Retrograde Metastasis of Cutaneous Melanoma to Conjunctival Lymphatics

Conjunctival metastasis from cutaneous melanoma typically reaches the conjunctiva by hematogenous routes.^1-7 We report a unique case of presumed retrograde conjunctival metastasis via lymphatic channels.

A 61-year-old man developed cutaneous melanoma in the right preauricular skin. It was managed by surgical resections, skin grafts, irradiation, chemotherapy, and laser for local recurrences and cervical node metastasis. After 18 months, he was referred for progressive ipsilateral conjunctival pigmentation.

Examination disclosed cutaneous pigmentation and scarring in the right preauricular area (Figure 1A). The ipsilateral conjunctiva showed a peculiar widespread linear network of pigment (Figure 1B and C). The branching pattern was suggestive of lymphatic infiltration, and nearby conjunctival blood vessels were normal. Our clinical diagnosis was retrograde spread of cutaneous melanoma to conjunctival lymphatics.

Histopathologic analysis of a conjunctival biopsy disclosed epithelioid melanoma cells within lumina of dilated channels lined by endothelial cells, consistent with lymphatics (Figure 2A). Adjacent blood vessels contained erythrocytes but no tumor cells. The overlying conjunctival epithelium was normal without junctional activity. Immunohistochemically, the endothelium of the tumor-containing vessels was reactive to monoclonal antibody D2-40, a specific marker for lymphatic endothelial cells. In contrast, the adjacent non-tumor-containing blood vessels stained positive for CD34 and negative for D2-40 (Figure 2B and C).

The histopathologic diagnosis was retrograde conjunctival intralymphatic metastasis from cutaneous melanoma. The patient was treated with an iodine I 125 plaque delivering 60 Gy to the entire conjunctiva over 7 days. Despite a favorable local response to irradiation, the patient died of disseminated melanoma after 16 months.

Metastatic melanoma to the conjunctiva is rare.^1,2 Strempel³ reported a case in 1982 and found no previously reported cases. In 1989, Jakobiec et al⁴ described 5 cases of cutaneous melanoma metastatic to the conjunctiva. In 1996, Kiratli et al⁵ described 10 patients with conjunctival metastasis, in 2 of whom cutaneous melanoma was the primary site. Kwapiszeski and Savitt⁶ reported a case in 1997 and Shields et al⁷ reported another case in 2004. In both of these cases, the conjunctival metastasis was the first sign of dissemination of known cutaneous melanoma.^6,7

In the aforementioned cases, the metastases reached the conjunctiva by hematogenous routes. However, Jakobiec and associates mentioned 2 patients in whom localized melanoma developed in the ipsilateral inferior conjunctival fornix years after excision of limbal melanoma.⁴ It is uncertain whether they represented tumor growth from surgical seeding or intralymphatic metastasis. The lesions were unlike the peculiar branching pattern seen in our case.

To confirm that the tumor-containing vessels were lymphatic channels and not blood vessels, immunostaining with lymphatic-specific endothelial cell marker D2-40 was performed.⁸ It has been used to demonstrate lymphatic vessels in the optic nerve sheath.⁸ In our case, the positive reaction confirmed that the tumor-containing vessels were lymphatics. The nearby blood vessels containing erythrocytes were nonreactive to D2-40 and reactive to CD34.

Regional metastasis from conjunctival melanoma occurs via lymphatics to regional lymph nodes, but histopathologic analysis almost never reveals tumor in lymphatics as seen in our case. Melanoma metastasis to the conjunctiva is by hematogenous routes from the primary site. One might speculate that in our patient the conjunctival metastasis developed from retrograde lymphatic flow from the preauricular tumor. The extensive scarring in that area may have forced the proliferating recurrent melanoma cells to pursue this reverse route to the conjunctiva. In summary, we report a clinicopathologic correlation of an unusual and possibly unique case of cutaneous melanoma metastatic to conjunctival lymphatics.

Correspondence: Dr J. A. Shields, Ocular Oncology Service, Wills Eye Institute, 840 Walnut St, Philadelphia, PA 19107 (jerry.shields@shieldsoncology.com).

Author Contributions: Dr J. A. Shields had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This study was supported by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (Drs J. A. Shields and C. L. Shields); the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (Dr J. A. Shields); a donation from Michael, Bruce, and Ellen Ratner, New York, New York (Drs J. A. Shields and C. L. Shields); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia (Dr C. L. Shields); and the Noel T. and Sara L. Simmonds Endowment for Ophthalmic Pathology, Philadelphia (Dr Eagle).

Previous Presentation: This paper was presented at the annual meeting of the Eastern Ophthalmic Pathology Society; September 15, 2006; Halifax, Nova Scotia, Canada.