What are the other Names for this Condition? (Also known as/Synonyms)

• Melanoma arising in Large Congenital Nevus
• Malignant Melanoma arising in GCN
• Melanoma arising in Giant Congenital Naevus

What is Melanoma arising in Giant Congenital Nevus? (Definition/Background Information)

• A nevus (plural nevi) is a mole on the skin that can occur on any part of the body. A melanocytic nevus is benign tumor of melanocytic (pigment-based) cells that occur on the skin
• A melanoma is a type of cancer that develops from the melanocytic cells, called melanocytes. Melanocytes are cells that produce melanin; the pigment that gives skin its color
• Melanoma arising in Giant Congenital Nevus is a rare form of melanoma that is seen mostly in children. It arises from the skin component of a giant congenital nevus (GCN), which may be described as a very large birthmark that usually forms in children following birth
• The giant congenital nevus may undergo malignant transformations in the presence of other factors and form a malignant melanoma. Hence, a GCN may be described as a premalignant stage to melanoma development
• The melanoma may arise on any part of the body; it is usually seen on the trunk. The lesions are usually irregular and can ulcerate. Metastasis due to Malignant Melanoma arising in Giant Congenital Nevus is not uncommon
• Once a definitive diagnosis has been established, the tumor may be surgically removed (excised). Depending on how far the condition has progressed, additional modes of therapy may be needed. The outcome of Melanoma arising in Giant Congenital Nevus is generally guarded due to the aggressive nature of the tumor

Who gets Melanoma arising in Giant Congenital Nevus? (Age and Sex Distribution)

• 1 in every 100 children is believed to have a pigmented lesion that is of congenital origin (occurring by birth). The presence of a giant congenital nevus is estimated at an incidence of 1 in every 20,000 child; of this, about 6% of the children with GCN may develop melanoma at the site of the nevus
• Both children and adults may be affected by Malignant Melanoma arising in Giant Congenital Nevus; a bimodal distribution pattern is noted. Most cases (around 70%) are noted in early childhood, before the child reaches puberty or about 10 years of age; following this, the cases peak in adulthood too
• Both males and females are affected and no preference for either gender is noted
• Cutaneous melanomas occur more frequently in Caucasians compared to other races

What are the Risk Factors for Melanoma arising in Giant Congenital Nevus? (Predisposing Factors)

The following factors increase the risk for Melanoma arising in Giant Congenital Nevus:

• Presence of a giant congenital nevus, which is a very large nevus observed on any area of the body and having a congenital origin
• Nevus (medical term for mole) is a non-cancerous pigmented tumor. While most nevi never become cancerous (or malignant), a small number of atypical/dysplastic nevi (moles with abnormal shape/borders/color) may turn cancerous. When such dysplastic nevi run in families, the condition is called dysplastic nevus syndrome. Individuals with this condition have a 10% increased risk of developing melanoma. Despite the above and irrespective of the condition, whether the nevi are present since birth, or are normal, or atypical; the greater the number of moles, the higher is the risk
• Severe exposure to ultra violet (UV) rays is a major risk factor. UV rays are present in sunlight, and also in tanning lamps and beds
• Fair-skinned individuals are at a higher risk; more so those with freckles or those who develop sunburns easily
• Individuals with light or red hair color and those with blue eyes also have a higher risk
• Previous history of melanoma or a history of melanoma in parents/siblings
• An inherited condition called xeroderma pigmentosum, where the ability of the cells to repair sun-induced damage to genetic material is impaired
• Weakened immune system, as a result of infections (such as HIV infection), medications (chemotherapy and immunosuppressants), and due to the presence of cancers (such as lymphoma)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Melanoma arising in Giant Congenital Nevus? (Etiology)

The cause of Malignant Melanoma arising in Giant Congenital Nevus (which is a preexisting, large-sized mole) is unidentified. The exact reason behind why some moles turn cancerous, and others do not, is still not exactly known.

The potential causes for Melanoma arising in Giant Congenital Nevus may include:

• Uncontrolled activity of oncogenes (rogue genes that promote cell growth and division) or depressed action of tumor suppressor genes (genes that normally keep a check on cell growth and division) is thought to play a role in the development of melanomas
• About 50% of all melanomas have a mutation (change) involving the BRAF oncogene. Tumors arising in large-sized congenital moles are known to show the same genetic and chromosomal abnormalities as conventional skin melanomas
• UV-radiation induces damage to DNA (genetic material that determines all of our traits and functions), which in turn may turn-on oncogenes, or turn-off tumor suppressor genes
• In families with inherited melanomas, gene mutations that increase the risk of cancer are passed on from one generation to the next

What are the Signs and Symptoms of Melanoma arising in Giant Congenital Nevus?

Melanoma arising in Giant Congenital Nevus typically arises from the skin component of a large congenital nevus/mole. The signs and symptoms may include:

• Presence of a giant congenital nevus (GCN) covering a large area of the body; the size of these moles are generally in excess of 20 cm. The most common GCN locations include the torso and head and neck region
• The GCN is darkly pigmented in most cases – tan, brown, or black. The melanoma may have a non-uniform dark discoloration, or take on a blue-black or red color
• The melanoma is mostly seen to form from GCN on the back, chest, or abdomen region (trunk) of the child/adult. However, any part of the body may be involved
• The lesion appears as a nodule, or rarely, as a cyst, and shows a rapid increase in size
• Since, the GCN envelops the body skin; it may be difficult to spot any (melanoma) lesions. However, tumors on the edges of the nevus may be visible
• Melanomas arising in GCN are mostly well-defined, asymmetrical, and show ulceration
• Ulceration, bleeding, and crust formation may be a chronic and repetitive event
• A giant congenital nevus is often associated with many other benign and malignant tumors/conditions

How is Melanoma arising in Giant Congenital Nevus Diagnosed?

A thorough history and a complete physical exam by a physician are crucial for the diagnosis of Melanoma arising in Giant Congenital Nevus. This is followed by other tests and investigations which may include:

• Biopsy of skin: A sample of the skin, from any suspected area found on physical examination, is taken and examined under a microscope for signs of cancer by a pathologist. The types of biopsy performed include:
  • Excisional biopsy: After numbing the area with a local anesthetic, the entire mole is removed with a small border of surrounding skin. Where possible, this is the generally preferred method
  • Punch biopsy: After numbing the area with a local anesthetic, a circular blade is pressed into the skin around the suspicious area, and a round piece of skin removed. This type of biopsy is carried out, when the lesion (the suspicious area) is large in size
  • Incisional biopsy: After numbing the area with a local anesthetic, a portion of the tumor is removed using a surgical knife
  • Sentinel lymph node biopsy: Performed to determine if the melanoma has spread to nearby lymph nodes. A dye is injected into the area from where the melanoma is removed. The first lymph node that takes up the dye is biopsied and examined for cancer cells, under a microscope
• Sometimes, biopsy of other large lymph nodes in the area near the melanoma may be performed using fine needle aspiration cytology (FNAC) technique. In this, a sample of cells is removed from the mass, using a syringe with a hollow needle and then examined under a microscope
• If the melanoma is suspected to have metastasized (spread) to internal organs, imaging tests, such as X-ray, CT scans or MRI scans of the affected areas may be carried out
• In rare cases, biopsies of areas other than skin may have to be done, when the primary source/origin of the tumor cannot be determined
• A differential diagnosis to exclude proliferative nodules in congenital melanocytic nevus should be undertaken

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Melanoma arising in Giant Congenital Nevus?

The complications due to Melanoma arising in Giant Congenital Nevus may include:

• Severe emotional and psychological stress (for both the child and his/her family members)
• The more advanced cases of melanoma metastasize beyond the skin, to lymph nodes and other organs. Organs that are commonly involved in metastasis include:
  • Lung
  • Liver
  • Brain
  • Bone
  • Gastrointestinal tract
• A giant congenital nevus is associated with many malignant conditions including neurocutaneous melanocytosis (NCM, a congenital disorder with large or multiple congenital nevi and  melanocytic tumors in the leptomeninges in the central nervous system)
• Tumor recurrence following surgery may be noted
• Side effects that arise from the various treatment therapies

How is Melanoma arising in Giant Congenital Nevus Treated?

The choice of treatment for Melanoma arising in Giant Congenital Nevus depends on how far the cancer has progressed. This is estimated through staging of the tumor. Some of the factors taken into consideration during staging include:

• The thickness of the melanoma (also called Breslow’s measurement): Tumors can be thin, intermediate, or thick, depending on how deep into the skin they have penetrated. The thinner the tumor, the better the chances of a cure
• Presence of any ulceration (open sores) over the tumor
• Spread of melanoma to lymph nodes or other internal organs

The melanoma is sorted into one of four stages depending on how far it has progressed, with I and II being early stages, III and IV being later stages, where melanoma has spread to sites beyond the skin. While early stage melanomas can be treated by surgery alone, the later stages of the disease often require a combination of treatment measures.

Treatment options for melanoma include:

Surgery:

• Simple excision of the tumor along with some normal, non-cancerous skin at the edges (called margin). The width of the margin is based on the thickness of the tumor; as the thickness of the melanoma increases, the margin required increases as well
• Mohs micrographic surgery:
  • Being used of late by some surgeons as an alternative technique to standard excision of melanoma
  • A thin layer of skin is removed and checked for cancer. This process is the carried out continuously, until a cancer-free slice of skin is obtained
  • This procedure is used as a surgical treatment option for melanoma with the addition of immunohistochemical stains on the surgical specimens removed
• Lymph node dissection, in cases where the melanoma has spread to involve the nodes: Lymph nodes help in drainage of tissue fluid (lymph). However, removal of these nodes may therefore lead to a build-up of lymph causing swelling (lymphedema)

Chemotherapy:

• Drugs are used to kill the tumor cells, which may be given as oral pills, or injected into veins
• Side effects of chemotherapy may include nausea, vomiting, hair loss, loss of appetite, diarrhea, and fatigue, increased risk of infection, mouth sores, or easy bruising, depending on the drug used
• In cases, where the melanoma is advanced, but remains confined to an arm or leg; chemotherapy is only circulated through the affected the limb, by a process called isolated limb perfusion

Immunotherapy:

• This therapy stimulates the immune system and involves the use of substances produced naturally by the body or such similar synthetics, made in a laboratory
• Drugs used include, synthetic immune proteins and proteins that boost the immune system, called cytokines- interferon alpha or interleukin-2
• Side effects of cytokines may include chills, fatigue, fever, headaches and muscle aches; while synthetic immune proteins may cause the immune system to start attacking other parts of the body

Targeted therapy:

• Involves the use of drugs tailored to target the differences in a melanoma cell, as compared to a normal cell
• Half of all melanomas involve a mutation in the BRAF gene. Melanomas with this mutation are targeted by a drug vemurafenib
• Side effects may include nausea, joint pain, fatigue, rash, itching, hair loss, sensitivity to the sun, and rarely heart rhythm problems, liver problems, severe allergic reactions, and severe skin or eye problems

Radiation therapy:

• This uses high energy beams to kill cancer cells
• Generally, this method is not used to treat the original melanoma, but often to relieve symptoms, when the melanoma has spread to other organs; or following lymph node dissection, where many nodes were found to be cancerous
• The most common side effect is fatigue, but this gets resolved, once the treatment is complete

How can Melanoma arising in Giant Congenital Nevus be Prevented?

Currently, it may not be possible to prevent Melanoma arising in a Giant Congenital Nevus. However, the risk for melanoma may be lowered by considering the following factors:

• Avoid direct exposure to UV rays and remain in the shade, as and when possible
• When heading out into the sun:
  • Slip on a shirt
  • Slop on some sunscreen. Sunscreens with SPF values higher than 30, and those offering broad spectrum protections (against UV-A and UV-B rays), are recommended. Apply an ounce to all exposed areas, 30 minutes before heading outdoors. Reapply every two hours, and also after excessive sweating
  • Slap on a hat
  • Wrap on sunglasses

This is encapsulated as the “Slip! Slop! Slap! Wrap” method for skin cancer prevention. (Source: The American Cancer Society, Atlanta)

• Avoid tanning beds and sun lamps
• Perform self-examination of your skin, from head to toe, once a month
• Get a professional skin exam from a healthcare provider, once a year
• All patients with melanoma should undergo skin examinations regularly even after treatment, at least once a year throughout their lives

What is the Prognosis of Melanoma arising in Giant Congenital Nevus? (Outcomes/Resolutions)

• The prognosis of Melanoma arising in Giant Congenital Nevus is generally worse than other forms of cutaneous melanoma, since it is a very aggressive tumor
• In general, the detection and treatment of the condition is usually challenging. Melanoma arising in GCN is also observed to metastasize more often than other cutaneous melanomas
• The prognosis depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the melanoma is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage cancers, such as those with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the melanoma: Individuals with small-sized melanomas fare better than those with large-sized ones
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of melanoma of skin (meaning if the melanoma can be removed completely)
  • Whether the cancer is occurring for the first time, or is recurrent. Recurring cancers have worse prognosis compared to those that do not recur 
  • Response to treatment: Melanomas that respond well to treatment have better prognosis compared to melanomas that do not respond to treatment
  • Progression of the condition makes the outcome worse (progressive cutaneous melanoma)
• An early diagnosis and prompt treatment of the condition generally yields better outcomes than a late diagnosis and delayed treatment

Additional and Relevant Useful Information for Melanoma arising in Giant Congenital Nevus:

• Melanoma is the most common form of cancer in young adults aged 25-29 years. 1 in 50 Americans have a lifetime risk of developing melanoma
• The ‘Slip-Slop-Slap campaign’ was initially launched in Australia, by Cancer Council Victoria in the 1980s, to promote awareness about skin cancer and methods for its prevention. This was then adopted in New Zealand as the ‘Slip-Slop-Slap-Wrap campaign’ (Source: The Wikipedia)