CUTANEOUS MELANOMA METASTATIC TO THE VITREOUS CAVITY Shivani Gupta, MD, MPH,* Michael P. Blair, MD,* Amy Y. Lin, MD,† Odile David, MD, MPH,† Howard H. Tessler, MD,* Debra A. Goldstein, MD*
Purpose: To report a case of cutaneous melanoma metastatic to the vitreous cavity. Methods: Retrospective case report. A 72-year-old white man with a history of cutaneous melanoma but no known distant metastases presented with floaters and decreased vision. Results: The patient was initially treated for a presumptive diagnosis of ocular toxoplasmosis. After failure to respond to treatment, he underwent diagnostic pars plana vitrectomy. Pathology of the vitreous specimen was suggestive of metastatic melanoma, and systemic workup revealed metastases to the brain. Conclusion: In patients with a known history of cutaneous melanoma presenting with ocular inflammation, a high index of suspicion for metastatic disease should be maintained. RETINAL CASES & BRIEF REPORTS X:1–4, 2010
lymph nodes. At that time, computed tomography of the chest, abdomen, and pelvis was negative for metastatic disease. One month before presentation, the patient underwent excision of a squamous cell carcinoma from his left ear. He had not received radiation or chemotherapy. He had experienced an episode of floaters in the left eye in 1980, which had resolved without treatment. On examination, best-corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye. There was no relative afferent papillary defect. Slit-lamp examination of the right eye was normal and of the left eye revealed fine keratic precipitates, 1+ anterior chamber cell and flare, and fine rubeosis iridis. Gonioscopy revealed angle neovascularization. Intraocular pressure was 23 mmHg in the left eye. There were 2+ white anterior vitreous cells, with large white clumps of cells in a ‘‘string-of-pearls’’ pattern (Figure 1). Funduscopic examination was normal in the right eye and limited in the left eye secondary to dense anterior and posterior vitritis with snowballs, but no retinal or choroidal lesions were appreciated. Consideration was given to the diagnosis of intraocular lymphoma, toxoplasmosis, and metastatic disease. It was decided to treat the acute granulomatous inflammation as toxoplasmosis, with sulfadiazine, clindamycin, pyrimethamine, and prednisone as well as topical prednisolone acetate, and to obtain a workup consisting of angiotensin-converting enzyme, lysozyme, specific treponemal testing (fluorescent treponemal antibody absorption test), chest X-ray, and toxoplasmosis titers. All workup was normal, with the exception of measurable but not elevated toxoplasmosis titers. Ten days later, the inflammation had not improved, and the rubeosis had worsened. Diagnostic pars plana vitrectomy was performed after bevacizumab (Avastin; Genentech, San Francisco, CA) injection. No uveal masses were noted pre- or intraoperatively. Cytologic examination of the vitreous specimen revealed epithelioid cells, both individually and in loose clusters (Figure 2). The differential diagnosis included metastatic carcinoma and metastatic
From the *Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary; and †Department of Pathology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois.
W
hile the incidence of cutaneous melanoma is increasing, intraocular metastases remain uncommon.1 The most common site of intraocular involvement of metastatic cutaneous melanoma is the choroid, followed by the retina, iris, and ciliary body.2,3 Intraocular involvement limited to the vitreous cavity is exceedingly rare and, when present, is commonly accompanied by nonocular metastases.2 Common sites of metastases include lymph nodes, lung skin, subcutaneous tissues, liver, and brain.4 Here, we describe a case of vitreous metastasis without any known distant metastases at the time of presentation. Case Report A 72-year-old white man was referred to our institution with a 4-week history of floaters and decreased vision in the left eye. Medical history was significant for excision of a malignant melanoma from his back 5 months earlier with negative axillary The authors report no conflicting financial interests. Reprint requests: Shivani Gupta, MD, MPH, Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, College of Medicine, 1855 W. Taylor Street, MC 648, Chicago, IL 60612; e-mail: [email protected]
1
2
RETINAL CASES & BRIEF REPORTS´ 2010 VOLUME X NUMBER X
C O L O R
C O L O R Fig. 1. Slit-lamp photograph of the anterior vitreous. Note the large clumps of white cells in a ‘‘string-of-pearls’’ configuration.
melanoma. The cells were not morphologically compatible with metastatic squamous cell carcinoma. Thus, given the limited sample available for analysis, immunohistochemistry for S-100 protein was performed. The cells were strongly and diffusely positive for S-100, supporting the diagnosis of metastatic melanoma (Figure 3). Magnetic resonance imaging of the brain and orbits as well as computed tomography of the chest, abdomen, and pelvis done 3 weeks after initial presentation were significant for enhancing right occipital and left frontal lobe nodules strongly suggestive of metastatic disease. Mediastinal lymph nodes were noted but not enlarged by computed tomography criteria. The patient was treated by his oncologist with ipilimumab (MDX-010; Bristol-Myers Squibb, New York, NY, and Medarex, Inc, Princeton, NJ) for central nervous system metastases, which was initiated 1 month after initial presentation. Treatment with ipilimumab was subsequently discontinued after completion of the induction phase 2 months later because of Grade 3 immune-mediated colitis requiring hospitalization. The patient did not receive any radiotherapy. Follow-up imaging demonstrated improvement in the size of the intracranial lesions and the presence of stable hilar and mediastinal lymphadenopathy.
C O L O R
Fig. 3. S-100 immunohistochemical stain of vitreous specimen. Cells stain strongly and diffusely positive for S-100 protein (see arrows).
The patient received repeat injections of bevacizumab after vitrectomy for recurrent rubeosis and neovascular glaucoma. His vision declined to 20/400 because of progressive lens changes postoperatively as well as recurrent vitreous cells. He underwent repeat pars plana vitrectomy 4 months after his initial surgery for repair of a rhegmatogenous retinal detachment combined with cataract extraction and intraocular lens placement. Cytologic examination of the vitreous fluid revealed few atypical cells similar to those seen in the previous specimen, consistent with residual melanoma cells. The patient was followed closely and treated with intravitreal bevacizumab for recurrent rubeosis and with topical nonsteroidal anti-inflammatory medication for cystoid macular edema associated with epiretinal membrane. Fourteen-month follow-up imaging showed stable intracranial lesions without interval change as well as stable lymphadenopathy. Clinical ocular examination revealed best-corrected visual acuity of 20/300 and was significant for recurrence of large white anterior vitreous cells strongly suggestive of recurrent metastatic disease. The patient underwent repeat pars plana vitrectomy with vitreous biopsy demonstrating recurrence of metastatic disease, and subsequent enucleation of the globe was performed. Pathology of the enucleated specimen revealed metastatic malignant melanoma to vitreous with neovascularization of the iris and hyphema, vitreous hemorrhage, and choroidal hemorrhage. Tumor cells were not seen in the retina or choroid. Follow up CT and MRI imaging post-enucleation have remained stable.
Discussion
Fig. 2. Wright stain of vitreous specimen shows epithelioid cells as single cells and in loose clusters (see arrows).
A case report and review of the literature by Jaissle et al5 revealed a total of 18 patients and 23 affected eyes with vitreous metastasis from cutaneous melanoma since 1900. Of these, nine affected eyes of eight patients had isolated vitreous involvement. The remaining eyes had concurrent involvement of the
CUTANEOUS MELANOMA METASTATIC TO THE VITREOUS CAVITY
anterior segment, ciliary body, retina, or optic nerve. Of the 8 patients with isolated vitreous involvement, 6 were male, and the average age at diagnosis was 54 years. The disease was bilateral in four patients; however, in three patients, the other affected eye had involvement of adjacent ocular structures. Three patients had known or presumed central nervous system metastases at diagnosis, and another three were subsequently identified as having central nervous system involvement. Diagnostic specimens were obtained in six patients via pars plana vitrectomy or vitreous biopsy. Visual prognosis was variable, although generally poor, with 50% achieving a final visual acuity of hand motions or worse. Since the publication of this review, Prabhakaran and Font6 described the case of a 54-year-old man with a history of multiple cutaneous melanomas and dysplastic nevus syndrome but no known metastatic disease with unilateral vitreous metastases. The patient presented with decreased vision, and examination demonstrated a cloudy vitreous. Vitreous tap revealed neoplastic cells characteristic of malignant melanoma. Subsequent enucleation was performed and pathology did not reveal involvement of other ocular structures. Floaters and decreased vision are the most common presenting complaints in patients with vitreous involvement, although neovascular glaucoma is present in approximately 40% of cases and can lead to redness and pain.2,5–10 The majority of patients present clinically with golden brown or brownish cell clumps in the anterior vitreous, which may serve as a useful clinical sign to aid in diagnosis.5 It has been proposed that in patients with a history of primary cutaneous melanoma and systemic metastases, pigmented cells in the vitreous support a presumptive diagnosis of vitreous metastasis.9 However, approximately 40% of patients have white or non-pigmented clumps, as did our patient, that may make the diagnosis more challenging.5 In these cases, other diagnoses such as large cell lymphoma, vitreous amyloidosis, and intermediate uveitis should be considered. The granulomatous inflammation with string-of-pearls clumps of cells in the vitreous resulted in an initial diagnosis of ocular toxoplasmosis in our patient, although no retinochoroidal lesions were clinically evident. Other reports have described initial diagnosis of uveitic entities such as intermediate uveitis, acute retinal necrosis, and atypical uveitis.2,7,9 In such patients, biopsy specimens of the vitreous may be required for diagnosis.2 In this case, definitive diagnosis was made after pathologic examination of a vitrectomy specimen. Due to the extensive iris and angle neovascularization,
3
injection of bevacizumab prior to vitrectomy was performed in an attempt to induce regression of neovascularization more quickly than would have been expected with vitrectomy alone. It was repeated again postoperatively because of recurrence of neovascularization with neovascular glaucoma. The use of bevacizumab in controlling melanoma-induced angiogenesis in a patient with isolated vitreous metastases and elevated vitreous levels of vascular endothelial growth factor has recently been described.11 In this previously published case, antiangiogenic effects were seen rapidly with complete resolution of neovascularization, although also requiring repeat injections for recurrence. The need for surgical intervention for glaucoma in this case was prevented with the use of bevacizumab. Filtering surgery should be avoided in patients with intraocular malignancy, even if metastatic in nature, because of the risk of inducing further extraocular spread and minimal effectivity that has been found with such procedures in eyes with intraocular tumors.12 Several theories regarding the mechanism of vitreous metastasis have been proposed. With isolated vitreous involvement, direct spread from surrounding tissues such as retina, ciliary body, optic disk, or iris has been suggested.2 In a report by Jaissle et al,5 an epiretinal plaque was associated with adjacent retinal hemorrhage and blockage on fluorescein angiography. This was presumed to be the site of intravascular tumor cell spread to the retrohyaloid space. There is no standard treatment for vitreous metastases because cases in the literature are so few. Asymptomatic lesions in patients receiving systemic chemotherapy for primary malignancies can be observed.2 Symptomatic patients can be treated with external beam or plaque radiotherapy, chemotherapy, or enucleation for blind painful eyes.2 Gu¨ndu¨z et al2 concluded that external beam therapy was ineffective in obtaining tumor control based on their experience with three patients with vitreous metastases. Robertson et al10 describe the treatment of patients with metastases to the retina and vitreous with both subconjunctival and systemic chemotherapy. This, however, was insufficient in promoting tumor regression. Shanker et al13 propose that vitrectomy may have both a diagnostic and a therapeutic role by improving visual acuity in a comfortable eye without the need for more intensive therapy, especially in patients with poor prognosis. In our case, vitrectomy was insufficient for tumor control, with recurrences of tumor cells seen after each vitrectomy. Treatment with immunomodulatory therapy in our patient did result in regression of brain lesions on MRI, but was insufficient to control the ocular disease, and enucleation was ultimately required.
4
RETINAL CASES & BRIEF REPORTS´ 2010 VOLUME X NUMBER X
In summary, we present the clinical and pathologic findings of cutaneous melanoma metastatic to the vitreous cavity. Initially treated as ocular toxoplasmosis, a final diagnosis was made only after analysis of the vitreous sample. This case highlights the importance of considering metastatic melanoma to the vitreous in the differential diagnosis of ocular inflammatory diseases, especially in patients with a history of cutaneous melanoma. A high index of suspicion should be maintained because ocular involvement may be the only presenting sign in a patient with coexisting distant metastases. Key words: cutaneous melanoma, intraocular metastasis, metastatic melanoma, toxoplasmosis, vitreous metastasis. References 1. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004;150:179–185. 2. Gu¨ndu¨z K, Shields JA, Shields CL, Eagle RC Jr. Cutaneous melanoma metastatic to the vitreous cavity. Ophthalmology 1998;105:600–605. 3. Zografos L, Mirimanoff RO, Angeletti CA, et al. Systemic melanoma metastatic to the retina and vitreous. Ophthalmologica 2004;218:424–433.
4. Rosenberg C, Finger PT. Cutaneous malignant melanoma metastatic to the eye, lids, and orbit. Surv Ophthalmol 2008;53: 187–202. 5. Jaissle GB, Szurman P, Rohbach JM, Gelisken F, Bartz-Schmidt KU. A case of cutaneous melanoma metastatic to the vitreous cavity: possible pathomechanism and review of the literature. Graefes Arch Clin Exp Ophthalmol 2007;245: 733–740. 6. Prabhakaran VC, Font RL. Cutaneous malignant melanoma metastatic to the vitreous. Retina 2007;27:379–381. 7. Cole EL, Zakov ZN, Meisler DM, Tuthill RJ, McMahon JT. Cutaneous malignant melanoma metastatic to the vitreous. Arch Ophthalmol 1986;104:98–101. 8. Char DH, Schwartz A, Miller TR, Abele JS. Ocular metastases from systemic melanoma. Am J Ophthalmol 1980;90:702–707. 9. Soheilian M, Mirbabai F, Shahsavari M, Parvin M, Manieei F. Metastatic cutaneous melanoma to the vitreous cavity masquerading as intermediate uveitis. Eur J Ophthalmol 2002;12:324–327. 10. Robertson DM, Wilkinson CP, Murray JL, Gordy DD. Metastatic tumor to the retina and vitreous cavity from primary melanoma of the skin: treatment with systemic and subconjunctival chemotherapy. Ophthalmology 1981;88: 1296–1301. 11. Jaissle GB, Ulmer A, Henke-Fahle S, Gerhard F, Bartz-Schmidt KU, Szurman P. Suppression of melanoma-associated neoangiogenesis by bevacizumab. Arch Dermatol 2008;144:525–527. 12. Radcliffe NM, Finger PT. Eye cancer related glaucoma: current concepts. Surv Ophthalmol 2009;54:47–73. 13. Shanker J, Damato BE, Hiscott P. Palliative vitrectomy for intraocular metastasis from cutaneous melanoma. Eye 2002; 16:600–662.
Purpose: To report a case of cutaneous melanoma metastatic to the vitreous cavity. Methods: Retrospective case report. A 72-year-old white man with a history of cutaneous melanoma but no known distant metastases presented with floaters and decreased vision. Results: The patient was initially treated for a presumptive diagnosis of ocular toxoplasmosis. After failure to respond to treatment, he underwent diagnostic pars plana vitrectomy. Pathology of the vitreous specimen was suggestive of metastatic melanoma, and systemic workup revealed metastases to the brain. Conclusion: In patients with a known history of cutaneous melanoma presenting with ocular inflammation, a high index of suspicion for metastatic disease should be maintained. RETINAL CASES & BRIEF REPORTS X:1–4, 2010
lymph nodes. At that time, computed tomography of the chest, abdomen, and pelvis was negative for metastatic disease. One month before presentation, the patient underwent excision of a squamous cell carcinoma from his left ear. He had not received radiation or chemotherapy. He had experienced an episode of floaters in the left eye in 1980, which had resolved without treatment. On examination, best-corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye. There was no relative afferent papillary defect. Slit-lamp examination of the right eye was normal and of the left eye revealed fine keratic precipitates, 1+ anterior chamber cell and flare, and fine rubeosis iridis. Gonioscopy revealed angle neovascularization. Intraocular pressure was 23 mmHg in the left eye. There were 2+ white anterior vitreous cells, with large white clumps of cells in a ‘‘string-of-pearls’’ pattern (Figure 1). Funduscopic examination was normal in the right eye and limited in the left eye secondary to dense anterior and posterior vitritis with snowballs, but no retinal or choroidal lesions were appreciated. Consideration was given to the diagnosis of intraocular lymphoma, toxoplasmosis, and metastatic disease. It was decided to treat the acute granulomatous inflammation as toxoplasmosis, with sulfadiazine, clindamycin, pyrimethamine, and prednisone as well as topical prednisolone acetate, and to obtain a workup consisting of angiotensin-converting enzyme, lysozyme, specific treponemal testing (fluorescent treponemal antibody absorption test), chest X-ray, and toxoplasmosis titers. All workup was normal, with the exception of measurable but not elevated toxoplasmosis titers. Ten days later, the inflammation had not improved, and the rubeosis had worsened. Diagnostic pars plana vitrectomy was performed after bevacizumab (Avastin; Genentech, San Francisco, CA) injection. No uveal masses were noted pre- or intraoperatively. Cytologic examination of the vitreous specimen revealed epithelioid cells, both individually and in loose clusters (Figure 2). The differential diagnosis included metastatic carcinoma and metastatic
From the *Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary; and †Department of Pathology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois.
W
hile the incidence of cutaneous melanoma is increasing, intraocular metastases remain uncommon.1 The most common site of intraocular involvement of metastatic cutaneous melanoma is the choroid, followed by the retina, iris, and ciliary body.2,3 Intraocular involvement limited to the vitreous cavity is exceedingly rare and, when present, is commonly accompanied by nonocular metastases.2 Common sites of metastases include lymph nodes, lung skin, subcutaneous tissues, liver, and brain.4 Here, we describe a case of vitreous metastasis without any known distant metastases at the time of presentation. Case Report A 72-year-old white man was referred to our institution with a 4-week history of floaters and decreased vision in the left eye. Medical history was significant for excision of a malignant melanoma from his back 5 months earlier with negative axillary The authors report no conflicting financial interests. Reprint requests: Shivani Gupta, MD, MPH, Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, College of Medicine, 1855 W. Taylor Street, MC 648, Chicago, IL 60612; e-mail: [email protected]
1
2
RETINAL CASES & BRIEF REPORTS´ 2010 VOLUME X NUMBER X
C O L O R
C O L O R Fig. 1. Slit-lamp photograph of the anterior vitreous. Note the large clumps of white cells in a ‘‘string-of-pearls’’ configuration.
melanoma. The cells were not morphologically compatible with metastatic squamous cell carcinoma. Thus, given the limited sample available for analysis, immunohistochemistry for S-100 protein was performed. The cells were strongly and diffusely positive for S-100, supporting the diagnosis of metastatic melanoma (Figure 3). Magnetic resonance imaging of the brain and orbits as well as computed tomography of the chest, abdomen, and pelvis done 3 weeks after initial presentation were significant for enhancing right occipital and left frontal lobe nodules strongly suggestive of metastatic disease. Mediastinal lymph nodes were noted but not enlarged by computed tomography criteria. The patient was treated by his oncologist with ipilimumab (MDX-010; Bristol-Myers Squibb, New York, NY, and Medarex, Inc, Princeton, NJ) for central nervous system metastases, which was initiated 1 month after initial presentation. Treatment with ipilimumab was subsequently discontinued after completion of the induction phase 2 months later because of Grade 3 immune-mediated colitis requiring hospitalization. The patient did not receive any radiotherapy. Follow-up imaging demonstrated improvement in the size of the intracranial lesions and the presence of stable hilar and mediastinal lymphadenopathy.
C O L O R
Fig. 3. S-100 immunohistochemical stain of vitreous specimen. Cells stain strongly and diffusely positive for S-100 protein (see arrows).
The patient received repeat injections of bevacizumab after vitrectomy for recurrent rubeosis and neovascular glaucoma. His vision declined to 20/400 because of progressive lens changes postoperatively as well as recurrent vitreous cells. He underwent repeat pars plana vitrectomy 4 months after his initial surgery for repair of a rhegmatogenous retinal detachment combined with cataract extraction and intraocular lens placement. Cytologic examination of the vitreous fluid revealed few atypical cells similar to those seen in the previous specimen, consistent with residual melanoma cells. The patient was followed closely and treated with intravitreal bevacizumab for recurrent rubeosis and with topical nonsteroidal anti-inflammatory medication for cystoid macular edema associated with epiretinal membrane. Fourteen-month follow-up imaging showed stable intracranial lesions without interval change as well as stable lymphadenopathy. Clinical ocular examination revealed best-corrected visual acuity of 20/300 and was significant for recurrence of large white anterior vitreous cells strongly suggestive of recurrent metastatic disease. The patient underwent repeat pars plana vitrectomy with vitreous biopsy demonstrating recurrence of metastatic disease, and subsequent enucleation of the globe was performed. Pathology of the enucleated specimen revealed metastatic malignant melanoma to vitreous with neovascularization of the iris and hyphema, vitreous hemorrhage, and choroidal hemorrhage. Tumor cells were not seen in the retina or choroid. Follow up CT and MRI imaging post-enucleation have remained stable.
Discussion
Fig. 2. Wright stain of vitreous specimen shows epithelioid cells as single cells and in loose clusters (see arrows).
A case report and review of the literature by Jaissle et al5 revealed a total of 18 patients and 23 affected eyes with vitreous metastasis from cutaneous melanoma since 1900. Of these, nine affected eyes of eight patients had isolated vitreous involvement. The remaining eyes had concurrent involvement of the
CUTANEOUS MELANOMA METASTATIC TO THE VITREOUS CAVITY
anterior segment, ciliary body, retina, or optic nerve. Of the 8 patients with isolated vitreous involvement, 6 were male, and the average age at diagnosis was 54 years. The disease was bilateral in four patients; however, in three patients, the other affected eye had involvement of adjacent ocular structures. Three patients had known or presumed central nervous system metastases at diagnosis, and another three were subsequently identified as having central nervous system involvement. Diagnostic specimens were obtained in six patients via pars plana vitrectomy or vitreous biopsy. Visual prognosis was variable, although generally poor, with 50% achieving a final visual acuity of hand motions or worse. Since the publication of this review, Prabhakaran and Font6 described the case of a 54-year-old man with a history of multiple cutaneous melanomas and dysplastic nevus syndrome but no known metastatic disease with unilateral vitreous metastases. The patient presented with decreased vision, and examination demonstrated a cloudy vitreous. Vitreous tap revealed neoplastic cells characteristic of malignant melanoma. Subsequent enucleation was performed and pathology did not reveal involvement of other ocular structures. Floaters and decreased vision are the most common presenting complaints in patients with vitreous involvement, although neovascular glaucoma is present in approximately 40% of cases and can lead to redness and pain.2,5–10 The majority of patients present clinically with golden brown or brownish cell clumps in the anterior vitreous, which may serve as a useful clinical sign to aid in diagnosis.5 It has been proposed that in patients with a history of primary cutaneous melanoma and systemic metastases, pigmented cells in the vitreous support a presumptive diagnosis of vitreous metastasis.9 However, approximately 40% of patients have white or non-pigmented clumps, as did our patient, that may make the diagnosis more challenging.5 In these cases, other diagnoses such as large cell lymphoma, vitreous amyloidosis, and intermediate uveitis should be considered. The granulomatous inflammation with string-of-pearls clumps of cells in the vitreous resulted in an initial diagnosis of ocular toxoplasmosis in our patient, although no retinochoroidal lesions were clinically evident. Other reports have described initial diagnosis of uveitic entities such as intermediate uveitis, acute retinal necrosis, and atypical uveitis.2,7,9 In such patients, biopsy specimens of the vitreous may be required for diagnosis.2 In this case, definitive diagnosis was made after pathologic examination of a vitrectomy specimen. Due to the extensive iris and angle neovascularization,
3
injection of bevacizumab prior to vitrectomy was performed in an attempt to induce regression of neovascularization more quickly than would have been expected with vitrectomy alone. It was repeated again postoperatively because of recurrence of neovascularization with neovascular glaucoma. The use of bevacizumab in controlling melanoma-induced angiogenesis in a patient with isolated vitreous metastases and elevated vitreous levels of vascular endothelial growth factor has recently been described.11 In this previously published case, antiangiogenic effects were seen rapidly with complete resolution of neovascularization, although also requiring repeat injections for recurrence. The need for surgical intervention for glaucoma in this case was prevented with the use of bevacizumab. Filtering surgery should be avoided in patients with intraocular malignancy, even if metastatic in nature, because of the risk of inducing further extraocular spread and minimal effectivity that has been found with such procedures in eyes with intraocular tumors.12 Several theories regarding the mechanism of vitreous metastasis have been proposed. With isolated vitreous involvement, direct spread from surrounding tissues such as retina, ciliary body, optic disk, or iris has been suggested.2 In a report by Jaissle et al,5 an epiretinal plaque was associated with adjacent retinal hemorrhage and blockage on fluorescein angiography. This was presumed to be the site of intravascular tumor cell spread to the retrohyaloid space. There is no standard treatment for vitreous metastases because cases in the literature are so few. Asymptomatic lesions in patients receiving systemic chemotherapy for primary malignancies can be observed.2 Symptomatic patients can be treated with external beam or plaque radiotherapy, chemotherapy, or enucleation for blind painful eyes.2 Gu¨ndu¨z et al2 concluded that external beam therapy was ineffective in obtaining tumor control based on their experience with three patients with vitreous metastases. Robertson et al10 describe the treatment of patients with metastases to the retina and vitreous with both subconjunctival and systemic chemotherapy. This, however, was insufficient in promoting tumor regression. Shanker et al13 propose that vitrectomy may have both a diagnostic and a therapeutic role by improving visual acuity in a comfortable eye without the need for more intensive therapy, especially in patients with poor prognosis. In our case, vitrectomy was insufficient for tumor control, with recurrences of tumor cells seen after each vitrectomy. Treatment with immunomodulatory therapy in our patient did result in regression of brain lesions on MRI, but was insufficient to control the ocular disease, and enucleation was ultimately required.
4
RETINAL CASES & BRIEF REPORTS´ 2010 VOLUME X NUMBER X
In summary, we present the clinical and pathologic findings of cutaneous melanoma metastatic to the vitreous cavity. Initially treated as ocular toxoplasmosis, a final diagnosis was made only after analysis of the vitreous sample. This case highlights the importance of considering metastatic melanoma to the vitreous in the differential diagnosis of ocular inflammatory diseases, especially in patients with a history of cutaneous melanoma. A high index of suspicion should be maintained because ocular involvement may be the only presenting sign in a patient with coexisting distant metastases. Key words: cutaneous melanoma, intraocular metastasis, metastatic melanoma, toxoplasmosis, vitreous metastasis. References 1. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004;150:179–185. 2. Gu¨ndu¨z K, Shields JA, Shields CL, Eagle RC Jr. Cutaneous melanoma metastatic to the vitreous cavity. Ophthalmology 1998;105:600–605. 3. Zografos L, Mirimanoff RO, Angeletti CA, et al. Systemic melanoma metastatic to the retina and vitreous. Ophthalmologica 2004;218:424–433.
4. Rosenberg C, Finger PT. Cutaneous malignant melanoma metastatic to the eye, lids, and orbit. Surv Ophthalmol 2008;53: 187–202. 5. Jaissle GB, Szurman P, Rohbach JM, Gelisken F, Bartz-Schmidt KU. A case of cutaneous melanoma metastatic to the vitreous cavity: possible pathomechanism and review of the literature. Graefes Arch Clin Exp Ophthalmol 2007;245: 733–740. 6. Prabhakaran VC, Font RL. Cutaneous malignant melanoma metastatic to the vitreous. Retina 2007;27:379–381. 7. Cole EL, Zakov ZN, Meisler DM, Tuthill RJ, McMahon JT. Cutaneous malignant melanoma metastatic to the vitreous. Arch Ophthalmol 1986;104:98–101. 8. Char DH, Schwartz A, Miller TR, Abele JS. Ocular metastases from systemic melanoma. Am J Ophthalmol 1980;90:702–707. 9. Soheilian M, Mirbabai F, Shahsavari M, Parvin M, Manieei F. Metastatic cutaneous melanoma to the vitreous cavity masquerading as intermediate uveitis. Eur J Ophthalmol 2002;12:324–327. 10. Robertson DM, Wilkinson CP, Murray JL, Gordy DD. Metastatic tumor to the retina and vitreous cavity from primary melanoma of the skin: treatment with systemic and subconjunctival chemotherapy. Ophthalmology 1981;88: 1296–1301. 11. Jaissle GB, Ulmer A, Henke-Fahle S, Gerhard F, Bartz-Schmidt KU, Szurman P. Suppression of melanoma-associated neoangiogenesis by bevacizumab. Arch Dermatol 2008;144:525–527. 12. Radcliffe NM, Finger PT. Eye cancer related glaucoma: current concepts. Surv Ophthalmol 2009;54:47–73. 13. Shanker J, Damato BE, Hiscott P. Palliative vitrectomy for intraocular metastasis from cutaneous melanoma. Eye 2002; 16:600–662.
