Melanomas develop from melanocytes, which are sit- uated in the basal layer of the epidermis and originate from the neuroectoderm of the embryonic neural crest. Some melanocytes contain no visible pigment, but all are characterized by a positive dihydroxyphe- nyl alanine (DOPA) reaction – they can all convert DOPA into melanin. While most melanomas arise in the skin, they may also occur at other sites to which neural crest cells migrate, in particular the pigmented choroid layer of the eye.
Classification
Melanomas may be classified into the following.
• Intradermal melanoma or naevus (the common mole).
• Junctional melanoma or naevus.
• Compound melanoma or naevus.
• Juvenile melanoma.
• Malignant melanoma.
Nearly everyone possesses one or more moles; some have hundreds, although they may not become ap- parent until after puberty. Those moles that are en- tirely within the dermis remain benign, but a small percentage of the junctional naevi, so called because they are seen in the basal layer of the epidermis at its
junction with the dermis, may undergo malignant change (Figure 9.1).
Intradermal melanoma or naevus
This is the most common variety of mole. The nae- vus may be light or dark in colour and may be flat or raised, hairy or hairless. A hairy mole is nearly always intradermal. They may be found in any place in the body except the palm of the hand, the sole of the foot or the scrotal skin.
Histologically, there is a nest of melanocytes situ- ated entirely within the dermis where the cells form non-encapsulated masses. They never undergo ma- lignant change, and need no treatment unless the di- agnosis is uncertain.
Junctional melanoma or naevus
The junctional naevus is pigmented to a variable shade from light brown to almost black. It is nearly al- ways flat, smooth and hairless. It may occur anywhere on the body and, unlike the intradermal naevus, may be found on the palm of the hand, sole of the foot and the genitalia.
Histologically, naevus cells are seen in the basal layers of the epidermis from which the cells may spread to the surface.
Only a small percentage of junctional naevi under- go malignant change, but it is from this group that the vast majority of malignant melanomas arise.
Compound melanoma or naevus
Clinically, this is indistinguishable from the intrader- mal naevus, but histologically it has junctional ele- ments that make it potentially malignant.
Juvenile melanoma
Melanomas before puberty are relatively unusual, and may present as a dark nodule. Microscopically, they may be indistinguishable from malignant mela- noma yet fortunately, and surprisingly, these usu- ally pursue a completely benign course. Melanomas in children should therefore always be dealt with by conservative surgery in spite of their frightening his- tological appearance.
Malignant melanoma
Malignant melanomas arise in pre-existing naevi, either junctional naevi or compound naevi where there is a junctional component. They occur in white
The skin and its adnexae
55
(a) Normal (b) Intradermal melanoma
(c) Junctional melanoma (d) Malignant melanoma
Figure 9.1 (a) The normal skin contains melanocytes (shown as cells) and melanin pigment shown as dots. The pigment increases in sunburn and freckles. (b) A benign intradermal naevus; the melanocytes are clumped together in the dermis to form a localized benign tumour. (c) A junctional naevus with melanocytes clumping together in the basal layer of the epidermis. These are usually benign but may occasionally give rise to an invasive malignant melanoma (d).
people on light-exposed areas, hence the higher in- cidence on the legs of females. They are rarely found in the pigmented skin of dark-skinned races, tending to be found in the non-pigmented skin on the sole of the foot or, less commonly, the palm. A premalignant form, the lentigo maligna, also exists.
Presentations
The two main presentations of malignant melanoma are the superficial spreading type, and the nodular type.
• Superficial spreading melanoma. The most com- mon presentation of malignant melanoma is of a previously dormant naevus starting to spread
superficially. The surface has patches of deep pigmentation.
• Nodular melanoma. The naevus is nodular and deeply pigmented and may bleed or ulcerate.
Such a nodule may occur on a pigmented back- ground such as the lentigo maligna. It tends to in- vade deeply rather than spread superficially, and carries a poorer prognosis with earlier lymphatic involvement.
In addition to the common types of malignant melanoma above, less common forms include the following.
• Lentigo maligna. This is a brown pigmented patch with an irregular outline and is usually found
56
The skin and its adnexaeon the cheeks of elderly women, often called a Hutchinson’s freckle.5 The pale patch appears over several years; malignant change is indicated by deeper pigmentation or nodule formation.
• Acral melanoma. These are so called because they occur at the extremities, commonly on the palms and soles of the feet. It is this type that also occurs in dark- skinned races. The subungual melanoma is a variant of acral melanoma (see earlier in this chapter).
• Mucosal melanoma. Malignant melanoma may be found on the mucous membranes of the nose, mouth, anus and intestine.
• Choroid melanoma. Melanomas may arise from melanocytes in the pigment layer of the retina.
These are renowned for presenting many years after enucleation with hepatic metastases; hence, the aphorism ‘beware the patient with the large liver and the glass eye’.
• Amelanotic melanoma. Paradoxically, melano- mas are not always pigmented, but they remain DOPA positive.
Signs of malignant change in a melanoma
• Increase or irregularity in size.
• Increase or irregularity in pigmentation.
• Bleeding or ulceration.
• Spread of pigment from the edge of the naevus.
• Itching or pain.
• Formation of daughter or satellite nodules.
• Lymph node or distant spread.
Pathology
Microscopically, pleomorphic cells are seen, which spread through the layers of the epidermis and which are usually pigmented (occasionally the cells are amelanotic).
Spread
As well as local growth and ulceration, malignant melanomas seed by lymphatic permeation, which produces cutaneous nodules by progressive proxi- mal spread, and by lymphatic emboli to the regional lymph nodes. There is also widespread dissemina- tion by the bloodstream to any and every organ in the body. Free melanin in the blood may produce gener- alized skin pigmentation and melanuria in late cases.
Staging
The prognosis of malignant melanoma depends upon its degree of invasion, which is measured by the depth of invasion. The depth may be measured either by reference to the normal skin layers (Clark’s levels6) or, more simply and accurately, according to its measured depth (Breslow depth7). Because of its simplicity, Breslow’s method is now routinely adopted.
Treatment of pigmented lesions
The following is a general guide to the management of pigmented lesions of the skin.
Prophylactic removal
Any pigmented tumour on the hand, sole or genita- lia, or any that, in other situations, are subjected to trauma should be excised; these are the most com- mon among the small percentage of naevi to undergo malignant change. In addition, pigmented lesions should be removed for cosmetic reasons or if the pa- tient is acutely anxious about their presence – this is a particularly common phenomenon among doctors, nurses and medical students. Such lesions are sent for careful histological examination and should al- ways be removed in their entirety.
Suspicious naevi
If the pigmented lesion shows any of the features al- ready listed that suggest that malignant change has taken place, the naevus is first removed for urgent histological examination (frozen section). If malig- nant melanoma is confirmed, a wide local excision of the area is performed, with a margin of clearance pro- portional to the depth of invasion (Breslow depth).
Traditionally, this was translated into a centimetre margin for every millimetre of invasion; primary skin grafting may be required.
Sentinel lymph nodes
The sentinel node, the primary lymphatic drainage of the tumour, is identified and excised for histological examination. Identification of the sentinel node is by injection of vital blue dye around the primary mela- noma, combined with preoperative lymphoscintig- raphy to map the lymphatic drainage. If the sentinel node is involved, the regional nodes are excised by block dissection.
5Sir Jonathan Hutchinson (1828–1913), surgeon, The London Hospital, London, UK. Described numerous conditions and was first to perform a successful operation for reduction of an intussusception in a child.
6Wallace H. Clark Jr (1924–1997), pathologist,
Massachusetts General Hospital, Boston, USA. Described five levels of invasion of melanoma in 1967.
7Alexander Breslow (1928–1980), pathologist, George Washington University Hospital, Washington, DC, USA.
The skin and its adnexae
57
Adjuvant therapy
Malignant melanoma deposits often show regression when the primary lesion is excised, implying an immu- nological component. Immunotherapy with high-dose interferon-α2b may be effective at prolonging survival.
Interleukin 2 administration has also had some success.
Melanomas are generally radioresistant. Results of chemotherapy, including high-dose isolated per- fusion of a limb with cytotoxic chemotherapeutic agents, have been disappointing.
Prognosis
Prognosis depends on a large number of factors.
• Breslow depth of the primary lesion, measured vertically from the top of the granular layer to the deepest point of tumour invasion. This is the most important prognostic factor. Prognosis is good when this depth is less than 1.5 mm. The deeper the lesion, the greater the risk of lymph node metasta- sis and the worse the 5-year survival (Table 9.1).
• Type of lesion. A superficial spreading melanoma has a better prognosis than a penetrating and ul- cerating lesion.
• The anatomical site. Tumours on the trunk and scalp have a poor prognosis.
• Lymph node metastases. They indicate poor prog- nosis, more so if there are cutaneous deposits. The presence of sentinel node involvement, or satellite lesions, reduces 5-year survival to under 30%.