October 2014 Dermatologic Look-Alikes
October 2014 Dermatologic Look-Alikes
A man, aged 74 years, presents with 2 pink sores on his forehead that grew larger over the last year. Although not painful, the sores did itch occasionally and bled when he combed his hair. He had had nonmelanoma skin cancer, but no current significant medical conditions. Physical exam revealed 2 distinct papules: one red and friable and the other pink and slightly scaly with central ulceration. There was a significant background of actinic damage. Dermoscopic exam revealed arborizing blood vessels and flecks of pigment in both lesions.
A man, aged 83 years, presents to the clinic for a new growth on his forehead that had appeared 2 months prior and appeared to be enlarging rapidly. Although the growth was painless, it did bleed spontaneously. The patient’s medical history was notable for excessive sun exposure and multiple nonmelanoma skin cancers. Physical exam revealed a shiny, red, soft, 9-mm nodule on the left lateral forehead with a background of numerous actinic keratoses. A complete skin exam yielded several lesions that were suspicious for malignancy.
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CASE #1: Basal cell carcinoma
Basal cell carcinoma (BCC), a form of nonmelanoma skin cancer, is the most common cancer in the United States, with an average annual incidence of 2 million cases nationwide. The American Cancer Society estimates that in the Caucasian population, the risk for developing BCC is 33% to 39% for men and 23% to 28% for women during their lifetime.1
BCC results from damage to the DNA of the basal cells in the epidermal layer. It is believed that both genetic and environmental factors play a role in the formation of BCC.
Environmentally, excessive exposure to sunlight, particularly to the ultraviolet (UV)B wavelength, is the greatest contributor to BCC, causing slow but cumulative damage. Exposure during childhood seems to be the most harmful, although damage is not usually seen until decades later.2 Other forms of radiation exposure contributing to BCC include tanning beds, UV light therapy, and x-ray.
More recently, genetic mutations, with particular focus on the tumor protein p53 (TP53) gene, are being recognized as risk factors for BCC.3
BCC presents as a slow-growing, painless lesion. Although the classic presentation of BCC is a pink papule or pimple, it may appear as a waxy plaque or ulcer with a white, pink, flesh, or brown color. Clinical presentation often correlates with pathologic subtype, some of which include nodular, infiltrative, micronodular, morpheaform, ulcerative, and superficial.4
BCC occurs most commonly in older people with a fair complexion (Fitzpatrick skin types I and II) who have a history of abundant sun exposure. Incidence is somewhat higher in males, possibly because of their higher incidence of recreational and occupational sun exposure.
The variable clinical presentation of BCC often leads to a misdiagnosis of benign lesion or dermatitis. Superficial BCCs may be mistaken for an eczema, guttate psoriasis, or actinic keratosis. Morpheaform BCCs are often mistaken for a scar.
Pigmented BCCs can be overlooked as a dysplastic nevus. Nodular BCCs can be confused with other benign or malignant skin tumors, such as sebaceous hyperplasia, intradermal nevus, and much less commonly, amelanotic melanoma or Merkel cell carcinoma.
Dermoscopy is valuable in identifying BCCs clinically. Asymmetric arborizing blood vessels, structureless or leaflike areas, blue/gray lobules, and flecks of pigment are all features that can help confirm a diagnosis of BCC.5 Ultimately, a skin biopsy is necessary to confirm the diagnosis of BCC and to determine the histologic subtype.
Most BCCs are treated with surgical intervention. Lesions on the head or neck and those that are larger in size are best treated with Mohs micrographic surgery, a procedure involving staged excisions until surgical margins are deemed clear. Simple excisions are indicated for other BCCs that require histopathologic confirmation of clear margins.2 Electrodessication and curettage is often performed for superficial BCCs located in areas that are not sensitive cosmetically.
Because BCCs are radiosensitive, radiation therapy can be a consideration for patients with large tumors or those who are not candidates for surgical therapy. Similarly, radiation therapy can be used postoperatively for aggressive BCCs.
Photodynamic therapy is usually reserved as adjunctive treatment, as its long-term benefit is unknown.6
Several topical treatments exist. Imiquimod is approved by the FDA for superficial BCCs occurring in areas other than the face. It is applied 5 times a week without occlusion for 6 or more weeks.7 Tazarotene and 5-fluorouracil 5% have also been used for low-risk BCCs.
In 2012, the FDA approved vismodegib, the first oral medication for the treatment of advanced BCC. Because of its unpleasant side-effect profile, however, vismodegib is usually reserved for cases where more standard treatments have failed.
Although patients with BCC have an excellent prognosis, morbidity and significant cosmetic impairment can occur. Metastasis occurs less than 0.5% of the time and usually occurs in large recurring tumors of the head and neck.
All health-care providers should feel confident in regularly educating patients about skin-cancer prevention. Sunscreen with a SPF of 30 or higher should be applied daily to all areas of the skin that are exposed to the sun, as well as reapplied every 2 hours while outdoors or more often when swimming or sweating.
Patients with risk factors should be referred to a dermatology provider for a full skin examination, as BCC that is detected early has an excellent prognosis with a 100% survival rate for lesions that have not metastasized.
The patient in this case was counseled regarding the suspected diagnoses. A skin biopsy confirmed that both lesions were BCC; one was the nodular subtype and the other was ulcerative. Simple excision with primary closure gave the patient an acceptable cosmetic outcome.
CASE #2: Merkel cell carcinoma
Merkel cell carcinoma (MCC), also known as neuroendocrine carcinoma of the skin or trabecular cancer, is a rare malignant tumor of the skin. It forms when the Merkel cells, which function as mechanoreceptors and are located in the basal layer of epidermis, grow uncontrollably.8 MCC carries a poor prognosis; it spreads quickly, usually to the local lymph nodes, liver, lung, and bones.
In the United States, the incidence of MCC is estimated at 1,500 cases per year.9 In the last few years, however, the number of cases has increased rapidly, at an average of 8% per year.10 MCC occurs twice as often in males as in females. Approximately one-third of patients with MCC will succumb to the cancer, which has a mortality rate that is significantly higher than that of malignant melanoma. Most patients with MCC die of the disease within 3 years of initial diagnosis.
MCC presents as a solitary, fast-growing, painless lump in sun-exposed skin. The growth is often firm and flesh, red, or purple in color, and telangiectasias are often present on the surface of the tumor. The head, neck, and arms are favored sites for MCC presentation.
Risk factors include a compromised immune system, history of excessive sun exposure, fair skin type, previous skin cancers, and increasing age. The average age at time of diagnosis is 74 years. Some authors have provided the acronym AEIOU to describe MCC: asymptomatic, expanding rapidly, immunosuppression, older than 50, and ultraviolet-exposed location.11
In addition to these risk factors, a new virus, named Merkel cell polyomavirus, was discovered in 80% of MCCs.12,13
Skin biopsy and histologic examination are necessary to diagnose MCC. Often, special stains, such as low-molecular-weight keratin and cytokeratin 20, are necessary for the pathologist to differentiate MCC from other forms of cancer.
Clinically, MCC presents similarly to basal cell carcinoma, amelanotic melanoma, and cutaneous lymphoma, while histologically, it must be differentiated from small-cell lung cancer, neuroblastoma, lymphoma, and small-cell endocrine carcinoma.1
Histologic examination shows a dermal or subcutaneous tumor. The cells have scanty cytoplasms and hyperchromatic nuclei with a fine granular and dusty chromatin pattern. Numerous apoptotic nuclei and mitotic figures are seen.
Treatment for MCC includes surgery, radiation, and/or chemotherapy. Several treatment protocols and guidelines exist, although recommendations will depend on the disease stage.8 A full workup including a chest x-ray and, possibly, a positron emission tomography/computed tomography scan is necessary for disease staging.
Surgical therapy involves a wide local excision, usually with a sentinel lymph-node biopsy. If the biopsy is positive, then a regional or radical lymph-node dissection is necessary. Radiation can be administered externally or internally. Chemotherapy is usually reserved for more advanced disease, and it is unfortunately usually only palliative.
With localized disease, 5-year survival is estimated at 64%,1 whereas patients with locoregional disease, which is categorized as stage II, have only an estimated 47% survival rate. Unfortunately, stage-III disease, with distant metastasis, carries only a 9-month survival rate.
Very close follow-up is recommended for all patients with a history of MCC. A full skin examination should be performed every 3 months for the first year and then at least biannually. Clinicians should have a low threshold for biopsy of suspicious skin lesions. In addition, chest x-ray should be performed yearly for early detection of recurrences.
The patient in this case was referred to an oncologic surgeon. Initial workup, including lymph-node biopsy, did not reveal evidence of metastatic disease. He underwent a wide local excision that required advanced plastic-surgery techniques for closure.
When the patient returned to the office 3 months later, he did not show clinical signs of recurrence, but he did have numerous actinic keratoses, which are precancerous lesions that required treatment. n
Esther Stern, NP-C, is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J.
- James WD, Berger T, Elston D, eds. Epidermal nevi, neoplasms, and cysts. Andrews’ Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa.: Elsevier Saunders; 2006: 646-650.
- Drake LA, Ceilley RI, Cornelison RL, et al; The American Academy of Dermatology Committee on Guidelines of Care. Guidelines of care for basal cell carcinoma. J Am Acad Dermatol. 1992;26(1):117-120.
- Frey LM, Houben R, Bröcker EB. Pigmentation, melanocyte colonization, and p53 status in basal cell carcinoma. J Skin Cancer. 2011;349726. Available at hindawi.com/journals/jsc/2011/349726
- Miller SJ. Biology of basal cell carcinoma (Part I). J Am Acad Dermatol. 1991;24(1):1-13.
- 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 Dermatol. 2010;62(1):67-75. Available at jaad.org/article/S0190-9622(09)00664-1/abstract
- Bath-Hextall FJ, Perkins W, Bong J, Williams HC. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2007;1:CD003412.
- Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009;145(12):1431-1438.
- Ratner D, Nelson BR, Brown MD, Johnson TM. Merkel cell carcinoma. J Am Acad Dermatol. 1993;29(2 Pt 1):143-156.
- Merkel cell carcinoma: Information for patients and their physicians. merkelcell.org. Updated January 27, 2014.
- Nasseri E. Merkel cell carcinoma. Can Fam Physician. 2012;58(9):967-969. Available at cfp.ca/content/58/9/967.full .
- Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58(3):375-381. Available at jaad.org/article/S0190-9622(07)02389-4/abstract.
- Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096-1100. Available at ncbi.nlm.nih.gov/pmc/articles/PMC2740911.
- Ramirez-Fort M, Khan F, Nguyen H, et al. Observation: A case of Merkel cell carcinoma infected by Merkel cell polyomavirus DNA. J Am Acad Dermatol. 2013;68(4 Suppl 1):AB131. Available at eblue.org/article/S0190-9622(12)01824-5/abstract.
All electronic documents accessed on October 1, 2014.