PHOTODYNAMIC THERAPY FOR IRIS METASTASIS FROM A MEDIASTINAL CARCINOID TUMOR Edoardo Midena, MD,*† Stela Vujosevic, MD,† Elisabetta Pilotto, MD*
Purpose: Intraocular metastasis from a carcinoid tumor is a rare event with anecdotal reports of iris involvement. We describe a case of iris metastasis from a carcinoid tumor treated with photodynamic therapy (PDT). Methods: An isolated iris tumor was observed in a 36-year-old man. Anterior segment photography, fluorescein angiography, and fine-needle aspiration biopsy were performed. The tumor was treated with a bolus application of PDT. Regular follow-up (including clinical and angiographic evaluations) was performed over 2 years. Results: The iris mass was cytologically consistent with metastasis from a mediastinal carcinoid tumor. The metastasis showed prominent vascularization. Bolus PDT was applied with complete and long-term regression of the iris tumor. At the 24-month follow-up, the patient was still alive, and no recurrence had been documented. Conclusions: PDT may be an effective therapeutic option in selected cases of iris metastasis. RETINAL CASES & BRIEF REPORTS 2:175–177, 2008
From the *Department of Ophthalmology, University of Padova, Padova, Italy; and †Fondazione G.B. Bietti per l’Oftalmologia, IRCCS, Rome, Italy.
Since then, no other metastases were found. At presentation, visual acuity was 20/20 in the right eye and 20/80 in the left eye, with normal intraocular pressure in both eyes. The right eye was fully normal. Anterior segment examination of the left eye showed an elevated, hypopigmented, vascularized iris lesion with the following (base ⫻ base ⫻ thickness) parameters: 3.5 ⫻ 2.9 ⫻ 0.19 mm. It was located in the inferotemporal quadrant, extending up to and over the pupillary edge and touching the lens surface. At fluorescein angiography, the lesion was characterized by early-phase intense hyperfluorescence due to prominent vascularization and marked late-phase intrinsic vessel leakage. Fundus examination of the left eye was unremarkable. To make a final diagnosis, fineneedle aspiration biopsy of the iris lesion was performed. A 25gauge blunt, spinal needle was used for fine-needle aspiration biopsy. This gauge allowed us to obtain, in a safe way, enough material for accurate cytologic examination. Because of high intrinsic vascularization and hypopigmentation, the iris metastasis was treated with a modified PDT protocol, previously described for highly vascularized choroidal tumors.4 Intravenous verteporfin (6 mg/m2) was infused over a 1-minute bolus. Five minutes after the end of the sensitizer application, a 689-nm laser light delivered 100 J/cm2 at an intensity of 600 mW/cm2 over 83 seconds. The size of the treatment spot (3,500 m) was calculated based on the greatest linear dimension of iris metastasis. No additional safety margins were added. The shorter infusion time, when compared with the standard PDT protocol, was used with rationale to increase the efficacy and concentration of verteporfin within the tumor and to increase the photodynamic effect on larger vessels due to an increased light dose.5 The patient
C
arcinoid tumor is a rare neoplasm that usually arises from the gastrointestinal tract and bronchus and rarely from the thymus and ovary.1 The most common sites of metastases are lymph nodes (44%), bone (33%), and liver (22%). The eye is rarely affected (1%).2 The most common site of intraocular metastasis is the choroid. Iris involvement has been rarely reported.3 We report a case of iris metastasis from a mediastinal carcinoid tumor that was successfully treated with a bolus application of photodynamic therapy (PDT). Case Report A 36-year-old man was referred in May 2004 with decreased and blurred vision for 12 weeks in the left eye. His medical history was positive for pulmonary lobectomy and radiotherapy for atypical carcinoid tumor with lymph node metastases 9 months earlier. The authors have no financial interest in this report. Reprint requests: Edoardo Midena, MD, Department of Ophthalmology, University of Padova, Via Giustiani 2, 35128 Padova, Italy; e-mail: [email protected]
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Fig. 1. A, Iris metastasis from a lung carcinoid tumor in the left eye. Color photography of the anterior segment shows an elevated, hypopigmented, highly vascularized iris lesion (3.5 ⫻ 2.9 ⫻ 0.19 mm). B, Late-phase fluorescein angiogram of iris metastasis showing a densely vascularized tumor with significant leakage. C, Cytologic sample from the iris lesion: aggregate of monomorphous neoplastic cells, with stippled nuclear chromatin and small nucleoli, consistent with atypical recurrent carcinoid tumor (Papanicolaou stain; original magnification, ⫻400).
was observed with complete ophthalmologic examination, anterior segment photography, and fluorescein angiography at 1 week, 1 month, and then every 3 months up to 24 months after treatment. Sampled material collected by fine-needle aspiration biopsy was composed of aggregates of monomorphous neoplastic cells, with stippled nuclear chromatin and small nucleoli, consistent with the diagnosis of atypical recurrent carcinoid tumor (Fig. 1). One week after PDT, the iris tumor shrank and flattened (1.5 ⫻ 1.9 ⫻ 0.1 mm). Large tumor vessels also disappeared. At fluorescein angiography, there were no signs of significant vessel leakage. Two years after referral, the patient was alive, and the iris lesion was still atrophic without signs of any leakage by fluorescein angiography. There were some posterior synechiae, iris atrophy at the site of treatment, and localized lens opacity that did not require any treatment (Fig. 2). Moreover, there were no signs of metastatic disease in both eyes or elsewhere.
Discussion Iris metastases are relatively rare.3 In their review of 40 cases, Shields et al3 documented that iris metastasis accounted for ⬇8% of all uveal metastases. This finding is consistent with other case series, where iris
metastasis accounted for 5% to 10% of all uveal metastases.6 The most frequent primary tumors metastasizing to the iris are lung carcinoma in males and breast carcinoma in females. The final diagnosis of iris metastasis rests on cytologic confirmation, made easily possible by fine-needle aspiration biopsy.3 Iris metastasis from a carcinoid tumor was reported to account for ⬇8% of all iris metastases.3 It usually causes solitary metastasis with a peculiar orange pink flesh color. Carcinoid metastasis to the uvea is a quite vascularized lesion. Fluorescein angiography documents early-phase filling of numerous tumor blood vessels and late-phase leakage of the lesion.3 Because of its high intrinsic vascularization and hypopigmentation, metastasis from a carcinoid tumor may represent a target for conservative treatment with PDT. PDT for choroidal metastasis from a carcinoid tumor has been reported by Harbour.7 He described one case of PDT
Fig. 2. A, Color photography of iris metastasis 24 months after photodynamic therapy showing persistent atrophy of the lesion with posterior synechiae, iris atrophy at the site of treatment, and localized lens opacity. B, Late-phase fluorescein angiogram of the same lesion showing tumor shrinkage and no vessel leakage.
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PDT FOR IRIS METASTASIS FROM A CARCINOID TUMOR
for choroidal metastasis from a carcinoid tumor resistant to both chemotherapy and radiotherapy, which was successfully treated, at least on a short-term basis, with PDT. PDT has been recently used for several anterior segment diseases, such as corneal neovascularization, pterygium, and conjunctival squamous cell carcinoma.8 –10 To our knowledge, our case is the first report of a solitary iris metastasis successfully treated with PDT. PDT induces intraluminal photothrombosis in endothelium-line structures and therefore may provide long-term regression of iris carcinoid metastasis. The treatment of iris metastasis should be conservative, safe, and psychologically well accepted by the patient. PDT may represent a new, safe, noninvasive treatment for small vascularized intraocular metastasis. Key words: fluorescein angiography, iris metastasis, photodynamic therapy.
2.
3. 4.
5.
6.
7.
8.
9.
References 1.
Harbour JW, De Potter P, Shields CL, Shields JA. Uveal metastasis from carcinoid tumor. Clinical observations in nine cases. Ophthalmology 1994;10:1084–1090.
10.
Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265– 1276. Shields JA, Kiratli H, de Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119:422–430. Barbazetto I, Schmidt-Erfurth U. Photodynamic therapy of choroidal hemangioma: two case reports. Graefes Arch Clin Exp Ophthalmol 2000;238:214–221. Jurklies B, Anastassiou G, Ortmans S, et al. Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma. Br J Ophthalmol 2003;87:84–89. Stephens RF, Shields JA. Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases. Ophthalmology 1979;86:1336–1349. Harbour JW. Photodynamic therapy for choroidal metastasis from carcinoid tumor. Am J Ophthalmol 2004;137:1143– 1145. Fossarello M, Peiretti E, Zucca I, Serra A. Photodynamic therapy of corneal neovascularization with verteporfin. Cornea 2003;22:485–488. Fossarello M, Peiretti E, Zucca I, et al. Photodynamic therapy of pterygium with verteporfin: a preliminary report. Cornea 2004;23:330–338. Barbazetto IA, Lee TC, Abramson DH. Treatment of conjunctival squamous cell carcinoma with photodynamic therapy. Am J Ophthalmol 2004;138:183–189.
Purpose: Intraocular metastasis from a carcinoid tumor is a rare event with anecdotal reports of iris involvement. We describe a case of iris metastasis from a carcinoid tumor treated with photodynamic therapy (PDT). Methods: An isolated iris tumor was observed in a 36-year-old man. Anterior segment photography, fluorescein angiography, and fine-needle aspiration biopsy were performed. The tumor was treated with a bolus application of PDT. Regular follow-up (including clinical and angiographic evaluations) was performed over 2 years. Results: The iris mass was cytologically consistent with metastasis from a mediastinal carcinoid tumor. The metastasis showed prominent vascularization. Bolus PDT was applied with complete and long-term regression of the iris tumor. At the 24-month follow-up, the patient was still alive, and no recurrence had been documented. Conclusions: PDT may be an effective therapeutic option in selected cases of iris metastasis. RETINAL CASES & BRIEF REPORTS 2:175–177, 2008
From the *Department of Ophthalmology, University of Padova, Padova, Italy; and †Fondazione G.B. Bietti per l’Oftalmologia, IRCCS, Rome, Italy.
Since then, no other metastases were found. At presentation, visual acuity was 20/20 in the right eye and 20/80 in the left eye, with normal intraocular pressure in both eyes. The right eye was fully normal. Anterior segment examination of the left eye showed an elevated, hypopigmented, vascularized iris lesion with the following (base ⫻ base ⫻ thickness) parameters: 3.5 ⫻ 2.9 ⫻ 0.19 mm. It was located in the inferotemporal quadrant, extending up to and over the pupillary edge and touching the lens surface. At fluorescein angiography, the lesion was characterized by early-phase intense hyperfluorescence due to prominent vascularization and marked late-phase intrinsic vessel leakage. Fundus examination of the left eye was unremarkable. To make a final diagnosis, fineneedle aspiration biopsy of the iris lesion was performed. A 25gauge blunt, spinal needle was used for fine-needle aspiration biopsy. This gauge allowed us to obtain, in a safe way, enough material for accurate cytologic examination. Because of high intrinsic vascularization and hypopigmentation, the iris metastasis was treated with a modified PDT protocol, previously described for highly vascularized choroidal tumors.4 Intravenous verteporfin (6 mg/m2) was infused over a 1-minute bolus. Five minutes after the end of the sensitizer application, a 689-nm laser light delivered 100 J/cm2 at an intensity of 600 mW/cm2 over 83 seconds. The size of the treatment spot (3,500 m) was calculated based on the greatest linear dimension of iris metastasis. No additional safety margins were added. The shorter infusion time, when compared with the standard PDT protocol, was used with rationale to increase the efficacy and concentration of verteporfin within the tumor and to increase the photodynamic effect on larger vessels due to an increased light dose.5 The patient
C
arcinoid tumor is a rare neoplasm that usually arises from the gastrointestinal tract and bronchus and rarely from the thymus and ovary.1 The most common sites of metastases are lymph nodes (44%), bone (33%), and liver (22%). The eye is rarely affected (1%).2 The most common site of intraocular metastasis is the choroid. Iris involvement has been rarely reported.3 We report a case of iris metastasis from a mediastinal carcinoid tumor that was successfully treated with a bolus application of photodynamic therapy (PDT). Case Report A 36-year-old man was referred in May 2004 with decreased and blurred vision for 12 weeks in the left eye. His medical history was positive for pulmonary lobectomy and radiotherapy for atypical carcinoid tumor with lymph node metastases 9 months earlier. The authors have no financial interest in this report. Reprint requests: Edoardo Midena, MD, Department of Ophthalmology, University of Padova, Via Giustiani 2, 35128 Padova, Italy; e-mail: [email protected]
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Fig. 1. A, Iris metastasis from a lung carcinoid tumor in the left eye. Color photography of the anterior segment shows an elevated, hypopigmented, highly vascularized iris lesion (3.5 ⫻ 2.9 ⫻ 0.19 mm). B, Late-phase fluorescein angiogram of iris metastasis showing a densely vascularized tumor with significant leakage. C, Cytologic sample from the iris lesion: aggregate of monomorphous neoplastic cells, with stippled nuclear chromatin and small nucleoli, consistent with atypical recurrent carcinoid tumor (Papanicolaou stain; original magnification, ⫻400).
was observed with complete ophthalmologic examination, anterior segment photography, and fluorescein angiography at 1 week, 1 month, and then every 3 months up to 24 months after treatment. Sampled material collected by fine-needle aspiration biopsy was composed of aggregates of monomorphous neoplastic cells, with stippled nuclear chromatin and small nucleoli, consistent with the diagnosis of atypical recurrent carcinoid tumor (Fig. 1). One week after PDT, the iris tumor shrank and flattened (1.5 ⫻ 1.9 ⫻ 0.1 mm). Large tumor vessels also disappeared. At fluorescein angiography, there were no signs of significant vessel leakage. Two years after referral, the patient was alive, and the iris lesion was still atrophic without signs of any leakage by fluorescein angiography. There were some posterior synechiae, iris atrophy at the site of treatment, and localized lens opacity that did not require any treatment (Fig. 2). Moreover, there were no signs of metastatic disease in both eyes or elsewhere.
Discussion Iris metastases are relatively rare.3 In their review of 40 cases, Shields et al3 documented that iris metastasis accounted for ⬇8% of all uveal metastases. This finding is consistent with other case series, where iris
metastasis accounted for 5% to 10% of all uveal metastases.6 The most frequent primary tumors metastasizing to the iris are lung carcinoma in males and breast carcinoma in females. The final diagnosis of iris metastasis rests on cytologic confirmation, made easily possible by fine-needle aspiration biopsy.3 Iris metastasis from a carcinoid tumor was reported to account for ⬇8% of all iris metastases.3 It usually causes solitary metastasis with a peculiar orange pink flesh color. Carcinoid metastasis to the uvea is a quite vascularized lesion. Fluorescein angiography documents early-phase filling of numerous tumor blood vessels and late-phase leakage of the lesion.3 Because of its high intrinsic vascularization and hypopigmentation, metastasis from a carcinoid tumor may represent a target for conservative treatment with PDT. PDT for choroidal metastasis from a carcinoid tumor has been reported by Harbour.7 He described one case of PDT
Fig. 2. A, Color photography of iris metastasis 24 months after photodynamic therapy showing persistent atrophy of the lesion with posterior synechiae, iris atrophy at the site of treatment, and localized lens opacity. B, Late-phase fluorescein angiogram of the same lesion showing tumor shrinkage and no vessel leakage.
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PDT FOR IRIS METASTASIS FROM A CARCINOID TUMOR
for choroidal metastasis from a carcinoid tumor resistant to both chemotherapy and radiotherapy, which was successfully treated, at least on a short-term basis, with PDT. PDT has been recently used for several anterior segment diseases, such as corneal neovascularization, pterygium, and conjunctival squamous cell carcinoma.8 –10 To our knowledge, our case is the first report of a solitary iris metastasis successfully treated with PDT. PDT induces intraluminal photothrombosis in endothelium-line structures and therefore may provide long-term regression of iris carcinoid metastasis. The treatment of iris metastasis should be conservative, safe, and psychologically well accepted by the patient. PDT may represent a new, safe, noninvasive treatment for small vascularized intraocular metastasis. Key words: fluorescein angiography, iris metastasis, photodynamic therapy.
2.
3. 4.
5.
6.
7.
8.
9.
References 1.
Harbour JW, De Potter P, Shields CL, Shields JA. Uveal metastasis from carcinoid tumor. Clinical observations in nine cases. Ophthalmology 1994;10:1084–1090.
10.
Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265– 1276. Shields JA, Kiratli H, de Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119:422–430. Barbazetto I, Schmidt-Erfurth U. Photodynamic therapy of choroidal hemangioma: two case reports. Graefes Arch Clin Exp Ophthalmol 2000;238:214–221. Jurklies B, Anastassiou G, Ortmans S, et al. Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma. Br J Ophthalmol 2003;87:84–89. Stephens RF, Shields JA. Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases. Ophthalmology 1979;86:1336–1349. Harbour JW. Photodynamic therapy for choroidal metastasis from carcinoid tumor. Am J Ophthalmol 2004;137:1143– 1145. Fossarello M, Peiretti E, Zucca I, Serra A. Photodynamic therapy of corneal neovascularization with verteporfin. Cornea 2003;22:485–488. Fossarello M, Peiretti E, Zucca I, et al. Photodynamic therapy of pterygium with verteporfin: a preliminary report. Cornea 2004;23:330–338. Barbazetto IA, Lee TC, Abramson DH. Treatment of conjunctival squamous cell carcinoma with photodynamic therapy. Am J Ophthalmol 2004;138:183–189.
