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Fluorescein and Ultrasound in Diagnosis of Intraocular Tumors
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21. Werner, S. C. : Prednisone in emergency treatment of malignant exophthalmos. Lancet 1:1004, 1966. 22. Henderson, J. W . : Optic neuropathy of exophthalmic goiter (Graves' Disease). Arch. Ophth. 59:471, 1958; Tr. Am. Ophth. Soc. 55:353, 1957. 23. Naffziger, H. C. : Progressive exophthalmos associated with disorders of the thyroid gland. Ann. Surg. 108 :529, 1938. 24. Poppen, J. L. : Exophthalmos—intractable and nonintractable : Its causes and surgical treatment. Proc. Interstate Post-grad. Med. Assembly North Am. p. 266, 1942. 25. Mann, I. : Exophthalmic ophthalmoplegia and its relation to thyrotoxicosis. Am. J. Ophth. 29:654, 1946. 26. Jones, E. : Malignant (thyrotropic) exophthalmos. Am. J. Ophth. 34:296, 1951.
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27. Thomas, H. M. : Exophthalmos in the light of current antithyroid therapy. Am. J. Med. 11:581, 1951. 28. Naffziger, H. C. : Progressive exophthalmos : An Hunterian lecture. Bull. Am. Coll. Surgeons. 40:33, 53, 1955. 29. Shtulman, D. R. : Ophthalmologic characteristics of malignant exophthalmos. Vest. Oftal. 75:45, 1962. 30. Smith, J. P. : Progressive exophthalmos : Case presentation—preliminary report of new surgical technique used in treatment. Tr. Am. Laryng. Rhin. Oto. Soc. p. 232, 1965 ; Laryngoscope 75:1160, 1965. 31. Day, R. M. and Carroll, F. D. : Corticosteroids in the treatment of optic nerve involvement associated with thyroid dysfunction. Arch. Ophth. 79:279, 1968.
FLUORESCEIN A N D U L T R A S O U N D IN DIAGNOSIS O F INTRAOCULAR TUMORS KURT
A.
GITTER,
ARTHUR
M.D.,*
H.
DAVID
KEENEY,
MEYER,
M.D.
M.D., Lov
AND JOHNNY
M.D.,
K. SARIN,
JUSTICE,
JR.
Philadelphia, Pennsylvania
The differential diagnosis of elevated intraocular lesions is frequently difficult. This report analyzes the combined use of intravenous fluorescein for fundus angiography and unidirectional time-amplitude ultrasonography (A-scan) for the detection of intraocular masses and evaluation of their solid or serous nature. MATERIAL
A N D METHODS
Thirty consecutive patients with visible intraocular masses were studied in the Ultrasound Department of the Wills Eye Hospital from May to December 1967. A 5-mm-wide transducer emitting pulsed unfocused ultrasound at 7.5 megacycles/second was used.'' Eyes were examined first in the anteriorposterior direction (through the lens) and then subsequently in each quadrant using 1 % methylcellulose as a coupling medium as From the Wills Eye Hospital. Supported in part by U S P H S Training Grant NB-5076 from the National Institute of Neurological Diseases and Blindness. * Present address : Department of Ophthalmology, New York Medical College, Fifth Avenue at 106th Street, New York 10029. t Smith Kline Instrument Co.—Eckoline 12 and 20 instruments.
described in prior reports. All ultrasonogram interpretations were made during examination and after careful ophthalmoscopy. Photographs of echo patterns displayed on the oscilloscope were recorded during moments of critical reflections. Fundus photography and rapid sequence fluorescein angiography utilizing Zeiss equipment were also performed, as described by Justice and Sever, and later evaluated on each patient* The patients were followed clinically and the histopathology of 22 globes was correlated with pre-enucleation of ultrasonic and angiographic findings. 1
2
C L A S S I F I C A T I O N OF LESIONS
Patients were subdivided into Categories I, II and III, depending on tumor area and elevation (projection into the vitreous) as estimated by ophthalmoscopy and measured pathologically in histologic sections. Eight patients were placed into Category I (small clinical masses elevated less than 2.5 mm). Nine patients were placed in Category II (medium-sized ocular lesions approximately 2.5 to 5 mm in height as judged ophthalmost Smith, Miller and Patch Co.—5 ml of 10% fluorescein sodium solution.
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TABLE 1 SUBDIVISION OF 30 INTRAOCULAR TUMORS INTO CATEGORIES ON THE BASIS OF SIZE OF THE LESION Histopathologic Confirmation
Category
No. of Patients
Size of Lesion
I II III
9
8
Less than 2 . 5 mm elevation 2 . 5 to 5 mm elevation Greater than 5 mm, occupying more than one quadrant of globe
13
2
7
13
copically or by examination of tissue sections of the eye). The remaining 13 patients, all with intraocular masses elevated S mm or more and/or extending through more than one quadrant of the globe, were placed in Category III (table 1 ) . RESULTS CATEGORY
I
Normal ultrasonograms were obtained in each of the eight patients in Category I (fig. 1 ) . Fluorescein angiography performed on these patients was far more helpful in making a final diagnosis (table 2 ) . Two patients (Cases 2 and 3) had localized hemangiomas of the choroid not associated with the SturgeWeber syndrome. Intravenous fluorescein dye studies (Case 3 ) revealed (fig. 2 ) early fluorescence throughout the lesion and "multi-lakelike staining" in the late phases of angiography, as recently described by Norton. Both patients were treated by xenon photocoagulation. Two patients, (Cases 1 and 5) had slightly elevated, pigmented choroidal lesions clinically interpreted as malignant melanomas. Both revealed early fluorescence in the arteriovenous phase of angiography. In 8
Fig. 1 (Gitter, Meyer, Sarin, Keeney and Justice) Normal ultrasonogram of right and left eye revealing echoes from the anterior ( 1 ) and posterior lens capsule (2) and posterior bulbar wall ( 3 ) with echo-free vitreous cavity ( 4 ) and variable normal retrobulbar echoes ( 5 ) . Identical ultrasonograms were obtained in all category I patients.
TABLE 2 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN EIGHT PATIENTS WITH LESIONS ELEVATED LESS THAN 2 . 5 MM (CATEGORY I)
Cases 1 2 3 4 5 6 7 8
Clinical Dx Mai. mel. of choroid Choroidal hemangioma Choroidal hemangioma ? Mai. mel. of choroid Mai. mel. of choroid Metastatic CA Metastatic CA ? Mai. mel.
Fluorescem Helpful Helpful Helpful Helpful Helpful Helpful Helpful Helpful
Ultrasound P
a
t
t
e
r
Rx
n
Normal Normal Normal Normal Normal Normal Normal Normal
Photo 3 X -(-enucleation Photocoagulation Photocoagulation None, follow-up Enucleated Medical or X-ray Medical or X-ray None, follow-up
Histopathology Mai. mel. of choroid Not obtained Not obtained Not obtained M . M . of Choroid Not obtained Not obtained Not obtained
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Fig. 2 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of a choroidal hemangioma with green filter ( A ) and the associated angiograms revealing staining during the arterial phase ( B ) , early A - V phase ( C ) and late phase ( D ) of angiography.
Case 1, photocoagulation was attempted on three occasions, but the lesion continued to increase in size. The diagnosis of malignant malanoma of the choroid was confirmed following enucleation. In Case S there was a dark, slightly elevated posterior pole lesion interpreted as malignant melanoma. Leakage of dye throughout the lesion during the arteriovenous phase of angiography was consistent with the above diagnosis (fig. 3 ) . Following examinations at varying intervals, the clinical diagnosis of melanoma remained un-
changed and the globe was enucleated. Histopathologic examination demonstrated choroidal malignant melanoma. Two other Category I patients (Cases 6 and 7) with metastatic lesions of the posterior pole, associated with known primary malignancies of breast and prostate, demonstrated fluorescence of the lesion. The remaining two patients (Cases 4 and 8) had small pigmented, elevated posterior pole lesions interpreted as possible early melanomas. The angiographic patterns of both patients also revealed early
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Fig. 3 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of pigmented, slightly elevated posterior pole lesion (with red filter) with overlying depigmented area interpreted as malignant melanoma ( A ) . Angiograms revealed spotlike bright fluorescence in the arteriovenous phase ( B ) with persistent and more marked staining in later phases ( C ) . The histopathology ( D ) demonstrates a densely pigmented choroidal lesion (verified malignant melanoma) with overlying serous macula detachment (arrow).
arterial or arteriovenous fluorescence of the mass with associated serous macular elevations and demonstrable leakage of dye into these areas (fig. 4 ) . Both patients are reexamined at bimonthly intervals to document any possible growth and extent of these masses. CATEGORY
II
Of nine patients (six with malignant melanomas of the choroid, and three with metastatic carcinomas), angiography revealed early fluorescence of the lesion in six, whereas ultrasonographic tracings compati-
ble with solid neoplasm were obtained in eight (table 3 ) . Histologic conformations of all six melanomas and one metastatic prostatic carcinoma of the choroid were obtained following enucleation. Case 4 demonstrated abnormal ultrasonic patterns compatible with neoplasm and angiographic dye studies revealing early fluorescence of the lesion. The enucleated specimen demonstrated an amelanotic melanoma elevated approximately 4 mm (fig. 5 ) . In one patient (Case 9 ) , prior to the development of an overlying retinal detachment, both the angiogram and ultrasonogram revealed evidence of a probable
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Fig. 4. (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of a mildly elevated pigmented posterior pole lesion ( A ) revealing bright staining in the arteriovenous phase ( B ) with an associated serous macular detachment ( C ) which filled with fluorescein dye at later stages ( D ) , interpreted as possible malignant melanoma.
neoplasm; six months later (July 1967), a bullous detachment developed which partially obscured the tumor. The ultrasonogram detected only the overlying serous retinal detachment (fig. 6 ) , whereas the angiogram could not be adequately visualized. Case 2, a metastatic carcinoma, demonstrated angiographic and ultrasonic findings compatible with neoplasm (fig. 7 ) . In Case 7, although minimal late fluores-
cence of the mass was noted, early fluorescein-staining was absent. In Case 8 the ocular media were mildly hazy, preventing good angiographic photographs. CATEGORY
III
Thirteen patients, all with clinical diagnoses of malignant melanoma, had histologic confirmation of choroidal malignant melanoma (table 4 ) . In seven of these 13, flúores-
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TABLE 3 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN NINE PATIENTS WITH LESIONS ELEVATED 2 . S - 5 . 0 MM (CATEGORY I I ) Cases
Clinical Dx
Fluorescein
Ultrasound Pattern
Rx
1 2 3
Mai. mel. of choroid Metastacic CA Metastatic CA
Helpful Helpful Helpful
Solid detach. Solid detach. Solid detach.
Enucleated Medical Rx Medical Rx
4 5 6 7 8 9
M . M . of Choroid Amelanotic mal. mel. Mai. mel. of choroid Metastatic CA Mal. mel. of choroid Mai. mel. vs met. ca; retinal detachment
Helpful Helpful Helpful Helpful Not helpful Not helpful
Solid detach. Solid detach. Solid detach. Solid detach. Solid detach. Serous retinal detachment
Enucleated Enucleated Enucleated Medical Rx Enucleated Enucleated
cein angiography was not helpful. Although slight areas of fluorescence were noted at varying angiographic stages in all seven patients, the amount of fluorescence was minimal and in no instance was the early arterial or arteriovenous fluorescence pattern noted, as commbnly found in Category I and Category II patients. In four eyes, a rim or "circumferential ring" of fluorescein dye was found outlining the borders of the tumor mass during late phases of angiography, photographically recorded by bringing the focal point of the camera forward to the iris plane. In other patients (Cases 5 and 9 ) angiography was performed, but due to overlying vitreous hemorrhage in one and generalized vitreous haze in the other, interpretations were limited. Ultrasonograms characteristic of solid detachments were obtained in all 13 Category III patients. Cases 7 and 8 demonstrate the characteristic ultrasonograms obtained with large intraocular tumors and their associated fluorescein angiograms revealing "ring fluorescence" in one and the absence of fluorescence in the other (figs. 8 and 9 ) . DISCUSSION
Data from this series revealed that ultrasonography in masses greater than 2.5 mm in height yields characteristic solid tumor patterns, (fig. 10). These were characterized by high-amplitude echoes in the vitreous cav-
Pathology Mai. mel. of choroid CA of Lung Disseminated CA (prostatic) Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid No specimen M . M . of choroid Mai. mel. of choroid with total retinal detachment
ity, representing differences in acoustical density at the interface between vitreous and tumor, followed by irregular lower amplitude echoes emanating from the tumor mass, extending to the posterior bulbar wall as first described by Oksala. Normal vitreous is free of echo activity due to its acoustic homogeneity. These solid detachment patterns, consistently found with proper methods of examination when the tumor is ultrasonically detectable (2.5 mm high or more) can not always be differentiated from patterns obtained with other conditions ; that is, subretinal organized hemorrhages, choroidal hemorrhages, Coats' disease with exudative detachment, total retinal detachment with underlying exudate, and retinitis proliferans.* These diseases are also capable of producing solid detachment-type ultrasonograms which may create confusion in eyes with opaque media in which fundus visualization is precluded." At times, these conditions can be differentiated from neoplastic tissue on the basis of variations in acoustic properties (reflection and absorption), clinically determined by changing the amplification and sensitivity of the incoming and receiving sonic pulse. Neoplastic tissue in most instances has greater acoustical impedance and is more echo-reflecting than hemorrhage, exudate, or fibrosis. 4
* Meyer, D., Gitter, K. and Sarin L. K. : Ultrasonography, malignant melanoma (in preparation).
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Fig. 5 (Gitter, Meyer, Sarin, Keeney and Justice). Early arteriovenous ( A ) and late stage angiograms ( B ) of an amelanotic melanoma of the choroid ( C ) . The ultrasonogram ( D ) in the upper tracing might be mistaken for a serous retinal detachment (arrow) although minimal abnormal echo activity is present in the subretinal space The lower tracing of the same eye (arrow) clarifies the solid detachment pattern (P = posterior bulbar wall).
In time-amplitude ultrasonography, probe placement on the globe must be perpendicular to the intraocular lesion investigated or the acoustical reflections will not be retrieved by the transducer for display on the oscilloscope. If overlying retinal detachments exist, incorrect probe placement may reveal the presence of retinal detachment only, and miss the tumor, as evident in Case 9, Table
3. Unfortunately, choroidal lesions less than 2.5 mm in height may exist and yield normal ultrasonic patterns with present instruments. This is partially explained by the factors of sonic resolution, as determined in part by frequency, beam width (dependent on transduced diameter and collimation of the sound beam), the presence or absence of focusing devices, and acoustic artifacts (mostly
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ton, Gass, Smith and associates first differentiated malignant melanomas from metastatic lesions on the basis of fluorescence of the former and absence of dye in the latter. More recently, they - reported that metastic lesions also can fluoresce and that early arterial filling of choroidal lesions cannot differentiate hemangiomas from melanomas. They also reported the absence of fluorescein in choroidal nevi. 9
8
8
Snyder has demonstrated variability of fluorescence in metastatic lesions ranging from poor fluorescence to bright staining. He concluded that although bright, prompt, patchy fluorescence in the arterial of A - V phases of angiography often is seen with melanomas, pathognomonic patterns for melanoma, metastatic, and benign lesions did not exist. 11
Fig. 6 (Gitter, Meyer, Sarin, Keeney and Justice). Ultrasonogram ( A ) (upper and lower tracings) demonstrate a characteristic serous retinal detachment pattern characterized by a single high amplitude spike (arrow) in the vitreous cavity followed by acoustic silence until the posterior bulbar wall ( P ) . The enucleated specimen ( B ) reveals a flat choroidal tumor (arrow) with large overlying bullous retinal detachment.
caused by velocity changes and divergence of sound by the lens). Photographic recording of intravenous dye injections was first described by Novotny and Alvis in 1961. Maclean and Maumenee had previously reported the use of fluorescein in detecting hemangiomas of the choroid. Subsequently, ophthalmic fluorescein angiography was intensively investigated at the Bascom Palmer Eye Institute. ' ' - -" Nor6
7
2 3 8
10
Our studies indicate that fluorescein angiography is particularly helpful in differential diagnosis of intraocular tumors when the lesion is flat or mildly elevated, or the limits of extension are small. In these tumors (too small for ultrasound detection), the characteristic fluorescence of melanomas in the early arterial or arteriovenous phases of angiography is helpful in distinguishing them from other pigmented fundus lesions. Clinical nevi of the choroid have not been found to fluoresce although nevi with overlying drusen can appear as fluorescence or pseudofluorescence. If, indeed, malignant malanomas can arise from preexisting nevi, as suggested by Yanoff and Zimmerman, theoretically, a stage could exist in which a flat pigmented lesion having the clinical appearance of a nevus would fluoresce. Conversely, it may be assumed that certain early melanomas may not yet have the vascular supply or capillary permeability changes necessary to produce leakage of fluorescein. 12
Angiographic differentiation of melanomas from fresh hemorrhagic lesions, whether choroidal, subretina, or under the pigment epithelium, can be made, as the pattern obtained from the latter characteristically reveals an absence or exclusion of dye
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Fig. 7 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of an elevated metastatic lesion with adjacent salt and pepper fundus ( A ) revealing fluorescence during the A - V phase with transmission of choroidal fluorescence through the depigmented areas ( B ) and continued leakage of dye at late stages of angiography ( C ) . Note absence of fluorescence in the depigmented areas in later stages ( C ) verifying "pseudofluorescence." The ultrasonogram ( D ) reveals an abnormal solid detachment (arrow) in the involved eye ( lower tracing ) compared to the normal eye ( upper tracing) ( P = posterior bulbar wall).
within the area outlined by the hemorrhage. Even the background choroidal fluorescence normally seen in the posterior pole is obscured by hemorrhagic lesions. The "circumferential ring" pattern of fluorescein outlining large tumors was found in four of 13 patients and may be characteristic of certain large intraocular neoplasms. Gass
(Gass, J. D. M.—Personal communication, December 1967) has observed similar "ringlike" configurations in large lesions, despite absence of otherwise identifying fluorescein patterns. However, characteristic fluorescence of the mass in early phases of angiography is not detected photographically in large intraocular lesions (Category I I I ) .
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TABLE 4 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN 13 PATIENTS WITH LESIONS ELEVATED MORE THAN S MM (CATEGORY I I I ) Cases
Dx
Fluorescein
Ultrasound Pattern
1 2 3 4 S 6
Mai. Mai. Mai. Mai. Mai. Mai.
mel. mel. mel. mel. mel. mel.
"Ring" fluorescence Questionable value Not helpful Not helpful Not helpful; vitreous hemorrhage Not helpful
Solid Solid Solid Solid Solid Solid
detachment detachment detachment detachment detachment detachment
7 8 9 10 11 12 13
Mai. Mai. Mai. Mai. Mai. Mai. Mai.
mel. mel. mel. mel. mel. mel. mel.
"Ring" fluorescence "Ring" fluorescence Not helpful; hazy vitreous "Ring" fluorescence Not helpful Not helpful Not helpful
Solid Solid Solid Solid Solid Solid Solid
detachment detachment detachment detachment detachment detachment detachment
Histopathology Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Amelanotic mal. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid
Fig. 8 (Gitter, Meyer, Sarin, Keeney and Justice). Large intraocular melanoma which did not reveal characteristic fluorescence ( A ) . The ultrasonogram ( B ) depicts solid detachment patterns both when the probe was placed on the opposite scleral wall directed toward the tumor (upper tracing) and directly on the sclera overlying the tumor (tower tracing). The histopathologic specimen ( C ) confirmed a malignant melanoma of the choroid.
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Fig. 9 (Gitter, Meyer, Sarin, Keeney and Justice). External ( A ) and late angiogram ( B ) of intraocular melanoma revealing "ring fluorescence." The ultrasonogram ( C) in upper and lower tracing reveals a classic solid detachment pattern with an initial high-peaked echo from tumor surface (1) followed by irregular echoes throughout the vitreous cavity mass (2) extending to the posterior bulbar wall ( 3 ) . The gross specimen reveals a large choroidal melanoma ( D ) .
The value of fluorescein angiography in choroidal hemangiomas, previously described by others " ' is well demonstrated in our two cases. Besides aiding localization of leakage areas to determine sites for photocoagulation, intravenous fluorescein helped to define the extent of the lesion and to quantitate therapeutic progress. Fluorescein angiography is not of value in the presence of opaque media, whereas ultrasonic examination can be particularly helpful 3
7 13
in such eyes. Similarly, in the presence of overlying serous retinal detachments, whether total or quadrantic, photographic recording and interpretation of fluorescein angiography becomes more difficult. The presence of vitreous opacities, whether hemorrhagic, exudative or degenerative, also impairs photographic recording of intravenous fluorescein angiography. Whenever fluorescein angiography is not satisfactory, due to opaque media, ultrasound may be a helpful
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Fig. 10 (Gitter, Meyer, Sarin, Kenney and Justice). Schematic of normal eye with normal echoes obtained from crystal artifact ( A ) , anterior and posterior lens capsules ( B and C ) , posterior bulbar wall ( D ) and retrobulbar part ( E ) . The shaded preretinal area measuring Zy* mm in height represents the area in which intraocular neoplasms are ultrasonically silent with present instruments.
A B C
D E
part of the examination. Even in eyes with total obscuration of the fundus, due to hemorrhage, cataracts, corneal opacities, etc, ultrasound can help evaluate the posterior segment. Although both techniques offer major aids in the diagnosis of intraocular neoplasms, clinical evaluation by the physician, utilizing all diagnostic modalities, including contact lens, slitlamp, biomicroscopy, direct and indirect ophthalmoscopy with scleral depression, and transillumination, is fundamental and cannot be superseded by the two valuable procedures described. SUMMARY
Thirty patients with visible intraocular tumors were studied using time-amplitude ultrasonography and fluorescein angiography. Results demonstrated that ultrasound revealed solid detachment (tumor-type) patterns in all patients with lesions elevated mm or more, whereas tumors less elevated yielded normal ultrasonograms with present instrumentation. Fluorescein angiography was of particular diagnostic aid in evaluating the flatter lesions. Limitations of both techniques as regards tumor size, configuration and vascularity, as well as the clarity of the ocular media, are discussed. The combined utilization of both modali-
ties according to their specific areas of applicability greatly enhances the diagnostic evaluation of intraocular tumors. ACKNOWLEDGMENTS W e are grateful to P. Robb McDonald, M.D. and the Retina Service at Wills Eye Hospital for encouragement and guidance as well as the use of many of their patients in this series. W e thank William R. Green, M . D . for aiding in the pathology as well as assisting the editing of this manuscript REFERENCES
1. Gitter, K. A., Meyer, D., White R. A , Sarin, L. K. and Keeney, A . H. : Uses of diagnostic ultrasound in ophthalmology. Scientific exhibit at American Medical Association, 1967. 2. Justice, J. J., Jr. and Sever, R. J. : Technique of Fluorescein Fundus Photography. Neuro-ophthalmology: Vol. 2, (ed. Smith, J. L . ) Symposium of University of Miami. St. Louis, Mosby, 1965, p. 82. 3. Norton, E. W . D. and Gutman, F.: Fluorescein angiography and hemangiomas of the choroid. Arch. Ophth. 78:121, 1967. 4. Oksala, A . : Echogram in melanoma of the choroid. Brit J. Ophth. 43:408, 1959. 5. Gitter, K. A., Meyer, D. and Sarin, L. K : Ultrasound to evaluate eyes with opaque media. A . M. J. Ophth. 64:100, 1967. 6. Novotny, H . R. and Alvis, D. L. : A method of photographing fluorescence in circulating blood in the human retina. Circulation 24:82, 1961. 7. Maclean, A . L. and Maumenee, A . E. : Hemangioma of the choroid: Am. J. Ophth. 50:3, 1960. 8. Norton, E. W . D., Smith, J. L., Curtin, V . T. and Justice, J., Jr.: Fluorescein fundus photography: A n aid in the differential diagnosis of poste-
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rior ocular lesions. Tr. Am. Acad. Ophth. Otolarvng. 68:755, 1964. 9. Norton, E. W . D„ Gass, .1. D., Smith, J. L., Curtin, V. T., David, N. J. and Justice, J., Jr. Fluorescein in the study of macular disease—Symposium : Macular Diseases. Tr. Am. Acad. Ophth. Otolaryng. 69:631, 1965. 10. Gass, J. D. M. : Pathogenesis of disciform detachment of the neuroepithelium Am. J. Ophth. 63 :573, 1967.
HEMANGIOPERICYTOMA KENNETH
L.
11. Snyder W . B., Allen, L. and Frazier, O. : Fluorescence angiography of ocular tumors. Tr. Am. Acad. Ophth. Otolaryng. 71:820, 1967 12. Yanoff, M. and Zimmerman, L. E. : Histogenesis of malignant melanomas of the uvea. Arch. Ophth. 77 :331, 1967. 13. Smith, J. L , David, N. J., Hart, L. M., Levenson, D. S. and Tillett, C. W . : Hemangiomas of the choroid : Fluorescein photography and photocoagulation. Arch. Ophth. 69:51, 1963.
OF T H E LID A N D ORBIT MACOUL,
M.D.
Palo Alto, California T h e hemangiopericytoma is a m o n o m o r phous tumor derived from a specific vascular element,
the
pericyte.
1,2
The
proliferating
pericytes are found outside the walls of capillaries. T h i s vascular tumor is slowly invasive,
occasionally
recur. ' 3
metastatic
and tends
to
4
T h i s paper describes the slowly destructive course of the disease in a patient w h o refused treatment until two years after initial appearance of the tumor. CASE
REPORT
A 68-year-old woman entered Stanford Medical Center for removal of a large mass involving both orbits and the forehead. Two years prior to admission, a nontender mass appeared in the right upper eyelid. A biopsy revealed hemangiopericytoma. However, the patient refused hospitalization and medical care and did not return until two years later. During this period the tumor had grown to enormous size over the forehead, into both orbits, and into the anterior cranial fossa. Physical examination revealed a well-nourished woman with a huge frontal tumor. The mass was soft, spongy, slightly tender, nonpulsatile, and without a bruit, and extended over the forehead into the bridge of the nose and into the right and left orbits. The right eye was proptotic, being displaced downward and outward (fig. 1 ) . The right upper lid was ptotic, and contained large collateral veins. The right conjunctiva was suffused. The left superior rectus, right superior oblique, and right superior rectus muscles were paralyzed. Retinal veins were dilated in the right eye. With correction, the patient was able to count fingers at nine feet with the right eye; corrected visual acuity in the left eye was 20/30. The pupils were equal, round, and reacted to light. The ocular tension was normal in both eyes From the Division of Ophthalmology, Stanford University Medical Center.
Fig. 1 (Macoul). Proptotic right eye displaced down and out. Note ptosis of right upper lid with large collateral veins. and bilateral posterior subcapsular cataracts were present Arteriography showed that the tumor was fed by collaterals of the right and left external and internal carotid arteries. Surgical exposure revealed that the large mass had destroyed both frontal sinuses, the roof and medial walls of both orbits, the ethmoid sinuses and the greater and lesser wings of the sphenoid bone bilaterally. The tumor had invaded the anterior cranial fossa and infiltrated both frontal lobes. The mass could not be removed completely because of extensive brain involvement. The patient subsequently received radiotherapy (6,000 rads over a five-week period). An arteriogram 10 weeks after surgery revealed recurrent or residual tumor in the anterior falx cerebri, the left side of the nose, and the medial aspect of the left orbit. The patient has continued to do well VA years postoperatively. MICROSCOPIC
The
unencapsulated
EXAMINATION
tumor consisted
of
broad sheets of oval-to-spindle-shaped cells
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21. Werner, S. C. : Prednisone in emergency treatment of malignant exophthalmos. Lancet 1:1004, 1966. 22. Henderson, J. W . : Optic neuropathy of exophthalmic goiter (Graves' Disease). Arch. Ophth. 59:471, 1958; Tr. Am. Ophth. Soc. 55:353, 1957. 23. Naffziger, H. C. : Progressive exophthalmos associated with disorders of the thyroid gland. Ann. Surg. 108 :529, 1938. 24. Poppen, J. L. : Exophthalmos—intractable and nonintractable : Its causes and surgical treatment. Proc. Interstate Post-grad. Med. Assembly North Am. p. 266, 1942. 25. Mann, I. : Exophthalmic ophthalmoplegia and its relation to thyrotoxicosis. Am. J. Ophth. 29:654, 1946. 26. Jones, E. : Malignant (thyrotropic) exophthalmos. Am. J. Ophth. 34:296, 1951.
719
27. Thomas, H. M. : Exophthalmos in the light of current antithyroid therapy. Am. J. Med. 11:581, 1951. 28. Naffziger, H. C. : Progressive exophthalmos : An Hunterian lecture. Bull. Am. Coll. Surgeons. 40:33, 53, 1955. 29. Shtulman, D. R. : Ophthalmologic characteristics of malignant exophthalmos. Vest. Oftal. 75:45, 1962. 30. Smith, J. P. : Progressive exophthalmos : Case presentation—preliminary report of new surgical technique used in treatment. Tr. Am. Laryng. Rhin. Oto. Soc. p. 232, 1965 ; Laryngoscope 75:1160, 1965. 31. Day, R. M. and Carroll, F. D. : Corticosteroids in the treatment of optic nerve involvement associated with thyroid dysfunction. Arch. Ophth. 79:279, 1968.
FLUORESCEIN A N D U L T R A S O U N D IN DIAGNOSIS O F INTRAOCULAR TUMORS KURT
A.
GITTER,
ARTHUR
M.D.,*
H.
DAVID
KEENEY,
MEYER,
M.D.
M.D., Lov
AND JOHNNY
M.D.,
K. SARIN,
JUSTICE,
JR.
Philadelphia, Pennsylvania
The differential diagnosis of elevated intraocular lesions is frequently difficult. This report analyzes the combined use of intravenous fluorescein for fundus angiography and unidirectional time-amplitude ultrasonography (A-scan) for the detection of intraocular masses and evaluation of their solid or serous nature. MATERIAL
A N D METHODS
Thirty consecutive patients with visible intraocular masses were studied in the Ultrasound Department of the Wills Eye Hospital from May to December 1967. A 5-mm-wide transducer emitting pulsed unfocused ultrasound at 7.5 megacycles/second was used.'' Eyes were examined first in the anteriorposterior direction (through the lens) and then subsequently in each quadrant using 1 % methylcellulose as a coupling medium as From the Wills Eye Hospital. Supported in part by U S P H S Training Grant NB-5076 from the National Institute of Neurological Diseases and Blindness. * Present address : Department of Ophthalmology, New York Medical College, Fifth Avenue at 106th Street, New York 10029. t Smith Kline Instrument Co.—Eckoline 12 and 20 instruments.
described in prior reports. All ultrasonogram interpretations were made during examination and after careful ophthalmoscopy. Photographs of echo patterns displayed on the oscilloscope were recorded during moments of critical reflections. Fundus photography and rapid sequence fluorescein angiography utilizing Zeiss equipment were also performed, as described by Justice and Sever, and later evaluated on each patient* The patients were followed clinically and the histopathology of 22 globes was correlated with pre-enucleation of ultrasonic and angiographic findings. 1
2
C L A S S I F I C A T I O N OF LESIONS
Patients were subdivided into Categories I, II and III, depending on tumor area and elevation (projection into the vitreous) as estimated by ophthalmoscopy and measured pathologically in histologic sections. Eight patients were placed into Category I (small clinical masses elevated less than 2.5 mm). Nine patients were placed in Category II (medium-sized ocular lesions approximately 2.5 to 5 mm in height as judged ophthalmost Smith, Miller and Patch Co.—5 ml of 10% fluorescein sodium solution.
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TABLE 1 SUBDIVISION OF 30 INTRAOCULAR TUMORS INTO CATEGORIES ON THE BASIS OF SIZE OF THE LESION Histopathologic Confirmation
Category
No. of Patients
Size of Lesion
I II III
9
8
Less than 2 . 5 mm elevation 2 . 5 to 5 mm elevation Greater than 5 mm, occupying more than one quadrant of globe
13
2
7
13
copically or by examination of tissue sections of the eye). The remaining 13 patients, all with intraocular masses elevated S mm or more and/or extending through more than one quadrant of the globe, were placed in Category III (table 1 ) . RESULTS CATEGORY
I
Normal ultrasonograms were obtained in each of the eight patients in Category I (fig. 1 ) . Fluorescein angiography performed on these patients was far more helpful in making a final diagnosis (table 2 ) . Two patients (Cases 2 and 3) had localized hemangiomas of the choroid not associated with the SturgeWeber syndrome. Intravenous fluorescein dye studies (Case 3 ) revealed (fig. 2 ) early fluorescence throughout the lesion and "multi-lakelike staining" in the late phases of angiography, as recently described by Norton. Both patients were treated by xenon photocoagulation. Two patients, (Cases 1 and 5) had slightly elevated, pigmented choroidal lesions clinically interpreted as malignant melanomas. Both revealed early fluorescence in the arteriovenous phase of angiography. In 8
Fig. 1 (Gitter, Meyer, Sarin, Keeney and Justice) Normal ultrasonogram of right and left eye revealing echoes from the anterior ( 1 ) and posterior lens capsule (2) and posterior bulbar wall ( 3 ) with echo-free vitreous cavity ( 4 ) and variable normal retrobulbar echoes ( 5 ) . Identical ultrasonograms were obtained in all category I patients.
TABLE 2 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN EIGHT PATIENTS WITH LESIONS ELEVATED LESS THAN 2 . 5 MM (CATEGORY I)
Cases 1 2 3 4 5 6 7 8
Clinical Dx Mai. mel. of choroid Choroidal hemangioma Choroidal hemangioma ? Mai. mel. of choroid Mai. mel. of choroid Metastatic CA Metastatic CA ? Mai. mel.
Fluorescem Helpful Helpful Helpful Helpful Helpful Helpful Helpful Helpful
Ultrasound P
a
t
t
e
r
Rx
n
Normal Normal Normal Normal Normal Normal Normal Normal
Photo 3 X -(-enucleation Photocoagulation Photocoagulation None, follow-up Enucleated Medical or X-ray Medical or X-ray None, follow-up
Histopathology Mai. mel. of choroid Not obtained Not obtained Not obtained M . M . of Choroid Not obtained Not obtained Not obtained
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Fig. 2 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of a choroidal hemangioma with green filter ( A ) and the associated angiograms revealing staining during the arterial phase ( B ) , early A - V phase ( C ) and late phase ( D ) of angiography.
Case 1, photocoagulation was attempted on three occasions, but the lesion continued to increase in size. The diagnosis of malignant malanoma of the choroid was confirmed following enucleation. In Case S there was a dark, slightly elevated posterior pole lesion interpreted as malignant melanoma. Leakage of dye throughout the lesion during the arteriovenous phase of angiography was consistent with the above diagnosis (fig. 3 ) . Following examinations at varying intervals, the clinical diagnosis of melanoma remained un-
changed and the globe was enucleated. Histopathologic examination demonstrated choroidal malignant melanoma. Two other Category I patients (Cases 6 and 7) with metastatic lesions of the posterior pole, associated with known primary malignancies of breast and prostate, demonstrated fluorescence of the lesion. The remaining two patients (Cases 4 and 8) had small pigmented, elevated posterior pole lesions interpreted as possible early melanomas. The angiographic patterns of both patients also revealed early
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Fig. 3 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of pigmented, slightly elevated posterior pole lesion (with red filter) with overlying depigmented area interpreted as malignant melanoma ( A ) . Angiograms revealed spotlike bright fluorescence in the arteriovenous phase ( B ) with persistent and more marked staining in later phases ( C ) . The histopathology ( D ) demonstrates a densely pigmented choroidal lesion (verified malignant melanoma) with overlying serous macula detachment (arrow).
arterial or arteriovenous fluorescence of the mass with associated serous macular elevations and demonstrable leakage of dye into these areas (fig. 4 ) . Both patients are reexamined at bimonthly intervals to document any possible growth and extent of these masses. CATEGORY
II
Of nine patients (six with malignant melanomas of the choroid, and three with metastatic carcinomas), angiography revealed early fluorescence of the lesion in six, whereas ultrasonographic tracings compati-
ble with solid neoplasm were obtained in eight (table 3 ) . Histologic conformations of all six melanomas and one metastatic prostatic carcinoma of the choroid were obtained following enucleation. Case 4 demonstrated abnormal ultrasonic patterns compatible with neoplasm and angiographic dye studies revealing early fluorescence of the lesion. The enucleated specimen demonstrated an amelanotic melanoma elevated approximately 4 mm (fig. 5 ) . In one patient (Case 9 ) , prior to the development of an overlying retinal detachment, both the angiogram and ultrasonogram revealed evidence of a probable
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Fig. 4. (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of a mildly elevated pigmented posterior pole lesion ( A ) revealing bright staining in the arteriovenous phase ( B ) with an associated serous macular detachment ( C ) which filled with fluorescein dye at later stages ( D ) , interpreted as possible malignant melanoma.
neoplasm; six months later (July 1967), a bullous detachment developed which partially obscured the tumor. The ultrasonogram detected only the overlying serous retinal detachment (fig. 6 ) , whereas the angiogram could not be adequately visualized. Case 2, a metastatic carcinoma, demonstrated angiographic and ultrasonic findings compatible with neoplasm (fig. 7 ) . In Case 7, although minimal late fluores-
cence of the mass was noted, early fluorescein-staining was absent. In Case 8 the ocular media were mildly hazy, preventing good angiographic photographs. CATEGORY
III
Thirteen patients, all with clinical diagnoses of malignant melanoma, had histologic confirmation of choroidal malignant melanoma (table 4 ) . In seven of these 13, flúores-
O C T O B E R , 1968
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TABLE 3 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN NINE PATIENTS WITH LESIONS ELEVATED 2 . S - 5 . 0 MM (CATEGORY I I ) Cases
Clinical Dx
Fluorescein
Ultrasound Pattern
Rx
1 2 3
Mai. mel. of choroid Metastacic CA Metastatic CA
Helpful Helpful Helpful
Solid detach. Solid detach. Solid detach.
Enucleated Medical Rx Medical Rx
4 5 6 7 8 9
M . M . of Choroid Amelanotic mal. mel. Mai. mel. of choroid Metastatic CA Mal. mel. of choroid Mai. mel. vs met. ca; retinal detachment
Helpful Helpful Helpful Helpful Not helpful Not helpful
Solid detach. Solid detach. Solid detach. Solid detach. Solid detach. Serous retinal detachment
Enucleated Enucleated Enucleated Medical Rx Enucleated Enucleated
cein angiography was not helpful. Although slight areas of fluorescence were noted at varying angiographic stages in all seven patients, the amount of fluorescence was minimal and in no instance was the early arterial or arteriovenous fluorescence pattern noted, as commbnly found in Category I and Category II patients. In four eyes, a rim or "circumferential ring" of fluorescein dye was found outlining the borders of the tumor mass during late phases of angiography, photographically recorded by bringing the focal point of the camera forward to the iris plane. In other patients (Cases 5 and 9 ) angiography was performed, but due to overlying vitreous hemorrhage in one and generalized vitreous haze in the other, interpretations were limited. Ultrasonograms characteristic of solid detachments were obtained in all 13 Category III patients. Cases 7 and 8 demonstrate the characteristic ultrasonograms obtained with large intraocular tumors and their associated fluorescein angiograms revealing "ring fluorescence" in one and the absence of fluorescence in the other (figs. 8 and 9 ) . DISCUSSION
Data from this series revealed that ultrasonography in masses greater than 2.5 mm in height yields characteristic solid tumor patterns, (fig. 10). These were characterized by high-amplitude echoes in the vitreous cav-
Pathology Mai. mel. of choroid CA of Lung Disseminated CA (prostatic) Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid No specimen M . M . of choroid Mai. mel. of choroid with total retinal detachment
ity, representing differences in acoustical density at the interface between vitreous and tumor, followed by irregular lower amplitude echoes emanating from the tumor mass, extending to the posterior bulbar wall as first described by Oksala. Normal vitreous is free of echo activity due to its acoustic homogeneity. These solid detachment patterns, consistently found with proper methods of examination when the tumor is ultrasonically detectable (2.5 mm high or more) can not always be differentiated from patterns obtained with other conditions ; that is, subretinal organized hemorrhages, choroidal hemorrhages, Coats' disease with exudative detachment, total retinal detachment with underlying exudate, and retinitis proliferans.* These diseases are also capable of producing solid detachment-type ultrasonograms which may create confusion in eyes with opaque media in which fundus visualization is precluded." At times, these conditions can be differentiated from neoplastic tissue on the basis of variations in acoustic properties (reflection and absorption), clinically determined by changing the amplification and sensitivity of the incoming and receiving sonic pulse. Neoplastic tissue in most instances has greater acoustical impedance and is more echo-reflecting than hemorrhage, exudate, or fibrosis. 4
* Meyer, D., Gitter, K. and Sarin L. K. : Ultrasonography, malignant melanoma (in preparation).
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Fig. 5 (Gitter, Meyer, Sarin, Keeney and Justice). Early arteriovenous ( A ) and late stage angiograms ( B ) of an amelanotic melanoma of the choroid ( C ) . The ultrasonogram ( D ) in the upper tracing might be mistaken for a serous retinal detachment (arrow) although minimal abnormal echo activity is present in the subretinal space The lower tracing of the same eye (arrow) clarifies the solid detachment pattern (P = posterior bulbar wall).
In time-amplitude ultrasonography, probe placement on the globe must be perpendicular to the intraocular lesion investigated or the acoustical reflections will not be retrieved by the transducer for display on the oscilloscope. If overlying retinal detachments exist, incorrect probe placement may reveal the presence of retinal detachment only, and miss the tumor, as evident in Case 9, Table
3. Unfortunately, choroidal lesions less than 2.5 mm in height may exist and yield normal ultrasonic patterns with present instruments. This is partially explained by the factors of sonic resolution, as determined in part by frequency, beam width (dependent on transduced diameter and collimation of the sound beam), the presence or absence of focusing devices, and acoustic artifacts (mostly
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ton, Gass, Smith and associates first differentiated malignant melanomas from metastatic lesions on the basis of fluorescence of the former and absence of dye in the latter. More recently, they - reported that metastic lesions also can fluoresce and that early arterial filling of choroidal lesions cannot differentiate hemangiomas from melanomas. They also reported the absence of fluorescein in choroidal nevi. 9
8
8
Snyder has demonstrated variability of fluorescence in metastatic lesions ranging from poor fluorescence to bright staining. He concluded that although bright, prompt, patchy fluorescence in the arterial of A - V phases of angiography often is seen with melanomas, pathognomonic patterns for melanoma, metastatic, and benign lesions did not exist. 11
Fig. 6 (Gitter, Meyer, Sarin, Keeney and Justice). Ultrasonogram ( A ) (upper and lower tracings) demonstrate a characteristic serous retinal detachment pattern characterized by a single high amplitude spike (arrow) in the vitreous cavity followed by acoustic silence until the posterior bulbar wall ( P ) . The enucleated specimen ( B ) reveals a flat choroidal tumor (arrow) with large overlying bullous retinal detachment.
caused by velocity changes and divergence of sound by the lens). Photographic recording of intravenous dye injections was first described by Novotny and Alvis in 1961. Maclean and Maumenee had previously reported the use of fluorescein in detecting hemangiomas of the choroid. Subsequently, ophthalmic fluorescein angiography was intensively investigated at the Bascom Palmer Eye Institute. ' ' - -" Nor6
7
2 3 8
10
Our studies indicate that fluorescein angiography is particularly helpful in differential diagnosis of intraocular tumors when the lesion is flat or mildly elevated, or the limits of extension are small. In these tumors (too small for ultrasound detection), the characteristic fluorescence of melanomas in the early arterial or arteriovenous phases of angiography is helpful in distinguishing them from other pigmented fundus lesions. Clinical nevi of the choroid have not been found to fluoresce although nevi with overlying drusen can appear as fluorescence or pseudofluorescence. If, indeed, malignant malanomas can arise from preexisting nevi, as suggested by Yanoff and Zimmerman, theoretically, a stage could exist in which a flat pigmented lesion having the clinical appearance of a nevus would fluoresce. Conversely, it may be assumed that certain early melanomas may not yet have the vascular supply or capillary permeability changes necessary to produce leakage of fluorescein. 12
Angiographic differentiation of melanomas from fresh hemorrhagic lesions, whether choroidal, subretina, or under the pigment epithelium, can be made, as the pattern obtained from the latter characteristically reveals an absence or exclusion of dye
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Fig. 7 (Gitter, Meyer, Sarin, Keeney and Justice). Ophthalmoscopic appearance of an elevated metastatic lesion with adjacent salt and pepper fundus ( A ) revealing fluorescence during the A - V phase with transmission of choroidal fluorescence through the depigmented areas ( B ) and continued leakage of dye at late stages of angiography ( C ) . Note absence of fluorescence in the depigmented areas in later stages ( C ) verifying "pseudofluorescence." The ultrasonogram ( D ) reveals an abnormal solid detachment (arrow) in the involved eye ( lower tracing ) compared to the normal eye ( upper tracing) ( P = posterior bulbar wall).
within the area outlined by the hemorrhage. Even the background choroidal fluorescence normally seen in the posterior pole is obscured by hemorrhagic lesions. The "circumferential ring" pattern of fluorescein outlining large tumors was found in four of 13 patients and may be characteristic of certain large intraocular neoplasms. Gass
(Gass, J. D. M.—Personal communication, December 1967) has observed similar "ringlike" configurations in large lesions, despite absence of otherwise identifying fluorescein patterns. However, characteristic fluorescence of the mass in early phases of angiography is not detected photographically in large intraocular lesions (Category I I I ) .
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TABLE 4 CORRELATION OF FLUORESCEIN AND ULTRASOUND FINDINGS IN 13 PATIENTS WITH LESIONS ELEVATED MORE THAN S MM (CATEGORY I I I ) Cases
Dx
Fluorescein
Ultrasound Pattern
1 2 3 4 S 6
Mai. Mai. Mai. Mai. Mai. Mai.
mel. mel. mel. mel. mel. mel.
"Ring" fluorescence Questionable value Not helpful Not helpful Not helpful; vitreous hemorrhage Not helpful
Solid Solid Solid Solid Solid Solid
detachment detachment detachment detachment detachment detachment
7 8 9 10 11 12 13
Mai. Mai. Mai. Mai. Mai. Mai. Mai.
mel. mel. mel. mel. mel. mel. mel.
"Ring" fluorescence "Ring" fluorescence Not helpful; hazy vitreous "Ring" fluorescence Not helpful Not helpful Not helpful
Solid Solid Solid Solid Solid Solid Solid
detachment detachment detachment detachment detachment detachment detachment
Histopathology Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Amelanotic mal. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid Mai. mel. of choroid
Fig. 8 (Gitter, Meyer, Sarin, Keeney and Justice). Large intraocular melanoma which did not reveal characteristic fluorescence ( A ) . The ultrasonogram ( B ) depicts solid detachment patterns both when the probe was placed on the opposite scleral wall directed toward the tumor (upper tracing) and directly on the sclera overlying the tumor (tower tracing). The histopathologic specimen ( C ) confirmed a malignant melanoma of the choroid.
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Fig. 9 (Gitter, Meyer, Sarin, Keeney and Justice). External ( A ) and late angiogram ( B ) of intraocular melanoma revealing "ring fluorescence." The ultrasonogram ( C) in upper and lower tracing reveals a classic solid detachment pattern with an initial high-peaked echo from tumor surface (1) followed by irregular echoes throughout the vitreous cavity mass (2) extending to the posterior bulbar wall ( 3 ) . The gross specimen reveals a large choroidal melanoma ( D ) .
The value of fluorescein angiography in choroidal hemangiomas, previously described by others " ' is well demonstrated in our two cases. Besides aiding localization of leakage areas to determine sites for photocoagulation, intravenous fluorescein helped to define the extent of the lesion and to quantitate therapeutic progress. Fluorescein angiography is not of value in the presence of opaque media, whereas ultrasonic examination can be particularly helpful 3
7 13
in such eyes. Similarly, in the presence of overlying serous retinal detachments, whether total or quadrantic, photographic recording and interpretation of fluorescein angiography becomes more difficult. The presence of vitreous opacities, whether hemorrhagic, exudative or degenerative, also impairs photographic recording of intravenous fluorescein angiography. Whenever fluorescein angiography is not satisfactory, due to opaque media, ultrasound may be a helpful
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Fig. 10 (Gitter, Meyer, Sarin, Kenney and Justice). Schematic of normal eye with normal echoes obtained from crystal artifact ( A ) , anterior and posterior lens capsules ( B and C ) , posterior bulbar wall ( D ) and retrobulbar part ( E ) . The shaded preretinal area measuring Zy* mm in height represents the area in which intraocular neoplasms are ultrasonically silent with present instruments.
A B C
D E
part of the examination. Even in eyes with total obscuration of the fundus, due to hemorrhage, cataracts, corneal opacities, etc, ultrasound can help evaluate the posterior segment. Although both techniques offer major aids in the diagnosis of intraocular neoplasms, clinical evaluation by the physician, utilizing all diagnostic modalities, including contact lens, slitlamp, biomicroscopy, direct and indirect ophthalmoscopy with scleral depression, and transillumination, is fundamental and cannot be superseded by the two valuable procedures described. SUMMARY
Thirty patients with visible intraocular tumors were studied using time-amplitude ultrasonography and fluorescein angiography. Results demonstrated that ultrasound revealed solid detachment (tumor-type) patterns in all patients with lesions elevated mm or more, whereas tumors less elevated yielded normal ultrasonograms with present instrumentation. Fluorescein angiography was of particular diagnostic aid in evaluating the flatter lesions. Limitations of both techniques as regards tumor size, configuration and vascularity, as well as the clarity of the ocular media, are discussed. The combined utilization of both modali-
ties according to their specific areas of applicability greatly enhances the diagnostic evaluation of intraocular tumors. ACKNOWLEDGMENTS W e are grateful to P. Robb McDonald, M.D. and the Retina Service at Wills Eye Hospital for encouragement and guidance as well as the use of many of their patients in this series. W e thank William R. Green, M . D . for aiding in the pathology as well as assisting the editing of this manuscript REFERENCES
1. Gitter, K. A., Meyer, D., White R. A , Sarin, L. K. and Keeney, A . H. : Uses of diagnostic ultrasound in ophthalmology. Scientific exhibit at American Medical Association, 1967. 2. Justice, J. J., Jr. and Sever, R. J. : Technique of Fluorescein Fundus Photography. Neuro-ophthalmology: Vol. 2, (ed. Smith, J. L . ) Symposium of University of Miami. St. Louis, Mosby, 1965, p. 82. 3. Norton, E. W . D. and Gutman, F.: Fluorescein angiography and hemangiomas of the choroid. Arch. Ophth. 78:121, 1967. 4. Oksala, A . : Echogram in melanoma of the choroid. Brit J. Ophth. 43:408, 1959. 5. Gitter, K. A., Meyer, D. and Sarin, L. K : Ultrasound to evaluate eyes with opaque media. A . M. J. Ophth. 64:100, 1967. 6. Novotny, H . R. and Alvis, D. L. : A method of photographing fluorescence in circulating blood in the human retina. Circulation 24:82, 1961. 7. Maclean, A . L. and Maumenee, A . E. : Hemangioma of the choroid: Am. J. Ophth. 50:3, 1960. 8. Norton, E. W . D., Smith, J. L., Curtin, V . T. and Justice, J., Jr.: Fluorescein fundus photography: A n aid in the differential diagnosis of poste-
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rior ocular lesions. Tr. Am. Acad. Ophth. Otolarvng. 68:755, 1964. 9. Norton, E. W . D„ Gass, .1. D., Smith, J. L., Curtin, V. T., David, N. J. and Justice, J., Jr. Fluorescein in the study of macular disease—Symposium : Macular Diseases. Tr. Am. Acad. Ophth. Otolaryng. 69:631, 1965. 10. Gass, J. D. M. : Pathogenesis of disciform detachment of the neuroepithelium Am. J. Ophth. 63 :573, 1967.
HEMANGIOPERICYTOMA KENNETH
L.
11. Snyder W . B., Allen, L. and Frazier, O. : Fluorescence angiography of ocular tumors. Tr. Am. Acad. Ophth. Otolaryng. 71:820, 1967 12. Yanoff, M. and Zimmerman, L. E. : Histogenesis of malignant melanomas of the uvea. Arch. Ophth. 77 :331, 1967. 13. Smith, J. L , David, N. J., Hart, L. M., Levenson, D. S. and Tillett, C. W . : Hemangiomas of the choroid : Fluorescein photography and photocoagulation. Arch. Ophth. 69:51, 1963.
OF T H E LID A N D ORBIT MACOUL,
M.D.
Palo Alto, California T h e hemangiopericytoma is a m o n o m o r phous tumor derived from a specific vascular element,
the
pericyte.
1,2
The
proliferating
pericytes are found outside the walls of capillaries. T h i s vascular tumor is slowly invasive,
occasionally
recur. ' 3
metastatic
and tends
to
4
T h i s paper describes the slowly destructive course of the disease in a patient w h o refused treatment until two years after initial appearance of the tumor. CASE
REPORT
A 68-year-old woman entered Stanford Medical Center for removal of a large mass involving both orbits and the forehead. Two years prior to admission, a nontender mass appeared in the right upper eyelid. A biopsy revealed hemangiopericytoma. However, the patient refused hospitalization and medical care and did not return until two years later. During this period the tumor had grown to enormous size over the forehead, into both orbits, and into the anterior cranial fossa. Physical examination revealed a well-nourished woman with a huge frontal tumor. The mass was soft, spongy, slightly tender, nonpulsatile, and without a bruit, and extended over the forehead into the bridge of the nose and into the right and left orbits. The right eye was proptotic, being displaced downward and outward (fig. 1 ) . The right upper lid was ptotic, and contained large collateral veins. The right conjunctiva was suffused. The left superior rectus, right superior oblique, and right superior rectus muscles were paralyzed. Retinal veins were dilated in the right eye. With correction, the patient was able to count fingers at nine feet with the right eye; corrected visual acuity in the left eye was 20/30. The pupils were equal, round, and reacted to light. The ocular tension was normal in both eyes From the Division of Ophthalmology, Stanford University Medical Center.
Fig. 1 (Macoul). Proptotic right eye displaced down and out. Note ptosis of right upper lid with large collateral veins. and bilateral posterior subcapsular cataracts were present Arteriography showed that the tumor was fed by collaterals of the right and left external and internal carotid arteries. Surgical exposure revealed that the large mass had destroyed both frontal sinuses, the roof and medial walls of both orbits, the ethmoid sinuses and the greater and lesser wings of the sphenoid bone bilaterally. The tumor had invaded the anterior cranial fossa and infiltrated both frontal lobes. The mass could not be removed completely because of extensive brain involvement. The patient subsequently received radiotherapy (6,000 rads over a five-week period). An arteriogram 10 weeks after surgery revealed recurrent or residual tumor in the anterior falx cerebri, the left side of the nose, and the medial aspect of the left orbit. The patient has continued to do well VA years postoperatively. MICROSCOPIC
The
unencapsulated
EXAMINATION
tumor consisted
of
broad sheets of oval-to-spindle-shaped cells