Tumor-associated lymphangiogenesis in conjunctival malignant melanoma

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in BJO and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence Abstract Background: To evaluate whether tumor-associated lymphangiogenesis, i.e. the formation of new lymphatic vessels (LVs) induced by a tumor, occurs in and around conjunctival malignant melanoma (MM). Methods: Clinical files and conjunctival specimens of 20 patients with histologically diagnosed conjunctival MM were analyzed. Sections were stained with LYVE-1 and podoplanin antibodies as specific lymphatic endothelial markers and Ki67 as proliferation marker. The tumor area and the area covered by LV (LVA), the LV number (LVN), and the LV density (LVD) were measured within the tumor and in the peritumoral area in digital images of the specimen. The LV results were correlated with the histopathological characteristics, tumor location, recurrence rate, mitomycin C therapy and presence of metastases. Results: LVs were detected in all specimens within the tumor and peritumorally. Significantly more Ki67 + proliferating lymphatic endothelial cells were detected in the tumor and in the peritumoral tissue up to 300 µm compared to the surrounding normal conjunctiva (>300 µm distance). There was a slightly positive correlation between the tumor size and the LVN and LVA in the 50 µm zone adjacent to the tumor. We did not find significant correlations between LVs and histopathological and clinical characteristics (location, shape, relapses, metastases), possibly due to small sample sizes. Non-limbal tumors with involvement of tarsus or fornix showed a tendency of higher LVD compared to limbal tumors. Conclusion: Conjunctival MMs display tumor-associated LV within and around the tumor. The MM seems to induce lymphangiogenesis not only in the tumor, but also in its proximity.