A Myxoid Fibrotic Reaction Pattern is Associated with Metastatic Risk in Cutaneous Squamous Cell Carcinoma
Eugenia Hernández-Ruiz, Inmaculada Hernández-Muñoz, Emili Masferrer, Carla Ferrándiz-Pulido, Evelyn Andrades, Javier Gimeno, Xavier Duran, Vicente García-Patos, Ramon M. Pujol, Agusti Toll
Although desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopathological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immunosuppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.
Cutaneous squamous cell carcinomas are the second most frequent non-melanoma skin cancers. Despite their generally good prognosis, approximately 2–5% metastasize, usually to regional lymph nodes. Recent works have elucidated the relevance of the tumour microenvironment, consisting of a stromal reaction, a vascular and lymphatic network and the presence of specific inflammatory cell subpopulations, in the development of metastases. In this study we have characterized different types of stromal reaction patterns in cutaneous squamous cell carcinoma, including desmoplasia, and have found that the presence of a myxoid peritumoral infiltration, easily recognisable by hematoxylin eosin stains, is associated with an increased metastatic risk.