In Vivo Reflectance Confocal Microscopy for Melanoma

  • Marco Campoli
  • Jean Luc Perrot
  • Elisa Cinotti


Cutaneous melanoma includes a heterogeneous subset of malignant melanocytic proliferations that differ significantly in their epidemiology, morphology, growth dynamics, genetics, and clinical behavior. Reflectance confocal microscopy (RCM) is well suited to image melanocytic lesions because melanin acts as a naturally occurring “endogenous” contrast. RCM evaluation has the potential to increase sensitivity (improves melanoma detection) and specificity (reduces excisions of benign lesions) for melanoma. In fact, the use of RCM allows to highlight useful microscopic features.


Reflectance confocal microscopy Dermoscopy Melanoma Melanocytic Diagnosis and malignant 


  1. 1.
    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.PubMedGoogle Scholar
  2. 2.
    Rajadhyaksha M, González S, Zavislan JM, Rox Anderson R, Webb RH. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with Histology11The authors have declared conflict of interest. J Investig Dermatol. 1999;113:293–303.PubMedGoogle Scholar
  3. 3.
    Longo C, et al. Is confocal microscopy a valuable tool in diagnosing nodular lesions? A study of 140 cases. Br J Dermatol. 2013;169:58–67.PubMedGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Yamashita T, Kuwahara T, González S, Takahashi M. Non-invasive visualization of melanin and melanocytes by reflectance-mode confocal microscopy. J Investig Dermatol. 2005;124:235–40.PubMedGoogle Scholar
  6. 6.
    Stanganelli I, et al. Integration of reflectance confocal microscopy in sequential dermoscopy follow-up improves melanoma detection accuracy. Br J Dermatol. 2015;172:365–71.PubMedGoogle Scholar
  7. 7.
    Ferrari B, et al. Dermoscopic difficult lesions: an objective evaluation of reflectance confocal microscopy impact for accurate diagnosis. J Eur Acad Dermatol Venereol. 2015;29:1135–40.PubMedGoogle Scholar
  8. 8.
    Alarcon I, et al. Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions. Br J Dermatol. 2014;170:802–8.PubMedPubMedCentralGoogle Scholar
  9. 9.
    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;171:1044–51.PubMedGoogle Scholar
  10. 10.
    Guitera P, et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Investig Dermatol. 2009;129:131–8.PubMedGoogle Scholar
  11. 11.
    Pellacani G, et al. Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma. J Eur Acad Dermatol Venereol. 2016;30:413–9.PubMedGoogle Scholar
  12. 12.
    Waddell A, Star P, Guitera P. Advances in the use of reflectance confocal microscopy in melanoma. Melanoma Management. 2018;5:MMT04.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Longo C, Pellacani G. Melanomas. Dermatol Clin. 2016;34:411–9.PubMedGoogle Scholar
  14. 14.
    Cicchiello M, Lin MJ, Pan Y, McLean C, Kelly JW. An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma: pathways for diagnosis of NM versus SSM. Australas J Dermatol. 2016;57:97–101.PubMedGoogle Scholar
  15. 15.
    Moloney FJ, Menzies SW. Key points in the dermoscopic diagnosis of hypomelanotic melanoma and nodular melanoma: Dermoscopy of amelanotic and nodular melanoma. J Dermatol. 2011;38:10–5.PubMedGoogle Scholar
  16. 16.
    Segura S, et al. In vivo microscopic features of nodular melanomas: dermoscopy, confocal microscopy, and Histopathologic correlates. Arch Dermatol. 2008;144(10):1311–20.PubMedGoogle Scholar
  17. 17.
    Lallas A, et al. Diagnosis and management of facial pigmented macules. Clin Dermatol. 2014;32:94–100.PubMedGoogle Scholar
  18. 18.
    Cinotti E, et al. Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna. J Eur Acad Dermatol Venereol. 2018;32:1284–91.PubMedGoogle Scholar
  19. 19.
    Star P, Guitera P. Lentigo Maligna, macules of the face, and lesions on sun-damaged skin. Dermatol Clin. 2016;34:421–9.PubMedGoogle Scholar
  20. 20.
    Guitera P, 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 Investig Dermatol. 2010;130:2080–91.PubMedGoogle Scholar
  21. 21.
    Langley RGB, Burton E, Walsh N, Propperova I, Murray SJ. In vivo confocal scanning laser microscopy of benign lentigines: comparison to conventional histology and in vivo characteristics of lentigo maligna. J Am Acad Dermatol. 2006;55:88–97.PubMedGoogle Scholar
  22. 22.
    Ahlgrimm-Siess V, et al. Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study. Br J Dermatol. 2009;161:1307–16.PubMedGoogle Scholar
  23. 23.
    Tannous ZS, Mihm MC, Flotte TJ, González S. In vivo examination of lentigo maligna and malignant melanoma in situ, lentigo maligna type by near-infrared reflectance confocal microscopy: comparison of in vivo confocal images with histologic sections. J Am Acad Dermatol. 2002;46:260–3.PubMedGoogle Scholar
  24. 24.
    Guitera P, et al. Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors. Br J Dermatol. 2014;170:1305–12.PubMedGoogle Scholar
  25. 25.
    Guitera P, et al. Improving management and patient Care in Lentigo Maligna by mapping with in vivo confocal microscopy. JAMA Dermatol. 2013;149:692.PubMedGoogle Scholar
  26. 26.
    Reed JA, Shea CR. Lentigo maligna: melanoma in situ on chronically sun-damaged skin. Arch Pathol Lab Med. 2011;135:838–41.PubMedGoogle Scholar
  27. 27.
    Phan A, et al. Acral lentiginous melanoma: histopathological prognostic features of 121 cases. Br J Dermatol. 2007;157:311–8.PubMedGoogle Scholar
  28. 28.
    Cinotti E, et al. Reflectance confocal microscopy features of acral lentiginous melanoma: a comparative study with acral nevi. J Eur Acad Dermatol Venereol. 2016;30:1125–8.PubMedGoogle Scholar
  29. 29.
    LeBoit PE. A diagnosis for maniacs. Am J Dermatopathol. 2000;22:556–8.PubMedGoogle Scholar
  30. 30.
    Saida T, Koga H, Goto Y, Uhara H. Characteristic distribution of melanin columns in the cornified layer of acquired acral nevus: an important clue for histopathologic differentiation from early acral melanoma. Am J Dermatopathol. 2011;33:468–73.PubMedGoogle Scholar
  31. 31.
    Chen LL, Jaimes N, Barker CA, Busam KJ, Marghoob AA. Desmoplastic melanoma: a review. J Am Acad Dermatol. 2013;68:825–33.PubMedGoogle Scholar
  32. 32.
    Pizzichetta MA, et al. Amelanotic/hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol. 2004;150:1117–24.PubMedGoogle Scholar
  33. 33.
    Menzies SW, et al. Dermoscopic evaluation of Amelanotic and Hypomelanotic melanoma. Arch Dermatol. 2008;144(9):1120–7.PubMedGoogle Scholar
  34. 34.
    Gill M, González S. Enlightening the Pink Dermatologic Clinics. 2016;34:443–58.PubMedGoogle Scholar
  35. 35.
    Losi A, et al. Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy. Br J Dermatol. 2014;171:48–54.PubMedGoogle Scholar
  36. 36.
    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 Investig Dermatol. 2012;132:2386–94.PubMedGoogle Scholar
  37. 37.
    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.PubMedGoogle Scholar
  38. 38.
    Langley RGB, et al. The diagnostic accuracy of in vivo confocal scanning laser microscopy compared to Dermoscopy of benign and malignant melanocytic lesions: a prospective study. Dermatology. 2007;215:365–72.PubMedGoogle Scholar
  39. 39.
    Gerger A, et al. Diagnostic image analysis of malignant melanoma in in vivo confocal laser-scanning microscopy: a preliminary study. Skin Res Technol. 2008;14:359–63.PubMedGoogle Scholar
  40. 40.
    Gerger A, et al. Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors. Cancer. 2006;107:193–200.PubMedGoogle Scholar
  41. 41.
    Borsari S, et al. In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ melanomas. Br J Dermatol. 2018;179:163–72.PubMedGoogle Scholar
  42. 42.
    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;127:2759–65.PubMedGoogle Scholar
  43. 43.
    Pellacani G, Cesinaro AM, Seidenari S. Reflectance-mode confocal microscopy for the in vivo characterization of pagetoid melanocytosis in melanomas and nevi. J Invest Dermatol. 2005;125:532–7.PubMedGoogle Scholar
  44. 44.
    Hibler BP, et al. Handheld reflectance confocal microscopy to aid in the management of complex facial lentigo maligna. Cutis. 2017;99:346–52.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Bolshinsky V, et al. Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy. J Am Acad Dermatol. 2016;74:102–7.PubMedGoogle Scholar
  46. 46.
    Chen C-SJ, Elias M, Busam K, Rajadhyaksha M, Marghoob AA. Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma. Br J Dermatol. 2005;153:1031–6.PubMedGoogle Scholar
  47. 47.
    Hibler BP, Cordova M, Wong RJ, Rossi AM. Intraoperative real-time reflectance confocal microscopy for guiding surgical margins of lentigo maligna melanoma. Dermatol Surg. 2015;41:980–3.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Champin J, et al. In vivo reflectance confocal microscopy to optimize the spaghetti technique for defining surgical margins of Lentigo Maligna. Dermatol Surg. 2014;40:247–56.PubMedGoogle Scholar
  49. 49.
    Couty E, et al. In vivo reflectance confocal microscopy combined with the ‘spaghetti technique’ for the identification of surgical margins of lentigo maligna: experience in 70 patients. J Eur Acad Dermatol Venereol. 2018;32:e366–8.PubMedGoogle Scholar
  50. 50.
    Kose K, et al. Video-mosaicing of reflectance confocal images for examination of extended areas of skin in vivo. Br J Dermatol. 2014;171:1239–41.PubMedPubMedCentralGoogle Scholar
  51. 51.
    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.PubMedGoogle Scholar
  52. 52.
    Alarcon I, et al. In vivo reflectance confocal microscopy to monitor the response of lentigo maligna to imiquimod. J Am Acad Dermatol. 2014;71:49–55.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Marco Campoli
    • 1
  • Jean Luc Perrot
    • 2
  • Elisa Cinotti
    • 1
  1. 1.Department of Medical, Surgical and Neurological Science, Dermatology SectionUniversity of Siena, S. Maria alle Scotte HospitalSienaItaly
  2. 2.Department of DermatologyUniversity Hospital of St-EtienneSaint-EtienneFrance

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