Lentigo Maligna Melanoma
Lentigo Maligna Melanoma (LMM) is a type of skin cancer, wherein skin invasion by the melanocytes is observed against a background of lentigo maligna.
What are the other Names for this Condition? (Also known as/Synonyms)
- Cutaneous Melanoma, Lentigo Maligna Type
- LMM (Lentigo Maligna Melanoma)
- Malignant Melanoma of Skin, Lentigo Maligna Type
What is Lentigo Maligna Melanoma? (Definition/Background Information)
- Normal skin is composed of 3 layers - the epidermis, the dermis, and the subcutis. The epidermis and dermis are separated by a layer, called the basement membrane
- 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
- Lentigo Maligna Melanoma (LMM) is a type of skin cancer, wherein skin invasion by the melanocytes is observed against a background of lentigo maligna
- Lentigo maligna is a type of melanoma in situ of skin, generally occurring as pigmented lesions on the face and other regions, following severe sun-exposure and skin damage
- Sometimes, a large area of the skin may be involved and an irregularly pigmented patch seen. Lentigo Maligna Melanoma can also spread/metastasize to other areas of the body
- The condition is diagnosed with the help of a biopsy. Once a definitive diagnosis is made, it is surgically removed (excised). Typically the prognosis of Lentigo Maligna Melanoma, which has been diagnosed early and excised completely, is good
Who gets Lentigo Maligna Melanoma? (Age and Sex Distribution)
- Lentigo Maligna Melanoma is a subtype of invasive melanoma of skin and constitutes between 5-15% of all cutaneous melanomas
- It can occur in young as well as old individuals; however, most of the cases are observed between the age range of 40-80 years (average age of 65 years)
- Older adults are affected more with this form of melanoma; the other subtypes are more often seen in a slightly younger population
- Both male and female genders are affected, though a male predominance is observed
- In general, melanomas of skin occur more frequently in Caucasians, as compared to other races
What are the Risk Factors for Lentigo Maligna Melanoma? (Predisposing Factors)
The following factors increase the risk of Lentigo Maligna Melanoma:
- The presence of lentigo maligna: The larger the size of the lentigo maligna, the greater is the chance of invasion, and thus of Lentigo Maligna Melanoma development. In general, if the lesions are over 4 cm in size, then there is a 50% chance of invasion into the deeper skin layers
- Exposure to the ultraviolet (UV) rays of sun is a major risk factor. UV rays are present in sunlight, and also in tanning lamps and beds. A severe exposure to sunlight is a major risk factor for lentigo maligna; the severe exposure mostly occurs due to the nature of one’s work/occupation
- 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; more the number of moles, more is the risk
- The presence of actinic keratosis; a precancerous condition caused by sun exposure
- Fair-skinned individuals are at a higher risk; more so those with freckles or those who develop sunburns easily
- 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: It is important to note that unlike the superficial spreading and other cutaneous forms of melanoma, the number of melanocytes and moles/nevi in the skin is not a major risk factor for LMM development.
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 Lentigo Maligna Melanoma? (Etiology)
Lentigo Maligna Melanoma is associated with severe sun-exposure and develops from the melanocytes in the skin. A long-term (accumulated) exposure to sunlight that results in DNA damage, is generally observed with this skin condition.
- 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
- 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
- In individuals with xeroderma pigmentosum, gene mutations on TP53 have been reported in LMM
- In rare cases, an association of lentigo maligna with BRAF gene mutation has been noted. Also, chromosomal losses on chromosomes 13 and 10 have been reported
- 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 Lentigo Maligna Melanoma?
Lentigo Maligna Melanoma signs and symptoms may include the following:
- All the signs of a cutaneous melanoma, including irregularly-shaped pigmented area on the skin that is changing, can be seen
- Presence of a pigmented skin lesion on the sun-exposed area of the body; in most cases, the face (or head and neck region) is involved
- When the skin lesions are seen outside the face (called Extra-facial LMM), then the chest and back are the frequent areas of presentation in men; whereas, in women, the lower legs (mostly) and the arms may be involved
- The skin lesion is usually small-sized, slow-growing, around or greater than 6-10 mm in size, and of non-uniform discoloration (usually light brown or black)
- In some cases, larger areas may show irregularly-shaped but flat, light or dark (variable) pigmented, skin patches
- In case of larger skin lesions or patches, there may be a presence of nodules within the irregular formation
- The skin pigment (in such large patches) may take on varying dark to light shades. Due to this, it sometimes becomes difficult to differentiate between the boundaries of discolored patterns and normal skin; i.e., the edges of the lesions may be skin-colored (called amelanotic lentigo maligna)
- A suspicious pigmented area/spot showing a spread of color to the surrounding skin and with swelling, redness or itching (due to inflammation). Such areas may also be scaly, or exhibit some oozing of fluid, or bleeding
How is Lentigo Maligna Melanoma Diagnosed?
A thorough history and a complete physical exam by a physician are crucial for the diagnosis of Lentigo Maligna Melanoma. Sun exposure for a long duration is usually noted by the healthcare provider.
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
- 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 may be necessary prior to establishing a definitive diagnosis, by excluding Paget’s disease of skin and squamous cell carcinoma in situ (mostly when amelanotic lentigo maligna is observed)
Note: It is very important to distinguish between lentigo maligna and Lentigo Maligna Melanoma.
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 Lentigo Maligna Melanoma?
The complications of Lentigo Maligna Melanoma may include:
- The more advanced cases of LMM metastasize beyond the skin to the lymph nodes and other organs. Organs that are commonly involved in metastasis include the:
- Gastrointestinal tract
- Recurrence following surgical removal of the skin lesions is not uncommon
How is Lentigo Maligna Melanoma Treated?
The choice of treatment for Lentigo Maligna Melanoma 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:
- 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 rarely used as a surgical treatment option for melanoma
- 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)
- 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
- 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
- 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
- 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 Lentigo Maligna Melanoma be Prevented?
A few steps to prevent Lentigo Maligna Melanoma 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 Lentigo Maligna Melanoma? (Outcomes/Resolutions)
- The prognosis of Lentigo Maligna Melanoma is nearly similar to other forms of cutaneous melanoma
- Individuals with early-stage Malignant Melanoma of Skin, Lentigo Maligna Type have better outcomes compared to those with more advanced melanoma, where the cancer has spread to the lymph nodes or other organs
- 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
- Thickness of the tumor
- Individuals with bulky disease have a poorer prognosis
- Involvement of vital organs may complicate the condition
- The surgical respectability 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 Lentigo Maligna Melanoma:
- 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)
What are some Useful Resources for Additional Information?
Melanoma Research Foundation (MRF)
1411 K Street, NW Suite 800, Washington, DC 20005
Phone: (202) 347-9675
Toll-Free (800) 673-1290
Fax: (202) 347-9678
American Cancer Society (ACS)
1599 Clifton Road, NE Atlanta, GA 30329-4251
Toll-Free: (800) 227-2345
TTY: (866) 228-4327
Skin Cancer Foundation
149 Madison Avenue Suite 901 New York, NY 10016
Phone: (212) 725-725-5176
AIM at Melanoma
3217 Bob O Link Court, Plano, TX 75093
National Cancer Institute (NCI)
U.S. National Institutes of Health
Public Inquiries Office
Building 31, Room 10A03
31 Center Drive, MSC 8322 Bethesda, MD 20892-2580
Phone: (301) 435-3848
Toll-Free: (800) 422-6237
TTY: (800) 332-8615
References and Information Sources used for the Article:
LeBoit P.E., Burg G., Weedon D., Sarasain A. (Eds): World Health Organization Classification of Tumours, Pathology and Genetics of Skin Tumours. IARC Press; Lyon 2006
http://www.cancer.org/cancer/skincancer-melanoma/ (accessed on 01/12/2017)
http://www.cancer.org/cancer/skincancer-melanoma/moreinformation/skincancerpreventionandearlydetection/skin-cancer-prevention-and-early-detection-u-v-protection (accessed on 01/12/2017)
http://www.skincancer.org/skin-cancer-information/melanoma (accessed on 01/12/2017)
http://www.skincancer.org/skin-cancer-information/melanoma/melanoma-warning-signs-and-images/do-you-know-your-abcdes (accessed on 01/12/2017)
http://www.skincancer.org/skin-cancer-information/melanoma/melanoma-warning-signs-and-images/the-ugly-duckling-sign (accessed on 01/12/2017)
http://www.mayoclinic.com/health/melanoma/DS00439 (accessed on 01/12/2017)
http://www.melanoma.org/understand-melanoma (accessed on 01/12/2017)
https://www.dermnetnz.org/topics/lentigo-maligna-and-lentigo-maligna-melanoma (accessed on 01/12/2017)
Helpful Peer-Reviewed Medical Articles:
Hedblad, M. A., & Mallbris, L. (2012). Grenz ray treatment of lentigo maligna and early lentigo maligna melanoma. Journal of the American Academy of Dermatology, 67(1), 60-68.
Alarcón, I., Carrera, C., Puig, S., & Malvehy, J. (2014). Clinical usefulness of reflectance confocal microscopy in the management of facial lentigo maligna melanoma. Actas Dermo-Sifiliográficas (English Edition), 105(3), e13-e17.
Scope, A., Wang, S. Q., & Rabinovitz, H. S. (2012). Lentigo maligna melanoma. An Atlas of Dermoscopy. Second Edition. Kindle eBook, 223-9.
Cohen, L. M. (1995). Lentigo maligna and lentigo maligna melanoma. Journal of the American Academy of Dermatology, 33(6), 923-936.
Cohen, L. M., McCALL, M. W., & Zax, R. H. (1998). Mohs Micrographic Surgery for Lentigo Maligna and Lentigo Maligna Melanoma. A Follow‐up Study. Dermatologic surgery, 24(6), 673-677.
Shin, T. M., Sobanko, J. F., Etzkorn, J. R., & Miller, C. J. (2017). Mohs Surgery for Lentigo Maligna Melanoma. In Lentigo Maligna Melanoma (pp. 73-87). Springer International Publishing.
Price, L. (2004). Lentigo maligna melanoma. Dermatology nursing, 16(5), 454.
Semmelmayer, U., Burgdorf, W. H. C., & Stolz, W. (2004). Lentigo maligna melanoma. An Atlas of Dermoscopy.
Swetter, S. M., Boldrick, J. C., Jung, S. Y., Egbert, B. M., & Harvell, J. D. (2005). Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990–2000. Journal of investigative dermatology, 125(4), 685-691.