Reflectance Confocal Microscopy for the Diagnosis and Management of Skin Diseases

  • Radhika SrivastavaEmail author
  • Catherine Reilly
  • Babar Rao


Reflectance Confocal Microscopy (RCM) is a noninvasive imaging modality that captures horizontal greyscale images of the skin at cellular resolution. RCM can be used to in the diagnosis and management of numerous dermatologic diseases, encompassing both neoplastic and inflammatory conditions, with high accuracy when compared to traditional histopathology.


Reflectance Confocal Microscopy Squamous Cell Carcinoma Basal Cell Carcinoma Psoriasis Cutaneous infections Melanoma, Melanocytic Nevi 


  1. 1.
    Minsky M. Memoir on inventing the confocal scanning microscope. Scanning. 1988;10:128–38.CrossRefGoogle Scholar
  2. 2.
    Rajadhyaksha M, González 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(3):293–303.CrossRefGoogle Scholar
  3. 3.
    Current Procedural Terminology, Professional Edition. Chicago IL: American Medical Association; 2016. The preliminary physician fee schedule for 2017 is available at
  4. 4.
    Yamashita T, Kuwahara T, González S, Takahashi M. Non-invasive visualization of melanin and melanocytes by reflectance-mode confocal microscopy. J Invest Dermatol. 2005;124(1):235–40.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Rajadhyaksha M, Grossman M, Esterowitz D, Webb HR, Anderson RR. In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol. 1995;104(6):946–52.CrossRefGoogle Scholar
  6. 6.
    Rao BK, Pellacani G. Atlas of confocal microscopy in dermatology: clinical, confocal, and histological images. New York: NIDIskin LLC; 2013.Google Scholar
  7. 7.
    Scope A, et al. In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: consensus terminology glossary and illustrative images. J Am Acad Dermatol. 2007;57(4):644–58.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Pellacani G, et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127(12):2759–65.PubMedCrossRefGoogle Scholar
  9. 9.
    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(2):216–29.PubMedCrossRefGoogle Scholar
  10. 10.
    Guitera P, et al. 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(10):2386–94.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Pellacani G, et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. 2012;66(3):e109–21.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Pellacani G, et al. Towards an in vivo morphologic classification of melanocytic nevi. J Eur Acad Dermatol Venereol. 2014;28(7):864–72.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    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(8):2080–91.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    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(2):329–33.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Stevenson AD, Mickan S, Mallett S, Ayya M. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Dermatol Pract Concept. 2013;3(4):19–27.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Alarcon I, Carrera C, Palou J, Alos L, Malvehy J, Puig S. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170(4):802–8.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Guitera P, et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Invest Dermatol. 2009;129(1):131–8.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Xiong YQ, 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(9):1627–35.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Rao BK, Mateus R, Wassef C, Pellacani G. In vivo confocal microscopy in clinical practice: comparison of bedside diagnostic accuracy of a trained physician and distant diagnosis of an expert reader. J Am Acad Dermatol. 2013;69(6):e295–300.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Guitera P, et al. Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions. Br J Dermatol. 2016;175(6):1311–9.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Pellacani G, et al. The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology. J Eur Acad Dermatol Venereol. 2018;32(10):1687–94.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Yélamos O, et al. Correlation of handheld reflectance confocal microscopy with radial video mosaicing for margin mapping of lentigo maligna and lentigo maligna melanoma. JAMA Dermatol. 2017;153(12):1278–84.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Champin J, et al. In vivo reflectance confocal microscopy to optimize the spaghetti technique for defining surgical margins of lentigo maligna. Dermatol Surg. 2014;40(3):247–56.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Waddell A, Star P, Guitera P. Advances in the use of reflectance confocal microscopy in melanoma. Melanoma Manag. 2018;5(1):MMT04.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    González S, Tannous Z. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. J Am Acad Dermatol. 2002;47(6):869–74.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Navarrete-Dechent C, et al. Reflectance confocal microscopy terminology glossary for nonmelanocytic skin lesions: a systematic review. J Am Acad Dermatol. 2019;80:1414–27.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Ahlgrimm-Siess V, et al. Confocal microscopy in skin cancer. Curr Dermatol Rep. 2018;7(2):105–18.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Kadouch DJ, et al. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy. J Eur Acad Dermatol Venereol. 2015;29(10):1890–7.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Longo C, et al. Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy. J Am Acad Dermatol. 2014;71(4):716–724.e1.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Navarrete-Dechent C, Mori S, Cordova M, Nehal KS. Reflectance confocal microscopy as a novel tool for presurgical identification of basal cell carcinoma biopsy site. J Am Acad Dermatol. 2019;80(1):e7–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Pan ZY, Lin JR, Cheng TT, Wu JQ, Wu WY. In vivo reflectance confocal microscopy of Basal cell carcinoma: feasibility of preoperative mapping of cancer margins. Dermatol Surg. 2012;38(12):1945–50.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Venturini M, Gualdi G, Zanca A, Lorenzi L, Pellacani G, Calzavara-Pinton PG. A new approach for presurgical margin assessment by reflectance confocal microscopy of basal cell carcinoma. Br J Dermatol. 2016;174:380–5.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Sierra H, Yélamos O, Cordova M, Chen CJ, Rajadhyaksha M. Reflectance confocal microscopy-guided laser ablation of basal cell carcinomas: initial clinical experience. J Biomed Opt. 2017;22:1–13.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Maier T, Kulichova D, Ruzicka T, Berking C. Noninvasive monitoring of basal cell carcinomas treated with systemic hedgehog inhibitors: pseudocysts as a sign of tumor regression. J Am Acad Dermatol. 2014;71(4):725–30.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Dinnes J, et al. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018;12:CD013191.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Nguyen KP, Peppelman M, Hoogedoorn L, Van Erp PE, Gerritsen MP. 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(6):549–65.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Francisco G, et al. No wonder it itches: quick bedside visualization of a scabies infestation using reflectance confocal microscopy. J Cutan Pathol. 2018;45(12):877–9.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Cinotti E, Perrot J-L, Labeille B, Cambazard F. On the feasibility of confocal microscopy for the diagnosis of scabies. Ann Dermatol Venereol. 2013;140:215–6.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Hoogedoorn L, Peppelman M, van de Kerkhof PC, van Erp PE, Gerritsen MJ. 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(5):1222–48.PubMedCrossRefGoogle Scholar
  41. 41.
    Cinotti E, Perrot JL, Labeille B, Cambazard F. Reflectance confocal microscopy for cutaneous infections and infestations. J Eur Acad Dermatol Venereol. 2016;30(5):754–63.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Ruini C, Sattler E, Hartmann D, Reinholz M, Ruzicka T, von Braunmühl T. Monitoring structural changes in Demodex mites under topical Ivermectin in rosacea by means of reflectance confocal microscopy: a case series. J Eur Acad Dermatol Venereol. 2017;31(6):e299–301.PubMedCrossRefGoogle Scholar
  43. 43.
    Pharaon M, Gari-Toussaint M, Khemis A, et al. Diagnosis and treatment monitoring of toenail onychomycosis by reflectance confocal microscopy: prospective cohort study in 58 patients. J Am Acad Dermatol. 2014;71:56–61.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Hui D, Xue-cheng S, Ai-e X. Evaluation of reflectance confocal microscopy in dermatophytosis. Mycoses. 2013;56:130–3.PubMedCrossRefGoogle Scholar
  45. 45.
    Lacarrubba F, Verzì AE, Pippione M, Micali G. Reflectance confocal microscopy in the diagnosis of vesicobullous disorders: case series with pathologic and cytologic correlation and literature review. Skin Res Technol. 2016;22(4):479–86.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Debarbieux S, Depaepe L, Poulalhon N, Dalle S, Balme B, Thomas L. Reflectance confocal microscopy characteristics of eight cases of pustular eruptions and histopathological correlations. Skin Res Technol. 2013;19(1):e444–52.PubMedCrossRefGoogle Scholar
  47. 47.
    Goldgeier M, Alessi C, Muhlbauer JE. Immediate noninvasive diagnosis of herpesvirus by confocal scanning laser microscopy. J Am Acad Dermatol. 2002;46(5):783–5.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Scope A, Benvenuto-Andrade C, Gill M, Ardigo M, Gonzalez S, Marghoob AA. Reflectance confocal microscopy of molluscum contagiosum. Arch Dermatol. 2008;144:34.Google Scholar
  49. 49.
    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(2):364–74.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Ardigo M, Agozzino M, Franceschini C, Lacarrubba F. Reflectance confocal microscopy algorithms for inflammatory and hair diseases. Dermatol Clin. 2016;34(4):487–96.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Iftimia N, et al. Combined reflectance confocal microscopy/optical coherence tomography imaging for skin burn assessment. Biomed Opt Express. 2013;4(5):680–95.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Altintas AA, et al. To heal or not to heal: predictive value of in vivo reflectance-mode confocal microscopy in assessing healing course of human burn wounds. J Burn Care Res. 2009;30(6):1007–12.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Srivastava R, Reilly C, Francisco GM, Bhatti H, Rao BK. Life of a wound: serial documentation of wound healing after shave removal using reflectance confocal microscopy. J Drugs Dermatol. 2019;18(5):217–9.Google Scholar
  54. 54.
    Cameli N, Mariano M, Serio M, Ardigò M. Preliminary comparison of fractional laser with fractional laser plus radiofrequency for the treatment of acne scars and photoaging. Dermatol Surg. 2014;40(5):553–61.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Stumpp OF, Bedi VP, Wyatt D, Lac D, et al. In vivo confocal imaging of epidermal cell migration and dermal changes post nonablative fractional resurfacing: study of the wound healing process with corroborated histopathologic evidence. J Biomed Opt. 2009;14(2):024018.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Terhorst D, Maltusch A, Stockfleth E, Lange-Asschenfeldt S, et al. Reflectance confocal microscopy for the evaluation of acute epidermal wound healing. Wound Repair Regen. 2011;19(6):671–9.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Lange-Asschenfeldt S, Bob A, Terhorst D, Ulrich M, et al. Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing. J Biomed Opt. 2012;17(7):076016.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Rajadhyaksha M, Marghoob A, Rossi A, Halpern AC, Nehal KS. Reflectance confocal microscopy of skin in vivo: from bench to bedside. Lasers Surg Med. 2017;49(1):7–19.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Rao BK, John AM, Francisco G, Haroon A. Diagnostic accuracy of reflectance confocal microscopy skin. Arch Pathol Lab Med. 2019;143:326–9.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Hashemi P, et al. Langerhans cells and melanocytes share similar morphologic features under in vivo reflectance confocal microscopy: a challenge for melanoma diagnosis. J Am Acad Dermatol. 2012;66(3):452–62. Scholar
  61. 61.
    Jain M, Pulijal SV, Rajadhyaksha M, Halpern AC, Gonzalez S. 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(8):962–5.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Radhika Srivastava
    • 1
    Email author
  • Catherine Reilly
    • 1
  • Babar Rao
    • 1
  1. 1.Center for DermatologyRutgers Robert Wood Johnson Medical SchoolSomersetUSA

Personalised recommendations