Melanoma and skin cancer

From Oncology for Medical Students
Clinical oncology for students > Melanoma and skin cancer

Export options


Epidemiology

Incidence

Australia and New Zealand skin cancer and melanoma rates are the highest in the world. Non-melanoma skin cancer (NMSC) is the commonest type, with 1 in 2 Australians diagnosed with a BCC or SCC. Melanoma in Australia was diagnosed in some 12,510 (7,440 males and 5,070 females) in 2012, based on state cancer registry data; with some 200,000 cases occurring worldwide. In Australia, the lifetime risk of cutaneous melanoma by the age of 85 was 1 in 14 for males and 1 in 23 for females.

Australia and New Zealand have the highest melanoma incidence rates in the world at about 62.7 per 100,000 population for males and 39.9 per 100,000 for females. The rates decrease in approximate proportion to skin colour, with rates of about 3 per 100,000 for very dark skinned Indigenous people.


Mortality

In 2012, an estimated 1,560 people (1,070 males and 495 females) died from melanoma. In 2010, the lifetime risk of death from melanoma by 85 years of age was 1 in 85 for males and 1 in 226 in females. Melanoma represents the sixth most common cause of death in men and tenth most common in females. The rate of death from SCC was not recorded accurately enough in most centres worldwide to determine figures. Mortality from BCC is very rare.


Prevalence and survival

In Australia, the prevalence of NMSC is not accurately known, but is extremely high. In 2007, there were 136,016 people alive following diagnosis of melanoma of the skin over the prior 26 years (70,654 males and 65,362 females). For the 2006-2010 period, the probability of survival for 5 years was 89% for males and 94% for females. In 2010-2011, melanoma accounted for 1.2% of all cancer-related hospitalisations, or 10,457 hospitalisations.

Back to top

Risk factors

Personal history

The previous diagnosis of melanoma in a person increases the risk of subsequent primary melanoma in that individual by about tenfold.

Family history

The history of a first-degree relative diagnosed with melanoma increases the risk of melanoma by in that individual by about two-fold.

Skin type, eye colour, hair colour

The less the melanin pigmentation in the skin, eye iris and hair, the greater the risk of melanoma and other skin cancers that individual has. Lighter vs darker for all features approximately doubles the risk.

Environmental exposure

The association between UV intensity and duration of exposure, especially associated with sunburn, has been well documented. Higher exposure has relative risk of 1.5 times that of lower exposure.

Genetics

The precise role of genetics in determining melanoma risk is currently unclear and made complex by the many factors that determine skin melanin levels, hereditary traits and cellular repair mechanisms.

Back to top

Cancer biology: Molecular and genetic basis

The molecular genetics of melanoma is gradually being elucidated, but apart from some pathways concerned with B-raf, Mek and C-kit, relatively little is clearly understood.

Back to top

Clinical presentation

Typical skin cancer presentations are: BCC: Pink, nodular, raised lesion with 'pearly' edges; or flat pink lesion.

SCC: Whitish-pink, scaly, crusted, raised lesion; or pink flat lesion.

Melanoma: Has many clinical forms being termed the 'chamelion' of cancers. The primary melanoma may be flat or raised, visible, itch or bleed, but occasionally the effects of metastatic spread may be the first apparent sign.

Primary melanoma is typically a pigmented, variegated skin lesion with recent change(s) in size, shape or colour. Morphological types include: Superficial spreading, nodular, acral lentiginous, lentigo maligna. Amelanotic melanoma is not uncommon and is often nodular, sometimes being confused with a basal cell carcinoma or squamous cell carcinoma. Melanoma may involve the keratinised skin of the sun-exposed, as well as occasionally the non-exposed regions of the body, including the mouth, nasal cavities, ear canal, vagina, and anal canal. Very rarely, the oesophagus, stomach, small bowel or other organs can be involved with a primary melanoma, however, most melanomas in these locations are metastases.

Secondary melanoma is metastatic usually from a cutaneous site, and can occur to any site, with skin/subcutaneous, lung, liver, bone, brain, gut, adrenal gland and nerve being most common in approximately that order. Most metastases are asymptomatic. Skin lumps are perhaps the commonest sign, than tiredness, fatigue, weight loss, cough, jaundice, fracture, neurological disturbance, bowel obstruction or gastrointestinal bleeding.

Back to top

Diagnosis and staging

Diagnosis is usually by pathology using excision biopsy for primary lesions and fine /core needle biopsy for secondaries. Occasionally, punch or shave biopsies may be required, but these may complicate pathological diagnosis and/or treatment, and are less preferred, especially for melanoma. Lactate dehydrogenase (LDH) may be a useful bio-marker in melanoma for metastatic disease, later recurrence, or risk of this. CT scanning (head/ chest/ abdomen; with neck/ pelvis depending on the melanoma site) may be useful to detect potentially operable/ treatable metastases for patients with higher risk melanomas (Breslow > 2.5mm; ulcerated; high mitotic rate; elevated serum LDH). The scanning results may alter surgery type. Head MRI scanning may be more useful to detect small brain metastases, or to clarify metastases, especially in the neck. CT and MRI scanning may be useful for SCC, and rarely for advanced BCC.


Staging (see TNM or AJCC for details): The Tumour; Node; Metastasis (TNM) classification, or American Joint Committee on Cancer (AJCC) is usually used for staging of skin cancers into Stage I and II (localised); Stage III (regional spread); and Stage IV (distant spread).

BCC: staging is usually not performed as most are confined to skin. Larger lesions are staged T1 <2cm diameter; T2 >2cm diameter; T3 invasion of bone or nerve; T4 skull invasion.

SCC: Tis - insitu SCC; T1 <2cm diameter; T2 >2cm diameter; T3 invasion of bone or nerve; T4 skull invasion. N0: No lymph nodes spread; N1: Spread to 1 draining lymph node ≤ 3 centimeters (cm) diameter; N2: Spread to 1 ipsilateral draining lymph node [a = 1 LN 3-6cm size; b = >1 LN <6cm; c = contralateral lymph node(s)] N3: any LN ≥ 6 cm across. M0: No spread; M1: Spread to distant organs.

Melanoma: Tis: Melanoma in situ; T1: < 1.0 mm thick; T2: 1.01 and 2.0 mm; T3: 2.01 and 4.0 mm; T4a: > 4.0 mm. [a is added if absent; b if ulceration and/or the mitotic rate ≥ 1/mm2 is present.] N0: No lymph nodes spread; N1: Spread to 1 draining lymph node; N2: Spread to 2-3 nodes, OR local intransit; N3: Spread to ≥ 4 nodes, OR spread to lymph nodes that are clumped together, OR spread of melanoma to nearby skin or toward a lymph node area and into the lymph node(s). [a is added if microscopic; b if visible; c for satellite/ intransit.] M0: No distant metastasis; M1a: Skin/subcutaneous tissue, or non-draining lymph nodes; normal blood LDH level; M1b: Metastasis to the lungs; normal blood LDH level; M1c: Metastasis to other organs, OR an elevated blood LDH level. Stage I (localised); Stage II (deeper localised); Stage III (regional spread); Stage IV (distant spread).

Back to top

Prognosis

Prognosis for skin cancer is based on the characteristics of the primary tumour, and the AJCC and TNM Staging system. BCC grows locally and usually has a good prognosis. Further new BCC/SCC are common. Recurrence rates from BCC and SCC excised with adequate clear margins are low.

SCC: Approximate 10-year survival rates are Stage I & II 60-80%; Stage III 20%; Stage IV 10%.

Melanoma: Approximate 10-year survival rates: Stage I 90-95% Stage II 40-70%; Stage III 25-70%; Stage IV <10%. Cure rates are high for Stage I, and decrease for Stage II, II and IV respectively (see AJCC JCO, 2009 for further details).

Back to top

Principles of management

Surgery: Most skin cancer is effectively treated by surgery alone, especially for early stage primary lesions. This is both diagnostic and curative. Even a considerable proportion surgery of metastatic spread: locally, intra-lymphatic (intransit), and to regional lymph node basins, is effectively treated by surgery, and provides diagnosis, useful local disease control, and can be curative. Adjuvant treatments remain incomplete, and the effectiveness of these remains situational. Surgical treatment of metastases remains a challenge, however, good palliation and even long-term survivals can be produced by selective surgery for metastases. It remains unpredictable exactly which patients will gain the benefit after resection.

Medical: The mainstay of medical management has been dacarbazine and fotemustine chemotherapy with low rates of response and very low cure rates. Recent evaluation of small molecule inhibitors against MEK and mutant BRAF, and CTLA and PD1 inhibitory monoclonal antibodies have improved response rates and survival, but long term cure rates remain to be proven. These are promising developments. It remains unpredictable exactly which patients will gain the benefit after medical therapy.

Radiation: The role of adjuvant radiotherapy has been defined better for treatment of melanoma and SCC, with >3 positive nodes or extra-capsular spread being two key indicators for radiation. Radiation is useful for symptom control, especially for bone metastases.

Palliative care: Good pain control, social/community supports, and planning are essential for managing patients and their families at home and through often-difficult treatments, hospital visits and end of life matters/decisions.

GP, nursing and allied health: Often the role of the many important individuals including community nurses, GP, rehabilitation staff, orthotist, physiotherapist, psychologist, pharmacist and occupational therapist, are vital for adequate recovery, comfort and quality of life.

Back to top

Follow-up and survivorship

Effective follow-up is an uncertain area with little guiding evidence. After skin cancer excision the principal risks are development of another primary lesion and recurrence. No regimen template appears completely encompassing to reduce these risks. Many recurrent or new lesions are detected by the patient between follow-up visits. After excision of in-situ skin lesions, 6-12 monthly follow-up is probably adequate; after invasive lesions, 4-monthly for 2 years; 6-monthly for 2 years and then yearly thereafter is usually appropriate. For higher risk individuals more intensive follow-up is recommended.

Back to top

Screening and prevention

Screening for skin cancer has been problematic as many people need to be screened to detect small numbers of cancers, even despite the relatively high incidence. Although the rate of skin cancer is 1 in 2 Australians we have difficulty with accurate prediction of exactly who will develop the cancer. The best 'yield' for detection of skin cancers come from those groups of people who are at highest risk. These include those with a previous skin cancer, a strong family history of skin cancer (especially melanoma), those with high sun exposure, numerous sunburns, fairer skin and features, albinism, renal dialysis/transplant patients or those living in certain geographical locations. Even in these groups, many people do not develop skin cancers, while some develop many.

Prevention is of two main types: primary and secondary.

Primary prevention is best applied early in life, to restrict the damaging effects of the sun and UV-light from causing skin cancer. Avoidance of the sun at UV levels above 3, and protection using shade or clothing are the most effective measures. Sunscreen reduces the burn-rate, but is of limited value.

Secondary prevention is for patients who have had a skin cancer removed previously, who are at greater risk of another second primary cancer in the future, and may develop an occult skin cancer.

Back to top

References

  1. Australian Institute of Health and Welfare. Cancer in Australia: An overview 2012. Canberra: AIHW; 2012 [cited 2014 May 29]. Report No.: Cancer series no. 74. Cat. no. CAN 70. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129542353
  2. Australian Cancer Network Melanoma Guidelines Revision Working Party. Clinical practice guidelines for the management and treatment of melanoma in Australia and New Zealand: Evidence based best practice guidelines. Wellington: Cancer Council Australia, Australian Cancer Network and Ministry of Health, New Zealand; 2008 [cited 2014 May 29] Available from: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cp111.pdf

Back to top