Vascular structures

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Anatomy of normal skin vasculature

The skin receives vascular supply through superficial and deep vascular plexuses in the dermis. These plexuses constitute anatomic landmarks in skin histology—the superficial vascular plexus marks the junction between the papillary and reticular dermis, whereas the deep vascular plexus separates the reticular dermis from subcutaneous fat (Lever). The superficial plexus is made up of anastomosing small-caliber arterioles that branch into capillaries, which extend into dermal papillae to supply the overlying epidermis, as well as envelop adnexal structures. The deep plexus is made up of medium-caliber vessels, which emanate from larger vessels that traverse the adipose septae of the subcutis. Additionally, the deep plexus connects with the superficial vascular plexus through vertically oriented vessels.

Vascular Structures

In recent years, more attention has been given to the vascular patterns of pigmented and nonpigmented lesions. The increased availability of dermoscopes using polarized light allow for the inspection of a lesion without the need to contact the lesion. This prevents blood vessel compression, which in part helps in making the blood vessel morphology more conspicuous. The recognition of vascular structures under dermoscopy has become increasingly important for a range of diagnoses. The identification of specific vascular characteristics is an important element of the two-step dermoscopic algorithm. When the lesion is categorized as a nonmelanocytic lesion, vascular features can help to diagnose the lesion more specifically, and hence guide management (Level 5 of the revised two-step dermoscopic algorithm). If the lesion is clearly recognized as a melanocytic tumor, then the identification of vessel type and distribution may facilitate the differentiation between benign and malignant diagnoses (Level 6 of the revised two-step dermoscopic algorithm). For more ambiguous cases in which the lesion cannot be easily classified as melanocytic or nonmelanocytic, the clinician may need to rely on vascular structures as the only recognizable features that can assist in the diagnosis. In conclusion, it has become apparent that a finite number of morphologically distinct blood vessels can be visualized under dermoscopy. The vessel morphology and distribution along with other accompanying features can assist the clinician in correctly identifying many benign and malignant lesions. In general, vessels in melanocytic lesions include dotted vessels, comma vessels, linear irregular vessels/serpentine vessels, milky red globules, vascular blush, and polymorphous vessels. Vessels suggestive of nonmelanocytic lesions include arborizing vessels, hairpin vessels, glomerular vessels, crown vessels, and dotted vessels in a string of pearls pattern.

Comma vessels Dotted vessels Hairpin vessels Elongated hairpin vessels
C-shaped or slightly curved vessels Tiny, red dots densely aligned next to each other Small, linear looped vessels Elongated, linear looped vessels
Inflammatory scalp diseases (seborrheic dermatitis, psoriasis), healthy persons Healthy persons in the frontal area, eczema Healthy persons in the frontal area Cicatricial alopecia (lichen planopilaris, folliculitis decalvans), T-cell lymphoma

Straight linear vessels Thin arborizing vessels Thick arborizing vessels Capillary blood extravasations
Straight linear vessels Thinner than the average terminal hair arborizing vessels Thicker than the average terminal hair arborizing vessels Round or oval, sharply demarcated, intensely red areas
Pemphigus vulgaris Healthy persons (the occipital and temporal area), seborrheic dermatitis Discoid lupus erythematosus, basal cell carcinoma Active psoriasis

Concentric perifollicular vessels Milky red globules Linear helical vessels Lace-like vessels
Vessels (loops or linear) arranged concentrically around a follicular unit Globules or larger areas of a fuzzy or unfocused milky red color Linear vessels twisted along a central axis Combination of serpentine and looped vessels
Cicatricial alopecia (lichen planopilaris, folliculitis decalvans) T-cell lymphoma, psoriasis Psoriasis, pemphigus, T-cell lymphoma Psoriasis

Glomerular vessels Serpentine vessels Thick root-like vessels Vessel nets
Coiled or twisted vessels Bending, scarcely branching vessels Thick, irregularly banded, linear vessels Interfollicular network of blood vessels
Psoriasis Discoid lupus erythematosus Discoid lupus erythematosus, congenital capillary malformations Healthy persons, after topical corticosteroids

Currently two different terminologies are used: the descriptive terminology and the metaphoric terminology. dermoscopedia uses both approaches because most individuals are more familiar with the metaphoric terms than with the descriptive terms.

Vessels in the tumor microenvironment

The architecture and distribution of vascular structures, determined in part by neoangiogenic factors, angiogenic inhibitors, and tumor–stromal interactions, differ with tumor type. Oncogene activation in tumors drives angiogenesis by the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and by inhibiting antiangiogenic factors, such as thrombospondin-1. Fibroblasts and endothelial cells are among the many stromal cells involved in the metastatic process, especially those adjacent to the tumor, that is, on the “tumor front.” The tumor microenvironment refers to tumor cells themselves and the surrounding stromal cells and components, such as cytokines, chemokines, collagen, elastin, and growth factors. The interaction of all microenvironment components play an important role in tumor growth and progression. For example, melanoma cells interact with the stroma by way of cytokines, growth factors, and direct cell–cell contact. Melanoma cells release autocrine growth factors, which stimulate proliferation of melanoma cells, as well as paracrine growth factors, including VEGF and platelet-derived growth factor (PDGF), which are involved in angiogenesis and invasion. VEGF has been detected in vertical growth phase melanoma and melanoma metastases, in contrast to benign melanocytic lesions that show no immunoreactivity for VEGF.

Appropriate dermoscopic technique for the visualization of vascular structures: Care must be exercised to insure that blood vessels, if present, are adequately visualized using dermoscopy. Cutaneous blood vessels can readily be blanched by even slight pressure on the skin surface. Thus, non- polarized dermoscopy utilizing alcohol as the fluid interface, where the glass plate of the dermoscope is pressed firmly against the skin surface, has the tendency to blanch out much of the cutaneous vasculature. To prevent this blanching effect, it is advised that the fluid interface (oil or alcohol) be replaced with ultrasound gel. The high viscosity of gel allows one to place the dermoscope onto the lesion with minimal pressure while maintaining full contact between the glass plate and the skin. Fortunately, polarized noncontact dermoscopes have eliminated the need for direct contact between the glass plate and skin, thereby eliminating the need for a liquid interface. Utilizing noncontact polarized dermoscopy has given us the ability to not only observe blood vessels, but also to indirectly assess the vascular volume within skin lesions. An increased vascular volume can be appreciated as a vascular blush (milky red area, pink veil).

Arborizing blood vessels

Arborizing vessels appear under dermoscopy as bright red, thick diameter vessels (0.2 mm or more) from which emanate branching vessels with progressively thinner diameters[1]. These "tree-like vessels" are sharply in focus due to their superficial location, situated slightly below the epidermis, and exhibit irregular branching into fine terminal capillaries of small diameter (10 μm).

Arborizing blood vessels schematic

Differential diagnosis

Arborizing vessels are present in more than 80% of basal cell carcinomas (BCCs), and were classically considered to yield a positive predictive value (PPV) of 94%, and sensitivity and specificity of 96.1% and 90.9%, respectively [2] [3]. However, In a recent study from korea, only 54% of the lesions that displayed arborizing vessels were found to be BCCs [4]. The difference in the PPV of arborizing vessels for the diagnosis of BCC can be explained by the type of lesions that are included in each analysis. If an analysis includes only lesions that are in the differential diagnosis for BCC, the PPV of arborizing vessels may be higher than in an analysis that included all lesions, regardless of their differential diagnosis. This highlights the fact that dermoscopic features should be analyzed based on the context of the lesion on which they appear.

A basal cell carcinoma displaying prominent arborizing vessels

Adnexal tumors can sometimes appear similar to BCCs and may display arborizing vessels. Although uncommon, arborizing vessels may be seen in benign lesions, such as fibrous papules, intradermal nevi, cysts and hypertrophic scars and keloids; however, in these lesions the vessels are usually not in sharp focus. In addition, arborizing vessels can, on rare occasions, be seen in invasive cancers, including melanoma and Merkel cell carcinoma.

There are several histologic variants of BCC, including nodular, superficial, and infiltrative. Each of these BCC subtypes can present as amelanotic lesions or they can present with pigment. BCCs that are amelanotic can be identified based on the presence of arborizing vessels, shiny white areas, crystalline structures, and/or ulceration. Pigmented BCCs (pBCC), which may clinically mimic melanoma, contain specific dermoscopic structures that aid in their proper diagnosis. Menzies model for dermoscopic diagnosis of pBCCs (sensitivity of 93% and specificity of 89–92%) includes arborizing vessels as an important diagnostic feature. Arborizing vessels were observed in 52% of pBCCs, compared with 23% of melanomas and only 8% of benign skin lesions [5]. While arborizing vessels are often quite prominent in nodular BCC, they tend to be less conspicuous in superficial BCCs (sBCC) and in fibroepithelioma of Pinkus, a rare BCC subtype. In sBCC it is common to see short fine telangiectasias, which are sharply in focus and arranged irregularly throughout the lesion. Additional presence of shiny white-to-red areas and multiple small ulcer- ations or erosions can provide reassurance that the lesion under investigation is a superficial BCC. These fine arborizing vessels, which are described as smaller in diameter than typical arborizing vessels and with less branching, have also been noted in fibroepithelioma of Pinkus. In addition, Pinkus tumors are often accompanied by dotted vessels at the lesion’s periphery.

Short-fine telangiectasia in a superficial BCC

Hairpin vessels

Hairpin (looped) vessels are characterized by vessels that resemble hairpins, consisting of a U-shape with a sharp bend at one end. These looped hairpin vessels can appear distorted when the hairpin configuration twists around its own axis.

Hairpin vessels schematics.jpg

Differential diagnosis

Hairpin vessels are found in melanocytic and nonmelanocytic tumors. Relatively thin, uniform hairpin vessels are often seen in keratinizing tumors, such as seborrheic keratoses (SKs). In these benign keratinizing tumors, a whitish halo often surrounds the vessels. This whitish halo probably represents viable tumor keratinocytes surrounding the dermal papilla, which contains the hairpin vessel. In a study of pigmented SKs, hairpin vessels were seen in 63% of lesions; more specifically, these vessels were seen in 50% of plaque-type SKs and 43% of papular/nodular SKs but were only seen in 6% of patch type SKs[6]. In another study looking at lesions with vascular dermoscopic structures, 51.2% of SKs contained hairpin vessels, conferring a PPV of 70%[2]. In keratoacanthomas, hairpin vessels are located peripherally, with a yellow keratotic center. In contrast, hairpin vessels in melanomas are often surrounded by a pink halo. Hairpin vessels may also be observed in warts, SCCs, BCCs, dermal nevi, and Spitz nevi.

Hairpin vessels.JPG

Milky red globules /areas

Milky red globules[7] are, as their name suggests, globules with a milky reddish coloring. These vascular structures may be observed within or near areas with a milky red color [2].

Milky red globules schematics.jpg

Differential diagnosis

Although milky red globules are not seen frequently, when present, they are highly suggestive of invasive melanoma [1]. They may be valuable in the recognition of thicker amelanotic/hypomelanotic melanoma (AHM), which often do not have many noticeable or identifying features. In AHM, milky red globules/red areas were reported in 31% of thin melanomas (1mm) and in 93.3% of thick melanomas (1mm), as compared with 17.3% and 9.1% of amelanotic /hypomelanotic benign melanocytic lesions and amelanotic/hypomelanotic non-melanocytic lesions, respectively. In another study, 4.7% of melanomas with vascular structures on dermoscopy contained milky red globules/areas, correlating with a PPV of 77.8%; only 0.5% of nonmelanoma lesions had these structures. Vascular blush, also known as erythematous blush, pink veil, or milky red areas, represents a red or pink region that corresponds to an area with increased vascularity. Thus, vascular blush can be seen in lesions, such as dermatofibromas, vascular tumors, such as pyogenic granulomas, inflammatory lesions, and both melanoma and nonmelanoma skin cancers. Although vascular blush can be seen in nevi, it tends to be more common and conspicuous in melanoma.

Glomerular vessels

Glomerular vessels are the dermoscopic manifestations of tortuous, dilated capillaries [1]. They are named as such because their morphology is reminiscent of the convoluted capillaries that comprise the glomerular apparatus of the kidney[2]. Glomerular vessels are larger than dotted vessels and can be positioned in clusters throughout the lesion. Histologically these vessels correlate to dilated capillaries in the dermal papillae and papillary dermis [8].

Glomerular vessels schematics.jpg

Differential diagnosis

Most commonly, glomerular vessels are associated with SCCs, in which the glomerular vessels are principally distributed focally in clusters and at the periphery of the lesion together with hyperkeratosis (i.e., scaly surface). In a study of Bowen’s disease (BD), 80% of pigmented BD and 100% of nonpigmented BD displayed glomerular vessels [9]. In another study, glomerular vessels were seen in 81.2% of BD cases with a PPV of 61.9%. In contrast, glomerular vessels were seen in only 1.3% of melanomas, 12.2% of SKs, and 7.1% of invasive SCCs [2]. Glomerular vessels can also be seen in clear cell acanthoma where the vessels will be arranged in a string of pearls distribution, in psoriasis where the vessels are distributed throughout the lesion in an organized pattern, and in stasis dermatitis where these vessels will be visible in normal appearing skin. Lastly, glomerular vessels can also be seen in melanoma, especially within metastatic foci.

Glomerular vessels appearing on a squamous cell carcinoma

Comma vessels

Comma vessels are slightly curved vessels that appear to take the shape of a comma[1]. These vessels tend to appear slightly out of focus, as their deeper location within the dermis does not allow for sharp visualization under dermoscopy.

Untitled Artwork (12).jpg

Differential diagnosis

Comma vessels are most commonly associated with dermal nevi. In a study of dermal/ congenital nevi, 66.3% exhibited this vascular pattern, with a PPV of 94% [2]. In another study, comma vessels, when distributed in an organized fashion and when they comprise the predominant observed vessel morphology, are predictive that the lesion in question is not a melanoma [10]. In other words, comma vessels are highly suggestive of benign nevi with dermal nevi being the most common, but they can also be seen in compound nevi.

Dotted vessels

Dotted vessels appear as small red dots with a diameter of 0.01–0.02 mm, and they represent vessels aligned perpendicular to the skin surface [3].

Dotted vessels schematics.jpg

Differential diagnosis

Dotted vessels can be seen in inflamed skin, traumatized skin, or in skin overlying stasis. However, they can also be seen in cutaneous tumors. The presence of dotted vessels often implies that a lesion is melanocytic; in one study, 90% of the lesions with dotted vessels were melanocytic [2]. In melanocytic tumors, dotted vessels confer a PPV of 38% for melanoma, 16% for dermal/congenital nevi, 21% for Clark nevi, and 16% for Spitz nevi. In benign nevi, dotted vessels correspond to vessels at the tips of the dermal papillae and dermoscopically often appear to be situated within the holes of the pigment network. In melanoma, dotted vessels, which are frequently found in conjunction with other vessel types, can be seen anywhere within the lesion but tend to be present at a higher concentration toward the center of the lesion [11]. In a study of amelanotic and hypomelanotic melanomas (AHM), dotted vessels were more commonly seen in melanomas <1mm in thickness (27.6%) when compared with those >1 mm in thickness (20.0%); when evaluating purely amelanotic melanomas, dotted vessels were seen in 60% of cases [12]. In another study, Bono and colleagues reported the presence of dotted vessels in 100% of thin amelanotic melanomas (<1mm) (n = 9) [13]. The aforementioned data suggests that dotted vessels may be one of the first morphologic types of neoangiogenic vessels visible in melanoma because they appear to be more prevalent in thinner tumors.

In a study analyzing amelanotic/hypomelanotic benign melanocytic lesions (AHBML) and amelanotic/hypomelanotic nonmelanocytic lesions (AHNML) (tumors), dotted vessels were observed in 32.7% and 21.8% of lesions, respectively[12]. In nonmelanocytic lesions, dotted vessels are commonly seen in psoriasis, clear cell acanthomas (CCA), and squamous cell carcinoma (SCC). The distribution and arrangement of dotted vessels within the aforementioned lesions can be very helpful in diagnosis. Dotted vessels in psoriasis are relatively uniform in size and are distributed homogenously throughout the plaque [14]. When dotted vessels are arranged in a “string of pearls” or serpiginous distribution, then the diagnosis of CCA is almost certain. Dotted vessels present focally at the periphery or throughout the entire lesion and in association with adherent scale is suggestive of SCC [11].

Squamous cell carcinoma presenting with dotted vessels

Amelanotic melanoma presenting with dotted vessels

Another more recently described vascular feature is the pattern of follicular red dots, which have been described in active discoid lupus erythematosus. The follicular red dots are seen surrounding the hair follicle openings and consist of regularly distributed, concentric reddish dots in a region of alopecia. This may represent dilation of blood vessels with extravasation of red blood cells surrounding the widened infundibula.

Linear irregular vessels

Linear irregular or serpentine vessels are red vascular structures with a range of size, shape, and distribution [2].

Linear irregular vessels schematics.jpg

Differential diagnosis

Linear irregular vessels can be identified in melanoma, basal cell carcinomas, and dysplastic nevi [11][1]. In one study, 33.3% of melanomas had these vessels, with a PPV of 67.6% [2]. In another study of amelanotic/hypomelanotic melanoma (AHM), linear–irregular vessels were seen in 10.3% of thin AHM (<1 mm), in 0% of thick AHM (>1mm), and 0% in amelanotic/hypomelanotic benign melanocytic lesions[12]. Thus, similar to dotted vessels, the presence of these vessels suggests that the melanoma is still relatively thin.

Melanoma showing linear irregular vessels

Polymorphous vessels

Polymorphous vessels are used to describe the vasculature of lesions in which two or more types of vessel morphologies are detected[15].

Polymorphous vessels schematics.jpg

Differential diagnosis

The presence of polymorphous vessels may suggest a diagnosis of melanoma[1]. The most common combination of vessel types seen in melanoma is the presence of both dotted vessels and linear–irregular vessels[2]. In a study of lesions with vascular features seen on dermoscopy, only 20% of the lesions contained polymorphous structures, which correlated with a PPV of 52.6% for melanoma[2]. More specifically, the combination of dotted and linear–irregular vessels was found in 18% of amelanotic/hypomelanotic melanomas but only extremely rarely in other nonmelanoma amelanotic/hypomelanotic lesions (1.8% of AHNML and 0% of AHBML)[12]. Polymorphous vessels in combinations other than dotted vessels and linear–irregular vessels may be observed in cutaneous melanoma metastases[16]. They can also be seen in papillomatous melanocytic nevi[17] and other tumors, such as eccrine poromas[18].

Corkscrew / tortous vessels

Corkscrew vessels schematics.jpg

Differential diagnosis

Corkscrew vessels have been observed in nodular melanoma, desmoplastic melanoma, and cutaneous melanoma metastases[19].

Crown vessels

Crown vessels comprise linear, curved vessels with minimal branching, situated along the periphery and extending toward the center without crossing it, giving the appearance of a crown[2].

Differential diagnosis

Crown vessels are characteristic of sebaceous hyperplasia; this pattern was seen in 83.3% of sebaceous hyperplasia with a PPV of 83.3%[20]. Crown vessels may also be seen in molluscum contagiosum [21].

Sebaceous hyperplasia schematic.jpg
Sebaceous hyperplasia displaying crown vessels

Strawberry pattern

Actinic keratosis schematic.jpg

The term “strawberry pattern” refers to the distinctive dermoscopic appearance of facial actinic keratoses, consisting of a pink/red pseudonetwork with blurry vessels coursing between hair follicle openings filled with keratotic plugs [22].

Actinic keratosis diplaying strawberry pattern (bottom part of the lesion)

String of pearls pattern

String of pearls schematic.jpg

This pattern represents the unique appearance of dotted or glomerular vessels arranged in a serpiginous distribution that may appear like a “string of pearls.” This pattern is highly suggestive of a diagnosis of clear cell acanthoma[15].

Clear cell acanthoma displaying string of pearls pattern

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