- Email: [email protected]
Calcification in choroidal melanoma after transpupillary thermotherapy
accumulation and melanin production, 123I-IMP has been used clinically in attempts to detect malignant melanoma.3,4 However, most of the clinical interest in 123I-IMP as a diagnostic radiopharmaceutical has been devoted to skin melanoma and its metastases. In this study, the results of single photon emission computed tomography (SPECT) using 123I-IMP performed in 20 patients with suspected uveal or ocular adnexal melanoma were evaluated. Orbital SPECT images were obtained 20 minutes (early phase) and 24 hours (late phase) after the intravenous injection of 111 MBq of 123 I-IMP. None of the 20 patients had accumulation of 123 I-IMP on early phase SPECT, whereas 8 patients showed marked accumulation in the area corresponding to the uveal tumor in the late phase (Figure 1). In six out of eight patients with positive results of 123I-IMP SPECT, clinical examinations, including indirect ophthalmoscopy, ultrasonography, and magnetic resonance imaging (MRI) of the eyeballs, were consistent with the diagnosis of uveal melanoma, whereas the other two patients showed atypical ocular fundus manifestation and MRI, in which it was difficult to make a diagnosis as uveal melanoma. In eight patients with high accumulation of 123I-IMP in the uveal tumor at late phase, seven patients underwent enucleation and all of them were histologically proven as choroidal or ciliary body melanoma, whereas the other patient was found to have iris melanoma based on the results of ultrasound biomicroscopy, MRI, and clinical course (Table 1). The patient with iris melanoma has been followed up for 5 years without any medical treatment. Twelve out of 20 patients with no accumulation of 123 I-IMP on either early or late phases of SPECT images were found to have clinically or histologically iris nevus, choroidal nevus, melanocytoma of the optic disk, choroidal hemangioma, metastatic choroidal tumor, and other ocular adnexal tumors (Table 2). In vitro studies have shown that 123I-IMP uptake by amelanotic melanoma cell lines is much lower than by melanotic melanoma cell lines and these results are reflected by clinical data obtained from patients with skin melanoma.5 In the present study, the histologic features were compared with the results of intensity of accumulated 123 I-IMP, evaluated as scintillation counts/pixel in corresponding areas. However, no relationship was demonstrated between semiquantitatively assessed 123I-IMP SPECT images and tumor size as well as histologic features, including cell type, amount of melanin pigment, and extraocular infiltration of the tumor cells (Table 1). Diagnosis of primary uveal melanoma is currently made on the basis of characteristic ocular manifestations, ultrasonography, and MRI findings. However, some cases exist in which atypical ocular and radiologic manifestations may lead to misdiagnosis. Therefore, more specific examinations should be applied to obtain a correct diagnosis for atypical cases. Although various radiopharmaceuticals such as iodine-125 chloroquine analogue and radiolabeled VOL. 132, NO. 6
antibody have been applied for the detection of malignant melanoma, no satisfactory results have been obtained so far.4 The results of the present study suggest that the 123IIMP SPECT technique may be not only sensitive, but also specific for the detection of uveal malignant melanoma. The high rate of detection by the 123I-IMP images in patients with uveal melanoma compared with skin melanoma mentioned before5 may be caused by abundant vascular distribution in the uveal tissue as well as high resolution of images obtained by SPECT to determine localized tumors. N-isopropyl p-[123I]-iodoamphetamine SPECT may be an effective procedure for the diagnosis of uveal melanoma, in which it is difficult to establish a diagnosis by conventional methods. REFERENCES
1. Winchell HS, Baldwin RM, Lin TH. Development of I-123labeled amines for brain studies: localization of I-123 iodophenylalkyl amines in rat brain. J Nucl Med 1980;21:940 –946. 2. Holman BL, Hill TC, Polak JF, et al. Cerebral perfusion imaging with iodine 123-labeled amines. Arch Neurol 1984; 41:1060 –1065. 3. Wada M, Ichiya Y, Katsuragi M, et al. Scintigraphic visualization of human malignant melanoma with N-isopropyl-p-[I123] iodoamphetamine. Clin Nucl Med 1985;10:415– 417. 4. Ono S, Fukunaga M, Otsuka N, et al. Visualization of ocular melanoma with N-isopropyl p-[123I]-iodoamphetamone. J Nucl Med 1988;29:1448 –1450. 5. Cohen MB, Saxton RE, Lake RR, et al. Detection of malignant melanoma with iodine-123 iodoamphetamine. J Nucl Med 1988;29:1200–1206.
Calcification in Choroidal Melanoma After Transpupillary Thermotherapy Hayyam Kiratli, MD, and Sevgu¨ l Bilgic¸ , MD PURPOSE:
To report the response of calcification in choroidal melanoma after transpupillary thermotherapy. METHODS: Interventional case report. A 66-year-old male with a posterior uveal melanoma measuring 10 ⴛ 8 ⴛ 4.4 mm underwent infrared diode laser transpupillary thermotherapy three times, each 12 weeks apart. For each treatment, a 3-mm spot size of 1-minute duration was used, and the power setting varied between 450 mW and 500 mW. RESULTS: Two months after the last transpupillary thermotherapy session, A- and B-mode echographic patterns Accepted for publication Jul 17, 2001. From the Ocular Oncology Service, Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey. Inquiries to Hayyam Kiratli, MD, Associate Professor of Ophthalmology, Hacettepe Hastanesi Go¨ z ABD, Sihhiye TR-06100 Ankara, Turkey; fax: ⫹90 312 309 4101; e-mail: [email protected]
BRIEF REPORTS
939
FIGURE 1. (Left) Left fundus view at initial presentation. (Right) B-scan ultrasonography of the left eye shows the juxtapapillary tumor before treatment.
FIGURE 2. (Right) B-scan echography of the left eye shows intratumoral calcification. (Left) Arrows on this photograph of the left fundus indicate the area from where echoes suggestive of calcification were obtained.
strongly suggestive of intratumor calcification were observed. The tumor regressed to 2.8 mm in thickness, but calcification persisted. Local recurrence or distant metastasis was not detected during a follow-up of 14 months. CONCLUSION: Clinically detectable calcification is extremely rare in choroidal melanomas. Tumor regression with slowly progressive calcification may occur after transpupillary thermotherapy. (Am J Ophthalmol 2001;132:939 –941. © 2001 by Elsevier Science Inc. All rights reserved.)
T
scribes intralesional calcification that ocurred in a choriodal melanoma after transpupillary thermotherapy. A 66-year-old male was examined for the complaint of gradual loss of vision in his left eye. His best-corrected visual acuity was RE: 20/20 and LE: 20/40. The anterior segments and intraocular pressures were normal. In the left eye, fundus examination disclosed a macular choroidal melanoma that measured 10 ⫻ 8 mm in basal dimensions. A small nodular portion was overhanging the optic disk (Figure 1, left). A small amount of orange pigment was observed on the superior part of the lesion. Minimal subretinal fluid was found over the tumor. Echographic tumor thickness was measured at 4.4 mm (Figure 1, right). On A-scan, the tumor had low-to-medium internal reflectivity. Ultrasonography and magnetic resonance imaging scans did not suggest optic nerve invasion or extrascleral extension. As the patient refused enucleation, he was offered transpupillary thermotherapy, which was per-
RANSPUPILLARY THERMOTHERAPY IS INCREASINGLY
used in the primary management of some selected posterior uveal melanomas. Some unusual tumor responses and complications are inevitably encountered as experience and a number of patients treated with this technique grow in ocular oncology centers. The present interventional case report covering 14 months of follow-up de940
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
DECEMBER 2001
formed three times, each 12 weeks apart. A 3-mm spot size for 1 minute/spot was used. The power setting was 500 mW for the first session, 450 mW for the second, and 500 mW for the third. Two months after the last session, high internal reflectivity on A-scan and a hyperechogenic area on B-scan over the surface of the tumor became evident (Figure 2, left). This area also produced a barely detectable orbital shadowing. Meanwhile, the tumor showed signs of regression and the thickness was reduced to 2.8 mm (Figure 2, right). His visual acuity was LE: 20/200. In the following 3 months, gradual regression continued but the presumed calcification site persisted. The patient did not have hypercalcemia at any time on his routine systemic examinations. Deposition of calcium in the absence of hypercalcemia is a sign of previous cell injury and may occur in dead or dying tissues.1 Mitochondria are the sites where the dying cell starts to accumulate calcium salts.1 Transpupillary thermotherapy results in cell necrosis primarily by disruption of mitochondria at subcoagulation temperatures of 45°C to 60°C.2 Histopathological studies on melanomas previously treated with transpupillary thermotherapy revealed dilated and occluded vessels, loss of cytoplasm, and shrunken nuclei, but failed to show calcification.3 Oosterhuis and associates4 reported that a week after transpupillary thermotherapy, increased reflectivity on B-scan approximately 3 mm depth from the apex of the tumor was a common finding. However, this finding disappeared within 2 months as the tumors flattened.4 We believe that this does not represent true calcification. In our case, the echoes suggestive of calcification were detected exactly where tumor necrosis was expected. Intratumoral calcification after brachytherapy is exceedingly rare. In 1300 patients treated with Ru-106 plaque brachytherapy, only 3 developed high reflectivity and orbital shadowing compatible with calcification.5 The present case suggests that calcification in choroidal melanoma may also be encountered after transpupillary thermotherapy. REFERENCES
1. Robbins SL, Cotran RS, Kumar V. Pathologic basis of disease. 3rd ed. Philadelphia: W.B. Saunders Company; 1984:35. 2. Journe´ e-de Korver JG, Oosterhuis JA, Kakabeeke-Kemme HM, de Wolff-Rouendaal D. Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma. Doc Ophthalmol 1992;82:185–191. 3. Journe´ e-de Korver JG, Oosterhuis JA, de Wolff-Rouendaal D, Kemme H. Histopathological findings in human choroidal melanomas after transpupillary thermotherapy. Br J Ophthalmol 1997;81:234 –239. 4. Oosterhuis JA, Journe´ e-de Korver JG, Kakabeeke-Kemme HM, Bleeker FC. Transpupillary thermotherapy in choroidal melanomas. Arch Ophthalmol 1995;113:325–321. 5. Kellner U, Foerster MH, Bornfeld N. Calcification-like echographic pattern in uveal melanomas treated with brachytherapy. Br J Ophthalmol 1993;77:827.
VOL. 132, NO. 6
Choroidal Melanoma Metastatic to the Contralateral Choroid Arun D. Singh, MD, Jerry A. Shields, MD, Carol L. Shields, MD, and Takami Sato, MD PURPOSE:
To report metastasis of choroidal melanoma to the contralateral choroid. METHODS: Interventional case report. In a 49-year-old Caucasian female, a primary choroidal melanoma, left eye, was diagnosed and treated with Ruthenium-106 plaque radiotherapy. The choroidal melanoma showed excellent regression with flattening of the mass and adjacent chorioretinal atrophy. RESULTS: Fifteen years after brachytherapy for choroidal melanoma, left eye, the patient developed a metastatic melanoma to the contralateral choroid as the first sign of metastasis. No history of oculo(dermal) melanocytosis or cutaneous melanoma existed. Systemic evaluation disclosed multiple metastases confined to the liver. CONCLUSION: Metastasis to the contralateral choroid can be the first sign of metastasis from choroidal melanoma. (Am J Ophthalmol 2001;132:941–943. © 2001 by Elsevier Science Inc. All rights reserved.)
U
VEAL MELANOMA METASTASIZES MOST COMMONLY
to liver, lungs, and bone.1 Rarely uveal melanoma metastasize to the contralateral orbital and adnexal structures.2 Metastasis of choroidal melanoma to the contralateral choroid is also rare.2 We report a patient with primary choroidal melanoma, who subsequently developed metastasis to the contralateral choroid as the first sign of metastatic disease. ● CASE:
A 49-year-old healthy Caucasian female was examined for a suspicious choroidal nevus in the left eye in 1985. Ocular and systemic history were noncontributory. The visual acuity was 20/20 in each eye. Anterior segment examination of both eyes and fundus examination of the right eye were normal with no evidence of a choroidal nevus or oculo(dermal)melanocytosis. Ophthalmoscopic examination of the left eye showed a bilobed, pigmented choroidal mass measuring 8 mm in diameter and 3 mm in thickness. Six months later, evidence of growth existed, with a development of localized retinal detachment (Figure 1, top). A diagnosis of primary choroidal melanoma was made, and the patient was treated with a 15-mm Ruthenium-106 plaque radiotherapy (apical dose: 86 Gy).
Accepted for publication Jun 26, 2001. From the Oncology Service (A.D.S., C.L.S., J.A.S.), Wills Eye Hospital, and the Division of Medical Oncology (T.S.), Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania. Supported by the Sarah B. Kant Fund, Philadelphia, Pennsylvania (A.D.S.). Inquiries to Arun D. Singh, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, Pennsylvania 19107; fax: (215) 928-1140; e-mail: [email protected]
BRIEF REPORTS
941
antibody have been applied for the detection of malignant melanoma, no satisfactory results have been obtained so far.4 The results of the present study suggest that the 123IIMP SPECT technique may be not only sensitive, but also specific for the detection of uveal malignant melanoma. The high rate of detection by the 123I-IMP images in patients with uveal melanoma compared with skin melanoma mentioned before5 may be caused by abundant vascular distribution in the uveal tissue as well as high resolution of images obtained by SPECT to determine localized tumors. N-isopropyl p-[123I]-iodoamphetamine SPECT may be an effective procedure for the diagnosis of uveal melanoma, in which it is difficult to establish a diagnosis by conventional methods. REFERENCES
1. Winchell HS, Baldwin RM, Lin TH. Development of I-123labeled amines for brain studies: localization of I-123 iodophenylalkyl amines in rat brain. J Nucl Med 1980;21:940 –946. 2. Holman BL, Hill TC, Polak JF, et al. Cerebral perfusion imaging with iodine 123-labeled amines. Arch Neurol 1984; 41:1060 –1065. 3. Wada M, Ichiya Y, Katsuragi M, et al. Scintigraphic visualization of human malignant melanoma with N-isopropyl-p-[I123] iodoamphetamine. Clin Nucl Med 1985;10:415– 417. 4. Ono S, Fukunaga M, Otsuka N, et al. Visualization of ocular melanoma with N-isopropyl p-[123I]-iodoamphetamone. J Nucl Med 1988;29:1448 –1450. 5. Cohen MB, Saxton RE, Lake RR, et al. Detection of malignant melanoma with iodine-123 iodoamphetamine. J Nucl Med 1988;29:1200–1206.
Calcification in Choroidal Melanoma After Transpupillary Thermotherapy Hayyam Kiratli, MD, and Sevgu¨ l Bilgic¸ , MD PURPOSE:
To report the response of calcification in choroidal melanoma after transpupillary thermotherapy. METHODS: Interventional case report. A 66-year-old male with a posterior uveal melanoma measuring 10 ⴛ 8 ⴛ 4.4 mm underwent infrared diode laser transpupillary thermotherapy three times, each 12 weeks apart. For each treatment, a 3-mm spot size of 1-minute duration was used, and the power setting varied between 450 mW and 500 mW. RESULTS: Two months after the last transpupillary thermotherapy session, A- and B-mode echographic patterns Accepted for publication Jul 17, 2001. From the Ocular Oncology Service, Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey. Inquiries to Hayyam Kiratli, MD, Associate Professor of Ophthalmology, Hacettepe Hastanesi Go¨ z ABD, Sihhiye TR-06100 Ankara, Turkey; fax: ⫹90 312 309 4101; e-mail: [email protected]
BRIEF REPORTS
939
FIGURE 1. (Left) Left fundus view at initial presentation. (Right) B-scan ultrasonography of the left eye shows the juxtapapillary tumor before treatment.
FIGURE 2. (Right) B-scan echography of the left eye shows intratumoral calcification. (Left) Arrows on this photograph of the left fundus indicate the area from where echoes suggestive of calcification were obtained.
strongly suggestive of intratumor calcification were observed. The tumor regressed to 2.8 mm in thickness, but calcification persisted. Local recurrence or distant metastasis was not detected during a follow-up of 14 months. CONCLUSION: Clinically detectable calcification is extremely rare in choroidal melanomas. Tumor regression with slowly progressive calcification may occur after transpupillary thermotherapy. (Am J Ophthalmol 2001;132:939 –941. © 2001 by Elsevier Science Inc. All rights reserved.)
T
scribes intralesional calcification that ocurred in a choriodal melanoma after transpupillary thermotherapy. A 66-year-old male was examined for the complaint of gradual loss of vision in his left eye. His best-corrected visual acuity was RE: 20/20 and LE: 20/40. The anterior segments and intraocular pressures were normal. In the left eye, fundus examination disclosed a macular choroidal melanoma that measured 10 ⫻ 8 mm in basal dimensions. A small nodular portion was overhanging the optic disk (Figure 1, left). A small amount of orange pigment was observed on the superior part of the lesion. Minimal subretinal fluid was found over the tumor. Echographic tumor thickness was measured at 4.4 mm (Figure 1, right). On A-scan, the tumor had low-to-medium internal reflectivity. Ultrasonography and magnetic resonance imaging scans did not suggest optic nerve invasion or extrascleral extension. As the patient refused enucleation, he was offered transpupillary thermotherapy, which was per-
RANSPUPILLARY THERMOTHERAPY IS INCREASINGLY
used in the primary management of some selected posterior uveal melanomas. Some unusual tumor responses and complications are inevitably encountered as experience and a number of patients treated with this technique grow in ocular oncology centers. The present interventional case report covering 14 months of follow-up de940
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
DECEMBER 2001
formed three times, each 12 weeks apart. A 3-mm spot size for 1 minute/spot was used. The power setting was 500 mW for the first session, 450 mW for the second, and 500 mW for the third. Two months after the last session, high internal reflectivity on A-scan and a hyperechogenic area on B-scan over the surface of the tumor became evident (Figure 2, left). This area also produced a barely detectable orbital shadowing. Meanwhile, the tumor showed signs of regression and the thickness was reduced to 2.8 mm (Figure 2, right). His visual acuity was LE: 20/200. In the following 3 months, gradual regression continued but the presumed calcification site persisted. The patient did not have hypercalcemia at any time on his routine systemic examinations. Deposition of calcium in the absence of hypercalcemia is a sign of previous cell injury and may occur in dead or dying tissues.1 Mitochondria are the sites where the dying cell starts to accumulate calcium salts.1 Transpupillary thermotherapy results in cell necrosis primarily by disruption of mitochondria at subcoagulation temperatures of 45°C to 60°C.2 Histopathological studies on melanomas previously treated with transpupillary thermotherapy revealed dilated and occluded vessels, loss of cytoplasm, and shrunken nuclei, but failed to show calcification.3 Oosterhuis and associates4 reported that a week after transpupillary thermotherapy, increased reflectivity on B-scan approximately 3 mm depth from the apex of the tumor was a common finding. However, this finding disappeared within 2 months as the tumors flattened.4 We believe that this does not represent true calcification. In our case, the echoes suggestive of calcification were detected exactly where tumor necrosis was expected. Intratumoral calcification after brachytherapy is exceedingly rare. In 1300 patients treated with Ru-106 plaque brachytherapy, only 3 developed high reflectivity and orbital shadowing compatible with calcification.5 The present case suggests that calcification in choroidal melanoma may also be encountered after transpupillary thermotherapy. REFERENCES
1. Robbins SL, Cotran RS, Kumar V. Pathologic basis of disease. 3rd ed. Philadelphia: W.B. Saunders Company; 1984:35. 2. Journe´ e-de Korver JG, Oosterhuis JA, Kakabeeke-Kemme HM, de Wolff-Rouendaal D. Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma. Doc Ophthalmol 1992;82:185–191. 3. Journe´ e-de Korver JG, Oosterhuis JA, de Wolff-Rouendaal D, Kemme H. Histopathological findings in human choroidal melanomas after transpupillary thermotherapy. Br J Ophthalmol 1997;81:234 –239. 4. Oosterhuis JA, Journe´ e-de Korver JG, Kakabeeke-Kemme HM, Bleeker FC. Transpupillary thermotherapy in choroidal melanomas. Arch Ophthalmol 1995;113:325–321. 5. Kellner U, Foerster MH, Bornfeld N. Calcification-like echographic pattern in uveal melanomas treated with brachytherapy. Br J Ophthalmol 1993;77:827.
VOL. 132, NO. 6
Choroidal Melanoma Metastatic to the Contralateral Choroid Arun D. Singh, MD, Jerry A. Shields, MD, Carol L. Shields, MD, and Takami Sato, MD PURPOSE:
To report metastasis of choroidal melanoma to the contralateral choroid. METHODS: Interventional case report. In a 49-year-old Caucasian female, a primary choroidal melanoma, left eye, was diagnosed and treated with Ruthenium-106 plaque radiotherapy. The choroidal melanoma showed excellent regression with flattening of the mass and adjacent chorioretinal atrophy. RESULTS: Fifteen years after brachytherapy for choroidal melanoma, left eye, the patient developed a metastatic melanoma to the contralateral choroid as the first sign of metastasis. No history of oculo(dermal) melanocytosis or cutaneous melanoma existed. Systemic evaluation disclosed multiple metastases confined to the liver. CONCLUSION: Metastasis to the contralateral choroid can be the first sign of metastasis from choroidal melanoma. (Am J Ophthalmol 2001;132:941–943. © 2001 by Elsevier Science Inc. All rights reserved.)
U
VEAL MELANOMA METASTASIZES MOST COMMONLY
to liver, lungs, and bone.1 Rarely uveal melanoma metastasize to the contralateral orbital and adnexal structures.2 Metastasis of choroidal melanoma to the contralateral choroid is also rare.2 We report a patient with primary choroidal melanoma, who subsequently developed metastasis to the contralateral choroid as the first sign of metastatic disease. ● CASE:
A 49-year-old healthy Caucasian female was examined for a suspicious choroidal nevus in the left eye in 1985. Ocular and systemic history were noncontributory. The visual acuity was 20/20 in each eye. Anterior segment examination of both eyes and fundus examination of the right eye were normal with no evidence of a choroidal nevus or oculo(dermal)melanocytosis. Ophthalmoscopic examination of the left eye showed a bilobed, pigmented choroidal mass measuring 8 mm in diameter and 3 mm in thickness. Six months later, evidence of growth existed, with a development of localized retinal detachment (Figure 1, top). A diagnosis of primary choroidal melanoma was made, and the patient was treated with a 15-mm Ruthenium-106 plaque radiotherapy (apical dose: 86 Gy).
Accepted for publication Jun 26, 2001. From the Oncology Service (A.D.S., C.L.S., J.A.S.), Wills Eye Hospital, and the Division of Medical Oncology (T.S.), Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania. Supported by the Sarah B. Kant Fund, Philadelphia, Pennsylvania (A.D.S.). Inquiries to Arun D. Singh, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, Pennsylvania 19107; fax: (215) 928-1140; e-mail: [email protected]
BRIEF REPORTS
941