Tsai, Ming-RungMing-RungTsaiYU-HSIANG CHENGJAU-SHIUH CHENYI-SHUAN SHEENYI-HUA LIAOCHI-KUANG SUN2019-12-042019-12-0420141083-3668https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897753109&doi=10.1117%2f1.JBO.19.3.036001&partnerID=40&md5=03a6bf41db8b7daa1f23236aa4454f5dhttps://scholars.lib.ntu.edu.tw/handle/123456789/434802In vivo harmonic generation microscopy (HGM) has been applied successfully in healthy human skin and can achieve a submicron resolution, similar to histopathologic examination, even at a penetration depth up to 270 μm. This study aims to investigate the clinical applicability of HGM imaging for differential diagnosis of nonmelanoma pigmented skin lesions. A total of 42 pigmented skin tumors, including pigmented basal cell carcinoma, melanocytic nevus, and seborrheic keratosis were evaluated by HGM ex vivo or in vivo. Based on the standard histopathologic characteristics, we established the corresponding HGM imaging criteria for each pigmented tumor. Diagnostic performance of HGM for differentiating nonmelanoma pigmented skin tumors was evaluated through the observers' direct general assessment (overall evaluation) or the presence of two imaging criteria with the highest sensitivity and specificity (major criteria evaluation). Our results show that, based on the direct general assessment, the sensitivity is 92% [95% confidence interval (CI): 67 to 97%] and the specificity is 96% (95% CI: 83 to 99%); by major criteria evaluation, 94% sensitivity (95% CI: 70 to 99%) and 100% specificity (95% CI: 87 to 100%) are achieved. Our study indicates that HGM serves as a promising histopathological examination tool for noninvasive differential diagnostics of nonmelanoma pigmented skin tumors. ? The Authors.[SDGs]SDG3Basal cell carcinoma; Diagnostic performance; Differential diagnosis; Harmonic generation microscopy; Histopathological examinations; Melanocytic nevi; Seborrheic keratosis; Sensitivity and specificity; Dermatology; Diagnosis; Skin; Tumors; Harmonic generation; adult; aged; article; basal cell carcinoma; classification; cytochemistry; differential diagnosis; female; fluorescence imaging; human; image processing; male; methodology; microscopy; middle aged; pathology; pigmented nevus; seborrheic keratosis; skin disease; very elderly; young adult; Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Diagnosis, Differential; Female; Histocytochemistry; Humans; Image Processing, Computer-Assisted; Keratosis, Seborrheic; Male; Microscopy; Middle Aged; Nevus, Pigmented; Optical Imaging; Skin Diseases; Young Adultjournal article10.1117/1.JBO.19.3.036001245899852-s2.0-84897753109