Skip to main content

Reflectance Confocal Microscopy in Oncological Dermatology

  • Chapter
  • First Online:
Lasers in Dermatology and Medicine

Abstract

Imaging techniques capable of non-invasive, high-resolution, skin imaging in vivo have been the focus of recent attention in the dermatology field. These efforts are directed to improve the diagnostic accuracy of skin cancer, especially cutaneous melanoma. Reflectance-mode confocal microscopy (RCM) allows real time non-invasive histological imaging with cytological detail comparable to conventional histology of the skin when exploring cutaneous structures between the stratum corneum and the upper reticular dermis. RCM consists of a light source for illumination of a small spot within translucent tissue; and a point detector that detects back-scattered and reflected light though a pinhole. The pinhole prevents out-of-focus light from reaching the detector; as a result, only the optical plane in focus (confocal) is detected. Similar to dermoscopy images, real time images obtained by RCM are oriented horizontal to skin surface (optical transversal sections). Melanin provides strong contrast because of its high refractive index (1.7) relative to the surrounding epidermis; the melanosome size, similar to the near-infrared wavelengths (800–1064 nm), produces strong back scattering of the beam. Thus, cells containing melanin, such as pigmented keratinocytes, melanocytes, or melanophages, appear very bright when illuminated in this manner. Similarly, other organelles or cytoplasmic granules provide good contrast (albeit less intense than melanin), resulting in good imaging of cells containing them, such as Langerhans cells, lymphocytes, or cytoplasmic granules in keratinocytes at the stratum granulosum. Major confocal imaging criteria of pigmented lesions such as benign and malignant melanocytic tumors have been established. RCM imaging criteria of other skin cancers such as basal cell carcinoma, squamous cell carcinoma, oral cavity neoplasm, and mycosis fungoides have also been evaluated. RCM shows promise for: (1) guidance during biopsy collection; (2) monitoring histological architectural changes or dynamic process such as inflammatory response or capillary flow; (3) histological correlation with dermoscopic features; (4) monitoring of the response of a given lesion to treatment; and (5) demarcation of the extension of a lesion before proceeding to invasive treatments such as surgical excisions. The main limitation of RCM is its relatively low penetration through the dermis; currently, a maximum depth of 250–300 μm can be achieved, preventing imaging of structures located in deep dermis and hypodermis. The main challenge is the interpretation of images. Specific photographic atlas, courses and development of teledermatology may solve this problem.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.00
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Carli P, De Giorgi V, Soyer HP, Stante M, Mannone F, Giannotti B. Dermatoscopy in the diagnosis of pigmented skin lesions: a new semiology for the dermatologist. J Eur Acad Dermatol Venereol. 2000;14:353–69.

    CAS  PubMed  Google Scholar 

  2. Tearney GJ, Brezinski ME, Southern JF, Bouma BE, Hee MR, Fujimoto JG. Determination of the refractive index of highly scattering human tissue by optical coherence tomography. Opt Lett. 1995;20:2258–60.

    CAS  PubMed  Google Scholar 

  3. Mansotti L. Basic principles and advanced technical aspects of ultrasound imaging. In: Guzzardi R, editor. Physics and engineering of medical imaging. Boston: Martinus Nijhoff; 1987. p. 263–317.

    Google Scholar 

  4. Markisz J, Aquilia M. Technical magnetic resonance imaging. Stanford: Appleton & Lange; 1996.

    Google Scholar 

  5. Suihko C, Swindle LD, Thomas SG, Serup J. Fluorescence fibre-optic confocal microscopy of skin in vivo: microscope and fluorophores. Skin Res Technol. 2005;11:254–67.

    PubMed  Google Scholar 

  6. New KC, Petroll WM, Boyde A, Martin L, Corcuff P, Leveque JL, et al. In vivo imaging of human teeth and skin using real time confocal microscopy. Scanning. 1991;13:369–72.

    Google Scholar 

  7. Corcuff P, Leveque JL. In vivo vision of the human skin with the tandem scanning microscope. Dermatology. 1993;186:50–4.

    CAS  PubMed  Google Scholar 

  8. Rajadhyaksha M, Grossman M, Esterowitz D, Webb RH, Anderson RR. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol. 1995;104:946–52.

    CAS  PubMed  Google Scholar 

  9. Minsky M. Microscopy apparatus. US Patent No. 3013467, 1957.

    Google Scholar 

  10. Cavanagh HD, Jester JV, Essepian J, Shields W, Lemp MA. Confocal microscopy of the living eye. CLAO J. 1990;16:65–73.

    CAS  PubMed  Google Scholar 

  11. Jester JV, Andrews PM, Petroll WM, Lemp MA, Cavanagh HD. In vivo, real-time confocal imaging. J Electron Microsc Tech. 1991;18(1):50–60.

    CAS  PubMed  Google Scholar 

  12. Andrews PM, Petroll WM, Cavanagh HD, Jester JV. Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys. Am J Anat. 1991;191:95–102.

    CAS  PubMed  Google Scholar 

  13. Masters BR, Thaer AA. In vivo human corneal confocal microscopy of identical fields of subepithelial nerve plexus, basal epithelial, and wing cells at different times. Microsc Res Tech. 1994;29:350–6.

    CAS  PubMed  Google Scholar 

  14. Rajadhyaksha M, Gonzalez S, Zavislan JM, Anderson RR, Webb RH. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol. 1999;113:293–303.

    CAS  PubMed  Google Scholar 

  15. Gonzalez S, White WM, Rajadhyaksha M, Anderson RR, Gonzalez E. Confocal imaging of sebaceous gland hyperplasia in vivo to assess efficacy and mechanism of pulsed dye laser treatment. Lasers Surg Med. 1999;25:8–12.

    CAS  PubMed  Google Scholar 

  16. Gonzalez S, Sackstein R, Anderson RR, Rajadhyaksha M. Real-time evidence of in vivo leukocyte trafficking in human skin by reflectance confocal microscopy. J Invest Dermatol. 2001;117:384–6.

    CAS  PubMed  Google Scholar 

  17. Aghassi D, Anderson RR, Gonzalez S. Time-sequence histologic imaging of laser-treated cherry angiomas with in vivo confocal microscopy. J Am Acad Dermatol. 2000;43:37–41.

    CAS  PubMed  Google Scholar 

  18. Aghassi D, Gonzalez E, Anderson RR, Rajadhyaksha M, Gonzalez S. Elucidating the pulsed-dye laser treatment of sebaceous hyperplasia in vivo with real-time confocal scanning laser microscopy. J Am Acad Dermatol. 2000;43:49–53.

    CAS  PubMed  Google Scholar 

  19. Sánchez V, Cuevas J, Vañó-Galván S, González S. Laser for in vivo skin cancer diagnosis. Reflectance confocal microscopy. Dermatologic surgery. Hoboken, NJ: Wiley-Blackwell; 2012. p. 368–75.

    Google Scholar 

  20. González S, Sánchez V, González-Rodríguez A, Parrado C, Ullrich M. Patrones de microscopia confocal para el cáncer cutáneo no melanoma y aplicaciones clínicas. Actas Dermosifiliogr. 2014;105:446–58.

    PubMed  Google Scholar 

  21. Huzaira M, Rius F, Rajadhyaksha M, Anderson RR, Gonzalez S. Topographic variations in normal skin, as viewed by in vivo reflectance confocal microscopy. J Invest Dermatol. 2001;116:846–52.

    CAS  PubMed  Google Scholar 

  22. Gonzalez S, Tannous Z. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. J Am Acad Dermatol. 2002;47:869–74.

    PubMed  Google Scholar 

  23. Gonzalez S, Rajadhyaksha M, Anderson RR. Non-invasive (real-time) imaging of histologic margin of a proliferative skin lesion in vivo. J Invest Dermatol. 1998;111:538–9.

    CAS  PubMed  Google Scholar 

  24. Ulrich M, Lange-Asschenfeldt S, Gonzalez S. In vivo reflectance confocal microscopy for early diagnosis of nonmelanoma skin cancer. Actas Dermosifiliogr. 2012;103:784–9.

    CAS  PubMed  Google Scholar 

  25. Nori S, Rius-Diaz F, Cuevas J, Goldgeier M, Jaen P, Torres A, et al. Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study. J Am Acad Dermatol. 2004;51:923–30.

    PubMed  Google Scholar 

  26. Guitera P, Menzies SW, Longo C, Cesinaro AM, Scolyer RA, Pellacani G. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J Invest Dermatol. 2012;132:2386–94.

    CAS  PubMed  Google Scholar 

  27. Kadouch DJ, Schram ME, Leeflang MM, Limpens J, Spuls PI, de Rie MA. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29(10):1890–7.

    CAS  PubMed  Google Scholar 

  28. Gonzalez S, Gill M, Halpern A. Reflectance confocal microscopy of cutaneous tumors: an atlas with clinical, dermoscopic and histological correlations. London: Informa Healthcare; 2008.

    Google Scholar 

  29. Sanchez V, Ulrich M, Lange-Asschenfeldt S, Gonzalez S. Chapter 17: Reflectance confocal microscopy in skin cancer. In: Baldi A, Pasquali P, Spugnini EP, editors. Skin cancer: a practical approach. Current Clinical Pathology. New York: Humana Press; 2014.

    Google Scholar 

  30. Longo C, Lallas A, Kyrgidis A, Rabinovitz H, Moscarella E, Ciardo S, et al. Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy. J Am Acad Dermatol. 2014;71(4):716–24.

    PubMed  Google Scholar 

  31. Aghassi D, Anderson RR, Gonzalez S. Confocal laser microscopic imaging of actinic keratoses in vivo: a preliminary report. J Am Acad Dermatol. 2000;43:42–8.

    CAS  PubMed  Google Scholar 

  32. Pellacani G, Ulrich M, Casari A, Prow TW, Cannillo F, Benati, et al. Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology. J Eur Acad Dermatol Venereol. 2015;29(11):2216–21.

    CAS  PubMed  Google Scholar 

  33. Tan JM, Lambie D, Sinnya S, Sahebian A, Soyer HP, Prow TW, et al. Histopathology and reflectance confocal microscopy features of photodamaged skin and actinic keratosis. J Eur Acad Dermatol Venereol. 2016;30(11):1901–11.

    CAS  PubMed  Google Scholar 

  34. Ulrich M, Maltusch A, Rowert-Huber J, Gonzalez S, Sterry W, Stockfleth E, et al. Actinic keratoses: non-invasive diagnosis for field cancerisation. Br J Dermatol. 2007;156:13–7.

    PubMed  Google Scholar 

  35. Astner S, Ullrich M, Cuevas J, Gonzalez S. Squamous neoplasias. In: González S, Gill M, Halpern AC, editors. Reflectance confocal microscopy of cutaneous tumors: an atlas with clinical, dermoscopic and histological correlations. London: Informa Healthcare; 2008.

    Google Scholar 

  36. Moscarella E, Rabinovitz H, Zalaudek I, Piana S, Stanganelli I, Oliviero MC, et al. Dermoscopy and reflectance confocal microscopy of pigmented actinic keratoses: a morphological study. J Eur Acad Dermatol Venereol. 2015;29(2):307–14.

    CAS  PubMed  Google Scholar 

  37. Sanchez Yus E, Cros LA. Bowen’s disease and erythroplasia of Queyrat. Actas Dermosifiliogr. 1980;71:85–8.

    CAS  PubMed  Google Scholar 

  38. Alfaro-Rubio A, Nagore E, Serra C, Botella R, Sanmartin O, Requena C, et al. Perianal Bowen’s disease treated with imiquimod. Actas Dermosifiliogr. 2005;96:468–70.

    PubMed  Google Scholar 

  39. Ulrich M, Kanitakis J, Gonzalez S, Lange-Asschenfeldt S, Stockfleth E, Roewert-Huber J. Evaluation of Bowen disease by in vivo reflectance confocal microscopy. Br J Dermatol. 2012;166:451–3.

    CAS  PubMed  Google Scholar 

  40. Rishpon A, Kim N, Scope A, Porges L, Oliviero MC, Braun RP, et al. Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses. Arch Dermatol. 2009;145:766–72.

    PubMed  Google Scholar 

  41. Mancebo SE, Cordova M, Myskowski PL, Flores ES, Busam K, Jawed SI, et al. Reflectance confocal microscopy features of mycosis fungoides and Sézary syndrome: correlation with histopathologic and T-cell receptor rearrangement studies. J Cutan Pathol. 2016;43(6):505–15.

    PubMed  PubMed Central  Google Scholar 

  42. Longo C, Zalaudek I, Moscarella E, Lallas A, Piana S, Pellacani G, et al. Clonal seborrheic keratosis: dermoscopic and confocal microscopy characterization. J Eur Acad Dermatol Venereol. 2014;28(10):1397–400.

    CAS  PubMed  Google Scholar 

  43. Agero AL, Busam KJ, Benvenuto-Andrade C, Scope A, Gill M, Marghoob AA, et al. Reflectance confocal microscopy of pigmented basal cell carcinoma. J Am Acad Dermatol. 2006;54(4):638–43.

    PubMed  Google Scholar 

  44. Pellacani G, Guitera P, Longo C, Avramidis M, Seidenari S, Menzies S. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127:2759–65.

    CAS  PubMed  Google Scholar 

  45. Longo C, Fantini F, Cesinaro AM, Bassoli S, Seidenari S, Pellacani G. Pigmented mammary Paget disease: dermoscopic, in vivo reflectance-mode confocal microscopic, and immunohistochemical study of a case. Arch Dermatol. 2007;143:752–4.

    PubMed  Google Scholar 

  46. Guitera P, Scolyer RA, Gill M, Akita H, Arima M, Yokoyama Y, et al. Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol. 2013;27:e24–9.

    CAS  PubMed  Google Scholar 

  47. Richtig E, Ahlgrimm-Siess V, Arzberger E, Hofmann-Wellenhof R. Noninvasive differentiation between mamillary eczema and Paget disease by in vivo reflectance confocal microscopy on the basis of two case reports. Br J Dermatol. 2011;165:440–1.

    CAS  PubMed  Google Scholar 

  48. Pan ZY, Liang J, Zhang QA, Lin JR, Zheng ZZ. In vivo reflectance confocal microscopy of extramammary Paget disease: diagnostic evaluation and surgical management. J Am Acad Dermatol. 2012;66:e47–53.

    PubMed  Google Scholar 

  49. Terrier JE, Tiffet O, Raynaud N, Cinotti E. In vivo reflectance confocal microscopy combined with the “spaghetti” technique: a new procedure for defining surgical margins of genital Paget disease. Dermatol Surg. 2015;41(7):862–4.

    CAS  PubMed  Google Scholar 

  50. Langley RG, Rajadhyaksha M, Dwyer PJ, Sober AJ, Flotte TJ, Anderson RR. Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo. J Am Acad Dermatol. 2001;45:365–76.

    CAS  PubMed  Google Scholar 

  51. Busam KJ, Charles C, Lee G, Halpern AC. Morphologic features of melanocytes, pigmented keratinocytes, and melanophages by in vivo confocal scanning laser microscopy. Mod Pathol. 2001;14:862–8.

    CAS  PubMed  Google Scholar 

  52. Pellacani G, Cesinaro AM, Longo C, Grana C, Seidenari S. Microscopic in vivo description of cellular architecture of dermoscopic pigment network in nevi and melanomas. Arch Dermatol. 2005;141:147–54.

    PubMed  Google Scholar 

  53. Pellacani G, Cesinaro AM, Seidenari S. In vivo assessment of melanocytic nests in nevi and melanomas by reflectance confocal microscopy. Mod Pathol. 2005;18:469–74.

    PubMed  Google Scholar 

  54. Pellacani G, Cesinaro AM, Seidenari S. In vivo confocal reflectance microscopy for the characterization of melanocytic nests and correlation with dermoscopy and histology. Br J Dermatol. 2005;152:384–6.

    CAS  PubMed  Google Scholar 

  55. Puig S, Di Giacomo TB, Serra D, Cabrini F, Alos L, Palou J, et al. Reflectance confocal microscopy of blue nevus. Eur J Dermatol. 2012;22:552–3.

    PubMed  Google Scholar 

  56. Hoffman-Wellenhof R, Pellacani G, Malvehy J, Soyer HP. Reflectance confocal microscopy for skin diseases. London: Springer; 2012.

    Google Scholar 

  57. Lovatto L, Carrera C, Salerni G, Alós L, Malvehy J, Puig S. In vivo reflectance confocal microscopy of equivocal melanocytic lesions detected by digital dermoscopy follow-up. J Eur Acad Dermatol Venereol. 2015;29(10):1918–25.

    CAS  PubMed  Google Scholar 

  58. Pellacani G, Cesinaro AM, Grana C, Seidenari S. In vivo confocal scanning laser microscopy of pigmented Spitz nevi: comparison of in vivo confocal images with dermoscopy and routine histopathology. J Am Acad Dermatol. 2004;51:371–6.

    PubMed  Google Scholar 

  59. Pellacani G, Longo C, Ferrara G, Cesinaro AM, Bassoli S, Guitera P, et al. Spitz nevi: in vivo confocal microscopic features, dermatoscopic aspects, histopathologic correlates, and diagnostic significance. J Am Acad Dermatol. 2009;60:236–47.

    PubMed  Google Scholar 

  60. Guida S, Pellacani G, Cesinaro AM, Moscarella E, Argenziano G, Farnetani F, et al. Spitz naevi and melanomas with similar dermoscopic patterns: can confocal microscopy differentiate? Br J Dermatol. 2016;174(3):610–6.

    CAS  PubMed  Google Scholar 

  61. Gerger A, Koller S, Weger W, Richtig E, Kerl H, Samonigg H, et al. Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors. Cancer. 2006;107:193–200.

    PubMed  Google Scholar 

  62. Pellacani G, Cesinaro AM, Seidenari S. Reflectance-mode confocal microscopy of pigmented skin lesions—improvement in melanoma diagnostic specificity. J Am Acad Dermatol. 2005;53:979–85.

    PubMed  Google Scholar 

  63. Pellacani G, Cesinaro AM, Seidenari S. Reflectance-mode confocal microscopy for the in vivo characterization of pagetoid melanocytosis in melanomas and nevi. J Investig Dermatol. 2005;125:532–7.

    CAS  PubMed  Google Scholar 

  64. Gonzalez S, Gonzalez E, White WM, Rajadhyaksha M, Anderson RR. Allergic contact dermatitis: correlation of in vivo confocal imaging to routine histology. J Am Acad Dermatol. 1999;40:708–13.

    CAS  PubMed  Google Scholar 

  65. Segura S, Puig S, Carrera C, Palou J, Malvehy J. Development of a two-step method for the diagnosis of melanoma by reflectance confocal microscopy. J Am Acad Dermatol. 2009;61:216–29.

    PubMed  Google Scholar 

  66. Pellacani G, Farnetani F, Gonzalez S, Longo C, Cesinaro AM, Casari A, et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. 2012;66:e109–21.

    PubMed  Google Scholar 

  67. Guitera P, Pellacani G, Crotty KA, Scolyer RA, Li LX, Bassoli S, et al. The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. J Invest Dermatol. 2010;130:2080–91.

    CAS  PubMed  Google Scholar 

  68. Losi A, Longo C, Cesinaro AM, Benati E, Witkowski A, Guitera P, et al. Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy. Br J Dermatol. 2014;171(1):48–54.

    CAS  PubMed  Google Scholar 

  69. Scope A, Mahmood U, Gareau DS, Kenkre M, Lieb JA, Nehal KS, et al. In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins. Br J Dermatol. 2010;163:1218–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Curiel-Lewandrowski C, Williams CM, Swindells KJ, Tahan SR, Astner S, Frankenthaler RA, et al. Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches. Arch Dermatol. 2004;140:1127–32.

    PubMed  Google Scholar 

  71. Busam KJ, Hester K, Charles C, Sachs DL, Antonescu CR, Gonzalez S, et al. Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy. Arch Dermatol. 2001;137:923–9.

    CAS  PubMed  Google Scholar 

  72. Scope A, Gill M, Benveuto-Andrade C, Halpern AC, Gonzalez S, Marghoob AA. Correlation of dermoscopy with in vivo reflectance confocal microscopy of streaks in melanocytic lesions. Arch Dermatol. 2007;143:727–34.

    PubMed  Google Scholar 

  73. Pellacani G, Pepe P, Casari A, Longo C. Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study. Br J Dermatol. 2014;171(5):1044–51.

    CAS  PubMed  Google Scholar 

  74. Tannous Z, Al-Arashi M, Shah S, Yaroslavsky AN. Delineating melanoma using multimodal polarized light imaging. Lasers Surg Med. 2009;41:10–6.

    PubMed  Google Scholar 

  75. Rajadhyaksha M, Menaker G, Flotte T, Dwyer PJ, Gonzalez S. Confocal examination of nonmelanoma cancers in thick skin excisions to potentially guide mohs micrographic surgery without frozen histopathology. J Invest Dermatol. 2001;117:1137–43.

    CAS  PubMed  Google Scholar 

  76. Tannous Z, Torres A, Gonzalez S. In vivo real-time confocal reflectance microscopy: a noninvasive guide for Mohs micrographic surgery facilitated by aluminum chloride, an excellent contrast enhancer. Dermatol Surg. 2003;29:839–46.

    PubMed  Google Scholar 

  77. Chung VQ, Dwyer PJ, Nehal KS, Rajadhyaksha M, Menaker GM, Charles C, et al. Use of ex vivo confocal scanning laser microscopy during Mohs surgery for nonmelanoma skin cancers. Dermatol Surg. 2004;30:1470–8.

    PubMed  Google Scholar 

  78. Flores ES, Cordova M, Kose K, Phillips W, Rossi A, Nehal K, et al. Intraoperative imaging during Mohs surgery with reflectance confocal microscopy: initial clinical experience. J Biomed Opt. 2015;20(6):61103.

    PubMed  Google Scholar 

  79. Guitera P, Moloney FJ, Menzies SW, Stretch JR, Quinn MJ, Hong A, et al. Improving management and patient care in lentigo maligna by mapping with in vivo confocal microscopy. JAMA Dermatol. 2013;149(6):692–8.

    PubMed  Google Scholar 

  80. Morton CA, McKenna KE, Rhodes LE, British Association of Dermatologists Therapy G, Audit S, The British Photodermatology G. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008;159:1245–66.

    CAS  PubMed  Google Scholar 

  81. Segura S, Puig S, Carrera C, Lecha M, Borges V, Malvehy J. Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: a role for confocal microscopy and photodynamic therapy. J Eur Acad Dermatol Venereol. 2011;25:819.

    CAS  PubMed  Google Scholar 

  82. Venturini M, Sala R, Gonzàlez S, Calzavara-Pinton PG. Reflectance confocal microscopy allows in vivo real-time noninvasive assessment of the outcome of methyl aminolaevulinate photodynamic therapy of basal cell carcinoma. Br J Dermatol. 2013;168(1):99–105.

    CAS  PubMed  Google Scholar 

  83. Szeimies RM, Radny P, Sebastian M, Borrosch F, Dirschka T, Krahn-Senftleben G, et al. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study. Br J Dermatol. 2010;163:386–94.

    PubMed  Google Scholar 

  84. Padilla RS, Sebastian S, Jiang Z, Nindl I, Larson R. Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression. Arch Dermatol. 2010;146:288–93.

    CAS  PubMed  Google Scholar 

  85. Astner S, Swindells K, González S, Stockfleth E, Lademann J. Confocal microscopy: innovative diagnostic tools for monitoring of noninvasive therapy in cutaneous malignancies. Drug Discov Today. 2008;5:e81–91.

    Google Scholar 

  86. Seyed Jafari SM, Timchik T, Hunger RE. In vivo confocal microscopy efficacy assessment of daylight photodynamic therapy in actinic keratosis patients. Br J Dermatol. 2016;175(2):375–81.

    CAS  PubMed  Google Scholar 

  87. Goldgeier M, Fox CA, Zavislan JM, Harris D, Gonzalez S. Noninvasive imaging, treatment, and microscopic confirmation of clearance of basal cell carcinoma. Dermatol Surg. 2003;29:205–10.

    PubMed  Google Scholar 

  88. Torres A, Niemeyer A, Berkes B, Marra D, Schanbacher C, Gonzalez S, et al. 5% imiquimod cream and reflectance-mode confocal microscopy as adjunct modalities to Mohs micrographic surgery for treatment of basal cell carcinoma. Dermatol Surg. 2004;30:1462–9.

    PubMed  Google Scholar 

  89. Ulrich M, Krueger-Corcoran D, Roewert-Huber J, Sterry W, Stockfleth E, Astner S. Reflectance confocal microscopy for noninvasive monitoring of therapy and detection of subclinical actinic keratoses. Dermatology. 2010;220:15–24.

    CAS  PubMed  Google Scholar 

  90. Nadiminti H, Scope A, Marghoob AA, Busam K, Nehal KS. Use of reflectance confocal microscopy to monitor response of lentigo maligna to nonsurgical treatment. Dermatol Surg. 2010;36:177–84.

    CAS  PubMed  Google Scholar 

  91. Garcia MS, Ono Y, Martinez SR, Chen SL, Goodarzi H, Phan T, et al. Complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream. Melanoma Res. 2011;21:235–43.

    CAS  PubMed  Google Scholar 

  92. Turza K, Dengel LT, Harris RC, Patterson JW, White K, Grosh WW, et al. Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis. J Cutan Pathol. 2010;37:94–8.

    PubMed  Google Scholar 

  93. Ahlgrimm-Siess V, Hofmann-Wellenhof R, Cao T, Oliviero M, Scope A, Rabinovitz HS. Reflectance confocal microscopy in the daily practice. Semin Cutan Med Surg. 2009;28:180–9.

    CAS  PubMed  Google Scholar 

  94. Guitera P, Haydu LE, Menzies SW, Scolyer RA, Hong A, Fogarty GB, et al. Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors. Br J Dermatol. 2014;170(6):1305–12.

    CAS  PubMed  Google Scholar 

  95. Alarcon I, Carrera C, Alos L, Palou J, Malvehy J, Puig S. In vivo reflectance confocal microscopy to monitor the response of lentigo maligna to imiquimod. J Am Acad Dermatol. 2014;71(1):49–55.

    CAS  PubMed  Google Scholar 

  96. Richtig E, Ahlgrimm-Siess V, Koller S, Gerger A, Horn M, Smolle J, et al. Follow-up of actinic keratoses after shave biopsy by in-vivo reflectance confocal microscopy – a pilot study. J Eur Acad Dermatol Venereol. 2010;24:293–8.

    CAS  PubMed  Google Scholar 

  97. Ahlgrimm-Siess V, Horn M, Koller S, Ludwig R, Gerger A, Hofmann-Wellenhof R. Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in vivo reflectance confocal microscopy: a preliminary study. J Dermatol Sci. 2009;53:60–4.

    PubMed  Google Scholar 

  98. Ulrich M, Gonzalez S, Lange-Asschenfeldt B, Roewert-Huber J, Sterry W, Stockfleth E, et al. Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy. J Eur Acad Dermatol Venereol. 2011;25:276–84.

    CAS  PubMed  Google Scholar 

  99. Malvehy J, Roldán-Marín R, Iglesias-García P, Díaz A, Puig S. Monitoring treatment of field cancerisation with 3% diclofenac sodium 2.5% hyaluronic acid by reflectance confocal microscopy: a histologic correlation. Acta Derm Venereol. 2015;95(1):45–50.

    CAS  PubMed  Google Scholar 

  100. Sierra H, Larson BA, Chen CS, Rajadhyaksha M. Confocal microscopy to guide erbium:yttrium aluminum garnet laser ablation of basal cell carcinoma: an ex vivo feasibility study. J Biomed Opt. 2013;18(9):095001.

    PubMed  PubMed Central  Google Scholar 

  101. Sierra H, Cordova M, Chen CS, Rajadhyaksha M. Confocal imaging-guided laser ablation of basal cell carcinomas: an ex vivo study. J Invest Dermatol. 2015;135(2):612–5.

    CAS  PubMed  Google Scholar 

  102. Hibler BP, Sierra H, Cordova M, Phillips W, Rajadhyaksha M, Nehal KS, et al. Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof-of-principle pilot study. Br J Dermatol. 2016;174(6):1359–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Izatt JA, Kulkarni MD, Hsing-Wen W, Kobayashi K, Sivak MV Jr. Optical coherence tomography and microscopy in gastrointestinal tissues. IEEE J Sel Top Quantum Electron. 1996;2:1017–28.

    CAS  Google Scholar 

  104. Vargas G, Chan KF, Thomsen SL, Welch AJ. Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin. Lasers Surg Med. 2001;29:213–20.

    CAS  PubMed  Google Scholar 

  105. Rajadhyaksha M, Gonzalez S, Zavislan JM. Detectability of contrast agents for confocal reflectance imaging of skin and microcirculation. J Biomed Opt. 2004;9:323–31.

    CAS  PubMed  Google Scholar 

  106. Gruber MJ, Wackernagel A, Richtig E, Koller S, Kerl H, Smolle J. Digital image enhancement for in vivo laser scanning microscopy. Skin Res Technol. 2005;11:248–53.

    PubMed  Google Scholar 

  107. Ono I, Sakemoto A, Ogino J, Kamiya T, Yamashita T, Jimbow K. The real-time, three-dimensional analyses of benign and malignant skin tumors by confocal laser scanning microscopy. J Dermatol Sci. 2006;43:135–41.

    PubMed  Google Scholar 

Download references

Acknowledgements

This work has been partially supported by a grant from Ministerio de Economía y Competitividad of Spain (Instituto de Salud Carlos III, PI15/00974 financed jointly by the European Regional Development Funds, FEDER). S.G. also plays a role of Consultant for Caliber I.D., the manufacturer of the comercial reflectance confocal system.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Salvador González .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Serrano, P.FC., Segurado-Miravalles, G., González, S. (2018). Reflectance Confocal Microscopy in Oncological Dermatology. In: Nouri, K. (eds) Lasers in Dermatology and Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-76118-3_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-76118-3_22

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-76116-9

  • Online ISBN: 978-3-319-76118-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics