Sensitivity and specificity of multiphoton laser tomography for in vivo and ex vivo diagnosis of malignant melanoma.

The incidence of malignant melanoma has shown a dramatic increase over the past three decades. Patient outcome and curability depend on early diagnosis. In vivo multiphoton laser tomography represents a recently developed diagnostic tool that allows non-invasive tissue imaging. We aim to demonstrate the application of multiphoton laser tomography for the in vivo differentiation and diagnosis of melanoma. Laser radiation in the near infrared spectrum was used to image endogenous fluorophores by multiphoton excitation. Eighty-three melanocytic skin lesions have been investigated. The results showed distinct morphological differences in melanoma compared with melanocytic nevi. In particular, six characteristic features of malignant melanoma were specified and statistically evaluated. Sensitivity values up to 95% (range: 71-95%) and specificity values up to 97% (range: 69-97%) were achieved for diagnostic classification. Logistic regression analysis was performed to identify the most significant diagnostic criteria. We found that architectural disarray of the epidermis, poorly defined keratinocyte cell borders as well as the presence of pleomorphic or dendritic cells were of prime importance. By means of this procedure accuracy values up to 97% were reached. These findings underline the potential applicability of multiphoton laser tomography in melanoma diagnosis of melanocytic skin lesions.

[1]  Karsten König,et al.  Clinical multiphoton tomography , 2008, Journal of biophotonics.

[2]  I. Riemann,et al.  In vivo Drug Screening in Human Skin Using Femtosecond Laser Multiphoton Tomography , 2006, Skin Pharmacology and Physiology.

[3]  P. G. Lang,et al.  Skin Biopsy Rates and Incidence of Melanoma: Population Based Ecological Study , 2006 .

[4]  J C Bamber,et al.  Differentiation of common benign pigmented skin lesions from melanoma by high‐resolution ultrasound , 2000, The British journal of dermatology.

[5]  Martin Kaatz,et al.  In vivo multiphoton tomography of inflammatory tissue and melanoma , 2005, SPIE BiOS.

[6]  A. Blum,et al.  Epidemiology of Cutaneous Melanoma in Germany and Worldwide , 2001, Skin Pharmacology and Physiology.

[7]  Thilo Gambichler,et al.  Characterization of benign and malignant melanocytic skin lesions using optical coherence tomography in vivo. , 2007, Journal of the American Academy of Dermatology.

[8]  Andreas Volkmer,et al.  Femtosecond Two‐photon Excited Fluorescence of Melanin* , 1999, Photochemistry and photobiology.

[9]  Mackie,et al.  Clinical accuracy of the diagnosis of cutaneous malignant melanoma , 1998, The British journal of dermatology.

[10]  P. Aegerter,et al.  Is dermoscopy (epiluminescence microscopy) useful for the diagnosis of melanoma? Results of a meta-analysis using techniques adapted to the evaluation of diagnostic tests. , 2001, Archives of dermatology.

[11]  Karsten König,et al.  Morphological skin ageing criteria by multiphoton laser scanning tomography: non‐invasive in vivo scoring of the dermal fibre network , 2008, Experimental dermatology.

[12]  H. Kittler,et al.  Diagnostic accuracy of dermoscopy. , 2002, The Lancet. Oncology.

[13]  Stefan Puschmann,et al.  Skin imaged by femtosecond laser irradiation: a risk assessment for in vivo applications , 2006, SPIE Photonics Europe.

[14]  Iris Riemann,et al.  High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. , 2003, Journal of biomedical optics.

[15]  Haishan Zeng,et al.  Cutaneous melanin exhibiting fluorescence emission under near-infrared light excitation. , 2006, Journal of biomedical optics.

[16]  Maria Goeppert-Mayer.  Über Elementarakte mit zwei Quantensprüngen , 1931 .

[17]  Ashfaq A Marghoob,et al.  Instruments and new technologies for the in vivo diagnosis of melanoma. , 2003, Journal of the American Academy of Dermatology.

[18]  Riccardo Bono,et al.  Sensitivity, specificity, and diagnostic accuracy of three dermoscopic algorithmic methods in the diagnosis of doubtful melanocytic lesions: the importance of light brown structureless areas in differentiating atypical melanocytic nevi from thin melanomas. , 2007, Journal of the American Academy of Dermatology.

[19]  F. Sera,et al.  Magnetic resonance imaging in the diagnosis of melanoma:in vivo preliminary studies with dynamic contrast-enhanced subtraction , 2002, Melanoma research.

[20]  S. Menzies,et al.  Increase in the sensitivity for melanoma diagnosis by primary care physicians using skin surface microscopy , 2000, The British journal of dermatology.

[21]  P. So,et al.  Multi-photon Excitation Microscopy and Confocal Microscopy Imaging of In Vivo Human Skin: A Comparison , 1999, Microscopy and Microanalysis.

[22]  K. König,et al.  Two-photon microscopes and in vivo multiphoton tomographs--powerful diagnostic tools for tissue engineering and drug delivery. , 2006, Advanced drug delivery reviews.

[23]  Maria Smedh,et al.  Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics. , 2008, The Journal of investigative dermatology.

[24]  R. Wolfe,et al.  Comparative performance of 4 dermoscopic algorithms by nonexperts for the diagnosis of melanocytic lesions. , 2005, Archives of dermatology.

[25]  K. Jöckel,et al.  Malignant melanoma and nonmelanoma skin cancers in Northrhine‐Westphalia, Germany: a patient‐ vs. diagnosis‐based incidence approach , 2007, International Journal of Dermatology.

[26]  W. Webb,et al.  Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Steven F. Morris,et al.  The Diagnostic Accuracy of in vivo Confocal Scanning Laser Microscopy Compared to Dermoscopy of Benign and Malignant Melanocytic Lesions: A Prospective Study , 2007, Dermatology.