Reflectance Confocal Microscopy - Real-Time In Vivo Imaging of Basal and Squamous Cell Carcinomas

• Anna Haydee Chacon

  Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

• Uzma Farooq

  Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

• Katlein Franca

  Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

• Jennifer Ledon

  Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

• Jessica Savas

  Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

• Keyvan Nouri

  Ophthalmology & Otolaryngology; Louis C. Skinner, Jr. M.D. Endowed Chair in Dermatology; Richard Helfman Professor of Dermatologic Surgery; Vice-Chairman of the University of Miami Medical Group; Chief of Dermatology Services at Sylvester Comprehensive Cancer Center/University of Miami Hospital and Clinics; Director of Mohs, Dermatologic & Laser Surgery; Director of Surgical Training; Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, USA

 Reflectance and confocal microscopy (RCM) is an in vivo non-invasive imaging tool that captures horizontal images of the epidermis and superficial dermis at nearly the same resolution of routine histopathology. Due to the overlying superficial scaling, RCM characterization of squamous cell carcinomas (SCCs) and associated keratinizing tumors is difficult to visualize due to the obscure appearance of underlying structures. To date, although an increasing frequency of abnormal RCM features are observed across the spectrum, only a few authors have described the features of SCCs. One recent study suggested a disarranged and atypical honeycomb pattern along with round nucleated cells within the spinous/granular layers and round vessels traversing through dermal papilla as key features of SCC.

Meanwhile several RCM features have been linked to basal cell carcinomas (BCCs) regardless of type including:

1. Variable architectural disarray of the epidermis
2. A uniform pattern of elongated monomorphic nuclei polarized along the same axis
3. Abundant vessels with prominent tortuosity
4. Mononuclear inflammatory infiltrate admixed with carcinoid basal cells
5. Tightly packed cells in the papillary dermis with a nodular/cord-like growth pattern
6. Palisading tumor cell nuclei
7. Peri-tumoral dark cleft-like spaces representing mucinous edema
8. The presence of bright dendritic cells and melanophages in pigmented BCC

Our objective is to identify and describe characteristic RCM findings of SCCs and BCCs by imaging biopsy-proven lesions and reviewing the most recent literature. We will also explain how these features may facilitate diagnosis and recognize future trends for research. Applications of RCM criteria concerning surgical management of these lesions will also be discussed.

Aghassi D, Anderson RR, Gonzalez S. Confocal laser microscopic imaging of actinic keratoses in vivo: a preliminary report. J Am Acad Dermatol 2000; 43(1 Pt 1): 42-8. http://dx.doi.org/10.1067/mjd.2000.105565

Calzavara-Pinton P, Longo C, Venturini M, Sala R, Pellacani G. Reflectance confocal microscopy for in vivo skin imaging. Photochem Photobiol 2008; 84(6): 1421-30. http://dx.doi.org/10.1111/j.1751-1097.2008.00443.x

Rishpon A, Kim N, Scope A, et al. Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses. Arch Dermatol 2009; 145(7): 766-72. http://dx.doi.org/10.1001/archdermatol.2009.134

Horn M, Gerger A, Koller S, et al. The use of confocal laser-scanning microscopy in microsurgery for invasive squamous cell carcinoma. Br J Dermatol 2007; 156(1): 81-4. http://dx.doi.org/10.1111/j.1365-2133.2006.07574.x

Ahlgrimm-Siess V, Cao T, Oliviero M, Hofmann-Wellenhof R, Rabinovitz HS, Scope A. The vasculature of nonmelanocytic skin tumors on reflectance confocal microscopy: vascular features of squamous cell carcinoma in situ. Arch Dermatol 2011; 147(2): 264. http://dx.doi.org/10.1001/archdermatol.2010.416

Braga JC, Scope A, Klaz I, et al. The significance of reflectance confocal microscopy in the assessment of solitary pink skin lesions. J Am Acad Dermatol 2009; 61(2): 230-41. http://dx.doi.org/10.1016/j.jaad.2009.02.036

Chung VQ, Dwyer PJ, Nehal KS, et al. Use of ex vivo confocal scanning laser microscopy during Mohs surgery for nonmelanoma skin cancers. Dermatologic surgery: official publication for American Society for Dermatologic Surgery [et al.] 2004; 30(12 Pt 1): 1470-8.

Yaroslavsky AN, Barbosa J, Neel V, DiMarzio C, Anderson RR. Combining multispectral polarized light imaging and confocal microscopy for localization of nonmelanoma skin cancer. J Biomed Optics 2005; 10(1): 14011. http://dx.doi.org/10.1117/1.1854173

Scope A, Mahmood U, Gareau DS, et al. In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins. Br J Dermatol 2010; 163(6): 1218-28. http://dx.doi.org/10.1111/j.1365-2133.2010.10063.x

Nori S, Rius-Diaz F, Cuevas J, 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(6): 923-30. http://dx.doi.org/10.1016/j.jaad.2004.06.028

Gerger A, Horn M, Koller S, et al. Confocal examination of untreated fresh specimens from basal cell carcinoma: implications for microscopically guided surgery. Arch Dermatol 2005; 141(10): 1269-74. http://dx.doi.org/10.1001/archderm.141.10.1269

Agero AL, Busam KJ, Benvenuto-Andrade C, et al. Reflectance confocal microscopy of pigmented basal cell carcinoma. J Am Acad Dermatol 2006; 54(4): 638-43. http://dx.doi.org/10.1016/j.jaad.2005.11.1096

Scope A, Mecca PS, Marghoob AA. skINsight lessons in reflectance confocal microscopy: rapid diagnosis of pigmented basal cell carcinoma. Arch Dermatol 2009; 145(1): 106-7. http://dx.doi.org/10.1001/archdermatol.2008.577

Segura S, Puig S, Carrera C, Palou J, Malvehy J. Dendritic cells in pigmented basal cell carcinoma: a relevant finding by reflectance-mode confocal microscopy. Arch Dermatol 2007; 143(7): 883-6. http://dx.doi.org/10.1001/archderm.143.7.883

Ahlgrimm-Siess V, Cao T, Oliviero M, Hofmann-Wellenhof R, Rabinovitz HS, Scope A. The vasculature of nonmelanocytic skin tumors in reflectance confocal microscopy: vascular features of basal cell carcinoma. Arch Dermatol 2010; 146(3): 353-4. http://dx.doi.org/10.1001/archdermatol.2009.380

Sauermann K, Gambichler T, Wilmert M, et al. Investigation of basal cell carcinoma [correction of carcionoma] by confocal laser scanning microscopy in vivo. Skin Res Technol 2002; 8(3): 141-7. http://dx.doi.org/10.1034/j.1600-0846.2002.20345.x

Gonzalez S, Tannous Z. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. J Am Acad Dermatol 2002; 47(6): 869-74. http://dx.doi.org/10.1067/mjd.2002.124690

Marra DE, Torres A, Schanbacher CF, Gonzalez S. Detection of residual basal cell carcinoma by in vivo confocal microscopy. Dermatologic surgery: official publication for American Society for Dermatologic Surgery [et al.] 2005; 31(5): 538-41.

Karen JK, Gareau DS, Dusza SW, Tudisco M, Rajadhyaksha M, Nehal KS. Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy. Br J Dermatol 2009; 160(6): 1242-50. http://dx.doi.org/10.1111/j.1365-2133.2009.09141.x

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. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 2003; 29(8): 839-46.

Ulrich M, Roewert-Huber J, Gonzalez S, Rius-Diaz F, Stockfleth E, Kanitakis J. Peritumoral clefting in basal cell carcinoma: correlation of in vivo reflectance confocal microscopy and routine histology. J Cutaneous Pathol 2011; 38(2): 190-5. http://dx.doi.org/10.1111/j.1600-0560.2010.01632.x

Patel YG, Nehal KS, Aranda I, Li Y, Halpern AC, Rajadhyaksha M. Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions. J Biomed Optics 2007; 12(3): 034027.http://dx.doi.org/10.1117/1.2750294

Torres A, Niemeyer A, Berkes B, et al. 5% imiquimod cream and reflectance-mode confocal microscopy as adjunct modalities to Mohs micrographic surgery for treatment of basal cell carcinoma. Dermatologic surgery: official publication for American Society for Dermatologic Surgery [et al.] 2004; 30(12 Pt 1): 1462-9.

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(1): 60-4. http://dx.doi.org/10.1016/j.jdermsci.2008.08.005

Moore MM, Geller AC, Zhang Z, et al. Skin cancer examination teaching in US medical education. Arch Dermatol 2006; 142(4): 439-44. http://dx.doi.org/10.1001/archderm.142.4.439

• PDF