When A Healthy 85-Year-Old Patient Presents With Changing Leg Lesions

An 85-year-old Asian-American female presented to the clinic with a complaint of right shin and posterior calf lesions that had changed recently, and she requested a biopsy as they looked concerning to her. The patient was a poor historian, but her daughter related their presence for at least two years. She added that the lesions had grown larger and more irregular over the past several weeks. The patient’s medical history and surgical history were unremarkable, and she related no current medications or allergies. She had no personal or family history of skin cancer and was a former smoker. The lesions had grown larger and more irregular as of late.

Physical exam demonstrated well-demarcated ulcerations with jagged, undermined, violaceous borders distributed on the right posterior thigh (multiple lesions), and right calf. There was no drainage from the ulcerations and the bases consisted of a combination of granular and fibrous tissue. There was surrounding erythema and some eschar within the ulcerations. There was 1+ pitting edema on exam.

On physical exam, one could observe two very different lesions on her right leg. On the anterior shin, she had a 1 cm scaly lesion on an erythematous base, with what looked like a central ulceration, although there was no drainage or deep probing noted. Posteriorly, however, she had a 2.5cm tan lesion with some scale and multiple areas of dark brown pigmentation, including one area with some elevation. The skin around these lesions was thin and waxy. There was no associated edema, ecchymosis, rashes or evidence of trauma.

A shave biopsy utilizing a #15 scalpel blade on both lesions targeted the elevated spots to evaluate for malignancy. Anesthesia included 1 to 2cc of 1% lidocaine with epinephrine. The biopsy took place without incident. The patient then changed the dressing on the resulting wounds with bacitracin and a bandaid daily until healed.

The biopsy results demonstrated “intra-epidermal proliferation of atypical keratinizing epithelial cells” with nuclear pleomorphism and mitotic figures but without dermal invasion. While a Fontana-Masson stain did reveal melanin pigment, Melan-A and SOX-10 immunostains did not show melanocytic neoplasia. This led to a diagnosis of squamous cell carcinoma in-situ (ie Bowen’s disease). After informing the patient of the diagnosis and various treatment options, due to the patient’s age and skin quality, we opted for non-surgical treatment. In the hope of providing a positive outcome with minimal risk, she underwent treatment with topical imiquimod 5% cream applied to the lesions daily, five days a week, for nine weeks.

Key Questions To Consider

1. What signs and symptoms did this patient exhibit that would lead a clinician to perform biopsies?
2. What conditions might be included in a differential diagnosis for this case?
3. What factors might influence the choice of biopsy technique?

Answering The Key Diagnostic Questions

1. In this case, the size and changing nature of the lesions, along with a lack of clear etiology were some of the reasons biopsy was chosen.
2. Differential diagnosis may include, but not be limited to: squamous cell carcinoma, basal cell carcinoma, actinic keratosis, trauma, or insect bite.
3. Size and type of lesion in question, skin quality, and factors associated with healing potential.

Understanding Squamous Cell Carcinoma

Nonmelanoma skin cancer is the most common cancer in the United States. Squamous cell carcinoma (SCC) makes up 20 percent of those nonmelanoma skin cancers, while basal cell carcinoma (BCC) makes up 80 percent.¹ Accordingly, SCC is the second most common cancer among white people. It is most common among middle-aged and elderly patients. The lifetime risk in 1994 was 9 to 14 percent among males and 4 to 9 percent among females, with higher incidences in the lower latitudes, increasing age, and sun exposure. The past 2 decades have shown a sharp increase in incidence.¹ Lifetime risk in the US is 14 to 20 percent, with a 50 to 200 percent increase in the last three decades, and will likely continue to increase because of the aging population.² Now, SCC results in 1 million cases annually in the United States and causes up to 9,000 deaths.²

UV radiation is important in the genesis of an SCC. Predisposing factors include exposure to sunlight during childhood, sunburns, ionizing radiation, light skin, hazel or blue eyes, blonde or red hair, outdoor occupations, freckling or facial telangiectasia, living in the South, and psoriasis treatment with oral psoralen and ultraviolet A radiation (PUVA). The UV radiation damages the cell and its repair system and alters the immune system while also inducing mutation of the p53 tumor-suppression genes. Keratinocytes undergo clonal expansion and form actinic keratoses, which go on to form SCCs. In the setting of immunosuppression, UV radiation is still a key factor in its development, but the faulty immune system increases the occurrence of SCC signficantly.¹

SCCs are most common in the sun-exposed areas of the body, but unlike BCCs, they appear more commonly on the scalp, backs of the hands, and ear. Usually, they start as an actinic keratosis (AK), which presents as an area of increased vascularity with thickened skin and an adherent yellow scale. Most of these remain superficial; however, a small percentage of these (0.025 to 16 percent per year) will convert to SCC.³ There is no definite way to distinguish between an AK and an SCC without a biopsy, although an increase in thickness, redness, pain, ulceration, and size can suggest malignant transformation to SCC. Some have even suggested that an AK is simply an SCC within the epidermis.¹ One study suggested that dynamic optical coherence tomography may aid in differentiating between the two without performing an invasive biopsy.⁴

Histologically, one will see atypical keratinocytes with nuclear pleomorphism, disordered maturation, and an increased number of mitotic figures. In AKs, the atypical keratinocytes do not fill the epidermis, but in SCC, they fill the epidermis and extend beyond its borders—except in squamous cell carcinoma in situ (SCCIS). Especially when one suspects metastasis, physicians should perform the biopsy and ensure they get deep enough to fully evaluate the extent of the cancer and palpate lymph nodes to rule out deep invasion.^1,2

Evaluating Essential Treatment Options

There are multiple treatment options for squamous cell carcinoma, both surgical and more conservative, depending on the invasiveness of the lesion. SCC is low risk, and treatment may include topical creams like 5-FU or imiquimod; additionally, more destructive methods can be used such as cryotherapy or electrodessication and curettage, or even both. Studies have shown that when combining cryotherapy or electrodessication with curettage, success rates and scar formation are similar.⁵ Newer methods such as Methyl Aminolevulinate Photodynamic Therapy with or without Ablative Fractional Laser treatment show promise in treating microinvasive SCC with minimal adverse events such as pain and unacceptable scar cosmesis.⁶

Excision is recommended for more invasive SCC, or low-risk SCC not responding to topicals if the patient is a good surgical candidate. For local low-risk SCC, the excision should include at least 4 to 6 mm borders, with a recurrence rate of 8.1 percent.² For larger tumors, Mohs surgery provides a way to excise the entire lesion with minimal borders and only a 3 percent recurrence rate.² Wide local excision with primary delayed closure is also acceptable. Local regional or distant metastatic disease requires lymphadenectomy when the lymph nodes are involved. One should also consider concurrent chemoradiation therapy pending margin clearance or if there is extracapsular extension from the lymph nodes (See figure 21-36 and Table 2).

After a diagnosis of SCC, the National Comprehensive Cancer Network (NCCN) recommends follow-up and screening every 3 to 12 months for 2 years after initial diagnosis, then every 2 years. For regional disease, follow-up is recommended every 1 to 3 months for the first year and every 2 to 4 months for the second year. One should follow up every 4 to 6 months in year three and then every 6 to 12 months for life.² The patient should receive instruction on photoprotective measures, including sunscreen application, which can decrease SCC by 40 percent.² Some have suggested that calcium supplementation with or without vitamin D may reduce the risk of SCC, although more studies are needed to confirm this.⁷ The patient should also be encouraged to do self-examinations as much as possible and look for concerning lesions.

Critical Concepts Regarding Prognosis

Classically SCCs were thought to metastasize infrequently; however, more recently, it has been discovered that certain factors—such as sites of radiation and chronic ulcers—are more likely to metastasize¹ (See Table 1). It usually metastasizes to the lungs, liver, brain, skin, and bone. Of note, multiple staging systems for cutaneous SCC predict metastasis—with an incidence of 2 to 5 percent —including the American Joint Committee on Cancer 8th Edition (AJCC8), Brigham and Women’s Hospital (BWH), Tubingen and Salamanca T3 refinement. While the BWH staging system was the most accurate, none of the systems had a high positive predictive value, so SCC staging systems still need improvement.⁸ In addition to the risk of metastasis, the five-year probability of another nonmelanoma skin cancer is 40.7 percent, and the 10-year probability is 59.6 percent.2 After more than one SCC, it is 82 percent and 91.2 percent, respectively.² Annual disease-specific mortality in the US is 1.5 to 2 percent, but in other countries, it is 4 percent.² 

Dr. Vella is a fellowship-trained podiatrist who practices in Gilbert and Sun City, AZ

Editor’s Note: For more engaging patient case presentations, see our other Dermatology Diagnosis columns that appear in print and online. The Podiatric Dermatology Resource Center also showcases the latest diagnostic concepts and therapeutic pathways, along with podcasts and more.

References
1.    Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy, Fifth Ed. Mosby Elsevier;2010.
2.    Waldman A, Schmults C. Cutaneous squamous cell carcinoma. HemOnc Clin N Amer. 2019;33(1):1-12.
3.    Vlahovic TC, Schleicher SM. Skin Disease of the Lower Extremities: A Photographic Guide. HMP Communications;2012.
4.    Themstrup L, Pellacani G, Welzel J, et al. In vivo microvascular imaging of cutaneous actinic keratosis, Bowen’s disease and squamous cell carcinoma using dynamic optical coherence tomography. J Eur Acad Dermatol Venereol. 2017;31(10):1655-1662.
5.    Fournier S, Laroche A, Leblanc M, et al. Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodessication in the management of minimally invasive basal and squamous cell carcinomas. J Cutan Med Surg. 2020;24(6):596-600.
6.    Choi S, Kim K, Song K. Effect of methyl aminolevulinate photodynamic therapy with and without ablative fractional laser treatment in patients with microinvasive squamous cell carcinoma: a randomized clinical trial. JAMA Dermatol. 2017;153(3):289-295.
7.    Passarelli MN, Karagas MR, Mott LA, et al. Risk of keratinocyte carcimonas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial. Am J Clin Nutr. 2020;112(6):1532-1539.
8.    Venables ZC, Tokez S, Hollestein LM, et al. Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data. Br J Dermatol. 2022;186(5):835-842.