uncoordinated with that of normal tissue with capacity to metastasize
to lymph nodes and other organs
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? Deals chiefly with the malignant tumors arising from epidermal cells
? Basal cell carcinoma
? Squamous cell carcinoma
? Malignant melanoma
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Basal cell carcinoma (BCC)
? The most common cancers in humans
? All BCCs - Mutations activating the Hedgehog signaling pathway
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? Exposure to UV light? Associated with PTCH1 gene mutation in most cases
? BCCs are locally destructive but rarely metastatic
? BCCs - primarily treated by surgical excision, electrodesiccation &
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curettage, Mohs micrographic surgery and topical agentsEpidemiology
? BCC - The most common cancer in humans
? Estimated - >3 million new cases occur each year in the USA
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? Men - affected slightly more often than are women? Tumors - More frequent in patients older than 60 years of age
? Majority of BCCs- located on the head and neck
Risk factors
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? Risk factors for BCC - ultraviolet radiation (UVR) exposure, light hair
and eye color, northern European ancestry and inability to tan
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? BCC is rare in dark skin - the inherent photoprotection of melanin &melanosomal dispersion
Clinical Features
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? Subtypes?Nodular BCC - the most common clinical subtype
?Pigmented BCC - a subtype of nodular BCC that exhibits increased melanization
?Superficial BCC - most commonly on the trunk
?Morpheaform (sclerosing/infiltrating) BCC - an aggressive growth variant
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?Basosquamous carcinoma - a form of aggressive growth BCC; can be confusedwith squamous cell carcinoma (SCC)
?Fibroepithelioma of Pinkus
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Clinical Features
? Presence of any nonhealing lesion Should raise the suspicion of
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skin cancer? BCC - usually on sun-exposed areas of the head & neck
? Can occur anywhere on the body
? Commonly seen features - translucency, ulceration, telangiectasias,
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and the presence of a rolled border
? Characteristics - Differ for different clinical subtypes
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Nodular BCC
? The most common clinical subtype
? Occurs most often on the sunexposed areas of the head & neck
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? Appears as a translucent papule or nodule? Usually telangiectasias and often a rolled border
? Larger lesions with central necrosis - referred to by the historical term
`rodent ulcer'
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Pigmented BCC
? A subtype of nodular BCC ? exhibits increased melanization
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? Pigmented BCC - Presents as a hyperpigmented, translucent papuleSuperficial BCC
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? Superficial BCC - most commonly on the trunk? Appears as - a well-demarcated erythematous patch
? The DD nummular (discoid) dermatitis
? An isolated patch of "eczema" that does not respond to treatment -
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raise suspicion for superficial BCCMorpheaform BCC
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? An aggressive growth variant? Lesions of morpheaform BCC - have an ivorywhite appearance
? May resemble a scar or a small lesion of morphea
? The appearance of scar tissue [in the absence of trauma/ previous surgical
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procedure or the appearance of atypical-appearing scar tissue at a previouslytreated lesion] - alert for possibility of morpheaform BCC
? The extent - often larger than the clinical appearance
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Basosquamous carcinoma
? A form of aggressive growth BCC
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? Can be confused with squamous cell carcinoma (SCC)? Histologically - Shows both basal cell and SCC differentiation in a
continuous fashion
Diagnosis
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? Diagnosis - Accurate interpretation of the skin biopsy results
? The preferred method of biopsy - shave biopsy, punch biopsy
? Punch biopsy - Useful for flat lesions of morpheaform BCC & for
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recurrent BCC occurring in a scar? During biopsy - adequate tissue
Management
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? Management of BCC - guided by anatomic location & histological
features
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? Approaches include standard surgical excision or destruction byvarious other physical modalities, Mohs micrographic surgery (MMS)
topical chemotherapy
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? Best chance to cure - Through `adequate initial treatment'
recurrent tumors are more likely to be resistant to further treatments
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? May cause further local destructionMohs micrographic surgery
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? Developed in 1938 by Frederic E. Mohs, a general surgeon? A microscopically controlled surgery used to treat common types of
skin cancer
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? During the surgery, after each removal, the tissue is examined forcancer cells
? Provides informed decision for additional tissue removal
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? Improves prognosis - After 5 years, MMS-treated BCCs recurred in1.4% of primary & 4% of recurrent tumors
? Preferred treatment for any BCC where tissue conservation is desired
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? Standard surgical excision? Curettage & desiccation
? Cryosurgery
? Imiquimod (5% cream)
? 5-Fluorouracil
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? Photodynamic therapy (PDT)Squamous cell carcinoma (SCC)
? SCC - second most common skin cancer, in immunocompetent after
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basal cell carcinoma
? The most common skin cancer - in immunosuppressed organ
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transplantation recipients? Majority of SCC - present with early-stage disease
? Prognosis - excellent in the majority of cases
? Risk of developing metastasis from SCC is generally low
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Risk factors? Ultraviolet radiation (both UVB and UVA) ? most important
environmental risk factor for the development of SCC with a strong
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dose-response association
? Genetic predisposition - potentiate the risk of environmental factors
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such as UVR? Clinical skin phenotypes - Light complexion (as in photo types I, II)
? Physical & chemical carcinogens- Arsenic, used in various
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medications, tainted wine and unprocessed well water may stimulate
skin carcinogenesis; Cutting oils - a risk of SCC development in certain
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industrial occupations; SCC on the scrotum of chimney sweeps -attributed to chronic exposure to ash & polycyclic aromatic
hydrocarbons derived from carbon compounds (e.g. coal tar)
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? Immunosuppression including iatrogenic (e. g. solid organ
transplantation recipients, with autoimmune or rheumatoid disease),
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Hematopoietic stem cell transplantation, Infection with HIV/AIDS? Viral infection ? HPVs
? Chronic inflammation & chronic injury of the skin ? chronic ulcers
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(Marjolin's), burn scars & radiation dermatitis? Chronic inflammatory disorders - discoid lupus erythematodes,
mucosal & hypertrophic lichen planus, lichen sclerosus & dystrophic
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epidermolysis bullosa
Epidemiology
? SCC incidence - increases with age; most patients =/> 60
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? Higher in men than in women? Sun-sensitive individuals with red hair, blue eyes & fair complexion -
higher risk than individuals with darker pigmentation
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? Race- Australians, exposed to very high, long-term UVR levels ? morelikely to develop SCC than other populations
Clinical Features
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? Variable & depends on the histologic subtype and location
? Typically, SCCs arise on sun-exposed areas
? The face, head, and neck region & the forearms & dorsum of the
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hands? The typical clinical finding ? includes slowly enlarging, firm, skin-
colored to erythematous plaques or nodules
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? Marked hyperkeratosis
? Ulceration, exophytic or infiltrative growth patterns - seen
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Verrucous SCC
? Verrucous SCC - a slowly growing ulcerated plaque or an exophytic
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cauliflower-like slowly growing tumor? Typical locations
? Oral cavity (oral florid papillomatosis)
? Genitoanal region (giant condyloma acuminatum; Buschke-L?wenstein)
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? Plantar skin (epithelioma cuniculatum)? Amputation stumps
? Less common than other forms of invasive SCC
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Diagnosis? The standard pathology report to indicate:
? Histologic subtype (acantholytic, spindle cell, verrucous, or
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desmoplastic type)? Grade of differentiation (G1 to G4)
? Maximum vertical tumor diameter in millimeters
? Extent of dermal invasion (Clark level)
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? Presence or absence of perineural, vascular, or lymphatic invasion? Information about whether the margins are free or not
Treatment
? Treatment modality for the primary lesion - major determinant for
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the risk of local recurrence
? Ideal management - local tumor control along with maximal
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preservation of function and cosmesisSurgical excision
? Surgery excision - preferably microscopically controlled surgery (Mohs
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surgery) - primary mode of therapy
? For localized lesions - cure rate of 95%
? SCC - local in-transit metastasis- may be removed by wide surgical
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excision or treated by irradiation of a wide field around the primary
lesion
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? Treatment of nodal metastasis - lymph node dissection, radiation, ora combination of both
Other therapies
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? Topical therapeutic treatments- e.g. imiquimod, topical orintralesional 5-fluoruracil, cryotherapy & PDT ? Lack of evidence for
the efficacy
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? Radiation therapy - patient preference and other factors, e.g.
problematic locations for surgery
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? Limited data on the efficacy of chemotherapy for metastatic SCC? Standard options in metastatic or unresectable disease ? systemic
platinum-based chemotherapeutic regimens, 5-
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fluorouracil/capecitabine, or monotherapy/chemotherapy withmethotrexate
Prognosis
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? Majority of SCCs- low risk? If early stage- result in a high cure rate with excellent prognosis
? Prognosis for locally advanced SCC at the time of diagnosis & patients
with progressive disease after first-line surgical therapy - usually poor
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? A poorer outcome of immunosuppressed patients with advanced
disease
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Melanoma? Melanoma (Gr. melas [dark], oma [tumor]) - malignant tumor arising
from melanocytic cells
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? Can occur anywhere where melanocytes are found
? The most frequent type - cutaneous melanoma
? Also at the mucosal, the uveal, or even the meningeal membrane
? 10% melanomas ? detected by lymph node metastases [with so-
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called "unknown primary"]
Epidemiology
? Rising incidence worldwide - Countries with white inhabitants, with
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highest incidence rates in Australia (35 new cases/year/100,000)
? North America (21.8 new cases/100,000)
? Europe (13.5 new cases/100,000)
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? Median age - for melanoma diagnosis is 63 years with 15% being <45years
? Melanoma ? Accounts for only 4% of all skin cancer diagnoses in the
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USA
? Responsible for 75% of skin cancer deaths
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Risk factors? History of sunburns and/or heavy sun exposure
? Fitzpatrick skin phototypes I & II
? Blue or green eyes, blonde or red hair, fair complexion
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? >100 typical nevi, or any atypical nevi? Prior personal or family history of melanoma
? p16 mutation
Clinical Features
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? Subtypes?Superficial spreading melanoma
?Nodular melanoma
?Lentigo maligna
?Lentigo maligna melanoma
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?Acral lentiliginous melanoma?Desmoplastic melanoma
?Mucosal melanoma
Superficial spreading melanoma
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? Most common subtype, accounting for approximately 70%
? Most common on intermittently sunexposed areas
? The lower extremity of women; the upper back of men
? Irregular borders and irregular pigmentation
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? May present subtly as a discrete focal area of darkening? Varying shades of brown typify most melanocytic lesions
? Also aspects of dark brown to black, blue-gray, red, and gray-white
(which may represent regression) may be found
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Nodular melanoma
? Approximately 15%-30% of all melanomas
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? The trunk - the most common site? Remarkable for rapid evolution - often arising over several weeks to
months
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? May lack an apparent radial growth phase? Typically appears as a uniformly dark blue-black or bluish-red raised
lesion
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? 5% are amelanoticLentigo maligna & Lentigo maligna melanoma
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? Lentigo maligna - melanoma in situ with a prolonged radial growthphase
? Eventually becomes invasive Lentigo maligna melanoma
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? Diagnosed most commonly in the seventh to eighth decades(uncommon before the age 40)
? Most common location - the chronically sun-exposed face, on the
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cheeks and nose in particular
? Clinical appearance - flat, slowly enlarging, brown, freckle-like macule
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with irregular shape & differing shades of brown and tanComplications
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? Usual y based on metastatic disease - symptoms associated with theaffected organ
? Pain (any metastases)
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? Convulsion (brain metastases)
? Instabilities, # - (bone metastases)
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? Later - symptoms associated with progression of the disease & death in thepal iative setting
? Cutaneous changes - localized or diffuse hypo- or hyperpigmentation
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? Development of a melanoma-associated vitiligo [an accompanying
autoimmune disease against melanocytes] - in 4%; associated with a better
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prognosisDiagnosis
? Early detection - the key to improve prognosis
? Melanoma - Change in color and increase in size (or a new lesion) are
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the 2 most common early characteristics noticed by patients that may
be useful in discriminating between melanoma and other benign
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lesions? Physical examination
? Dermascopy
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? Pathology- Excisional skin biopsy? Large lesion and/or located on anatomic areas such as the palm/sole,
digit, face, or ear, an incisional skin biopsy may be performed
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? Lymph node examination f/b USG/excisional biopsy? Tomographic investigations like computed tomography (CT), magnetic
resonance imaging (MRI) & positron emission tomography (PET) -
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generally not recommended at the stage of primary melanoma - rateof false positive findings is far too high (8%-15%), e.g. unspecific lung
lesions
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Management? The standard of therapy - wide local excision (WLE)
? The purpose - to prevent local recurrence due to subclinical persistent
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disease? The risk of satel ite metastases - related to primary melanoma thickness
? Current recommendations on the clinical margins - depending on the
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Breslow thickness of the primary?For melanoma in situ - a 0.5-1-cm margin
?For melanoma <1?mm Breslow depth ?a 1-cm margin
?For melanoma 1 to 2?mm thick - a 1- to 2-cm margin
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?For melanoma >2?mm thick - a 2-cm margin is recommended? Wider excisions with up to 5-cm margins - not show a benefit for local
recurrence rate
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? Standard of therapy for macroscopic (stage II B/I IC) lymph nodes ?
CLND of the involved regional basin
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? Uncontrolled nodal disease - Major cause of melanoma-relatedmorbidity with a significant high negative impact on QoL
? CLND for regional metastatic melanoma - associated with long-term
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survival
Adjuvant therapy
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? Adjuvant therapy - for patients with surgically resected disease who
are at high risk for relapse such as those with thick primary
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melanomas or nodal disease? Interferon-alpha
? Anti-CTLA-4 antibody (ipilimumab) ? an immune checkpoint blocker
? Adjuvant radiotherapy after CLND
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