Fig. 4From: Cutaneous clear cell/signet-ring cell squamous cell carcinoma arising in the right thigh of a patient with type 2 diabetes: combined morphologic, immunohistochemical, and etiologic analysisHypothesis regarding the involvement of type 2 DM in the pathogenesis of cSCC. Epidemiological studies suggest that hyperglycemia, hyperinsulinemia, and immune disorders in patients with type 2 DM increase the risk of malignant transformation. DM-related chronic ulcer is proposed as a precancerous lesion. Type 2 DM can enhance the expression of p63, which in turn activate the downstream element FGFR2. It may also increase the secretion of FGF7 in stromal cells and affect FGFR2 through paracrine stimulates. Indirect evidence indicates that PI3K/AKT signaling may be involved and contribute to the malignant transformation of squamous cellBack to article page