Nodular melanoma is one of the most aggressive types of skin cancer. It accounts for approximately 15-20% of all diagnosed melanoma cases. Nodular melanoma grows rapidly and infiltrates deep parts of the skin. It often metastasizes to other organs. The prognosis depends on the degree of malignancy of this type of neoplasm. What causes nodular melanoma and how can it be treated?
Nodular melanomadevelops from already existing pigmented lesions or from scratch from he althy skin. The lesion is most often visible as a dark, raised mark on the neck, face, legs or other parts of the body often exposed to sunlight. Despite the relatively rare occurrence, nearly half of all deaths in melanoma are cases of the nodular variant.
Types of melanoma
Melanomas are malignant neoplasms that originate from skin pigment cells, i.e. melanocytes. They are located under the squamous epithelium layer in the basal layer of the skin.
It is these cells that produce melanin, the pigment that gives our skin color, which acts as a natural filter when sunbathing. As a result of long-term exposure to UV radiation, the physiological repair systems of melanocytes may be damaged and transformed into a cancer cell.
When classifying neoplasm according to the way it grows, there are 4 basic types of melanoma:
Superficial spreading melanoma (SSM)
The most common type, mainly in young people. Superficial spreading melanomaaccounts for 70% of all melanomas .
As the name suggests, this tumor grows within the superficial layer of the skin, penetrating deeper only at an advanced stage. Usually, it begins with pigmented lesions, popular irregularly shaped birthmarks.
Their color can vary and ranges from brown, red to blue. The development of this type of neoplastic lesion is often slow and takes many months or even years.
Lentigo maligna melanoma (LMM)
This type of melanoma most often affects the elderly(mainly in women over 70). Similar to superficial spreading lesions, it appears in the form of a beige or brownish spot.
It is most often associated with prolonged exposure to the sun, almost always on the face, ears or upper body. The nature of these types of changes is mild and their growth is very slow.
Acral melanoma (ALM)
The melanoma variant most commonly diagnosed in African Americans and Eastern peopleis rare in white people (only 5% of melanoma cases). It derives from the lentil blotch and also develops in the superficial layers of the skin.
Usually located on the soles of the feet and palms, as irregular moles with ulcerative surfaces. A special, rare subtype is the so-called subungual melanoma.
Acral melanoma generally progresses faster than the above two types (SSM, LMM) and may metastasize.
Nodular melanoma NM
A type of cancer that occurs at all ages and races . It develops from already existing pigmentary changes or from scratch from he althy skin.
This type of melanoma, unlike those mentioned above, grows deep into the skin layers from the very beginning (shows the so-called vertical growth), therefore it can often metastasize to the surrounding lymph nodes, and over time to more distant organs (such as lungs, liver, bones).
Practically at the time of diagnosis, it is a very dangerous invasive lesion with a very quick course (from a few months to about 2 years).
Nodular melanoma - causes
Although there is no single cause of skin cancer development - melanoma, there are risk factors associated with the likelihood of developing this disease in the future.
The main "culprit" of skin lesions, including nodular melanoma, is undoubtedly ultraviolet radiation(UVA and UVB), from both sunbathing and sunbathing in solarium.
This radiation causes:
- direct DNA strand breakage in cells,
- disturbance of repair processes
- and the formation of harmful mutations, often leading to the activation of neoplastic pathways.
As a curiosity, it is possible to quote the fact that in Australians living in a hot climate, skin cancer is detected up to 100 times more often than in Europeans!
Reluctance to use sunscreen may be an indirect reason whynodular melanoma is diagnosed twice as often in men.
This neoplasm is most often located around the neck, upper back and ears, i.e. parts of the body that are often and involuntarily exposed to the sun.
Other risk factors are also:
- light skin tone (red hair / freckles)
- light eye color
- family history of melanoma
- occurrence of numerous birthmarks
- permanent irritation of existing moles, chemically or mechanically (e.g. by cosmetic procedures).
Nodular melanoma - symptoms
The nodular variant of melanoma is diagnosed in patients of almost all ages, but most cases are reported between the ages of 40 and 60.
Symptoms are conditioned by the genesis of the tumor, where there are two types:
- The mark reappears (de novo)- the change is visible on the previously he althy part of the skin. Its edge may be irregular or not sharp, the color is patchy, the epidermis may be very thin, flaky or have a tendency to ulcerate. This form accounts for the overwhelming majority of nodular melanomas.
- The disease develops on a pre-existing nevus- so far not showing any disturbing symptoms, a pigmented nevus may thicken and increase in diameter. There may also be a change in color, shape, bleeding and itching.
Usuallynodular melanoma appears as dark nevus 1 to 2 cm in diameter , most often located on:
- face,
- nape,
- upper back,
- legs.
Sometimes these tumors can grow in size quickly. However, the most dangerous invasive changes will progress into the layers of the skin, making the progression of melanoma invisible to the naked eye.
Although nodular melanomas appear mostly dark, heavily pigmented, there are also lighter, beige, multicolored, or even colorless lesions (such as in the rare, malignant form of pigmentless melanoma).
Therefore, the observation of color is only one of the features that should be taken into account when verifying and diagnosing suspicious birthmarks.
Nodular melanoma - diagnosis
The patient's medical history should include the following information:
- about changes appearing on the skin,
- disturbing birthmarks,
- sunburn
- or using the solarium.
In initial diagnosticsskin lesions, sometimes dermatoscopy or videodermatoscopy are used.
The next step will be to compare the clinical picture of the suspicious lesion based on 2 specialized scales -ABCD system(for early lesions) andBreslow's scale(for locally advanced changes).
Unfortunately,the basis for the diagnosis of nodular melanoma is only a biopsyexcising the entire pigmented lesion and subjecting it to histopathological analysis.
Examination of the material should also include the collection of necessary clinical information (the so-called microstage I), including:
- thickness of the change in mm (according to the Breslow scale),
- presence or absence of epidermis,
- degree of infiltration of the deeper layers of the skin (according to Clark's scale),
- histological subtype,
- notch margin width,
- presence of a pigmented nevus,
- number of mitoses per 1 mm2 (for vertical growth),
- presence of vascular and nerve invasions,
- presence of a lymphocytic infiltrate.
The Clark's Scale , important in the pathomorphological assessment of nodular melanoma, is a five-step classification system for the growth of the neoplastic lesion into the skin:
- I ° - tumor confined to the epidermis,
- II ° - the tumor invades the papillary layer of the skin,
- III ° - the tumor reaches the reticular layer of the skin, but does not infiltrate it,
- IV ° - the tumor invades the reticular layer,
- V ° - the tumor invades the subcutaneous tissue.
Since nodular melanoma is a lesion with a high metastatic potential, the so-called sentinel node, i.e. the lymph node which is most often the first site of the probable tumor metastasis.
For this purpose, dye-isotope analysis is performed during the so-called lymphoscintigraphy, or node biopsy.
Additionally, the tests performed during the diagnosis of melanomas are:
- blood tests:
- morphology,
- liver tests,
- activity of the enzyme LDH (lactate dehydrogenase),
- Chest X-ray
- and ultrasound of the abdominal cavity.
Nodular melanoma - treatment
Treatment of nodular melanoma depends primarily on the clinical and pathological stage of the neoplasm. Generally, it consists in a radical excision of the lesion, together with a skin margin of approximately 1 cm (for neoplasms up to 2 mm thick).
If the thickness of the infiltration is greater, a wider margin of he althy skin is also used, often with a fascia underneath it.
If within a nodesentinel after a histopathological examination, tumor metastases will be detected, it will probably be necessary to perform the so-called radical lymphadectomy, i.e. surgical removal of all local lymph nodes.
Sometimes, when surgery could not be complete, or when bone metastases occur, radiation therapy is introduced as an adjuvant treatment.
On the other hand, chemotherapy in the treatment of malignant melanoma is not very effective (only about 20% of patients show a positive response to treatment) and therefore - rarely used.
The greatest hope in the treatment of nodular melanoma is the so-called targeted therapies. They work by blocking mutations and metabolic pathways that are characteristic of cancer cells.
One of the most significant "places" in the genome of malignant melanomas is the somatic mutation of the BRAF gene, which occurs in over half of patients.
This mutation causes increased reactivity of the MAPK pathway associated with uncontrolled cell division, cell differentiation and overall tumor growth.
"Targeted" drugs aimed specifically at blocking the action of the mutant BRAF protein include :
- vemurafenib,
- dabrafenib
- and trametnib.
These drugs have been approved for the treatment of patients with advanced, most often metastatic skin melanomas with the BRAF mutation.
Nodular melanoma - prognosis
The prognosis in nodular melanoma depends on the degree of malignancy and the depth of infiltration of individual layers of the skin.
It is assumed that in the early stages, when the lesion reaches a thickness of 1 mm, the cure rate of patients is high, approximately 90-100%.
In neoplasms classified as stage IV and V according to Clark's scale, i.e. where there are frequent lymph node metastases, the 5-year survival period of patients is estimated at about 40 to 70%.