Malignant melanoma is a cancer or neoplasma of the melanocyte cells which develops from melanocytes.

            Epidemiology

            The annual incidence of malignant melanoma is 10 per 100,000 inhabitants. In Australia there is the highest incidence of melanoma in the world, 57 per 100,000 inhabitants. In Israel there is also an increased incidence of malignant melanoma, 40 per 100,000 inhabitants. In the US in 2014 are expected to be diagnosed 76,100 cases of cutaneous melanoma. The incidence of melanoma increases by 5-7% annually, only lower annual growth of lung cancer in women. Lifetime risk of developing melanoma in 1935 was 1/1500, the risk to life in 2000 was estimated at 1/75. Although malignant melanoma justified only 5% of skin cancers it is responsible for three times more deaths each year than non-melanoma skin cancers. ASCO estimates that in 2014 the US will die by 9700 people malignant melanoma. Melanoma can occur at any age, but the average age at diagnosis is 57 years and 75% of patients aged <70 years. Melanoma is the most common malignancy in women aged 25-29 years and justify more than 7,000 deaths annually.

In Romania the estimated incidence for 2000 was 8.91 per 100,000 population and mortality of 2.46 per 100,000 inhabitants.

Risk Factors

1. Malignant melanoma previous

2. Family history of melanoma

3. Dysplastic nevus syndrome (BK mole syndrome)

4. Increased number of benign nevi> 5 nevi with a diameter> 5 mm or> 50 nevi with diameters> 2 mm

5. Skin phenotype: white skin, blond or red hair, blue eyes, freckled

6. The tendency to burn instead of tan

7. History of blistering sunburn in childhood

8. Excessive exposure to sun

9. Large congenital nevi (> 20 mm in diameter)

10. Multiple congenital nevi (> 5% of body surface)

11. Immunosuppressed patients

Clinical-pathological classification of malignant melanoma extraocular

            1. Malignant melanoma with superficial dissemination 70%

            2. Nodular malignant melanoma 10-15% (malignant melanoma amelanocytic)

1. Malignant melanoma pigmented (lentigo malignant) 10-15%

            4. Acrally pigmented malignant melanoma 2-8%

                        -Periangular malignant melanoma

            Signs and symptoms:

            Amendments to a preexisting lesions (nevus) as regards color, width or thickness increase, itching, soreness, bleeding.

            Multiple primary melanoma occurs in 4-5%.

            Relapses skin into the subcutaneous tissue and lymph nodes are the most common (59%).

            Metastasis in the order of frequency of appearance: in the lung, liver, intestine, brain, adrenal, kidney, and bone.

            Tumor biopsy for lesions less than 2cm excisional biopsy is recommended that fully includes removing the lesion with a small margin of normal skin (1-2mm).

            For lesions larger than 2 cm is recommended which should include incisional biopsy of the lesion center, subcutaneous fat and normal skin.

            Principles of pathology:

– Biopsy should be read by a pathologist experienced in skin lesions

– The minimum elements that should include a histopathological bulletin are in mm Breslow tumor thickness, histological ulceration (presence or absence), mitotic rate dermal / mm, Clark level for lesions> 1 mm, the peripheral edges and deep biopsy (negative or Positive)

– Microsatelitosis: is defined as the presence of a tumor larger networks of 0.05 mm in diameter reticular dermis, fat or blood vessels tassel below the main invasive tumors but separated from it by at least 0.3 mm normal tissue. Microscopic satellites commonly associated with regional lymph node metastases than the thickness of the tumor.

– Location tumor

– Tumor regression

– Vertical growth phase

–  Angiolymphatic invasion

– Neurotropism

– Sub histologically

– Desmoplasia – pure or mixed (associated with fusiform cells or epithelioid cells)

            Screening consists of historical and whole body examination in daylight. For the general population over the age of 20 years recommended a skin exam to 3 years, and at-risk populations clinical examination is recommended annually.

            Prevention is by avoiding sun exposure between the hours of 1000 and 1600, the use of protective substances, protective clothing, self-examination, atypical nevi excision in patients with personal history of melanoma.

            The diagnosis is confirmed by histopathological examination. Histopathological examination should include width ulceration, Clark level, Breslow depth of invasion, mitotic index, vascular and lymphatic invasion.

            Micro- staging

Breslow thickness of the primary tumor is a prognostic parameter. Tumor thickness was measured from the granular layer of the epidermis to the deepest melanocytic cells. The likelihood of metastasis when tumor thickness greater than 1,75-2mm.

pT1- tumor ≤ 0.75 mm in thickness

pT2- tumor> 0.75 mm but ≤ 1.5 mm in thickness

pT3- tumor> 4 mm but ≤ 1.5 mm in thickness

pT4 – tumors> 4 mm in thickness

            Based on the depth of local invasion considers the risk of local recurrence and metastasis away:

v melanoma with depth of invasion <1 mm: the risk of local recurrence and metastasis distance is less than 5%

v malignant melanoma invasion depth of between 1 mm -4mm has a high risk of metastasis to regional metastases to 40% and less than 20%

v malignant melanoma invasion depth> 4mm has a likelihood of regional metastases and metastases to 60% from 70%

v

Clark level of invasion

q Clark Level I: the lesion is located in the epidermis, without invading the basement membrane.

q Clark Level II: basal membrane damage exceeded invade the papillary dermis.

q Clark Level III papillary dermis lesion invades interface / reticular dermis.

q Clark Level IV: lesion invades the reticular dermis.

q Clark Level V: lesion invades the underlying subcutaneous fat.

– Table no. AJCC staging malignant melanoma 1 (2010)

            Primary Tumor (T)

pTx- primary tumor cannot be assessed

pT0- no evidence of primary tumor

pTis- in situ melanoma, Clark level (malignant noninvasive, atypical melanocytic hyperplasia, severe melanocytic dysplasia)

pT1 – tumor ≤ 1 mm in thickness and invades the papillary dermis (Clark level II)

                        a. without ulceration; b. With ulceration

pT2 – Tumor> 1 mm but <2 mm in thickness and / or invades the papillary dermis interface / reticular dermis (Clark level III)

                        a. without ulceration; b. with ulceration

pT3 – Tumor> 2 mm ≤ 4 mm in thickness and / or invades the reticular dermis (Clark level IV)

pT3a – without ulceration

pT3b – with ulceration

pT4 – tumors> 4 mm in thickness and / or satellite tumors at a distance <2 cm of the primary tumor

pT4a – without ulceration

pT4b – with ulceration

            Regional lymph nodes (N)

Nx – regional lymph nodes cannot be assessed

N0- no regional lymph node metastasis

N1- metastasis in a single lymph node

                        a.micrometastases (clinically occult)

                        b. macrometastases (clinically apparent)

N2 – metastases in lymph 2-3 lymph nodes

                        N2a.- micrometastases

                        N2b.-macrometastaze

                        N2c.-transit metastases, lymph node metastases without satellites

Metastasis in transit involving the skin or the subcutaneous tissue more than 2 cm from the primary tumor, but does not exceed the regional lymph nodes.

                        N3 4 or more lymph nodes or lymph nodes block the transit or satellite metastases in lymph node metastasis

            Distant metastasis (M)

MX distant metastasis can ot be assessed

M0 – no distant metastases

M1a – metastatic cutaneous or subcutaneous tissue or lymph nodes beyond the regional lymph nodes, normal LDH

M1b- visceral metastases, normal LDH

M1c- All types of visceral metastases or distant but increased LDH

            Selected

            Stg.0 N0 M0 pTis

            Stg.IA N0 M0 pT1a

            Stg.IB pT1b, N0 M0 pT2a

            Stg.IIA pT2b, N0 M0 pT3a

            Stg.IIB pT3b, N0 M0 pT4

            Stg.III any T N1-3 M0

            Stg IIIA pT1-4a N1A-N2a M0

            Stg IIIB pT1-4b N1A-N2a M0

                                    pT1-4a N1b-M0 N2b

                                    any M0 T N2c

            Stg.IV Any T Any N M1

            For staging it is recommended:

· History, clinical examination,

· Blood count, biochemical tests of renal, hepatic, LDH,

· Chest x-ray, bone scans, liver and brain (only in case of suspicion of metastases)

· C. T. lung, liver, brain only in case of suspicion of metastatic disease or stg.II and III,

· Lymphoscintigraphy for sentinel node detection

Histological and immunohistochemical examination.

· Cranial MRI is recommended in patients with distant metastases to detect asymptomatic metastatic disease. In patients without metastases is recommended only in case of symptoms.

· Ultrasound is the best imaging test to diagnose lymph node invasion

· PET / CT (FDG) are the best imaging study to detect other metastatic locations. It is recommended in patients with lymph node metastases, transit or satellite metastases in patients with advanced metastatic disease or to detect other remote locations disease.

            Tumor markers

            Lactic dehydrogenase (LDH) is a tumor marker for liver or lung metastatic disease. LDH is increased in several diseases including malignancies. Although the specificity and sensitivity of this test is to show that low LDH is a predictive factor for poor prognosis. LDH is considered part in melanoma staging system.

            Level S-100 β polypeptide Patients positive for this marker have a lower survival than patients negative 2.7 times.

TREATMENT

            Therapeutic Indication

            Stg.I and II

a) pT1 and pT2 <1mm. Indicate wide surgical excision and follow-up

b) pT2> 1 mm and pT3. Wide surgical excision is recommended, lymphoscintigraphy or injection of dye around the tumor to detect sentinel lymph node biopsy followed by sentinel lymph node:

1) negative sentinel lymph node. Indicate tracking.