Melanoma

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Introduction:

• Melanoma is a malignant tumour developed at the expense of melanocytes (melanocytes that are normally stored in isolation between the keratinocytes of the dermo-epidermal junction are responsible for making a pigment designed to protect the vis peau -to ultraviolet radiation: melanin, they have a ubiquitous distribution: skin, mucous membrane, retinal)
• Sun exposure, clear phototype and the presence of a large number of nevus are recognized risk factors
• His diagnosis is based on the clinic, assisted by dermatoscopy and confirmed by histology
• Early diagnosis and correct exeresis are the keys to primary prognosis
• Prognostic markers are mostly histological
• Prevention is based on modifying risk behaviours, early detection and prevention of suspicious lesions

Epidemiology:

• Incidence: doubles about every 10 years in white-population countries living in sunny areas, in most European countries, the incidence is estimated at 5-10 new cases/100,000 inhabitants/one. This incidence peaks (40 new cases per 100,000 inhabitants/year) among whites in Australia, while it is very low in countries where the subjects are black or yellow
• Age of events: it is a tumour that affects all ages, outside the child, in which melanoma is exceptional
• Sex-ratio: female predominance
• In Algeria: a retrospective study from 1985 to 1995 of 116 patients showed: higher incidence in the west of the country (53.17%), age: 40-50 years (33.80%), sex: 55.70% of women, nodular aspect (74.31%), seat: lower limbs (55.70%), land: de novo de novo (82.07%), consultation is late, Clark level: V (47.91%)
• Melanoma mortality is high, hence the value of early diagnosis and effective surgical treatment to improve prognosis
• Etiological factors: Melanoma appears as a result of the interaction between individual predisposition factors and environmental factors

Individual factors:

• Phototype: The sensitivity of the skin to the sun is defined by the phototype. Subjects with light skin and blond hair and especially red hair are the most sensitive to the sun (phototype I/II), the clearer the subject (no or very few melanic pigments) the more susceptible he is to UV radiation. The peak incidence of melanoma is observed in the redhead
• Naevic phenotype: the number, size and appearance of nevus

Atypical nevus syndrome: a particular shape, defined by the presence in large numbers of nevus (50), often of large size (6 mm in diameter), having atypical aspects (irregular edges, polychromy). These subjects will be closely monitored because of the high risk of developing melanoma

Giant congenital Novus: exists at birth, it covers a part of the newborn's body or the entire body of the newborn

Family factor: about 10% of melanomas occur in a "family melanoma" context, defined as at least 2 melanomas over 3 generations, prompting the identification of the familial predisposition gene to melanoma

Environmental factors (solar exposure): The sun is the only environmental factor involved in the epidemiology of melanoma. We can see:

• Intermittent acute exposure: a type of sunburn during childhood, is complicated by melanoma of the young adult, the latter appears on areas interested in sunburn (back, shoulder, leg)
• Chronic and progressive exposure: melanoma in the elderly, melanoma develops on areas continuously exposed to the sun (cephalic extremity: Dubreuilh melanoma)
• Melanomas of the palms, plants and mucous membranes are not directly related to sun exposure

Other factors:

• Immunodepression: promotes the occurrence of melanoma (renal transplant, treatment with cytotoxic immunosuppressants…)
• DNA Repair Disorders: As in Xeroderma pigmentosum, comes with a high risk (x 1000)

So the risk markers for melanoma:

• Family and personal history (the same causes produce the same effects) of melanoma
• Light color of skin and hair and especially red marker with sphelides, blond red hair
• High number of nevus, the risk increases with the number of nevus and atypical nevus syndrome represents the extreme of the risky naevic phenotype
• A history of intense sun exposure during leisure activities with sunburn
• Forerunners: the majority of melanomas are born de novo, in skin, apparently healthy without precursor, the risk of malignant transformation of common nevus is very low, congenital nevus have a higher risk of transformation if they are of large in size (20 cm) they are rare and, as a result, cause very few melanomas to occur. There is no point in doing the preventive systematic exeresis of the common threads only the early preventive exerism of large congenital nevus is desirable

Positive diagnosis:

• The diagnosis of melanoma, clinically suspected by inspection, sometimes assisted by a dermatoscope is affirmed by the anatomopathological examination which also conditions the initial therapeutic decision and the evaluation of prognosis
• Suspicion: is clinical

ABCDE Rule:

• A: Asymmetrical
• B: Irregular edges, often checked or polycyclic
• C: Inhomogeneous colour (brown, black, brown or blue, depigmented areas, inflammatory halo)
• D: Diameter – 6 cm
• E: Permanent evolution, documented (extension in size, shape, relief, colour)

Pruritus or bleeding on contact are also possible when the tumour progresses

A different lesion from the other nevus of the subject (sign of the "naughty duckling") is suspect

Any suspected melanoma lesions must be excised for a histopathological examination

• Diagnosis: is histological, only histological analysis can confirm the diagnosis of melanoma, this must be performed on a complete exeresis piece carrying lesion in its entirety as well as the banks

Melanoma Histogenesis: Takes place in a biphasic mode:

• In a first phase, the extension is intra-epidermal horizontal, above the basal membrane
• In a second phase, the extension is vertical, with invasion of the superficial dermis (micro-invasive phase) and then the deep dermis and the hypodermis (invasive phase). The melanoma has, in good standing:

Intra-epidermal component: made of melanocytes that form a tablecloth or libraries arranged irregularly along the basal, associated with an invasion of the surface layers of the epidermis by isolated migrating tumour cells and anarchic

Dermal component: invasive, sometimes associated with an inflammatory reaction

The histological examination allows:

• To affirm the melanocytic nature of the tumor: melanc pigment, disposition, immunohistochemistry…
• To affirm the malignancy of the tumour: a number of architectural and cytological criteria allow us to affirm the malignancy of the lesion, that is to say, to distinguish between nevus and melanoma: architectural disorder, presence of atypies nucleo-cytoplasmic, mitotic images, vascular embolisms, neurotropic extension or loss of morphological gradient usually observed in nevus from area to depth

The anatomopathological report should specify, for each lesion, a number of parameters that allow:

• To estimate a prognosis:

Breslow Index: it represents the measurement in millimetres, under an optical microscope, of the maximum thickness between the grainy layer of the epidermis at the top and the deepest malignant melanic cell.  Melanomas that do not invade the dermis are not measured and are called "in situ", and there is a quasi-linear correlation between tumor thickness and average survival time

• To clarify whether or not the exeresis is complete

Dermatoscopic examination (epiluminescence): is a non-invasive complementary examination method that uses a semiology of its own, based on the analysis of the image observed as a whole and facilitates differential diagnosis but operator-dependent and be subject to the pitfalls

Anatomopathological classification:

There are 4 major types of melanoma, depending on their clinical and histopathological appearance and their mode of progression

• Superficial Spreading Melanoma (SSM): represents 60-70% of melanomas, it comes in the form of a pigmented macule that can secondaryly take on relief with the appearance of a nodular component. This melanoma most frequently sits on the lower limb in women and in the back in men. The horizontal growth phase usually precedes the vertical phase of several months
• Nodular melanoma: represents 10-20% of melanomas, it immediately presents itself in the form of a nodule and its growth is rapid. Its development is immediately vertical (without horizontal phase) and the metastatic risk is important, so it leaves little time for screening at a thin stage (bad prognosis)
• Dubreuilh melanoma (malignant lentigo): which accounts for 5-10% of melanomas, it sits, with predilection, on photo-exposed areas (face, décolleté, forearm) and occurs in the elderly subject. The clinical aspect is that of a macule and then a pigmented tablecloth, which has a horizontal evolution for months and years, which leaves a lot of time for an exeresis before dermal invasion
• Lentignous acral melanoma (acrolentiginous): which accounts for 2-10% of melanomas in white matter and up to 60% of melanomas in black subjects. The clinical aspect is that of a pigmented macule that sits favorably at the ends (palms, plants, fingers, toes), the horizontal growth phase is usually very slow and leaves plenty of time for a pre-eresis dermal invasion

Special clinical forms:

• Mucosa melanoma: it accounts for 5% of all melanomas, it is usually late diagnosis melanomas and poor prognosis, especially since the tumour probably has faster access to lymph node drainage (melanoma vulva, nasal cavity melanoma, anorectal melanoma…)
• Child melanoma: it remains exceptional and its diagnosis is difficult, in fact, false diagnoses of melanoma correspond, in fact, to inflammatory evolutionary nevus.  Child melanomas most often occur de novo, congenital melanomas remain exceptional
• Achromic melanoma: these melanomas that are not pigmented usually occur in the form of a pink or red lesion, their diagnosis is difficult because they can simulate a number of lesions (basal cell carcinoma, botryomycome, etc.). Their prognosis is generally bleak: on the one hand because of a frequent delay in diagnosis, on the other hand because they are willingly fast-growing nodular forms.
• Ungueal melanoma: belongs to the group of acrolentiginous melanomas, which has the same epidemiological and prognostic characteristics. Preferred seat: big toe or thumb, appearance: brown or black macule at the nail bed and sub-ungueal fold (Hutchinson sign), melanonychic band, acquired longitudinal, ungueal dystrophy, matrix destruction, ulcerated tumor, hence the value of biopsy

Differential diagnosis:

It should rule out other black tumors that are much more common than melanoma

• Melanocytic tumors: clinically atypical nevus have aspects that sometimes meet the criteria of beginner melanomas, spelias…
• Non–melanocytic tumours:

Seborrheic Keratosis: usually multiple lesions, sitting on the seborrheic areas of the face and trunk, the clinical aspect is that of yellowish, brown or frankly black lesions, with a wart surface and riddled with corks keratosic damage to the skin. Differential diagnosis with melanoma is usually easy, dermatoscopy makes it easy to correct the diagnosis in difficult cases

Tattooed basal cell carcinoma: it can be confusing with an SSM or with nodular melanoma, the beaded appearance of the lesion or the presence of telangiectasies can guide diagnosis, dermatoscopy may also be useful

Histiocytofibroma pigmented: nodular lesions, strictly intradermal, which can be pigmented, the palpation of these lesions which is quite characteristic (undue lozenge) usually helps to correct the diagnosis

Hemangioma: it can take a bluish or black coloration when irritated or thrombosised, dermatoscopy is also characteristic

Botryomycoma: it can pose a diagnostic problem with achromic nodular melanoma, its post-trauma occurrence may help the diagnosis

Subungueal Hematoma: It is generally easy to differentiate from sub-ungueal melanoma.  If there is any doubt, the exeresis must be made in order to have histological confirmation of the exact nature of the lesion

Soft fibrome (molluscum pendulome)

Evolution:

• The usual spontaneous evolution is marked by a local invasion with possible extension to adjacent or remote skin, regional ganglia and appearance of metastases, usually multiple (soft tissue, lung, liver, brain, bone…)
• The majority of metastases occur between 2 and 5 years after treatment of the primary tumour

Clinical and histopathological criteria for prognosis (poor prognosis factors)

• Melanoma in old age
• Melanoma occurs in men (male sex)
• Location of cephalic melanoma and mucous membrane melanoma are poor prognosis (due to early lymph node invasion)
• Anatomoclinic type (nodular melanoma has a poor prognosis)
• The existence of ulceration (clinical or histopathological)
• Node invasion
• The existence of metastases and their number
• The main prognostic factor for melanoma independent of all other factors: tumor thickness (Breslow index) with an almost linear correlation between thickness and mortality

Treatment:

• Apart from surgical treatment, which may, in some cases, be a curative treatment, other treatments remain palliative
• The goal of treatment is to ensure long-term survival and avoid locoregional recurrences and skin, lymph node and visceral metastases

Surgical: Surgical exeresis must be early, in the non-invasive stage, as it allows healing

• At the stage of lymph node invasion or metastasis, treatment will involve surgical exeresis of melanoma followed by metastasis when possible.

Chemotherapy: various drugs and protocols are used but melanoma remains insensitive to chemotherapy

Radiation therapy: is useful in case of lymph node or metastatic disease

Biotherapy and anti-tumor vaccination: appear to be promising pathways

Prevention:

• Primary prevention (risk reduction): requires information from populations about the risk of sun exposure and the reduction of these exposures (limitation of exposures to higher hours of sunshine, protection  dress and repeated use of external photo-protectors), it is aimed primarily at children but remains important at all ages of life, so there is no interest in making the preventive systematic exeresis of the common threads, only the exeresis early prevention of large congenital nevus is desirable
• Secondary prevention (screening): must be early to improve prognosis, the later a melanoma is detected, the more likely it is to be invasive (vertical phase) and metastasize. Physicians need to be able to examine their patients' coats in its entirety and need to identify suspicious pigmented lesions, the general public should be aware of the signs of call that should prompt access, high-risk families must be subject to special medical supervision, subjects at risk should be informed and subjects at very high risk (first melanoma, atypical nevus syndrome) should have specific medical follow-up (photographic, dermatoscopic)

Conclusion:

• Melanoma is an aggressive tumor with significant metastatic potential, so the incidence is increasing
• Wide surgical exeresis at an early stage is the only potentially curative treatment since metastatic potential is significant and no therapeutics are currently effective at this stage.
• The main prognostic factor is the Breslow index
• Patient information (in order to modify risky solar behaviours) and screening for suspicious lesions form the basis of prevention