9th July 2023

Tumours and Pigmentation

Non-Melanoma Skin Cancer (NMSC)

Basal Cell Carcinoma (BCC)

The most common form of skin cancer which generally has a good prognosis due to its slow local invasion and infrequent metastasis. Risk factors include prolonged and cumulative UV exposure on sun-exposed sites, fair skin, and previous solar damage such as AKs. Biopsy confirms the histological subtype and informs management. Nodular BCC is the most common. Most BCCs are treated surgically, such as by excision, Mohs micrographic surgery (lesions that are high risk, recurrent or if sited on areas of cosmetic concern), curettage and cautery, and cryotherapy. Non-surgical treatments include topical creams such as 5-FU (cytotoxic agent) and Imiquimod (immunomodulating agent), PDT and radiotherapy.

Table 1: Three different types of BCCs with associated descriptions and treatment options.

Nodular BCC with overlying telangiectasia sited on the nasolabial fold.

Image Source: Wikimedia Commons (2017). Basal-cell Carcinoma, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Basal-cell_Carcinoma.jpg (Accessed on: 3 November 2021).

Squamous Cell Carcinoma (SCC)

SCC risk factors are similar to BCCs, but also include a background of Bowen’s disease (SCC in-situ), chronic ulcers (leading to a Marjolin ulcer), smoking, HPV infections and immunosuppression. Presentation is often of a rough or scaly papule/plaque that may bleed and later ulcerate. SCCs are more aggressive than BCCs, with a greater potential to metastasise, requiring a 2WW referral. Lesion size informs the full-thickness biopsy margin:

• Low-risk lesion: ≤20mm: ≥4mm margins
• High-risk lesion: >20mm: ≥6mm margins

Biopsy confirms diagnosis, assesses histological margins and level of differentiation. This informs management and prognosis. Invasive SCCs penetrate beyond the basement membrane, for which further body imaging should be considered, e.g. CT, MRI.

Table 2: SCC types with potential treatment options

Bowen’s disease on the finger. 

Image Source: Wikimedia Commons (2009). Bowen11, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Bowen11.jpg (Accessed on: 3 November 2021).

Melanoma Skin Cancer (MSC)

Risk factors

Melanoma is the most aggressive form of skin cancer arising from uncontrolled proliferation of melanocytes, which reside in the epidermis. Environmental and genetic risk factors (such as xeroderma pigmentosum) are important. Like Non-Melanoma Skin Cancer (NMSC), these include UV damage, fair features, and immunosuppression. Personal history of any skin cancer, family history, >50 naevi or >5 atypical naevi (≥6mm) should also be considered.

Types

Clinical presentation depends on the type of melanoma (see table 3). Rarer forms include amelanotic, mucosal and ocular.

Table 3: Table outlining the more typical forms of melanoma with associated details

Extensive acral lentiginous melanoma of the left sole of the foot.

Image Source: Wikimedia Commons (2020). Photography of a large acral lentiginous melanoma, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Photography_of_a_large_acral_lentiginous_melanoma.jpg (Accessed on: 2 November 2021).

Investigation/Treatment

The ABCDE approach can be useful for detection. Other signs include itching, bleeding, and tenderness. A full-thickness excisional biopsy is diagnostic and prognostic. Breslow’s thickness (invasion depth) is an important prognostic marker and informs the margins of further surgery (Wide local Excision [WLE]). A WLE assists with staging and can be therapeutic. Sentinel lymph node biopsy (SLNB) can detect melanoma spread to nearby lymph nodes, which may indicate further dissection and imaging with CT, MRI, or PET scans. Adjuvant treatments include immunotherapy and targeted therapies.

Other Neoplasms

Mycosis Fungoides

The most common type of primary cutaneous T-cell lymphoma (CTCL) in which clonal T lymphocytes accumulate in the skin. Presentation is variable with different sized heterogeneous erythematous patches and plaques. Diagnosis is challenging and requires blood tests, biopsies, and specialist input. It is not curable, and relapses are common after treatment.

Sezary Syndrome

A rare leukaemic variant of CTCL in which atypical T cells (Sezary cells) accumulate in the skin, blood, and lymph nodes. It presents as pruritic erythroderma (≥90% body surface affected) and lymphadenopathy.

Systemic Mastocytosis

Clonal neoplastic mast cells proliferate and accumulate in bodily tissues such as the skin, bone marrow, lymph nodes and other organs. Mast cell activation releases histamine and triggers an inflammatory response. Cutaneous involvement can present with itch, swelling and erythema. Systemic involvement can present in various ways, such as hypotension, flushing and abdominal pain. Serum tryptase levels may be raised and a tissue biopsy confirms the diagnosis.

Benign Lesions

Actinic keratosis (AK)

Premalignant lesions arising from chronic UV radiation. Often seen in older patients, fair skin, and sun-exposed sites. Present as multiple small flesh-coloured/yellow scaly macules/plaques with irregular borders. Often a clinical diagnosis. Risk of developing into SCCs and, therefore, should be treated. Topical creams (Imiquimod, 5-FU, Diclofenac) are often used. Surgical options include cryotherapy and curettage.

Leukoplakia

Leukoplakia refers to white-grey patches or plaques on the oral mucosa which are not characterised as any specific disease. Once a cause is established, this can be due to a variety of conditions, including candidiasis, lichen planus, and SCC. It is strongly associated with smoking and alcohol intake. Biopsy is often required to exclude SCC in-situ which can progress to invasive SCC if not treated. Therefore, depending on the cause, leukoplakia can be considered premalignant.

Dermatofibroma

Dermal fibroblast proliferation gives rise to a fibrous red/brown papule or nodule, known as cutaneous fibrous histiocytoma. May arise at sites of previous injury and often seen on the lower leg. Characteristically, the lesion dimples when squeezed, the dimple sign. Often a clinical diagnosis which requires no treatment. Recurrence is common if excised.

Keratoacanthoma 

Squamoproliferative lesions arising from the pilosebaceous unit on sun-exposed areas. Initially a papule, it rapidly becomes a nodule, often with a keratin core. Unclear aetiology, yet risk factors include UV, smoking, older age, and immunosuppression. Lesions regress over time. However, they are clinically challenging to distinguish from SCCs and, therefore, must be surgically excised for histological confirmation.

Seborrhoeic keratosis (SK)ff

Plaque with a classic ‘stuck-on’ like appearance of variable shapes, sizes, and colours. Texture varies from verrucous to smooth, and they can vary in number. Often sited on the torso and typically found in patients >50 years with fairer skin. Lesions are painless but sometimes pruritic. Often a clinical diagnosis that requires no treatment unless clothing friction causes irritation.

Capillary haemangioma

A benign proliferation of capillaries that present as red papules and whose frequency increases with advancing age. Histologically similar to a larger lobular form called pyogenic granuloma; a single red nodule which grows rapidly and can bleed and ulcerate. The cause is unknown but associated with trauma and hormones (oral contraceptives and pregnancy).

Other Pigmented Lesions

Vitiligo

Vitiligo is an acquired depigmentation disorder due to epidermal melanocyte loss. Lack of melanin production presents as well-defined depigmented macules or patches, often in a symmetrical pattern and can be localised or progressive. Whilst it can occur on any site, acral, periorificial and genital areas are typically affected. Risk factors include auto-immune disorders, family history, cutaneous trauma, and age <30 years. It is often a clinical diagnosis. Treatments include topical and systemic immunosuppression, phototherapy, or a combination to stimulate re-pigmentation.

Melasma

Melasma is an acquired disorder of facial hyperpigmentation resulting from the overproduction of melanin from melanocytes. It often presents as bilateral and irregular hyperpigmented macules or patches, typically affecting women aged 20-40 years with Fitzpatrick skin type III-IV. Causes include family history, UV exposure and hormones (such as pregnancy, oestrogen/progesterone use in the form of contraceptives and hormone replacement therapies). Sun protection is important, and whilst several topical treatments are available, resolution is often slow, and recurrence is high.