DISCIFORM LESION OVERLYING MELANOCYTOMA SIMULATING PROGRESSION OF CHOROIDAL MELANOMA* BY Melvin L. Rubin, MD THE HEMORRHAGIC DISCIFORM TYPE OF FUNDUS LESION IS A RECOGNIZED CONSE-
quence of a number of diverse clinical entities-notably, disciform senile macular degeneration, presumed ocular histoplasmosis, angioid streaks, traumatic choroidal tears, and drusen of the optic nerve. A case will be presented which implicates still another etiology; the progression of clinical signs simulated the growth of a malignant choroidal tumor. CASE REPORT
A 49-year-old white woman was referred to the University ofFlorida Retina Clinic for evaluation of a small pigmented fundus lesion nasally and adjacent to the left optic disc. The lesion was discovered following a routine cataract extraction. Three years previously, the patient had a cystic hygroma removed from the left side of her neck without complications. One year previously she had a benign breast cyst removed. Otherwise, she was quite healthy. She did have a family history of cataracts developing at an early age (between age 30 and 50). Vision with an aphakic contact lens correction for both eyes was 20/30 in the right eye and 20/25 in the left eye; tension was 16 mm Hg in each eye. Aside from bilateral cataract extractions, the interesting findings was limited to her left fundus, where a 2 x 3 disc-diameter pigmented lesion was visible adjacent to the left optic nerve head (Fig. 1). The lesion appeared to be slightly thickened on Hruby lens exam, and several whitish drusen were present on the surface. No subretinal fluid nor any hemorrhage was present. A tangent screen examination showed an enlarged blind spot with an absolute scotoma corresponding to the size of the lesion. Unfortunately, in 1968, no fluorescein angiography was available. Our clinical impression was that the lesion represented a choroidal nevus, although ajuxtapapillary malignant melanoma could not be excluded. Simple photographic follow-up of the lesion was suggested. *From the Department of Ophthalmology, University of Florida Medical Center,
Gainesville, Florida. TR. AM. OPHTH. Soc., vol. LXXIV, 1976
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FIGURE 1
Clinical photograph of left fundus taken at the initial examination of,a 49-year-old white woman. The pigmented lesion is nasal and adjacent to the optic nerve head and is 2 x 3 disc diameters in size. It is slightly elevated and has multiple drusen on the surface.
At the 3 and 6 month visits, there were no detectable changes in the lesion. At 9 months, the patient complained of the sudden onset of a dense vitreous floater which we found to be caused by a detached vitreous ring from the optic nerve head. No retinal tear was evident and no change was seen in the tumor. During the next several years she was followed by her local ophthalmologist. She developed a rhegmatogenous retinal detachment due to a flap tear in the upper-temporal quadrant of the same eye. This was successfully treated by her ophthalmologist with cryopexy, exoplant, and an encircling #40 silastic band. When we examined her again 1% years after the initial examination, her retina was fully attached; her best acuity was 20/60 in that eye. Her previous detachment had been limited to the upper-temporal quadrant and did not involve the macula nor the nasal area occupied by the lesion in question. Ophthalmoscopic examination at this time (Fig. 2) showed that the pigmented area was still unchanged. However, there were now two small zones of what appeared to be subretinal neovascularization at the nasal margin of the lesion and at the 8 o'clock position (See arrows in Fig. 2). A fluorescein angiogram was done. In the early arterial phase, it showed a blocking defect nasal to the disc that corresponded to the pigmented tumor. In the A-V phase, within the tumor zone, a pattern of vascularity gradually became evi-
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FIGURE 2
Follow-up clinical photograph taken 18 months later. The size of the pigmented lesion is apparently unchanged; however, two, small pinkish patches of subretinal neovascularization were clinically visible (arrows) with a contact lens. There was no subretinal fluid present.
dent and appeared to indicate the presence of an independent vascular supply to the tumor. These vessels were incompetent to fluorescein, the angiogram showing leakage and staining in the late frames of the study (Fig. 3). Our diagnostic impression now favored a malignant choroidal tumor; that is, the angiogram and clinical findings were felt to be compatible with, though not diagnostic of, a choroidal melanoma. However, because there was still no obvious change in size or shape of the pigmented lesion itself, a continued follow-up was suggested. She was to be seen by her local ophthalmologist in one month and again by us in three months. For some unexplained reason, she was lost to followup for two more years! At that time we were again asked to examine her, because she had mild vitreous hemorrhage. Her vision in the left eye had decreased to 20/100 due to the vitreous blood. The appearance of lesion had grossly changed (Fig. 4). Overlying the tumor and extending well beyond it was a serosanguinous retinal detachment. Under the detachment, adjacent to the nasal edge of the pigmented lesion, a pinkish colored elevation was visible. Rimming the edge of the detachment were some subretinal hemorrhages and whitish coagulum, especially nasally and inferiorly. In other words, the lesion had the clinical characteristics of a disciform chorioretinopathy, though in an unusual position. A careful analysis of the overall size of the pigmented lesion itself still did not reveal any grossly apparent change from the
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FIGURE 3
Fluorescein angiogram, performed on the same day as the clinical photograph in Figure 2. This study was interpreted as showing a choroidal tumor compatible with but not diagnostic of a melanoma, producing subretinal neovascularization nasally. A: 16 seconds following injection-early A-V phase: Field shown includes macula, on right. In the earlier, choroidal phase, the zone occupied by the tumor "blocked" the choroidal fluorescence. At the stage shown here, small vessels are visible in the tumor zone and could represent either choriodal neovascularization overlying the tumor or blood vessels integral to the tumor itself; however, a stereoscopic examination of this angiogram, indicates that most of the vessels in the area of the tumor lie within the tumor. B: 22 seconds: At the site of the white arrows shown in Figure 2, the vessels lie superficial to the tumor and probably represent the zones of subretinal neovascularization which were visible clinically. Now the angiogram delineates other zones of subretinal neovascularization which were not visible clinically. These extended further nasally than the tumor edge. Compare this angiogram to the shape of the tumor in Figure 2. c: 3%3 seconds: Fluorescein leaks occur from almost all the blood vessels ofthe tumor and from the neovascular patches. D: 94 seconds: The fluorescein leaks have extended and stained the surrounding tissues.
previous photographs; yet, the general pathologic involvement was now clinically more extensive. The problem was discussed with the patient. Though fundus lesions which look similar are usually benign, the location of the disciform lesion in her eye was unusual. So, while the clinical picture was not a typical one for a malignant melanoma, we were nevertheless suspicious; and unfortunately, we had no reasonable way of ruling out a malignancy. It is possible that a repeat fluorescein angiogram might have helped; however, since the patient had a severe wheezing reaction following the previous intravenous fluorescein, it was decided not to repeat the
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FIGURE 4
Follow-up clinical photograph taken two years after Figure 3 (3% years after the initial photograph). Overlying the tumor, whose exact borders cannot now be delineated, and extending well beyond it nasally is a serosanguinous retinal detachment, rimmed with subretinal hemorrhage at the nasal margin and whitish "exudates" along its upper and lower borders. The clinical picture is one of a disciform detachment of the RPE and retina. The black index lines show the approximate plane in which histopathologic sectioning was done.
study. A general physical, a pelvic examination, and a roentgenogram of the chest were all within normal limits. Following our discussion and another consultation with her internist, she became convinced that she did have an intraocular melanoma and had her local ophthalmologist enucleate her eye without further ado. Taking account of her personality, her history, and her decrease in vision, we could not consider her decision to have the eye removed an unreasonable one. Following enucleation, the formalin fixed eyeball was mailed, with no accompanying clinical summary, directly to our Department of Pathology where sections were prepared that were not optimally oriented.
PATHOLOGIC DESCRIPTION GROSS
Aside from the encircling silastic band, the exoplant affixed to the upper temporal region of sclera, and the extensive areas of focal depigmentation
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_ FIGURE 5
Photomicrographs of tumor (H & E). A: Brownish-black lenticular shaped choroidal lesion under a detached retina (x 10). B: Subretinal coagulum with hemorrhagic debris. The zone of more recent hemorrhage is nasal (X40). c: Note the large number of blood vessels located within the tumor itself (x 120). D: Bleached preparation showing that tumor is composed of large polygonal cells with distinct borders and small nuclei without prominent mitoses-the characteristic appearance of a choroidal melanocytoma. Arrow indicates the relatively normal pigment epithelial layer overlying the tumor (x 180).
and hyperpigmentation evident overlying the buckle, the primary pathology of interest to us was limited to the posterior pole. The disc and macula were unremarkable. Just nasal to the nerve head was a gray-white lesion approximately 3 disc diameters in size. At the nasal border of the lesion was another elevated buff-brown spot. Crosssection of the entire zone exposed a flat, brownish-black lenticular lesion in the choroid (Fig. 5). The lesion was 2% mm in diameter and approximated the thickness of the overlying sclera. Just nasal and overlying the pigmented tumor was the buff-colored subretinal fluid, which elevated the retina at least by 2 mm. The remainder of the choroid and sclera seemed normal. MICROSCOPIC
Occasional mononuclear cells were scattered in the overlying vitreous along with numerous eosinophilic fragments consistent with red cell de-
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FIGURE 6
Photomicrographs of bleached preparation (H & E). A: Cystoid changes are present in the retina overlying the tumor (at arrow 1) and the disciform lesion. The retinal pigment epithelium (RPE) which is clearly visible on the right (just superficial to the tumor) appears normal. Towards the center (at the tumor edge) the RPE thins out and Bruch's membrane splits (arrows 2), with the intervening space filled mostly with fluid and hemorrhagic debris of more recent onset, in contrast to the coagulum in the central subretinal space which is filled with cholesterol clefts and signifies a hemorrhage of longer standing. Area shown within the bracketed central zone is enlarged in b (X50). B: Enlarged view of central area above, at site where Bruch's membrane has split. The dark arrow lies in the plane of the choriocapillaris. The clear arrows identify two blood vessels within and on the retinal side of Bruch's membrane. These subretinal neovascularchannels are thesine qua non of adiagnosis of disciform detachment of the retina (X350).
bris. The retina was detached overlying a lenticular shaped, highly pigmented choroidal tumor. In this region, the retina showed cystoid changes in the outer plexiform layer, the spaces being filled with homogeneous eosinophilic material amongst which were scattered foamy macrophages. In the bleached preparation, the choroidal tumor was composed of relatively large polygonal cells with distinct cell borders and finely granular cytoplasm (Fig. 6). These cells contained small, oval central nuclei with a
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fine chromatin pattern without prominent mitoses. The overlying Bruch's membrane and retinal pigment epithelium were intact except at the nasal edge of the tumor. Bruch's membrane had indistinct borders, and some of the choriocapillaris vessels were occluded on PAS staining. Additionally, capillary vessels were found on the retinal side of Bruch's membrane surrounded by hemorrhage and proteinaceous eosinophilic material. The retinal pigment epithelium was partly detached from Bruch's membrane and separated from it by the new vessels and the hemorrhage and transudate. Elsewhere, eosinophilic proteinaceous material separated the pigment epithelium from the overlying retina. DIAGNOSIS
The diagnosis was melanocytoma of choroid; subretinal hemorrhage, vascularization and disciform retinal detachment adjacent to the tumor. The localized area of hemorrhagic detachment of the retinal pigment epithelium which forms a disciform retinal detachment appeared to be pathogenically related to the melanocytoma. The diagnosis of melanocytoma was confirmed by the Armed Forces Institute of Pathology. DISCUSSION
Typically, nevi and benign pigmentations are dense and relatively avascular, and this helps explain their usual appearance on the fluorescein angiogram-where background choroidal fluorescence 'is decreased or "blocked." Melanomas on the other hand, are usually highly vascular, containing vessels which readily leak fluorescein. This was one factor which led us astray in our clinical diagnosis. In fact, we initially were unaware that vascularization of benign pigmented choroidal tumors occurred at all. We have since learned that nevi and melanocytomata do develop their own blood supplies, though this if far less frequent than in melanomas. Hence, since such integral vascularization can be present, the clinician should not try to discriminate between benign and malignant lesions angiographically on a vascularity basis alone,1 as we discovered retrospectively. Melanocytomas are rare in caucasians compared to their incidence in any of the more highly pigmented races, yet this patient had no Negroid nor Mediterranean ancestry, as far as she knew. The relationship between this tumor and the overlying disciform lesion deserves comment, but no profound elaboration of the many clinical entities associated with subretinal neovascularization is necessary. Suffice
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to say, in each instance a defect in Bruch's membrane is present through which an abnormal neovascular network grows. From these vessels, a transudation of fluid and hemorrhage may occur. When an accompanying hemorrhage takes place, it can be found either within the fragmented Bruch's membrane, under the pigment epithelium, in the subretinal space, or even in the vitreous. The process is a self limited one although recurrent hemorrhages can occur. The coagulum and hemorrhage typically undergo eventual resolution with fibrosis. In this eye, two small neovascular nets were visible ophthalmoscopically on the surface of the tumor prior to the development of the clinically evident disciform lesion. Such neovascular ingrowths can pierce cracks in Bruch's membrane and have been reported overlying certain pigmented lesions of the choroid such as some nevi and melanomata. However, to the best of my knowledge, this type ofclinical picture has not been previously reported in a histologically proven melanocytoma. Shields and Font2 have reported a case of a melanocytoma which simulated a melanoma but not with the accompanying neovascularization and disciform lesion as in this case. However, a melanocytoma is really only one discrete type of uveal nevus,3 so perhaps the association should not be too unexpected. We have studied some of Gass' clinical photographs and angiogram examples shown in his texts4'5 and suggest that some of his "nevi" may actually also represent melanocytomata. Another interesting point is evident in our case. It seems that the primary site of the neovascularization occurred eccentric to the main tumor mass rather then centrally. This is in contrast to what one might expect using a priori inductive reasoning. Logically, one would think that a tumor would be more likely to interfere with the metabolism of the overlying Bruch's membrane centrally and disrupt it where the lesion is usually thickest. While the eccentric positioning in this eye may represent only a spurious finding, it could also represent a predilective site. Apropos of this point, many of Gass' photographs4'5 also show that neovascularization may occur nearer to the edges of a pigmented lesion than centrally. In any event, eccentricity of the neovascularization apparently can occur as part of the natural pathogenic process; thus, one should not argue that the eccentric position per se reduces the probability of a cause and effect relationship between the tumor and the defects in Bruch's membrane. One might still question whether the Bruch's defect in this eye is related to the tumor or to some other cause. For example, it could have been associated with some inadvertant trauma to this area, such as the cryoprobe during the retinal detachment surgery. Prior to that
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intervention, no clinical signs of neovascularization were present. Vigorous manipulation with this instrument certainly could have caused a tear in Bruch's membrane which might have initiated the process, but this is highly unlikely. There would have been no clinical reason for instrumentation to take place on the nasal side of the disc, since the retinal tear giving rise to the detachment was located in the upper-temporal quadrant, well away from the area of the tumor. So, while such a possibility cannot be completely excluded, it is felt to be highly improbable. The relationship between the disciform lesion and the melanocytoma itself might be more tenous had the combination been located on the temporal side of the optic nerve. In that position, a disciform clinical picture might have been attributed to an early disciform macular degeneration rather than to the tumor. Senile disciform lesions are known to occur extramacularly even nasal to the disc, however, this patient is rather young to warrant the diagnosis of senile degenerative changes; moreover, there was no sign of any such tendency in the macula of this or of the other eye. Gass5 points out that when subretinal neovascular membranes occur from any cause within the macular area, they are more apt to bleed. They may create the characteristic localized disciform hemorrhagic detachment of the pigment epithelium since the choroidal blood flow is maximal there. It is of interest that this disciform lesion occurred extramacularly and still bled, despite the location. Considering the overall circumstantial evidence presented, it appears that the disciform lesion in this patient is causally related to the underlying, adjacent melanocytoma.
SUMMARY
A 49-year-old white patient presented with a small pigmented lesion nasal to the disc. The clinical appearance of the area in question was noted to change over a four year period and simulated a progressively enlarging choroidal melanoma. On enucleation, the lesion was histopathologically proven to be a melanocytoma located nasal to the optic nerve head. It caused-or was at least associated with-an overlying disciform hemorrhagic and transudative response secondary to a neovascular ingrowth through Bruch's membrane. Thus, a melanocytoma must now be considered another of the possible causes of a disciform-shaped fundus lesion.
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Rubin ACKNOWLEDGEMENT
Sincere appreciation is extended to Professor Ian Hood, M. D., University of Florida Department of Pathology, for his valuable assistance with the histopathology and the diagnosis. REFERENCES 1. Wessing A: Fluorescein Angiography of the Retina. St. Louis, Mosby, 1969, p 166. 2. Shields JA, Font RL: Melanocytoma of Choroid Clinically Simulating a Malignant Melanoma. Arch Ophthalmol 87:396, 1972. 3. Naumann G, Yanoff M, Zimmerman LE: Histogenesis of Malignant Melanomas of the Uvea. Arch Ophthalmol 76:784, 1966. 4. Gass JDM: Stereoscopic Atlas of Macular Diseases. St. Louis, Mosby, 1970. 5. Gass JDM: Differential Diagnosis of Intraocular Tumors. St. Louis, Mosby, 1974.
DISCUSSION
DR MICHAEL J. HOGAN. It has become increasingly apparent that small benign pigmented and unpigmented nevi of the choroid can induce changes in the choriocapillaris, Bruch's membrane, retinal pigment epithelium and sensory retina that lead to clinical symptoms. The case reported today by Dr Rubin is an undoubted choroidal nevus, melanocytic type, that eventually was associated with neovascularization of Bruch's membrane and subepithelial region and subsequent bleeding. Of great interest was the hemorrhage into the vitreous from this relatively innocuous appearing lesion. Unfortunately the sections of the eye do not reveal the route taken by the blood through the retina into the vitreous. I believe that the manipulations involved in the retinal detachment surgery on this eye initiated changes that eventually caused the neovascularization and bleeding. It has been shown that the choroidal vessels at the edge ofsuch nevi are dilated and it is conceivable they might be damaged by surgery. There is evidence that 32p studies can lead to bleeding when used for the diagnosis of melanomas and it seems likely that the distortions induced in the eye during retinal surgery can lead to alterations in the tissues around a nevus. For this reason we never do 32p studies on small relatively flat pigmented lesions of the choroid, especially if they are posterior to the equator. This is an ideal case to be presented for publication because it calls our attention again to the comments by Zimmerman in his Bedell lecture that not all clinical tests are infallible and that small pigmented lesions should be watched for a considerable period before recommending enucleation (Am J Ophthalmol 75:917-929, 1973). Even a change in size ofmoderate dimension does not provide an indication for surgery. In the present case there were other circumstances that led to enucleation, but in most cases the surgeon should assume a positive attitude and oppose surgery until he is convinced there is clear cut aggressive behaviour on the part of the tumor.
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No special distinction should be made in this case that the tumor is a melanocytoma. The commonest cell in choroidal nevi is the plump polyhedral nevus cell that comprised this tumor. A spectrum of cells from this type to spindle cells is found in such tumors, intermediate forms being recognized in some tumors. Ordinarily the plump polyhedral form is heavily pigmented, whereas the spindle cells are sparsely pigefe whereas the spindle cells are sparsely pigmented. From a standpoint of behaviour they are probably the same in the uveal tract. In the past, stress was placed on the presence or absence of a scotoma to help differentiate benign from malignant lesions. It is true that if there is no scotoma the chance of malignancy is less, but if one is present it does not necessarily indicate malignancy. Fluorescein studies may be positive in some choroidal nevi, and for this reason care should be taken in rendering a judgement as to the presence of a malignant melanoma. The 32p test may be positive in a patient with a small pigmented choroidal lesion. Even so this result should not be used as an evidence for removal of the eye. All other findings should be utilized in the decision on management. I am happy to have been asked to discuss this paper, especially when it has been presented by a friend I have known since his beginning in medicine. DR STEWART M. WOLFF. I am happy to have this chance to comment on Doctor Rubin's very interesting paper. It points up the protean nature ofdisciform lesions. I, too, have a patient with a serous detachment of the retina over a melanocytoma with reduction of vision. In another instance, Doctors Harold Spalter and Frank Carroll and I, have seen a peripheral disciform lesion at the locus of an old histoplasma scar which was indistinguishable from a melanoma. The hemorrhagic phase finally subsided, leaving a large, flat peripheral scar. Finally, just before I left Baltimore, Doctor Stuart Fine showed me a hemorrhagic disciform lesion at the site of an old rubella maculopathy. Thank you very much. DR MELVIN RUBIN. I would like to thank the discussors for their comments. In regard to the question that Doctor Hogan raised about the decrease in vision after retinal detachment surgery, it is probably not too unusual for a patient having retinal detachment surgery, especially with a temporal retinal detachment, to be left with some reduced vision postoperatively. As I recall from the operative note of the surgeon who did the surgery, the macula was not detached preoperatively. On the other hand, it is possible he was wrong and the macula was flatly detached. Since I did not see the patient preoperatively, I do not know. But, of course, if the macula had been detached, that would certainly explain why the vision was decreased. Dr Hogan, it is interesting that in the patients whose slides you showed, of nevi or melanocytoma, the lesions were in the macular areas. This serves to substantiate Gass's comment that I mentioned, that is, that when this type of choroidal lesion lies in the posterior pole, it is more likely to bleed. However, I feel that similar lesions found at other locations in the fundus can still bleed on their own-though
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their own initiation of subretinal neovascularization. In this case in particular, I do not feel that it is necessary to incriminate surgical trauma as the precipitant, though it certainly could have been. As a retinal detachment surgeon, I have some idea of just how much surgical manipulation is necessary to repair a superior temporal tear. So, even though I was not present at the surgery, my best guess is still that there would not have been enough trauma instigated to initiate the process. These lesions are sufficiently active to cause changes in Bruch's membrane and initiate the neovascularization without implicating the surgery. But obviously, I cannot know for sure, and Dr Hogan may be quite correct in his analysis. Again, I would like to thank the discussants and especially Dr Hogan for his valuable and kind discussion of this, my first AOS paper. I am particularly proud since it was he who first introduced me to ophthalmology and afforded me the opportunity ofworking with him in an ophthalmic laboratory. For his gift in showing me the ophthalmic "light" and for his gentle ways, I'll always be grateful. Thank you.
quence of a number of diverse clinical entities-notably, disciform senile macular degeneration, presumed ocular histoplasmosis, angioid streaks, traumatic choroidal tears, and drusen of the optic nerve. A case will be presented which implicates still another etiology; the progression of clinical signs simulated the growth of a malignant choroidal tumor. CASE REPORT
A 49-year-old white woman was referred to the University ofFlorida Retina Clinic for evaluation of a small pigmented fundus lesion nasally and adjacent to the left optic disc. The lesion was discovered following a routine cataract extraction. Three years previously, the patient had a cystic hygroma removed from the left side of her neck without complications. One year previously she had a benign breast cyst removed. Otherwise, she was quite healthy. She did have a family history of cataracts developing at an early age (between age 30 and 50). Vision with an aphakic contact lens correction for both eyes was 20/30 in the right eye and 20/25 in the left eye; tension was 16 mm Hg in each eye. Aside from bilateral cataract extractions, the interesting findings was limited to her left fundus, where a 2 x 3 disc-diameter pigmented lesion was visible adjacent to the left optic nerve head (Fig. 1). The lesion appeared to be slightly thickened on Hruby lens exam, and several whitish drusen were present on the surface. No subretinal fluid nor any hemorrhage was present. A tangent screen examination showed an enlarged blind spot with an absolute scotoma corresponding to the size of the lesion. Unfortunately, in 1968, no fluorescein angiography was available. Our clinical impression was that the lesion represented a choroidal nevus, although ajuxtapapillary malignant melanoma could not be excluded. Simple photographic follow-up of the lesion was suggested. *From the Department of Ophthalmology, University of Florida Medical Center,
Gainesville, Florida. TR. AM. OPHTH. Soc., vol. LXXIV, 1976
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FIGURE 1
Clinical photograph of left fundus taken at the initial examination of,a 49-year-old white woman. The pigmented lesion is nasal and adjacent to the optic nerve head and is 2 x 3 disc diameters in size. It is slightly elevated and has multiple drusen on the surface.
At the 3 and 6 month visits, there were no detectable changes in the lesion. At 9 months, the patient complained of the sudden onset of a dense vitreous floater which we found to be caused by a detached vitreous ring from the optic nerve head. No retinal tear was evident and no change was seen in the tumor. During the next several years she was followed by her local ophthalmologist. She developed a rhegmatogenous retinal detachment due to a flap tear in the upper-temporal quadrant of the same eye. This was successfully treated by her ophthalmologist with cryopexy, exoplant, and an encircling #40 silastic band. When we examined her again 1% years after the initial examination, her retina was fully attached; her best acuity was 20/60 in that eye. Her previous detachment had been limited to the upper-temporal quadrant and did not involve the macula nor the nasal area occupied by the lesion in question. Ophthalmoscopic examination at this time (Fig. 2) showed that the pigmented area was still unchanged. However, there were now two small zones of what appeared to be subretinal neovascularization at the nasal margin of the lesion and at the 8 o'clock position (See arrows in Fig. 2). A fluorescein angiogram was done. In the early arterial phase, it showed a blocking defect nasal to the disc that corresponded to the pigmented tumor. In the A-V phase, within the tumor zone, a pattern of vascularity gradually became evi-
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FIGURE 2
Follow-up clinical photograph taken 18 months later. The size of the pigmented lesion is apparently unchanged; however, two, small pinkish patches of subretinal neovascularization were clinically visible (arrows) with a contact lens. There was no subretinal fluid present.
dent and appeared to indicate the presence of an independent vascular supply to the tumor. These vessels were incompetent to fluorescein, the angiogram showing leakage and staining in the late frames of the study (Fig. 3). Our diagnostic impression now favored a malignant choroidal tumor; that is, the angiogram and clinical findings were felt to be compatible with, though not diagnostic of, a choroidal melanoma. However, because there was still no obvious change in size or shape of the pigmented lesion itself, a continued follow-up was suggested. She was to be seen by her local ophthalmologist in one month and again by us in three months. For some unexplained reason, she was lost to followup for two more years! At that time we were again asked to examine her, because she had mild vitreous hemorrhage. Her vision in the left eye had decreased to 20/100 due to the vitreous blood. The appearance of lesion had grossly changed (Fig. 4). Overlying the tumor and extending well beyond it was a serosanguinous retinal detachment. Under the detachment, adjacent to the nasal edge of the pigmented lesion, a pinkish colored elevation was visible. Rimming the edge of the detachment were some subretinal hemorrhages and whitish coagulum, especially nasally and inferiorly. In other words, the lesion had the clinical characteristics of a disciform chorioretinopathy, though in an unusual position. A careful analysis of the overall size of the pigmented lesion itself still did not reveal any grossly apparent change from the
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FIGURE 3
Fluorescein angiogram, performed on the same day as the clinical photograph in Figure 2. This study was interpreted as showing a choroidal tumor compatible with but not diagnostic of a melanoma, producing subretinal neovascularization nasally. A: 16 seconds following injection-early A-V phase: Field shown includes macula, on right. In the earlier, choroidal phase, the zone occupied by the tumor "blocked" the choroidal fluorescence. At the stage shown here, small vessels are visible in the tumor zone and could represent either choriodal neovascularization overlying the tumor or blood vessels integral to the tumor itself; however, a stereoscopic examination of this angiogram, indicates that most of the vessels in the area of the tumor lie within the tumor. B: 22 seconds: At the site of the white arrows shown in Figure 2, the vessels lie superficial to the tumor and probably represent the zones of subretinal neovascularization which were visible clinically. Now the angiogram delineates other zones of subretinal neovascularization which were not visible clinically. These extended further nasally than the tumor edge. Compare this angiogram to the shape of the tumor in Figure 2. c: 3%3 seconds: Fluorescein leaks occur from almost all the blood vessels ofthe tumor and from the neovascular patches. D: 94 seconds: The fluorescein leaks have extended and stained the surrounding tissues.
previous photographs; yet, the general pathologic involvement was now clinically more extensive. The problem was discussed with the patient. Though fundus lesions which look similar are usually benign, the location of the disciform lesion in her eye was unusual. So, while the clinical picture was not a typical one for a malignant melanoma, we were nevertheless suspicious; and unfortunately, we had no reasonable way of ruling out a malignancy. It is possible that a repeat fluorescein angiogram might have helped; however, since the patient had a severe wheezing reaction following the previous intravenous fluorescein, it was decided not to repeat the
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FIGURE 4
Follow-up clinical photograph taken two years after Figure 3 (3% years after the initial photograph). Overlying the tumor, whose exact borders cannot now be delineated, and extending well beyond it nasally is a serosanguinous retinal detachment, rimmed with subretinal hemorrhage at the nasal margin and whitish "exudates" along its upper and lower borders. The clinical picture is one of a disciform detachment of the RPE and retina. The black index lines show the approximate plane in which histopathologic sectioning was done.
study. A general physical, a pelvic examination, and a roentgenogram of the chest were all within normal limits. Following our discussion and another consultation with her internist, she became convinced that she did have an intraocular melanoma and had her local ophthalmologist enucleate her eye without further ado. Taking account of her personality, her history, and her decrease in vision, we could not consider her decision to have the eye removed an unreasonable one. Following enucleation, the formalin fixed eyeball was mailed, with no accompanying clinical summary, directly to our Department of Pathology where sections were prepared that were not optimally oriented.
PATHOLOGIC DESCRIPTION GROSS
Aside from the encircling silastic band, the exoplant affixed to the upper temporal region of sclera, and the extensive areas of focal depigmentation
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_ FIGURE 5
Photomicrographs of tumor (H & E). A: Brownish-black lenticular shaped choroidal lesion under a detached retina (x 10). B: Subretinal coagulum with hemorrhagic debris. The zone of more recent hemorrhage is nasal (X40). c: Note the large number of blood vessels located within the tumor itself (x 120). D: Bleached preparation showing that tumor is composed of large polygonal cells with distinct borders and small nuclei without prominent mitoses-the characteristic appearance of a choroidal melanocytoma. Arrow indicates the relatively normal pigment epithelial layer overlying the tumor (x 180).
and hyperpigmentation evident overlying the buckle, the primary pathology of interest to us was limited to the posterior pole. The disc and macula were unremarkable. Just nasal to the nerve head was a gray-white lesion approximately 3 disc diameters in size. At the nasal border of the lesion was another elevated buff-brown spot. Crosssection of the entire zone exposed a flat, brownish-black lenticular lesion in the choroid (Fig. 5). The lesion was 2% mm in diameter and approximated the thickness of the overlying sclera. Just nasal and overlying the pigmented tumor was the buff-colored subretinal fluid, which elevated the retina at least by 2 mm. The remainder of the choroid and sclera seemed normal. MICROSCOPIC
Occasional mononuclear cells were scattered in the overlying vitreous along with numerous eosinophilic fragments consistent with red cell de-
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FIGURE 6
Photomicrographs of bleached preparation (H & E). A: Cystoid changes are present in the retina overlying the tumor (at arrow 1) and the disciform lesion. The retinal pigment epithelium (RPE) which is clearly visible on the right (just superficial to the tumor) appears normal. Towards the center (at the tumor edge) the RPE thins out and Bruch's membrane splits (arrows 2), with the intervening space filled mostly with fluid and hemorrhagic debris of more recent onset, in contrast to the coagulum in the central subretinal space which is filled with cholesterol clefts and signifies a hemorrhage of longer standing. Area shown within the bracketed central zone is enlarged in b (X50). B: Enlarged view of central area above, at site where Bruch's membrane has split. The dark arrow lies in the plane of the choriocapillaris. The clear arrows identify two blood vessels within and on the retinal side of Bruch's membrane. These subretinal neovascularchannels are thesine qua non of adiagnosis of disciform detachment of the retina (X350).
bris. The retina was detached overlying a lenticular shaped, highly pigmented choroidal tumor. In this region, the retina showed cystoid changes in the outer plexiform layer, the spaces being filled with homogeneous eosinophilic material amongst which were scattered foamy macrophages. In the bleached preparation, the choroidal tumor was composed of relatively large polygonal cells with distinct cell borders and finely granular cytoplasm (Fig. 6). These cells contained small, oval central nuclei with a
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fine chromatin pattern without prominent mitoses. The overlying Bruch's membrane and retinal pigment epithelium were intact except at the nasal edge of the tumor. Bruch's membrane had indistinct borders, and some of the choriocapillaris vessels were occluded on PAS staining. Additionally, capillary vessels were found on the retinal side of Bruch's membrane surrounded by hemorrhage and proteinaceous eosinophilic material. The retinal pigment epithelium was partly detached from Bruch's membrane and separated from it by the new vessels and the hemorrhage and transudate. Elsewhere, eosinophilic proteinaceous material separated the pigment epithelium from the overlying retina. DIAGNOSIS
The diagnosis was melanocytoma of choroid; subretinal hemorrhage, vascularization and disciform retinal detachment adjacent to the tumor. The localized area of hemorrhagic detachment of the retinal pigment epithelium which forms a disciform retinal detachment appeared to be pathogenically related to the melanocytoma. The diagnosis of melanocytoma was confirmed by the Armed Forces Institute of Pathology. DISCUSSION
Typically, nevi and benign pigmentations are dense and relatively avascular, and this helps explain their usual appearance on the fluorescein angiogram-where background choroidal fluorescence 'is decreased or "blocked." Melanomas on the other hand, are usually highly vascular, containing vessels which readily leak fluorescein. This was one factor which led us astray in our clinical diagnosis. In fact, we initially were unaware that vascularization of benign pigmented choroidal tumors occurred at all. We have since learned that nevi and melanocytomata do develop their own blood supplies, though this if far less frequent than in melanomas. Hence, since such integral vascularization can be present, the clinician should not try to discriminate between benign and malignant lesions angiographically on a vascularity basis alone,1 as we discovered retrospectively. Melanocytomas are rare in caucasians compared to their incidence in any of the more highly pigmented races, yet this patient had no Negroid nor Mediterranean ancestry, as far as she knew. The relationship between this tumor and the overlying disciform lesion deserves comment, but no profound elaboration of the many clinical entities associated with subretinal neovascularization is necessary. Suffice
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to say, in each instance a defect in Bruch's membrane is present through which an abnormal neovascular network grows. From these vessels, a transudation of fluid and hemorrhage may occur. When an accompanying hemorrhage takes place, it can be found either within the fragmented Bruch's membrane, under the pigment epithelium, in the subretinal space, or even in the vitreous. The process is a self limited one although recurrent hemorrhages can occur. The coagulum and hemorrhage typically undergo eventual resolution with fibrosis. In this eye, two small neovascular nets were visible ophthalmoscopically on the surface of the tumor prior to the development of the clinically evident disciform lesion. Such neovascular ingrowths can pierce cracks in Bruch's membrane and have been reported overlying certain pigmented lesions of the choroid such as some nevi and melanomata. However, to the best of my knowledge, this type ofclinical picture has not been previously reported in a histologically proven melanocytoma. Shields and Font2 have reported a case of a melanocytoma which simulated a melanoma but not with the accompanying neovascularization and disciform lesion as in this case. However, a melanocytoma is really only one discrete type of uveal nevus,3 so perhaps the association should not be too unexpected. We have studied some of Gass' clinical photographs and angiogram examples shown in his texts4'5 and suggest that some of his "nevi" may actually also represent melanocytomata. Another interesting point is evident in our case. It seems that the primary site of the neovascularization occurred eccentric to the main tumor mass rather then centrally. This is in contrast to what one might expect using a priori inductive reasoning. Logically, one would think that a tumor would be more likely to interfere with the metabolism of the overlying Bruch's membrane centrally and disrupt it where the lesion is usually thickest. While the eccentric positioning in this eye may represent only a spurious finding, it could also represent a predilective site. Apropos of this point, many of Gass' photographs4'5 also show that neovascularization may occur nearer to the edges of a pigmented lesion than centrally. In any event, eccentricity of the neovascularization apparently can occur as part of the natural pathogenic process; thus, one should not argue that the eccentric position per se reduces the probability of a cause and effect relationship between the tumor and the defects in Bruch's membrane. One might still question whether the Bruch's defect in this eye is related to the tumor or to some other cause. For example, it could have been associated with some inadvertant trauma to this area, such as the cryoprobe during the retinal detachment surgery. Prior to that
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intervention, no clinical signs of neovascularization were present. Vigorous manipulation with this instrument certainly could have caused a tear in Bruch's membrane which might have initiated the process, but this is highly unlikely. There would have been no clinical reason for instrumentation to take place on the nasal side of the disc, since the retinal tear giving rise to the detachment was located in the upper-temporal quadrant, well away from the area of the tumor. So, while such a possibility cannot be completely excluded, it is felt to be highly improbable. The relationship between the disciform lesion and the melanocytoma itself might be more tenous had the combination been located on the temporal side of the optic nerve. In that position, a disciform clinical picture might have been attributed to an early disciform macular degeneration rather than to the tumor. Senile disciform lesions are known to occur extramacularly even nasal to the disc, however, this patient is rather young to warrant the diagnosis of senile degenerative changes; moreover, there was no sign of any such tendency in the macula of this or of the other eye. Gass5 points out that when subretinal neovascular membranes occur from any cause within the macular area, they are more apt to bleed. They may create the characteristic localized disciform hemorrhagic detachment of the pigment epithelium since the choroidal blood flow is maximal there. It is of interest that this disciform lesion occurred extramacularly and still bled, despite the location. Considering the overall circumstantial evidence presented, it appears that the disciform lesion in this patient is causally related to the underlying, adjacent melanocytoma.
SUMMARY
A 49-year-old white patient presented with a small pigmented lesion nasal to the disc. The clinical appearance of the area in question was noted to change over a four year period and simulated a progressively enlarging choroidal melanoma. On enucleation, the lesion was histopathologically proven to be a melanocytoma located nasal to the optic nerve head. It caused-or was at least associated with-an overlying disciform hemorrhagic and transudative response secondary to a neovascular ingrowth through Bruch's membrane. Thus, a melanocytoma must now be considered another of the possible causes of a disciform-shaped fundus lesion.
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Sincere appreciation is extended to Professor Ian Hood, M. D., University of Florida Department of Pathology, for his valuable assistance with the histopathology and the diagnosis. REFERENCES 1. Wessing A: Fluorescein Angiography of the Retina. St. Louis, Mosby, 1969, p 166. 2. Shields JA, Font RL: Melanocytoma of Choroid Clinically Simulating a Malignant Melanoma. Arch Ophthalmol 87:396, 1972. 3. Naumann G, Yanoff M, Zimmerman LE: Histogenesis of Malignant Melanomas of the Uvea. Arch Ophthalmol 76:784, 1966. 4. Gass JDM: Stereoscopic Atlas of Macular Diseases. St. Louis, Mosby, 1970. 5. Gass JDM: Differential Diagnosis of Intraocular Tumors. St. Louis, Mosby, 1974.
DISCUSSION
DR MICHAEL J. HOGAN. It has become increasingly apparent that small benign pigmented and unpigmented nevi of the choroid can induce changes in the choriocapillaris, Bruch's membrane, retinal pigment epithelium and sensory retina that lead to clinical symptoms. The case reported today by Dr Rubin is an undoubted choroidal nevus, melanocytic type, that eventually was associated with neovascularization of Bruch's membrane and subepithelial region and subsequent bleeding. Of great interest was the hemorrhage into the vitreous from this relatively innocuous appearing lesion. Unfortunately the sections of the eye do not reveal the route taken by the blood through the retina into the vitreous. I believe that the manipulations involved in the retinal detachment surgery on this eye initiated changes that eventually caused the neovascularization and bleeding. It has been shown that the choroidal vessels at the edge ofsuch nevi are dilated and it is conceivable they might be damaged by surgery. There is evidence that 32p studies can lead to bleeding when used for the diagnosis of melanomas and it seems likely that the distortions induced in the eye during retinal surgery can lead to alterations in the tissues around a nevus. For this reason we never do 32p studies on small relatively flat pigmented lesions of the choroid, especially if they are posterior to the equator. This is an ideal case to be presented for publication because it calls our attention again to the comments by Zimmerman in his Bedell lecture that not all clinical tests are infallible and that small pigmented lesions should be watched for a considerable period before recommending enucleation (Am J Ophthalmol 75:917-929, 1973). Even a change in size ofmoderate dimension does not provide an indication for surgery. In the present case there were other circumstances that led to enucleation, but in most cases the surgeon should assume a positive attitude and oppose surgery until he is convinced there is clear cut aggressive behaviour on the part of the tumor.
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No special distinction should be made in this case that the tumor is a melanocytoma. The commonest cell in choroidal nevi is the plump polyhedral nevus cell that comprised this tumor. A spectrum of cells from this type to spindle cells is found in such tumors, intermediate forms being recognized in some tumors. Ordinarily the plump polyhedral form is heavily pigmented, whereas the spindle cells are sparsely pigefe whereas the spindle cells are sparsely pigmented. From a standpoint of behaviour they are probably the same in the uveal tract. In the past, stress was placed on the presence or absence of a scotoma to help differentiate benign from malignant lesions. It is true that if there is no scotoma the chance of malignancy is less, but if one is present it does not necessarily indicate malignancy. Fluorescein studies may be positive in some choroidal nevi, and for this reason care should be taken in rendering a judgement as to the presence of a malignant melanoma. The 32p test may be positive in a patient with a small pigmented choroidal lesion. Even so this result should not be used as an evidence for removal of the eye. All other findings should be utilized in the decision on management. I am happy to have been asked to discuss this paper, especially when it has been presented by a friend I have known since his beginning in medicine. DR STEWART M. WOLFF. I am happy to have this chance to comment on Doctor Rubin's very interesting paper. It points up the protean nature ofdisciform lesions. I, too, have a patient with a serous detachment of the retina over a melanocytoma with reduction of vision. In another instance, Doctors Harold Spalter and Frank Carroll and I, have seen a peripheral disciform lesion at the locus of an old histoplasma scar which was indistinguishable from a melanoma. The hemorrhagic phase finally subsided, leaving a large, flat peripheral scar. Finally, just before I left Baltimore, Doctor Stuart Fine showed me a hemorrhagic disciform lesion at the site of an old rubella maculopathy. Thank you very much. DR MELVIN RUBIN. I would like to thank the discussors for their comments. In regard to the question that Doctor Hogan raised about the decrease in vision after retinal detachment surgery, it is probably not too unusual for a patient having retinal detachment surgery, especially with a temporal retinal detachment, to be left with some reduced vision postoperatively. As I recall from the operative note of the surgeon who did the surgery, the macula was not detached preoperatively. On the other hand, it is possible he was wrong and the macula was flatly detached. Since I did not see the patient preoperatively, I do not know. But, of course, if the macula had been detached, that would certainly explain why the vision was decreased. Dr Hogan, it is interesting that in the patients whose slides you showed, of nevi or melanocytoma, the lesions were in the macular areas. This serves to substantiate Gass's comment that I mentioned, that is, that when this type of choroidal lesion lies in the posterior pole, it is more likely to bleed. However, I feel that similar lesions found at other locations in the fundus can still bleed on their own-though
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their own initiation of subretinal neovascularization. In this case in particular, I do not feel that it is necessary to incriminate surgical trauma as the precipitant, though it certainly could have been. As a retinal detachment surgeon, I have some idea of just how much surgical manipulation is necessary to repair a superior temporal tear. So, even though I was not present at the surgery, my best guess is still that there would not have been enough trauma instigated to initiate the process. These lesions are sufficiently active to cause changes in Bruch's membrane and initiate the neovascularization without implicating the surgery. But obviously, I cannot know for sure, and Dr Hogan may be quite correct in his analysis. Again, I would like to thank the discussants and especially Dr Hogan for his valuable and kind discussion of this, my first AOS paper. I am particularly proud since it was he who first introduced me to ophthalmology and afforded me the opportunity ofworking with him in an ophthalmic laboratory. For his gift in showing me the ophthalmic "light" and for his gentle ways, I'll always be grateful. Thank you.
