Alexander Witkowski

Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy

Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma.

Reflectance confocal microscopy correlates of dermoscopic patterns of facial lesions help to discriminate lentigo maligna from pigmented nonmelanocytic macules

The clinical recognition of lentigo maligna (LM) and LM melanoma can be very challenging due to the overlapping features it shares with other pigmented macules of the skin. Noninvasive diagnostic techniques can assist in the differential diagnosis.

Cost–benefit of reflectance confocal microscopy in the diagnostic performance of melanoma

The sub‐optimal diagnostic accuracy for melanoma leads to excise a high number of benign lesions, with consequent costs. Reflectance confocal microscopy (RCM) improves diagnostic specificity, thus possibly inducing a reduction in unnecessary excisions and related costs.

CD271 is expressed in melanomas with more aggressive behaviour, with correlation of characteristic morphology by in vivo reflectance confocal microscopy.

Melanoma is the most highly aggressive type of skin cancer. Its resistance to existing treatments and the rapid rise in incidence underscore the importance of acquiring a better understanding of melanomagenesis.

Non-invasive diagnosis of pink basal cell carcinoma: how much can we rely on dermoscopy and reflectance confocal microscopy?

Non‐pigmented ‘pink’ cutaneous lesions in differential diagnosis with basal cell carcinoma may present a challenge for clinicians. Our objective was to determine the potential improvement of diagnostic accuracy using combined dermoscopy‐reflectance confocal microscopy (RCM) image evaluation.

Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna

Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques.

Improving Diagnostic Accuracy of Dermoscopically Equivocal Pink Cutaneous Lesions with Reflectance Confocal Microscopy in Telemedicine Settings: Double Reader Concordance Evaluation of 316 Cases.

Background Solitary pink lesions in differential diagnosis with hypopigmented/amelanotic melanoma present a diagnostic challenge in daily practice and are regularly referred for second expert opinion. Reflectance confocal microscopy (RCM) has been shown to improve diagnostic accuracy of dermoscopically equivocal pink lesions. No studies have been performed to evaluate the effect of adding a second expert reader and automatic removal of lesions with discordant management recommendations and its potential effect on diagnostic sensitivity and final management of these lesions in retrospective or telemedicine settings. Objective To improve diagnostic accuracy and reduce potential mismanagement of dermoscopically equivocal pink cutaneous lesions by implementing double reader concordance evaluation of RCM images. Methods 316 dermoscopically equivocal pink lesions with dermoscopy-RCM image sets were evaluated retrospectively. Accuracy of three readers was evaluated by single reader evaluation of dermoscopy only and dermoscopy-RCM image sets and finally by double reader evaluation of dermoscopy-RCM image sets. Lesions with discordant diagnosis between two readers were automatically recommended for excision. Results Dermoscopy only evaluation resulted in an overall sensitivity of 95.9% and specificity of 33.6%, with 1 of 12 amelanotic melanomas mismanaged. Dermoscopy-RCM image set single reader evaluation resulted in an overall sensitivity of 93.9% and overall specificity of 54.2%, with 1 of 12 melanomas mismanaged. Dermoscopy-RCM image set double reader concordance evaluation resulted in an overall sensitivity of 98.3% and specificity of 42.7%, with no amelanotic melanoma mismanagement. Conclusion Evaluation of dermoscopy-RCM image sets of equivocal pink lesions by a single reader in telemedicine settings is limited by the potential for misdiagnosis of dangerous malignant lesions. Double reader concordance evaluation with automatic referral of lesions for removal in the case of discordant diagnosis improves the diagnostic sensitivity in this subset of lesions and reduce potential misdiagnosis in settings where a second expert opinion may be employed.

Telediagnosis with Confocal Microscopy: A Reality or a Dream?

Reflectance confocal microscopy (RCM) is becoming more popular among dermatologists aiming to improve their bedside diagnostic accuracy and reduce unnecessary removal of benign cutaneous lesions. With increased interest in the field, limitation of experts, and dedicated training programs, telemedicine application to RCM (teleconfocal) helps to connect patients with experts at a distance. Diagnostic accuracy of store-and-forward telemedicine review of RCM images, patient safety, and cost-effectiveness are important considerations for proper acceptance and usage of the technology in the medical community.

Proteomic analysis of PTCH1+/- fibroblast lysate and conditioned culture media isolated from the skin of healthy subjects and nevoid basal cell carcinoma syndrome patients.

Background. The pathogenesis underlying the increased predisposition to the development of basal cell carcinomas (BCCs) in the context of Gorlin-Goltz syndrome is linked to molecular mechanisms that differ from sporadic BCCs. Patients with Gorlin syndrome tend to develop multiple BCCs at an early age and present with tumors of non-sun-exposed skin. The aim of this study was to compare the proteomic profile of cultured fibroblast and fibroblast conditioned culture media of PTCH1+ and nonmutated fibroblasts. Results. Proteomic analysis was performed using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry in PTCH1+ fibroblast conditioned media isolated from not affected sun-protected skin areas of Gorlin patients and from healthy subjects. 12 protein cluster peaks, >5 kDa, had significant differences in their peak intensities between PTCH1+ and PTCH1− subject groups. We detected a strongly MMP1 overexpression in PTCH1+ fibroblasts obtained from NBCCS patients with respect to healthy donors. Conclusion. Protein profiles in the fibroblast conditioned media revealed statistically significant differences between two different types (missense versus nonsense) of PTCH1 mutations. These differences could be useful as signatures to identify PTCH1 gene carriers at high risk for the development of NBCCS-associated malignancies and to develop novel experimental molecular tailored therapies based on these druggable targets.

Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases

Background Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population. Objective To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings. Methods 1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting. Results Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas. Conclusion Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.