world cancer report - iarc

Fig. 5.131 Primary melanoma with a coastline border
and multiple colours, including classic blue
black pigmentation.
the lesion from the granular cell layer of
the epidermis to the deepest detectable
melanoma cell (tumour thickness). In
recent years, one additional criterion,
ulceration, has been shown to be important
in prognosis and is included in the
AJCC/UICC classification system (Table
5.14).
While it is clear that the genetic make-up
of the melanoma-prone population is very
important, few melanomas can be
ascribed to specific genetic defects in
these populations. While 10% of melanoma
patients have a first degree relative
affected, less than 3% of melanomas in
Australia (where the incidence of
melanoma is high) can be ascribed to an
inherited gene defect [3]. Familial melanoma
is even more rare in lower incidence
countries.
Fig. 5.132 Melanoma with an elevated nodule.
Loss-of-function mutations in the human
melanocortin-1 receptor (MC1-R) have
been associated with red hair, fair skin
and decreased ability to tan [5], all physical
characteristics which affect susceptibility
to skin cancer. About 20% of
melanoma-prone families possess
germline mutations in the CDKN2A gene,
which encodes p16 INK4A [6]. Mutations in
the gene encoding CDK4 have been identified
but are extremely rare [7].
Genes identified as having a role in sporadic
melanoma development include
CDKN2A and PTEN, while chromosomal
regions 1p, 6q, 7p and 11q may also be
involved [6]. About 20% of melanomas
possess mutations in the p53 gene.
Nodular melanomas display amplification
of the MYC oncogene. Inactivation of
p16 INK4A is associated with a poorer prog-
Classification Surgical excision margins
Tis in situ melanoma/no invasion 5 mm
of the dermis
T1 ≤ 1 mm (in thickness) 10 mm
T2 1.1 mm – 2.0 mm 10 mm
T3 2.1 mm – 4.0 mm Minimum 10 mm, maximum 20 mm
T4 > 4 mm Minimum 20 mm, maximum 30 mm
Each T level is classified: There is no evidence that a margin
A – if ulceration is present greater than 1 cm improves survival but
B – if no ulceration is present it may decrease local recurrence.
Table 5.14 Classification of melanoma (American Joint Committee on Cancer/International Union
Against Cancer) and corresponding recommended excision margins.
nosis. Alterations in the cyclin-dependent
kinase PITSLRE have been identified in
advanced melanomas [8]. The recent discovery
of a role for the BRAF gene in
melanoma illustrates the impact of large
scale international collaboration [9].
Management
Treatment of primary melanoma is essentially
surgical and is related specifically to
the tumour thickness measurement. The
primary tumour is excised with a margin of
normal skin, the excision being based on
the tumour thickness measurement [10].
As the primary melanoma becomes thicker
(deeper), the risk for metastatic spread
rises and thus survival outcomes are related
specifically to the tumour thickness
measurement (Fig. 5.134).
Melanoma metastasizes via the lymphatic
system and also via the systemic circulation.
Approximately 50% of melanomas
metastasize first to the lymph nodes, thus
making the management of lymph node
metastases an important part of the treatment.
Elective lymph node dissection (i.e.
prophylactic removal of lymph nodes) is
now rarely practised in the management
of primary melanoma. The standard management
for lymph nodes in patients with
primary melanoma is an observation policy
and therapeutic node dissection if
lymph nodes become involved. However,
selective lymphadenectomy [11] is under
clinical trial at the present time. This tech-
Fig. 5.133 Surface microscopy of a melanoma,
showing pseudopods, blue-grey veil and multiple
colours.
Melanoma
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