Primary cutaneous melanoma

Last revised by Daniel MacManus on 7 Jun 2024

Primary cutaneous melanoma is the most common subtype of melanoma, a malignant neoplasm that arises from melanocytes. Melanocytes predominantly occur in the basal layer of the epidermis but do occur elsewhere in the body. Primary cutaneous melanoma is by far the most common type of primary melanoma, although it may occur in other tissues, e.g. primary uveal melanoma.

In general, melanoma is one of the less common types of skin cancer. However, it causes the majority (75%) of skin cancer-related deaths because of its tendency to metastasize, commonly to skin and subcutaneous tissue, lymph nodes, lung, liver, bone and brain (see metastatic melanoma).

It is worth noting that although ubiquitous in the medical literature, prefacing 'melanoma' with the term ‘malignant’ is not only unnecessary (all true melanomas are malignant) but also potentially confusing; the absence of the term ‘malignant’ in a pathology report in no way implies a ‘non-malignant’ lesion. Even melanoma that has not as yet demonstrated histological invasion (in situ melanoma) is still considered a malignant neoplasm, albeit with a very low to absent rate of metastatic spread.  

Common risk factors for malignant melanoma include:

  • unprotected exposure to high levels of ultraviolet radiation

  • history of blistering sunburn especially in childhood

  • familial predisposition due to fair skin and shared lifestyle factors that include increased sun exposure

  • mixed cancer syndrome (autosomal dominant) e.g. familial atypical multiple mole-melanoma (FAMMM syndrome) a CDKN2A mutation, see below

  • xeroderma pigmentosum, a rare autosomal recessive condition that prevents the skin from repairing itself after UV damage

  • exposure to radiation and some chemicals such as solvents

  • impaired immunity, including increased age

  • male gender

FAMMM patients have > 50 atypical nevi and have a personal and/ or family history for melanoma. Melanomas develop at a young age and patients have an increased incidence of metachronous tumors. Patients have an increased incidence of pancreatic, gastrointestinal, breast, lung, larynx, and other skin cancers.

Since sun exposure is a risk factor, there is significant variable incidence across the globe. Incidence is highest in countries with high sun exposure and a fair-skinned immigrant population, e.g. Australia.The proportion of inherited cancer syndromes therefore varies markedly depending on geographic location.

Melanocytes are cells that produce melanin, the pigment responsible for skin color. They arise from the neural crest in the embryo and migrate throughout the body, the vast majority ending up at the dermo-epidermal junction of the skin, where they provide melanin for the epidermal keratinocytes. The concentration of melanocytes in the base of the epidermis does not differ significantly between ethnic groups, but in fact it is the secretion of melanin that results in ethnic variability of skin color. 

Melanocytes that undergo malignant change show varied architectural patterns of growth. This forms the basis of the histological subtyping, with the four most important/common subtypes being:

  • lentigo maligna (in situ, also known as the Hutchinson melanotic freckle) and lentigo maligna melanoma (invasive) - seen in sun-damaged skin, especially the face of older patients

  • superficial spreading melanoma

  • acral lentiginous melanoma: involves hands and feet

  • nodular melanoma: prominent vertical growth pattern, with absent residual radial growth component, i.e. ‘growing down, not around’

Multiple additional rarer subtypes are also described based on cell morphology or unusual growth patterns. These are usually distinguished for reasons of diagnostic difficulty (clinical or histological) but some are merely described because of fascinating morphology. These include, but are certainly not limited to:

  • desmoplastic melanoma: melanocytes are spindled and relatively bland, sometimes making both initial diagnosis and demarcation of the lesions borders very difficult, the latter making complete excision difficult

  • nevoid (minimal deviation) melanoma: ‘benign’ low-power growth pattern

  • amelanotic melanoma: as the term implies, these lesions are non-pigmented clinically and are often removed without a clinical suspicion of melanoma

  • or the unusually named melanoma of the animal type

Most subtypes appears to have minimal independent prognostic significance. 

Although primary cutaneous melanoma is the most common location for melanoma, melanocytes are also found in smaller numbers throughout the body, especially mucosal surfaces of the gastrointestinal tract (oral cavity to anus), the genital tract, and the eye; melanoma arising in any of these sites is a rare but recognized event. See also malignant uveal melanoma, primary malignant melanoma of the prostate and melanoma of the urethra.

See full article here.

Prognostic staging for malignant melanoma is accomplished using the American Joint Committee on Cancer (AJCC), 8th edition melanoma staging system which has been in use since January 1, 2018 7.

Prognostic staging integrates the Breslow thickness or historically the Clark level 1,2, 6

  • <0.76 mm: 5-year survival rate: 95% to 100%

  • 0.76-1.5 mm: 5-year survival rate: 80% to 96%

  • 1.5-4 mm:  5-year survival rate: 60% to 75%

  • >4 mm: 5-year survival rate: 37% to 50%

Clark level, which is based on the depth of tumor invasion into the layers of the skin, stopped being used in melanoma staging with the introduction of the AJCC (American Joint Committee on Cancer) 7th edition in 2009. High Clark level was replaced by mitotic rate which was found to be a stronger prognostic factor than a high Clark level 6.

  • level I: tumor cells are maintained above the basement membrane

  • level II: tumor cells have infiltrated the papillary dermis

  • level III: tumor cells extend between papillary and reticular dermis, but do not invade the reticular dermis

  • level IV: tumor cells have infiltrated the reticular dermis

  • level V: tumor cells extend into subcutaneous tissue​

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