Gradual Development of Ulcerating Lesions

Answer: D

Squamous cell carcinoma (SCC) is the second most common type of skin cancer after BCC and represents approximately 20% of skin cancers.¹¹ Approximately 700,000 new cases of SCC are diagnosed per year.¹¹ The incidence of SCC is rising due to multifactorial causes including an aging population, use of tanning beds, and increased ability for detection.^4,11

SCC tends to occur in older white patients, although individuals from all races are affected.⁴ The average age of onset is in the mid-60s.¹² SCC affects men about 2 to 3 times more often than women; this has typically been attributed to increased lifetime UV light exposure in men.¹³ There is an increased incidence of cases of SCC in populations that live near the equator.⁴ Patients who are on immunosuppressive medications, such as organ transplant recipients, are at increased risk for SCC.⁴ Environmental exposure to arsenic can predispose individuals to SCC.⁴ Overall, the most important risk factors for SCC development include UV light exposure, increasing age, fair skin, and immunosuppression.^4,13

A keratinocyte is the predominant cell type in the epidermis. Repeated damage to keratinocyte DNA, typically by UV radiation, can result in an accumulation of mutations that ultimately results in malignant transformation of these cells. The most commonly mutated gene in SCC is the TP53 tumor suppressor gene.¹³ Mutated TP53 allows the cell to proliferate in an uncontrolled fashion and resist apoptosis. Malignant transformation of the epidermal keratinocyte can ultimately lead to dysplasia and SCC.¹³

Actinic keratosis, or solar keratosis, is the premalignant lesion of SCC and presents as a sand-paper like texture of the skin. It may also present with hyperkeratotic papules on an erythematous base. Actinic keratoses should be removed, typically by cryotherapy, or monitored closely for transformation into SCC.¹⁴ Bowen disease, or SCC in situ, presents with full thickness atypia without invasion. It appears as scaly, red plaques that are localized and slow-growing.¹⁴ Typically, SCC presents as a pruritic, nonhealing ulcer or an abnormal growth in an area of the skin that receives ample sun exposure, such as the face, scalp, neck, trunk, and lower lip.The lesion may also appear as a pink papule or nodule. It may have scales or crust and bleed easily.¹⁴

On histologic evaluation, SCC appears as nests of squamous epithelial cells extending down into the dermis. A large nucleus surrounded by abundant eosinophilic cytoplasm indicates malignant cells.¹⁵ Occasional keratin pearls may be visualized. A grade of well differentiated, moderately differentiated, or poorly differentiated is assigned based on how closely the carcinoma resembles squamous epithelium. Perineural invasion of SCC occurs in approximately 5% to 14% of cases.^14,15 Perineural involvement presents as facial muscle twitching, weakness, or numbness.¹⁵

The differential diagnosis for SCC is broad and includes other skin conditions such as proliferative actinic keratosis, basal cell carcinoma, sebaceous carcinoma, Bowenoid papulosis, keratoacanthoma, verrucous hyperplasia, inverted follicular keratosis, pseudoepitheliomatous hyperplasia, and amelanocytic melanoma.¹⁶ The broad differential diagnosis emphasizes the importance of skin biopsy for suspected SCC, because the histology will be used to differentiate between the potential skin conditions.¹⁶

Whenever cutaneous malignancy is suspected, biopsy should be performed.¹⁷ Types of biopsy include excisional, incisional, or punch. The most common type of biopsy performed for SCC is excisional biopsy, as it is both diagnostic and therapeutic.¹⁷ The full thickness of the skin should be examined in the biopsy; therefore, a shave biopsy is not recommended. Histological presentation of SCC involves significant squamous cell atypia, abnormal keratinization, and invasive features.¹⁷

Of note, for SCC measuring >2 cm in diameter, metastasis to regional lymph nodes should be considered.¹⁴ Metastasis is more likely to occur with SCC vs BCC; however, both are less likely to metastasize than melanoma. The 5-year rate of metastasis for smaller lesions is 5%; it is 30% for lesions >2 cm.¹⁴

Several therapies exist for SCC, such as surgical excision, electrodesiccation and curettage, and radiation therapy. The preferred treatment method is surgical excision, which allows for histologic verification of the tumor margins.^4,18 Specifically, Mohs micrographic surgery is a surgical technique that allows for removal of the SCC and simultaneous maximization of tissue preservation. Mohs is ideal for SCC that is high risk, poorly defined, or recurrent, and it has the highest cure rate.¹⁸ Typically, electrodesiccation and curettage are performed for low-risk, localized, and superficial SCC. It is fast and minimally invasive; however, no specimen is available for margin evaluation, which may result in tumor recurrence.¹⁸ Radiation therapy is reserved for patients who are unable to undergo surgical removal of the lesion.^4,18 Adjuvant chemotherapy may be used for patients with high-risk SCC. Precancerous lesions can be treated topically with 5-fluorouracil, capecitabine, and diclofenac sodium, or with photodynamic therapy.¹⁸

For the patient in this case, biopsy of the suspicious lesion revealed SCC, and the patient subsequently underwent wide local excision, allowing for tissue preservation and clear margins. To prevent subsequent lesions, the patient was advised to avoid ultraviolet exposure, especially during the middle of the day, and to wear sun-protective clothing such as long sleeves and hats.¹⁰ The patient was also advised to wear sunscreen with a sun protection factor of 30 or higher and UVA and UVB protection if spending time outdoors.¹⁰

Yelena Dokic, BSA, is a medical student; McKenna E. Boyd, BS, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine in Houston, Texas.

References

1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 2015;151(10):1081-1086.
2. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: epidemiology; pathophysiology; clinical and histological subtypes; and disease associations. J Am Acad Dermatol. 2019;80(2):303-317.
3. Dourmishev LA, Rusinova D, Botev I. Clinical variants, stages, and management of basal cell carcinoma. Indian Dermatol Online J. 2013;4(1):12-17.
4. Garcovich S, Colloca G, Sollena P, et al. Skin cancer epidemics in the elderly as an emerging issue in geriatric oncology. Aging Dis. 2017;8(5):643-661. 
5. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis. J Am Acad of Dermatol. 2010;62(1):67-75.
6. Busam KJ. Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier/Saunders; 2016.
7. Elsherbiny RE, Umair A, Azzeghaiby SN, Alzoghaibi I, Dabour S, Tarakji B. Detection of basal cell carcinoma–a guide line for general practitioners in dentistry. Br J Med Med Res. 2014;4(26):4352-4363. 
8. Stratman EJ, Elston DM, Miller SJ. Skin biopsy: identifying and overcoming errors in the skin biopsy pathway. J Am Acad Dermatol. 2016;74(1):19-25.
9. Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med. 2015;88(2):167-179.
10. Stratton SP. Prevention of non-melanoma skin cancer. Curr Oncol Rep. 2001;3(4):295-300. 
11. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68(6):957-966. 
12. Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978-2012. JAMA Dermatol. 2014;150(10):1063-1071. 
13. 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.
14. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Eng J Med. 2001;344(13):975-983.
15. Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutaneous squamous cell carcinoma: a review. J Skin Cancer. 2011;2011:210813. 
16. Tan K-B, Tan S-H, Aw DC-W, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation. J Skin Cancer. 2013;2013:752864.
17. Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician. 2004;70(8):1481-1488.
18. Potenza C, Bernardini N, Balduzzi V, et al. A review of the literature of surgical and nonsurgical treatments of invasive squamous cells carcinoma. BioMed Res Int. 2018;2018:9489163. 

From the July/August 2019 Issue of Clinical Advisor