Dermoscopic algorithms for skin cancer triage

INTRODUCTION — Dermoscopy is a noninvasive, in vivo technique used for the evaluation of skin lesions. It allows for the visualization of subsurface skin structures in the epidermis, dermoepidermal junction, and upper dermis, which are otherwise not visible to the naked eye [1-3].

Different studies, systematic reviews, and meta-analyses have demonstrated that dermoscopy increases the diagnostic accuracy for the diagnosis of skin cancer, including melanoma, compared with naked-eye examination [4-10]. In general dermatology and primary care settings, the main purpose of dermoscopy in the evaluation of skin lesions is to help the clinician decide whether or not to perform a skin biopsy, refer to an expert, reassure the patient, or monitor the lesion over time with sequential digital dermoscopy imaging to determine its biologic nature [4].

Triage refers to the sorting out and classification of patients and lesions to determine priority of need and proper place of treatment [11]. In the setting of skin cancer triage, dermoscopy is an important tool that helps identify lesions for which malignancy needs to be ruled out. In the triage setting, a correct management decision (eg, reassure, biopsy, or refer) is paramount, whereas making a specific diagnosis is less important. For the purpose of deciding which lesion(s) should be biopsied, several simplified algorithms have been proposed [12-15].

This topic will review several dermoscopic algorithms for pigmented and nonpigmented lesions (table 1). The principles of dermoscopy and dermoscopic evaluation of skin, mucosal, and nail lesions are discussed separately.

●(See "Overview of dermoscopy".)

●(See "Dermoscopic evaluation of skin lesions".)

●(See "Dermoscopy of pigmented lesions of the palms and soles".)

●(See "Dermoscopy of facial lesions".)

●(See "Dermoscopy of mucosal lesions".)

●(See "Dermoscopy of nail pigmentations".)

DERMOSCOPY TECHNIQUES — Dermoscopy can be performed by using a contact or noncontact mode and a polarized or nonpolarized light source; the combinations result in three dermoscopic techniques that allow the visualization of skin structures that are not visible to the naked eye:

●Nonpolarized dermoscopy, contact (classic dermoscopy)

●Polarized dermoscopy, contact

●Polarized dermoscopy, noncontact

The contact mode requires direct contact between the scope lens and the skin surface. In contrast to nonpolarized light, which always requires a liquid interface (eg, ultrasound gel, 70% ethanol), polarized light does not require a liquid interface. However, using a liquid interface in the polarized contact mode provides a clearer image.

Polarized light allows for the visualization of the deeper skin layers. Therefore, colors (eg, pink, red, and white (figure 1)) and structures, including vascular structures (table 2A-B) and shiny white structures (eg, shiny white lines, rosettes, shiny white blotches and strands (figure 2A-C)), are more conspicuous with polarized dermoscopy [16-18]. Since these structures are important for the identification of skin cancer, the use of polarized dermoscopy is preferred for skin cancer screening [16].

ALGORITHMS FOR PIGMENTED LESIONS

The three-point checklist — The three-point checklist was initially developed for nonexperts as a skin cancer screening tool with high sensitivity for pigmented skin cancer, including pigmented melanoma and pigmented basal cell carcinoma (BCC) (table 3) [12,19]. This method is based upon three dermoscopic criteria:

●Asymmetry of pattern and distribution of dermoscopic structures

●Atypical network

●Blue-white structures

The asymmetric distribution of colors and structures within a lesion is considered the best predictor of malignancy, followed by blue-white structures and atypical network [19]. One point is assigned to each criterion present in the lesion. A total score of two points is considered positive and provides sufficient evidence to warrant a biopsy or referral to an expert.

The three-point checklist has a sensitivity of 79 to 91 percent and a specificity of 71 to 72 percent for the diagnosis of melanoma and BCC [4,19]. It should be noted that the three-point checklist was designed to help identify lesions suspicious for pigmented melanoma or BCC that needed to be biopsied for histopathologic examination.

The three-point checklist was not designed nor tested for its ability to identify lesions suspicious for pigmented squamous cell carcinoma (SCC). Although pigmented SCC in situ (Bowen disease) often manifests dermoscopic asymmetry, white color in the form of rosettes (seen only with polarized light dermoscopy) and white circles, many pigmented SCCs reveal only dermoscopic asymmetry without blue-white color or atypical network and dots. To avoid missing a pigmented SCC when utilizing the three-point checklist, any pigmented lesion with focal adherent keratin or a rough texture that manifests an asymmetric dermoscopic pattern should be considered suspicious and biopsied (picture 1).

Limitations — The three-point checklist can only be applied in the evaluation of pigmented lesions. Thus, this algorithm cannot aid in the detection of amelanotic or hypomelanotic skin cancers, including melanoma, BCC, and SCC. In addition, benign lesions revealing blue-white color (eg, seborrheic keratosis) or asymmetric distribution of bluish structures (eg, angioma, angiokeratoma) may be misclassified as suspicious and undergo unnecessary biopsy.

The AC rule — The AC rule was developed as a simple rule to identify lesions suspicious for melanoma [13]. This method is based on two dermoscopic criteria:

●Asymmetry in distribution of dermoscopic structures and colors

●Color variation; multiple colors within the lesion with black or blue-gray color being most suggestive of melanoma

The AC rule has been tested among laypersons, demonstrating a high sensitivity (93 percent) and acceptable specificity (64 percent) for melanoma. It was also tested by experienced clinicians, demonstrating a high sensitivity (87 percent) and specificity (92 percent) (picture 2) [13,20].

Limitations — The AC rule can only be used in the evaluation of pigmented lesions. In addition, benign lesions such as pigmented seborrheic keratoses and angiomas revealing an asymmetric distribution of structures may be misclassified as suspicious and subjected to biopsy.

The blue-black rule — The "blue-black rule" was introduced as a means to identify pigmented nodular melanomas, which often appear as symmetric papules or nodules [14]. This rule is based on the presence of blue-black color, defined as the presence of a combination of blue and black color involving at least 10 percent of the lesion surface area.

In one study of 283 pigmented lesions (170 malignant), the presence of a blue-black color in a papule or nodule demonstrated a 78 percent sensitivity for melanoma [14]. The sensitivity increased to up to 85 percent when the observers also looked for the classic melanoma-specific structures (ie, atypical network, negative network, irregular streaks, irregular dots/globules, and irregular brown structureless areas) (figure 3).

Specificity for melanoma was 81 percent when using the blue-black rule only, 98 percent when using the classic melanoma-specific structures only, and 81 percent when using both criteria (ie, blue-black rule and classic melanoma structures). In addition to detecting nodular melanoma, the presence of blue-black color can also aid in the detection of other heavily pigmented skin malignancies, including pigmented nodular BCCs (picture 3) [14].

Limitations — The blue-black rule is not useful for the detection of skin cancers lacking blue or black color. Moreover, benign lesions showing blue-black color (ie, thrombosed angiomas, angiokeratoma, seborrheic keratosis) would be misclassified as suspicious and subjected to unnecessary biopsy.

Chaos and clues — The "chaos and clues" algorithm was developed for the evaluation of pigmented skin lesions (algorithm 1) [15]. Chaos and clues uses five basic geometric elements to describe dermoscopic structures:

●Lines

●Pseudopods

●Circles

●Clods (any well-circumscribed, solid structure of any shape)

●Dots

Lines are further subclassified into five subtypes, namely reticular, branched, parallel, radial, and curved [15]. Based upon this rule, any lesion manifesting dermoscopic chaos requires further in-depth dermoscopic analysis to determine whether it contains any specific clues for malignancy.

"Chaos" is defined as the asymmetric distribution of dermoscopic structures or colors. While a pigmented cutaneous malignancy will almost always display chaos, there are lesions not displaying chaos for which malignancy should still be considered. Exceptions to the chaos rule include:

●Any changing lesion in an adult patient

●Any lesion on the head or neck showing gray color (even if present only focally)

●Any pigmented nodular lesion (see 'The blue-black rule' above)

●Any acral volar lesion with a parallel ridge pattern

Lesions that do not display chaos and do not conform to one of the four exceptions listed above are likely benign and can be monitored over time for change. In contrast, if chaos is present, the observer should evaluate the lesion for the presence of any of the following clues for malignancy (table 4):

●Eccentric structureless area of any color, except skin color

●Thick lines, reticular or branched

●Gray or blue structures (ie, lines, circles, clods and dots)

●Black dots or clods, located in the periphery

●Radial lines or pseudopods, segmental (or focal)

●White lines, including lines arranged perpendicularly to each other (only seen with polarized dermoscopy) and reticular white lines (seen with both polarized and nonpolarized dermoscopy)

●Polymorphous vessels (more than one vessel morphology)

●Lines parallel, ridges (volar) or chaotic (nails)

If any of these clues are present, the lesion should be biopsied and sent for histopathologic examination.

The chaos and clues algorithm has a sensitivity for any malignancy (ie, melanoma, BCC, SCC) of 91 percent and a specificity of 63 percent (picture 4) [21].

Limitations — The chaos and clues algorithm can only be used in the evaluation of pigmented lesions. It cannot assist in the detection of amelanotic or hypomelanotic skin cancers. In addition, skin cancers, including melanoma, manifesting a more symmetric starburst pattern may be misclassified as benign lesions.

Although searching for and identifying the clues to malignancy improves the sensitivity and specificity for detecting skin cancer, it does add a layer of complexity that makes this algorithm less than ideal to implement in a skin cancer triage setting.

ALGORITHMS FOR NONPIGMENTED LESIONS

Prediction without pigment — The "prediction without pigment" algorithm was created for the evaluation of amelanotic lesions, with the purpose of helping the clinician decide whether or not to perform a skin biopsy [22]. This algorithm consists of three criteria that need to be evaluated in sequence (algorithm 2 and table 4):

●Ulceration without a history of trauma – The presence of ulceration can be detected either clinically or dermoscopically.

●White clues (picture 5), including:

•White lines:

-Reticular white lines.

-Polarizing-specific white lines. This structure is usually seen in malignant lesions, in particular invasive melanomas. However, it may also be seen in other malignant lesions, such as basal cell carcinoma (BCC).

•Keratin clues (applicable only in the evaluation of palpable lesions), including:

-White circles (associated with squamous cell carcinoma [SCC])

-White structureless areas, defined as structureless white zones

-Surface keratin

●Vascular pattern – The significance of vascular structures and patterns (picture 5) is dependent on the morphology of the lesion (ie, flat versus raised):

•Flat lesions – For macular lesions, the clinician needs to determine whether the vascular pattern is monomorphous or polymorphous:

-Monomorphous vascular pattern – Lesions displaying a monomorphous vascular pattern other than clods-only (lacunae) should be considered suspicious (eg, monomorphous serpentine vessels in BCC, monomorphous coiled vessels in SCC, monomorphic dotted vessels in melanoma).

-Polymorphous vascular pattern – Lesions revealing this pattern should be considered suspicious.

•Raised lesions – Lesions displaying only clods (lacunae) are considered benign angiomas. For all other palpable lesions, the observer needs to determine the vessel arrangement:

-Radial (eg, SCC, keratoacanthoma, ulcerated BCC, sebaceous hyperplasia, molluscum contagiosum)

-Branched (eg, BCC, SCC, keratoacanthoma, cysts)

-Serpiginous (eg, clear cell acanthoma)

-Centered (eg, papillomatous intradermal nevi, seborrheic keratosis)

In raised lesions, blood vessel patterns other than those described above are considered nonspecific. Lesions with nonspecific vessel arrangement should be biopsied to rule out malignancy.

Limitations — The "prediction without pigment" algorithm was designed only for the evaluation of nonpigmented lesions and cannot be used for evaluating pigmented or hypopigmented lesions.

TRIAGE AMALGAMATED DERMOSCOPIC ALGORITHM — Based on the strengths and limitations of the aforementioned triage algorithms, the authors designed a relatively simple three-step algorithm with the aim of guiding the health provider's management decision in a skin cancer triage setting [23-28]. The triage amalgamated dermoscopic algorithm (TADA; (algorithm 3)) integrates key criteria suggesting malignancy derived from existing algorithms for pigmented and nonpigmented lesions (see 'Algorithms for pigmented lesions' above and 'Algorithms for nonpigmented lesions' above):

●Disorganized pattern (asymmetric distribution of colors and structures)

Or

●Organized pattern with any of the following four structures or four colors:

•Structures – Streaks forming a starburst pattern, negative network, vessels, or ulceration

•Colors – Blue-black, gray or white color seen in white circles, or shiny white structures

This algorithm is relatively simple and easy to use, requires minimal training, and can guide the management of suspicious skin lesions in a skin cancer triage setting (picture 6A-B). The sensitivity and specificity of TADA for malignant lesions was 94.8 and 72.3 percent, respectively [23,24].

The use of TADA involves the following steps:

●Step 1: Is the lesion an unequivocal seborrheic keratosis, hemangioma, or dermatofibroma? – In the first step, the clinician determines first whether a lesion is one of the most common benign lesions encountered in clinical practice (ie, unequivocal seborrheic keratosis, angioma, or dermatofibroma) (algorithm 3). Experienced clinicians can also recognize other benign lesions with unequivocal dermoscopic patterns, such as sebaceous hyperplasia, clear cell acanthoma, or intradermal nevus. If the lesion is an obvious benign lesion based on both clinical and dermoscopic morphology, the patient can be reassured and no further evaluation is required [24,25,29].

Despite the fact that some seborrheic keratoses, angiomas, and dermatofibromas may reveal suspicious dermoscopic features, such as asymmetry [30], most can be correctly diagnosed based upon their overall clinical and dermoscopic patterns when viewed with polarized and nonpolarized light. It is important to recognize these benign lesions and exclude them from further evaluation to avoid unnecessary biopsies.  

Lesions entering TADA steps 2 and 3 should be evaluated with polarized light.

●Step 2: Does the lesion manifest a disorganized pattern? – In the second step, lesions that are not identified as unequivocally benign are examined for dermoscopic features that are associated with malignancy. Any isolated neoplasm should be considered suspicious if it reveals a disorganized or asymmetric pattern (algorithm 3). A dermoscopic pattern takes into account the distribution of colors and structures within the lesion. As a result, dermoscopic asymmetry is defined as a disorganized or chaotic distribution of colors and structures (picture 6A). Asymmetry in dermoscopy is the single most important feature that helps discriminate benign from malignant lesions [13,31-33]. In addition, asymmetry is a reproducible feature that consistently shows the highest interobserver agreement [19,34]. (See 'The three-point checklist' above and 'The AC rule' above.)

If the lesion reveals a disorganized pattern, a skin biopsy should be performed. If, on the other hand, the lesion demonstrates an organized pattern, the observer proceeds to step 3 of TADA.

●Step 3: Does the organized-appearing lesion manifest one of two patterns, two structures, or four colors? – Skin cancers manifesting an organized and symmetric pattern are a rare occurrence. Equivocal lesions that do not reveal a disorganized or asymmetric dermoscopic pattern should be evaluated further to rule out cancer if they present any of the following features:

•Any of two patterns:

-Streaks or globules forming a starburst pattern – Since some spitzoid melanomas may show a starburst pattern, all lesions manifesting an organized and symmetric starburst pattern should be classified as suspicious, especially in individuals older than 12 years. (See "Spitz nevus and atypical Spitz tumors".)

-Negative network pattern – The presence of a negative network is associated with Spitz nevi, melanoma, and melanomas arising in nevi. It is not possible to reliably differentiate Spitz nevi from melanoma; thus, all lesions with a negative network should undergo a biopsy.

•Any of two structures:

-Vessels – Lesions revealing vessels of any morphology should be considered concerning and biopsied.

-Ulceration – Ulceration, in particular, without a history of trauma (picture 6B).

•Any of four colors:

-Blue, black, or gray – The presence of a blue-black color has a fairly high sensitivity for nodular melanoma [14]. Gray color has been demonstrated to be an important clue for skin cancer in the chaos and clues algorithm [15]. Thus, the blue-black or gray color criterion is particularly useful in the diagnosis of symmetric nodular-pigmented melanomas, melanomas with regression, and melanomas occurring in sun-damaged skin, including lentigo maligna and lentigo maligna melanoma (picture 6B) [35,36]. (See 'The blue-black rule' above.)

-White – White structures include shiny white structures (ie, lines, rosettes, blotches, and strands) and white circles. Shiny white structures are only visible with polarized light [29,37,38]. Although several benign lesions (including dermatofibromas, lichen planus-like keratosis, and Spitz nevi) may occasionally reveal these structures, it is advisable that any lesion revealing white color be viewed with suspicion in a skin cancer triage setting.

Organized lesions with any of the above-mentioned features should be considered for biopsy and sent for histopathologic examination. Lesions that should also be considered suspicious and biopsied include:

●Any volar lesion with a parallel ridge pattern (picture 7), even if symmetrically distributed

●Any changing lesion in an adult patient

If none of the above criteria are present and the lesion is not palpable, it can be dermoscopically monitored over time; usually, short-term monitoring (three months) is an adequate interval to detect change in melanomas.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dermoscopy".)

SUMMARY

●Dermoscopy increases the sensitivity for the diagnosis of melanoma compared with naked-eye examination and improves the recognition of numerous pigmented and nonpigmented skin lesions. (See 'Introduction' above.)

●Making a correct management decision (ie, reassurance, referral, or skin biopsy) is the main goal of skin cancer triage. For this purpose, several simple and rapid algorithms are available to clinicians with varying degrees of training in dermoscopy, including the three-point checklist (table 3), the AC (asymmetry in distribution of dermoscopic structures and colors, color variation) rule (picture 2), and chaos and clues (algorithm 1). (See 'Algorithms for pigmented lesions' above and 'Algorithms for nonpigmented lesions' above.)

●The triage amalgamated dermoscopic algorithm (TADA; (algorithm 3)) incorporates criteria with high sensitivity and specificity extracted from available algorithms to be used in the setting of skin cancer triage. (See 'Triage amalgamated dermoscopic algorithm' above.)