1、Basal Cell CarcinomaAuthor: Michael L Ramsey, MD, Director, Mohs Surgery Fellowship, Co-Director, Procedural Dermatology Fellowship, Department of Dermatology, Geisinger Medical CenterCoauthor(s): Lindsay Dane Sewell, MD, Staff Physician, Department of Dermatology, Geisinger Medical CenterContributo
2、r Information and DisclosuresUpdated: Sep 11, 2009IntroductionBackgroundBasal cell carcinoma (BCC) is the most common malignancy in humans. It typically occurs in areas of chronic sun exposure. BCC is usually slow growing and rarely metastasizes, but it can cause clinically significant local destruc
3、tion and disfigurement if neglected or inadequately treated. Prognosis is excellent with proper therapy.PathophysiologyMany believe that basal cell carcinomas (BCCs) arise from pluripotential cells in the basal layer of the epidermis or follicular structures. These cells form continuously during lif
4、e and can form hair, sebaceous glands, and apocrine glands. Tumors usually arise from the epidermis and occasionally arise from the outer root sheath of a hair follicle, specifically from hair follicle stem cells residing just below the sebaceous gland duct in an area called the bulge.The patched/he
5、dgehog intracellular signaling pathway plays a role in both sporadic BCCs and in nevoid BCC syndrome (Gorlin syndrome). This pathway influences differentiation of a variety of tissues during fetal development. After embryogenesis, it continues to function in regulation of cell growth and differentia
6、tion. Loss of inhibition of this pathway is associated with human malignancy, including BCC.The hedgehog gene encodes an extracellular protein that binds to a cell membrane receptor complex to start a cascade of cellular events leading to cell proliferation. Of the 3 known human homologs, Sonic hedg
7、ehog (SHH) protein is the most relevant to BCC. Patched (PTCH) is a protein that is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream
8、genes.1,2 When SHH is present, it binds to PTCH, which then releases and activates SMO. SMO signaling is transduced to the nucleus via Gli. When SHH is absent, PTCH binds to and inhibits SMO. Mutations in the PTCH gene prevent it from binding to SMO, simulating the presence of SHH . The unbound SMO
9、and downstream Gli are constitutively activated, thereby allowing hedgehog signaling to proceed unimpeded. The same pathway may also be activated via mutations in the SMO gene, which also allows unregulated signaling of tumor growth. How these defects cause tumorigenesis is not fully understood, but
10、 most BCCs have abnormalities in either PTCH or SMO genes. Some even consider defects in the hedgehog pathway to be requirements for BCC development.UV-induced mutations in the TP53 tumor suppressor gene, which resides on band 17p13.1, have been found in some cases of BCC.3 Activated BCL2 (an antiap
11、optosis proto-oncogene) also is commonly found in BCCs and may be detected immunohistochemically.FrequencyUnited StatesThe annual incidence of basal cell carcinoma (BCC) is approximately 900,000 cases (550,000 in men, 350,000 in women). The age-adjusted incidence per 100,000 white individuals is 475
12、 cases in men and 250 cases in women. The estimated lifetime risk of BCC in the white population is 33-39% in men and 23-28% in women.Mortality/MorbidityBasal cell carcinoma (BCC) can cause clinically significant morbidity if allowed to progress. Because this cancer most commonly affects the head an
13、d neck, cosmetic disfigurement is not uncommon. Loss of vision or the eye may occur with orbital involvement. Perineural spread can result in loss of nerve function and in deep and extensive invasion of the tumor. These neoplasms are often friable and prone to ulceration; thus, they provide a nidus
14、for infection. Death from BCC is extremely rare.RaceBasal cell carcinoma (BCC) is generally a disorder of white individuals, especially those with fair skin. It is rare in dark-skinned individuals.SexThe male-to-female ratio for basal cell carcinoma (BCC) is approximately 3:2.AgeBasal cell carcinoma
15、 (BCC) most commonly occurs in adulthood, especially in elderly persons.ClinicalHistoryBasal cell carcinoma (BCC) patients often present with a nonhealing sore of varying duration. The lesions are typically seen on the face, ears, scalp, neck, or upper trunk. Mild trauma, such as face washing or dry
16、ing with a towel, initially may cause bleeding. A history of chronic recreational or occupational sun exposure is commonly elicited. Intense sun exposure often occurred in childhood or young adulthood.PhysicalSeveral clinical and histologic subtypes of basal cell carcinoma (BCC) may exhibit differen
17、t patterns of behavior. Recognizing the various types is important because aggressive therapy is often necessary for variants such as micronodular, infiltrating, or morpheaform BCC. When one examines possible skin cancers, the best plan is to use good lighting and magnification. The affected skin sh
18、ould be stretched, squeezed, and palpated to best estimate the size and depth of the tumor. Oblique illumination of the tumor can highlight surface changes, such as a rolled border. Nodular BCC: This is the most common variety of BCC. Nodular BCCs most commonly occur on the head, neck, and upper bac
19、k. They may have some of the following features: o Waxy papules with central depression (see Media File 2) o Pearly appearance o Erosion or ulceration o Bleeding o Crusting o Rolled (raised) border (see Media Files 4-5) o Translucency o Telangiectases over the surface o History of bleeding with mino
20、r traumaNodular basal cell carcinoma appearing as a waxy, translucent papule with central depression and a few small erosions.Scale, erythema, and a threadlike raised border are present in this superficial basal cell carcinoma on the trunk.Large, superficial basal cell carcinoma.Pigmented BCC: In ad
21、dition to features seen in lesions of nodular BCC, lesions of pigmented BCC contain increased brown or black pigment and are most common in individuals with dark skin (see Media File 7).Pigmented basal cell carcinoma has features of nodular basal cell carcinoma with the addition of dark pigmentation
22、 from melanin deposition. The pigmentation often has the appearance of dark droplets in the lesion, as shown here.Cystic BCC: Lesions of cystic BCC are translucent blue-gray cystic nodules that may mimic benign cystic lesions. Superficial BCC: This variety appears as scaly patches or papules that ar
23、e pink to red-brown, often with central clearing. A threadlike border is common. Erosion is less common in superficial BCC than in nodular BCC (see Media File 1). Superficial BCC is common on the trunk and has little tendency to become invasive. The papules may mimic psoriasis or eczema, but they ar
24、e slowly progressive and not prone to fluctuate in appearance. Numerous superficial BCCs may indicate arsenic exposure.This translucent pink papule has telangiectases and a crusted erosion, characteristic of nodular basal cell carcinoma.Micronodular BCC: This aggressive BCC subtype has the typical B
25、CC distribution. It is not prone to ulceration, it may appear yellow-white when stretched, and it is firm to the touch. It may have a seemingly well-defined border. Morpheaform and infiltrating BCC: These are aggressive BCC subtypes with sclerotic (scarlike) plaques or papules. The border is usually
26、 ill defined and often extends well beyond clinical margins. Ulceration, bleeding, and crusting are uncommon. It may be mistaken for scar tissue (see Media 8 and Media File 10).This infiltrating basal cell cancer has ill-defined borders and telangiectases.Large, scarlike morpheaform basal cell cance
27、r.Younger patients (2 cm in diameter on certain areas of body. Indicated only when surgical methods not appropriate. Dosing Interactions Contraindications PrecautionsAdultApply cream to treatment area (including 1 cm of skin around tumor) 5 d/wk at bedtime for 6 wk; leave on for 8 h, then wash areaP
28、ediatricNot established DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsInterferon alfa-2b (Intron A)Protein product manufactured with recombinant DNA technology. Mechanism of antitumor activity not clearly und
29、erstood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may be important. Investigational use for nodular BCC. Used in a randomized, placebo-controlled multicenter study (172 subjects). Intralesional injections of 1.5 million U administered 3
30、 times/wk for 3 wk yielded 86% complete-response rate; 29% for placebo. Study included nodular BCCs; similar study did not show efficacy for morpheaform or aggressive BCCs. Dosing Interactions Contraindications PrecautionsAdult1.5 million U intralesional injection 3 times/wk for 3 wkPediatricNot est
31、ablishedBasal Cell Carcinoma: Follow-upFollow-upPrognosis Basal cell carcinomas (BCCs) treated incompletely can recur. All treated sites must be monitored after therapy. Individuals with BCC have a 30% greater risk of having another BCC unrelated to the previous lesion compared with the risk in the
32、general population.Patient Education Avoidance of exposure to UV radiation is encouraged to prevent basal cell carcinoma (BCC). Helpful preventive measures include carefully planning outdoor activities before 10 am and after 4 pm, wearing a broad-brimmed hat during outdoor activities, and using suns
33、creens with sun protection factor of 30 or higher. For excellent patient education resources, visit eMedicines Cancer and Tumors Center and Burns Center. In addition, see eMedicines patient education articles Skin Cancer, Skin Biopsy, and Sunburn.Basal Cell Carcinoma: MultimediaMultimedia(Enlarge Im
34、age)Media file 1: This translucent pink papule has telangiectases and a crusted erosion, characteristic of nodular basal cell carcinoma.(Enlarge Image)Media file 2: Nodular basal cell carcinoma appearing as a waxy, translucent papule with central depression and a few small erosions.(Enlarge Image)Me
35、dia file 3: Nodular basal cell carcinoma. Nodular aggregates of basalioma cells are present in the dermis and exhibit peripheral palisading and retraction artifact. Melanin is also present within the tumor and in the surrounding stroma, as seen in pigmented basal cell carcinoma.(Enlarge Image)Media
36、file 4: Scale, erythema, and a threadlike raised border are present in this superficial basal cell carcinoma on the trunk.(Enlarge Image)Media file 5: Large, superficial basal cell carcinoma.(Enlarge Image)Media file 6: Histology of superficial basal cell carcinoma. Nests of basaloid cells are seen
37、budding from the undersurface of the epidermis.(Enlarge Image)Media file 7: Pigmented basal cell carcinoma has features of nodular basal cell carcinoma with the addition of dark pigmentation from melanin deposition. The pigmentation often has the appearance of dark droplets in the lesion, as shown h
38、ere.(Enlarge Image)Media file 8: This infiltrating basal cell cancer has ill-defined borders and telangiectases.(Enlarge Image)Media file 9: Postoperative wound after Mohs micrographic surgery demonstrates extensive subclinical involvement typical of many infiltrating and morpheaform basal cell carcinomas.(Enlarge Image)Media file 10: Large, scarlike morpheaform basal cell cancer.
