Vascular patterns in basal cell carcinoma: Dermoscopic, confocal and histopathological perspectives

Abstract

Basal cell carcinoma (BCC) is the most prevalent skin cancer in the Caucasian population. A variety of different phenotypic presentations of BCC are possible. Although BCCs rarely metastasize, these tumors commonly destroy underlying tissues and should therefore be treated promptly. As vascular formation and angiogenesis are indicators of tumor development and progression, the presence of blood vessels, their morphology and architecture are important markers in skin lesions, providing critical information towards pathogenesis and diagnosis. BCC commonly lacks pigmentation, therefore it is important to emphasize the usefulness of vascular feature detection, recognition, quantification and interpretation. To answer the question of whether vascular patterns observed on dermoscopy, reflectance confocal microscopy (RCM) and histopathology might reflect the biologic behavior of BCCs, we undertook this review article. Several studies have sought, by various means, to identify vascular features associated with the more aggressive BCC phenotypes. Dermoscopic vascular pattern assessment can facilitate diagnostic discrimination between BCC subtypes, more aggressive BCCs displaying less or no pink coloration and a relative absence of central tumor vessels. RCM, a novel, non-invasive imaging technique, allows for the quantification of blood vessel size, density, and flow intensity in BCCs. BCCs are distinguished on RCM chiefly by vessels that branch and intertwine between neoplastic aggregates, a pattern strongly reflecting tumor neo-angiogenesis. The analysis of these vascular morphological and distribution patterns can provide further support in the diagnosis, assessment, or monitoring of BCCs. Histopathology shows significantly higher microvessel densities in the peritumoral stroma of BCCs, when compared to normal skin or benign tumors. This angiogenic response in the stroma is associated with local aggressiveness, therefore the quantification of peritumoralmicrovessels may further assist with tumor evaluation. How dermoscopy and RCM vascular patterns in BCC correlate with histopathological subtype and thus help in discriminating aggressive subtypes definitely deserves further investigation.

Keywords: basal cell; biomarkers; carcinoma; confocal reflectance; dermoscopy; histology; microscopy; microvessels.

Figure 1.

Dermoscopic vascular features in BCC. (A) Arborizing vessels, arborizing microvessels (black circle). (B) Arborizing microvessels (black arrow) and short fine telangiectasia (white arrow). (C) Milky-pink background (black asterisks) and short fine telangiectasia (red circle). (D) Dotted (green circle), hairpin (white arrow), comma (black arrows) and glomerular vessels (green arrows).

Figure 2.

BCC vascular patterns by RCM. (A) RCM mosaic (1×1 mm) revealing horizontal, parallel oriented, tortuous, enlarged blood vessels with fast blood flow immediately beneath the surface in the tumoral area of a BCC. (B) RCM image (500×500 µm) showing blood vessels that surround tumor islands in a circular fashion in a nodular BCC. (C) RCM image (500×500 µm) of superficial, loop-like blood vessels with fast blood flow in the tumoral area of a BCC. (D) RCM image (500×500 µm) of a very large blood vessel located in the immediate proximity of BCC tumor islands.

Figure 3.

Microvascular architecture in basal cell carcinomas. (A and B) Nodular basal cell carcinoma. Numerous vessels branched and/or dilated in the vicinity of the tumor (H&E, ×200). (C) Numerous peritumoral vessels in the vicinity of the tumor (VEGF, ×400). (D) High density of vessels of variable calibers in peritumoral location (CD34, ×200). (E) Superficial basal cell carcinoma. Fewer peritumoral vessels than in nodular basal cell carcinoma (H&E, ×200). (F) Microvascular density in the periphery of a superficial basal cell carcinoma is lower than that in nodular basal cell carcinoma (CD34, ×200).