Histological findings after intralesional methotrexate treatment in cutaneous squamous cell carcinoma

Intralesional methotrexate (il‐MTX) has been reported as a useful therapy in keratoacanthoma (KA) and cutaneous squamous cell carcinoma (cSCC). However, the data available on the histological changes induced by this therapy are very scarce. We conducted a single center, prospective study that included 65 cases of cSCC treated with il‐MTX before surgical treatment. Two histological studies were conducted in all patients: before intralesional treatment and after surgical removal. Lesions were assessed longitudinally both clinically and histologically. 60 patients (92.3%) responded to il‐MTX treatment. There were no differences regarding aggressive histological features of the cSCC between responder and non‐responder patients. All cases showed a chronic inflammatory infiltrate after il‐MTX. Intratumoral necrosis areas were frequently observed. All cases showed local fibrosis with fine thickening of collagen bundles. Il‐MTX induces a chronic lymphohistiocytic inflammatory reaction in both clinical responder and nonresponder patients. Tumor involution after il‐MTX is followed by a fine fibrosis that explains the great cosmetic results and improves the accuracy of the follow‐up.