An 82-year-old Caucasian female and retired small business owner presented for ongoing care of multiple pressure keratoses overlying arthritic, contracted toe joints on both feet. She had managed the pressure keratoses with periodic paring, buttress crest padding, digital strapping, felt toe regulators and extra-depth shoes.
Her past medical history included tachycardia requiring a pacemaker, hypertension controlled with hydrochlorothiazide and metoprolol (Toprol, AstraZeneca), and dyslipidemia managed with atorvastatin (Lipitor, Pfizer). The review of systems revealed the patient’s difficulty in finding words to express her thoughts, shortness of breath when walking and pedal swelling.
Significant physical examination findings included persistent eye blinks with the elicitation of the glabellar reflex. Normally, patients quickly learn to suppress eye blinks with one to two light forehead taps but this patient blinked with all five forehead taps, which is suggestive but not diagnostic of early dementia or Parkinson’s disease.1 Overlying pitting edema obscured pedal pulses but the ankle brachial index was a sufficient 0.6 bilaterally. The vibratory threshold was reduced to 10 seconds with normal being 18 seconds.
There were multiple, tender, hyperkeratotic plaques overlying the rigid hammertoes with a history of healed pressure ulceration of the left second toe. The patient was unaware of a 6 mm, non-painful, dry crust on the right anterior shin of unknown duration. She had Type I skin and blue eyes. Dermoscopy examination revealed erythema, hemorrhagic keratin and distorted capillary loops within the dermis consistent with Grade III actinic keratosis or possibly a more dysplastic atypical lesion.
Key Questions To Consider
1. What is the skin lesion?
2. How long has the lesion been present and what is the patient’s skin type?
3. What are the primary impression, mimicker, worst case scenario or esoteric differential diagnoses?
4. How can patients prevent these conditions?
Answering The Key Diagnostic Questions
1. The primary clinical impression was actinic keratosis pending biopsy.
2. The lesion has been present for an unknown duration. The patient had Type I skin so she is at risk for more skin cancer.
3. Seborrheic keratosis can mimic actinic keratosis clinically while squamous cell carcinoma would be a worst case scenario.
4. Prevention centers on reducing overall solar radiation exposure, particularly ultraviolet A exposure. Patients should wear a broad-spectrum sunscreen with a sun protection factor of at least 15 year round.
A Closer Look At Superficial Basal Cell Carcinoma
My suspicions warranted a referral for a biopsy. The shave biopsy found a cutaneous tumor composed of atypical basaloid cells with peripheral palisading, embedded in a fibromyxoid stroma throughout the dermis. These histopathological findings were consistent with superficial basal cell carcinoma. After total excision, periodic dermoscopic examinations did not detect local recurrence or additional atypical neoplasms.
Andrews discusses no less than 13 subtypes of basal cell carcinoma.2 Nodular basal cell carcinoma is the classical subtype that is most familiar. It presents as a waxy, semi-transparent nodule forming around a central depression that may ulcerate, crust and bleed.
Our patient had a frequent variant of basal cell carcinoma called superficial basal cell carcinoma, which commonly occurs on the trunk and distal extremities. Superficial basal cell carcinoma may resemble a patch of eczema or psoriasis that can grow to 10 to 15 cm in diameter. The edges may show a thread-like raised border. It presents as an erythematous plaque with telangiectasia along with atrophy and scarring. Large superficial basal cell carcinomas may develop multiple focal ulcerations, forming a so-called “field of fire.” These large superficial basal cell carcinomas can heal in one place, forming an atrophic scar and spreading to an adjacent areas.2 Distant spread of basal cell carcinoma is rare but it still can occur.3
A Guide To The Differential Diagnoses
Actinic keratosis. The clinical diagnosis of actinic keratosis or solar keratosis is usually straightforward.2 Multiple, red, scaly or crusted lesions measuring 3 to 6 mm that occur on any sun exposed areas of the body characterize actinic keratosis. They typically arise on the head, neck and arms but also occur frequently on the lower anterior legs and feet. They are often elevated, rough in texture and resemble warts. Most become red but some will be tan, pink and/or flesh-toned. Actinic keratoses represent the earliest clinical manifestation of sun-induced skin cancer and are the most common pre-cancer.4
We can divide actinic keratoses dermoscopically into three stages. Stage I may not even be red and it is often more tactile than visible. Stage II actinic keratoses often exhibit a strawberry pattern of red vessels with pink and enlarged, whitened hair follicles. Stage III actinic keratoses have white to yellow keratin filling hair follicles without background erythema. Importantly, untreated actinic keratoses progress to squamous cell carcinoma between 2 and 6 percent of the time. The squamous cell carcinoma is locally aggressive and rarely metastasizes.5,6 It is difficult to distinguish hypertrophic actinic keratoses from early squamous cell carcinoma and I recommend a low threshold for biopsy.2
One can treat single or isolated actinic keratoses with cryotherapy. One can treat multiple or extensive lesions via topical field therapy with 5-fluorouracil, imiquimod or photo activated aminolevulinic acid therapy. One can readily treat actinic keratoses of the lower limb with diclofenac 3% in hyaluronic gel (Solaraze, PharmaDerm) and periodic monitoring with dermoscopy.7
Seborrheic keratoses. These are benign, noninvasive, thickened epidermal lesions that actually are not associated with sebaceous glands despite what their name suggests. Seborrheic keratoses appear as somewhat greasy and stuck-on warts or moles. They typically occur on the face, shoulders, chest and back starting in middle age and beyond.7 Non-pigmented and pigmented seborrheic keratoses commonly occur on the lower legs. Seborrheic keratoses, even when they lack pigmentation, are usually more “stuck on” in appearance and more sharply marginated than actinic keratoses.2
Bowling lists six main dermoscopic features of seborrheic keratoses.8 A general cerebriform pattern, fingerprint structures, comedo openings, milia-like cysts, hairpin vessels and moth-eaten borders may be visible with the use of a dermatoscope. Since seborrheic keratoses are benign, one can treat them with cryotherapy, curettage or shave techniques. Applying ammonium lactate 12% lotion twice daily for two months may reduce the height of seborrheic keratoses but will not change the length or color of lesions.7
Squamous cell carcinoma. These begin at the site of multiple actinic keratoses. They typically arise on the sun-exposed areas of the body or any area of chronic irritation such as a non-healing leg ulcer. Squamous cell carcinoma begins as superficial, hard, dull, red lesions with telangectasias and capillary loops. Squamous cell carcinomas gradually enlarge, deepen and ulcerate.2
Although people with fair complexion, blond or red hair and blue, and green or gray eyes have the highest likelihood of developing skin cancer, African-American females who have lived in the southern United States are predisposed to developing skin cancer on the anterior shins.4 Men living near the equator are the most at risk for solar damage leading to skin cancer. In African-American female patients, squamous cell carcinoma more commonly affects the anterior leg than the sun-exposed areas of the face. Elderly women with a history of infrared heat exposure from open fireplaces are at higher risk for squamous cell carcinoma. Organ transplant recipients receiving anti-rejection therapies are also at higher risk.2
Dermoscopically, squamous cell carcinoma and keratoacanthoma share features of a central yellow keratinous plug(s) surrounded by hairpin vessels in a milky halo peripherally along with central arborising vessels.8 The primary treatment of squamous cell carcinoma is surgical excision. One should examine regional lymph nodes for enlargement as metastasis occurs in about 5 percent of the cases.2 One can limit the loss of good tissue and lower the risk of recurrence with Moh’s surgical techniques.
Key Insights On Prevention
Prevention centers on reducing overall solar radiation exposure, which is particularly more damaging at ultraviolet A (UVA) wavelengths. The American Academy of Dermatology recommends patients wear a broad spectrum sunscreen with a sun protection factor of at least 15 year round.9 If one applies this thickly enough (0.5 mm), this affords 93 percent protection against UVA and UVB for 30 to 90 minutes. While darker, tighter weaved, synthetic fiber, loose fitting clothing can provide more ultraviolet protection than lighter colored, loose weaved, natural fiber materials stretched over skin, clothing may only have an ultraviolet protection factor of 15.9
Lower legs and feet can be overexposed to damaging infrared heat, predisposing the lower extremity to skin cancer. Chronic heat exposure can cause erythema ab igne or toasted skin syndrome, which can be visible on the anterior legs and feet of patients raised in the rural southern U.S. who sat close to fireplaces and heating stoves in homes without central heating.10
Improving surveillance detects skin cancer earlier and improves outcomes. It is becoming more apparent that dermoscopy is a useful tool to clinically analyze skin lesions but Bowling reminds us “the clinic-pathological spectrum of keratinocyte dysplasia extends from actinic keratoses at one end of the spectrum through Bowen’s disease, and finally to squamous cell carcinoma.’’8 While there are some dermoscopic features that correlate with each condition, keratinocyte dysplasia is a spectrum and one must take dermoscopic features into account with all the clinical features and not consider dermoscopic features diagnostic on their own. Dermoscopy improves the triage of suspected skin cancer but does not replace appropriate biopsy.11
Dr. Bodman is an Associate Professor at the Kent State University College of Podiatric Medicine. He is a Diplomate of the American Board of Podiatric Medicine. Dr. Bodman is in private practice in Ohio.
1. Vreeling FW, Houx PJ, Jolles J, Verbey FRJ. Primitive reflexes in Alzheimer’s disease and vascular dementia. J Geriatr Psychiatry Neurol. 1995; 8(2):111-117.
2. James WD, Berger TG, Elston DM. Andrew’s Diseases of the Skin: Clinical Dermatology. Elsevier Saunders, Philadelphia, 2011, pp. 629-641.
3. Bader RS, Santacroce L, Diomede L, Kennedy AS. Basal cell carcinoma. Medscape. Available at http://emedicine.medscape.com/article/276624-overview . Updated March 27, 2014. Accessed June 21, 2014.
4. Gohara M, Perez M. Skin cancer and skin of color. Skin Cancer.org. Available at http://www.skincancer.org/skin-cancer-information/actinic-keratosis . Accessed May 13, 2014
5. Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Dtsch Dermatolo Ges. 2007;5(11):970-6.
6. Lee JH, Won CY, Kim GM, Kim SY. Dermoscopic features of actinic keratosis and follow up with dermoscopy: A pilot study. J Dermatol. 2014; 41(6):487-93.
7. Bogel, MA. Keratoses. In: Arndt A, Hsu J (eds.): Manual of Dermatologic Therapeutics, Chapter 22, Seventh Edition, Lippincott Williams & Wilkins, Philadelphia, 2007, p. 145.
8. Bowling J. Diagnostic Dermoscopy: the Illustrated Guide. Wiley-Blackwell, Hoboken, NJ, 2012, pp. 59-80.
9. Miller JD. Sun reactions and sun protection. In: Arndt A, Hsu J (eds.): Manual of Dermatologic Therapeutics, Chapter 33, Seventh Edition, Lippincott Williams & Wilkins, Philadelphia, 2007, p. 216.
10. Cho S, Shin MH, Kim YK, Seo JE, Lee YM, Park CH, Chung JH. Effects of infrared radiation and heat on human skin aging in vivo. J Investig Dermatol Symp Proc. 2009;14(1):15-9.
11. Argenziano G, Puig S, Zalaudek I, Sera F, Corona R, Alsina M, et al. Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer. J Clin Oncol. 2006;24(12):1877-82.