Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

Ashkenazy, Noy; Harbour, J. William; Dubovy, Sander R; Albini, Thomas A.; Sridhar, Jayanth; Patel, Nish; Hansen, Eric D.; Uchiyama, Eduardo; Rubsamen, Patrick E.; Correa, Zelia M.

Noy Ashkenazy

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida

https://orcid.org/0000-0001-7497-4439

J. William Harbour

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, Texas

Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida

Sander R Dubovy

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Florida Lions Ocular Pathology Laboratory, University of Miami Miller School of Medicine, Miami, Florida

Thomas A. Albini

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Jayanth Sridhar

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Nish Patel

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Henry Ford Hospital, Department of Ophthalmology, Detroit, Michigan

Eric D. Hansen

John A. Moran Eye Institute, University of Utah, Salt Lake City, Utah

Eduardo Uchiyama

Retina Group of Florida, Fort Lauderdale, Florida

Patrick E. Rubsamen

Retina Group of Florida, Fort Lauderdale, Florida

Zelia M. Correa Corresponding author: Zelia M. Correa E-mail: zcorrea@med.miami.edu

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida

https://orcid.org/0000-0003-2946-3757

Corresponding author: Zelia M. Correa E-mail: zcorrea@med.miami.edu

Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of interest to disclose.

Figuras (5)
Tabelas (2)

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Figure 1
Clinical findings of cases 1 and 5 masquerading as neovascular complications. Neovascular glaucoma in case 1. (A) Slit lamp photograph shows corneal edema, rubeosis, and hyphema. (B) B-scan with diffuse vitreous opacities with membrane formation without masses. (C) Hematoxylin-eosin staining of the cutaneous shoulder biopsy demonstrates atypical, pigmented cells with prominent nucleoli, corresponding with similar cells on vitreous cytology. Apparent non-clearing vitreous hemorrhage in case 5. (D) Slit lamp photograph at presentation, with pigmentary deposits on the posterior lens surface of the cataract. (E) Wide-field fundus photograph showed hazy media and diffuse pigmentary deposition in the posterior pole. (F) B-scan illustrated numerous vitreous opacities and clumping along the residual vitreous skirt (arrow) in this patient who was previously vitrectomized. OCT 1 month after the first intravitreal melphalan (G) and following two additional monthly injections (H) suggested a reduced metastatic tumor burden in the vitreous and on the retinal surface. A corresponding reduction in the pigmentation on wide-field fundus photographs were seen at these intervals (I, J).

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Figure 2
Clinical findings of case 2 masquerading as a posterior pigmented mass. (A) Posterior lenticular opacities. (B) B-scan shows dense vitreous cellularity, posterior vitreous detachment, and a hyperechoic lesion of minimal vascularity with biconvex cross-sectional shape, measuring 7.2 × 7.2 × 1.3 mm. (C) Intraoperative membrane peeling during diagnostic vitrectomy. Vitreous biopsy (D, E) showed atypical, pigmented cells with prominent nucleoli, in a background of erythrocytes. Cutaneous biopsy results from the original cheek lesion (F) are consistent with melanoma. No magnifications are available.

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Figure 3
Case 2. Gross enucleation specimen photographs (A-C) and histology slides (D-G). Gross specimens with extensive deposition of pigmented melanoma cells invading the iris, (A) ciliary body and angle (B), and posterior segment (C). The corresponding hematoxylin-eosin stains demonstrate invasion of the sclerotomy suture track (D, original magnification, ×200), trabecular meshwork (E, original magnification, ×200), iris surfaces (F, original magnification, ×100), and posterior lens capsule (G, original magnification, ×200). Coronal section of the enucleated globe (F). Disseminated melanoma cells are noted along the nasal retinal mass (a, 1; Melan-A, original magnification, ×100), optic nerve (b, 2; HMB-45, original magnification, ×40), fovea (c, 3; hematoxylin-eosin, original magnification, ×200), and perivascular distribution (d, 4-5: hematoxylin-eosin, original magnification, ×400 and ×200 respectively).

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Figure 4
Cases 3 and 4 presented vitreous metastasis of cutaneous melanoma masquerading as intermediate uveitis. (A) B-scan initially showed dense vitreous debris limiting the view to the fundus. (B) Intraoperative image of the diagnostic vitrectomy in case 3 shows a predominance of amelanotic cells. There were clear media and absence of chorioretinal lesions postoperatively following vitrectomy and six intravitreal injections of melphalan. The post-diagnostic vitrectomy findings in case 4 included (C) few vitreous opacities and punched-out chorioretinal scars seen on wide-field fundus photo and (D) OCT demonstrating an irregular retinal surface with few deep vitreous cells.

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Figure 5
Cytology results of diagnostic vitrectomy in cases 3 (A), 4 (B), and 5 (C). From left to right: (A) PAP (original magnification, ×600), Melan-A with red chromogen (original magnification, ×600), and SOX-10 (×600). (B) PAP (original magnification, ×600), Melan-A with red chromogen (original magnification, x600), SOX-10 with red chromogen (original magnification, x600). (C) PAP (original magnification, ×600), Melan-A with red chromogen (original magnification, ×600), SOX-10 with red chromogen (original magnification, ×600).

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Table 1
Demographics and clinical characteristics of ophthalmic findings in our patients with vitreous metastasis of cutaneous melanoma

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Table 2
Clinical characteristics of the systemic findings in our patients with vitreous metastasis of cutaneous melanoma

	Case 1	Case 2	Case 3	Case 4	Case 5
Age (years) at Presentation	37	87	68	88	82
Sex	Male	Male	Female	Female	Female
Duration of Symptom(s)	2 days	3 months (1 month worsening)	2 months	6 months	1 month
Laterality of Disease	Right	Left	Right	Right	Right
Presenting Symptom(s)	Vision loss Eye pain	Vision loss Floaters	Vision loss Floaters Flashes	Vision loss Floaters	Vision loss Floaters Referral(s/p PPV 3 months prior)
Presenting Sign(s)	NVG Hyphema	Vitreous hemorrhage	Anterior uveitis Intermediate uveitis	Pigment on the IOL capsule	Vitreous hemorrhage (Recurrent, with pigment)
Initial Examination Findings	Posterior synechiae Corneal edema No view of fundus	Cataract Pigment on capsule No view of fundus	Fine pigmented KP 2-3+ AC cell Koeppe nodules Pigment on capsule No view of fundus	Opacification of the IOL No view of the fundus	Cataract Pigment on the capsule Hazy view of the fundus Retina flat and pigment changes
B-scan ultrasound (Presentation)	Vitreous opacities Membrane No masses	Vitreous opacities Vascularized domeshaped mass 9:30 (7.5r × 7.5c × 1.3 mm)	Vitreous opacities No masses	Focal hyperechoic source (attached to vitreous skirt) No marked vitreous cells	Vitreous opacities Opacity on the vitreous skirt No masses
Intraoperative Findings (Additional)	CRVO (Diffuse DBH and CWS)	Retinal tear Pigmented ERM Retinal mass (nasal)	“Chalk-white” vitreous No focal retinal lesions	Multifocal chorioretinal lesions	Diffuse and perivascular pigmented deposits in the fundus
Melanin Status	Melanotic	Melanotic	Amelanotic	Amelanotic/melanotic	Melanotic
VA (Initial)	20/100 (uncorrected)	Hand motions	20/800 (BCVA)	20/30+2 (BCVA)	20/100 (BCVA)
VA (Final)	Not available	Enucleated	20/40 (BCVA) pre-RD HM (post-RD)	20/1000 (BCVA) pre-NVG NLP (post-NVG)	20/CF (BCVA)
Intraocular Pressure (Initial)	22	13	14	14	31
Intraocular Pressure (Final)	Not available	35	20	20	22
Ocular Treatments	1. Intravitreal bevacizumab 2. Phaco/ IOL/PPV/ Vit biopsy/IV triamcinolone 3. Unavailable thereafter	1. PPV/Vit biopsy 2. PPV/MP/EL/AFx 3. Melphalan × 2 (rescue) 4. Enucleation	1. Subtenons triamcinolone 2. PPV/Vit biopsy 3. Melphalan × 6 (monthly) 4. PPV/MP/Oil/ Melphalan for complex RD repair	1. PPV/Vit biopsy (outside) 2. Nd:YAG capsulotomy 3. Glaucoma medications 4. PPV/Vit biopsy 5. Methotrexate ×4 (weeks 1, 2, 6, and 10) for amelanotic globules	1. PPV/Vit biopsy (outside) 2. Phaco/IOL/PPV/Vit biopsy/ Melphalan 3. Melphalan × 3 (monthly)
Response to Ocular Treatments	Not available	Poor (iris bombe, episcleral pigment 6 weeks after the first melphalan injection)	Good	Stabilized until lost to follow-up	Good
Follow-up (Months) from DX	Not available	8.5	36	34	22
Final Ocular Disease Status	Not available	Enucleated due to NVG	No melanoma cells Pigment on the lens surface No glaucoma	Amelanotic globules/ haze (lens capsule and retinal surface) NVG after lost to follow-up	Inactive pigmented cells Secondary glaucoma

	Case 1	Case 2	Case 3	Case 4	Case 5
Prior Systemic Comorbidities	Healthy	Healthy	Healthy	Myelodysplastic syndrome	Healthy
Time of Skin Melanoma	2 years prior	<2 years prior	2 years prior	15 years prior	3 years prior
Year of Ocular Diagnosis	2007	2017	2019	2019	2019
Site of Skin Melanoma	Right shoulder	Right cheek	Right thigh Head and neck	Left arm	Unknown
Metastasis	Lymph nodes Axilla Chest wall	Lymph nodes Parotid gland	CNS (brain and spine)	Unknown (Patient refused imaging)	Unknown (Not available)
Prior Systemic Treatment	Surgical resection Systemic interferon (subcutaneous, intravenous) External beam radiation (3600 Gy)	Mohs surgery and right cheek Nivolumab	Chemotherapy Gamma knife External beam radiation Pembrolizumab	Surgical resection only No systemic therapy	Nivolumab
Systemic Treatment (Current)	Interferon	None(Last dose 3 weeks prior)	Pembrolizumab	No	None
Systemic Disease Status (by whole body imaging)	Active at the time of eye DX	Remission	Inactive/ controlled New cutaneous melanoma lesion	Unknown, clinically well (Patient refused imaging and denies non-ocular symptoms)	Remission
Vital Status	Unknown (Unavailable)	Unknown (Lost to follow-up)	Alive	Alive	Alive

[1] Corresponding author: Zelia M. Correa E-mail: zcorrea@med.miami.edu

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Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

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