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

• Borderline Melanocytic Lesion of Skin
• Cutaneous Minimal Deviation Melanoma
• MDM of Skin

What is Minimal Deviation Melanoma of Skin? (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 (or melanocytes)
• Minimal Deviation Melanoma (MDM) of Skin comprises a group of lesions described as nevomelanocytic tumors. These tumors are generally uncommon and mostly observed in young adults and older children
• Minimal Deviation Melanoma of Skin tumors are said to have a ‘borderline’ behavior. This means that the tumor cells are not as aggressive as a melanoma, but not as benign as a nevus i.e., they are more atypical. However, MDMs may appear to mimic a benign melanocytic tumor
• Currently, there are no well-established criteria to place/classify these tumors, and so, there is an ongoing debate on the definition and characteristics of Minimal Deviation Melanoma of Skin. Many researchers describe these tumors as variants of nevoid melanoma of skin
• Minimal Deviation Melanoma of Skin may originate from a preexisting mole, or from normally healthy skin (as a new growth). The risk for melanoma formation may include fair skin and sun-exposure
• Most lesions are noted on the trunk, but they may be present anywhere on the body. Minimal Deviation Melanomas of Skin are small-sized, mostly well-defined, solitary lesions. Tumors on the face and neck may present cosmetic concerns
• Minimal Deviation Melanoma of Skin is diagnosed with the help of a biopsy. Once a definitive diagnosis has been made, it is surgically removed (excised). Other treatment modes may be employed depending on the assessment of the healthcare provider
• The prognosis of Minimal Deviation Melanoma of Skin is said to be generally better than conventional melanomas. Even though metastasis is infrequently observed, tumor recurrences are known to take place

Who gets Minimal Deviation Melanoma of Skin? (Age and Sex Distribution)

• Minimal Deviation Melanoma of Skin is generally seen in older children and young adults (average age of presentation is 27 years); many cases are noted in individuals below 30 years
• Both males and females are seen with this condition
• Cutaneous melanomas occur more frequent in Caucasians, as compared to other races

What are the Risk Factors for Minimal Deviation Melanoma of Skin? (Predisposing Factors)

The following factors may increase the risk for Minimal Deviation Melanoma of Skin:

• Exposure to ultra violet (UV) rays is a major risk factor; the exposure may be intermittent or even severe. UV rays are present in sunlight, and also in tanning lamps and beds
• 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 or Familial Multiple Mole Melanoma  Syndrome (FAMMM). 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
• 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; 6-14% of the individuals with melanoma are found to have someone with melanoma in their family
• 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)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones 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 Minimal Deviation Melanoma of Skin? (Etiology)

Minimal Deviation Melanoma of Skin can arise from certain cells, called melanocytes, from skin that has been damaged or from normally healthy skin, due to a variety of factors. They are also known to arise from the skin component of a benign nevus/mole.

The potential causes for Cutaneous Minimal Deviation Melanoma 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
• 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
• Typically inherited or acquired melanomas show genetic mutations and chromosomal anomalies. Also about 50% of all melanomas have a mutation (change) involving the BRAF oncogene
• 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 Minimal Deviation Melanoma of Skin?

Minimal Deviation Melanoma of Skin may occur in a previously benign mole; de novo (new) melanomas may be seen in other cases. The signs and symptoms may include:

• The presence of slow-growing, regular-to-irregularly shaped, small nodules/plaques on the skin
• Some lesions are pigmented, while others may not show any discernible pigmentation
• Pigmented lesions may be in shades of brown-black or blue-black
• MDM of Skin may be commonly mistaken for a benign mole/nevus
• The skin lesions are usually solitary and firm; the tumor boundaries may be clearly defined
• Tumor sizes may be around 1 cm
• The skin areas most commonly affected include the chest, back, and abdomen. Other areas include the head and neck region and arms and legs
• Bleeding lesions and ulceration is uncommon; no tumor necrosis and invasion of fatty tissues beneath the skin are generally noted
• Some skin lesions may not have any signs and symptoms during the initial stages

How is Minimal Deviation Melanoma of Skin Diagnosed?

A thorough history and a complete physical exam by a physician are crucial for the diagnosis of Minimal Deviation Melanoma of Skin. This is followed by some tests which 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 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 tumor cannot be determined

A differential diagnosis to exclude the following tumors should be undertaken:

• Hemangioma
• Spitz nevus
• Epidermal cyst

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 Minimal Deviation Melanoma of Skin?

The complications of Minimal Deviation Melanoma of Skin may include the following:

• Spread of the tumor to local and other distant sites
• Recurrence following incomplete surgical excision; recurrences are not very commonly noted
• Side effects that arise from various treatment therapies

How is Minimal Deviation Melanoma of Skin Treated?

The choice of treatment for Minimal Deviation Melanoma of Skin 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: It is the treatment of choice.

• 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
• Slow Mohs Micrographic Surgery:
  • Performed by Mohs  surgeons as an alternative technique to standard excision of melanoma
  • A thin layer of skin is removed, stained,  and checked microscopically for cancer at the margins of the specimen. This process is the carried out continuously, until a cancer-free slice of skin is obtained
  • This procedure is ‘slower’ than Mohs Micrographic Surgery for basal cell carcinoma and squamous cell carcinoma because the staining process needed  for melanoma specimens takes much longer
• 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. 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 is observed to be effective in some cases.

• 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 Minimal Deviation Melanoma of Skin be Prevented?

A few steps to prevent of Minimal Deviation Melanoma of Skin may include:

• 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 Minimal Deviation Melanoma of Skin? (Outcomes/Resolutions)

• The prognosis of Minimal Deviation Melanoma of Skin is reported to be much better than the prognosis of other conventional forms of cutaneous melanoma. These tumors are not as aggressive as conventional melanomas of skin
• Tumor metastasis is not very commonly noted and recurrences are uncommon following surgery (though some tumors are known to recur after 4-5 years)
• However, Minimal Deviation Melanomas of Skin are poorly-understood tumors among the medical/scientific community. Accurate information on their behavior and properties are not well known or available
• Individuals with early-stage melanoma have better outcomes compared to those with more advanced melanoma, where the cancer has spread to lymph nodes or other organs
• 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 to 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)

Additional and Relevant Useful Information for Minimal Deviation Melanoma of Skin:

• 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)