rising incidence • the precise relationship between skin cancer and the risk of internal malignancy is not yet completely defined, and the issue remains controversial
Skin Cancer Diagnosis • Shave Biopsy • Punch Biopsy • Excisional Biopsy
General Approach to Management of Skin Cancer • Excision • Mohs Micrographic Surgery • Curettage and Electrodesiccation • Cryosurgery
The management of skin cancer is guided by • biologic and histologic nature of the tumor, • the anatomic site, • the underlying medical status of the patient • tumor is primary or recurrent.
Excision • Breadloaffashion, • occasionally result in a false-negative assessment of clear margins in cases of • infiltrating • aggressive-growth cancers • vertically prepared frozen specimens
Excision, especially when performed in a physician's office rather than in a hospital operating room, is effective and cost-efficient when the cancer is small (less than 1 cm), nonrecurrent, or noninfiltrative.
Mohs Micrographic Surgery • A key defining feature of MMS is that the surgeon excises, maps, and reviews the specimen personally, minimizing the chance of error in tissue interpretation and orientation.
MMS choice for • recurrent skin cancers, • primary skin cancers located on anatomic sites that require maximal tissue conservation for preservation of function and cosmesis • less expensive
Topical Therapy • Imiquimod • 5-Fluorouracil • Photodynamic Therapy • Radiation Therapy
Imiquimod • an immune-response modifier • induction of cytokine production Ifα ,Ý ,IL 12 • (FDA) for treatment of AKs and superficial BCCs on the trunk, neck, or extremities. • postoperatively • a significant inflammatory reaction.
5-Fluorouracil • FDA for the treatment of actinic keratoses and superficial BCCs • it remains a standard topical treatment for actinic keratoses. Total clearance rates range from roughly 10% to 98%. • Topical 5-FU induces erythema, epidermal pain, and erosion in the treatment area that may be exacerbated by prolonged ultraviolet irradiation
Photodynamic Therapy • ultimately cell death • direct effects on blood vessels :tumor destruction • only FDA approved for the treatment of AKs. Several studies report clearance rates of 81% to 100% for AKs.
Radiation Therapy • electrons (with bolus to bring the skin surface dose to 100%) or with superficially penetrating photons (x-rays). • Appropriate margins around gross disease or surgical scars should be carefully considered and should generally be at least 2 cm when using electrons. • Depending on the histology and nature of the lesion, margins may be wider
Late effects on normal tissues are related to fraction size, and can be minimized with a protracted fractionation scheme utilizing 2 Gy fractions to a total of 60 to 66 Gy for BCC or SCC. • Treatment may be accelerated with excellent local control but with greater risk of fibrosis, atrophy, and poor cosmesis. • Consideration of the permanent tissue effects of radiation therapy, such as chronic radiation dermatitis, delayed radiation necrosis, alopecia, and secondary cutaneous malignanciesmust be anticipated and managed. • Lesions involving the foot, skin over the tibia, or of the dorsum of the hand should be considered with care as they may require more intensive wound care and may not heal as readily following radiation.
Treatment Follow-Up • a history of BCC or SCC should be evaluated on an annual basis • more aggressive tumor, evaluation should be more frequent • in the case of SCC, should include examination of draining lymph nodes • Laboratory evaluation, may be necessary for types of particularly aggressive tumors. • Imaging studies
Precancerous Lesions Actinic Keratosis • very common lesions • on sun-exposed areas • in blond or red-haired, fair-skinned individuals with green or blue eyes • SCC in situ • caused by exposure to ultraviolet B (UVB) light • p53 mutations • spontaneous regression, persistence, or progression into invasive SCC
Molecular characterization of the role of the p53 tumor suppressor gene in AK, and its similar finding in SCC and BCC, suggests that the AKs represent an early stage in the molecular carcinogenesis of NMSC. • The risk for transformation of a single AK has been estimated to be as low as 1 per 1,000 per year.However, the long-term risk of the development of invasive SCC in patients with multiple AKs has been estimated to be as high as 10%.
Clinical Features • AKs are red, pink, or brown papules with a scaly to hyperkeratotic surface • sun-exposed areas and are especially common on the balding scalp, forehead, face, and dorsal hands • increase in prevalence with advancing age. • Bowenoid AK is indistinguishable from Bowen's disease (BD), also known as SCC in situ
Treatment • Use of broad-brimmed hats, sun-protective clothing, sunscreen, and judicious avoidance of sunlight can protect patients from sunlight and prevent the formation of AKs. • Due to their potential to develop into invasive SCC and the inability to determine which lesions will do so, AKs should usually be treated.
Txaks • cryosurgery, • C&D, • topical 5-FU, • immune modulators such as imiquimod, • photodynamic therapy, • chemical cauterization using trichloroacetic acid, • excision
Treatment of solitary lesions is straightforward with cryosurgery, which has been reported to have cure rates of 98%.
management of patients with hundreds of lesions • initially, the largest lesions are often treated by C&D. • Raised lesions of smaller size are then treated by destructive methods, especially the open-spray cryosurgery technique. • topical application of 5-FU with or without topical retinoids • Topical imiquimod • laser and chemical exfoliation,
Lesions that do not respond to treatment and show signs of bleeding, induration, rapid growth, or pain suggest progression to SCC and should be biopsied.
Basal Cell Carcinoma • 75% of all NMSCs and almost 1/4of all cancers diagnosed in the United States. • rarely metastasize • with 30% of lesions occurring on the nose. • Anywhere • BCCs are becoming more common in younger individuals.
pathogenesis of BCC • exposure to ultraviolet light (UVL), which trigger mutations in tumor suppressor genes. Individuals • white individuals • mutations in regulatory genes; • exposure to ionizing radiation • Arsenicals • polyaromatic hydrocarbons • psoralen-plus-UVA therapy • alterations in immune surveillance.
BCC can be a feature of inherited conditions : nevoid BCC syndrome (NBCCS) Bazex's syndrome Rombo syndrome unilateral basal cell nevus syndrome.
NBCCS • a rare autosomal dominant genetic disorder characterized by a predisposition to multiple BCC and other tumors, as well as a wide range of developmental defects. Patients with this syndrome may exhibit a broad nasal root, borderline intelligence, jaw cysts, palmar pits, and multiple skeletal abnormalities in addition to hundreds of BCCs . • This syndrome has significantly helped to elucidate the molecular pathogenesis of BCC.
NBCCS • a mutation in a tumor suppressor gene, • hit is inactivation of the normal homologue by environmental mutagenesis or random genetic rearrangement.
Sporadic BCCs • Inactivation of the patched gene (PTCH gene) • mutations in the p53 gene, in up to 60% of BCCs as well
Clinical Behavior of Basal Cell Cancer • This biologic behavior depends on angiogenic factors, stromal conditions, and the propensity for the cancer to follow anatomic paths of least resistance. In addition, size may play a role, as larger primary BCCs have higher recurrence rates.
BCCs can elicit angiogenic factors • telangiectatic vessels • antiangiogenic factors may play a potential therapeutic role • Necrosis • Tumor stroma is critical for both initiating and maintaining the development of BCC. • The concept of stromal dependence is supported by the low incidence of metastatic BCC.
the path of least resistance • perichondrium, • periosteum, • fascia, • tarsal plate eyelid,nose, and scalp • Embryonic fusion planes : inner canthus philtrum, middle to lower chin nasolabial groove preauricular area the retroauricularsulcus.
Perineural spread is infrequent but occurs most often in recurrent, aggressive lesions. • perineural extension : periauricular and malar areas. • Perineural invasion may present with paresthesia, pain, and weakness or, in some cases, paralysis.
Metastatic BCC • lung, • lymph nodes • esophagus • oral cavity • skin. survival of 8 to 10 months after diagnosis being the norm. Tx Platinum-based chemotherapy
Basal Cell Carcinoma Subtypes • Nodular a raised translucent papule or nodule with telangiectasia and has a propensity for involving sun-exposed areas of the face. • superficial, presents as an erythematous scaly or eroded macule on the trunk ,DDx: AK, SCC in situ, or a benign inflammatory lesion.
Morpheaform (also termed aggressive-growth BCC or infiltrative BCC) a flat, slightly firm lesion, without well-demarcated borders, and may be difficult to differentiate from a scar. Symptoms of bleeding, crusting, and ulceration are often not present in these tumor subtypes and can lead to a delay in diagnosis. The aggressive growth pattern of this subtype is highlighted by the fact that the actual size of the cancer is usually much greater than the clinical extent of the tumor
Pigmented variant of nodular BCC and may be difficult to differentiate from nodular melanoma. The presence of pigment may be of value in determining adequate margins for excision.
fibroepithelioma of Pinkus (FEP) FEP usually presents as a pink papule on the lower back. It may be difficult to distinguish clinically from amelanotic melanoma.
Histologic subtypes of BCC include • superficial, • nodular • micronodular, • infiltrative BCC • FEP, a polypoid lesion • Mixed histology
The recurrences are more frequent in BCCs with infiltrative and micronodular histology, • general, incompletely excised BCCs should be removed completely, preferably by MMS, especially if they occur in anatomically critical areas such as the central zone of the face, retroauricularsulcus, or periocular area.
The results indicate that patients with small BCCs that appear to be completely removed by initial biopsy may be at risk for recurrence if not treated further.