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Click hereA 23yo Siberian female patient presented with a changing lesion on her abdomen. The patient stated the lesion was present for about two years and it started off from within a freckle, which started to grow larger and somewhat darken in appearance. It had the clinical appearance of a melanoma and the dermoscopy 3-point checklist (designed to allow non-experts not to miss detection of melanomas) was used to determine whether this had a high likelihood of malignancy. It included
Asymmetry: asymmetry of colour and structure in one or two perpendicular axes
Macroscopy: Skin, left inframammary: Skin ellipse, 15 x 9 x 3mm with irregular pigmented lesion, 5 x 7mm, 1cm from nearest margin. Microscopy: Skin, left infra-mammary, skin ellipse: Malignant melanoma, superficial spreading subtype – Clark level III. Breslow thickness: 1mm. No ulceration identified No regression identified. Lymphovascular invasion is not identified. Perineural invasion is not identified. Mitotic rate is 2 per 10. Microsatellite lesions are not identified. Melanoma arises in the naevus. Margins: – Closest margin (radial): 1cm. Deep margin: 4mm Prof K Sheahan
The pathologist’s report above includes a macroscopic description (the naked eye view), of the specimen and a microscopic description. The following features suggest an invasive melanoma.
The report includes comments about cell type and its growth pattern, invasion of blood vessels or nerves, inflammatory response, regression and whether there is associated in-situ disease
Breslow thickness is reported for invasive melanomas. It is measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement. It is a strong
Breslow thickness is reported for invasive melanomas. It is measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement. It is a strong predictor of outcome; the thicker the melanoma, the more likely it is to metastasize
The deeper the Clark level, the greater the risk of metastasis. It is useful in predicting outcome in thin tumours, and less useful for thicker ones
Melanomas are described according to their appearance and behaviour. Those that start off as flat patches (i.e. have a horizontal growth phase) include:
These superficial forms of melanoma tend to grow slowly, but at any time, they may begin to thicken up or develop a nodule (i.e. progress to a vertical growth phase).
Melanomas that quickly invade deeper tissues include:
Histologic factors that affect metastatic potential include ulceration of the tumour, mitotic rate, presence of lymphovascular invasion, microsatellites, regression, perineural invasion, and the presence of lymphocytes infiltrating the tumour.
The main risk factors for developing superficial spreading melanoma include:
Affluence, Increasing age, female
Fair skin that burns easily. Red or light coloured hair,
Light coloured eyes and light coloured skin (Anglo-Celtic) (Gandini S et al 2005).
Checking for a melanoma
Glasgow 7-point checklist
Major features
Minor features
The primary mode of treatment for localized cutaneous melanoma is surgery. Surgical margins of 5 mm are currently recommended for melanoma in situ, and margins of 1 cm are recommended for melanomas ≤1 mm in depth (1). For tumors of intermediate thickness (1–4 mm Breslow depth), randomized prospective studies show that 2-cm margins are appropriate, although 1-cm margins have been proven effective for tumors of 1- to 2-mm thickness (2) (3). Margins of 2 cm are recommended for cutaneous melanomas greater than 4 mm in thickness (high-risk primaries) to prevent potential local recurrence in or around the scar site. Numerous adjuvant therapies have been investigated for the treatment of localized cutaneous melanoma following complete surgical removal. Adjuvant interferon (IFN) alfa-2b is the only adjuvant therapy approved by the US Food and Drug Administration for high-risk melanoma (4). While early-stage melanomas can often be cured with surgery, more advanced melanomas can be much harder to treat. But in recent years, newer types of immunotherapy and targeted therapies have shown a great deal of promise and have changed the treatment of this disease.
Drugs that block CTLA-4: Ipilimumab targets CTLA-4, a protein that normally suppresses the T-cell immune response, which helps melanoma cells survive. Ipilimumab has been shown to help people with advanced melanomas live longer. Combining ipilimumab with GM-CSF is better than using ipilimumab alone. The combination has fewer serious side effects.
Drugs that block PD-1 or PD-L1: Melanoma cells also use pathways in the body to avoid being detected, and a protein called PD-L1 on their surface helps them evade the immune system. Two drugs that block PD-1, pembrolizumab (Keytruda) and nivolumab (Opdivo), are now approved to treat advanced melanoma.
Melanoma vaccines: These are experimental therapies that have not yet been proven to be helpful.
Skin cancer is the most common malignancy in the United Kingdom and Ireland (5). Malignant melanoma is the most deadly cutaneous neoplasm. Numerous risk factors for development of melanoma have been identified, including white skin, fair hair, light eyes, sun sensitivity and a tendency to freckle. Other factors, include family history of melanoma, dysplastic nevi, increased numbers of typical nevi, large congenital nevi and immunosuppression. Although sun exposure is a risk factor for melanoma, cutaneous melanomas can also arise in areas of the body not exposed to the sun. Sun exposure in childhood and having more than one blistering sunburn in childhood are associated with an increased risk of melanoma (6). Most melanomas arise as superficial tumors confined to the epidermis. The prognosis for melanoma is closely related to the thickness of the tumour. In order to effectively treat melanomas, drugs that target proteins that normally suppresses the T-cell immune response or block ones that help them evade the immune system provide the best chance for treating patients with advanced melanoma. In early studies, combination drugs have shrunk tumors in about one half of pateints with melanoma.
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