Ectopic lymphoid structures in primary cutaneous melanoma

Abstract

Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO(+) memory T cells. A network of CD21(+) follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79(+) HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures. The appearance of B-cell aggregates did not show association with the outcome of the disease, although a trend for their higher prevalence was observed in thicker tumors. Our results show that neogenesis of lymphoid structures does occur in primary melanomas, albeit with lower frequency compared to that reported in metastases.

Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

“…53 Although high endothelial venules (HEVs) have been described in primary melanoma and have been linked to good clinical outcome, 54 , 55 conflicting results exist in regard to the presence of TLSs in primary melanoma, in spite of the fact that the latter frequently contain HEVs. 56 , 57 While we found a positive association between lymphatics and CD19 + cells in metastatic LNs, we did not detect many B cell clusters in the tumor samples examined here. The increased infiltration of B cells in association with lymphatic vessels in metastatic LNs may support the notion that lymphatics promote also the humoral immune response.…”

Reflections on the Histopathology of Tumor-Infiltrating Lymphocytes in Melanoma and the Host Immune Response

“…Moreover, Cipponi and colleagues (48) performed an analysis of the repertoire of rearranged immunoglobulin genes in B cells of the microdissected follicles within melanoma metastases and demonstrated clonal amplification, somatic mutation and isotype switching, all of which suggested a local antigen-driven B-cell response. TL-ELNs have recently been described in primary cutaneous melanoma as well (49), but this has not been observed by others in a very limited number of specimens examined (48). …”

Control of CD8 T-Cell Infiltration into Tumors by Vasculature and Microenvironment

“…Primary human melanomas do contain HEV-like vessels expressing PNAd and CCL21 (Avram et al, 2013; Cipponi et al, 2012; Martinet et al, 2012). However, TLS are either entirely absent or present in only a small fraction of primary tumors (Cipponi et al, 2012; Ladányi et al, 2014). In contrast, metastases were more likely to contain TLS in association with HEV (Cipponi et al, 2012).…”