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Melanoma

 

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A suspicious skin lesion can be noticed by:
- any doctor who, while examining the patient for any reason, inspected also their skin;
- any dermatologist during a routine inspection of the patient’s skin;
- the sick, themselves;
- family and friends of the sick.
Suspicious lesions are skin lesions that meet at least one criterion on the American ABCDE scale, a checklist helpful in detecting early signs of melanoma:
A. (asymmetry) – a melanoma is asymmetrical with respect to any axis, as opposed to benign lesions, which are usually circular or oval; it can also present an irregular shape composed of small elevations above the skin surface;
B. (borders) – irregular or ragged edges;
C. (colour) – variegated – from light brown to black or steely) – with uneven distribution of the pigment and, often, with its punctual deposits (particularly noticeable during dermatoscopy);
D. (diameter) – diameter > 5mm, or (dynamics) – dynamics of morphological changes in the tumour;
E. (evolution) – that is, acquisition of new characteristics in an already existing lesion: itching, bleeding, ulceration, quick growth; alternatively, another criterion, less often used nowadays: (elevation) – the mole or mark is raised above the level of the epidermis surrounding it (it concerns mainly advanced melanomas, melanomas in the early stages don’t form a palpable bulge),

or the British Glasgow scale, helpful in detecting locally advanced melanomas:
1. growth
2. change in shape
3. change in colour
4. inflammation
5. oozing or bleeding from the lesion or a visible crust
6. sensory disturbances (e.g., itch or hyperesthesia)
7. diameter > 7mm

The most common sites for melanomas are the lower leg (in women) and torso (in men). However, the location of the lesions, apart from limbs and torso, may be also face, neck and every other body part (scalp, feet, interdigital spaces, the areas around the genitals and the anus, etc.). A distinct form of this disease is e.g., subungual (nail bed) melanoma.

If a suspicious lesion is found, the next step is a visit to a dermatologist’s office equipped with a dermatoscope. An appointment with a dermatologist does not require a referral.
Dermatoscopy – the examination of skin lesions with a magnifier, a non-invasive, painless exam that lasts only a few minutes – enables doctors to identify additional features of the lesion, which allows them to determine with high probability whether the mark is just a benign lesion or a melanoma.

Remember:
- if somewhere on your body a new mark appeared that is different in colour than your skin (all shades of brown, black, steely, or red), has a worrisome shape, grows quickly, or has already reached a diameter of 6mm;
- if any of the already existing marks on your body started “behaving” differently, that is: itching, bleeding, growing, changing colour or shape, or if a crust appeared on it
immediately visit a dermatologist to undergo dermatoscopy.

Melanoma is a type of skin cancer that forms from melanocytes, which exist in the basal layer of the epidermis. Melanocytes produce melanin – the pigment that causes the skin to tan after exposure to UV radiation (the sun, solarium).

Due to external factors (e.g., solar ultraviolet radiation) or genetic predisposition (e.g., mutations of certain genes), melanocytes acquire new traits: they don’t die at the right time, they multiply uncontrollably, and, eventually, they form a tumour. This tumour grows rapidly, infiltrating and damaging the surrounding healthy tissue, and gains the ability to produce metastases – melanoma cells “break off” from the primary tumour and travel through blood and lymphatic vessels to remote areas, “settling” there and forming new tumours. This way a cancer originating in the skin begins to damage, for instance, lung, liver, or bone tissue, which causes the body to malfunction. With time, the condition of the sick person worsens, which ultimately leads to death.

Melanoma is one of the most aggressive malignant cancers. The course of the disease can be unpredictable – in contrast to many other types of cancer, even a very small primary tumour can be a source of metastases, and the stage in which the cancer spreads can be very short.
What is more, melanoma can recur even than ten years or more after the surgical treatment.
However, another characteristics of melanoma is that, because of the place in which it originates (the skin), it is possible to diagnose and treat it quickly – early diagnosis and proper removal of the lesion can successfully save the patient before the melanoma becomes life-threatening. Receiving the right treatment in the early stages of melanoma can considerably increase life expectancy and even give a chance of full recovery to 60-90% of patients.
About 20% of people with melanoma are diagnosed in the later stages, either when the cancer is locally advanced (it has affected the neighbouring lymph nodes) or when it has already spread throughout the body (it has metastasized). The chances for even 5-year survival are in such situations considerably diminished – only 5-10% of the patients with a metastasized melanoma live that long.
In Poland melanoma still is relatively rare (2400 new cases per year); however, it is a type of malignant cancer with dynamically increasing incidence rate: in Poland, it doubles every 10 years. The average age at the time of diagnosis is 50, but melanoma affects also much younger people, even as young as 20-30 year old.

It has been proven that the following factors increase the risk of melanoma:
• intensive exposure to natural (sunrays) or artificial (solaria) UV radiation;
• constant mechanical or chemical irritation of an existing lesion (e.g., repeated and long-lasting “rubbing” of the lesion with a belt buckle or a part of a bra, or using caustic substances as skin ointments – e.g., creams, salves, and other substances without the proper certificates);
• low level of skin pigmentation (people with fair complexion, particularly those with red hair and/or those with low tolerance for sunbathing);
• genetic predisposition (e.g., FAMS, the familial atypical mole syndrome);
• history of melanoma, either personal or in the family.

You can prevent melanoma by using primary and secondary preventive strategies. The primary strategies involve behaviour preventing even the occurrence of the disease; the secondary involve its early detection.

If you want to reduce the risk of melanoma:
1. don’t sunbathe;
2. avoid direct sunlight between 11 a.m. and 4 p.m.;
3. use creams and lotions with UV filters, cover your head (hats, caps), and wear sunglasses when in direct sunlight;
4. don’t use solariums!
5. once a year visit a dermatologist to have your skin inspected, especially if you:
- have fair complexion,
- get sunburnt easily or have low tolerance for sunbathing,
- have many marks on your skin,
- have family history of melanoma,
- have already had melanoma before.

Today, the diagnostic standard, that is the battery of medical tests most effective in diagnosing and treating melanoma, consists of the following:

To find and diagnose melanoma:
1. A careful inspection of the patient’s skin conducted by a general practitioner during any health exam;
2. A careful inspection of the patient’s skin conducted by a dermatologist during a routine check-up (done at least once a year) and a following examination of suspicious skin lesions with a dermatoscope.
The latter helps to identify the traits of the lesions that cannot be seen “with the naked eye,” such as:
1) asymmetrical structure,
2) atypical pigment network,
3) blue-white veil
Presence of at least two out of the three indicates that the lesion most likely is a melanoma and should be removed). Diagnostic sensitivity of dermatoscopy can reach over 93%;
3. Histopathology (microscopic examination) of a suspicious lesion that has been removed. It helps to conclusively determine whether we are dealing with a melanoma or another type of lesion (e.g., a benign mark). If the lesion turns out to be a melanoma, the histopathology report includes a description of distinctive traits of the tumour, which helps to determine the stage of the disease and plan further course of action, including the choice of the right treatment.

Before and during treatment:
1. If the doctor deems the melanoma locally advanced (the primary tumour is quite large and/or it has spread to the neighbouring lymph nodes) or if the patient reports suspicious symptoms, additional tests are ordered to determine whether the cancer has metastasized. Those tests may include one or more of the following:
- ultrasonography (an ultrasound exam) of lymph nodes (e.g., in the neck, armpit, or groin),
- a chest X-ray and/or CT scan,
- an abdominal ultrasound and/or CT or MRI scan,
- a cranial (head) CT and/or MRI scan,
- positron emission tomography (PET),
- bone scintigraphy,
- a biopsy of a lesion suspected of being metastasis (e.g., a biopsy of a swollen lymph node or a biopsy of a liver tumour),
- other tests deemed appropriate in a given situation
The results of the tests determine the selection of further treatment.
2. If the melanoma has been detected in the early stages and the patient does not report any suspicious symptoms, there is no need for additional tests, as the risk of metastases is very low.

After treatment:
For the first 2 years after the treatment for melanoma, patients should visit their attending physicians for a routine check-up every 3-4 months. During the check-up, the doctor carefully inspects the area of the scar formed after the surgical removal of the melanoma, (possibly) the lymph nodes, and the patient’s whole body to rule out possible skin metastases or a new melanoma. The doctor may also order an ultrasound of lymph nodes and an abdomen and a chest X-ray.
Other tests are prescribed only if there is a suspicion of metastatic disease.
For the following 3 years the follow-up visits should occur every 6 months, and after that, once a year.
The highest risk of a recurrence of melanoma is during the first 3 years after the treatment.

The treatment for melanoma may involve:
1. Surgery
2. Radiotherapy
3. Chemotherapy, immunotherapy, targeted drugs.

Melanoma can be fully cured only with surgical treatment, by cutting out all cancer cells from the body of the patient. Other forms of treatment are used as adjuvant therapy (to lower the risk of a relapse) or palliative care (to relieve symptoms related to the progression of the disease and/or to increase life expectancy of the patients with melanoma too advanced to cure).
Melanoma should be treated only in institutions with adequate experience in treating this type of cancer (cancer centres).

Surgical treatment consists of several stages:
1. Excisional biopsy;
2. Radical scar excision and sentinel lymph node biopsy (only in certain cases);
3. Radical lymphadenectomy (only in certain cases);
4. Metastasectomy (only in certain cases).

1. Excisional biopsy
A patient eligible for excisional biopsy is any patient on whom a dermatologist found a skin lesion bearing characteristics of melanoma (more about dermatoscopy here: What Tests Will the Doctor Order?).
The procedure is performed by a surgical oncologist. The surgeon removes the lesion with a small (only 2-3 mm) margin of the healthy tissue, then sends it for a histopathology (microscopic examination), conducted by a pathomorphologist. The wait for the results can last even up to several weeks.
The pathomorphologist performs an in-depth characterization of the tumour and gives the final diagnosis. If it is melanoma the report of the test will include the following information:
- the Breslow thickness (the thickness of the tumour measured from its surface to its deepest part, or in more medical terms, from the granular layer of the epidermis or the floor of an ulceration to the most deeply infiltrating nests of melanocytes);
- presence or absence of ulceration on the surface of the tumour;
- mitotic rate (number of mitoses per square millimetre);
- presence of regression;
- presence or absence of blood vessel or lymphatic invasion;
- presence or absence of microscopic satellite lesions (clumps of melanocytes with diameter > 0,05 mm located more than 0,3 mm from the invasive component of the primary tumour);
- margins of the healthy tissue around and under the tumour.
All this information helps determine the stage of the disease (measured according to the scale where stage 0 is melanoma in situ, i.e., not yet able to metastasize, and stages I-IV are invasive melanomas) and estimate the level of its malignancy and the risk of its recurrence and spread. The information largely influences also the choice of further treatment and the individual prognosis.
Important prognostic factors (i.e., factors affecting the prognosis for the progression of the disease and for the chances of full recovery) include the Breslow thickness, presence of a (micro)ulceration of the primary tumour, and the mitotic rate.
Undergoing an excisional biopsy usually does not involve hospitalization, and the local anaesthesia used during the procedure makes it completely painless.

2. Radical scar excision and sentinel lymph node biopsy
If the histopathology report is positive for cancer, the surgical oncologist will always widen the margins of excision, as there is a risk that parts the tumour were not removed from the healthy tissue and some cancer cells remain in the area around the biopsy wound. Depending on the Breslow thickness of the melanoma, the biopsy scar is excised with the margin of healthy tissue of 1 cm to 2 cm.
During the procedure, a sentinel lymph node biopsy will be performed in patients whose histopathology after the excision biopsy showed at least one of the following:
- the Breslow thickness of the tumour ≥ 1mm;
- (micro)ulceration on the surface of the tumour;
- mitotic rate ≥ 1 per 1 mm²,
because among these patients the risk of metastasis to the nearest lymph node through the lymphatic vessels is very high.
During a sentinel lymph node biopsy, the surgeon first uses a special dye which shows which node lymph travels to from the site of the primary tumour, and then removes that node.
The entire matter removed during both procedures (the scar with the healthy tissue margin and the sentinel node) is submitted for a histopathology, the results of which determine what, if any, further treatment is necessary.

3. Radical lymphadenectomy
If the histopathology (microscopic examination) of the sentinel node shows a metastasis, the next step is lymphadenectomy, that is, removal of the whole group of nodes the sentinel node originally belonged to (e.g. the cervical nodes on either side of the neck, axillary nodes, or inguinal nodes) – the risk that the cancer has metastasized to other nodes in the group is high. Lymphadenectomy is called radical because – as it was mentioned earlier – a full recovery is possible only by removing every single melanoma cell from the body. Otherwise, a relapse and further metastases will quickly follow.
Presence or absence of metastases in lymph nodes is the most significant prognostic factor in melanoma. The chances of full recovery of a patient with metastases in lymph nodes lessen considerably but still exist. Even in this stage, conquering the disease is still possible (but not certain!), provided that the right surgical treatment is received immediately.

4. Metastasectomy
In some cases, a single metastasis (e.g., in the lungs, brain, liver, bowel, or skin) is identified at the same time as the primary tumour. Such situations are very rare – usually there are multiple metastases and surgical treatment is impossible, as it would considerably damage the affected organ or result in haemorrhaging and, in consequence, death of the patient.
A single metastasis, if deemed operable – that is, if its removal would not kill or seriously cripple the patient because of its size and location – should be operated on. Such procedure is called metastasectomy and involves excision of the metastasis of the malignant cancer.

Thanks to this procedure some patients’ lifespans are lengthened by many years and some patients are even completely cured (unfortunately not many).
The role of radiotherapy in melanoma treatment is not significant. It is used either as adjuvant therapy in addition to the surgical treatment – e.g., irradiation of the site of lymph node excision if the cancer in the removed node infiltrated the node’s capsule – or as palliative therapy in metastasized melanoma – e.g., in cases of non-operable brain or bone metastases. However, this kind of treatment does not affect the progression of the disease much.
Chemotherapy also has small impact on melanoma – on average, it stops the progression of the disease for about 2 months.
Targeted drug therapy (BRAF inhibitor) – approx. 50% of melanomas contain a mutation in the BRAF gene. Administering BRAF inhibitor is much more effective than chemotherapy, and it considerably lengthens lifespans of some patients with non-operable lesions.
Immunotherapy (in melanoma, administering a drug containing ipilimumab) lengthens the life expectancy by several years in approx. 20% of patients with a metastasized melanoma. However, it is a very expensive treatment: in Poland, the average cost of the treatment for one patient with a metastasized melanoma is PLN 350 000 (approx. € 90 000); in Poland, it is refunded to a very limited extent.

Remember:
Melanoma can be cured only with surgical treatment. Other forms of therapy have limited effectiveness, and not all of them are easily available.
You can fully recover from melanoma if you seek help early. The chances of curing melanoma in the early stages reach up to 90%.

Active surveillance is necessary after the treatment for melanoma. The main reason for that is the high risk of a recurrence, resulting from a possibility that a microspread of the cancer occurred before or during the surgical treatment – that is, melanoma cells might have “broken away” from the primary tumour, infiltrated blood or lymph vessels, and “settled” in a neighbouring lymph node or a remote organ, such as the lungs, liver, bones, or brain; with time, they might form a new tumour there. There is also a risk that some cancer cells remained around the scar after the primary tumour biopsy, which might result in the so called local recurrence.

What is more, the risk of developing a new primary melanoma is much higher for survivors of melanoma than for those who have never suffered from it before.

The highest risk of a recurrence of melanoma is during the first 3 years after active treatment ends.

For the first 2 years after the treatment for melanoma, patients should visit their attending physicians for a routine check-up every 3-4 months. During the check-up, the doctor carefully inspects the area of the scar formed after the surgical removal of the melanoma, (possibly) the lymph nodes, and the patient’s whole body to rule out possible skin metastases or a new melanoma. The doctor may also order an ultrasound of lymph nodes and an abdomen and a chest X-ray.
Other tests are prescribed only if there is a suspicion of metastatic disease.

For the following 3 years the follow-up visits should occur every 6 months, and after that, once a year.

Scrupulous use of preventive healthcare strategies is crucial (see: How to Prevent Melanoma?).

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