Melanoma

What is Melanoma?

Melanoma is cancer that arises in the melanocyte cells of the skin. Dr. Robert Carswell coined the term melanoma (melas - dark; oma- tumor) in 1938. Melanocytes are pigment-containing cells that give brown or tan color to the skin(1^✔).

Melanoma and non-melanoma skin cancer (NMSC) are the common types of skin cancer(2^✔).

Melanoma is caused by DNA mutations. Long-term sun exposure or usage of tanning beds can cause melanoma. The ultraviolet (UV) rays damage the DNA of the skin over time and may thereby alter the normal functioning of the melanocytes. Cancerous moles are most frequently caused by prolonged exposure to UV light, especially UVA and UVB(3^✔).

Melanoma, or cancerous mole, develops as a result of DNA damage in skin cells. Melanoma is most often observed in adults. Melanoma in children is caused by either congenital moles that have become malignant or due to an inherited skin disorder (xeroderma pigmentosum)(4^✔).

Melanoma appears as an abnormal mole on certain regions of the body, such as the back, chest, legs, face, neck, or arms. Sometimes, an existing mole undergoes changes indicating a cancerous growth. The moles may either be brown, black, or with no dark color, such as tan, pink, or white. Cancer spreads to different parts of the body(5^✔).

What are the Types of Melanoma?

Depending on the site of occurrence, there are 3 types of melanoma:

Ocular melanoma

- Melanoma that occurs in the melanocytes of the eyes is called ocular melanoma. It can be further subdivided into conjunctival melanoma, choroidal melanoma, iris melanoma, and uveal melanoma(6^✔).

Cutaneous melanoma

- Melanoma that occurs in the skin is subdivided into 4 types:

• Nodular melanoma - This is an aggressive melanoma and accounts for - 15% to 30% of melanoma cases. Nodular melanoma is the second most common melanoma, but most commonly on the head (scalp) and neck. It is commonly observed in middle-aged people(7^✔).
• Superficial spreading melanoma - This type of melanoma accounts for 70% of melanoma cases and develops from an existing mole(8^✔).
• Acral lentiginous melanoma (Melanoma on foot) - Unlike most other melanomas, this type of melanoma is more common in dark-skinned individuals. This type of melanoma is found below the nails and on the palms and the soles of the feet(9^✔).
• Lentigo maligna melanoma (Melanoma onthe face) - Such tumors are large and flat and observed in light-skinned women, people who have spent a lot of time outdoors, and elderly people. These tumors occur on the face and do not spread much. They account for only approximately 10% of the cutaneous cases(10^✔).
• Amelanotic melanoma - Amelanotic melanoma (AM) is a rare form of melanoma that lacks visible pigment(11^✔). Amelanotic melanoma is a rare and aggressive type of melanoma. It is often diagnosed late because of the lack of melanin in its cells, and this causes treatment delay and, eventually, poor prognosis(12^✔).

Mucosal melanoma

- This type of tumor is difficult to detect and is found in the mucosal areas of the neck and head (scalp), the lower digestive and urinary tracts, and the vagina in females. They account for only 1% of all the cases of melanoma and patients with this type of cancer do not have a good survival rate(13^✔).

Oral melanoma

- Oral melanomas show an aggressive nature and worse prognosis than cutaneous melanoma. Oral melanoma is a very rare and aggressive carcinoma that accounts for 0.2% to 8% of all melanomas and 1% to 2% of all oral malignancies(14^✔).

Penile melanoma

- Penile melanoma accounts for 1.4% of all penile cancers and less than 0.1% of melanoma cases. Penile melanoma results from a malignant transformation of melanocytes in the neuroectodermal layer. Depending on their location on the penis, melanocytes can be considered cutaneous or mucosal(15^✔).

ICD-10-CM Code for Malignant Melanoma of Skin

Clinical Information

A type of primary melanoma that develops from atypical melanocytes in the skin. Melanocytic nevi, both acquired and congenital, and dysplastic nevi are examples of precursor lesions. There are several histologic variations of melanoma, such as superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, and lentigo maligna melanoma.

• Melanoma in situ isexcluded from type 1.
• Malignant melanoma of the genital organs' skin, sites of Merkel cell carcinoma other than the skin-code to malignant neoplasm of the location, information about Clinical Practiceis excluded from Type 2.

What are the Stages of Melanoma?

The American Joint Committee on Cancer TNM system is used with resultant clinical and pathologic staging assignments.

T (tumor) stage

Once the index lesion has been histologically confirmed as melanoma, additional characteristics that contribute to the T (tumor) stage include overall tumor thickness, the presence of ulceration, and the presence of mitosis in lesions <1 mm in thickness (T1).

N (nodal) stage

N (nodal) stage is determined by the number of involved lymph nodes. As previously discussed, nodal status should be initially assessed at the time of preoperative clinical examination. If palpable lymphadenopathy is encountered, nodal status should be confirmed via ultrasound-guided fine needle aspiration. If no clinical evidence of nodal involvement is present preoperatively, a sentinel lymph node biopsy (SLB) should be performed at the time of surgery for all lesions >1 mm in thickness. In addition, SLB should be considered for lesions between 0.76 and 1.0 mm thickness when high-risk features are present (lymphovascular invasion, high mitotic count, ulceration, etc.). Current guidelines do not recommend SLB for lesions ≤0.75 mm thick.

M (metastatic) stage

M (metastatic) stage is assigned based on the presence or absence of metastatic disease and, if present, is further classified by the location (skin, lymph nodes, viscera, lungs, or increased serum lactate dehydrogenase).

Melanoma without nodal or distant metastases is classified as Stage I or Stage II, depending on the depth of vertical invasion. Stage III disease includes patients with either gross or microscopic lymph node metastasis and Stage IV disease includes patients with evidence of distant metastasis.

Unlike other solid malignancies, the use of cross-sectional imaging and serum laboratory analysis to facilitate initial clinical staging is not routinely recommended outside of Stage IV disease. However, computed tomography (CT) (with or without positron emission tomography [PET]) and magnetic resonance imaging (MRI) should be considered for all patients with specific symptoms, Stage III disease, or even Stage II melanoma with high-risk features. In the setting of Stage IV melanoma, CT imaging of the chest, abdomen, and pelvis should be obtained, and a brain MRI can be considered(16^✔).

Melanoma Late Stage

Melanoma can spread to sections of your body far from where it began. Melanoma in this stage is known as progressed, metastatic, or stage IV. It has the ability to spread to your lungs, liver, brain, bones, digestive system, and lymph nodes. The majority of patients discover their skin cancer early, before it has progressed.

The vast majority of patients with newly diagnosed melanoma are "early-stage" - ie, clinically localized to the primary cutaneous site. For such patients, surgery represents the mainstay of treatment; current standards of surgical management have evolved based on evidence obtained from randomized trials, large multi-center and single institutional databases, and consensus panels. Treatment strategies include wide excision of the primary site with margins dictated by important biological features such as Breslow tumor thickness, and sentinel node biopsy to surgically evaluate the regional nodal basins at risk(17^✔).

What are the Risk Factors for Melanoma?

Some of the risk factors for melanoma are:

• Presence of a large number of moles (more than 100 normal moles) and changes in the moles - high risk
• Presence of atypical moles
• Family history (≥ 2 first-degree relatives with skin cancer)
• Presence of moles at birth (Congenital moles)
• Caucasian race
• Presence of a large number of freckles
• Skin that burns easily
• Frequent use of tanning beds before the age of 30
• Presence of blonde or red hair
• Weakened immune systems, such as HIV, or use of medications that suppress immunity
• Exposure to certain chemicals
• Presence of any other skin cancer
• Older people
• Light skin that does not tan well
• Presence of blue eyes
• Prolonged exposure to sunlight
• Exposure to damaging ultraviolet rays(18^✔)

What are the Symptoms & Signs of Melanoma?

The symptoms of melanoma vary between individuals. A new mole or a noticeable change in an old mole should be considered a warning sign to undergo further testing. The most common sign of skin melanoma is a cancerous mole.

The ABCDEF acronym is used to clinically identify melanoma.

A - Asymmetry of a mole

B - Irregularity of the borders of the mole

C - Color difference in the mole: Moles that change in color, become darker, or show multiple colors should be suspected for the presence of melanoma

D - Diameter of the mole. Melanoma usually occurs in moles with a diameter of more than 6 mm

E - Evolving mole. A cancerous mole will show changes in height and width

F - Feeling around the mole. There may be a change in sensation around the mole(19^✔).

How do you Diagnose Melanoma?

For the initial diagnosis, a suspicious mole is examined with an instrument called the dermatoscope which is like a magnifying glass. Malignant melanoma is assessed by a biopsy. The entire lesion mole should ideally be removed with an adequate margin during the biopsy.

Melanomas are also classified based on the degree of invasion (Clark's Stages I- V) with the higher stages determining a greater degree of invasion. Stages I and II have a good survival rate while those with melanoma stage IIB or higher have a poor survival rate.

Additionally, liver function tests and a chest x-ray are obtained to detect any spread of melanoma(20^✔).

How do you Treat Melanoma?

There are different ways to treat melanoma based on the stage of the disease.

Surgery: Tumors are excised with a 1 cm margin for a 1 mm thick lesion and a 2 cm margin for a 1 mm to 4 mm thick tumors(21^✔).

Lymph node removal: Lymph nodes surrounding the lesions are removed in patients below the age of 60 when the thickness of the tumor is in the range of 1 mm to 4 mm(22^✔).

Sentinel lymph node biopsy is used to determine the degree of spread of cancer to lymph nodes and the chances of survival of the patient. The sentinel lymph node is the first draining lymph node of the region and is identified using a radioactive tracer or a dye(23^✔).

Vaccines: Patients may be treated with vaccines to stimulate the immune system. Immunotherapy with medications like pembrolizumab, nivolumab, and ipilimumab is also useful in treating melanomas. High-dose interferon a2b has been used as adjuvant therapy for people at a high risk of relapse for cancer following the surgical removal of the melanoma, but does not appear to improve overall survival(24^✔).

Targeted therapy: Targeted therapy using BRAF inhibitors dabrafenib and vemurafenib and MEK inhibitors trametinib and cobimetinib are beneficial in the treatment of melanoma. A combination of dabrafenib and trametinib, and vemurafenib and cobimetinib has also been found to produce a good response(25^✔).

Chemotherapy: Drugs such as temozolomide, dacarbazine, a combination of dacarbazine, cisplatin, carmustine, and tamoxifen (DBCT), or cisplatin, vinblastine, and dacarbazine (CVD), are also used to treat melanoma. Chemotherapy is also sometimes combined with immunotherapy like interleukin 2 (IL-2) and interferon a2b (IFNa2b) in the treatment of melanoma(26^✔).

How do you Prevent Melanoma?

Melanoma may be prevented if appropriate measures are taken. A prior history of melanoma places the individual at a greater risk.

Primary Prevention:

• People who are at risk of getting melanoma should avoid the sun and protect their skin from getting burnt.
• They should expose very little skin by wearing protective clothing. Those who avoid the sun require vitamin D supplementation to make up for vitamin D deficiency.
• A broad spectrum sunscreen with sun protection factors (SPF) ranging between 20 and 30 should be used along with an ultraviolet A (UVA) rating of 5 stars.
• The progress of the moles should be monitored with photography.
• Individuals who are at a high risk of getting melanoma should meet adermatologist to learn about ways to self-examine themselves.
• Sunbeds and sunlamps should be avoided(27^✔).

Melanoma Prognosis

Poor prognostic factors include the following:

• Tumor thickness (worse prognosis in thicker lesions)
• Evidence of tumor in regional lymph nodes (stage III disease)
• A higher number of positive lymph nodes
• Presence of distant metastasis (stage IV disease)
• Anatomic site (trunk and/or face lesions have worse prognoses than extremity lesions)
• Presence of ulceration
• Presence of regression on histologic examination (controversial)
• Male sex

Prognosis depends on the disease stage at diagnosis, as follows:

• Patients with stage I disease - 5-year survival rate of greater than 90%
• Patients with stage II disease - 5-year survival rate ranging from 45% to 77%
• Patients with stage III disease - 5-year survival rate ranging from 27% to 70%
• Patients with metastatic disease have a grim prognosis, with a 5-year survival rate of less than 20%(19^✔).

References:

1. Sir Robert Carswell (1793-1857): coining the term "melanoma" - (https://pubmed.ncbi.nlm.nih.gov/22740229/)
2. Skin Cancer - (https://www.ncbi.nlm.nih.gov/books/NBK441949/)
3. UV Radiation and the Skin - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709783/)
4. Imaging of pediatric cutaneous melanoma - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986774/)
5. Common Moles, Dysplastic Nevi, and Risk of Melanoma - (https://www.cancer.gov/types/skin/moles-fact-sheet)
6. Ocular Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK551647/)
7. Melanoma Of The Head And Neck - (https://www.ncbi.nlm.nih.gov/books/NBK513248/)
8. Is superficial spreading melanoma still the most common form of malignant melanoma? - (https://pubmed.ncbi.nlm.nih.gov/18485983/)
9. Acral Lentiginous Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK559113/)
10. Lentigo Maligna Melanoma - (https://pubmed.ncbi.nlm.nih.gov/29489150/)
11. Amelanotic melanoma: a unique case study and review of the literature - (https://pubmed.ncbi.nlm.nih.gov/29602781/)
12. Amelanotic nodular melanoma misdiagnosed as a benign skin lesion: A rare case report from Syria - (https://pubmed.ncbi.nlm.nih.gov/35145679/)
13. Mucosal Melanoma - (https://pubmed.ncbi.nlm.nih.gov/34503731/)
14. Oral Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK513276/)
15. Penile melanoma: a 20-Year analysis of six patients at the National Cancer Institute of Peru, Lima - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406220/)
16. Chapter 6Clinical Presentation and Staging of Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK481857/)
17. Evidence-based treatment of early-stage melanoma - (https://pubmed.ncbi.nlm.nih.gov/21858828/)
18. Epidemiology and Risk Factors of Melanoma: A Review - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366310/)
19. Malignant Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK470409/)
20. Current state of melanoma diagnosis and treatment - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804807/)
21. Chapter 7Surgical Management of Melanoma - (https://www.ncbi.nlm.nih.gov/books/NBK481850/)
22. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity - (https://pubmed.ncbi.nlm.nih.gov/22677239/)
23. Sentinel Lymph Node Biopsy in Cutaneous Melanoma: Standard and New Technical Procedures and Clinical Advances. A Systematic Review of the Literature - (https://pubmed.ncbi.nlm.nih.gov/27749418/)
24. Melanoma vaccines - (https://pubmed.ncbi.nlm.nih.gov/10750729/)
25. Targeted Therapy Drugs for Melanoma Skin Cancer - (https://www.cancer.org/cancer/melanoma-skin-cancer/treating/targeted-therapy.html)
26. Chemotherapy for Melanoma - (https://pubmed.ncbi.nlm.nih.gov/26601864/)
27. Primary prevention of skin cancer: a review of sun protection in Australia and internationally - (https://pubmed.ncbi.nlm.nih.gov/15306621/)

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