Sociedade Brasileira de Dermatolodia Surgical & Cosmetic Dermatology


ISSN-e 1984-8773

Volume 4 Number 2

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Review articles

Reflectance skin confocal microscopy of basal cell carcinoma

Microscopia confocal reflectante a laser: carcinoma basocelular

Alessandra Cristine Marta1, Giovanni Pellacani 1, Mariana de Figueiredo Silva1, Rute Facchini Lellis1, Marcus Maia1

Assistant Physician, Dermatology Clinic,
Santa Casa de Misericórdia de São Paulo –
São Paulo (SP), Brazil1, PhD; Professor, Università Degli Studi Di
Modena e Reggio Emilia – Modena, Italy2, Dermatology Specialist, Santa Casa de
Misericórdia de São Paulo3, Assistant Physician, Anatomical Pathology
Department, Santa Casa de Misericórdia de
São Paulo4, PhD; Adjunct Head of Dermatology, Santa
Casa de Misericórdia de São Paulo5

Received on: 25 February 2012
Approved on: 10 May 2012
This study was carried out at the Santa Casa
de Misericórdia de São Paulo – São Paulo (SP),
Financial support: None
Conflict of interest: None



Basal cell carcinoma is the most common malignant skin tumor. Reflectance confocal microscopy is a non-invasive technique that provides real-time, in vivo, horizontal tissue images, at a quasi-histological resolution, by employing a low-power laser beam of 830 nm. In this paper, we review the major morphological criteria for diagnosing this tumor using reflectance skin confocal microscopy.



Basal cell carcinoma (BCC), first described by Jacob in 1827, is the most common type of malignant skin tumor, accounting for 80% of non-melanoma skin cancers. 1

In vivo reflectance confocal microscopy (RCM) is a noninvasive diagnostic tool that uses an 830 nm low-power laser beam to obtain real-time, high resolution (cellular) imaging of the superficial layers of the skin down to a 250 mm depth. In this technique, contrast is provided by differences in the refractive index of different cellular organelles within the tissue. Images obtained are similar to those of conventional histopathology.

A number of reports on RCM and BCC have been published, and five major morphological criteria have been defined for its diagnosis to date.2


Under skin confocal microscopy, BCC presents different features that have direct histological correlations, which can be used in pre-surgical diagnosis. Since RCM allows the visualization of horizontal sections of the skin, the description of BCC''''''''s characteristic features seen through RCM are listed from the epidermis down to the dermis, for practical reasons.

The epidermis usually presents variable degrees of keratinocytic atypia that can reach a marked pleomorphism of the keratinocyte shape and nuclei, along with parakeratotic nuclei in the stratum corneum, which are linked to the degree of actinic damage. Conversely, the presence of elongated monomorphic keratinocytes, with polarization of the nuclei oriented along them (Figure 1), seemed to be the most sensitive and specific feature to help diagnose BCC. 2,3

At the dermal-epidermal junction, one of the most characteristic features of BCCs is the identification of compact aggregates of tightly packed tumor cells, which form tubercles or cord-like structures and nodules. 4 Those structures usually present a peripheral nuclear palisading that corresponds to peripheral basaloid nuclei that are arranged perpendicularly to the axis of the tumoral island (Figure 2). It is possible to observe a high reflectivity (combined with intervening areas of low reflectivity) in the tumoral islands. Bright dendritic structures that correspond to melanocytes, 5 usually with small cellular bodies, round large plump cells, and/or small bright particles, which correspond to inflammatory infiltrate, are likewise found within the tumoral islands – particularly in the BCC pigmented type. Those islands may be surrounded by a dark zone that corresponds to the separation of the tumor from the stromal tissue, which is also typically seen in histopathological analysis. This tumor-stroma "border" corresponds to an area that is particularly rich in mucin, which surrounds the tumor parenchyma. 6 In hypopigmented/amelanotic BCC, tumor cords and islands are barely visible and appear as hyporeflective areas (dark silhouettes) that are darker than the epidermis or dermal collagen (Figure 3). 7

The stroma surrounding the tumor is highly refractive; collagen bands display a "frayed" appearance. Scattered bright particles, which correspond to leukocytes, and/or plump bright cells, which correspond to melanophages, can be detected between tumoral cords and islands. In addition to these features, BCC presents abundant elongated and/or twisted blood vessels, visible immediately beneath the epidermis and juxtaposed to the tumor parenchyma, sometimes presenting the rolling of leukocytes along the endothelial lining. 8

In sum, RCM diagnosis of BCC has been defined based on five major criteria: elongated monomorphic basaloid nuclei, polarization of those nuclei along the same axis, prominent inflammatory infiltrate, increased dermal vasculature with twisted tumor vessels, and pleomorphism of the overlying epidermis, with the disappearance of the normal honeycomb pattern. In the analyzed studies, the presence of polarized nuclei presented the highest sensitivity (91.6%) and specificity (97%). Moreover, the presence of four or more criteria suggested a sensitivity of 82.9% and specificity of 95.7%.

Regarding the differences between subtypes of BCC, nodular variants also present aggregated tumor cell nests in the upper dermis that are often adjacent to large and dilated blood vessels.

Superficial BCCs are concentrated in the lower part of the epidermis and the superficial dermis. Aggregates of polarized cells with elongated nuclei oriented along the same axis can be seen in the basal cell layer and in the superficial dermis, though the diagnosis is not straightforward in all cases.

In addition to the aggregates of monomorphic cells with elongated nuclei in the upper dermis, infiltrative BCCs present a dense and cell-rich stroma. Peripheral palisading is usually absent, and the borders between tumor cell aggregates and stroma are poorly defined, making the diagnosis of this variant even more challenging.

Conversely, the diagnosis of pigmented variants of BCC is usually straightforward with RCM, due to the marked brightness of the tumoral islands, which also show highly refractive dendritic cells (which correspond to melanocytes) and bright oval- and star-shaped structures with indistinct borders (which correspond to melanophages in traditional histology) (Figure 4).


Real-time, near-infrared laser-scanning RCM provides a way to diagnose BCCs in vivo with reliable sensitivity and specificity, and may potentially eliminate the need for invasive diagnostic biopsies. This is particularly useful in cases of flat or barely palpable lesions located in aesthetically sensitive areas, where non-surgical treatments such as imiquimod or photodynamic therapy are most frequently recommended.


1 . Rubin AL, Chen EH, Ratner D. Basal cell carcinoma. N Engl J Med. 2005; 353(21): 2262-9.

2 . Nori S, Rius-Díaz 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(6): 923-30.

3 . Gonzalez S, Tannous Z. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. J Am Acad Dermatol. 2002; 47(6): 869-74.

4 . 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.

5 . 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.

6 . Ulrich M, Roewert-Huber J, González 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 Cutan Pathol. 2011; 38(2): 190-5.

7 . Braga JCT, Scope A, Klaz I, Mecca P, Gonzalez S, Rabinovitz H, 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.

8 . 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(2): 384-6.

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