from diagnosis to therapy
Basal cell carcinoma or epithelioma (also called simply basalioma) is the most frequent human cancer: it is estimated that there are 150,00 new cases per year in Italy, and 1,000,000 in the USA, which also makes it the most rapidly increasing human tumour .
Its name comes from the fact that the degenerating cells are located in the basal layer of the epidermis, and are therefore called basal cells.
Unlike other tumours, it has little or no tendency to metastasise, although this does not mean it is “benign”: it is in fact difficult to eradicate in 5-10% of cases, and tends to relapse and invade and destroy neighbouring tissues, including muscles, cartilage and bone.
Like most tumours, the best weapon available to medicine is early diagnosis and treatment.
Ninety percent of cases are caused by excessive exposure to the sun or ultraviolet (UV) lamps, and appear on the least protected ares of the skin, such as the face, the scalps of bald men, the ears, the shoulders, and the back.
The remaining 10% are due to genetic factors (the familial form) or the use of treatments with immunosuppressants (organ transplants), cortisone (chronic or autoimmune inflammatory diseases), or chemotherapeutic agents (neoplasms); X-ray treatments (radiotherapy, cobaltotherapy) also induce basal cell carcinoma or epithelioma.
People at risk
The people at risk of developing UV-induced basal cell carcinoma or epithelioma (90% of the cases) are:
· those who are markedly sensitive to UV rays, who usually have pale skin, fair hair and blue eyes, or freckles and ginger or copper-coloured hair;
· those who spend a lot of time in the open air;
· those who spend (or have spent) long periods in tropical or equatorial areas;
· those who use UV lamps to get an artificial suntan.
In order to ensure an early diagnosis and therefore effective treatment, it is important to know the alarm signals:
· the appearance of a lesion in which the skin detaches and bleeds until a scab is formed, which then falls off and reforms in continuation
· the appearance of an inflammatory plaque for no apparent reason that slowly spreads
· The formation of flesh-coloured or reddened nodule
· the appearance of a round erosion where the skin does not reform
· the appearance of an area of scar-like tissue not preceded by a trauma or cut
Dermatologists can usually diagnose a basal cell carcinoma or epithelioma simply on the basis of its appearance, but more difficult cases may require a “dermoscopic” examination.
This involves looking at the lesion through a magnifying lens and recognising the specific characteristics of the tumour.
In cases in which the clinical or dermoscopic diagnosis is unclear, a sample of the lesioned skin is taken under local anesthesia for histological examination.
The clinical forms of basal cell carcinoma or epithelioma
Basal cell carcinoma or epithelioma has many clinical forms.
The nodular form is the most frequent.
Confusion with nevi
Many, especially facial nevi, have a nodular appearance and may therefore be confused with the nodular form of basal cell carcinoma or epithelioma.
The most salient difference is that a nevus is present for many years whereas basal cell carcinoma or epithelioma have a recent onset.
|Miescher’s nevus of the face||Basal cell epithelioma|
Ulcerated basal cell epithelioma Miescher’s nevus
Ulcerated nodular form
This is an evolution of the nodular form because, with the passing of time, tumoral nodules tend to ulcerate, bleed, and form a scab.
The diagnosis should be made before reaching the ulcerated stage.
Unlike the nodular form, this may not be noticed for many years. It appears as a whitish area similar to a scar and its tumoral nature is only recognised because it is edged by small nodules that look like rosary beads.
It expands slowly and ulceration is delayed.
It is insidious not only because it is diagnosed late, but also because it is not very responsive to specific treatments.
This appears as a crusty and scaling reddish patch with well-defined margins and a slightly raised border. It usually appears on the back, also in multiple form.
Patients usually do not notice this lesion, which can therefore expand until it reaches a considerable size.
This appears as a patch with rounded borders that harden and become cicatricial. It grows slowly and is unlikely to bleed. It is not painful or itchy.
Patients are often unaware of its presence.
Basal cell carcinoma or epithelioma: treatment options
Although they rarely metastasise and are therefore relatively benign, basal cell carcinomas or epitheliomas have a surprising capacity to reform after any type of treatment.
One reason for this behaviour is that they do not have defined margins and there may be nests of tumoral cells even some distance from the identified nucleus.
Another reason is that the skin generating a basal carcinoma or epithelioma has already been sufficiently damaged to reproduce another immediately or later.
This tumour also follows the rule that the earlier it is identified and the sooner it is treated, the greater the likelihood of therapeutic success.
Surgery is still the standard reference treatment.
It is usually performed under local anesthesia and the tumour is removed radically with a part of the surrounding apparently healthy tissue.
In the case of larger tumours and those located in particular areas, removal is followed by reconstruction using skin flaps or grafts.
Surgery is expensive, and characterised by possible relapses and often unaesthetic scarring.
A basal cell carcinoma or epithelioma can be destroyed by both high and low temperatures generated by radiofrequencies, LASER, liquid nitrogen, etc.
However, thermal destruction is burdened by a number of inconveniences, such as scarring, damage to healthy tissue, the possibility of infection in the treated area, and relapses.
For these reasons, it has been replaced by more appropriate techniques.
Basal cell carcinomas or epitheliomas can also be eliminated mechanically using a cutting spoon (or curette) that separates tumoral and healthy tissue.
However, the drawbacks of mechanical destruction are unsightly scarring and the high rate of relapses.
Although possible, destruction by X-rays has now been abandoned because of the danger of damaging healthy cells and thus provoking the onset of a new, radiation-induced tumour.
Treatment with topical drugs
Basal cell carcinomas or epitheliomas have been treated using a cream containing 5-fuorouracil (5-FU), a chemotherapeutic agent that blocks cell reduplication, but frequent relapses and difficulties in managing the drug have limited its use.
Imiquimod, an immunomodulatory drug, has also been used in a cream formulation, but its use has been limited by the fact that it causes skin irritation, requires long healing times, leads to frequent relapses, and is expensive.
Photodynamic therapy (PDT) was first used at the beginning of the 1900s when it was realised that the application of products excitable by light followed by exposure to sunlight was capable of destroying skin tumours.
This is due to the then unknown photodynamic phenomenon.
Photodynamic phemonenon (PP)
The PP is due to the fact that many natural and synthetic compounds can be excited by light energy (photons).
A compound molecularly excited by light tends to return to its ground state immediately and, when doing so, releases energy.
In its turn, the released energy is capable of creating unstable forms of oxygen known as oxygen radicals or reactive oxygen species (ROS).
ROS react immediately by oxidising lipids and proteins.
Cells are particularly sensitive to the development of ROS and suffer often irreversible damage that leads to their death.
Unlike other methods that use toxic drugs or destructive radiation (X-rays, UV) to kill cells, PDT works naturally by exploiting cell components without damaging the DNA contained within the cell nucleus.
The vital cell components are in fact oxidised outside the nucleus.
The photosensitiser is the cardinal element of PDT.
Many natural and synthetic compounds can be considered photosensitising: i.e. capable of developing ROS once illuminated.
The most widely used photosensitiser in dermatology is aminolevulinic acid (5-ALA or simply ALA).
Aminolevulinic acid is the first compound in the synthesis of porphyrins, which lead to hemoglobulin, the protein present in red blood cells that transports oxygen to the tissues.
Inside the cell mitochondria, 5-ALA leads to the synthesis of protoporphyrin IX, the precursor of hemoglobin.
The molecule is highly unstable and, if illuminated by a light of the appropriate wavelength, becomes excited and generates energy.
The energy generated inside the cell causes the formation of unstable ROS. These immediately oxidise lipids and proteins, thus blocking the functions of the cell and leading to apoptosis.
The selectively of ALA for tumoral cells
All cells have the enzymes necessary to transform ALA into protoporphyin IX, but the fact that epithelioma cells are in a state of accelerated reduplication means that they synthesise much more protoporphyrin IX than normal cells and so, when the light is applied, it is these tumoral cells that suffer the greatest damage.
The safety of the photodynamic phenomenon
The cell destruction induced by the PP simulates cell death due to oxidation as a result of natural aging. This means that, unlike in the case of X-rays, UV light or chemotherapy, etc., there is no possibility of damaging the genetic inheritance contained in the cell’s DNA.
It is possible that the PP does not manage to destroy all of the tumoral cells and so the tumour may relapse, but it does not give rise to any greater damage.
Photodynamic therapy is therefore considered extremely safe.
Light sources and red light
In order to obtain the PP, it is necessary to excite protoporphyrin IX using a light with a particular wavelength.
The chosen wavelength is 630 nanometres (nm), which is within the range of visible red light. There are two reasons for this choice: the peak absorption of protoporphyrin IX is at 630 nm
and, as shown in the figure below, red light has the greatest skin penetrance.
It is not necessary to use the light produced by a LASER beam in order to excite protoporphyrin IX. A LASER us used when it is wanted to exploit heat in order to cut or destroy tissue, whereas the PP is a photochemical process that takes place without heat and so it is sufficient to have a source of intense but cold light.
LED lamps are currently used because the light emission is constant, they do not develop heat, they last a long time, and they are not too expensive.
A LED S.630 light source (Alpha Strumenti)
Photodynamic therapy (PDT): treatment protocol for basal cell carcinoma or epithelioma
The protocol for the ALA-PDT of basal cell carcinoma or epithelioma has many variants depending on the type of tumour and its site, the type of skin, and the duration of the lesion, etc.
The most common variables are the time of exposure to ALA and the number of PDT sessions.
1 Examination, photographicdocumentation, additionalinvestigations
2 Presentation of an information sheet in order to obtain the patient’s informed consent
3 Preparation of the lesion for PDT when necessary
4 Application of 10% ALA in an appropriate vehicle
5 Occlusion of the treated part by means of polyethylene film (or something similar) in order to favour the penetration of the product
6 The treated part is covered to prevent the penetration of light
7 A wait of 4-18 hours for the development of protoporphyrin IX depending on the indication
8 Subsequentremoval of the dressing
9 Observation of fluorescence using Wood’s light as an index of the development of protoporphyrin IX
10 Exposure of the ALA-treated area to infra-red light until the fluorescence disappears (about 10 minutes, depending on the light source)
11 In the case of the onset of intense pain, temporary discontinuation of the illumination and cooling of the treated area with vaporised water (fan with water spray, water in pressurised spray can)
12 At the end of the period of red light exposure, check the disappearance of fluorescence using Wood’s light
13 If fluorescence is still present, extend the time of illumination
14 At the end of the procedure, medicate the treated area with PEG ointment and cover with gauze
15 At home, continue medication with PEG ointment once a day for one week
16 After 15 days, second PDT session following the same procedure as above
17 Clinical check-ups should be arranged for the third, sixth and twelfth month.
18 If a relapse occurs, further PDT sessions or an alternative treatment can be planned
The results that can be obtained using ALA-PDT to treat basal cell carcinoma or epithelioma
According to the data in the international literature, the rate of cure of basal cell carcinoma or epithelioma using ALA-PDT is similar to that obtained by means of traditional surgery, and better than that which can be obtained using destructive methods (LASER, cryotherapy, radiotherapy, etc.).
The advantages of ALA-PDT are:
1 No scarring and a better aesthetic result
2 No needforanesthesia
3 No damage to the tissues surrounding the lesion
4 The possibility of treating more than one lesion at a time
5 The possibility of treating lesions that are extensive or otherwise unsuitable for surgery
6 The possibility of treating subjects for whom surgery is contraindicated
For these reasons, ALA-PDT is considered the first-choice treatment for basal cell carcinoma or epithelioma, and should be proposed to patients affected by such skin tumours.
Examples of treatment with PDT