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.Weconductedasingle center,prospectivestudythatincluded65 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.