A 65-year-old man presents with two lesions on his face. The patient states that the lesions have slowly grown on his cheek and lower lip over the past year. They are not painful and do not itch. He decided to come in because they cause him trouble when shaving. On examination, the patient has a 1.0 × 0.8-cm pearly papule with overlying telangiectasias and a rolled border on his right lower cheek and a 1.2 × 1.0-cm pearly papule with overlying telangiectasias and a rolled border on his right lower lip. Aside from the lesions, the patient does not have any other medical problems. The patient does not have any relevant social or family history.
A 70-year-old man presents with a lesion on his left ear. The patient states that he has had a nonhealing lesion on his left ear for approximately 18 months. It did not bother him until approximately 6 months ago, when the lesion and surrounding skin started to hurt. On examination, the patient has a large ulceration with overlying crust. The surrounding skin appears erythematous and inflamed. The lesion is tender on contact. Aside from the lesion, the patient does not have any other medical problems. The patient does not have any relevant social or family history.
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Case #1: Basal cell carcinoma
Basal cell carcinoma (BCC) is the most common form of cancer that occurs in white individuals, and its incidence continues to rise worldwide.1-3 The pathophysiology of BCC is not completely understood, but it is known that there are multiple genetic mutations that arise within the cells that lead to their clonal proliferation and tumor generation. Specific mutations in the hedgehog signaling pathway that lead to constituent pathway activation have been identified in both sporadic and familial cases of BCC.4 Additional loss of function mutations in PTCH1 and tumor suppressor genes such as p53 have been identified, all of which contribute to the cell’s ability to escape the normal regulatory pathways.4
Many risk factors for the development of BCC have been identified. However, exposure to ultraviolet (UV) radiation appears to be the most widely recognized and strongest risk factor.5 Increased duration and severity of UV exposure, as well as exposure in childhood and adolescence, contribute to the development of disease.5 In a study by Kricker and colleagues,6 it was found that intense, intermittent sun exposure was a greater risk to the future development of BCC than the same degree of continuous exposure. Family history of skin cancer, physical characteristics, including fair complexion, light hair and eye color, and various chemical exposures (eg, arsenic), are some of the additional risk factors that contribute to the development of BCC.2,7 Interplay between UV radiation exposure, genetic predisposition, inherent physical characteristics, and exposure to any risk factor all contribute to the likelihood of developing BCC.
BCC presents commonly on the sun-exposed areas of the body; the majority of cases occur on the head and neck, followed by the trunk and extremities.4,8 There are many different clinicopathologic types of BCC; the predominant 3 types are nodular, superficial, and morpheaform.1-4,9 The most common form of BCC is the nodular form, which typically presents clinically as a pearly papule or nodule with overlying telangiectasias and a rolled border, with occasional central crusting or ulceration.4 The superficial form of BCC presents as a scaly erythematous patch or plaque. Both the nodular and superficial forms can contain melanin, giving a brown, black, or blue hue to the lesions.4 The morpheaform type appears as an indurated, whitish, scar-like plaque with indistinct margins.4
The differential diagnosis of BCC varies based on its different forms. The differential diagnosis may include sebaceous hyperplasia, squamous cell carcinoma (SCC), trichoepithelioma, fibrous papules, and molluscum.10 In order to differentiate these various lesions from one another, a biopsy for histopathologic examination is helpful. Histologically, BCCs are a group of epithelial intradermal tumors whose cellular components resemble the undifferentiated basal cells of the epidermis and its appendages.8 Arrangement of cells into palisades at the tumor periphery is characteristic. Visible desmosomal intracellular structures are absent, and the tumor cells have a paucity of cytoplasm.8
Diagnosis of BCC is established histologically by the features described above, and can often be accomplished by a superficial shave biopsy due to the raised nature of the lesions.11 However, if the lesions are small enough and have clear, distinct borders, punch biopsies or excisional biopsies can be employed and can be both diagnostic and therapeutic if clear margins are achieved.11
Treatment of BCC varies based on the tumor’s size, morphology, and extent of growth. Because of the low metastatic potential of BCC, treatment focuses on local control rather than systemic therapy.4 After biopsy, once the diagnosis of BCC is confirmed, most lesions can be treated with either wide local excision or electrodessication and curettage. If a full thickness excisional biopsy produces clear margins, then no further treatment is required for BCC. An additional treatment option is 5-fluorouracil, applied topically or intralesionally.11,12 Recurrent cases of BCC, cases involving cosmetically sensitive areas (such as the face), those with indistinct margins, and lesions >2 cm should be referred for complete excision via Mohs micrographic surgery.11 Mohs micrographic surgery allows tissue sparing by taking smaller margins and checking them under the microscope while the patient waits.
The patient in this vignette was diagnosed with 2 nodular BCCs after shave biopsies were performed. Because the lesions were on the patients face, the patient was referred to a Mohs surgeon for treatment.
Case #2: Squamous cell carcinoma
Cutaneous squamous cell carcinoma (cSCC) is a locally invasive tumor that is second only to basal cell carcinoma as the most common form of skin cancer in white individuals; over 700,000 new cases are diagnosed each year in the United States.13-15 Although locally invasive, cSCC does have metastatic potential greater than that of BCC, giving it a slightly worse prognosis.15 The prevalence of SCC in men is twice that of women, and risk increases with increasing age, particularly in those over age 70 years.13
The development of cSCC is the result of multiple events that interact together to result in aberrant cell proliferation that escapes the cell cycle and ultimately results in cancer. Often, precursor lesions (actinic keratoses) arise before progressing to cSCC.14,16 Although the risk of transformation of actinic keratoses to invasive cSCC is low, the presence of precursor lesions signifies a greater risk for disease.14 Not all cases of cSCC are preceded by precancerous lesions, however, and may arise spontaneously without warning.
There are many risk factors that contribute to the development of cSCC. Like BCC, exposure to UV radiation has proven to be one of the strongest risk factors. However, cumulative UV radiation exposure appears to play more of a role in the development cSCC, whereas intense, intermittent UV radiation exposure is linked more to BCC.6,14 A study of the latitude in which individuals live and the incidence of cSCC found that the incidence doubles with each 8- to 10-degree decline in latitude, further emphasizing the relationship between UV exposure and cSCC.14 Sun exposure, phenotype, genotype, immune status, and chemical exposures all play a role in the development of cSCC. Some of these factors include fair complexion, light-colored hair, blue eyes, immunodeficiency, and exposure to substances such as arsenic or polycyclic aromatic hydrocarbons.2,7,14
The clinical presentation of cSCC can vary from scaly red patches, to hyperkeratotic papules, to nonhealing ulcers.13 The classic lesions are described as firm, skin-colored or pink papules or plaques that can be smooth or hyperkeratotic, and have the potential for ulceration.15 Some patients complain of pain at the area of the lesion. However, these lesions often go unnoticed due to the absence of pain.13 Although cSCC can present anywhere on the body, the lesions are often found in sun-exposed areas. The most common location of invasive SCC is the head and neck, followed by the trunk.16
cSCC can be described histologically as a proliferation of anastomosing nests, sheets, and strands of atypical keratinocytes originating in the epidermis and infiltrating into the dermis.18 Characteristic squamous pearls can be seen. Prominent intracellular bridges are characteristic, and epithelial cells exhibit glassy eosinophilic cytoplasm and often a large nucleus.17,18 Morphologic features can vary based on the histologic subtype of the lesion, grades of differentiation, and depth and degree of invasion.17
The differential diagnosis for cSCC includes many lesions that mimic the appearance of cSCC. Variants of BCC, sebaceous carcinoma, and spindle cell melanoma all have features that can appear very similar to those of cSCC.15 In many cases, these tumors are hard to distinguish clinically from cSCC, and a biopsy must be performed for histopathologic examination. Inverted follicular keratosis can also mimic cSCC, and commonly presents as a scaly papule, nodule, or plaque. In contrast to cSCC, inverted follicular keratosis has a circumscribed border and a lack of significant cellular atypia.15 Keratoacanthomas are well-differentiated squamoproliferative tumors that some clinicians consider a variant of cSCC. Features that differentiate keratoacanthomas from cSCC include a limited pushing deep front, distinct tumor-stromal interface, and lesional squamous cells with abundant cytoplasm centrally.15 These lesions usually lack the significant stromal desmoplasia and cellular atypia seen in cSCC.15
The diagnosis of cSCC is established histologically, and requires a biopsy sample from the lesion in question. The type of biopsy taken generally depends on the size of the lesion and may include a punch, shave, or excisional biopsy.17 Hematoxylin and eosin staining techniques are normally sufficient to make the diagnosis, but in the rare cases of an unclear diagnosis, immunohistochemical markers may be used.17
Treatment for cSCC varies depending on whether or not the disease is superficial or invasive. For individuals with SCC in situ, nonsurgical destructive treatment options including electrodessication and curettage may be used.16,17 Treatment of invasive cSCC is achieved via surgical excision. Wide local excision is considered first-line treatment and is the most effective means for achieving a cure in invasive cSCC, because it allows for detection of tumor-free margins.17 Recurrent cases of cSCC, cases involving cosmetically sensitive areas (such as the face), those with indistinct margins, and lesions >2 cm should be referred for complete excision via Mohs micrographic surgery. If tissue margins are not tumor free or if there is substantial perineural involvement, adjuvant radiation therapy should be considered.17 For patients with metastatic cSCC, chemotherapeutic agents can be used.17
The patient in this vignette was diagnosed with cSCC after a shave biopsy was performed. Due to the location on the ear, the patient was referred to a Mohs surgeon who was able to clear the cSCC and reconstruct his left ear.
Joan Fernandez, BS, is a medical student at the Baylor College of Medicine, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.
- Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 2012;166:1069-1080.
- Verkouteren JAC, Ramdas KHR, Wakkee M, Nijsten, T. Epidemiology of basal cell carcinoma: scholarly review. Br J Dermatol. 2017;177:359-372.
- Robinson JK, Rigel DS, Amonette RA. Trends in sun exposure knowledge, attitudes, and behaviors: 1986 to 1996. J Am Acad Dermatol. 1997;37(2 Pt 1):179-186.
- Rubin AI, Chen EH, Ratner D. Basal cell carcinoma. N Engl J Med. 2005;535:2262-2269.
- Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol. 1995;131:157-163.
- Kricker A, Armstrong BK, English DR, Heenan PJ. Does intermittent sun exposure cause basal cell carcinoma? A case-control study in Western Australia. Int J Cancer. 1995;60:489-494.
- Maloney ME. Arsenic in dermatology. Dermatol Surg. 1996 22:301-304.
- Kerr JF, Searle J. A suggested explanation for the paradoxically slow growth rate of basal-cell carcinomas that contain numerous mitotic figures. J Pathol. 1972;107:41-44.
- Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of basal cell carcinoma: Study of a series of 1039 consecutive neoplasms. J Am Acad Dermatol. 1990;23(6 Pt 1):1118-1126.
- Crowson AN. Basal cell carcinoma: biology, morphology and clinical implications. Mod Pathol. 2006;19(suppl 2):S127-S147.
- Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician. 2004;70:1481-1488.
- Miller BH, Shavin JS, Cognetta A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel. J Am Acad Dermatol. 1997;36:72-77.
- Davis J, Bordeaux J. Squamous cell carcinoma. JAMA Dermatol. 2013;149:1448.
- Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol. 1992;26(3 Pt 2):467-484.
- Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation. J Skin Cancer. 2013; 2013:752864. doi: 10.1155/2013/752864.
- Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344:975-983.
- Stratigos A, Garbe C, Lebbe C, et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51:1989-2007.
- Roewert-Huber J. Invasive squamous cell carcinoma. In: Stockfleth E, Rosen T, Schumaak S, eds. Managing Skin Cancer. New York, NY: Springer; 2010:24-26.