Management of conjunctival malignant melanoma with orbital recurrence: a case report

Introduction

Conjunctival melanoma is a malignant neoplastic of the ocular surface. The incidence of conjunctival melanoma has remained stable over the last decade with an incidence of less than one person per million population (incidence =0.38 per 1 million persons). It is rapidly progressive and potentially deadly tumor (1).

We report a rare case of conjunctival melanoma with local recurrence and discuss the use of biological therapies in the treatment of this malignant tumor. We present this article in accordance with the CARE reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-24-50/rc).

Case presentation

We report a case of a 55-year-old male patient, who presented to the ophthalmology department with complaints of a painless slowly growing mass in the lower eyelid near the lateral canthus of the right eye.

The patient reported that he had a surgical removal of a pigmented conjunctival lesion a year before (Figure 1A), but didn’t come to any of his follow-up visits due to personal reasons.

Figure 1 Conjunctival melanoma. (A) Pigmented conjunctival melanoma involving the caruncle. (B) Photography of right eye showing a tumefaction of the inferior lid next to the external canthus (black arrow). (C) Slit-lamp photography of a right eye showing a conjunctival melanoma involving as a pigmented lesion of 1 mm on the palpebral conjunctiva of the inferior lid (white arrow). (D) Photography showing a voluminous cervical adenopathy. (E) Cervical lymphadenopathy lesions were not seen on PET. (F) Perioperative photography showing the infiltrated cervical lymphadenopathy. PET, positron emission tomography.

The operative report of the surgical procedure done a year ago, reported a wide local excision of the tumor, with a clear margin of 4 mm using no touch technique with double freeze thaw cryotherapy of the conjunctival margins and the scleral bed. Histopathology of the lesion was in favor of a conjunctival nodular melanoma. The excision margins of the specimen were reported less than 1 mm from the tumor for both lateral and posterior margins.

On examination, visual acuity was 10/10 for both eyes. The examination of the right eye found a tumefaction of the inferior lid next to the external canthus (Figure 1B). The palpation of this tumefaction found a painless mass of tissular consistency. A pigmented lesion of 1 mm on the palpebral conjunctiva of the inferior lid was found on the right eye (Figure 1C). The rest of the examination of both eyes was normal. Also, a voluminous right cervical adenopathy of 10 cm was found (Figure 1D).

Given the history of the patient, and the findings of the clinical examination a local recurrence of the melanoma was suspected and a computed tomography (CT) was requested. The CT of the orbit found a right intraconal orbital mass of about 12 mm × 10 mm and a homolateral adenopathy of 22 mm × 30 mm of the ganglionar chain Ib.

On concentration with oncologist, we requested also a whole body CT, positron emission tomography (PET)-CT scan, echography of the parotid gland to assess the extension of the melanoma recurrence.

• The whole body CT found no distant metastasis.
• PET CT scan showed a nodular hypermetabolic right retro-orbital tissue infiltration hypermetabolic adenopathy frankly suspicious. Furthermore, no visceral or bone secondary hypermetabolic localization was found (Figure 1E).
• The bone scan didn’t show any evidence in favor of a secondary bone location.
• A cervical ultrasound was done and found a suspicious right subangulo-mandibular lymphadenopathy. The parotid and submaxillary glands were unremarkable.

Following a multidisciplinary consultation meeting between oncologists, radiologists and surgeons, the decision was to exenterate the right eye and to resect the cervical lymphadenopathy with lymph node dissection of the chains I, II, III, IV (Figure 1F).

Indeed surgery was done and the patient had chemotherapy sessions.

The pathological examination of the surgical specimen was in favor of a nodular melanoma and the margins were clear. The pathological examination found: reactional lymph nodes in the chain Ia. For the chain Ib the histological examination of the specimen found the presence of 8 lymph nodes, the largest of which is metastatic measuring 3.5 cm × 4.5 cm × 2 cm. This lymph nodes examined microscopically is completely infiltrated with capsular rupture. The collected salivary gland is free from tumor infiltration. The other nodes collected from the chains II, III, and IV were reactional.

The patient’s melanoma was stage T3cN1M0 following the American Joint Committee on Cancer (AJCC) staging system because it has spread to nearby lymph nodes and treatment with pembrolizumab (immunotherapy) was started after the surgery for a period of one year in association with radiotherapy on the lymph node areas given the capsular effraction. The rationale for using pembrolizumab is that pembrolizumab had lower rates of adverse events than cytotoxic T-lymphocyte associated protein 4 (CTLA-4) checkpoint inhibitor ipilimumab, with superior overall survival (2-4) (Figure 2: timeline).

Figure 2 Timeline.

The patient is still followed by the oncology department to this day: one year after the surgical procedure.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Conjunctival melanoma is a rare but potentially deadly tumor that arises from the melanocytes of the conjunctival epithelium of the eye (5).

Local tumor recurrence is frequent and concerns half of patients with conjunctival melanoma. One in four of the patients with conjunctival melanoma present distant metastasis on the ipsilateral preauricular nodes, submandibular lymph nodes, the liver, the brain and the lungs (6,7).

Melanoma presents a well-expressed lymphoid infiltration and is an immunogenic compared to other cancers (8). Therefore, as a part of the development of new treatments against melanoma, multiple monoclonal antibodies directed against targets such as CTLA-4, anti-programmed death ligand-1 (PDL-1), and anti-programmed cell death protein 1 (PD-1) have been studied (8).

To date, the mutation BRAF is the one found at the highest rate in patients with conjunctival melanoma. This mutation inhibits apoptosis and promotes cellular proliferation. However, the clinical trials to control the efficacity of BRAF inhibitors: dabrafenib and vemurafenib in the treatment of conjunctival melanoma are still ongoing (9).

Otherwise anti-CTLA4 treatment: ipilimumab may have a synergistic effect when used in association with vemurafenib (10).

Bennett Yau-Bun Hong reported that the use of immune checkpoint inhibitor therapy instead of exenteration showed good results in two cases of patients with locally advanced conjunctival melanoma (11). Therefore, the use of immune checkpoint inhibitors could be used to avoid orbital exenteration by decreasing significantly the size of locally advanced conjunctival melanoma (11).

Also, an article published by Sagiv concerning 5 patients with metastatic conjunctival melanoma showed the efficacity of the treatment with anti-PD-1 immunotherapy (12).

Despite the proven effectiveness of immunotherapy in the treatment of locally advanced conjunctival melanoma, side effects of these therapies have been reported. Therefore, patients with conjunctival melanoma treated with immunotherapy should be monitored closely (13).

Conclusions

In conclusion, conjunctival malignant melanoma is a rare and severe tumor with a poor prognosis. The overall quantity of available literature is still limited, both for potential benefits as well as the varied adverse effects of biological therapies in the treatment of this melanoma. However, the results in the cases of conjunctival melanomas in which these biological therapies have been used are promising.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-24-50/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-24-50/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-24-50/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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