False-Positive Results With the Radioactive Phosphorus Test Hanna F.
Shammas, MD; Thomas C. Burton, MD;
\s=b\ A chorioretinal granuloma that contained acid-fast bacilli and a choriodal nevus that consisted of benign nevus cells yielded false-positive radioactive phosphorus tests. The \g=b\ emission exceeded that of the control areas by more than 100% in each case. The granuloma had Infiltrated the sclera, permitting inflammatory tissue to be in closer proximity to the counting probe than was the normal choroid. The reason for the increased metabolic activity of the nevus cells remains unexplained.
(Arch Ophthalmol 95:2190-2192, 1977)
The
radioactive phosphorus (,JP) uptake test is gaining more popularity in the diagnosis of intraocular tumors. The test is considered to be highly reliable.'"' Shields et al' reported no false-positive results in a series of almost 600 "-P tests. This report describes two cases in which a choroidal melanoma was suspected on fundus examination, fluorescein angiography, and echography. The ;'-'P test was falsely positive in each case.
Thomas A.
Weingeist, MD
lesion was suspected clinically, but a necrotic choroidal melanoma could not be excluded. Fluorescein angiography demonstrated diffuse, late staining of the mass, which was compatible with a melanoma. Eehographic examination with A-scan and B-scan techniques disclosed a solid, elevated lesion, which was 6.2 mm in thickness and consistent with a choroidal melanoma.
Forty-eight hours after intravenous injection of 750 fiCi (>f sodium phosphate P 32, the sciera was exposed by a 360° limbal peritomy, and the tumor outline was
marked with diathermy. The average control reading was 65 counts per minute (CPM). The average tumor reading was 134 CPM, an increase of 106% compared to the control sites. The right eye was enucleated during the same operative procedure. Histopathological studies showed a
large, chorioretinal, inflammatory
mass,
with central necrosis and infiltration of the sciera (Fig 2, top and center). The mass was composed predominantly of lymphocytes, epithelioid cells, and giant cells (Fig 2, bottom). Acid-fast organisms were de-
tected with the Kinyoun stain. Cask 2.-A 76-year-old woman was discovered to have an elevated choroidal mass, on a routine eye examination. Visual acuity was reduced to 20/40 in each eye owing to cataractous changes. Fundus examination of the right eye revealed a slightly elevated, pigmented lesion that was located temporally between the ora serrata and equator and measured approximately 5 mm in diameter. On the surface of the tumor, there appeared to be several oval and round pigment epithelial detachments, ranging up to 1 mm in diameter. A zone of atrophy of the pigment epithelium surrounded the lesion. Fundus photography and fluorescein
angiography were not entirely satisfactory owing to lens opacities. In the regions of suspected pigment epithelial detachments, there was early, blocked, choroidal fluorescence and late staining. Echographic
examination disclosed
a
solid, low-reflective choroidal lesion, 1.2 mm
in thickness. The tumor pattern
was
suspicious for melanoma, although a definitive diagnosis could not be made because of the small prominence of the lesion.
REPORT OF CASES Cask. l.-A 30-year-old man had noticed decreased visual acuity in the right eye for ten days. The past medical history was not
contributory. Visual acuity measured 20/2,000 in the right eye and 20/20 in the left. The fundus of the right eye contained a large, elevated, nonpigmented mass in the superotemporal quadrant. There was overlying hemorrhage and a secondary retinal detachment involving the macula (Fig 1). Cells were observed in the vitreous. An
inflammatory
for publication March 28, 1977. From the Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa
Accepted
City. Reprint requests to the C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 (Dr Shammas).
Fig 1.—Case 1. Large, elevated, nonpigmented mass superotemporal quadrant of fundus of right eye.
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
with subretinal
hemorrhages
in
Forty-eight hours after intravenous injection of 670 (iCi of sodium phosphate P 32, the sciera was exposed by a 360° limbal peritomy. The tumor was outlined with surface diathermy, using the indirect ophthalmoscope. The average control reading was 55 CPM. The average tumor count
169 CPM, an increase of 207% to the control sites. Because of the small dimensions of the tumor mass, the good visual acuity, and the lack of documentation of tumor growth, it was decided to observe the course of the tumor. An enucleation was performed four months later because the tumor appeared to have enlarged slightly. On histopalhological examination, the choroidal mass was diffusely pigmented, containing plump, dendritic, balloon- and spindle-shaped nevus cells (Fig 3, top and bottom). Serial sections failed to reveal the presence of malignant cells. Associated with the nevus were drusen or small detachments of the retinal pigment epithelium.
was
compared
COMMENT Most false-positive results with the :'-'P test have occurred with the transconjunctival approach and were at-
tributed to inflammation, subconjunctival hemorrhage, scierai thinning, or incorrect placement of the probe over extraocular muscles.'"'" A 30%- increase in 3aP uptake compared with control areas was previously regarded as a positive test. This low level probably resulted in more frequent
false-positive tests. In 1970, Hagler et al' described a modification in the technique, stressing precise localization of the lesion by indirect ophthalmoscopy, conjunctival incision, and accurate positioning of the counting probe. A 60% or greater increase in counts
was
considered
positive for malignancy. Using the same technique, Cox" reported three cases of choroidal
hemangioma with uptakes exceeding 100% compared with the controls. Two cases were confirmed histologically. In
our
series of 185 "P tests,
an
Cross section of globe
Fig 2.—Case 1. Top, showing large, chorioretinal inflammatory mass with central necrosis (hematoxylineosin, original magnification x 5). Center, Scierai infiltration by inflammatory cells (hematoxylin-eosin, original magnification X32). Bottom, Inflammatory mass containing lymphocytes, epithelioid cells, and giant cells (hematoxylin-eosin, original magnification x320).
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
Fig 3.—Case 2. Top, Diffusely pigmented choroidal mass. Note presence of drusen or small detachments of retinal pigment epithelium (hematoxylin-eosin, original magnification x 32). Bottom, Choroidal mass showing plump dendritic, balloonand spindle-shaped nevus cells (hematoxylin-eosin, original magnification x320).
tiloma of the sciera," and granulation tissue prolapsing through a scierai dehiscence."1 In each case, the inflammatory tissue was closer to the probe when compared with the choroid of the control areas. Since ß particles emitted by :,-P have a short range of tissue penetration and decrease exponentially with increasing tissue thickness, the relative proximity of the probe to the radiation source is of crucial importance.The second benign lesion that yielded an elevated '-P uptake was a choroidal nevus with overlying pigment epithelial detachments. The mechanism for the apparently increased metabolic activity in this case is unknown. The ;|'-'P test usually is performed for suspected malignancies, and uncommonly is performed for clinically benign lesions. Routine testing might reveal that choroidal nevi are metabolically more active than previously suspected. Occasional false-positive tests with radioactive phosphorus should not be regarded as a denial of the high reliability that was indicated by previous investigations. Such results merely show that complete dependence cannot be placed on any one test to determine the presence or absence of intraocular malignancies.
uptake of at least 100%> compared with
control counts was considered to be positive. We had two false-positive results that were confirmed histologi-
cally. One patient had a chorioretinal granuloma that infiltrated the sciera. False-positive results have been reported previously with scleritis,: gran-
Nonproprietary
Name and
Trademark of Drug Sodium phosphate P S2-Phosvhotove.
References 1. Hagler WS, Jarrett WH II, Humphrey WT: The radioactive phosphorus uptake test in diagnosis of uveal melanoma. Arch Ophthalmol 83:548-557, 1970. 2. Chua J: Value of 32P test in diagnosis of intraocular tumors, in Blodi FC (ed): Current Concepts in Ophthalmology, IV. St Louis, CV
Mosby Co, Publishers, 1974,
pp 250-263. 3. Ruiz RS, Howerton EE Jr: 32P testing for posterior segment lesions. Trans Am Acad Ophthalmol Otolaryngol 79:287-296, 1975. 4. Shields JA, Hagler WS, Federman JL, et al: The significance of the 32P uptake test in the diagnosis of posterior uveal melanomas. Trans Am Acad Ophthalmol Otolaryngol 79:297-306, 1975.
5. Kennedy RJ, Glasser O, Kazdan P: The use of radioactive phosphorus in the detection of intraocular tumors. Cleve Clin Q 21:133-140, 1954. 6. Eisenberg IJ, Leopold IH, Sklaroff D: Use of radioactive phosphorus in detection of intraocular neoplasms. Arch Ophthalmol 51:633-641, 1954. 7. Turner IS, Leopold IH, Eisenberg IJ: The radioactive phosphorus (32P) uptake test in ophthalmology: A review of the literature and analysis of results in two hundred sixty-two cases of ocular and adnexal pathology. Arch Ophthalmol 55:52-83, 1956. 8. Dunphy EB, Dowling JL Jr, Scott A: Experience with radioactive phosphorus in tumor
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
detection. Arch Ophthalmol 57:485-490, 1957. 9. Carmichael PL, Leopold IH: The radioactive
phosphorus
test
in
ophthalmology.
Am
J
Ophthalmol 49:484-488, 1960. 10. Goldberg B, Tabowitz D, Kara GB, et al: The use of 32P in the diagnosis of ocular tumors: I.
A clinical report of 125 cases. Arch Ophthalmol 1961. 11. Cox MS, in discussion, Ruiz RS, Howerton EE Jr: 32P testing for posterior segment lesions; and Shields JA, Hagler WS, Federman JL, et al: The significance of the 32P uptake test in the diagnosis of posterior uveal melanomas. Trans
65:196-211,
Am Acad 1975.
Ophthalmol Otolaryngol 79:307-309,
Shammas, MD; Thomas C. Burton, MD;
\s=b\ A chorioretinal granuloma that contained acid-fast bacilli and a choriodal nevus that consisted of benign nevus cells yielded false-positive radioactive phosphorus tests. The \g=b\ emission exceeded that of the control areas by more than 100% in each case. The granuloma had Infiltrated the sclera, permitting inflammatory tissue to be in closer proximity to the counting probe than was the normal choroid. The reason for the increased metabolic activity of the nevus cells remains unexplained.
(Arch Ophthalmol 95:2190-2192, 1977)
The
radioactive phosphorus (,JP) uptake test is gaining more popularity in the diagnosis of intraocular tumors. The test is considered to be highly reliable.'"' Shields et al' reported no false-positive results in a series of almost 600 "-P tests. This report describes two cases in which a choroidal melanoma was suspected on fundus examination, fluorescein angiography, and echography. The ;'-'P test was falsely positive in each case.
Thomas A.
Weingeist, MD
lesion was suspected clinically, but a necrotic choroidal melanoma could not be excluded. Fluorescein angiography demonstrated diffuse, late staining of the mass, which was compatible with a melanoma. Eehographic examination with A-scan and B-scan techniques disclosed a solid, elevated lesion, which was 6.2 mm in thickness and consistent with a choroidal melanoma.
Forty-eight hours after intravenous injection of 750 fiCi (>f sodium phosphate P 32, the sciera was exposed by a 360° limbal peritomy, and the tumor outline was
marked with diathermy. The average control reading was 65 counts per minute (CPM). The average tumor reading was 134 CPM, an increase of 106% compared to the control sites. The right eye was enucleated during the same operative procedure. Histopathological studies showed a
large, chorioretinal, inflammatory
mass,
with central necrosis and infiltration of the sciera (Fig 2, top and center). The mass was composed predominantly of lymphocytes, epithelioid cells, and giant cells (Fig 2, bottom). Acid-fast organisms were de-
tected with the Kinyoun stain. Cask 2.-A 76-year-old woman was discovered to have an elevated choroidal mass, on a routine eye examination. Visual acuity was reduced to 20/40 in each eye owing to cataractous changes. Fundus examination of the right eye revealed a slightly elevated, pigmented lesion that was located temporally between the ora serrata and equator and measured approximately 5 mm in diameter. On the surface of the tumor, there appeared to be several oval and round pigment epithelial detachments, ranging up to 1 mm in diameter. A zone of atrophy of the pigment epithelium surrounded the lesion. Fundus photography and fluorescein
angiography were not entirely satisfactory owing to lens opacities. In the regions of suspected pigment epithelial detachments, there was early, blocked, choroidal fluorescence and late staining. Echographic
examination disclosed
a
solid, low-reflective choroidal lesion, 1.2 mm
in thickness. The tumor pattern
was
suspicious for melanoma, although a definitive diagnosis could not be made because of the small prominence of the lesion.
REPORT OF CASES Cask. l.-A 30-year-old man had noticed decreased visual acuity in the right eye for ten days. The past medical history was not
contributory. Visual acuity measured 20/2,000 in the right eye and 20/20 in the left. The fundus of the right eye contained a large, elevated, nonpigmented mass in the superotemporal quadrant. There was overlying hemorrhage and a secondary retinal detachment involving the macula (Fig 1). Cells were observed in the vitreous. An
inflammatory
for publication March 28, 1977. From the Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa
Accepted
City. Reprint requests to the C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 (Dr Shammas).
Fig 1.—Case 1. Large, elevated, nonpigmented mass superotemporal quadrant of fundus of right eye.
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
with subretinal
hemorrhages
in
Forty-eight hours after intravenous injection of 670 (iCi of sodium phosphate P 32, the sciera was exposed by a 360° limbal peritomy. The tumor was outlined with surface diathermy, using the indirect ophthalmoscope. The average control reading was 55 CPM. The average tumor count
169 CPM, an increase of 207% to the control sites. Because of the small dimensions of the tumor mass, the good visual acuity, and the lack of documentation of tumor growth, it was decided to observe the course of the tumor. An enucleation was performed four months later because the tumor appeared to have enlarged slightly. On histopalhological examination, the choroidal mass was diffusely pigmented, containing plump, dendritic, balloon- and spindle-shaped nevus cells (Fig 3, top and bottom). Serial sections failed to reveal the presence of malignant cells. Associated with the nevus were drusen or small detachments of the retinal pigment epithelium.
was
compared
COMMENT Most false-positive results with the :'-'P test have occurred with the transconjunctival approach and were at-
tributed to inflammation, subconjunctival hemorrhage, scierai thinning, or incorrect placement of the probe over extraocular muscles.'"'" A 30%- increase in 3aP uptake compared with control areas was previously regarded as a positive test. This low level probably resulted in more frequent
false-positive tests. In 1970, Hagler et al' described a modification in the technique, stressing precise localization of the lesion by indirect ophthalmoscopy, conjunctival incision, and accurate positioning of the counting probe. A 60% or greater increase in counts
was
considered
positive for malignancy. Using the same technique, Cox" reported three cases of choroidal
hemangioma with uptakes exceeding 100% compared with the controls. Two cases were confirmed histologically. In
our
series of 185 "P tests,
an
Cross section of globe
Fig 2.—Case 1. Top, showing large, chorioretinal inflammatory mass with central necrosis (hematoxylineosin, original magnification x 5). Center, Scierai infiltration by inflammatory cells (hematoxylin-eosin, original magnification X32). Bottom, Inflammatory mass containing lymphocytes, epithelioid cells, and giant cells (hematoxylin-eosin, original magnification x320).
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
Fig 3.—Case 2. Top, Diffusely pigmented choroidal mass. Note presence of drusen or small detachments of retinal pigment epithelium (hematoxylin-eosin, original magnification x 32). Bottom, Choroidal mass showing plump dendritic, balloonand spindle-shaped nevus cells (hematoxylin-eosin, original magnification x320).
tiloma of the sciera," and granulation tissue prolapsing through a scierai dehiscence."1 In each case, the inflammatory tissue was closer to the probe when compared with the choroid of the control areas. Since ß particles emitted by :,-P have a short range of tissue penetration and decrease exponentially with increasing tissue thickness, the relative proximity of the probe to the radiation source is of crucial importance.The second benign lesion that yielded an elevated '-P uptake was a choroidal nevus with overlying pigment epithelial detachments. The mechanism for the apparently increased metabolic activity in this case is unknown. The ;|'-'P test usually is performed for suspected malignancies, and uncommonly is performed for clinically benign lesions. Routine testing might reveal that choroidal nevi are metabolically more active than previously suspected. Occasional false-positive tests with radioactive phosphorus should not be regarded as a denial of the high reliability that was indicated by previous investigations. Such results merely show that complete dependence cannot be placed on any one test to determine the presence or absence of intraocular malignancies.
uptake of at least 100%> compared with
control counts was considered to be positive. We had two false-positive results that were confirmed histologi-
cally. One patient had a chorioretinal granuloma that infiltrated the sciera. False-positive results have been reported previously with scleritis,: gran-
Nonproprietary
Name and
Trademark of Drug Sodium phosphate P S2-Phosvhotove.
References 1. Hagler WS, Jarrett WH II, Humphrey WT: The radioactive phosphorus uptake test in diagnosis of uveal melanoma. Arch Ophthalmol 83:548-557, 1970. 2. Chua J: Value of 32P test in diagnosis of intraocular tumors, in Blodi FC (ed): Current Concepts in Ophthalmology, IV. St Louis, CV
Mosby Co, Publishers, 1974,
pp 250-263. 3. Ruiz RS, Howerton EE Jr: 32P testing for posterior segment lesions. Trans Am Acad Ophthalmol Otolaryngol 79:287-296, 1975. 4. Shields JA, Hagler WS, Federman JL, et al: The significance of the 32P uptake test in the diagnosis of posterior uveal melanomas. Trans Am Acad Ophthalmol Otolaryngol 79:297-306, 1975.
5. Kennedy RJ, Glasser O, Kazdan P: The use of radioactive phosphorus in the detection of intraocular tumors. Cleve Clin Q 21:133-140, 1954. 6. Eisenberg IJ, Leopold IH, Sklaroff D: Use of radioactive phosphorus in detection of intraocular neoplasms. Arch Ophthalmol 51:633-641, 1954. 7. Turner IS, Leopold IH, Eisenberg IJ: The radioactive phosphorus (32P) uptake test in ophthalmology: A review of the literature and analysis of results in two hundred sixty-two cases of ocular and adnexal pathology. Arch Ophthalmol 55:52-83, 1956. 8. Dunphy EB, Dowling JL Jr, Scott A: Experience with radioactive phosphorus in tumor
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
detection. Arch Ophthalmol 57:485-490, 1957. 9. Carmichael PL, Leopold IH: The radioactive
phosphorus
test
in
ophthalmology.
Am
J
Ophthalmol 49:484-488, 1960. 10. Goldberg B, Tabowitz D, Kara GB, et al: The use of 32P in the diagnosis of ocular tumors: I.
A clinical report of 125 cases. Arch Ophthalmol 1961. 11. Cox MS, in discussion, Ruiz RS, Howerton EE Jr: 32P testing for posterior segment lesions; and Shields JA, Hagler WS, Federman JL, et al: The significance of the 32P uptake test in the diagnosis of posterior uveal melanomas. Trans
65:196-211,
Am Acad 1975.
Ophthalmol Otolaryngol 79:307-309,
