Current and future applications of confocal laser scanning microscopy imaging in skin oncology (Review)

Ilie,Mihaela   Adriana; Caruntu,Constantin; Lupu,Mihai; Lixandru,Daniela; Tampa,Mircea; Georgescu,Simona-Roxana; Bastian,Alexandra; Constantin,Carolina; Neagu,Monica; Zurac,Sabina   Andrada; Boda,Daniel

doi:10.3892/ol.2019.10066

Current and future applications of confocal laser scanning microscopy imaging in skin oncology (Review)

Authors:
- Mihaela Adriana Ilie
- Constantin Caruntu
- Mihai Lupu
- Daniela Lixandru
- Mircea Tampa
- Simona-Roxana Georgescu
- Alexandra Bastian
- Carolina Constantin
- Monica Neagu
- Sabina Andrada Zurac
- Daniel Boda
View Affiliations

Affiliations: Dermatology Research Laboratory, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Biochemistry, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Dermatology, MEDAS Medical Center, 030442 Bucharest, Romania, Department of Dermatology, ‘Victor Babes’ Hospital, ‘Carol Davila’ University of Medicine and Pharmacy, 030303 Bucharest, Romania, Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Pathology, Colentina Clinical Hospital, 020125 Bucharest, Romania
Published online on: February 25, 2019 https://doi.org/10.3892/ol.2019.10066
Pages: 4102-4111
Copyright: © Ilie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Confocal laser scanning microscopy (CLSM) is a modern imaging technique that enables the in vivo or ex vivo characterization of skin lesions located in the epidermis and superficial dermis with a high quasi-microscopic resolution. Currently, it is considered to be the most promising imaging tool for the evaluation of superficial skin tumors. The in vivo mode adds the advantage of noninvasive, dynamic, in real-time assessment of the tumor associated vasculature and inflammation. It offers the possibility to repeatedly examine the same skin area without causing any damage and to monitor disease progression and treatment outcome. Furthermore, this novel technology allows the evaluation of the entire lesion and can be used to guide biopsies and to define tumor margins before surgical excision or other invasive therapies. CLSM diagnostic features may differentiate between the various histologic subtypes of skin tumors and therefore helps in choosing the best therapeutic approach. In this study, we present the CLSM characteristic features of the most common melanocytic and non-melanocytic skin tumors, as well as future possible CLSM applications in the study of experimental skin tumorigenesis on animal models.

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1	Diaconeasa A, Boda D, Neagu M, Constantin C, Căruntu C, Vlădău L and Guţu D: The role of confocal microscopy in the dermato-oncology practice. J Med Life. 4:63–74. 2011.PubMed/NCBI
2	Aghassi D, González E, Anderson RR, Rajadhyaksha M and González S: Elucidating the pulsed-dye laser treatment of sebaceous hyperplasia in vivo with real-time confocal scanning laser microscopy. J Am Acad Dermatol. 43:49–53. 2000. View Article : Google Scholar : PubMed/NCBI
3	González S, Swindells K, Rajadhyaksha M and Torres A: Changing paradigms in dermatology: Confocal microscopy in clinical and surgical dermatology. Clin Dermatol. 21:359–369. 2003. View Article : Google Scholar : PubMed/NCBI
4	Rajadhyaksha M, González S, Zavislan JM, Anderson RR and Webb RH: In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison with histology. J Invest Dermatol. 113:293–303. 1999. View Article : Google Scholar : PubMed/NCBI
5	González S, Sackstein R, Anderson RR and Rajadhyaksha M: Real-time evidence of in vivo leukocyte trafficking in human skin by reflectance confocal microscopy. J Invest Dermatol. 117:384–386. 2001. View Article : Google Scholar : PubMed/NCBI
6	Peppelman M, Wolberink EA, Gerritsen MJ, van de Kerkhof PC and van Erp PE: Application of leukotriene B4 and reflectance confocal microscopy as a noninvasive in vivo model to study the dynamics of skin inflammation. Skin Res Technol. 21:232–240. 2015. View Article : Google Scholar : PubMed/NCBI
7	Batani A, Brănișteanu DE, Ilie MA, Boda D, Ianosi S, Ianosi G and Caruntu C: Assessment of dermal papillary and microvascular parameters in psoriasis vulgaris using in vivo reflectance confocal microscopy. Exp Ther Med. 15:1241–1246. 2018.PubMed/NCBI
8	Căruntu C, Boda D, Căruntu A, Rotaru M, Baderca F and Zurac S: In vivo imaging techniques for psoriatic lesions. Rom J Morphol Embryol. 55 (Suppl 3):1191–1196. 2014.PubMed/NCBI
9	Ghiţă MA, Căruntu C, Rosca AE, Căruntu A, Moraru L, Constantin C, Neagu M and Boda D: Real-time investigation of skin blood flow changes induced by topical capsaicin. Acta Dermatovenerol Croat. 25:223–227. 2017.PubMed/NCBI
10	Căruntu C and Boda D: Evaluation through in vivo reflectance confocal microscopy of the cutaneous neurogenic inflammatory reaction induced by capsaicin in human subjects. J Biomed Opt. 17:0850032012. View Article : Google Scholar : PubMed/NCBI
11	Okabe M, Ikawa M, Kominami K, Nakanishi T and Nishimune Y: ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett. 407:313–319. 1997. View Article : Google Scholar : PubMed/NCBI
12	Meyer LE, Otberg N, Sterry W and Lademann J: In vivo confocal scanning laser microscopy: Comparison of the reflectance and fluorescence mode by imaging human skin. J Biomed Opt. 11:0440122006. View Article : Google Scholar : PubMed/NCBI
13	Skvara H, Plut U, Schmid JA and Jonak C: Combining in vivo reflectance with fluorescence confocal microscopy provides additive information on skin morphology. Dermatol Pract Concept. 2:3–12. 2012. View Article : Google Scholar : PubMed/NCBI
14	Rajadhyaksha M, Grossman M, Esterowitz D, Webb RH and Anderson RR: In vivo confocal scanning laser microscopy of human skin: Melanin provides strong contrast. J Invest Dermatol. 104:946–952. 1995. View Article : Google Scholar : PubMed/NCBI
15	Pellacani G, Guitera P, Longo C, Avramidis M, Seidenari S and Menzies S: The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 127:2759–2765. 2007. View Article : Google Scholar : PubMed/NCBI
16	Guida S, Longo C, Casari A, Ciardo S, Manfredini M, Reggiani C, Pellacani G and Farnetani F: Update on the use of confocal microscopy in melanoma and non-melanoma skin cancer. G Ital Dermatol Venereol. 150:547–563. 2015.PubMed/NCBI
17	Pellacani G, De Pace B, Reggiani C, Cesinaro AM, Argenziano G, Zalaudek I, Soyer HP and Longo C: Distinct melanoma types based on reflectance confocal microscopy. Exp Dermatol. 23:414–418. 2014. View Article : Google Scholar : PubMed/NCBI
18	Serban ED, Farnetani F, Pellacani G and Constantin MM: Role of in vivo reflectance confocal microscopy in the analysis of melanocytic lesions. Acta Dermatovenerol Croat. 26:64–67. 2018.PubMed/NCBI
19	González S, Sánchez V, González-Rodríguez A, Parrado C and Ullrich M: Confocal microscopy patterns in nonmelanoma skin cancer and clinical applications. Actas Dermosifiliogr. 105:446–458. 2014. View Article : Google Scholar : PubMed/NCBI
20	Białek-Galas K, Wielowieyska-Szybińska D, Dyduch G and Wojas-Pelc A: The use of reflectance confocal microscopy in selected inflammatory skin diseases. Pol J Pathol. 66:103–108. 2015. View Article : Google Scholar : PubMed/NCBI
21	Constantin MM, Bucur S, Serban DE, Caruntu C, Orzan OA and Constantin T: Dermoscopic and laser confocal features of an exogenous ochronosis case. G Ital Dermatol Venereol. Jun 29–2018.(Epub ahead of print). PubMed/NCBI
22	Lange-Asschenfeldt S, Bob A, Terhorst D, Ulrich M, Fluhr J, Mendez G, Roewert-Huber HJ, Stockfleth E and Lange-Asschenfeldt B: Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing. J Biomed Opt. 17:0760162012. View Article : Google Scholar : PubMed/NCBI
23	Altintas AA, Altintas MA, Ipaktchi K, Guggenheim M, Theodorou P, Amini P and Spilker G: Assessment of microcirculatory influence on cellular morphology in human burn wound healing using reflectance-mode-confocal microscopy. Wound Repair Regen. 17:498–504. 2009. View Article : Google Scholar : PubMed/NCBI
24	Altintas AA, Guggenheim M, Oezcelik A, Gehl B, Aust MC and Altintas MA: Local burn versus local cold induced acute effects on in vivo microcirculation and histomorphology of the human skin. Microsc Res Tech. 74:963–969. 2011. View Article : Google Scholar : PubMed/NCBI
25	Longo C, Ragazzi M, Rajadhyaksha M, Nehal K, Bennassar A, Pellacani G and Malvehy Guilera J: In vivo and ex vivo confocal microscopy for dermatologic and Mohs surgeons. Dermatol Clin. 34:497–504. 2016. View Article : Google Scholar : PubMed/NCBI
26	Bennàssar A, Vilata A, Puig S and Malvehy J: Ex vivo fluorescence confocal microscopy for fast evaluation of tumour margins during Mohs surgery. Br J Dermatol. 170:360–365. 2014. View Article : Google Scholar : PubMed/NCBI
27	Miller DL and Weinstock MA: Nonmelanoma skin cancer in the United States: Incidence. J Am Acad Dermatol. 30:774–778. 1994. View Article : Google Scholar : PubMed/NCBI
28	Lomas A, Leonardi-Bee J and Bath-Hextall F: A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 166:1069–1080. 2012. View Article : Google Scholar : PubMed/NCBI
29	Chen CS, Sierra H, Cordova M and Rajadhyaksha M: Confocal microscopy-guided laser ablation for superficial and early nodular Basal cell carcinoma: A promising surgical alternative for superficial skin cancers. JAMA Dermatol. 150:994–998. 2014. View Article : Google Scholar : PubMed/NCBI
30	Lupu M, Caruntu C, Ghita MA, Voiculescu V, Voiculescu S, Rosca AE, Caruntu A, Moraru L, Popa IM, Calenic B, et al: Gene expression and proteome analysis as sources of biomarkers in basal cell carcinoma. Dis Markers. 2016:98312372016. View Article : Google Scholar : PubMed/NCBI
31	Ghita MA, Caruntu C, Rosca AE, Kaleshi H, Caruntu A, Moraru L, Docea AO, Zurac S, Boda D, Neagu M, et al: Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma. Oncol Lett. 11:3019–3024. 2016. View Article : Google Scholar : PubMed/NCBI
32	Longo C, Lallas A, Kyrgidis A, Rabinovitz H, Moscarella E, Ciardo S, Zalaudek I, Oliviero M, Losi A, Gonzalez S, et al: Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy. J Am Acad Dermatol. 71:716–724. 2014. View Article : Google Scholar : PubMed/NCBI
33	Căruntu C, Boda D, Guţu DE and Căruntu A: In vivo reflectance confocal microscopy of basal cell carcinoma with cystic degeneration. Rom J Morphol Embryol. 55:1437–1441. 2014.PubMed/NCBI
34	Peppelman M, Wolberink EA, Blokx WA, van de Kerkhof PC, van Erp PE and Gerritsen MJ: In vivo diagnosis of basal cell carcinoma subtype by reflectance confocal microscopy. Dermatology. 227:255–262. 2013. View Article : Google Scholar : PubMed/NCBI
35	Nori S, Rius-Díaz F, Cuevas J, Goldgeier M, Jaen P, Torres A and González S: Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: A multicenter study. J Am Acad Dermatol. 51:923–930. 2004. View Article : Google Scholar : PubMed/NCBI
36	González S and Tannous Z: Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. J Am Acad Dermatol. 47:869–874. 2002. View Article : Google Scholar : PubMed/NCBI
37	Stephens A, Fraga-Braghiroli N, Oliviero M, Rabinovitz H and Scope A: Spoke wheel-like structures in superficial basal cell carcinoma: A correlation between dermoscopy, histopathology, and reflective confocal microscopy. J Am Acad Dermatol. 69:e219–e221. 2013. View Article : Google Scholar : PubMed/NCBI
38	Ulrich M, Roewert-Huber J, González S, Rius-Diaz F, Stockfleth E and Kanitakis J: Peritumoral clefting in basal cell carcinoma: Correlation of in vivo reflectance confocal microscopy and routine histology. J Cutan Pathol. 38:190–195. 2011. View Article : Google Scholar : PubMed/NCBI
39	Que SK, Fraga-Braghiroli N, Grant-Kels JM, Rabinovitz HS, Oliviero M and Scope A: Through the looking glass: Basics and principles of reflectance confocal microscopy. J Am Acad Dermatol. 73:276–284. 2015. View Article : Google Scholar : PubMed/NCBI
40	Lupu M, Caruntu C, Solomon I, Popa A, Lisievici C, Draghici C, Papagheorghe L, Voiculescu VM and Giurcaneanu C: The use of in vivo reflectance confocal microscopy and dermoscopy in the preoperative determination of basal cell carcinoma histopathological subtypes. DermatoVenerol. 62:7–13. 2017.
41	Segura S, Puig S, Carrera C, Palou J and Malvehy J: Dendritic cells in pigmented basal cell carcinoma: A relevant finding by reflectance-mode confocal microscopy. Arch Dermatol. 143:883–886. 2007. View Article : Google Scholar : PubMed/NCBI
42	Pan ZY, Lin JR, Cheng TT, Wu JQ and Wu WY: In vivo reflectance confocal microscopy of basal cell carcinoma: Feasibility of preoperative mapping of cancer margins. Dermatol Surg. 38:1945–1950. 2012. View Article : Google Scholar : PubMed/NCBI
43	Webber SA, Wurm EMT, Douglas NC, Lambie D, Longo C, Pellacani G and Soyer HP: Effectiveness and limitations of reflectance confocal microscopy in detecting persistence of basal cell carcinomas: A preliminary study. Australas J Dermatol. 52:179–185. 2011. View Article : Google Scholar : PubMed/NCBI
44	Ahlgrimm-Siess V, Horn M, Koller S, Ludwig R, Gerger A and Hofmann-Wellenhof R: Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in vivo reflectance confocal microscopy: A preliminary study. J Dermatol Sci. 53:60–64. 2009. View Article : Google Scholar : PubMed/NCBI
45	Voiculescu V, Calenic B, Ghita M, Lupu M, Caruntu A, Moraru L, Voiculescu S, Ion A, Greabu M, Ishkitiev N, et al: From normal skin to squamous cell carcinoma: A quest for novel biomarkers. Dis Markers. 2016:45174922016. View Article : Google Scholar : PubMed/NCBI
46	Boda D, Neagu M, Constantin C, Voinescu RN, Caruntu C, Zurac S, Spandidos DA, Drakoulis N, Tsoukalas D and Tsatsakis AM: HPV strain distribution in patients with genital warts in a female population sample. Oncol Lett. 12:1779–1782. 2016. View Article : Google Scholar : PubMed/NCBI
47	Boda D, Docea AO, Calina D, Ilie MA, Caruntu C, Zurac S, Neagu M, Constantin C, Branisteanu DE, Voiculescu V, et al: Human papilloma virus: Apprehending the link with carcinogenesis and unveiling new research avenues (Review). Int J Oncol. 52:637–655. 2018.PubMed/NCBI
48	Georgescu SR, Sârbu MI, Matei C, Ilie MA, Caruntu C, Constantin C, Neagu M and Tampa M: Capsaicin: Friend or foe in skin cancer and other related malignancies? Nutrients. 9:13652017. View Article : Google Scholar
49	Lupu M, Caruntu A, Caruntu C, Papagheorghe LML, Ilie MA, Voiculescu V, Boda D, Constantin C, Tanase C, Sifaki M, et al: Neuroendocrine factors: The missing link in non-melanoma skin cancer (Review). Oncol Rep. 38:1327–1340. 2017. View Article : Google Scholar : PubMed/NCBI
50	Solomon I, Voiculescu VM, Caruntu C, Lupu M, Popa A, Ilie MA, Albulescu R, Caruntu A, Tanase C, Constantin C, et al: Neuroendocrine factors and head and neck squamous cell carcinoma: An affair to remember. Dis Markers. 2018:97878312018. View Article : Google Scholar : PubMed/NCBI
51	Tampa M, Caruntu C, Mitran M, Mitran C, Sarbu I, Rusu LC, Matei C, Constantin C, Neagu M and Georgescu SR: Markers of oral lichen planus malignant transformation. Dis Markers. 2018:19595062018. View Article : Google Scholar : PubMed/NCBI
52	González S and Ahlgrimm-Siess V: Reflectance confocal microscopy in dermatology: Fundamentals and clinical applications. Aula Médica. p1112012.
53	Rossi R, Mori M and Lotti T: Actinic keratosis. Int J Dermatol. 46:895–904. 2007. View Article : Google Scholar : PubMed/NCBI
54	Wolff K and Johnson RA: Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. 6th. McGraw-Hill; New York, NY: pp. 267–270. 2009
55	Aghassi D, Anderson RR and González S: Confocal laser microscopic imaging of actinic keratoses in vivo: A preliminary report. J Am Acad Dermatol. 43:42–48. 2000. View Article : Google Scholar : PubMed/NCBI
56	Peppelman M, Nguyen KP, Hoogedoorn L, van Erp PE and Gerritsen MJ: Reflectance confocal microscopy: Non-invasive distinction between actinic keratosis and squamous cell carcinoma. J Eur Acad Dermatol Venereol. 29:1302–1309. 2015. View Article : Google Scholar : PubMed/NCBI
57	Rishpon A, Kim N, Scope A, Porges L, Oliviero MC, Braun RP, Marghoob AA, Fox CA and Rabinovitz HS: Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses. Arch Dermatol. 145:766–772. 2009. View Article : Google Scholar : PubMed/NCBI
58	Branzan AL, Landthaler M and Szeimies RM: In vivo confocal scanning laser microscopy in dermatology. Lasers Med Sci. 22:73–82. 2007. View Article : Google Scholar : PubMed/NCBI
59	Chung VQ, Dwyer PJ, Nehal KS, Rajadhyaksha M, Menaker GM, Charles C and Jiang SB: Use of ex vivo confocal scanning laser microscopy during Mohs surgery for nonmelanoma skin cancers. Dermatol Surg. 30:1470–1478. 2004. View Article : Google Scholar : PubMed/NCBI
60	Lupu M, Caruntu A, Caruntu C, Boda D, Moraru L, Voiculescu V and Bastian A: Non-invasive imaging of actinic cheilitis and squamous cell carcinoma of the lip. Mol Clin Oncol. 8:640–646. 2018.PubMed/NCBI
61	Clark AL, Gillenwater AM, Collier TG, Alizadeh-Naderi R, El-Naggar AK and Richards-Kortum RR: Confocal microscopy for real-time detection of oral cavity neoplasia. Clin Cancer Res. 9:4714–4721. 2003.PubMed/NCBI
62	Zurac S, Neagu M, Constantin C, Cioplea M, Nedelcu R, Bastian A, Popp C, Nichita L, Andrei R, Tebeica T, et al: Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors. Oncol Lett. 11:3354–3360. 2016. View Article : Google Scholar : PubMed/NCBI
63	Neagu M, Constantin C and Zurac S: Immune parameters in the prognosis and therapy monitoring of cutaneous melanoma patients: Experience, role, and limitations. BioMed Res Int. 2013:1079402013. View Article : Google Scholar : PubMed/NCBI
64	Neagu M, Constantin C, Manda G and Margaritescu I: Biomarkers of metastatic melanoma. Biomarkers Med. 3:71–89. 2009. View Article : Google Scholar
65	Neagu M, Constantin C and Tanase C: Immune-related biomarkers for diagnosis/prognosis and therapy monitoring of cutaneous melanoma. Expert Rev Mol Diagn. 10:897–919. 2010. View Article : Google Scholar : PubMed/NCBI
66	Surcel M, Constantin C, Caruntu C, Zurac S and Neagu M: Inflammatory cytokine pattern is sex-dependent in mouse cutaneous melanoma experimental model. J Immunol Res. 2017:92121342017. View Article : Google Scholar : PubMed/NCBI
67	Caruntu C, Mirica A, Rosca A, Mirica R, Caruntu A, Tampa M, Matei C, Constantin C, Neagu M, Badarau A, et al: The role of estrogens and estrogen receptors in melanoma development and progression. Acta Endo Buc. 12:234–241. 2016. View Article : Google Scholar
68	Caruntu C, Boda D, Constantin C, Caruntu A and Neagu M: Catecholamines increase in vitro proliferation of murine B16F10 melanoma cells. Acta Endo Buc. 10:545–558. 2014. View Article : Google Scholar
69	Neagu M, Constantin C, Dumitrascu GR, Lupu AR, Caruntu C, Boda D and Zurac S: Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis. Discoveries (Craiova). 3:e382015. View Article : Google Scholar
70	Ene CD, Anghel AE, Neagu M and Nicolae I: 25-OH vitamin D and interleukin-8: Emerging biomarkers in cutaneous melanoma development and progression. Mediators Inflamm. 2015:9048762015. View Article : Google Scholar : PubMed/NCBI
71	Solovastru LG, Vâta D, Statescu L, Constantin MM and Andrese E: Skin cancer between myth and reality, yet ethically constrained. Rev Rom Bioet. 12:47–52. 2014.
72	Rigel DS, Friedman RJ, Kopf AW and Polsky D: ABCDE - an evolving concept in the early detection of melanoma. Arch Dermatol. 141:1032–1034. 2005. View Article : Google Scholar : PubMed/NCBI
73	Grob JJ and Bonerandi JJ: The ‘ugly duckling’ sign: Identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol. 134:103–104. 1998. View Article : Google Scholar : PubMed/NCBI
74	Hansen C, Wilkinson D, Hansen M and Argenziano G: How good are skin cancer clinics at melanoma detection? Number needed to treat variability across a national clinic group in Australia. J Am Acad Dermatol. 61:599–604. 2009. View Article : Google Scholar : PubMed/NCBI
75	Sidhu S, Bodger O, Williams N and Roberts DL: The number of benign moles excised for each malignant melanoma: The number needed to treat. Clin Exp Dermatol. 37:6–9. 2012. View Article : Google Scholar : PubMed/NCBI
76	Goodson AG, Florell SR, Hyde M, Bowen GM and Grossman D: Comparative analysis of total body and dermatoscopic photographic monitoring of nevi in similar patient populations at risk for cutaneous melanoma. Dermatol Surg. 36:1087–1098. 2010. View Article : Google Scholar : PubMed/NCBI
77	Moloney FJ, Guitera P, Coates E, Haass NK, Ho K, Khoury R, O'Connell RL, Raudonikis L, Schmid H, Mann GJ, et al: Detection of primary melanoma in individuals at extreme high risk: A prospective 5-year follow-up study. JAMA Dermatol. 150:819–827. 2014. View Article : Google Scholar : PubMed/NCBI
78	March J, Hand M and Grossman D: Practical application of new technologies for melanoma diagnosis: Part I. Noninvasive approaches. J Am Acad Dermatol. 72:929–942. 2015. View Article : Google Scholar : PubMed/NCBI
79	Ulrich M and Lange-Asschenfeldt S: In vivo confocal microscopy in dermatology: From research to clinical application. J Biomed Opt. 18:0612122013. View Article : Google Scholar : PubMed/NCBI
80	Carrera C, Puig S and Malvehy J: In vivo confocal reflectance microscopy in melanoma. Dermatol Ther (Heidelb). 25:410–422. 2012. View Article : Google Scholar
81	Longo C, Farnetani F, Ciardo S, Cesinaro AM, Moscarella E, Ponti G, Zalaudek I, Argenziano G and Pellacani G: Is confocal microscopy a valuable tool in diagnosing nodular lesions? A study of 140 cases. Br J Dermatol. 169:58–67. 2013. View Article : Google Scholar : PubMed/NCBI
82	Gerger A, Koller S, Weger W, Richtig E, Kerl H, Samonigg H, Krippl P and Smolle J: Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors. Cancer. 107:193–200. 2006. View Article : Google Scholar : PubMed/NCBI
83	Sokołowska-Wojdyło M, Olek-Hrab K and Ruckemann-Dziurdzińska K: Primary cutaneous lymphomas: Diagnosis and treatment. Postepy Dermatol Alergol. 32:368–383. 2015. View Article : Google Scholar : PubMed/NCBI
84	Ion A, Popa IM, Papagheorghe LML, Lisievici C, Lupu M, Voiculescu V, Caruntu C and Boda D: Proteomic approaches to biomarker discovery in cutaneous T-cell lymphoma. Dis Markers. 2016:96024722016. View Article : Google Scholar : PubMed/NCBI
85	Fabbrocini G, Mazzella C, Cantelli M, Baldo A, Russo D, De Rosa G and Monfrecola G: Reflectance confocal microscopy as new diagnostic tool in folliculotropic mycosis fungoides. Skin Appendage Disord. 4:118–121. 2018. View Article : Google Scholar : PubMed/NCBI
86	Mancebo SE, Cordova M, Myskowski PL, Flores ES, Busam K, Jawed SI, Skripnik A, Rajadhyaksha M and Querfeld C: Reflectance confocal microscopy features of mycosis fungoides and Sézary syndrome: Correlation with histopathologic and T-cell receptor rearrangement studies. J Cutan Pathol. 43:505–515. 2016. View Article : Google Scholar : PubMed/NCBI
87	Li W, Dai H, Li Z and Xu AE: Reflectance confocal microscopy for the characterization of mycosis fungoides and correlation with histology: A pilot study. Skin Res Technol. 19:352–355. 2013. View Article : Google Scholar : PubMed/NCBI
88	Lange-Asschenfeldt S, Babilli J, Beyer M, Ríus-Diaz F, González S, Stockfleth E and Ulrich M: Consistency and distribution of reflectance confocal microscopy features for diagnosis of cutaneous T cell lymphoma. J Biomed Opt. 17:0160012012. View Article : Google Scholar : PubMed/NCBI
89	Koller S, Gerger A, Ahlgrimm-Siess V, Weger W, Smolle J and Hofmann-Wellenhof R: In vivo reflectance confocal microscopy of erythematosquamous skin diseases. Exp Dermatol. 18:536–540. 2009. View Article : Google Scholar : PubMed/NCBI
90	Agero AL, Gill M, Ardigo M, Myskowski P, Halpern AC and González S: In vivo reflectance confocal microscopy of mycosis fungoides: A preliminary study. J Am Acad Dermatol. 57:435–441. 2007. View Article : Google Scholar : PubMed/NCBI
91	Ardigò M, Donadio C, Vega H, Cota C, Moscarella E and Agozzino M: Concordance between in vivo reflectance confocal microscopy and optical histology of lymphomatoid papulosis. Skin Res Technol. 19:308–313. 2013. View Article : Google Scholar : PubMed/NCBI
92	Ardigò M, El Shabrawi-Caelen L and Tosti A: In vivo reflectance confocal microscopy assessment of the therapeutic follow-up of cutaneous T-cell lymphomas causing scalp alopecia. Dermatol Ther (Heidelb). 27:248–251. 2014. View Article : Google Scholar
93	de Vries E, Trakatelli M, Kalabalikis D, Ferrandiz L, Ruiz-de-Casas A, Moreno-Ramirez D, Sotiriadis D, Ioannides D, Aquilina S, Apap C, et al EPIDERM Group, : Known and potential new risk factors for skin cancer in European populations: A multicentre case-control study. Br J Dermatol. 167 (Suppl 2):1–13. 2012. View Article : Google Scholar : PubMed/NCBI
94	Maru GB, Gandhi K, Ramchandani A and Kumar G: The role of inflammation in skin cancer. Adv Exp Med Biol. 816:437–469. 2014. View Article : Google Scholar : PubMed/NCBI
95	Neagu M, Caruntu C, Constantin C, Boda D, Zurac S, Spandidos DA and Tsatsakis AM: Chemically induced skin carcinogenesis: Updates in experimental models (Review). Oncol Rep. 35:2516–2528. 2016. View Article : Google Scholar : PubMed/NCBI
96	Abel EL, Angel JM, Kiguchi K and DiGiovanni J: Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications. Nat Protoc. 4:1350–1362. 2009. View Article : Google Scholar : PubMed/NCBI
97	Hashemi P, Pulitzer MP, Scope A, Kovalyshyn I, Halpern AC and Marghoob AA: Langerhans cells and melanocytes share similar morphologic features under in vivo reflectance confocal microscopy: A challenge for melanoma diagnosis. J Am Acad Dermatol. 66:452–462. 2012. View Article : Google Scholar : PubMed/NCBI
98	Li Y, Gonzalez S, Terwey TH, Wolchok J, Li Y, Aranda I, Toledo-Crow R and Halpern AC: Dual mode reflectance and fluorescence confocal laser scanning microscopy for in vivo imaging melanoma progression in murine skin. J Invest Dermatol. 125:798–804. 2005. View Article : Google Scholar : PubMed/NCBI
99	Izatt JA, Kulkarni MD, Hsing-Wen W, Kobayashi K and Sivak MV: Optical coherence tomography and microscopy in gastrointestinal tissues. IEEE J Sel Top Quantum Electron. 2:1017–1028. 1996. View Article : Google Scholar
100	Ono I, Sakemoto A, Ogino J, Kamiya T, Yamashita T and Jimbow K: The real-time, three-dimensional analyses of benign and malignant skin tumors by confocal laser scanning microscopy. J Dermatol Sci. 43:135–141. 2006. View Article : Google Scholar : PubMed/NCBI
101	Skvara H, Kittler H, Schmid JA, Plut U and Jonak C: In vivo fluorescence confocal microscopy: Indocyanine green enhances the contrast of epidermal and dermal structures. J Biomed Opt. 16:0960102011. View Article : Google Scholar : PubMed/NCBI