Border intradermal nevus

Intraepidermal, or borderline nevus is one of the many varieties of nevus, which has its own distinct characteristics and features. This neoplasm is small, but quite dangerous: it has a tendency to overgrow and malignancy. Because of this, dermatologists rank the borderline nevus as melanoma-dangerous growths.

Epidemiology

Borderline nevi are common: in about 30% of cases among all such neoplasms. Sometimes they appear in the form of multiple elements, but more often are located singly. The size of one growth does not exceed ten millimeters. Epidermal nevi are characterized by a prevalence of about one in 1000 live births and equally affect men and women. [1],  [2]It is estimated that a third of people with epidermal nevi involving other organ systems; therefore, this condition is considered epidermal nevus syndrome (ENS), and it has been reported that up to 10% of people with epidermal nevus can develop additional symptoms of the syndrome. This syndrome usually manifests itself at birth (due to skin lesions that are most often seen in the middle of the face from the forehead down to the nose) and is often associated with seizures, mental disability, eye problems, bone defects and atrophy of the brain.[3]

A neoplasm can appear at any age, although it is most often found in patients aged 14-25. [4]

Borderline nevus most often occurs:

• for people who often sunbathe, visit a solarium, or work in the open air;
• in people who are forced to regularly contact with chemical solutions and substances;
• in patients suffering from endocrine diseases, or those undergoing treatment with hormonal drugs.

Causes of the border nevus

Scientists are sure that the borderline nevus is "outlined" in the course of fetal development. The cells of the future neoplasm are the precursors of healthy melanocytes, which, nevertheless, linger in the deeper layers of the dermis and form in the form of clusters. Under the influence of certain factors, such cells begin to produce pigments, which we notice on the skin as moles.

A significant role in the appearance of borderline nevi is played by sunlight. They can be safely called the main activators of nevus cells that accumulate in the layers of the dermis. With a sufficient dose of solar radiation, these structures begin to accelerate the production of melanin, which is found on the skin, like a well-known mole.

In addition, altered hormonal activity can become a stimulating moment. For example, in pregnant women, adolescents, or during therapy with hormonal drugs, the number of nevi on the body increases, and existing borderline nevi can grow or change their configuration.

Risk factors

Almost all scientists support the theory of the innate nature of the borderline nevus. Even despite the fact that the growth can appear ten or twenty years after the birth of a person. The fact that the nevus sooner or later still reveals itself can be associated with the action of certain factors:

• hormonal changes - for example, with the onset of pregnancy, menopause, lactation period, against the background of hormone therapy, etc.;
• abuse of tanning - both in the sun and in the solarium;
• genetic disorders accompanied by abnormal development of melanoblasts;
• dermatitis and other dermatological diseases (acne, eczema, etc.);
• damage and injury to the skin;
• viral infections.

In addition, people who work or have regular contact with chemicals and other toxic substances are at risk.

Pathogenesis

Borderline nevus is initially formed from melanocytes, which begin their development at the prenatal stage. The neoplasm is formed from nerve fibers. Normally, each cell structure has its own tubule for excretion of the pigment substance, but there are no such tubules in the altered cells. Therefore, melanin does not go out, but accumulates in a limited area, which explains the formation of dark spots. Genetic and clinical mosaicism is described. [5]  It was found that germline mutations in the FGFR3 gene are the etiology of congenital epidermal nevus. [6]

Border nevus is formed at the boundaries of the upper and middle skin layers, bypassing the basal layer. Most often they talk about the congenital nature of the growth, although it can appear in adolescents, and even at 20 or 30 years old.

According to the degree of danger of malignant degeneration, the borderline nevus is put on a par with Ota nevus, Dubreuil melanosis, and giant pigmented nevus. [7]

Symptoms of the border nevus

The most common lesion was the head and neck, and 13% of the patients had widespread lesions. [8]The borderline nevus looks like a flat nodular formation with a gray, black, brownish tint. The size of the nevus varies from a couple of millimeters to one centimeter, although some experts say about large-sized spots.

On top of the neoplasm is smooth, dry, sometimes a little uneven. The main distinguishing point: hair on the borderline nevus never sprouts, although the growth can be located almost anywhere on the body, and even on the feet or palms.

The neoplasm is more often single, but multiple arrangement also occurs.

The first signs of degeneration of the borderline nevus are a change in the color shade and / or its size, the formation of cracks, sores, tubercles on its surface, the appearance of redness, the disappearance of clarity of outlines. These symptoms indicate the need to urgently visit a dermatologist.

Stages

The degeneration of the borderline nevus into a malignant tumor usually goes through several stages:

1. The initial stage of development, without metastases. The duration of the stage varies from 12 months to five years. The chances of cure are up to 99%.
2. The nevus becomes convex up to about 4 mm. Malignant transformation into a dysplastic process is observed within a few months. The chances of cure are up to 80%.
3. Within 1-3 months, metastases begin to spread, which are found in the lymphatic system, brain, internal organs. The nevus itself is ulcerated. The chances of a cure are no more than 50%.
4. Aggressive stage, which ends within a few weeks - in 85% of cases, the patient dies.

Forms

Specialists distinguish between potentially dangerous and safe borderline nevi, according to the degree of probability of their transformation into malignant melanoma. In addition, other types of neoplasms are isolated. [9], [10]

• Acquired borderline nevus is a neoplasm that was discovered not from the moment of birth, but somewhat later - for example, after a couple of years, or even in adulthood. True, doctors say that this does not mean at all that the nevus was not laid yet in utero. Just a combination of some factors contributed to the later manifestation of the growth.
• Border pigmented nevus is a pigmented nodular formation, with sizes up to 10 mm, with any location on the body. A variety of such neoplasms is considered to be a cockade nevus - a growth with enhanced pigmentation along the peripheral border, which gives it a ring-shaped appearance. Both pigmented and cockard nevus are melanoparous elements.
• Melanocytic borderline nevus is a neoplasm provoked by excessive reproduction of epidermal melanoblasts, which, in turn, is caused by a malfunction of gene regulation. Initially, a borderline nevus forms in the epidermis. After a while, part of the melanocytes are transported to the dermis, and another part remains in the epidermal layer: this is how a complex melanocytic nevus is formed. [11], [12]
• Nevus with borderline activity is characterized by prevailing intradermal structures. In this case, border activity refers to the proliferation of melanocytes, which can be focal or widespread.
• Border dysplastic nevus is a pigmented mole of a borderline location, of irregular ovoid shape, with fuzzy contours and uneven pigmentation (the central part has one color and the edges have a different color). Such a neoplasm is often classified as a clinical marker of an increased risk of melanoma formation. [13]

Complications and consequences

The most undesirable and unfavorable complication of borderline nevus is its transformation into a malignant tumor -  melanoma . Such a transformation does not occur “out of the blue”: this requires the influence of certain factors that create the necessary conditions for rebirth. For example, the risk of malignancy is significantly increased if the nevus is regularly exposed to tanning or injuring. [14]

To avoid complications, doctors advise removal of borderline nevi, even if they do not bother or modify. Transformation into melanoma, melanoblastoma, skin cancer is difficult to treat and often leads to the death of the patient. Particularly attentive should be people with fair skin, blond or red hair, as well as those who have a large number of various moles on their body, including borderline nevus.

Relapse of borderline nevus

In approximately 80% of patients, borderline nevus can reoccur after laser or destructive removal of the nevus. The growth develops in the same or in another place. Some patients have to get rid of the obsessive nevus several times.

Doctors note: the most radical method of removal is the surgical method, when the neoplasm is excised together with the surrounding healthy tissue, the volume of which depends on the shape of the nevus. The larger the growth, the more it is prone to re-development. If a person has already had relapses, then he should pay special attention to the prevention of complications:

• Stay less in the sun, especially during active hours (from 11-00 to 16-00);
• eat quality food rich in vitamins and minerals;
• give up bad habits, lead a healthy lifestyle;
• try to wear high-quality natural clothing, not to injure the skin, even if there are no nevuses and birthmarks on it.

Diagnostics of the border nevus

Diagnosis of borderline nevus begins with a medical history, with an external examination and dermatoscopy. Histology is performed only after removal of the neoplasm, but not earlier than this moment. Histopathological changes associated with the aging of melanocytic nevi, such as fatty degeneration, fibrosis and neural changes, are found in lobed intradermal nevus. [15] The fact is that the process of taking material (biopsy) is also a damaging factor that can cause subsequent malignant transformation of the growth. [16] 

Blood tests include the following research options:

• blood test for coagulation quality;
• blood for tumor markers;
• blood test for LDH (lactate dehydrogenase).

Instrumental diagnostics, first of all, consists in conducting dermatoscopy - this is a method that helps to consider changes inside the skin that are inaccessible to the naked eye. Additionally, the doctor can prescribe an ultrasound scan of the nearest lymph nodes, chest x-ray, osteosyntigraphy to exclude malignant processes in the body.

Differential diagnosis

Differential diagnosis should be carried out with other forms of hyperpigmentation - and first of all, with chloasma that looks like a mole, or with hemangioma . But it is more important to pay attention to the degeneration of the borderline nevus into malignant melanoma in a timely manner. The tumor process sometimes develops almost imperceptibly, against the background of a slight dysplastic syndrome: the contours of the spot expand slightly, the surface becomes tuberous, and the adjacent healthy skin turns red. Since degeneration often occurs after a mechanical injury to the skin, it is important to regularly examine growths that form on the plantar and palmar surfaces of the limbs, between the fingers and near the nail plates. In such places, it is recommended to remove moles, regardless of their type and degree of danger.

Treatment of the border nevus

After the diagnosis, the doctor will consider all possible treatment options, although the conservative method is usually not discussed: the border nevus is removed in one of the following ways:

• Cryodestruction is a procedure for freezing a growth with liquid nitrogen (less commonly with carbonic acid or ice). [17]
• Electrocoagulation is a method that involves the destruction of the neoplasm with the help of high temperature, provoked by the action of a directed current. [18]
• Laser removal is one of the most popular methods in which the affected tissue is "vaporized" by a directed laser beam.
• Radiosurgical procedure - involves the excision of the growth of a certain length of radio waves, using a Surgitron hardware device.

Medicines can be recommended only at the stage of recovery after removal of the border nevus.

Physiotherapeutic treatment consists of the following procedures:

• UHF coagulation - involves the use of an electrode with a high-frequency current supply of 27.12 MHz and a power of 1 mA. At the end of the procedure, the coagulation section is treated with a 5% solution of potassium permanganate. [19]
• Laser thermocoagulation - is carried out using continuous and pulsed optical irradiation of the infrared range, with a maximum power of 3-5 W and a diameter of the focused beam of 0.25-0.5 mm, with a radiated power of 10-15 watts. [20],  [21], [22]

Medications Your Doctor May Prescribe

To speed up the healing process after removal of the borderline nevus, the doctor may recommend the use of such drugs:

• vitamin products to improve plastic metabolism (folic acid, B vitamins, ascorbic acid, tocopherol);
• non-steroidal anabolic agents (Riboxin, potassium orotate, methyluracil);
• biogenic stimulants (aloe extract, FiBS, Plazmol);
• immunomodulatory agents (Timalin, Pyrogenal, Levamisole);
• non-specific regenerating agents (sea buckthorn oil, Apilak, Rumalon, Actovegin).

Examples of the use of these medicines are highlighted in the following table:

Methyluracil	Adult patients are prescribed one tablet 4 times a day, for a month. Treatment may be accompanied by headache, heartburn, allergic reactions.
Aloe extract	1 ml is injected subcutaneously daily for several weeks. Possible side effects: dyspepsia, changes in blood pressure, allergies, dizziness, itching.
Thymalin	Intramuscularly administered with saline, 5-20 mg daily. The course of treatment is from three to ten days. Side effects may be limited by local reaction in the injection zone.
Actovegin	Take 1-2 tablets three times a day, for 4-6 weeks. The medicine is well tolerated, rarely allergies, fever.
Vitamin E	The dose of the drug is selected individually, not exceeding the daily amount of 1000 mg. Possible side effects include nausea, headache, fatigue, and allergies.

Alternative treatment

There are many alternative recipes that suggest effects on birthmarks and nevi. Most of them do not approve of doctors - especially when it comes to melanoma-dangerous neoplasms, which include borderline nevus. In relation to them, it is better to apply a radical removal, turning to the surgeon for help.

However, many patients try to get rid of moles in the following ways:

• Flaxseed oil and flower honey are mixed in equal parts. The mixture is rubbed into the nevus three times a day, daily.
• Wipe the growth with fresh pineapple juice, several times a day.
• A drop of onion juice or apple cider vinegar is dripped on a nevus daily.
• A mole is lubricated with lemon and garlic juice.
• Pound into powder 100 g of seeds from cherry, pour 500 ml of any vegetable oil, kept in the refrigerator for a couple of weeks. The oil obtained is used daily for application to the nevi: it is left on the outgrowth for about twenty minutes, after which it is washed off with water.

You should not rely on alternative methods if the borderline nevus has begun to show at least one sign of malignant degeneration - for example, it has begun to increase, change shape or color, become vague, swollen, etc. It is always better and safer to consult a doctor in advance.

Surgery

The choice for the treatment of small epidermal nevuses is surgical excision. 

Surgical excision, dermabrasion, cryosurgery, electrosurgery and laser surgery were used to treat epidermal nevi. [23],  [24],  [25] Dermabrasion, if the surface is associated with a high relapse rate and deep dermabrasion can lead to scarring thickened. Cryosurgery has similar risk limitations, including slow healing, infection, edema, and usually abnormal skin staining. Doctors have been laser-treating epidermal nevuses for decades. Recent advances in laser technology have enhanced the simplicity, accuracy and safety of such procedures. Several reliable and effective treatments have been developed for the treatment of epidermal nevuses using CO 2, long-pulse Nd: YAG and 585 nm pulsed dye lasers. However, relapses can occur months or years after removal of the epidermal nevi by any method. [26],  [27],  [28], [29]

Surgery is a long-standing and most effective way to get rid of all sorts of moles and warts, including borderline nevus. Preparation for the intervention is simple and short. The skin is treated with a special antiseptic, local anesthesia is performed. When the anesthesia works, the surgeon excises the nevus with a scalpel, capturing a bit of healthy surrounding tissue - for a more complete and one hundred percent removal of the growth.

Surgical treatment has its advantages:

• relapse of borderline nevus is excluded;
• the neoplasm can be sent for histology;
• the intervention is performed in outpatient settings, there is no need to go to hospital.

The operation is not without its drawbacks, for example:

• the seam heals a little longer than with other methods of removal - up to about one month;
• with improper care, there is a danger of suppuration;
• formation of an unaesthetic scar is possible.

However, with large nevuses, doctors insist on surgery. This is the surest way to get rid of the problem forever, to prevent malignancy and relapse of the tumor.

Prevention

It is almost impossible to prevent the formation of borderline nevus. However, patients prone to the appearance of moles should be vigilant and carefully examine their body for alterations and malignant transformation of pigmented neoplasms.

For preventive purposes, you must adhere to the following recommendations:

• prevent damage to the skin, and, in particular, any nevi;
• avoid prolonged exposure to sunlight, do not go to the solarium, do not allow sunburn;
• when working with chemicals and toxic substances, wear protective gloves;
• temper, strengthen the immune system, eat quality and fully.

If the borderline nevus is damaged for any reason, you should seek medical help from a dermatologist or oncologist. He will examine the growth and decide on the need to remove it.

Forecast

Doctors advise not to forget that the borderline nevus is able to degenerate into a malignant neoplasm, regardless of age. Therefore, you should always be careful and plan to inspect moles and spots at the dermatologist or oncologist, at least 1-2 times a year. If suspicious symptoms are detected, the growth is better to remove, not expecting further unfavorable development of the process.

Borderline nevus is a melanoma-dangerous pathology. But this does not mean that the transformation will be necessary: most patients live with such formations, and sometimes they are not even aware of their potential danger. Therefore, there is no need to panic. The main thing is to regularly examine the skin, pay attention to all available nevi, and record any changes on their part.