Cutaneous Squamous Cell Carcinoma in the Age of Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally. Because most cSCC cases are manageable by local excision/radiotherapy and hardly become life-threatening, they are often excluded from cancer registries in most countries. Compared with cutaneous melanoma that originates from the melanin-producing, neural crest-derived epidermal resident, keratinocyte (KC)-derived cancers are influenced by the immune system with regards to their pathogenetic behaviour. Congenital or acquired immunosurveillance impairments compromise tumoricidal activity and raises cSCC incidence rates. Intriguingly, expanded applications of programmed death-1 (PD-1) blockade therapies have revealed cSCC to be one of the most amenable targets, particularly when compared with the mucosal counterparts arisen in the esophagus or the cervix. The clinical observation reminds us that cutaneous tissue has a peculiarly high immunogenicity that can evoke tumoricidal recall responses topically. Here we attempt to redefine cSCC biology and review current knowledge about cSCC from multiple viewpoints that involve epidemiology, clinicopathology, molecular genetics, molecular immunology, and developmental biology. This synthesis not only underscores the primal importance of the immune system, rather than just a mere accumulation of ultraviolet-induced mutations but also reinforces the following hypothesis: PD-1 blockade effectively restores the immunity specially allowed to exist within the fully cornified squamous epithelium, that is, the epidermis.

Ganglioside GD3 May Suppress the Functional Activities of Benign Skin T Cells in Cutaneous T-Cell Lymphoma.

In cutaneous T-cell lymphoma (CTCL), which arises from skin-tropic memory T cells, malignant T cells and benign T cells are confined in the same skin lesions. It is thus difficult to evaluate the phenotypic characteristics and functional activities of benign T cells in CTCL. Disialoganglioside with three glycosyl groups (GD3) is increasingly expressed on the surface of solid malignant tumor cells and takes part in tumor progression and suppression of tumor immunity. However, the role of GD3 in CTCL is not well-understood. In this study, the malignant and benign T cells in CTCL skin lesions were distinguished by flow cytometry and their phenotypic characteristics were compared with those of T cells from control skin specimens. In CTCL skin lesions, the benign T cells included limited resident memory T cells (TRM), which are sessile in skin and known to exert strong antitumor function. The benign T cells showed diminished Th17 property, and the expression of GD3 was high in the malignant T cells. The expression of GD3 in the malignant T cells inversely correlated with IL-17A production from the benign CD4 T cells. GD3 from the malignant T cells was implied to be involved in suppressing the Th17 activity of the benign T cells independent of the regulation of TRM differentiation in CTCL. Revealing the role of GD3 in inhibiting the production of IL-17A in CTCL would aid the understanding of the suppressive mechanism of the antitumor activity by malignant tumor cells.

Local and disease control for nasal melanoma treated with radiation and concomitant anti-programmed death 1 antibody.

Mucosal melanoma of the nasal cavity is a rare disease that has been consistently associated with poor outcome. While complete surgical excision offers the only prospect of a cure, it is associated with a high risk of surgical morbidity due to the challenging anatomical location, and most patients still develop incurable metastatic disease. The efficacy of immunotherapy on mucosal melanoma is lower in comparison with cutaneous melanoma, and mucosal melanoma rarely has BRAF mutations. Although preclinical data have shown that combination treatment with immune checkpoint inhibitors and radiotherapy (RT) improve the response, there have been few reports on the combination of RT and anti-programmed death 1 therapy for mucosal melanoma of the nasal cavity. We retrospectively investigated 10 cases of mucosal melanoma of the nasal cavity in which combined treatment was applied. The local control (LC) rate of the primary lesion and regional lymph nodes was favorably 100%. On the other hand, the median progression-free survival (PFS) time was 29.6 weeks (range, 2-82). The 6-month PFS rate was 60%. Although severe mucositis occurred in one patient, the incidence of treatment-related adverse events was not significantly increased. RT with anti-programmed death 1 antibody therapy for mucosal melanoma of the nasal cavity was tolerable and had the potential to improve LC and PFS.

A Rare Case of Atrophic Dermatofibroma Featuring Linear Skin Dimple.

Dermatofibroma (DF) is a benign skin tumor that is well-known among dermatologists. We herein present a rare case of atrophic dermatofibroma presenting linear skin dimpling. The patient was a 25-year-old woman with a history of wild-type recessive dystrophic epidermolysis bullosa who had noticed linear concavity on her right lateral back 1 year before her initial presentation. Anetoderma, atrophic scar, localized morphea, or lupus erythematosus profundus were clinically suspected; however, a biopsy specimen from the dimpling lesion showed the fibrous and histiocytic tumor in the deep dermis. The spindle-to-rhomboid-shaped tumor cells were arranged with irregularly storiform pattern, and immunohistochemistry showed that the tumor cells were positive for factor XIIIa, and negative for CD34 and CD68. Elastica van Gieson staining showed an almost complete loss of elastic fibers, especially at the center of the lesion. The reduction of elastic fibers might have influenced the skin depression in this case. This rare case suggests the need to consider a subtype of DF in the differential diagnosis of dimpling skin lesions.