Dermatologic Look-Alikes

TABLE. Actinic Keratosis vs Squamous Cell Carcinoma

Actinic Keratosis1-7

Dermatologic presentation

• Scaly, rough, flesh-colored or erythematous papules and patches

• May be tender, itchy, or asymptomatic

• Gritty texture similar to sandpaper

• May contain pigment or telangiectasias

• Can vary from 1 mm to >2 cm

Squamous Cell Carcinoma8-16

• Ulcerated red plaque

• Central plug

Characteristic locations

• Head

• Neck

• Scalp

• Upper back

• Upper extremities

Potential risk factors

• UV and sunlight exposure

• Immunosuppression

• Lighter skin pigmentation

• Baldness

• Male gender

• Age greater than 70 years

Etiology

• DNA mutations (eg, in TP53) resulting from UV exposure

• Arise from keratinocyte proliferation at dermoepidermal junction

• Irregular epidermal differentiation and hyperkeratosis

Histology

• Acantholytic, atrophic, bowenoid, hypertrophic, lichenoid, or proliferative

• Atypical keratinocytes in basal epidermis or throughout entire epidermis in advanced lesions

• Lack polarity and nuclear pleomorphism

• Usually have increased mitotic figures

• Anaplastic and pleomorphic nuclei may be seen in stratum spinosum and stratum basale

• Alternating hyperkeratosis and parakeratosis in stratum corneum

• Dermis may contain inflammatory infiltrates with plasma cells/lymphocytes and solar elastosis

Diagnosis

Treatment

• Diagnosed clinically

• May be biopsied

• Carbon dioxide lasers

• Chemical peels

• Cryotherapy

• Curettage and electrodessication

• Dermabrasion

• Fluorouracil

• Imiquimod

• Photodynamic therapy

CDKN2A, cyclin-dependent kinase inhibitor 2A; TP53, tumor protein 53

• Forearms

• Hands

• Head

• Neck

• Scalp

• UV and sunlight exposure

• Immunosuppression

• Lighter skin pigmentation

• Baldness

• Male gender

• Age greater than 60 years

• UV exposure

• Mutations in TP53, CDKN2A, RAS, and NOTCH1

• Keratoacanthoma, verrucous carcinoma, desmoplastic, and adenosquamous

• Atypical keratinocytes in the epidermis with disordered maturation

• Hyperkeratosis and parakeratosis

• Downward proliferation of nests of keratinocytes extending into the dermis

• Atypical keratinocytes with pleomorphism, mitoses, and prominent nucleoli

• Clinical presentation

• Biopsy to confirm diagnosis

• Cryotherapy

• Electrodessication

• Fluorouracil

• Imiquimod

• Mohs surgery

• Radiotherapy

• Surgical excision which is often described as a pearly telangiectatic papule, though biopsy is also needed to confirm this diagnosis.16

Treatment of SCC involves excision, surgery, cryotherapy, and biologic agents. Low-risk, nonmetastatic SCC requires excision with a margin of 4- to 6-mm. Electrodesiccation, cryotherapy, and radiotherapy can be used for some low-risk SCCs. However, treatment with radiotherapy has a higher recurrence rate and cannot be used in patients younger than 55 years of age.16 Some high-risk tumors or tumors in anatomic areas needing tissue conservation may be candidates for Mohs surgery.16 Off-label use of topical imiquimod and fluorouracil can be somewhat effective in treating SCC.16 Follow-up appointments should occur once every 6 months for the first year and then at least yearly to check for recurrence and development of new lesions.16

Patients with high-risk SCC may require additional workup and treatment. Those with palpable lymphadenopathy need an ultrasound-guided fine-needle aspiration or biopsy of the lymph nodes. Lesions that are high risk may also require adjuvant radiation or chemotherapy in some instances.12

Patients who are at increased risk for SCC can be treated prophylactically with oral retinoids or niacinamide. Other options include field therapy with topical chemotherapy agents or photodynamic therapy to target AKs or SCCIS that could progress to SCC.12

The patient in this case was diagnosed with SCC via biopsy and given the size and location of her lesion, was referred to Mohs surgery for treatment. ■

Briana Fernandez and Shangyi Fu are medical students at Baylor College of Medicine in Houston, Texas; Tara L. Braun, MD, is a dermatologist at Elite Dermatology in Houston,Texas.

References

1. Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013;169(3):502-518.

2. Röwert-Huber J, Patel MJ, Forschner T, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification [published correction appears in Br J Dermatol. 2007;157(2):431]. Br J Dermatol. 2007;156 Suppl 3:8-12.

3. Siegel JA, Korgavkar K, Weinstock MA. Current perspective on actinic keratosis: a review. Br J Dermatol. 2017;177(2):350-358.

4. Dodds A, Chia A, Shumack S. Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014;4(1):11-31.

5. Jeffes EW 3rd, Tang EH. Actinic keratosis. Current treatment options. Am J Clin Dermatol. 2000;1(3):167-179.

6. Ceilley RI, Jorizzo JL. Current issues in the management of actinic keratosis. J Am Acad Dermatol. 2013;68(1 Suppl 1):S28-S38.

7. Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380(10):935-946.

8. Bonney V. Uterus showing squamous cell carcinoma of the cervix and adeno-carcinoma of the body. Proc R Soc Med. 1914;7(Obstet Gynaecol Sect):227-228.

9. Brantsch KD, Meisner C, Schönfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. 2008;9(8):713-720.

10. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):237-247.

11. Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012: empirical relationships. JAMA Dermatol. 2014;150(10):1063-1071.

12. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors. J Am Acad Dermatol. 2018;78(2):249-261.

13. South AP, Purdie KJ, Watt SA, et al. NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis. J Invest Dermatol. 2014;134(10):2630-2638.

14. Azorín D, López-Ríos F, Ballestín C, Barrientos N, Rodríguez-Peralto JL. Primary cutaneous adenosquamous carcinoma: a case report and review of the literature. J Cutan Pathol. 2001;28(10):542-545.

15. Soyer HP, Rigel DS, McMeinman E. Actinic keratosis, basal cell carcinoma, and squamous cell carcinoma. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Elsevier Limited; 2018:1872-1893.

16. Firnhaber JM. Basal cell and cutaneous squamous cell carcinomas: diagnosis and treatment. Am Fam Physician. 2020;102(6):339-346.