Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma

doi:10.1186/s40425-014-0041-1

. 2014 Dec 16;2(1):41.

doi: 10.1186/s40425-014-0041-1. eCollection 2014.

Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma

Joshua S Manusow¹, Leila Khoja², Nataly Pesin¹, Anthony M Joshua², Efrem D Mandelcorn¹

Affiliations

¹ University of Toronto Department of Ophthalmology and Vision Sciences, University Health Network/Toronto Western Hospital, 399 Bathurst Street, 6 East Room 415, Toronto, Ontario M5T 2S8 Canada.
² Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.

PMID: 25516805
PMCID: PMC4266968
DOI: 10.1186/s40425-014-0041-1

Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma

Joshua S Manusow et al. J Immunother Cancer. 2014.

. 2014 Dec 16;2(1):41.

doi: 10.1186/s40425-014-0041-1. eCollection 2014.

Authors

Joshua S Manusow¹, Leila Khoja², Nataly Pesin¹, Anthony M Joshua², Efrem D Mandelcorn¹

Affiliations

¹ University of Toronto Department of Ophthalmology and Vision Sciences, University Health Network/Toronto Western Hospital, 399 Bathurst Street, 6 East Room 415, Toronto, Ontario M5T 2S8 Canada.
² Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.

PMID: 25516805
PMCID: PMC4266968
DOI: 10.1186/s40425-014-0041-1

Abstract

We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis.

Keywords: Melanoma; Melanoma-associated Retinopathy (MAR); PD-1 inhibitor; Retinal vasculitis; Vitreous metastasis.

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Figures

**Figure 1**
**Retrolental cells.** Slit lamp photograph of the left eye disclosing cohesive, pigmented, retrolental cells.

**Figure 2**
**Retinal vasculitis.** Fluorescein angiogram of the left eye discloses a) diffuse retinal vasculitis in the mid frame with b) leakage in the late frame and c) resolution of vasculitis following vitrectomy.

**Figure 3**
**Histopathology.** Photomicrograph shows cohesive groups of malignant epithelioid cells displaying pleomorphic round eccentric nuclei with prominent nucleoli and abundant cytoplasm. a) Hematoxylin and eosin, 63× b) Diff-Quik, 100× . Immunohistochemistry discloses positive staining for c) S-100 stain, 40× and d) microphthalmia stain, 63×.

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References

1. Jaissle GB, Szurman P, Rohrbach 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. doi: 10.1007/s00417-006-0469-1. - DOI - PubMed
1. Gündüz K, Shields JA, Shields CL, Eagle RC., Jr Cutaneous melanoma metastatic to the vitreous cavity. Ophthalmology. 1998;105:600–605. doi: 10.1016/S0161-6420(98)94011-8. - DOI - PubMed
1. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: hiding in plain sight. Immunol Rev. 2006;213:48–65. doi: 10.1111/j.1600-065X.2006.00441.x. - DOI - PMC - PubMed
1. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459–465. doi: 10.1016/S1470-2045(12)70090-6. - DOI - PubMed
1. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma. N Engl J Med. 2013;369:134–144. doi: 10.1056/NEJMoa1305133. - DOI - PMC - PubMed

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[1] Jaissle GB, Szurman P, Rohrbach 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. doi: 10.1007/s00417-006-0469-1. - DOI - PubMed

[2] Jaissle GB, Szurman P, Rohrbach 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. doi: 10.1007/s00417-006-0469-1. - DOI - PubMed

[3] Gündüz K, Shields JA, Shields CL, Eagle RC., Jr Cutaneous melanoma metastatic to the vitreous cavity. Ophthalmology. 1998;105:600–605. doi: 10.1016/S0161-6420(98)94011-8. - DOI - PubMed

[4] Gündüz K, Shields JA, Shields CL, Eagle RC., Jr Cutaneous melanoma metastatic to the vitreous cavity. Ophthalmology. 1998;105:600–605. doi: 10.1016/S0161-6420(98)94011-8. - DOI - PubMed

[5] Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: hiding in plain sight. Immunol Rev. 2006;213:48–65. doi: 10.1111/j.1600-065X.2006.00441.x. - DOI - PMC - PubMed

[6] Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: hiding in plain sight. Immunol Rev. 2006;213:48–65. doi: 10.1111/j.1600-065X.2006.00441.x. - DOI - PMC - PubMed

[7] Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459–465. doi: 10.1016/S1470-2045(12)70090-6. - DOI - PubMed

[8] Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459–465. doi: 10.1016/S1470-2045(12)70090-6. - DOI - PubMed

[9] Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma. N Engl J Med. 2013;369:134–144. doi: 10.1056/NEJMoa1305133. - DOI - PMC - PubMed

[10] Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma. N Engl J Med. 2013;369:134–144. doi: 10.1056/NEJMoa1305133. - DOI - PMC - PubMed

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Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma

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Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma

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