8,9 or from neuro-ectodermal cells 13-15 cannot be elucidated here, although the latter view ap pears to apply better to our case. It is said that neurilemmoma of the eye may arise from Schwann cells around the ciliary nerves as they pass through the scleral canals or enter the uveal tract, 11 and that their nuclei show some degree of pali sading. F r o m Figures 9 and 10 one could be led to believe that we have here a neuri lemmoma, or at least a neurogenic giant growth. FROM THE
LITERATURE
A search for a similar case in the litera ture 16 " 18 reveals only one or two instances in which pigmented nevi of the skin became malignant and metastasized to the uvea. Bromser 1 6 was probably the first (1870) to report such a case, the metastatic nature of which was, however, denied by Fuchs (1882) and others, because the primarylesion on the cheek did not grow, the ocular
Fig. 11 (Covell and Markiewitz). Pigment granules in spindle cell (left) and mitosis (right), as seen in a typical field of the ocular lesion.
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NOTES, CASES, INSTRUMENTS
lesion grew extremely slowly (five years) and there were no other systemic metastases. 20 The case of Schiess-Gemuseus and Roth 2 2 involved the optic disc and neighboring retina, but not the choroid. The case reported by I'fluger 21 did not include a histologic examination and it was not decided where the lesion was, in the choroid or elsewhere. Wagenmann, 2 3 too, failed to present histologic documentation as to the site of the metastasis. The ciliary body was affected in Cordes and Horner's case, 24 as well as in that of Corrado. 2 5 In Adamiik's patient 2 ' 1 the primary lesion was in the conjunctiva only.
eludes a well-rounded account of the literature. SUMMARY A case of malignant melanoma of the skin with secondary metastasis to the choroid is presented with its clinical and pathologic aspects. T h e first manifestation of generalized involvement occurred in the choroid of the right eye. T h e ocular picture was histologically and grossly indistinguishable from a primary melanoma of the choroid. T h e possibility of more than one primary focus to explain the clinical and pathologic find; n g s must be considered. Some general aspects of the problem are
Eross 2 7 and Vannas 2 8 recently reported a large series of intraocular neoplasms and mention one or two instances of melanotic
discussed. 358 Commonwealth
,
Avenue.
ACKNOWLEDGMENT
metastases from the skin, without adequate ' ^ description. The most detailed account of such a metastatic lesion of the choroid (inVOlving epitheloid cells predominantly) is r J ° r , . . 1 furnished in F r y s paper, which also in-
„ . , , , , . . _. . Gratetul acknowledgment is made to Charles Snyder, librarian, Lncien Howe Library of Ophthalmology, Harvard Medical School, and to the Massachusetts Eye and Ear Infirmary, for friendly assistance in obtaining needed reference material.
REFERENCES
1. Fry, W. E.: Metastatic sarcoma of the choroid. Arch. Ophth., 9:248, 1933. 2. Verhoeff, F. H.: Personal communication. 3. Asbury, M. K., and Vail, D.: Multiple primary malignant neoplasms. Am. J. Ophth., 26:688, 1943. 4. Kirk, H., and Petty, R.: Malignant melanoma of the choroid. AMA Arch. Ophth., 56:843, 1956. 5. Lever, W. F.: Histopathology of the Skin. Philadelphia, Lippincott, 1954, pp. 458, 460. 6. Boyd, W.: Textbook of Pathology. Philadelphia, Lea, 1950, pp. 285, 296, 39. 7. Wilder, H. C, and Callender, G. R.: Melanoma of the choroid: The prognostic significance of argyrophil fibers. Am. J. Cancer, 25:251, 1935. 8. Friedenwald, J. S.: Melanoma of the choroid. In Penfield's: Cytology and Cellular Pathology of the Nervous System, New York, Hoeber, 1932, pp. 1063. 9. Reese, A. B.: Pigmented tumors. Am. J. Ophth., 27:217, 1944. 10. : Tumors of the Eye. New York, Hoeber, 1953, pp. 503, 507. 11. Armed Forces Institute Pathology: Ophthalmic Pathology: Atlas and Textbook. Philadelphia, Saunders, 1952, pp. 400, 452, 475. 12. Milares, T.: Structural differences in intraocular tumors and their metastases. Ophthalmologica, 98:271, 1940. 13. Theobald, G. D.: Neurogenic origin of choroidal sarcoma. AMA Arch. Ophth., 18:971, 1937. 14. Masson, P.: Les Naevi Pigmentaires. Ann. anat. Pat., 3:417, 657, 1926. 15. Gartner, S.: Malignant melanoma of the choroid and v. Recklinghausen disease. Am T Ophth 23:73, 1940. 16. Kreibig, W.: Zur Kenntnis Intraokularer Sarkommetastasen. Ztschr. f. Augenh., 87:265, 1935. 17. Elshnig, A.: Die Metastatischen Geschwiilste des Sehorgans. Arch. f. Augenh., 22:149, 1891. 18. Ten Doesschate, G.: Ueber Metastatisch Sarkoom in Het Oog. Nederl. Tijdschr. f Geneesk 21432, 1919. 19. Bromser, G.: Ueber ein Fall von Sekundareni Melanom der Chorioidea. Tuaug. Diss., Berlin, 1870. 20. Elschnig, H. H.: Metastatisches Aderhautsarkom. Arch. f. Ophth., 117:316, 1926. 21. Pfliiger, E.: Metastatisches Sarkom der Chorioidea. Arch. f. Augenh., 14:129, 1885. 22. Schiess-Gemuseus, R. M.: Metastatisches Sarcom der Papille u. Angrenzenden Retina Arch f Ophth., 25:177, 1879. 23. Wagenmann, D.: Ein Fall von Multiplen Melanosarkomen mit Eigenartigen Complicationen beiden Augen. Deutsch. Med. Wchnschr., 25:262, 1900.
NOTES, CASES, I N S T R U M E N T S 24. 25. 26. 27. 28. 29.
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Cordes, F. C : H o m e r , W. D.: Metastatic melanoma of both eyes. J.A.M.A., 95:655, 1930. Corrado, A.: Sul sarcoma metastatico del corpo ciliare. Arch. Ottal., 38:508, 1931. Adamiik, V.: Ein Fall v. Metastatischen Melanosarkom d. Uvea. Ztschr. f. Augenh., 21:505, 1909. Eross, S.: Intraokulare Karzinommetastasen. Klin. Monatsbl. f. Augenh., 135:417, 1959. Vannas, S.: Prognose der Malignen Geschwiilste, Klin. Monatsbl. f. Augenh., 135:686, 1959. Scruggs, J. H . : Malignant melanoma of the uvea. Am. J. Ophth., 49:594, 1960.
PAPILLOMA O F T H E LACRIMAL SAC J O H N S. CRAWFORD, Toronto, Ontario
M.D.
Tumors of the lacrimal sac are rare. Duke-Elder* has analyzed 117 of these cases, and found that the majority are granulomas and papillomatous polypi, carci nomas and sarcomas. Of the epithelial tumors, carcinomas are the most common, the occurrence of papillomas being about one third as common as carcinomas. From the clinical point of view, the ap pearances presented by the majority of these lesions are so alike that differential diag nosis is impossible until a biopsy has been done. The following case history is char acteristic. CASE HISTORY A 15-year-old boy ( D . S.) came to the eye clinic at the Toronto General Hospital on Septem ber 7, 1955, complaining of a swelling over the left lacrimal sac and extending into the nasal side of the upper lid. The lump measured approxi mately 8.0 by 8.0 mm. The lump was painless with no inflammation of the overlying skin. H e had come to the clinic because the swelling was affecting his appearance. The patient was not having any excessive tearing from this eye. On pressure over the lump nothing was expressed through the puncta. The patient was treated with antibiotic therapy and returned to clinic on October 5, 1955. At this visit he stated that on pressure over the mass, some pus was expressed through the puncta. Both puncta were dilated and irrigation of the sac was carried out; and saline passed freely into the nose. The local therapy was continued until November 23rd when the patient returned to clinic. At this visit a small curette was passed through the lower punctum and the sac curetted. The curettings were sent for smears and cultures. After this the mass * Duke-Elder, S.: Textbook of Ophthalmology. London, Kimpton, 1954, v. 5, pp. 5345-5358.
appeared to become somewhat smaller until about the end of December, 1955. During the first two weeks of January, 1956, the mass enlarged with the appearance of a mucopurulent discharge. The report on the curettings showed several pieces of stratified squamous epithelium, but no streptothrix were seen. There were many gram-positive bacilli. On February 13, 1956, the patient was taken to the operating room and, under a general anesthetic, an incision was made over the left lacrimal sac above the medial canthal ligament. The sac was identified and an incision made into it. A large mass of lobulated friable tissue presented itself and appeared to be on a pedunculated base. A photo graph was taken at this point showing the tumor in the sac (fig. 1). The tumor was clipped off with a polyp snare and sent for section. It had the appearance of a mulberry. The sac was examined and all traces of the tumor appeared to have been removed. The pathology report (figs. 2 and 3) was as follows: Vascular connective tissue cores are sur rounded by acanthotic squamous epithelium. The basal layers are intact and there is no evidence of malignancy. These tumors are likely to recur if not completely excised. Following the operation the wound healed up without any complications and all discharge dis appeared. During the summer of 1957, the patient noticed the gradual recurrence of the swelling over the tear sac. This increased to about the same size as when it first appeared in 1955. In October, 1957,
Fig. 1 (Crawford). Photograph, showing tumor in the sac.