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

• Malignant Subungual Melanoma
• Melanoma of Nail Matrix
• Nail Matrix Melanoma

What is Subungual Melanoma? (Definition/Background Information)

• A melanoma is a type of cancer that develops from cells, called melanocytes. Melanocytes are cells that produce melanin; the pigment that gives skin its color
• Melanoma of nail unit is a melanoma that affects the nail - either the fingernail or the toenail. There are 3 main types of nail unit melanoma and these include:
  • Subungual Melanoma
  • Ungual Melanoma
  • Periungual Melanoma
• Subungual Melanoma is melanoma of the nail affecting the tissue beneath the nail base, also known as the nail matrix. It is the region from where the nail forms and grows
• In general, there are 4 basic types of melanomas which include:
  • Superficial spreading melanoma: It is a common type of melanoma that arises from a benign mole. It can slowly appear to spread with change in pigmentation, but is capable of a rapid progression
  • Lentigo maligna melanoma: It is a less common type that is seen during middle-age or older age. The condition usually affects the face and may resemble sunspots
  • Acral lentiginous melanoma: This type may occur at locations distant from the central body, as they are found on the hands, feet, and below the nails. It is the least common type
  • Nodular melanoma: It is the most aggressive melanoma type most often affecting adult males
• Subungual Melanoma is diagnosed with the help of a biopsy. Once a definitive diagnosis has been made, it is surgically removed (excised). Depending on how far the disease has progressed, additional modes of therapy may be needed
• The prognosis of Subungual Melanoma is good when the diagnosis is made early; the prognosis is unfavorable with advancing disease

Who gets Subungual Melanoma? (Age and Sex Distribution)

• Subungual Melanoma is an uncommon condition. It is more commonly observed in middle-aged and older adults in the 40-70 year age category
• No gender predilection is observed and both males and females are affected
• Melanomas are generally observed in Caucasians (light-skinned individuals). However, among the various melanoma types affecting dark-skinned individuals, this melanoma type is the most common type

What are the Risk Factors for Subungual Melanoma? (Predisposing Factors)

The following factors increase the risk for Subungual Melanoma:

• Injury to the toes or fingers
• 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 more the number of moles, the greater is the 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), drugs (chemotherapy or immunosuppressants), and the presence of cancers (such as lymphoma)

Note: Current studies have shown that the development of Subungual Melanoma is not related to sun-exposure (or ultraviolet ray exposure). However, this factor has not yet been conclusively proven. In general, sun-exposure is an important risk factor for melanoma formation.

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 Subungual Melanoma? (Etiology)

Currently, the exact cause of development of Subungual Melanoma is unknown. However, the potential causes 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
• 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. Nevertheless, current scientific research shows that sunlight does not seem to be a significant factor for Subungual Melanoma
• 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 Subungual Melanoma?

A melanoma can develop from an existing mole or appear as a new spot. The signs and symptoms may include:

• A pigmented area that is Asymmetrical in shape, whose Borders are irregular or ragged
• A pigmented area that is not Colored uniformly, unlike a benign mole, which has an even distribution of shades
• Any suspicious looking spot, whose Diameter is more than ¼ inches (6 millimeters). Although, in melanoma of nail unit, it can be less than 6 mm
• Any suspicious looking spot that is Evolving, or changing in shape/color

These signs are often collectively referred to as the ‘ABCDE characteristics’ of melanoma, by physicians. (Source: The Skin Cancer Foundation, New York)

• A suspicious looking spot or a ‘potential melanoma’ often differs in appearance from other benign moles on the body. This variability is sometimes called the ugly duckling sign by physicians (Source: The Skin Cancer Foundation, New York)
• A suspicious pigmented area/spot showing a spread of color to the surrounding skin and with any swelling, redness or itching (due to inflammation). Such areas may also be scaly, or exhibit some oozing of fluid, or bleeding

The following signs and symptoms of Subungual Melanoma may be observed:

• This melanoma type appears like a streak along the nail; as the condition progresses, there may be several streaks of varying shades on the affected nail
• Hutchinson’s nail sign: The pigmented area extends to the nail bed, into the cuticle, and to lateral folds along the nail; the entire nail (or most part of the nail) may appear pigmented. It is an important diagnostic indicator for this melanoma type
• The melanoma may be black, blue, or brown in color; the color of the nail may be non-uniform. However, studies reveal that in about half of the cases, there may not be any pigmentation
• As the condition progresses, the size of the melanoma may increase affecting the nail integrity
• The nail may become brittle and crack/break while remaining attached to the base
• Ulceration and bleeding may occur if a nodule forms on the affected finger or toe
• In most cases, either the thumbnail or the big toenail is involved

How is Subungual Melanoma Diagnosed?

A thorough history and a complete physical exam by a physician are crucial for the diagnosis of Subungual Melanoma. This is followed by tests that may include:

• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Tissue biopsy: A sample from the affected nail region 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
  • Biopsies in the nail region (that are specialized techniques)
• 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 scan or MRI 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 melanoma cannot be determined
• A differential diagnosis to rule out other conditions (such as fungal infection of the nail or splinter hemorrhage) presenting similar signs and symptoms may have to 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 Subungual Melanoma?

Early stage melanomas include melanoma in situ (confined to just the upper skin layer called epidermis) or locally invasive melanomas that have spread to the deeper layers of the skin. Advanced stage Subungual Melanoma can invade into the tissue and bone beneath the nail. It can also metastasize beyond the nail and skin, to the lymph nodes and other organs.

Organs that are commonly involved in metastasis include:

• Lung
• Liver
• Brain
• Bone
• Gastrointestinal tract

How is Subungual Melanoma Treated?

The choice of treatment for Subungual Melanoma depends on how far the cancer has progressed. This is estimated through staging of the melanoma. 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
• Amputation of the affected finger or toe, when necessary
• 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
  • The frozen section technique of Mohs micrographic surgery is less often used as a surgical treatment option for melanoma. Instead, the slower process of Mohs surgery with immunohistochemical assisted margin control is used
• 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 the finger or toe; chemotherapy is only circulated through the affected 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. This is 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
• Localized radiation dermatitis can occur, with redness, sensitivity and burning
• Areas of irradiated skin have accelerated aging phenomena

How can Subungual Melanoma be Prevented?

The exact cause or risk factors for Subungual Melanoma have not been identified yet. Hence, currently, it is not possible to prevent the condition.

A few steps to diagnose the condition during its early stages may include:

• 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 individuals with melanoma should undergo skin examinations regularly even after treatment, at least once a year throughout their lives
• Close monitor of individuals receiving immunosuppressants for various reasons, or those with poor immune system

What is the Prognosis of Subungual Melanoma? (Outcomes/Resolutions)

• Individuals with early-stage Subungual Melanoma have better outcomes compared to those with more advanced melanoma, where the cancer has spread to lymph nodes or other organs
• Multiple studies have shown that the overall 5 year survival rate for this melanoma type is between 16 to 87%
• In general, 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 Subungual Melanoma (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 Subungual 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 Subungual Melanoma:

New types of melanoma treatment are currently under study. These include vaccines and newer targeted therapies that work on altered genes or proteins in melanoma cells.