Module 11: SCC Spectrum -- Bowen Disease, Keratoacanthoma, and Squamous Cell Carcinoma

The spectrum of premalignant and malignant keratinizing tumors comprises actinic (solar) keratosis (AK), Bowen disease (BD), keratoacanthoma (KA), and squamous cell carcinoma (SCC). These tumors may be viewed as lying on a continuum of keratinocyte dysplasia:

• AK Grade I: Atypia confined to the lower epidermis
• AK Grade II: Atypia extending to the mid-epidermis; prominent FPWH, strawberry pattern, scale
• AK Grade III (hypertrophic AK): Near-full-thickness dysplasia with prominent adherent scale-crust and structureless areas
• Bowen disease / SCC in situ: Full-thickness keratinocyte dysplasia
• Keratoacanthoma: Considered by many a well-differentiated SCC variant with rapid growth followed by spontaneous involution
• Invasive SCC: Dermal invasion, ranging from well-differentiated to poorly differentiated

Because these tumors exist on a spectrum, their clinical and dermoscopic features show considerable overlap, making strict categorical separation difficult in many cases.

The great majority of keratinizing tumors are nonpigmented, meaning their dermoscopic diagnosis relies on:

1. Clinical assessment: Texture, firmness, rate of growth, presence of ulceration, surface keratin
2. Keratin clues: Surface keratin, white circles, white structureless areas, four-dot clods (rosettes)
3. Vascular morphology: Dotted, glomerular/coiled, hairpin/looped, linear irregular/serpentine, polymorphous
4. Vessel arrangement and distribution: Clustered, linear, random, diffuse, focal
5. Additional dermoscopic criteria: Rosette sign (polarized light only), strawberry pattern

Keratin clues have been shown to be more robust than vessel clues and take diagnostic priority when present. White circles in SCC/KA carry 87% specificity.

• Contact dermoscopy may compress blood vessels, rendering them invisible. Using a viscous immersion medium (ultrasound gel) permits examination without excessive pressure.
• Polarized light dermoscopy eliminates pressure-induced compression entirely, greatly improving vascular visualization.
• Vessel morphology alone is less specific than other dermoscopic structures, as the same morphology may appear in different tumor types and even in inflammatory lesions.
• On the lower limbs, dotted and coiled vessels may be seen in lesions (e.g., BCC) that elsewhere rarely show these patterns.

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Keratinizing tumors represent a biological continuum of progressive keratinocyte dysplasia. While dermoscopy cannot always precisely place a given lesion on the spectrum, it provides critical information through two major categories of findings:

Keratin clues (structural features reflecting the keratinization process):

• Surface keratin (white-to-yellow scale)
• White circles (correlating with dilated, keratin-filled follicular openings or concentric keratinization)
• White structureless areas (corresponding to masses of highly keratinized keratinocytes)
• Four-dot clods / rosettes (polarized light only; keratin in follicular openings/eccrine ducts)

Vascular patterns (reflecting the neovascular response and tumor architecture):

• Dotted vessels
• Glomerular (coiled) vessels
• Hairpin (looped) vessels
• Linear irregular (serpentine) vessels
• Polymorphous (combinations of two or more types)

The arrangement and distribution of vessels provide additional specificity beyond morphology alone. For example, glomerular vessels are seen in BD (clustered/linear arrangement), stasis dermatitis (random distribution), and psoriasis (regular distribution throughout the lesion).

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4.2.1 Nonpigmented Bowen Disease

BD and intraepidermal carcinoma (IEC) represent SCC in situ of the skin. Although some consider BD and IEC to be separate entities based on epidemiologic, clinical, and histopathologic features, dermoscopic differences between the two are not well defined.

Archetypal dermoscopic pattern:

• Surface scale: White-to-yellow surface scale on an erythematous to yellow background
• Glomerular (coiled) vessels: Tortuous capillaries mimicking the glomerular apparatus of the kidney, arranged in clustered or linear patterns

The simultaneous finding of surface scale and focal clusters of glomerular vessels has been reported to give a 98% diagnostic probability that the lesion is BD.

Imaging challenges: Although glomerular/coiled vessels are usually easy to see through a dermatoscope, their coiled morphology is often difficult to capture on images. Due to their small size, lack of contrast, and camera resolution limitations, these vessels often appear as red dots in photographs. This creates potential confusion with the dotted vessels of melanocytic tumors (e.g., Spitz nevi). The key differentiator is distribution:

• BD: Vessels are clustered or in linear arrangement
• Spitz nevi: Vessels are symmetrically and randomly distributed

Additional clues distinguishing BD from Spitz nevi include reticular depigmentation (negative network) in Spitz nevi and surface scale in BD.

Differential diagnosis of BD: Features may occasionally overlap with BCC, amelanotic melanoma, seborrheic keratosis, lichen planus-like keratosis, and AK.

4.2.2 Pigmented Bowen Disease

Pigmented Bowen disease (pBD) is less frequent than its nonpigmented counterpart and is more common in darker skin phenotypes. In an analysis of more than 50 consecutive cases, the following dermoscopic patterns were identified:

1. Brown or gray dots: A strong diagnostic clue when arranged as linear radial lines at the periphery of the lesion
2. Pink or skin-colored eccentric structureless areas: A structureless zone eccentric within the lesion
3. Glomerular (coiled) vessels: Arranged randomly, as clusters, or in radial lines

Pigmented circles: Dermoscopic pigmented circles in pBD correlate on confocal microscopy with pigmented basal keratinocytes rimming the dermal papillae. The circular morphology is often only revealed at higher magnification. These may also be observed as pigmented circles in a linear arrangement.

Differentiating pBD from melanoma: pBD may occasionally mimic melanoma. Features supporting a diagnosis of pBD include:

• Adherently scaly surface
• Brown or gray dots arranged in linear radial lines at the periphery
• Focal glomerular (coiled) vessels

In contrast, melanoma typically shows:

• Brown/gray dots that do not follow a linear/radial pattern
• Dotted (red dots) or polymorphous vessel morphology (rather than glomerular)

4.2.3 Bowenoid Actinic Keratosis

Bowenoid AK reveals nearly full-thickness keratinocyte dysplasia histologically. Its dermoscopic appearance is similar to BD; however:

• Glomerular vessels tend to be regularly (uniformly) distributed rather than arranged in focal clusters as in classic BD
• The distinction between Bowenoid AK and BD is primarily histopathologic rather than dermoscopic

4.2.4 Erythroplasia of Queyrat

Erythroplasia of Queyrat (EQ) is Bowen disease of the glans penis. In a study of 14 cases compared with psoriasis, Zoon plasma cell balanitis, and candida balanitis:

• Glomerular (coiled) vessels, both clustered and randomly distributed, were highly predictive of EQ

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Check Your Understanding

What dermoscopic features characterize Bowen disease (SCC in situ)?

Bowen disease is characterized by glomerular (coiled) vessels arranged in clusters, surface scale/crust, and a pink-red background. The glomerular vessels are the most specific dermoscopic clue. Additional features may include brown dots arranged in linear patterns and small hemorrhagic foci.

Clinical Scenario

A 58-year-old woman presents with a persistent, erythematous, scaly plaque on the left lower leg that has been present for over a year. Dermoscopy reveals tightly coiled vessels (glomerular vessels) arranged in clusters distributed across the lesion surface. Brown dots and small globules are arranged in a linear fashion within the plaque. The surface shows fine scale. No white circles or hairpin vessels are identified.

What is your diagnosis and key dermoscopic findings?

Bowen disease (SCC in situ, pigmented variant)

Glomerular (coiled) vessels are the hallmark dermoscopic vascular feature of Bowen disease, corresponding to tightly coiled capillaries within the elongated dermal papillae of the acanthotic epidermis. The clustered distribution distinguishes them from the randomly scattered dots of melanoma. The linearly arranged brown dots and globules indicate pigmented Bowen disease, where aggregates of atypical basal pigmented keratinocytes create these structures. This pigmented variant can mimic melanoma, but the characteristic glomerular vessels and linear arrangement of pigmented structures support the diagnosis of Bowen disease.

Key Takeaways

• SCC in situ (Bowen disease) is characterized by glomerular vessels (coiled vessels resembling renal glomeruli) arranged in clusters, corresponding to dilated tortuous capillaries in dermal papillae.
• White circles (targetoid hair follicles) seen under polarized dermoscopy represent keratinizing concentric rings around follicular ostia and are a clue to keratinizing malignancy.
• Surface scale and keratin are prominent features of the SCC spectrum; thick yellow-white keratin masses suggest invasive SCC rather than in situ disease.

KA is considered by many to be a well-differentiated variant of SCC, with a typical clinical course of initial rapid growth followed by spontaneous involution over a period of a few months. Others consider it a distinct benign tumor, but this controversy does not affect dermoscopy findings.

Dermoscopic features:

KA exhibits the same keratin clues and vessel patterns as invasive SCC:

• Central keratin mass: A central yellowish to brownish structureless mass of keratin is the hallmark feature
• Keratin clues: Surface keratin, white circles, and white structureless areas are usually present. These clues are more robust than vessel clues and take diagnostic priority
• Vessels surrounding the central keratin:
• Hairpin (looped) vessels: Often with a white-to-yellow background halo -- the hallmark vascular pattern
• Linear irregular (serpentine or branched serpentine) vessels: Elongated and sometimes thick telangiectasias
• Glomerular (coiled) vessels: May also be seen
• Dotted (red dot) vessels: Occasionally present
• White structureless areas: Corresponding histologically to masses of highly keratinized keratinocytes
• White circles: Compelling clues to SCC/KA; these take priority over vessel clues

Important limitation: KA cannot reliably be distinguished from SCC dermatoscopically. Any lesion with KA features should be managed as a potential SCC.

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Invasive SCC is usually clinically straightforward -- a firm, tender, growing nodule. Pigmented variants are exceedingly rare. The differential diagnosis is wide, comprising the full range of pink and skin-colored nodules.

4.4.1 Nonpigmented Invasive SCC

Dermoscopic features:

Vascular patterns:

• Hairpin (looped) vessels: Often surrounded by a whitish background halo
• Dotted vessels
• Glomerular (coiled) vessels
• Linear irregular (serpentine) vessels
• Polymorphous pattern: Combinations of two or more vascular morphologies; the most frequent combination is linear irregular + dotted vessels

Keratin clues:

• Surface keratin: White-to-yellow scale
• White circles: 87% specificity for SCC/KA in a study of raised nonpigmented lesions
• White structureless areas: Corresponding to keratinized cell masses

Other features:

• Ulceration and blood crusts: Irregularly distributed reddish-orange to brownish to black blotches on the tumor surface
• Rosette sign: May be present (particularly in SCC arising from AK)
• Strawberry pattern: The AK pattern of white circles on a pink/red background may be seen adjacent to and contiguous with some SCCs when SCC arises in association with AK

4.4.2 Well-Differentiated vs. Poorly Differentiated SCC

Well-differentiated (KA-type) and poorly differentiated (desmoplastic-type) SCCs have distinct clinical and dermoscopic profiles:

Feature	Well/Moderately Differentiated	Poorly Differentiated
Growth pattern	Exophytic	Endophytic
Keratin clues	Present (scales, white circles, white structureless areas)	Absent or minimal
Predominant color	White and white-yellow	Red
Vascular features	Specific patterns (hairpin, glomerular)	Nonspecific (>50% surface covered by vessels, diffuse distribution, higher vessel caliber)
Hemorrhages/bleeding	Less common	Frequently present

Poor differentiation in SCC is frequently associated with:

• Endophytic growth
• No keratin clues
• Predominant red color
• More than 50% of the tumor surface covered by vessels
• Diffuse vessel distribution
• Higher vessel caliber
• Presence of hemorrhages/bleeding

Well-differentiated tumors frequently show:

• Exophytic growth
• Prominent scales and keratin clues
• Predominant white and white-yellow color

4.4.3 Pigmented Invasive SCC

Pigmented invasive SCC is rare and reveals dermatoscopically:

• Diffuse, homogeneous blue pigmentation
• Distinct, irregularly distributed blue-gray interfollicular pigment
• Dark brown to black crusts (if ulcerated)
• Vessels are usually not visible due to the pigmentation

The differential diagnosis includes pigmented BCC and melanoma.

Invasive SCC arising in pigmented Bowen disease may show dermoscopic features of pBD (brown/gray dots in linear arrangement, glomerular vessels).

4.4.4 SCC on Different Body Sites

Facial SCC: Often arises in association with AK, so the AK pattern of white circles on a pink/red background (strawberry pattern) may be seen adjacent to the SCC component. Elongated hairpin (looped) vessels are seen in the SCC, while the adjacent skin showing white circles represents the actinic keratosis component.

Nonfacial skin: Features tend to be less specific; surface scale and keratin may be the predominant findings with occasional dotted vessels.

Lower limbs: Special caution is needed -- dot and coiled vessels may be seen in lesions (such as BCC) that elsewhere only rarely show these patterns. This reduced specificity of vascular patterns on the lower extremities is an important diagnostic pitfall.

Glans penis (Erythroplasia of Queyrat): Glomerular vessels (clustered and random) are highly predictive of SCC in situ at this site.

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Check Your Understanding

What is the dermoscopic hallmark of invasive SCC, and how does the vascular pattern differ from SCC in situ?

Invasive SCC typically shows a central white structureless area (representing keratinization/fibrosis), blood spots/hemorrhage, and white circles around hair follicles. The vascular pattern shifts from glomerular vessels (SCC in situ) to hairpin/looped vessels and linear irregular vessels in invasive SCC. Polymorphous vessels may also be present.

Clinical Scenario

A 81-year-old man presents with a rapidly growing, dome-shaped nodule on the dorsal hand that appeared 3 weeks ago. The lesion has a central crater filled with keratin. Dermoscopy reveals a central yellowish-brown keratin mass, bright white circles surrounding keratin plugs, white structureless areas, and hairpin (looped) vessels with a white-to-yellow background halo arranged at the periphery.

What is your diagnosis and key dermoscopic findings?

Keratoacanthoma (well-differentiated SCC variant)

The central keratin mass is the hallmark dermoscopic feature of KA, corresponding to the crateriform architecture. White circles (87% specificity for SCC/KA) correspond to acanthosis and hypergranulosis of the infundibular epidermis. White structureless areas correspond to masses of highly keratinized keratinocytes. Hairpin vessels with a white-to-yellow background halo are the hallmark vascular pattern, created by capillary loops in distorted dermal papillae, with the white halo reflecting keratinized rete ridges. The keratin clues take diagnostic priority over vessel patterns. Importantly, KA cannot be reliably distinguished from invasive SCC by dermoscopy, so this lesion should be managed as a potential SCC.

Key Takeaways

• Invasive SCC shows polymorphous vessels, white structureless areas, and central keratin/ulceration; vessel heterogeneity increases with tumor thickness and invasion depth.
• Keratoacanthoma presents with a central keratin plug, hairpin vessels with white halos at the periphery, and a symmetric architecture that helps distinguish it from conventional SCC.
• Blood spots (hemorrhagic dots due to fragile tumor vessels) are a subtle but important clue to SCC that may be seen in both in situ and invasive forms.

SCC vs. Basal Cell Carcinoma

• BCC characteristically shows arborizing (branching tree-like) vessels, blue-gray ovoid nests, leaf-like areas, spoke-wheel structures, and ulceration
• SCC shows keratin clues (surface keratin, white circles, white structureless areas) and polymorphous vessels
• On the lower limbs, BCC may show atypical dot and coiled vessels, creating overlap with SCC patterns

SCC vs. Amelanotic Melanoma

• Amelanotic melanoma shows polymorphous vessels (including milky-red globules/areas) and shiny white structures
• SCC has prominent keratin clues that are absent in melanoma
• The strawberry pattern (white circles on red background) is a strong indicator of AK/SCC, not melanoma
• Melanoma may have focal scale/crust, but it will not encompass the entire surface and will not become as hyperkeratotic as AK/SCC

SCC vs. Viral Wart

• Warts show the "frog spawn" pattern with thrombosed capillaries arranged in a regular dot pattern
• SCC shows polymorphous vessels in irregular distribution with keratin clues

SCC vs. Hypertrophic AK

• The transition from Grade III (hypertrophic) AK to SCC in situ represents a histologic continuum
• Dermoscopically, the transition may be marked by the appearance of glomerular vessels in clustered arrangement (suggesting BD) or polymorphous vessels (suggesting invasive SCC)
• Large areas covered by scale-crust obscuring follicular openings suggest progression from AK toward SCC

Pigmented SCC vs. Pigmented BCC and Melanoma

• Pigmented SCC shows diffuse homogeneous blue pigmentation with irregular blue-gray interfollicular pigment
• Pigmented BCC shows blue-gray ovoid nests and leaf-like areas
• Melanoma shows atypical network, irregular dots/globules, regression structures

BD vs. Inflammatory Conditions (Psoriasis, Stasis Dermatitis)

• All may contain glomerular (coiled) vessels
• BD: Vessels in clustered or linear arrangement
• Dermatoses: Vessels regularly distributed throughout the lesion (random arrangement)
• BD has adherent surface scale; psoriasis has loosely adherent silvery scale

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Several dermoscopic features correlate with higher-risk SCC:

1. Absence of keratin clues: Poorly differentiated SCCs frequently lack surface keratin, white circles, and white structureless areas
2. Predominant red color: Indicates poor differentiation
3. Endophytic growth pattern: Associated with deeper invasion
4. High vascular surface coverage: More than 50% of the tumor surface covered by vessels suggests poor differentiation
5. Diffuse (non-focal) vessel distribution: Non-patterned, diffuse vascularity is a marker of poor differentiation
6. Higher vessel caliber: Larger-caliber vessels suggest more aggressive tumors
7. Hemorrhages and bleeding: Presence of hemorrhagic foci/blood crusts as irregularly distributed reddish-orange to brownish-black blotches
8. Ulceration: While present in various skin cancers, extensive ulceration in the context of a keratinizing tumor raises concern for invasive disease
9. Polymorphous vessels without keratin context: When polymorphous vessels dominate without accompanying keratin clues, this suggests poorly differentiated or more aggressive disease

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Check Your Understanding

What dermoscopic clue helps differentiate keratoacanthoma from conventional SCC?

Keratoacanthoma characteristically shows a central keratinous plug with a radial arrangement of hairpin (looped) vessels at the periphery, often surrounded by a white halo. The vessels radiate from the center outward. While overlap with SCC exists, the central keratin crater and radial vascular arrangement are more suggestive of keratoacanthoma.

Key Takeaways

• The SCC spectrum must be differentiated from AK (earlier stage), viral warts (frog-spawn vessels), irritated SK (similar surface features), and amelanotic melanoma (polymorphous vessels).
• Dermoscopic features progress along the AK-SCC continuum: scale and rosettes (AK) to glomerular vessels and white circles (Bowen) to polymorphous vessels and keratin masses (invasive SCC).
• Any growing keratinizing lesion with vascular polymorphism and white structureless areas that cannot be confidently diagnosed should be biopsied.