Malignant melanoma

Skin cancer ---> Melanoma skin cancer

Melanoma arises from malignant proliferation of melanocytes.
Epidemiology
The incidence of and mortality from melanoma are increasing. Its incidence is approximately 10 per 100 000 per year. The highest incidence occurs in white-skinned individuals in Australia and New Zealand. Melanoma is more common in women than in men.
Pathology
Ultraviolet exposure is a major etiological factor, particularly short, intense exposure resulting in sunburn during childhood. Phenotypic factors associated with melanoma include fair skin, red or blonde hair, blue eyes, inability to tan, freckles, lentigines, large numbers of benign melanocytic nevi and the presence of dysplastic nevi.
Important risk factors for malignant melanoma
Presence of precursor lesions (dysplastic melanocytic nevi)
Family history of melanoma in parents or siblings
Skin phototypes I and II with an inability to tan
Excess sun exposure, especially during childhood
Clinical features
Malignant melanoma has two patterns of growth, radial and vertical. Radial growth is horizontal within the epidermis and superficial dermal layers, as in the lentigo maligna, acral/mucosal lentiginous and superficial spreading types. During this stage of growth the tumor does not have the capacity to metastasize. Vertical growth occurs with time, and the melanoma grows downwards into the deeper dermal layers as an expansile mass, lacking cellular maturation. This correlates with the emergence of a clone of cells with metastatic potential. The nature and extent of this vertical growth phase determine the biological behavior of malignant melanoma. The different types of malignant melanoma are categorized on morphology and histological findings.
Superficial spreading
Superficial spreading is the most common variant of melanoma (70%), presenting as a macule or papule, usually greater than 0.5 cm in diameter. There is variable pigmentation (from pale brown to blue-black), an irregular edge, and surface oozing or crusting. In males it most frequently presents on the back, while in females the leg is the most common site. In the radial growth phase it is characterized by atypical melanocytes, singly and in clusters, widely scattered throughout the layers of the epidermis. Left untreated it may progress to the vertical growth phase over months to years.
Nodular melanoma
Nodular melanoma is the second most common variant (14%) and, by definition, presents in the vertical growth phase. It classically presents as a rapidly enlarging, frequently ulcerated, blue-black nodule.
Lentigo maligna
Lentigo maligna presents as an irregularly pigmented macule, slowly enlarging over many years, commonly on the cheek or temple of an elderly person. It is characterized by basally located atypical melanocytes. Development of a more rapidly growing, deeply pigmented papule or nodule indicates dermal invasion by malignant melanocytes (lentigo maligna melanoma).
Acral lentiginous melanoma
Acral lentiginous melanoma is an uncommon subtype, although it is the predominant variant in the Afro-Caribbean population. The sole of the foot is most often affected and lesions may also arise on the digits. Subungual or periungual melanoma, a variant of acral lentiginous melanoma, occurs either as a linear pigmented streak in the nail or an isolated nail dystrophy, accompanied by the pigmentation of the proximal nail fold (Hutchinson's sign).
Amelanotic melanoma
Amelanotic melanoma is a non-pigmented variant of melanoma.
Malignant melanoma on mucous membranes
Malignant melanoma on mucous membranes is very rare and may affect the vulva, urethra and anus. It has a poor prognosis, due in part to its often advanced stage at presentation.
Investigations
Skin biopsy
An excision skin biopsy must be performed to confirm the diagnosis. This will give important histological data and provide valuable staging information.
Management
The management of malignant melanoma varies according to the stage at presentation, and ranges from surgical excision to radiotherapy and chemotherapy.
Prognosis
Melanoma has a mortality rate of 25% and therefore early diagnosis and treatment is essential. Prognostic factors include thickness, level of invasion, gender and site of tumor.
Histological data from melanoma
Clarke's level
I melanoma cells confined to epidermis
II melanoma cells invade papillary dermis
III melanoma cells completely occupy papillary dermis
IV melanoma cells invade mid-reticular dermis
V melanoma cells invade subcutaneous fat

Tumor thickness in mm from granular layer of the epidermis to maximum depth (Breslow thickness)
Presence of radial or vertical growth
Tumor infiltrating lymphocytes
Mitoses per mm2
Presence or absence of tumor regression (mitosis, inflammatory infiltrate, pigmentary incontinence, fibrosis and dermal scarring, and vascular proliferation)
Microsatellites
Evidence of perineural infiltrate
Evidence of vascular and lymphatic invasion
Whether excision is complete

TNM staging system for melanoma
Stage (T) Primary tumor Lymph node (N) Distant metastases (M)
0 In situ tumors No nodes No Distant metastases (M)
IA -1mm, IIB 2.01-4 mm with ulceration No nodes No Distant metastases (M)
>4 mm, no ulceration No nodes No Distant metastases (M)
IIC >4 mm with ulceration No nodes No Distant metastases (M)
IIIA Any Breslow thickness, no ulceration Micrometastases in nodes No Distant metastases (M)
IIIB Any Breslow thickness with ulceration Micrometastases in nodes No Distant metastases (M)
Any Breslow thickness, no ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration No nodes but in-transit metastases or satellites None
IIIC Any Breslow thickness with ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration 4 or more palpable nodes or matted nodes or in-transit metastases with nodes No Distant metastases (M)
IV M1: skin, subcutaneous or distant lymph nodes
M2: lung
M3: all other sites or any site with raised lactate dehydrogenase

Squamous cell carcinoma : SCC

Skin cancer ---> Non melanoma skin cancer ---> squamous cell carcinoma

Squamous cell carcinoma is a malignant invasive proliferation of epidermal keratinocytes.
Epidemiology
Squamous cell carcinoma is the second most common type of skin cancer. It is more common in men and in the elderly population.
Pathology
There is a relationship with chronic ultraviolet exposure. Squamous cell carcinoma is especially common in individuals with skin phototypes I and II. Other etiological factors include topical and systemic carcinogens such as arsenic, photochemotherapy (PUVA) and chronic immunosuppression (following allogeneic organ transplantation or in those with lymphoma or leukemia). The lesions may also arise at sites of long-standing radiation dermatitis, scarring (discoid lupus erythematosus), ulceration and pre-existing lesions such as Bowen's disease. Some squamous cell carcinomas are associated with human papillomavirus infection. Smoking is associated with lesions on the lip.
Scope of disease
Squamous cell carcinoma is locally invasive and has the potential to metastasize to lymph nodes and other organs of the body.
Clinical features
Squamous cell carcinoma usually presents as an expanding plaque or nodule with an ill-defined, indurated base and surface crusting. The lesion may ulcerate. It is most often seen on sun-exposed sites (face, neck, forearms and dorsum of hands) in association with solar elastosis and multiple actinic keratoses. Local lymph nodes may be enlarged with metastatic involvement.
Investigations
Skin biopsy
A skin biopsy is required to establish a histopathological diagnosis and to gain information on the degree of differentiation, grade, depth and level of dermal invasion, the presence of perineural, vascular or lymphatic invasion, and clearance margins of the excised tissue.
Lymph node biopsies
Squamous cell carcinomas usually spread to local lymph nodes; therefore clinically enlarged nodes should be excised and submitted for histopathological analysis.
Initial management
Patient education
Sun avoidance, the use of sunscreen and protective clothing are the main steps in the prevention of actinic keratosis and further squamous cell carcinomas, particularly in patients receiving immunosuppression.
Multidisciplinary team approach
There is overlap between dermatologists, clinical oncologists and plastic surgeons in the management of patients with squamous cell carcinoma, and therefore a multidisciplinary approach is favored.
Surgical management
Curettage and cautery
Curettage and cautery may be feasible treatment options for small, well-defined, low-risk tumors.
Excision biopsy and regional node dissection
Surgical excision or Mohs' micrographic surgery is the treatment of choice for the majority of lesions. For low-risk tumors (less than 2 cm in diameter), excision with a 4 mm margin is expected to achieve complete cure in 95%.
Mohs' micrographic surgery is indicated for larger, higher-risk tumors. With this technique, each section is examined with frozen section analysis to determine the completeness of resection. It is particularly useful in difficult sites where wide surgical margins may be technically difficult to achieve without functional impairment.
Tumor-positive lymph nodes are usually managed by regional node dissection.
Medical management
Radiotherapy
Other treatment options include radiotherapy for non-resectable tumors or lymph node disease.
Prognosis
Squamous cell carcinoma has an overall remission rate after therapy of 90%. The factors that influence metastatic potential include anatomical site, tumor size, degree of differentiation and immunosuppression. Tumors arising in areas of radiation injury, chronic inflammation or chronic ulcers have the highest metastatic potential when compared to those from sun-exposed sites. Tumors more than 2 cm in diameter are 3 times as likely to metastasize compared to smaller tumors. Tumors more than 4 mm in depth or extending down to the subcutaneous tissue are more likely to recur and metastasize compared to thinner tumors. Poorer prognosis is associated with less well differentiated tumors, and tumors arising in patients who are immunosuppressed.

Basal cell carcinoma : BCC

Skin cancer ---> Non melanoma skin cancer ---> Basal cell carcinoma

Basal cell carcinoma (rodent ulcer) is a slow-growing, locally invasive tumor with virtually no capacity to metastasize.
Epidemiology
Basal cell carcinoma is the most common type of skin cancer, approximately 4 times more common than squamous cell carcinoma.
Pathology
The most significant etiological factor is chronic excess ultraviolet radiation exposure. As a result, exposed areas such as the head and neck are most commonly involved. Other risk factors include increasing age, male gender, and skin phototypes I and II. Histologically there is a proliferation of atypical basal keratinocytes.
Clinical features
The clinical appearances and morphology are diverse and include nodular, morphoeic, superficial multifocal, keratotic and pigmented varieties.
The nodular basal cell carcinoma tends to arise on the forehead, nose or adjacent to the inner canthus of the eye as a skin-colored or pigmented, translucent nodule with surface telangiectasia. Gradual enlargement leads to central ulceration (ulcerated basal cell carcinoma) with a peripheral, 'rolled' pearly edge. There may also be cystic change (cystic or nodulocystic basal cell carcinoma). The morphoeic (sclerosing) basal cell carcinoma presents as a firm, indurated, skin-colored, scar-like plaque with ill-defined edges, commonly on the nasolabial fold or forehead. Superficial multifocal basal cell carcinomas tend to arise on extra-facial sites as red, scaly plaques and have no relation to sun exposure. Pigmented basal cell carcinomas may be brown, blue or black with a smooth glistening surface. Keratotic basal cell carcinomas have evidence of keratinization on histology.
Initial investigations
Skin biopsy
A skin biopsy confirms the diagnosis and determines the histological subtype. Alternatively, cytology can be performed on skin scrapings.
Initial management
Multidisciplinary team approach
Depending on the size and site of the basal cell carcinoma, dermatologists, clinical oncologists and plastic surgeons may all be involved in the management. Therefore, a multidisciplinary approach is favored.
Surgical management
Curettage and cautery
Curettage and cautery is a suitable option for patients with low-risk lesions (small, well-defined, primary lesion) and can achieve 5-year cure rates of up to 97%. Patients with recurrent morphoeic tumors in high-risk sites such as the nose, nasolabial folds and around the eyes should undergo formal surgical excision.
Cryotherapy
Cryotherapy can be used on low-risk lesions with non-aggressive histology that are not recurrent lesions.
Surgical excision
The main aim of surgery is complete excision with a clear surgical margin.
Medical management
Radiotherapy
Radiotherapy is useful for treatment of basal cell carcinoma in locations where disfigurement results from surgical excision (although atrophy telangiectasia may develop in the long term and affect the cosmetic results). The 5-year cure is approximately 90%. Patients with recurrent lesions after radiotherapy should undergo surgical excision.
Topical 5-fluorouracil
Topical 5-fluorouracil is usually the treatment of choice for multiple superficial basal cell carcinomas on the trunk and lower limbs.
Palliative management options
Aggressive treatment can be inappropriate in elderly debilitated patients, especially for asymptomatic low-risk lesions. Palliative treatment such as debulking the tumor or radiotherapy may be more appropriate.
RECENT ADVANCES
Intralesional interferon and photodynamic therapy are still under investigation with some early promising results.
Prognosis
Metastasis is extremely rare and the morbidity is related to local tissue invasion and destruction. Patients with a single tumor are at a significant increased risk of developing subsequent basal cell carcinomas.