title: Differential diagnosis of nonmelanoma pigmented skin lesions based on harmonic generation microscopy.
abstract: In 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.
authors.affiliation: National Taiwan University, Graduate Institute of Photonics and Optoelectronics and Department of Electrical Engineering, Taipei 10617, TaiwanbNational Taiwan University, Molecular Imaging Center, Taipei 10617, Taiwan.
authors.forename: Ming-Rung
authors.initials: MR
authors.lastname: Tsai
authors.affiliation: National Taiwan University, Graduate Institute of Photonics and Optoelectronics and Department of Electrical Engineering, Taipei 10617, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Dermatology, Taipei 10002, Taiwan.
authors.forename: Jau-Shiuh
authors.initials: JS
authors.lastname: Chen
authors.affiliation: National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Dermatology, Taipei 10002, Taiwan.
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Sheen
authors.affiliation: National Taiwan University, Molecular Imaging Center, Taipei 10617, TaiwancNational Taiwan University Hospital and National Taiwan University College of Medicine, Department of Dermatology, Taipei 10002, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Liao
authors.affiliation: National Taiwan University, Graduate Institute of Photonics and Optoelectronics and Department of Electrical Engineering, Taipei 10617, TaiwanbNational Taiwan University, Molecular Imaging Center, Taipei 10617, TaiwandResearch Center for Applied Sciences.
authors.forename: Chi-Kuang
authors.initials: CK
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D017492:Keratosis, Seborrheic / Q000175:diagnosis; D008297:Male; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000175:diagnosis; D061848:Optical Imaging / Q000379:methods*; D012871:Skin Diseases / Q000145:classification / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult