Skin CancerAdvanced · 7 min read

Well-Differentiated Cutaneous SCC (WD-SCC) and Keratoacanthoma

The keratin-producing end of invasive SCC, defined dermoscopically by central keratin masses, white circles around follicles, white halos around vessels, and hairpin vessels.

By Dr. Yehonatan KaplanPublished Updated

In brief

Well-differentiated cutaneous SCC and keratoacanthoma represent the keratinizing, slow-growing end of invasive SCC. They share dominant features of keratin production: central keratin masses, white circles around follicles (acanthosis with hypergranulosis), white halos around vessels, and white structureless areas. Vascular structures, when present, tend to be hairpin or linear-irregular at the periphery. The Lallas BJD 2015 study demonstrated that this 'white-dominant' dermoscopic pattern is strongly associated with well or moderately differentiated histology and predicts a more favorable prognosis. Keratoacanthoma is now considered by most dermatopathologists a variant of well-differentiated SCC; it cannot be reliably distinguished from WD-SCC dermoscopically and should be managed surgically.

Clinical content

01Dermoscopically, well-differentiated SCC shows a 'white-dominant' palette: central keratin masses (yellow-white opaque structures), white circles around follicles (the most useful single sign distinguishing invasive SCC from in-situ disease), white perivascular halos, and white structureless areas. Lallas et al (BJD 2015) showed that white color in over 50 percent of the lesion surface decreased the odds of poorly differentiated SCC by 97 percent.

02Vascular structures in WD-SCC: peripheral hairpin vessels (vascular loops), linear-irregular vessels at the lesion edge. Vessel quantity is moderate (10-50 percent of lesion surface) and arrangement is peripheral, not diffuse. Large-caliber arborizing vessels are unusual; if seen, suspect non-well-differentiated tumor or BCC.

03Central scale or keratin distribution is a potent dermoscopic predictor of well or moderately differentiated histology. In Lallas 2015, central scale distribution was associated with a 36-fold reduced probability of poor differentiation. The crater-like central keratin plug surrounded by a smooth elevated peripheral rim is the classic clinical and dermoscopic appearance.

04Keratoacanthoma classic clinical course: rapid growth over 4-8 weeks to a dome-shaped erythematous nodule with a central keratin-filled crater, then a stable plateau, then sometimes spontaneous involution over 4-6 months. Most KAs are treated surgically because spontaneous regression is unpredictable, the tumor can metastasize (rare but documented), and histology cannot reliably distinguish KA from invasive SCC on partial biopsies.

05Dermoscopically KA shows: central keratin-filled crater with peripheral crown of radially oriented hairpin and linear vessels, white-yellow keratin mass in the center, surrounding red rim, sometimes white halos around the peripheral vessels. The pattern is largely indistinguishable from well-differentiated SCC and should be managed identically.

06The KA-vs-SCC continuum: most contemporary dermatopathologists view KA as a well-differentiated SCC variant. Both have the potential to invade and rarely metastasize, both should be excised completely with margin assessment. Watchful waiting for KA regression is reserved for selected patients with clear clinical regression already underway and not in critical sites.

07Other clinical clues to WD-SCC: hyperkeratotic firm nodule on chronically photodamaged skin (face, ears, dorsal hands, scalp), often arising in a background of multiple AKs and field cancerization. Tenderness on palpation, induration, and a cutaneous horn morphology (vertical column of keratin) are common. Underneath every cutaneous horn, especially on the face, ear, or dorsal hand, biopsy reveals SCC in about 20-30 percent of cases.

08Targetoid follicles (white circles), introduced by Zalaudek in JAAD 2012 and confirmed in Rosendahl 2012, remain the single most useful dermoscopic sign of invasion in a keratinocytic lesion. They reflect epidermal acanthosis with hypergranulosis around the follicular infundibulum, histologically a hallmark of invasive SCC.

09Polymorphic vessels can occur in WD-SCC, particularly toward the periphery, but the dominant impression should be white-keratin-rich rather than red-vascular-rich. If the lesion looks 'angry red' with diffuse polymorphous vessels and bleeding, it is more likely poorly differentiated (covered in the high-risk SCC topic).

Key dermoscopic features

Central keratin mass
Defining feature of WD-SCC and KA. Reflects abundant keratinization characteristic of well-differentiated tumors.Yellow-white to opaque central keratin filling, often crater-shaped, surrounded by a red rim of viable tumor.
White circles around follicles
The single most useful sign of invasive SCC. Acanthosis with hypergranulosis at the follicular infundibulum. Sensitivity 87 percent, specificity 79 percent (Rosendahl 2012).Bright white rings around yellow follicular ostia; multiple, scattered across the lesion.
White perivascular halos
Keratinization around vessels. Sign of well-differentiated tumor.White rim surrounding hairpin or linear vessels.
White structureless areas
Areas of dense keratinization or fibrosis without recognizable structure. More than 50 percent white color reduces odds of poor differentiation by 97 percent (Lallas 2015).Featureless homogeneous white zones, often peripheral.
Hairpin vessels (peripheral)
Vascular loops, often radially arranged at the lesion edge. Classic for KA and WD-SCC.U-shaped vascular loops, often with white halo, in a peripheral crown distribution.
Linear-irregular vessels
Dilated dermal vessels visible through partially keratinized epidermis. Common at the periphery of WD-SCC.Irregular linear vascular structures with variable thickness.
Crown vessels (KA)
Radially oriented hairpin vessels at the periphery of a central keratin crater. Pathognomonic clinical and dermoscopic appearance.Crown of radial vessels around a central keratin plug.
Cutaneous horn morphology
Vertical column of keratin extending above the skin. Underlying SCC in 20-30 percent on face/ears/dorsal hands.Tall keratin spire visible clinically; dermoscopy shows white-yellow opaque structures with peripheral red rim.
Yellow opaque structures
Areas of orthokeratosis or keratin pearls in nests of well-differentiated tumor.Yellow homogeneous structureless areas, often scattered or coalescent.
Blood spots within keratin
Common in KA and WD-SCC; small punctate bleeding within the keratin mass.Red-brown punctate dots within yellow-white keratin.

High yield clinical points15 pearls in 6 groups

Recognition & pattern analysis

5 points
1
White-dominant lesion = well or moderately differentiated. Lallas (BJD 2015) showed that white color in over 50 percent of the lesion surface reduced the odds of poorly differentiated SCC by 97 percent. The 'angry red' diffuse vascular pattern indicates poor differentiation.
2
Central keratin distribution favors WD-SCC over poorly differentiated. Central scale distribution was associated with 36-fold reduced odds of poor differentiation in the Lallas 2015 multivariate analysis. Peripheral or absent keratin should raise concern for poor differentiation.
3
Differentiate WD-SCC from BCC by following the white. BCC: arborizing vessels, blue-gray ovoid nests, leaf-like areas, ulceration. WD-SCC: white circles, central keratin, white structureless areas. Both can ulcerate but the surrounding palette differs.
4
Differentiate WD-SCC from amelanotic melanoma by vascular pattern and asymmetry. Amelanotic melanoma: chaotic polymorphous vessels with vascular blush, milky red areas, no white circles, irregular asymmetric architecture. WD-SCC: white circles, central keratin, more organized peripheral vessels.
5
Multiple eruptive KAs suggest a syndrome. Generalized eruptive KAs of Grzybowski, Muir-Torre syndrome, Ferguson-Smith syndrome, and Lynch-related KAs. Workup includes colonoscopy, urinary tract evaluation, and germline testing.

Diagnostic criteria & thresholds

1 point
1
White circles around follicles = invasive SCC. Rosendahl (Arch Dermatol 2012) established white circles as the most specific dermoscopic sign for invasive SCC vs in-situ disease, with 87 percent sensitivity and 79 percent specificity. They reflect acanthosis with hypergranulosis around the follicular infundibulum.

Management & treatment

1 point
1
Hairpin vessels in a peripheral crown = KA-like SCC. Radially oriented hairpin vessels around a central keratin plug is the classic KA pattern. Indistinguishable from well-differentiated SCC; treat surgically.

Pitfalls & mimics

3 points
1
KA is a variant of WD-SCC, manage surgically. Spontaneous regression cannot be reliably predicted. Partial biopsy cannot rule out invasive SCC. The Lin (Dermatol Pract Concept 2014) and Rosendahl (Arch Dermatol 2012) studies confirmed substantial dermoscopic overlap between KA and WD-SCC. Excision with margin assessment is the safe path.
2
Cutaneous horn underneath: biopsy the base, include reticular dermis. 20-30 percent of cutaneous horns on the face, ear, or dorsal hand harbor SCC. Shave biopsy of just the keratin will miss it; punch or saucerization of the base is required.
3
Targetoid hair follicles, white circles, and follicular keratosis are all the same finding. Different terminology in the literature for the bright white ring around a follicular ostium; do not be confused. Histologically: acanthosis with hypergranulosis around the infundibulum, hallmark of invasive SCC.

When to biopsy

3 points
1
Hyperkeratotic AK that becomes indurated has likely transitioned to invasive SCC. Induration on palpation is the simplest invasion alarm in any actinic field. Combined with new dermoscopic features (white circles, central keratin, hairpin vessels), it is sufficient indication for incisional biopsy with deep dermis.
2
Mohs is preferred for WD-SCC at high-risk anatomic sites. Face, ears, scalp, hands, feet, pretibia, anogenital. Mohs achieves 5-year recurrence rates of 3 percent vs 10 percent for standard excision and conserves tissue in cosmetically sensitive areas.
3
Watchful waiting for KA regression is rarely justified. Reserved for patients with clear regression already documented, willing to accept long-term scar, and in non-critical sites. The risk of misdiagnosing an invasive SCC as KA on initial biopsy is substantial.

Recent changes (2022 onward)

2 points
1
Most WD-SCCs are low-risk and curable with simple excision. 5-year recurrence rate after Mohs about 3 percent, after standard excision 8-10 percent (Rowe 1992 meta-analysis, NCCN 2025). Counsel patients accordingly.
2
Recurrence after Mohs is most often local, presenting with new induration and pain at the scar. Surveillance schedule for high-risk WD-SCC: every 3-6 months for 2 years, every 6-12 months thereafter (NCCN 2025). Patient education on self-examination of the surgical site is critical.

Lectures covering this topic6 lectures

AAD 2026U004 · #01
Real-Time Identification and Management of Actinic Keratoses
Drew A. Emge, MD, MSc
Excellence (main)DE-MAIN · #03
Basal Cell Carcinoma and Squamous Cell Carcinoma
G. Argenziano and A. Lallas
Academy 2025ACAD25 · #06
What We Have Learned in the Last Few Years About NMSC
Aimilios Lallas
Academy 2025ACAD25 · #14
Pink Tumors and Blood Vessels
Giuseppe Argenziano
Academy 2025ACAD25 · #16
Diving Into White Color
Aimilios Lallas
ADM 2025ANNUAL13 · #13
Histopathology Correlations: Non-Melanocytic
Ashfaq A. Marghoob, MD

Notable updates & conceptual milestones5 updates

Lallas progression model (BJD 2015)

2015

Established that dermoscopic features track histologic differentiation grade: white-dominant features = well/moderately differentiated, red-dominant features = poorly differentiated. Provides preoperative risk stratification before biopsy.

Polarized dermoscopy enhances visualization of white structures

2015-present

White circles, white perivascular halos, and white structureless areas are visible only or primarily under polarized light. Modern hybrid dermatoscopes allow toggling between polarized and non-polarized modes to maximize information.

OCT and LC-OCT for invasion confirmation

2020-2025

OCT shows breach of the dermoepidermal junction; LC-OCT provides high-resolution real-time confirmation of invasive nests and depth of invasion. Useful for surgical planning and for confirming invasion in equivocal hyperkeratotic AK.

RCM for in-vivo KA-vs-SCC discrimination

2020-2024

Pilot studies suggest specific RCM patterns (regular keratin-filled invagination with peripheral well-organized epithelium for KA vs irregular atypical nests for SCC) but overlap remains substantial. Histology still required.

AI dermoscopic classifier for keratinocyte cancer subtype

2023-2025

Convolutional neural networks trained on the ISIC archive can distinguish AK, Bowen's, WD-SCC, and BCC at sensitivities approaching 90 percent. Most useful as decision support for non-specialist clinicians.

Bottom line

The keratin-producing end of invasive SCC, defined dermoscopically by central keratin masses, white circles around follicles, white halos around vessels, and hairpin vessels.

15 clinical points · 5 recent updates · 10 references

References

Sources cited in the lecture content or that underpin the clinical points above. Verify with primary sources before practice changes.

  1. [1]
    Lallas A, Pyne J, Kyrgidis A, et al. The clinical and dermoscopic features of invasive cutaneous squamous cell carcinoma depend on the histopathological grade of differentiation. Br J Dermatol. 2015;172(5):1308-1315.
    PubMed: 25363081DOI: 10.1111/bjd.13510· Foundational paper correlating dermoscopic patterns with histologic differentiation grade. White-dominant lesion = well/moderate; red-dominant = poor.
  2. [2]
    Rosendahl C, Cameron A, Argenziano G, Zalaudek I, Tschandl P, Kittler H. Dermoscopy of squamous cell carcinoma and keratoacanthoma. Arch Dermatol. 2012;148(12):1386-1392.
    PubMed: 22986763DOI: 10.1001/archdermatol.2012.2974· Established white circles as the most specific dermoscopic feature for invasive SCC vs in-situ disease.
  3. [3]
    Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model. J Am Acad Dermatol. 2012;66(4):589-597.
    PubMed: 21839538DOI: 10.1016/j.jaad.2011.02.011· Introduced the targetoid hair follicles concept (later renamed white circles) and the AK to invasive SCC progression model.
  4. [4]
    Lin MJ, Pan Y, Jalilian C, Kelly JW. Dermoscopic characteristics of nodular squamous cell carcinoma and keratoacanthoma. Dermatol Pract Concept. 2014;4(2):2.
    · Confirmed substantial dermoscopic overlap between KA and well-differentiated nodular SCC; supports treating KA as SCC.
  5. [5]
    Pyne JH, Sapkota D, Wong JC. Squamous cell carcinoma: variation in dermatoscopic vascular features between well and non-well differentiated tumors. Dermatol Pract Concept. 2012;2(4):204a05.
    PubMed: 23785619DOI: 10.5826/dpc.0204a05· Established that vascular density and morphology correlate with histologic differentiation grade in SCC.
  6. [6]
    Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. J Am Acad Dermatol. 1992;26(6):976-990.
    PubMed: 1607418DOI: 10.1016/0190-9622(92)70144-5· Foundational meta-analysis establishing 5-year recurrence rates after Mohs (3 percent for primary SCC) vs other modalities.
  7. [7]
    Marrazzo G, Zitelli JA, Brodland D. Clinical outcomes in high-risk squamous cell carcinoma patients treated with Mohs micrographic surgery alone. J Am Acad Dermatol. 2019;80(3):633-638.
    PubMed: 30244064DOI: 10.1016/j.jaad.2018.09.015· Modern outcomes data confirming low recurrence and metastasis rates with Mohs alone for high-risk WD-SCC.
  8. [8]
    Soleymani T, Brodland DG, Arzeno J, Sharon DJ, Zitelli JA. Clinical outcomes of high-risk cutaneous squamous cell carcinomas treated with Mohs surgery alone. J Am Acad Dermatol. 2023;88(1):109-117.
    PubMed: 35760236DOI: 10.1016/j.jaad.2022.06.1167· Large prospective cohort confirming Mohs as primary curative therapy for high-risk WD-SCC, with limited need for adjuvant therapy.
  9. [9]
    Yelamos O, Braun RP, Liopyris K, et al. Dermoscopy and dermatopathology correlates of cutaneous neoplasms. J Am Acad Dermatol. 2019;80(2):341-363.
    PubMed: 30321581DOI: 10.1016/j.jaad.2018.07.026· Comprehensive correlation between dermoscopic features and histologic findings across keratinocyte cancers.
  10. [10]
    Tschetter AJ, Campoli MR, Zitelli JA, Brodland DG. Long-term clinical outcomes of patients with invasive cutaneous squamous cell carcinoma treated with Mohs micrographic surgery. J Am Acad Dermatol. 2020;82(1):139-148.
    PubMed: 31279037DOI: 10.1016/j.jaad.2019.06.1327· 5-year prospective multicenter cohort confirming low recurrence and metastasis after Mohs for invasive SCC.