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Noninvasive Imaging Tools in Dermatology
Author(s)
Radhika Srivastava, BA
Marco Manfredini, MD
Babar K. Rao, MD

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.1 Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.1

Figure 1. A, Melanocytic nevus using nonpolarized contact dermoscopy. B, Melanocytic nevus using polarized contact dermoscopy. C, In situ malignant melanoma using nonpolarized contact dermoscopy. D, In situ malignant melanoma using polarized contact dermoscopy.

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”2 In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.3

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.4 There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,5 while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).8 Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.9 Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.10

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.11 Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.12

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.13 Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice14; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.15

 

 

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,24 and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.27 However, RCM has been used to discriminate between in situ and invasive proliferations.28 Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections29,30 and inflammatory skin diseases.29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,34 delineate presurgical tumor margins,35,36 and monitor response to noninvasive treatments.37,38

Figure 2. A, Nonpolarized contact dermoscopy of a suspicious lesion showed prominent vessels, irregular pigmentation, and prominent follicular openings, which are not classic features of basal cell carcinoma. B, A reflectance confocal microscopy mosaic of the same lesion showed well-defined tumor nodules, resulting in a diagnosis of basal cell carcinoma.

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.39 Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.40 It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.39 The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.42 The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.43 Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.44 A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.45 Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.46

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)49; the combination of OCT with other imaging modalities50,51; the use of OCT to delineate presurgical margins52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.54,55

Figure 3. A, A nonpolarized contact dermoscopy image of a nodular pigmented basal cell carcinoma showed large blue-gray ovoid nests, arborizing vessels, and small fine telangiectases. B, A microvascular en face dynamic optical coherence tomography image (size, 6×6 mm; depth, 300 µm) of the same lesion revealed circumscribed areas (asterisks) and branching/arborizing vessels (arrows). C, A cross-sectional optical coherence tomography image of the same lesion showed ovoid structures (asterisks) corresponding with tumor nests with dark peripheral borders and thinning of the epidermis above them.

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

References
  1. Benvenuto-Andrade C, Dusza SW, Agero AL, et al. Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions. Arch Dermatol. 2007;143:329-338.
  2. Terushkin V, Oliveria SA, Marghoob AA, et al. Use of and beliefs about total body photography and dermatoscopy among US dermatology training programs: an update. J Am Acad Dermatol. 2010;62:794-803.
  3. Morris JB, Alfonso SV, Hernandez N, et al. Use of and intentions to use dermoscopy among physicians in the United States. Dermatol Pract Concept. 2017;7:7-16.
  4. Yélamos O, Braun RP, Liopyris K, et al. Dermoscopy and dermatopathology correlates of cutaneous neoplasms. J Am Acad Dermatol. 2019;80:341-363.
  5. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  6. Carli P, de Giorgi V, Chiarugi A, et al. Addition of dermoscopy to conventional naked-eye examination in melanoma screening: a randomized study. J Am Acad Dermatol. 2004;50:683-668.
  7. Lallas A, Zalaudek I, Argenziano G, et al. Dermoscopy in general dermatology. Dermatol Clin. 2013;31:679-694.
  8. Reiter O, Mimouni I, Gdalvevich M, et al. The diagnostic accuracy of dermoscopy for basal cell carcinoma: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:1380-1388.
  9. Papageorgiou V, Apalla Z, Sotiriou E, et al. The limitations of dermoscopy: false-positive and false-negative tumours. J Eur Acad Dermatol Venereol. 2018;32:879-888.
  10. Micali G, Verzì AE, Lacarrubba F. Alternative uses of dermoscopy in daily clinical practice: an update. J Am Acad Dermatol. 2018;79:1117-1132.e1.
  11. Rajadhyaksha M, Grossman M, Esterowitz D, et al. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol. 1995;104:946-952.
  12. Kose K, Gou M, Yélamos O, et al. Automated video-mosaicking approach for confocal microscopic imaging in vivo: an approach to address challenges in imaging living tissue and extend field of view. Sci Rep. 2017;7:10759.
  13. Rao BK, John AM, Francisco G, et al. Diagnostic accuracy of reflectance confocal microscopy for diagnosis of skin lesions [published online October 8, 2018]. Arch Pathol Lab Med. 2019;143:326-329.
  14. Current Procedural Terminology, Professional Edition. Chicago IL: American Medical Association; 2016. The preliminary physician fee schedule for 2017 is available at https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/PFS-Federal-Regulation-Notices-Items/CMS-1654-P.html.
  15. Jain M, Pulijal SV, Rajadhyaksha M, et al. Evaluation of bedside diagnostic accuracy, learning curve, and challenges for a novice reflectance confocal microscopy reader for skin cancer detection in vivo. JAMA Dermatol. 2018;154:962-965.
  16. Rao BK, Pellacani G. Atlas of Confocal Microscopy in Dermatology: Clinical, Confocal, and Histological Images. New York, NY: NIDIskin LLC; 2013.
  17. Scope A, Benvenuto-Andrande C, Agero AL, et al. In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: consensus terminology glossary and illustrative images. J Am Acad Dermatol. 2007;57:644-658.
  18. Gerger A, Hofmann-Wellenhof R, Langsenlehner U, et al. In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images. Br J Dermatol. 2008;158:329-333. 
  19. Stevenson AD, Mickan S, Mallett S, et al. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Dermatol Pract Concept. 2013;3:19-27.
  20. Alarcon I, Carrera C, Palou J, et al. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170:802-808.
  21. Lovatto L, Carrera C, Salerni G, et al. In vivo reflectance confocal microscopy of equivocal melanocytic lesions detected by digital dermoscopy follow-up. J Eur Acad Dermatol Venereol. 2015;29:1918-1925.
  22. Guitera P, Pellacani G, Longo C, et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Invest Dermatol. 2009;129:131-138.
  23. Xiong YQ, Ma SJ, Mo Y, et al. Comparison of dermoscopy and reflectance confocal microscopy for the diagnosis of malignant skin tumours: a meta-analysis. J Cancer Res Clin Oncol. 2017;143:1627-1635.
  24. Kadouch DJ, Schram ME, Leeflang MM, et al. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29:1890-1897.
  25. Dinnes J, Deeks JJ, Chuchu N, et al; Cochrane Skin Cancer Diagnostic Test Accuracy Group. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018;12:CD013191.
  26. Nguyen KP, Peppelman M, Hoogedoorn L, et al. The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review. Eur J Dermatol. 2016;26:549-565.
  27. Pellacani G, Ulrich M, Casari A, et al. Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology. J Eur Acad Dermatol Venereol. 2015;29:2216-2221.
  28. Manfredini M, Longo C, Ferrari B, et al. Dermoscopic and reflectance confocal microscopy features of cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2017;31:1828-1833.
  29. Hoogedoorn L, Peppelman M, van de Kerkhof PC, et al. The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: a systematic review. Br J Dermatol. 2015;172:1222-1248.
  30. Cinotti E, Perrot JL, Labeille B, et al. Reflectance confocal microscopy for cutaneous infections and infestations. J Eur Acad Dermatol Venereol. 2016;30:754-763.
  31. Ardigo M, Longo C, Gonzalez S; International Confocal Working Group Inflammatory Skin Diseases Project. Multicentre study on inflammatory skin diseases from The International Confocal Working Group: specific confocal microscopy features and an algorithmic method of diagnosis. Br J Dermatol. 2016;175:364-374.
  32. Ardigo M, Agozzino M, Franceschini C, et al. Reflectance confocal microscopy algorithms for inflammatory and hair diseases. Dermatol Clin. 2016;34:487-496.
  33. Manfredini M, Bettoli V, Sacripanti G, et al. The evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography [published online April 26, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15641.
  34. Navarrete-Dechent C, Mori S, Cordova M, et al. Reflectance confocal microscopy as a novel tool for presurgical identification of basal cell carcinoma biopsy site. J Am Acad Dermatol. 2019;80:e7-e8.
  35. Pan ZY, Lin JR, Cheng TT, et al. In vivo reflectance confocal microscopy of basal cell carcinoma: feasibility of preoperative mapping of cancer margins. Dermatol Surg. 2012;38:1945-1950.
  36. Venturini M, Gualdi G, Zanca A, et al. A new approach for presurgical margin assessment by reflectance confocal microscopy of basal cell carcinoma. Br J Dermatol. 2016;174:380-385.
  37. Sierra H, Yélamos O, Cordova M, et al. Reflectance confocal microscopy‐guided laser ablation of basal cell carcinomas: initial clinical experience. J Biomed Opt. 2017;22:1-13.
  38. Maier T, Kulichova D, Ruzicka T, et al. Noninvasive monitoring of basal cell carcinomas treated with systemic hedgehog inhibitors: pseudocysts as a sign of tumor regression. J Am Acad Dermatol. 2014;71:725-730.
  39. Levine A, Wang K, Markowitz O. Optical coherence tomography in the diagnosis of skin cancer. Dermatol Clin. 2017;35:465-488.
  40. Schneider SL, Kohli I, Hamzavi IH, et al. Emerging imaging technologies in dermatology: part I: basic principles. J Am Acad Dermatol. 2019;80:1114-1120.
  41. Mogensen M, Joergensen TM, Nümberg BM, et al. Assessment of optical coherence tomography imaging in the diagnosis of non‐melanoma skin cancer and benign lesions versus normal skin: observer‐blinded evaluation by dermatologists and pathologists. Dermatol Surg. 2009;35:965-972.
  42. Ferrante di Ruffano L, Dinnes J, Deeks JJ, et al. Optical coherence tomography for diagnosing skin cancer in adults. Cochrane Database Syst Rev. 2018;12:CD013189.
  43. Ulrich M, von Braunmuehl T, Kurzen H, et al. The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study. Br J Dermatol. 2015;173:428-435.
  44. Wessels R, de Bruin DM, Relyveld GM, et al. Functional optical coherence tomography of pigmented lesions. J Eur Acad Dermatol Venereol. 2015;29:738‐744.
  45. Gambichler T, Schmid-Wendtner MH, Plura I, et al. A multicentre pilot study investigating high‐definition optical coherence tomography in the differentiation of cutaneous melanoma and melanocytic naevi. J Eur Acad Dermatol Venereol. 2015;29:537‐541.
  46. Marneffe A, Suppa M, Miyamoto M, et al. Validation of a diagnostic algorithm for the discrimination of actinic keratosis from normal skin and squamous cell carcinoma by means of high-definition optical coherence tomography. Exp Dermatol. 2016;25:684-687.
  47. Boone MA, Suppa M, Dhaenens F, et al. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography. Arch Dermatol Res. 2016;308:7-20.
  48. Boone MA, Suppa M, Marneffe A, et al. A new algorithm for the discrimination of actinic keratosis from normal skin and squamous cell carcinoma based on in vivo analysis of optical properties by high-definition optical coherence tomography. J Eur Acad Dermatol Venereol. 2016;30:1714-1725.
  49. Themstrup L, Pellacani G, Welzel J, et al. In vivo microvascular imaging of cutaneous actinic keratosis, Bowen’s disease and squamous cell carcinoma using dynamic optical coherence tomography. J Eur Acad Dermatol Venereol. 2017;31:1655-1662.
  50. Alex A, Weingast J, Weinigel M, et al. Three-dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology. J Biophotonics. 2013;6:352-362.
  51. Iftimia N, Yélamos O, Chen CJ, et al. Handheld optical coherence tomography-reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins. J Biomed Opt. 2017;22:76006.
  52. Wang KX, Meekings A, Fluhr JW, et al. Optical coherence tomography-based optimization of Mohs micrographic surgery of basal cell carcinoma: a pilot study. Dermatol Surg. 2013;39:627-633.
  53. Chan CS, Rohrer TE. Optical coherence tomography and its role in Mohs micrographic surgery: a case report. Case Rep Dermatol. 2012;4:269-274.
  54. Gambichler T, Jaedicke V, Terras S. Optical coherence tomography in dermatology: technical and clinical aspects. Arch Dermatol Res. 2011;303:457-473.
  55. Manfredini M, Greco M, Farnetani F, et al. Acne: morphologic and vascular study of lesions and surrounding skin by means of optical coherence tomography. J Eur Acad Dermatol Venereol. 2017;31:1541-1546.
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Author and Disclosure Information

Ms. Srivastava and Dr. Rao are from the Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, New Jersey. Dr. Rao also is from Department of Dermatology, Weill Cornell Medical Center, New York, New York. Dr. Manfredini is from the Department of Dermatology, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.

Ms. Srivastava and Dr. Manfredini report no conflict of interest. Dr. Rao serves as a consultant for Caliber ID.

Correspondence: Babar K. Rao, MD, Department of Dermatology, Rutgers Robert Wood Johnson Medical School, 1 World’s Fair Dr, Ste 2400, Somerset, NJ 08873 (babarrao@gmail.com).

Issue
Cutis - 104(2)
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MDedge Dermatology
Cutis
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Melanoma
Nonmelanoma Skin Cancer
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Tech Talk
Author(s)
Radhika Srivastava, BA
Marco Manfredini, MD
Babar K. Rao, MD
Author(s)
Radhika Srivastava, BA
Marco Manfredini, MD
Babar K. Rao, MD
Author and Disclosure Information

Ms. Srivastava and Dr. Rao are from the Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, New Jersey. Dr. Rao also is from Department of Dermatology, Weill Cornell Medical Center, New York, New York. Dr. Manfredini is from the Department of Dermatology, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.

Ms. Srivastava and Dr. Manfredini report no conflict of interest. Dr. Rao serves as a consultant for Caliber ID.

Correspondence: Babar K. Rao, MD, Department of Dermatology, Rutgers Robert Wood Johnson Medical School, 1 World’s Fair Dr, Ste 2400, Somerset, NJ 08873 (babarrao@gmail.com).

Author and Disclosure Information

Ms. Srivastava and Dr. Rao are from the Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, New Jersey. Dr. Rao also is from Department of Dermatology, Weill Cornell Medical Center, New York, New York. Dr. Manfredini is from the Department of Dermatology, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.

Ms. Srivastava and Dr. Manfredini report no conflict of interest. Dr. Rao serves as a consultant for Caliber ID.

Correspondence: Babar K. Rao, MD, Department of Dermatology, Rutgers Robert Wood Johnson Medical School, 1 World’s Fair Dr, Ste 2400, Somerset, NJ 08873 (babarrao@gmail.com).

Article PDF
CT104002108_REV.PDF
Article PDF
CT104002108_REV.PDF

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.1 Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.1

Figure 1. A, Melanocytic nevus using nonpolarized contact dermoscopy. B, Melanocytic nevus using polarized contact dermoscopy. C, In situ malignant melanoma using nonpolarized contact dermoscopy. D, In situ malignant melanoma using polarized contact dermoscopy.

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”2 In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.3

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.4 There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,5 while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).8 Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.9 Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.10

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.11 Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.12

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.13 Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice14; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.15

 

 

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,24 and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.27 However, RCM has been used to discriminate between in situ and invasive proliferations.28 Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections29,30 and inflammatory skin diseases.29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,34 delineate presurgical tumor margins,35,36 and monitor response to noninvasive treatments.37,38

Figure 2. A, Nonpolarized contact dermoscopy of a suspicious lesion showed prominent vessels, irregular pigmentation, and prominent follicular openings, which are not classic features of basal cell carcinoma. B, A reflectance confocal microscopy mosaic of the same lesion showed well-defined tumor nodules, resulting in a diagnosis of basal cell carcinoma.

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.39 Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.40 It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.39 The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.42 The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.43 Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.44 A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.45 Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.46

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)49; the combination of OCT with other imaging modalities50,51; the use of OCT to delineate presurgical margins52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.54,55

Figure 3. A, A nonpolarized contact dermoscopy image of a nodular pigmented basal cell carcinoma showed large blue-gray ovoid nests, arborizing vessels, and small fine telangiectases. B, A microvascular en face dynamic optical coherence tomography image (size, 6×6 mm; depth, 300 µm) of the same lesion revealed circumscribed areas (asterisks) and branching/arborizing vessels (arrows). C, A cross-sectional optical coherence tomography image of the same lesion showed ovoid structures (asterisks) corresponding with tumor nests with dark peripheral borders and thinning of the epidermis above them.

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

Traditionally, diagnosis of skin disease relies on clinical inspection, often followed by biopsy and histopathologic examination. In recent years, new noninvasive tools have emerged that can aid in clinical diagnosis and reduce the number of unnecessary benign biopsies. Although there has been a surge in noninvasive diagnostic technologies, many tools are still in research and development phases, with few tools widely adopted and used in regular clinical practice. In this article, we discuss the use of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in the diagnosis and management of skin disease.

Dermoscopy

Dermoscopy, also known as epiluminescence light microscopy and previously known as dermatoscopy, utilizes a ×10 to ×100 microscope objective with a light source to magnify and visualize structures present below the skin’s surface, such as melanin and blood vessels. There are 3 types of dermoscopy: conventional nonpolarized dermoscopy, polarized contact dermoscopy, and nonpolarized contact dermoscopy (Figure 1). Traditional nonpolarized dermoscopy requires a liquid medium and direct contact with the skin, and it relies on light reflection and refraction properties.1 Cross-polarized light sources allow visualization of deeper structures, either with or without a liquid medium and contact with the skin surface. Although there is overall concurrence among the different types of dermoscopy, subtle differences in the appearance of color, features, and structure are present.1

Figure 1. A, Melanocytic nevus using nonpolarized contact dermoscopy. B, Melanocytic nevus using polarized contact dermoscopy. C, In situ malignant melanoma using nonpolarized contact dermoscopy. D, In situ malignant melanoma using polarized contact dermoscopy.

Dermoscopy offers many benefits for dermatologists and other providers. It can be used to aid in the diagnosis of cutaneous neoplasms and other skin diseases. Numerous low-cost dermatoscopes currently are commercially available. The handheld, easily transportable nature of dermatoscopes have resulted in widespread practice integration. Approximately 84% of attending dermatologists in US academic settings reported using dermoscopy, and many refer to the dermatoscope as “the dermatologist’s stethoscope.”2 In addition, 6% to 15% of other US providers, including family physicians, internal medicine physicians, and plastic surgeons, have reported using dermoscopy in their clinical practices. Limitations of dermoscopy include visualization of the skin surface only and not deeper structures within the tissue, the need for training for adequate interpretation of dermoscopic images, and lack of reimbursement for dermoscopic examination.3

Many dermoscopic structures that correspond well with histopathology have been described. Dermoscopy has a sensitivity of 79% to 96% and specificity of 69% to 99% in the diagnosis of melanoma.4 There is variable data on the specificity of dermoscopy in the diagnosis of melanoma, with one meta-analysis finding no statistically significant difference in specificity compared to naked eye examination,5 while other studies report increased specificity and subsequent reduction in biopsy of benign lesions.6,7 Dermoscopy also can aid in the diagnosis of keratinocytic neoplasms, and dermoscopy also results in a sensitivity of 78.6% to 100% and a specificity of 53.8% to 100% in the diagnosis of basal cell carcinoma (BCC).8 Limitations of dermoscopy include false-positive diagnoses, commonly seborrheic keratoses and nevi, resulting in unnecessary biopsies, as well as false-negative diagnoses, commonly amelanotic and nevoid melanoma, resulting in delays in skin cancer diagnosis and resultant poor outcomes.9 Dermoscopy also is used to aid in the diagnosis of inflammatory and infectious skin diseases, as well as scalp, hair, and nail disorders.10

Reflectance Confocal Microscopy

Reflectance confocal microscopy utilizes an 830-nm laser to capture horizontal en face images of the skin with high resolution. Different structures of the skin have varying indices of refraction: keratin, melanin, and collagen appear bright white, while other components appear dark, generating black-and-white RCM images.11 Currently, there are 2 reflectance confocal microscopes that are commercially available in the United States. The Vivascope 1500 (Caliber ID) is the traditional model that captures 8×8-mm images, and the Vivascope 3000 (Caliber ID) is a smaller handheld model that captures 0.5×0.5-mm images. The traditional model provides the advantages of higher-resolution images and the ability to capture larger surface areas but is best suited to image flat areas of skin to which a square window can be adhered. The handheld model allows improved contact with the varying topography of skin; does not require an adhesive window; and can be used to image cartilaginous, mucosal, and sensitive surfaces. However, it can be difficult to correlate individual images captured by the handheld RCM with the location relative to the lesion, as it is exquisitely sensitive to motion and also is operator dependent. Although complex algorithms are under development to stitch individual images to provide better correlation with the geography of the lesion, such programs are not yet widely available.12

Reflectance confocal microscopy affords many benefits for patients and providers. It is noninvasive and painless and is capable of imaging in vivo live skin as compared to clinical examination and dermoscopy, which only allow for visualization of the skin’s surface. Reflectance confocal microscopy also is time efficient, as imaging of a single lesion can be completed in 10 to 15 minutes. This technology generates high-resolution images, and RCM diagnosis has consistently demonstrated high sensitivity and specificity when compared to histopathology.13 Additionally, RCM imaging can spare biopsy and resultant scarring on cosmetically sensitive areas. Recently, RCM imaging of the skin has been granted Category I Current Procedural Terminology reimbursement codes that allow provider reimbursement and integration of RCM into daily practice14; however, private insurance coverage in the United States is variable. Limitations of RCM include a maximum depth of 200 to 300 µm, high cost to procure a reflectance confocal microscope, and the need for considerable training and practice to accurately interpret grayscale en face images.15

 

 

There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,24 and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.27 However, RCM has been used to discriminate between in situ and invasive proliferations.28 Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections29,30 and inflammatory skin diseases.29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,34 delineate presurgical tumor margins,35,36 and monitor response to noninvasive treatments.37,38

Figure 2. A, Nonpolarized contact dermoscopy of a suspicious lesion showed prominent vessels, irregular pigmentation, and prominent follicular openings, which are not classic features of basal cell carcinoma. B, A reflectance confocal microscopy mosaic of the same lesion showed well-defined tumor nodules, resulting in a diagnosis of basal cell carcinoma.

Optical Coherence Tomography

Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.39 Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.40 It can image boundaries of structures but cannot visualize individual cells.

There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.39 The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.40,41

Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.42 The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.43 Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.44 A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.45 Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.46

Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)49; the combination of OCT with other imaging modalities50,51; the use of OCT to delineate presurgical margins52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.54,55

Figure 3. A, A nonpolarized contact dermoscopy image of a nodular pigmented basal cell carcinoma showed large blue-gray ovoid nests, arborizing vessels, and small fine telangiectases. B, A microvascular en face dynamic optical coherence tomography image (size, 6×6 mm; depth, 300 µm) of the same lesion revealed circumscribed areas (asterisks) and branching/arborizing vessels (arrows). C, A cross-sectional optical coherence tomography image of the same lesion showed ovoid structures (asterisks) corresponding with tumor nests with dark peripheral borders and thinning of the epidermis above them.

Final Thoughts

In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.

References
  1. Benvenuto-Andrade C, Dusza SW, Agero AL, et al. Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions. Arch Dermatol. 2007;143:329-338.
  2. Terushkin V, Oliveria SA, Marghoob AA, et al. Use of and beliefs about total body photography and dermatoscopy among US dermatology training programs: an update. J Am Acad Dermatol. 2010;62:794-803.
  3. Morris JB, Alfonso SV, Hernandez N, et al. Use of and intentions to use dermoscopy among physicians in the United States. Dermatol Pract Concept. 2017;7:7-16.
  4. Yélamos O, Braun RP, Liopyris K, et al. Dermoscopy and dermatopathology correlates of cutaneous neoplasms. J Am Acad Dermatol. 2019;80:341-363.
  5. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  6. Carli P, de Giorgi V, Chiarugi A, et al. Addition of dermoscopy to conventional naked-eye examination in melanoma screening: a randomized study. J Am Acad Dermatol. 2004;50:683-668.
  7. Lallas A, Zalaudek I, Argenziano G, et al. Dermoscopy in general dermatology. Dermatol Clin. 2013;31:679-694.
  8. Reiter O, Mimouni I, Gdalvevich M, et al. The diagnostic accuracy of dermoscopy for basal cell carcinoma: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:1380-1388.
  9. Papageorgiou V, Apalla Z, Sotiriou E, et al. The limitations of dermoscopy: false-positive and false-negative tumours. J Eur Acad Dermatol Venereol. 2018;32:879-888.
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  11. Rajadhyaksha M, Grossman M, Esterowitz D, et al. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol. 1995;104:946-952.
  12. Kose K, Gou M, Yélamos O, et al. Automated video-mosaicking approach for confocal microscopic imaging in vivo: an approach to address challenges in imaging living tissue and extend field of view. Sci Rep. 2017;7:10759.
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  15. Jain M, Pulijal SV, Rajadhyaksha M, et al. Evaluation of bedside diagnostic accuracy, learning curve, and challenges for a novice reflectance confocal microscopy reader for skin cancer detection in vivo. JAMA Dermatol. 2018;154:962-965.
  16. Rao BK, Pellacani G. Atlas of Confocal Microscopy in Dermatology: Clinical, Confocal, and Histological Images. New York, NY: NIDIskin LLC; 2013.
  17. Scope A, Benvenuto-Andrande C, Agero AL, et al. In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: consensus terminology glossary and illustrative images. J Am Acad Dermatol. 2007;57:644-658.
  18. Gerger A, Hofmann-Wellenhof R, Langsenlehner U, et al. In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images. Br J Dermatol. 2008;158:329-333. 
  19. Stevenson AD, Mickan S, Mallett S, et al. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Dermatol Pract Concept. 2013;3:19-27.
  20. Alarcon I, Carrera C, Palou J, et al. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170:802-808.
  21. Lovatto L, Carrera C, Salerni G, et al. In vivo reflectance confocal microscopy of equivocal melanocytic lesions detected by digital dermoscopy follow-up. J Eur Acad Dermatol Venereol. 2015;29:1918-1925.
  22. Guitera P, Pellacani G, Longo C, et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Invest Dermatol. 2009;129:131-138.
  23. Xiong YQ, Ma SJ, Mo Y, et al. Comparison of dermoscopy and reflectance confocal microscopy for the diagnosis of malignant skin tumours: a meta-analysis. J Cancer Res Clin Oncol. 2017;143:1627-1635.
  24. Kadouch DJ, Schram ME, Leeflang MM, et al. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29:1890-1897.
  25. Dinnes J, Deeks JJ, Chuchu N, et al; Cochrane Skin Cancer Diagnostic Test Accuracy Group. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018;12:CD013191.
  26. Nguyen KP, Peppelman M, Hoogedoorn L, et al. The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review. Eur J Dermatol. 2016;26:549-565.
  27. Pellacani G, Ulrich M, Casari A, et al. Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology. J Eur Acad Dermatol Venereol. 2015;29:2216-2221.
  28. Manfredini M, Longo C, Ferrari B, et al. Dermoscopic and reflectance confocal microscopy features of cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2017;31:1828-1833.
  29. Hoogedoorn L, Peppelman M, van de Kerkhof PC, et al. The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: a systematic review. Br J Dermatol. 2015;172:1222-1248.
  30. Cinotti E, Perrot JL, Labeille B, et al. Reflectance confocal microscopy for cutaneous infections and infestations. J Eur Acad Dermatol Venereol. 2016;30:754-763.
  31. Ardigo M, Longo C, Gonzalez S; International Confocal Working Group Inflammatory Skin Diseases Project. Multicentre study on inflammatory skin diseases from The International Confocal Working Group: specific confocal microscopy features and an algorithmic method of diagnosis. Br J Dermatol. 2016;175:364-374.
  32. Ardigo M, Agozzino M, Franceschini C, et al. Reflectance confocal microscopy algorithms for inflammatory and hair diseases. Dermatol Clin. 2016;34:487-496.
  33. Manfredini M, Bettoli V, Sacripanti G, et al. The evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography [published online April 26, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15641.
  34. Navarrete-Dechent C, Mori S, Cordova M, et al. Reflectance confocal microscopy as a novel tool for presurgical identification of basal cell carcinoma biopsy site. J Am Acad Dermatol. 2019;80:e7-e8.
  35. Pan ZY, Lin JR, Cheng TT, et al. In vivo reflectance confocal microscopy of basal cell carcinoma: feasibility of preoperative mapping of cancer margins. Dermatol Surg. 2012;38:1945-1950.
  36. Venturini M, Gualdi G, Zanca A, et al. A new approach for presurgical margin assessment by reflectance confocal microscopy of basal cell carcinoma. Br J Dermatol. 2016;174:380-385.
  37. Sierra H, Yélamos O, Cordova M, et al. Reflectance confocal microscopy‐guided laser ablation of basal cell carcinomas: initial clinical experience. J Biomed Opt. 2017;22:1-13.
  38. Maier T, Kulichova D, Ruzicka T, et al. Noninvasive monitoring of basal cell carcinomas treated with systemic hedgehog inhibitors: pseudocysts as a sign of tumor regression. J Am Acad Dermatol. 2014;71:725-730.
  39. Levine A, Wang K, Markowitz O. Optical coherence tomography in the diagnosis of skin cancer. Dermatol Clin. 2017;35:465-488.
  40. Schneider SL, Kohli I, Hamzavi IH, et al. Emerging imaging technologies in dermatology: part I: basic principles. J Am Acad Dermatol. 2019;80:1114-1120.
  41. Mogensen M, Joergensen TM, Nümberg BM, et al. Assessment of optical coherence tomography imaging in the diagnosis of non‐melanoma skin cancer and benign lesions versus normal skin: observer‐blinded evaluation by dermatologists and pathologists. Dermatol Surg. 2009;35:965-972.
  42. Ferrante di Ruffano L, Dinnes J, Deeks JJ, et al. Optical coherence tomography for diagnosing skin cancer in adults. Cochrane Database Syst Rev. 2018;12:CD013189.
  43. Ulrich M, von Braunmuehl T, Kurzen H, et al. The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study. Br J Dermatol. 2015;173:428-435.
  44. Wessels R, de Bruin DM, Relyveld GM, et al. Functional optical coherence tomography of pigmented lesions. J Eur Acad Dermatol Venereol. 2015;29:738‐744.
  45. Gambichler T, Schmid-Wendtner MH, Plura I, et al. A multicentre pilot study investigating high‐definition optical coherence tomography in the differentiation of cutaneous melanoma and melanocytic naevi. J Eur Acad Dermatol Venereol. 2015;29:537‐541.
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  47. Boone MA, Suppa M, Dhaenens F, et al. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography. Arch Dermatol Res. 2016;308:7-20.
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  49. Themstrup L, Pellacani G, Welzel J, et al. In vivo microvascular imaging of cutaneous actinic keratosis, Bowen’s disease and squamous cell carcinoma using dynamic optical coherence tomography. J Eur Acad Dermatol Venereol. 2017;31:1655-1662.
  50. Alex A, Weingast J, Weinigel M, et al. Three-dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology. J Biophotonics. 2013;6:352-362.
  51. Iftimia N, Yélamos O, Chen CJ, et al. Handheld optical coherence tomography-reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins. J Biomed Opt. 2017;22:76006.
  52. Wang KX, Meekings A, Fluhr JW, et al. Optical coherence tomography-based optimization of Mohs micrographic surgery of basal cell carcinoma: a pilot study. Dermatol Surg. 2013;39:627-633.
  53. Chan CS, Rohrer TE. Optical coherence tomography and its role in Mohs micrographic surgery: a case report. Case Rep Dermatol. 2012;4:269-274.
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References
  1. Benvenuto-Andrade C, Dusza SW, Agero AL, et al. Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions. Arch Dermatol. 2007;143:329-338.
  2. Terushkin V, Oliveria SA, Marghoob AA, et al. Use of and beliefs about total body photography and dermatoscopy among US dermatology training programs: an update. J Am Acad Dermatol. 2010;62:794-803.
  3. Morris JB, Alfonso SV, Hernandez N, et al. Use of and intentions to use dermoscopy among physicians in the United States. Dermatol Pract Concept. 2017;7:7-16.
  4. Yélamos O, Braun RP, Liopyris K, et al. Dermoscopy and dermatopathology correlates of cutaneous neoplasms. J Am Acad Dermatol. 2019;80:341-363.
  5. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  6. Carli P, de Giorgi V, Chiarugi A, et al. Addition of dermoscopy to conventional naked-eye examination in melanoma screening: a randomized study. J Am Acad Dermatol. 2004;50:683-668.
  7. Lallas A, Zalaudek I, Argenziano G, et al. Dermoscopy in general dermatology. Dermatol Clin. 2013;31:679-694.
  8. Reiter O, Mimouni I, Gdalvevich M, et al. The diagnostic accuracy of dermoscopy for basal cell carcinoma: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:1380-1388.
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Issue
Cutis - 104(2)
Issue
Cutis - 104(2)
Page Number
108-113
Page Number
108-113
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MDedge Dermatology
Cutis
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MDedge Dermatology
Cutis
Topics
Melanoma
Nonmelanoma Skin Cancer
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Noninvasive Imaging Tools in Dermatology
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Noninvasive Imaging Tools in Dermatology
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Practice Points

  • There are several new noninvasive imaging tools in dermatology that can be utilized to aid in the diagnosis and management of skin disease, including dermoscopy, reflectance confocal microscopy, and optical coherence tomography.
  • Among these tools, there are several differences in cost, clinical integration, reimbursement, and accuracy.
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