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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 497-499

Clinical and histological work-up of vitreoretinal metastases from cutaneous malignant melanoma: A case report


1 Department of Ophthalmology and Optometry, Medical University Innsbruck, Anichstrasse, Innsbruck, Austria
2 Department of Dermatology and Venerology, Medical University Innsbruck, Anichstrasse, Innsbruck, Austria

Date of Submission12-Sep-2021
Date of Acceptance12-Nov-2021
Date of Web Publication13-Apr-2022

Correspondence Address:
Georgios Blatsios
Department of Ophthalmology and Optometry, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck
Austria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2359_21

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  Abstract 


We report a rare case of vitreoretinal metastases from cutaneous malignant melanoma (CMM). A 76-year-old patient with CMM presented at our clinic complaining of floaters and blurred vision in his right eye. After conducting an exploratory vitrectomy, the diagnosis of vitreoretinal metastases from CMM was made. Histopathology of the enucleated eye demonstrated residual clusters of malignant cells in the vitreous and focal invasion of the inner retina. CMM metastatic to the retina and vitreous is very rare. A detailed ophthalmological examination in all patients with metastatic CMM and complaints of ocular symptoms is highly recommended.

Keywords: Cutaneous malignant melanoma, histopathology, ocular oncology, vitreoretinal metastasis


How to cite this article:
Osl A, Blatsios G, Rauchegger T, Nguyen VA, Seifarth C, Haas G. Clinical and histological work-up of vitreoretinal metastases from cutaneous malignant melanoma: A case report. Indian J Ophthalmol Case Rep 2022;2:497-9

How to cite this URL:
Osl A, Blatsios G, Rauchegger T, Nguyen VA, Seifarth C, Haas G. Clinical and histological work-up of vitreoretinal metastases from cutaneous malignant melanoma: A case report. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 18];2:497-9. Available from: https://www.ijoreports.in/text.asp?2022/2/2/497/342950



Although cutaneous malignant melanoma (CMM) shows an increasing incidence rate, ocular metastases are very uncommon.[1] Metastases to the vitreous and retina are exceedingly rare, and only a few cases have been described in the literature.[2],[3] We present a patient with vitreal and retinal seeding of a metastatic CMM. To the best of our knowledge, this is the first report illustrating an enucleated eye with vitreoretinal metastases including unique images of the histopathological workup.


  Case Report Top


A 76-year-old patient complaining of blurred vision and floaters in his right eye was referred to our clinic. The patient had been treated for Hodgkin's lymphoma 16 years ago with good therapeutic results and no residuum. Four years ago, a cutaneous melanoma was diagnosed. As the patient developed multiple metastases during the following years, multimodal therapy was conducted. At first, immunotherapy was administered with Nivolumab (Opdivo®, Bristol-Meyers Squibb, New York, United States of America), and secondly with Ipilimumab (Yvervoy®, Bristol-Meyers Squibb, New York, United States of America); both had to be discontinued due to severe side effects. Because of further cerebral metastases, the patient received cytostatic therapy with Fotemustin (Muphoran®, Servier, Suresnes, France). Subsequently, all cerebral metastases receded over the course of several months due to late response to Ipilimumab.

Best-corrected visual acuity was 20/40 in the right eye. Biomicroscopic fundus examination revealed multiple small beige-colored cell aggregates in the vitreous body and spotted retinal infiltration of the macula and the temporal retina [Figure 1]a. Spectral-domain optical coherence tomography (SD-OCT) scans of the macula showed epiretinal clumps of cells [Figure 1]b. The examination of the left eye was unremarkable.
Figure 1: (a) Scanning laser ophthalmoscope image demonstrating multiple small beige-colored cell aggregates in the vitreous body and spotted retinal infiltration of the macula and the temporal retina. (b) Spectral-domain optical coherence tomography (SD-OCT) scans of the macula showing epiretinal clumps of cells

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Differential diagnoses included intraocular lymphoma, metastasis from CMM, and immunotherapy-associated intermediate uveitis. For further clarification, an exploratory vitrectomy was performed. Histopathologic examination confirmed the diagnosis of vitreoretinal metastases from CMM.

Recurrence was recorded after diagnostic surgery with progressive decrease in vision over the following weeks because of new metastatic lesions epiretinal and in the vitreous body. Furthermore, whitish, spherical-shaped precipitates occurred in the posterior capsular bag [Figure 2]. PET-CT scans showed no incidence of other metastases. Because the patient suffered from severe side effects of the immunotherapy and radiotherapy, which most likely causes additional adverse reactions, the decision was made to enucleate the right eye to prevent spreading to the orbit. The enucleation was performed 4 months after the exploratory vitrectomy.
Figure 2: Slit-lamp photograph showing whitish, spherical-shaped precipitates in the capsular bag

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Histological examination presented residual clusters of malignant cells in the vitreous body and epiretinal tumor cell aggregates with focal invasion of the inner retina [Figure 3]a. Examination of retinal specimen showed superficial infiltration of the nerve fiber layer by melanoma cells [Figure 3]b. In addition, tumor cells were found in the capsular bag [Figure 3]c and [Figure 3]d. Moreover, the cells of the capsular bag and the epi- and intraretinal clusters of tumor cells stained positive for Melan A [Figure 3]b* and HMB-45 (Human Melanoma Black). In a further immunohistochemical staining, BAP-1 was detected.
Figure 3: (a) Image of the enucleated eye, demonstrating massive vitreous body infiltration with malignant cells. (b) Hematoxylin/eosin stain of superficial infiltration of the nerve fiber layer (*: tumor cells stained positive for Melan A). (c) Hematoxylin/eosin stain of the anterior segment (part of the iris, ciliary body, capsular bag) with infiltration. (d) Detailed image of the infiltrated capsular bag

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A detailed follow-up after 30 months, including positron emission tomography in combination with computed tomography (PET-CT) and cerebral magnetic resonance imaging (MRI), did not demonstrate any new metastatic sites.


  Discussion Top


In patients with indeterminate intraocular tumors, additional cytological or histological confirmation is often necessary. Fine-needle aspiration and diagnostic vitrectomy are considered relatively safe methods; however, the increased risk of extraocular tumor spread and orbital seeding is of special concern, even in the case of metastatic disease.[4],[5] In addition, vitrectomy is only a diagnostic procedure and cannot prevent tumor recurrence.[1] For cytological detection of intraocular lymphoma, diagnostic vitrectomy is the gold standard[6] as intraocular lymphoma is known as a masquerade syndrome, which can imitate intermediate or posterior uveitis.[7] Immune checkpoint inhibitors such as Nivolumab and Ipilimumab can lead to intraocular inflammation too, resulting from an upregulation of the immune system with potentially autoimmune-like side effects.[8] In our case, the clinically seen non-pigmented cell aggregates formed clumps of variable shape not consistent with snowballs usually seen in intermediate uveitis. Therefore, our findings rather corresponded with melanoma cells than vitreous infiltration due to uveitis.

Histopathological findings and positive immunohistochemical markers for Melan A and HMB-45 after enucleation confirmed the diagnosis of vitreoretinal metastases from CMM and showed no evidence of extraocular tumor expansion. Nevertheless, regular follow-ups to assess possible extraocular tumor growth are necessary.

Because of the rarity of vitreoretinal metastases from CMM, only a few case reports have been published so far.[2] Soheilian et al.[1] reported in a review of literature of patients with CMM affecting the eye following sites of involvement: choroidal infiltration in 46% of the patients, followed by involvement of the retina (27%), iris (23%), ciliary body (22%), vitreous (18%), optic disc (12%), and anterior chamber (11%).

The most common treatment protocols for ocular metastases from CMM include chemotherapy, photon external beam radiation, brachytherapy, immunotherapy, and surgical resection.[3] Another cycle of immune checkpoint inhibitors, which became the first-line treatment for metastatic melanoma within the last decade, was not given because of previously occurred severe side effects.[9] Radiotherapy mainly leads to frustrating results.[3] Radiation can cause serious adverse events such as severe dry eye syndrome, exposure keratopathy, or keratinization of the conjunctiva.[10] Due to these possible complications, it was decided against external beam radiation in our case and an enucleation was performed.


  Conclusion Top


In conclusion, this case report presents a rare entity of CMM metastatic to retina and vitreous. A detailed ophthalmological examination in all patients with metastatic CMM and complaints of ocular symptoms, especially floaters and decreased vision, is therefore essential. Important differential diagnoses are uveitis and intraocular lymphoma. Therapy is challenging as there is no standardized therapy schedule and an individual approach is required. This report is important to raise awareness among clinicians of the potential for developing ocular metastases in CMM.

Acknowledgement

Not applicable.

Consent for publication

This case report was conducted in accordance with good clinical practices. We obtained written consent of the patient to use his data and images. There are no ethical conflicts to disclose.

List of abbreviations

  • CMM - Cutaneous malignant melanoma
  • SD-OCT - Spectral-domain optical coherence tomography
  • HMB - Human Melanoma Black


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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;12:324-7.  Back to cited text no. 1
    
2.
Zografos L, Mirimanoff R-O, Angeletti CA, Frosini R, Beati D, Schalenbourg A, et al. Systemic melanoma metastatic to the retina and vitreous. Ophthalmologica 2004;218:424-33.  Back to cited text no. 2
    
3.
Zografos L, Ducrey N, Beati D, Schalenbourg A, Spahn B, Balmer A, et al. Metastatic melanoma in the eye and orbit. Ophthalmology 2003;110:2245-56.  Back to cited text no. 3
    
4.
Bechrakis NE, Foerster MH, Bornfeld N. Biopsy in indeterminate intraocular tumors. Ophthalmology 2002;109:235-42.  Back to cited text no. 4
    
5.
Eide N, Walaas L. Fine-needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: A review. Acta Ophthalmologica 2009;87:588-601.  Back to cited text no. 5
    
6.
Le Guin CH, Metz K, Bornfeld N. [Primary Intraocular Lymphoma: Relevance of Diagnostic Vitrectomy]. Klin Monbl Augenheilkd 2017;234:1524-32.  Back to cited text no. 6
    
7.
Hwang CS, Yeh S, Bergstrom CS. Diagnostic vitrectomy for primary intraocular lymphoma: When, why, how? Int Ophthalmol Clin 2014;54:155-71.  Back to cited text no. 7
    
8.
Dalvin LA, Shields CL, Orloff M, Sato T, Shields JA. Checkpoint inhibitor immune therapy: Systemic indications and ophthalmic side effects. Retina (Philadelphia, Pa) 2018;38:1063-78.  Back to cited text no. 8
    
9.
Francis JH, Berry D, Abramson DH, Barker CA, Bergstrom C, Demirci H, et al. Intravitreous cutaneous metastatic melanoma in the era of checkpoint inhibition: Unmasking and masquerading. Ophthalmology 2020;127:240-8.  Back to cited text no. 9
    
10.
Hsu A, Frank SJ, Ballo MT, Garden AS, Morrison WH, Rosenthal DI, et al. Postoperative adjuvant external-beam radiation therapy for cancers of the eyelid and conjunctiva. Ophthalmic Plast Reconstr Surg 2008;24:444-9.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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