Review of vasculature visualized on dermoscopy

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1 doi: / Journal of Dermatology 2017; 44: REVIEW ARTICLE Review of vasculature visualized on dermoscopy Yaei TOGAWA Department of Dermatology, Chiba University Graduate School of Medicine, Chiba, Japan ABSTRACT Dermoscopy is a useful tool for finding and screening skin tumors, especially skin cancers. It is well known that it is useful to diagnose pigmented tumors, such as melanocytic lesions. In recent years, after the publication of a revised two-step algorithm in 2010, dermoscopy gradually has been used to diagnose non-pigmented or non-melanocytic lesions based on their vascular structures. Some skin lesions have specific vascular structures that aid in diagnosis. In this review, I discuss the various patterns of the vascular structures and their distribution, focusing on their clinical importance and usefulness in daily medical treatment. Key words: amelanotic/hypomelanotic melanoma, descriptive or metaphoric terms, non-pigmented or non-melanocytic lesions, non-polarized or polarized dermoscopes, vessel morphology. INTRODUCTION Dermoscopy is a non-invasive diagnostic technique that magnifies skin lesions to show the color and structural details of the epidermis, dermoepidermal junction and papillary dermis. 1 Non-polarized dermoscopes have been the standard instruments for capturing dermoscopic images, especially for inspection of structures in pigmented lesions. 2 However, commercially available dermoscopes that use the characteristic of cross-polarized light were introduced approximately 10 years ago, and allow monitoring of vascular structures in the skin. 1,3 Different vessel morphologies are associated with different melanocytic or non-melanocytic skin tumors; thus, the recognition of distinctive vascular structures may be helpful for diagnostic purposes, especially when the classic pigmented dermoscopic structures are lacking. 4 The DELTA 20T â (HEINE Optotechnik, Herrsching, Germany) contact dermoscope has precision optics superior to other dermoscopes and provides the ability to toggle between polarized and non-polarized illumination to enable the visualization of fine dermoscopic images, including vascular structures. To visualize and evaluate vascular structures, we must use appropriate devices and know how to use them properly. With contact dermoscopes, the contact glass plate must be set carefully on the lesion, with minimal downward pressure. 5 A translucent ultrasound gel, which is an effective contact medium with appropriate high viscosity, is also needed. To obtain a fine image, it is important to apply a sufficient amount of ultrasound gel to the lesion, which provides a soft surface for contact with the glass plate of the dermoscope. Because vascular structures are generally minute and subtle, it is desirable to record the dermoscopic image obtained and to project them on a large-sized PC monitor for review. After the Consensus Net Meeting on Dermoscopy in 2000, the results of which were discussed at the 1st World Congress of Dermoscopy, a two-step algorithm for a dermoscopic diagnostic method was established, mainly for pigmented skin lesions. 6 However, studies have also reported the usefulness of dermoscopy to evaluate amelanotic/hypomelanotic neoplasms, including their vascular structures. In addition, the differences between polarized dermoscopy and non-polarized dermoscopy have been discussed. 3,7,8 Thus, in 2010, Marghoob and Braun devised a revised two-step algorithm that includes polarized dermoscopy and blood vessel morphology (Fig. 1). 9 The first step of this algorithm includes seven different levels for differentiation between melanocytic lesions and nonmelanocytic lesions (Fig. 1b). Each specific or diagnostic structure of blood vessels is shown for non-melanocytic lesions and melanocytic lesions, in addition to vascular disease, in this algorithm. Menzies et al. tested this modified first-step algorithm (that included vascular structures) to differentiate melanocytic lesions from non-melanocytic lesions. 10 Pigmented lesions showed different results compared with amelanotic/hypomelanotic lesions. The first-step algorithm showed a very high sensitivity (98%) for both non-nodular invasive melanoma and nodular melanoma (NM), and also showed a high sensitivity for benign nodular melanocytic lesions (95%); meanwhile, the specificity was very low (62%). However, as with the original version, the first-step algorithm did not achieve good sensitivity for detecting amelanotic/hypomelanotic nodular lesions as being truly melanocytic (84% NM, 88% benign lesions). 11 In fact, 12 melanomas of both pigmented and hypopigmented lesions were misclassified as non-melanocytic, and 11 had features of basal cell carcinoma (BCC). Therefore, we should not overestimate this algorithm, and we should take clinical findings like palpation into consideration in diagnosis. For example, Correspondence: Yaei Togawa, M.D., Ph.D., Department of Dermatology, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba , Japan. togawa-yk@faculty.chiba-u.jp Received 4 October 2016; accepted 6 October Japanese Dermatological Association 525

2 Y. Togawa (a) Skin tumor Dermoscopic evaluation First step: Criteria of melanocytic or non-melanocytic lesion (tumor) are divided to the level 1 7. If the lesion meet the criteria of melanocytic lesion including vascular structures: Level 1, 6 and 7, then go to second step. Criteria of findings including vascular structures of non-melanocytic lesion as following were shown in the Level 1 to 5 of first step. Structureless or featureless lesion Second step shows criteria of melanoma: Pattern analysis ABCD rule Menzies method 7-point checklist CASH method Kittler method Dermatofibroma: Level 1 Basal cell carcinoma: Level 2 Seborrheic keratosis: Level 3 Hemangioma, angiokeratoma: Level 4 Keratoacanthoma: Level 5 Squamous cell carcinoma: Level 5 Clear cell acanthoma: Level5 Sebaceous hyperplasia, molluscum contagiosum: Level 5 Benign lesion (melanocytic nevus) Malignant lesion (melanoma) (b) First step Level 1: criteria of melanocytic lesion Pigment network Streaks Aggregated globules (excluding multiple blue-gray globules) Homogenous blue pigmentation Parallel pattern (acral) Pseudonetwork (face) If any above one is filled, melanocytic lesion will be suspected and go to second step. Level 3: criteria of seborrheic keratosis Multiple milia-like cysts Comedo-like openings Light-brown fingerprint-like structures Cerebriform pattern/fissures and ridges Crypts Moth-eaten borders Network-like structures Fat finger-like structures If any above one is filled, seborrheic keratosis will be suspected. Caution is needed for dermatofibroma, which shows delicate pigment network around central white patch. Pseudonetwork or pigment network is sometimes also present in senile fleck or seborrheic keratosis. Level 2: criteria of basal cell carcinoma Absence of pigment network and Arborizing vessels Leaf-like areas Large blue-gray ovoid nests Multiple blue-gray globules Spoke wheel areas Ulceration Shiny white areas If any above one is filled, basal cell carcinoma will be suspected. Advanced melanoma also show it sometimes. Level 4: vascular disease Red-blue to black lacunae/lagoonlikestructures (hemangiomaor angiokeratoma Red-bluish to reddish black homogenous areas (hematoma) Level 5: vascular findings of non-melanocytic lesion Glomerular vessels (squamous cell carcinoma or Bowen s disease) Crown vessels (sebaceous hypaerplasia, molluscum contagiosum) Pearls on a string/serpiginous vessels (clear cell acanthoma) Hairpin vessels (keratoacanthoma, seborrheic keratosis) Level 6: vascular findings of melanocytic lesion Comma-shaped blood vessels (dermal nevus) Dotted vessels (melanoma and same as following) Linear irregular vessels Atypical hairpin vessels Corkscrew/tortuous vessels Polymorphous vessels Level 7: non-specific structureless/featureless lesion can never exclude melanoma Structureless/featureless lesion Biopsy is recommended. Figure 1. Revised two-step algorithm for dermoscopy. 12 (a) Summary of the revised two-step algorithm. The item added in the revised edition is shown in red. (b). Levels 1 7 are in the first step of the revised two-step algorithm Japanese Dermatological Association

3 Vessels visualized on dermoscopy seborrheic keratosis (SK) has a rough surface, and BCC is hard to some extent, while melanocytic lesions including melanoma are generally not hard upon palpation. Zalaudek et al. suggested a three-step algorithm for dermoscopic diagnosis of a non-pigmented skin tumor, which depended on vascular morphology (Fig. 2), the architectural arrangement of the vasculature (Fig. 3), and other optional clues. 5,12 The additional clues, such as a white halo surrounding the vessels, provide further findings for diagnosis (Fig. 2d, as is usually seen in keratinizing tumors), 13 residual pigmentation (in melanocytic lesions showing hypopigmentation), surface scales, ulcerations, hairs, central duct openings, and so forth. Among the various vascular patterns that have been reported, the following six main categories of vascular morphologies 5 can be identified: comma, dotted, linear irregular, hairpin, glomerular and arborizing vessels (Fig. 2). In addition, the following three specific global morphologies can be identified: crown vessels surrounding a white center, strawberry pattern and milky red areas/globules. 4,13 15 With some exceptions, the comma (Fig. 4), dotted (Fig. 5) and linear irregular vessels (Fig. 6) are related to melanocytic lesions; for example, dermal nevi, Spitz nevi and amelanotic/hypomelanotic melanoma (AHM), respectively. 5 Hairpin (Fig. 7), glomerular (Fig. 8) and arborizing (Fig. 9) vessels are commonly suggestive of nonmelanocytic lesions. Hairpin vessels, encircled by a whitish halo, are indicative of SK and squamous cell carcinoma (SCC), including keratoacanthoma, and also verruca vulgaris. 4,16 Glomerular vessels, typically aggregated focally at the peripheral space of the lesion, are usually seen in Bowen s disease and intraepidermal carcinoma or SCC. 4 BCC often shows arborizing vessels, a feature that is rather specific. 4,13,14 Corkscrew or tortuous vessels (Fig. 6), in addition to dotted, linear irregular and atypical hairpin (serpentine) vessels on a pink background, are sometimes found in melanoma. 9 Vasculature that is distributed into a pearls on a string or serpiginous pattern is diagnostic for clear cell acanthoma (Fig. 10). 4 Crown vessels surrounding a white-yellow lobulated center (Fig. 11) are a hallmark of sebaceous (a) (b) (c) (d) (e) (f) (g) (h) (i) (j) k (l) (m) (n) Figure 2. (a f) Vessel morphology. (a f) Six main morphological categories of vascular patterns: (a) comma (curved), (b) dotted (dotted), (c) linear irregular (linear or serpentine), (d) hairpin (looped), (e) glomerular (coiled), (f) arborizing (serpentine, branched). (a c) Related to melanocytic lesions: dermal nevi, Spitz nevi, and amelanotic/hypomelanotin melanoma, respectively, (d f) usually suggestive of non-melanocytic tumors: seborrheic keratosis, squamous cell carcinoma and keratoacanthoma (hairpin), Bowen s disease and intraepidermal carcinoma (glomerular) and basal cell carcinoma (arborizing). (g n) Other characteristic vascular pattern: (g) corkscrew (helical), (h) tortuous (serpentine), (i) pearls on a string or serpiginous pattern (serpiginous), (j) polymorphous (polymorphous), (k) crown (radial branched and serpentine), (l) strawberry pattern (structureless, red, interrupted by follicular openings), (m) milky red globules (structureless zone, pink), (n) red-purple lacunae (clods, various reddish colors). (g,h,m) usually suggestive of melanoma, (i) hallmark of clear cell achanthoma, (i) related to malignant tumor including melanoma, (k) suggestive of sebaceous hyperplasia and molluscum contagiosum, (i) specific for actinic keratosis, (n) hallmark of hemangioma including angiokeratoima. This schema shows a white halo surrounding the hairpin vessels Japanese Dermatological Association 527

4 Y. Togawa (a) (b) (c) (d) (e) Figure 3. Vessel arrangement: (a) radial (i.e. senile sebaceous hyperplasia, keratoacanthoma, molluscum contagiosum), (b) serpiginous (i.e. clear cell acanthoma), (c) branched (i.e. basal cell carcinoma), (d) clustered (i.e. Bowen s disease), (e) centered dots (i.e. melanocytic lesions such as Spitz nevus or amelanotic/hypomelanotic melanoma). Figure 4. Comma vessels in a dermal nevus. Various sizes of comma vessels can be seen. Figure 5. Dotted vessels in a melanoma. Many dotted vessels are seen in the depigmented area for regression. hyperplasia and molluscum contagiosum. 17,18 A so-called strawberry pattern (Fig. 12) and milky red areas/globules (Fig. 13) are structures relatively diagnostic of actinic keratosis and thick AHM, respectively. 16 The presence of milky red areas/globules, also known as multiple shades of pink, probably represents an increased vascular volume and neoangiogenesis. 11 The combination vascular pattern, which contains more than one type of vessel in the same lesion, is termed polymorphous. If polymorphous vessels, including atypical linear vessels, or the predominance of atypical linear vessels are observed, malignant skin tumors should always be ruled out. 4,19 It is thought that the polymorphous vessels that consist of dotted and linear vessels placed in the center are most commonly associated with melanoma. 16 A hemangioma or angiokeratoma usually has red-purple or red-blue to black lacunae, and maroon (which is low red in another definition) also known as lagoon-like structures, as very specific features (Fig. 14). 9, Japanese Dermatological Association

5 Vessels visualized on dermoscopy Figure 6. Corkscrew or tortuous vessels in an amelanotic/hypomelanotic nodular melanoma. There are corkscrew or tortuous vessels (white arrowheads) and linear irregular vessels (blue arrowheads) in a pink background. They can be seen all over the lesion, including the peripheral space. Figure 9. Arborizing vessels in a basal cell carcinoma. Arborizing vessels are crooked and branched like lightning (white arrowheads). Figure 7. Hairpin vessels in seborrheic keratosis. Hairpin vessels with a white halo are a specific clue for keratinizing tumors. Figure 10. Pearls on a string or serpiginous pattern vessels in the nodule suggest a clear cell acanthoma. We could not perform a biopsy on this lesion, but clear cell acanthoma was highly suspected. This is the same case reported in a Japanese publication. 30 Figure 8. Glomerular vessels in Bowen s disease. Glomerular vessels in Bowen s disease are usually arranged regularly Japanese Dermatological Association Figure 11. Crown vessels in a sebaceous hyperplasia. Crown vessels surrounding a white-yellow polylobular center are a specific clue for sebaceous hyperplasia, while they sometimes mimic molluscum contagiosum (white arrowheads). 529

6 Y. Togawa Figure 12. Strawberry pattern in an actinic keratosis. Keratotic and plugging follicles with a reddish background caused by increasing superficial vascular volume are a specific clue for actinic keratosis (white dotted circle). Figure 13. Milky red areas/globules in a hypomelanotic melanoma. Milky red areas/globules are a specific clue for thick melanoma (white dotted circle). The milky red color likely indicates increased vascular volume and neoangiogenesis. Figure 14. Red-purple lacunae in an angiokeratoma. The lacunae show various shades of red-purple color (white arrowheads). Kittler et al. 21 have proposed a new definition of structures including the vasculature using purely morphological descriptive terminologies to avoid metaphoric terms, and recently, after the 3rd Consensus Conference of the International Society of Dermoscopy, standardization of that terminology was advocated (Table 1). 20 According to their definition, vessels can be categorized morphologically into only three main types: dots (dotted vessels), clods (red-purple lacunae) and linear (mildly curved vessels). Furthermore, with regard to morphology, linear vessels may be classified into five subtypes as follows: coiled (i.e. glomerular vessels), looped (i.e. hairpin vessels), serpentine (i.e. linear vessels with multiple bends, including linear irregular, arborizing and crown vessels), helical (i.e. corkscrew vessels) and curved (i.e. comma vessels). The present consensus is that both descriptive and metaphoric terms are appropriate and acceptable for the vocabulary of dermoscopy, and both terminologies should be used properly on demand. With regard to the morphology of vascular structures, vessels located in the superficial dermis (directly below the epidermis) are bright red and focused, while vessels found in the deeper dermis appear pink and blurred owing to the scattering of light by dermal collagen fibers. 5 Vessels that are situated parallel to the skin surface will be seen as lines on dermoscopy, while vessels arranged vertically appear as dots or loops. 5 Essentially, vasculature on dermoscopy strongly depends on tumor progression and volume. 10,13 In fact, the vascular patterns of flat and superficial AHM or BCC usually differ from their thick, nodular counterparts. 5 Because NM has a greater vertical growth rate than other melanoma subtypes, 22 NM lesions rarely appear as thinner small papules on first appearance, and only a small study of thin NM (1.3-mm thickness) has been reported. 23 It seems that NM lacks any distinct vascular pattern, although multiple shades of pink, white, red, blue, brown or gray may be the only clue for correct diagnosis. 11,24 29 In contrast, in a study of AHM, 11 thicker melanoma had an increased prevalence of all vessels, greater prevalence of pink color, and more hairpin and thick-type vessels, although dotted vessels were less frequently found as the predominant vessel type. Vasculature is very important in differentiating amelanotic/hypomelanotic NM from non-melanomas. 10 When nodular and other invasive melanomas (which were significantly thinner) were compared, NM had an increased prevalence of thick-type vessels, pink color and milky red areas/ globules. Milky red areas/globules, indicating greater angiogenesis, are an important feature of amelanotic/hypomelanotic NM. 10 NM lesions sometimes show an atypical vascular pattern with a predominance of linear irregular vessels and/or the presence of hairpin vessels, and rarely show arborizing or regular comma vessels (3.2%). 10 In a past report of a large series of AHM, the most specific single vascular structure for melanoma was the predominance of centrally positioned vessels. 11 On the other hand, the study of Menzies et al. 10 revealed that amelanotic/hypomelanotic NM showed a significantly greater proportion of lesions with peripherally positioned vessels. Their study and a past report supported that thick melanomas with a Breslow thickness of 1 mm showed twice the frequency of Japanese Dermatological Association

7 Vessels visualized on dermoscopy Table 1. Terms for vessel morphology and arrangement, with definitions Descriptive term Metaphoric term Definition Significance Vessel morphology Dots Tiny pinpoint vessels Flat melanocytic lesions, inflammatory diseases, Bowen s disease Clods Red-purple More or less sharply demarcated, roundish or oval areas with Hemangioma lacunae a reddish, red-bluish, maroon or dark red to black coloration, separated from each other by intervening stroma, without vessels inside the lacunae Linear Linear, mildly curved vessels, considered irregular when Various diagnoses different sizes, shapes and curves with a haphazard or random distribution, are presented and considered regular when short and fine (thin) linear vessels prevail Coiled Glomerular Tightly coiled vessels resembling the glomerular apparatus of Bowen disease the kidney Looped Hairpin Two parallel linear vessels forming a half looped or hairpin-like structure Seborrheic keratosis, viral warts Serpentine Linear irregular Tortuous Linear vessels with multiple bends Multiple bending with severely curved linear vessels Flat basal cell carcinoma, melanoma Helical Corkscrew Twisted looped vessels with bends twisted along a central axis Melanoma, metastasis Curved Monomorphous Polymorphous Vessel arrangement Radial Serpiginous Comma Crown vessels String of pearls Linear, curved, short vessels One type of vessel dominates Multiple types of vessels are present Radial, serpentine or arborizing vessels at the periphery of the lesion that radiate toward the center but do not cross the midline of the lesion Coiled or dotted vessels arranged in lines Dermal nevi Various diagnoses May indicate malignancy in appropriate context, for example, in flat melanocytic lesions Sebaceous hyperplasia Clear cell acanthoma Branched Bright red, sharply in focus, large or thick diameter vessels Basal cell carcinoma dividing into smaller vessels Clustered Coiled or glomerular vessels arranged in groups Bowen s disease Centered dots Targetoid vessels Red dots (vessels) in the center of hypopigmented and space between reticular lines Congenital melanocytic nevus Kittler et al. 21 peripheral vessels as thin melanomas with a thickness of 0.75 mm. 10,11 In our case of amelanotic/hypomelanotic NM, the vasculature was arranged throughout the entire lesion, including the peripheral space (Fig. 5). However, the specific features of NM remain largely unknown; thus, if we diagnose amelanotic/hypomelanotic NM, we should notice that thicker melanoma often shows milky red areas/globules and an increased prevalence of all vessels including hairpin and thicktype vessels that are peripherally positioned, although dotted vessels are less frequently found. CONCLUSION Vascular structures visualized on dermoscopy provide important clues for the diagnosis of skin tumors, including melanocytic lesions, especially AHM and NM. We should evaluate the vasculature of skin tumors in the same way as for pigmented 2017 Japanese Dermatological Association structures when we perform dermoscopic examinations, though many findings remain unclear. CONFLICT OF INTEREST: None declared. REFERENCES 1 Arrazola P, Mullani NA, Abramovits W. DermLite II: an innovative portable instrument for dermoscopy without the need of immersion fluids. Skinmed 2005; 4: Blum A, Jaworski S. Clear differences in hand-held dermoscopes. J Dtsch Dermatol Ges 2006; 4: Benvenuto-Andrade C, Dusza SW, Agero AL et al. Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions. Arch Dermatol 2007; 143: Argenziano G, Zalaudek I, Corona R et al. Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004; 140:

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