Freckles (Ephelides)
These spots, seen mostly on the cheeks, forehead and chin, may be light or darker brown. They generally increase in sunny seasons and decrease in seasons without sun.
At an early age they are called solar lentigines, while those that form in later life are called senile lentigines. Their size ranges from 2 to 20 cm, and their colour can vary from light brown to black. Lentigines can sometimes occur together with certain systemic diseases or may be a harbinger of disease.
Labial Melanotic Macule
It is often seen as brown macules on the lower lip. It is particularly common in young women. It resembles freckles but does not darken in the sun. It does not turn into cancer.
Benign Melanocytic Naevi
Benign melanocytic naevi first become noticeable at an average of one year after birth. They enlarge slowly and symmetrically over time, and their number peaks in the second and third decades of life. Naevi regress with advancing age and also disappear in the seventh and eighth decades.
Important aetiological factors involved in naevus development include genetics, age, skin type, sun and ultraviolet rays, hormones and immunosuppression. Recent studies support the view that the main environmental risk factor for the development of melanocytic naevi is exposure to sunlight. The amount of exposure to sunlight in the first two years of life in particular is important in the development of melanocytic naevi. The amount and intensity of sunlight to which children are exposed increases the incidence of acquired melanocytic naevi. An increase in the number of benign melanocytic naevi has been shown in people with fair skin, Fitzpatrick skin types I and II, those with freckles, those with light hair and eye colour, and with intense sun exposure. Intermittent sun exposure is more important than chronic long-term exposure, and it has even been reported that fewer melanocytic naevi are found in people who live under constant sunlight. Genetic characteristics also play an important role in naevus development. Increased naevus density and total naevus count have been found in twin studies and in family members of people with cutaneous malignant melanoma.
Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that causes benign hamartomatous polyposis in the gastrointestinal tract and mucocutaneous pigmentation. Although the polyps are most often seen in the jejunum and ileum, the duodenum, stomach and colon can also be involved. Malignant degeneration can rarely be observed in the polypoid lesions. Extraintestinal malignancies of the ovary, uterus, testis, lung, breast and pancreas may be seen.
Carney Complex
Spotty skin pigmentation; myxomas (benign (non-cancerous) connective tissue tumours); and benign or cancerous tumours (meaning they can spread to other parts of the body) of the endocrine (hormone-producing) glands.
Tumours can be benign or cancerous. A benign tumour can grow, but this does not mean it will spread. A cancerous tumour is malignant, meaning the cancer can grow and spread to other parts of the body.
Symptoms of Carney complex usually develop early, before the age of 20. Skin pigmentation and the heart tumour myxoma or other heart problems are usually the first signs of the condition.
Spotty skin pigmentation is found on the lips, the inner and outer corners of the eyes, the conjunctiva of the eye and around the genital area. Other common features of Carney complex are Cushing's syndrome and multiple thyroid nodules (tumours). The features of Cushing's syndrome are a combination of weight gain, high blood pressure, diabetes and easy bruising (caused by excess cortisol hormone). Although people with Carney complex have a high risk of cancer, most tumours are benign.
Carney complex is also referred to as:
- NAME syndrome: Naevi (meaning birthmarks or moles), Atrial myxoma, Myxoid neurofibroma and Ephelides (freckles).
- LAMB syndrome: Lentigines (age spots), Atrial myxoma and Blue naevi.
Causes of Carney Complex
Carney complex is a genetic disease. This means that the risk of developing cancer and the other features of Carney complex can be passed from generation to generation through gene mutations (changes) in a family. In particular, researchers have recently learned that the PRKAR1A gene, through its involvement with protein kinase A (PKA), which regulates the body's cell signalling, is associated with Carney complex. Researchers believe that more than 60% of people with Carney complex have a mutation in the PRKAR1A gene and over 6% have a deletion in this gene. To date, a total of 125 different PRKAR1A mutations have been found. Most of the mutations have been identified only in single families, i.e. they are unique. So far, no strong association has been seen between a particular type of mutation and certain symptoms of Carney complex or cancer.
People without a PRKAR1A mutation typically begin to show mild symptoms later in life. These people less often have other family members affected by Carney complex. In such a person, the gene mutation is considered to have occurred by chance, i.e. sporadically.
Recently, mutations in the PRKACB gene were found in a single patient with Carney complex. In addition, no other symptoms of Carney complex were found in children with Cushing's syndrome. Mutations in the PDE11A and PDE8B genes have also been found in young people with Cushing's syndrome. However, their connection with Carney complex remains questionable. Studies searching for other genes that may be associated with Carney complex are ongoing.
How Is Carney Complex Inherited?
Normally, each cell has two copies of each gene: one inherited from the mother and one from the father. Carney complex follows an autosomal dominant inheritance pattern if the mutation occurs in only one copy of a gene. This means that a parent with a gene mutation can pass on either a copy of the normal gene or a copy of the mutated gene. Therefore, a child with a parent who has the mutation has a 50% chance of inheriting it. The siblings or parents of an individual with the mutation also have a 50% chance of having the same mutation.
If one partner in a couple knows that they carry a gene mutation that increases the risk of this hereditary cancer syndrome, there are options for the couple if they wish to have children. Preimplantation genetic diagnosis (PGD) is a medical procedure performed together with in vitro fertilisation (IVF). It allows people who carry a specific known genetic mutation to have children who do not have the mutation. The woman's eggs are removed and fertilised in a laboratory. When the embryo reaches a certain size, a cell is removed and tested for the genetic disease in question. The parents can then choose to transfer an embryo if there is no mutation. PGD has been used for more than a decade and has recently been used for many hereditary cancer predisposition syndromes. However, financial, physical and emotional factors should be considered before starting this complex procedure. For more information, you can talk to IVF clinics.
How Common Is Carney Complex?
Carney complex is very rare. About 500 cases have been reported worldwide. The remaining 25% to 40% of cases appear to be sporadic and may be due to de novo causes, i.e. a new gene mutation.
How Is Carney Complex Diagnosed?
Carney complex is diagnosed if an individual has at least two of the 12 major features listed below. If a close family member – mother, father, sibling or child – has already been diagnosed with Carney complex, a person is considered to be affected if they have at least one of the following features.
Major diagnostic features of Carney complex:
- Spotty skin pigmentation with a specific pattern and location
- Myxoma (benign tumours)
- Cardiac myxoma (heart tumour)
- Myxomatosis of the breast
- Ductal adenomas of the breast
- Primary pigmented nodular adrenocortical disease (PPNAD) or an abnormal result on a urine test for Cushing's syndrome (Liddle test)
- Acromegaly: increase in the size of the face, hands and feet due to a pituitary tumour
- Testicular tumours: large-cell calcifying Sertoli cell tumours (LCCSCT)
- Thyroid cancer
- Psammomatous melanotic schwannoma: meaning a tumour that grows on nerves.
- Blue naevi (blue-black moles)
- Osteochondromyxoma (bone tumours)
Genetic tests for PRKAR1A gene mutations are available for people suspected of having Carney complex. If the patient has a PRKAR1A gene mutation and one of the tumours or other conditions above, Carney complex is then diagnosed. Genetic testing for the new genes (PRKACA, PRKACB, PDE11A and PDE8B) is not yet commercially available.
In addition, other physical signs are seen in people with Carney complex. These physical signs may point to Carney complex but are not considered major diagnostic features. Research is continuing to learn more about the symptoms associated with this condition.
- Marked freckling without darkly pigmented spots
- Blue naevi, if multiple and confirmed by biopsy
- Café au lait spots: light brown patches on the skin, or other birthmarks
- Cardiomyopathy
- Pilonidal sinus
- Extensive family history of Cushing's syndrome, acromegaly or sudden death
- Skin lesions called lipomas
- Polyps, meaning benign tumours in the large intestine, usually together with acromegaly.
- A single non-cancerous thyroid nodule in a young person, multiple thyroid nodules in an older person
- Family history of cancer (especially thyroid, colon, pancreatic and ovarian cancer)
What Are the Estimated Cancer Risks Associated with Carney Complex?
The risk of cancer is increased in people with Carney complex, but the specific risk of cancer is not known. The types of cancer reported in people with Carney complex are: adrenocortical carcinoma, pituitary gland tumours, and thyroid, colorectal, liver and pancreatic cancer. Ovarian cancer in women and testicular tumours involving Sertoli or Leydig cells in men have also been reported.
What Are the Screening Options for Carney Complex?
There are no specific screening guidelines for Carney complex. Recommended screening includes:
- Annual echocardiography, from infancy
- Regular skin assessments by a healthcare professional
- Annual blood tests starting in adolescence (serum cortisol, prolactin and IGF-1 levels)
- Examination of the thyroid gland, which may include ultrasound imaging.
- General screening of the endocrine system
- Testicular examination and/or ultrasound in men
New technologies are being developed, and screening guidelines for Carney complex may change over time. It is important to talk to your doctor about appropriate screening tests.
Solar Lentigo
This is a sun-triggered proliferation of melanocyte cells located in the epidermal layer of the skin. It occurs as numerous lesions (spots) in a significant proportion of people, especially those with fair skin and long-term sun exposure. It is most often located on sun-exposed areas such as the backs of the hands, forehead, the V of the chest, shoulders and back.
They are irregular macules, usually at skin level and sometimes with slight scaling, 0.5–1.5 cm in diameter, round or oval, with star-like extensions towards the periphery. Their colour varies between light brown and skin colour, and they can sometimes be black. They cause no symptoms. They are usually seen after the age of 40, but after the age of 30 in those living in sunny climates. They occur more often in people with fair skin. They appear after acute sunburn and after excessive doses of PUVA therapy.
Lentigo Simplex
These are sharply demarcated brown spots a few mm in diameter. They may be present at birth or form later. The sun plays no role in their formation. They can occur anywhere on the body. While most remain stable, some disappear on their own. Treatment is carried out for aesthetic reasons. Successful results are obtained with laser treatment.
Segmental Lentiginosis
Segmental lentiginosis is a rare pigmentation disorder characterised by numerous, millimetric, light brown, grouped macules located unilaterally and in a dermatomal pattern on normal-looking skin. It is also called partial unilateral lentiginosis, zosteriform lentiginosis, agminated lentiginosis or lentiginous mosaicism. This condition, which is usually congenital or appears in childhood, is most often limited to the skin, although a small number of cases with neurological abnormalities or eye involvement have been reported. Its histopathology shows features similar to lentigo simplex, and nest formation is usually absent.
Neurofibromatosis
Neurofibromatosis (NF) is a set of genetic diseases that cause tumours to grow along various nerves and also affect the development of non-nerve tissues such as bone and skin. NF causes tumours to grow anywhere in the body. It also leads to developmental abnormalities.
Types of neurofibromatosis
Neurofibromatosis (NF) is classified into two separate types:
NF 1 and NF 2
Neurofibromatosis 1 (NF1), also known as von Recklinghausen NF or peripheral NF, occurs in one in 4,000 births. It is characterised by multiple café-au-lait spots and neurofibromas on and under the skin. Enlargement and deformation of the bones and curvature of the spine (scoliosis) may also occur. Rarely, tumours may develop in the brain, on the cranial nerves or in the spinal cord. About 50% of people with NF have learning disabilities.
Neurofibromatosis 2 (NF 2), also known as bilateral acoustic NF (BAN), is rarer and occurs in one in 40,000 births. NF 2 is characterised by multiple tumours on the cranial and spinal nerves and other lesions of the brain and spinal cord. Tumours affecting both hearing nerves are its hallmark.
Hearing loss appearing in the teens or early twenties is usually the first symptom.
As NF1 is the most common type of neurofibromatosis, the medical information in these guidelines focuses on NF1. Of course, the basic idea is to broaden this network and, as far as possible, to bring together recommendations for the follow-up of individuals affected by NF2 as well.
Café-au-lait spots (CALS)
These are the most common finding of NF1; they are light brown patches on the skin and are described by the French term "café-au-lait", meaning coffee with milk.
Individuals with NF1 have 6 or more café-au-lait spots. If there are fewer, the diagnosis of NF is not certain, because 10% of the population have 1–2 café-au-lait spots. The size of the spots is defined as 5 mm or more in children and 15 mm or more in adults. In general, with a few exceptions, tumours are not related to the location of the café-au-lait spots.
In children with NF1, café-au-lait spots usually appear at birth or by the age of 2. The number of spots may increase during childhood and later. While the spots are lighter in early childhood, they darken with age.
In individuals with NF1, it is difficult to distinguish small, dark spots from freckles. In individuals without NF, freckling usually develops as a result of the skin's exposure to the sun. In individuals with NF1, however, café-au-lait spots and freckling occur in different areas of the body: for example, freckling in the armpits and groin is strong evidence for the diagnosis of NF1. Freckling in these areas begins at around 3–5 years of age.
Naevus Spilus
We treat this type of acquired pigmented naevus with Q-switched 694 nm ruby or 532 nm Nd:YAG lasers. Laser treatments applied to naevus spilus generally give pleasing results. In pigmentation caused by drug reactions, or pigmentation occurring after any treatment, we try to lighten the spots with Q-switched 1064 nm Nd:YAG laser treatments and lightening mesotherapy.
Becker Naevus
These are acquired (later-developing) brown patches, usually seen on the trunk or limbs, described as moles with thick, dark hair. In this condition there are two different problems that need to be treated. The first is the thick, dark hair. We treat this hair with 1064 nm Nd:YAG laser hair removal or electrolysis. We treat the dark patch on the skin with a 694 nm Q-switched ruby laser.
Mongolian Spot
These are bluish patches of varying size in the lower back area. It is a type of naevus. It is treated with a Q-switched 1064 nm Nd:YAG laser. It is performed under simple topical anaesthetic cream. In childhood cases, the patient is put to sleep with short-term intravenous anaesthesia, and only in this way can the treatment be completed. For this type of patch we recommend treatment more in infancy or childhood, because in infancy the skin is thinner, the treatment area is smaller and the skin is lighter in colour. Treatments carried out in this period are more successful.
Blue Naevus
This is an acquired, benign, firm, sharply demarcated papule or nodule ranging in colour from blue-grey to black, representing a localised proliferation of melanin-producing dermal melanocytes. It begins in childhood and young adulthood. It forms as a result of ectopic accumulations of cells called melanocytes in the dermis. It usually causes no complaints. They appear as papules or nodules, usually less than 10 mm in diameter, and may be round or oval.
They are mostly located on the backs of the hands and feet. They can also form on the buttocks, lower back, scalp and face. In most cases they do not change; rarely, malignant melanoma (the most serious skin cancer) can develop. A blue naevus less than 10 mm in diameter that has not changed for many years usually does not require excision. A blue naevus that appears suddenly, or changes in an existing one, require surgical removal and dermatopathological examination.
Naevus of Ota
Naevus of Ota is a type of benign naevus that appears on the face as a blue-brown patch, on one or both sides, and often also involves the eye. A study in Japan found its prevalence in the population to be 0.4–0.8%. It can appear at birth or in adolescence. Its cause is unknown. Although naevus of Ota is a benign formation, it carries a risk of malignant melanoma. Treatment of naevus of Ota is not compulsory. It is treated for cosmetic purposes. Lasers are effective in the treatment of naevus of Ota.
Lasers used in treatment:
– Q-switched Nd:YAG (532 nm) laser (KTP laser)
– Q-switched alexandrite (755 nm) laser
– Q-switched ruby (694 nm) laser
Naevus Cell Naevi
Benign melanocytic naevi are benign proliferations of melanocytes. They may be present at birth or may develop over the course of life. They are seen as patchy, papular or papillomatous skin lesions with variable pigmentation, in which histologically demonstrable aggregates of naevus cells are found in the epidermis, the dermis or both. Proliferation first occurs in the epidermis at the dermoepidermal junction, and therefore the first melanocytic naevi are known as junctional naevi. Subsequently, the naevus cells "drop" into the dermis. When the naevus cells are only within the dermis, they are known as intradermal naevi, and when both junctional and dermal components are present, they are called compound naevi.
Melanonychia Striata
These are broad dark lines extending from the proximal nail fold and cuticle to the free distal edge of the nail plate. In dark-skinned people they may be the result of normal physiology and require no treatment. Melanonychia striata is also seen in benign melanocytic naevi and malignant melanoma. Hutchinson's sign – the presence of melanin along the lunula, cuticle and proximal nail fold – may be a sign of melanoma in the nail matrix. Immediate biopsy and treatment are required.
Intradermal Naevus
This type of naevus, which can also be found on the mucosa and skin, is known as the ordinary mole and is seen in almost everyone. Typically, it is a congenital naevus with brown pigmentation. For most people, these moles cause no discomfort beyond cosmetic concerns.
Papillomatous Naevus
This type of lesion is most common on the scalp but can occur anywhere on the skin. A papillomatous naevus is broad (several centimetres) with a bumpy, uneven surface, and its colour ranges from brownish (rarely black or dark brown) to normal skin colour. Like fibroepithelial naevi, papillomatous naevi are often penetrated by hairs. After injury, a papillomatous naevus can become inflamed. Because of the location of the lesion on the face and other exposed areas of skin, patients develop a strong wish to get rid of the noticeable cosmetic defect, which is possible thanks to cosmetic treatment carried out for this purpose.
Treatment of Giant Congenital Naevi
Giant congenital hairy naevi are dark, hairy moles that are noticed when the baby is born or within the first year after birth, and are generally larger than the baby's palm. By definition, they are described as lesions that are larger than 20 cm in diameter in adulthood, cover more than 2% of the body surface area, or require tissue expansion for the defect left after excision to be closed in a single procedure, or can only be removed by serial excisions.
Although their prevalence in the population is reported as 1%, many of these are relatively small lesions. Lesions larger than 10 cm in diameter, which are considered large lesions, are seen in one in every 20,000 births. True giant naevi covering the whole trunk like a swimsuit are seen in approximately one in every 500,000 births.
Although they can be seen anywhere on the body, they usually appear on the head and buttock areas.
They carry a 2–4% risk of malignant change over a lifetime. However, some publications show this rate to be as high as 40%. For this reason, their removal is recommended. In particular, for lesions showing ulceration, colour variation, change in shape or nodularity (budding), the appropriate approach is to remove the whole lesion as soon as possible or, if it cannot be removed, to take a biopsy so that the changes can be evaluated under the microscope.
There is no complete consensus in the medical literature on the most appropriate method or timing for removing these lesions. The general view is that the whole lesion should be removed before puberty if possible. The aim here is to reduce the risk of cancer as much as possible while causing the patient as little cosmetic and/or functional loss as possible. Although some recommend superficial shaving techniques such as dermabrasion, curettage and laser ablation, common practice is surgical removal by full-thickness skin excision. After excision, if the skin edges can be brought together, the skin is closed with sutures. Where this is not possible, the resulting skin defect can be closed with a skin graft. Another approach is not to remove the lesion in one go, but to remove it in stages, each time suturing the healthy skin edge to the remaining edge of the lesion. With this method, called staged (serial) excision, the healthy skin gradually stretches and eventually slides into the place of the lesion. Another option is to place silicone balloons (tissue expanders) under the skin around the lesion and gradually inflate them to expand the healthy skin; once enough tissue has been obtained, the lesion is removed and the resulting defect is closed in a single procedure by advancing the expanded healthy skin.
Dysplastic Naevi (Dysplastic Moles)
This term is used for moles that look different from ordinary moles, i.e. that look "atypical". Although they are sometimes called atypical moles (naevi) because of their appearance, the most commonly used name is dysplastic naevus. Dysplastic moles are not moles that appear at birth. They can be familial (occurring in different members of a family) or can appear without other family members having them. There may be just one or many. They are most often located on the trunk and back. Although familial ones often appear by adolescence, in general they can appear at any age.
In appearance they are larger than other ordinary non-congenital moles. Their diameter is over 5–6 mm. They may be asymmetrical (if you fold the mole over itself along two different axes, it is not symmetrical). There may be light and dark brown areas within the mole. In shape, some may be raised above the skin and some may be level with the skin. A mole that is not raised above the skin may have a raised area in its centre. If we think of the flat part as the egg white and the raised central part as the yolk, such an appearance can be described as a "fried egg".
Halo Naevus
Some moles are surrounded by a white ring. This type of mole is seen in childhood and adolescence. They are harmless, and over time the central mole and the white ring disappear. Sometimes this colour change can also be seen in the skin cancer called melanoma; if there is any doubt, a biopsy may be needed.
Spitz Naevus
Spitz naevus (benign juvenile melanoma) is commonly seen in children but can also appear in adulthood. It is not a melanoma, but its clinical appearance and pathology closely resemble melanoma. It can be a red-brown, dome-shaped papule or nodule with a smooth or slightly raised surface, 0.3–1.5 cm in diameter. Its colour varies according to its blood supply. It may bleed when traumatised. It may be single or multiple. It appears suddenly and grows slowly.
Pseudomelanoma
Where a mole has been incompletely removed, slight pigmentation appears within weeks or months. This is a recurrence of the mole, but it has been given this name because it resembles melanoma pathologically.