Melanoma: Symptoms, Types, Causes and Treatment

Melanoma is often termed the most aggressive form of skin cancer, and its impact continues to grow worldwide. While it is highly curable in its early stages, delayed recognition and treatment can result in poor outcomes. In this comprehensive article, we explore the symptoms, different types, underlying causes, and current treatments for melanoma, synthesizing insights from leading research and clinical guidelines.

Symptoms of Melanoma

Melanoma can be insidious, with early symptoms often subtle or mistaken for benign skin changes. Recognizing these signs promptly can be life-saving, as early detection dramatically improves the chances of a cure.

Symptom	Description	Timing/Stage	Source(s)
Change in Lesion	Alteration in size, shape, or color of a mole or spot	Early	1 3
Itching	Persistent pruritus in or around a pigmented lesion	Early-Intermediate	1 3
Ulceration	Breakdown or sore on the lesion	Intermediate-Late	1 3
Bleeding	Bleeding from a mole or pigmented area	Late	1 3
Non-specific	Fatigue, pain, visual changes (if metastatic)	Advanced	2 4
Psychological	Depression, anxiety, cognitive/sleep issues	Any stage	2

Table 1: Key Symptoms of Melanoma

Recognizing Early Warning Signs

The majority of melanomas begin as a change in an existing mole or the appearance of a new, unusual-looking growth. The classic "ABCD" criteria help guide early detection:

• Asymmetry: One half doesn't match the other.
• Border: Irregular, notched, or blurred edges.
• Color: Multiple colors or uneven distribution.
• Diameter: Typically greater than 6 mm, though smaller lesions can also be melanoma.

Changes in the appearance of a mole—especially in size, shape, or color—are often the first signs noticed by patients. Unfortunately, people often delay seeking medical attention, even after noticing changes, which allows the lesion to grow thicker and more dangerous 1 3.

Progression to More Severe Symptoms

As melanoma advances, symptoms can escalate:

• Itching and Tenderness: These can persist for months and are linked to lesions of intermediate thickness 1.
• Ulceration and Bleeding: These are generally late findings and prompt more urgent medical attention but are usually associated with deeper, more advanced disease 1 3.
• Metastatic Symptoms: Once melanoma spreads beyond the skin, symptoms can become non-specific. Patients may experience unexplained pain, fatigue, weight loss, visual disturbances (such as double vision), or neurological issues, depending on where the melanoma has spread 2 4.

Psychological and Behavioral Symptoms

The diagnosis and treatment of melanoma can also impact mental health. Patients may experience depression, anxiety, sleep disturbances, and cognitive problems at all stages of the disease, emphasizing the need for holistic care 2.

Types of Melanoma

Melanoma is not a single disease but rather a group of related cancers arising from melanocytes. Each type has distinct features, behaviors, and genetic profiles.

Type	Key Features	Location/Population	Source(s)
Superficial Spreading	Most common; slow horizontal growth	Sun-exposed skin	7 8
Nodular	Rapid vertical growth; aggressive	Any skin; often trunk	7 8
Lentigo Maligna	Arises on chronically sun-damaged skin	Face, neck (elderly)	7 8
Acral Lentiginous	Palms, soles, nail beds; not sun-related	All ethnicities	5 8
Mucosal	Mucous membranes (mouth, anus, genitalia)	Rare; not sun-related	5 8
Uveal	Eye (uvea)	Rare	2 8

Table 2: Main Types of Melanoma

Cutaneous Melanoma Subtypes

• Superficial Spreading Melanoma: The most common form, accounting for the majority of diagnoses. It typically grows slowly along the surface before penetrating deeper 7 8.
• Nodular Melanoma: Characterized by rapid vertical growth, it appears as a raised bump and is more likely to metastasize early 7 8.
• Lentigo Maligna Melanoma: Develops on sun-damaged skin, especially in older adults. It starts as a flat or slightly raised mottled patch 7 8.

Less Common and Non-Cutaneous Types

• Acral Lentiginous Melanoma: Appears on the palms, soles, or under the nails. Unlike other forms, it is not linked to sun exposure and affects all ethnicities equally 5 8.
• Mucosal Melanoma: Develops on the lining of the mouth, anus, or genitalia. It is unrelated to UV exposure and tends to be diagnosed at a later stage due to its hidden location 5 8.
• Uveal Melanoma: Originates in the eye and is clinically and genetically distinct from cutaneous melanomas 2 8.

Genetic and Molecular Differences

Each subtype has unique genetic mutations. Cutaneous melanomas often have mutations related to UV exposure (such as BRAF and NRAS), while acral and mucosal melanomas have structural changes and mutations of unknown origin 5 9. These differences influence both prognosis and treatment response.

Causes of Melanoma

Understanding the causes and risk factors of melanoma provides a foundation for prevention and early detection strategies. The interplay between genetics, environment, and individual behavior is complex but increasingly understood.

Cause/Risk Factor	Description	Contribution	Source(s)
UV Exposure	Intermittent intense or cumulative sun	Major, especially fair skin	3 10 11 12 14
Genetics	Family history, specific gene mutations	High in familial cases	3 5 12
Skin Type	Fair skin, tendency to burn	Increases susceptibility	3 10 12
Number of Nevi	Large number of moles	Increased risk	3 12
Sunbed Use	Artificial UV exposure	Slightly increased risk	10 14
Other Factors	Diet, hormones, rare syndromes	Under investigation	12 14

Table 3: Causes and Risk Factors for Melanoma

Ultraviolet (UV) Radiation

The single most significant environmental risk factor is exposure to UV radiation, particularly intermittent, intense sun exposure leading to sunburns. This pattern explains why melanoma often occurs on body sites not continuously exposed to the sun, such as the trunk and legs 10 11 14. Artificial sources, such as tanning beds, are also implicated, though the risk increase is modest 10 14.

Genetic Predisposition

Some people inherit a high risk of melanoma, especially those with a strong family history or known gene mutations (e.g., CDKN2A, BRAF). Individuals with familial melanoma often have numerous atypical moles and a near 100% lifetime risk 3 5 12.

Skin Type and Other Personal Factors

• Fair skin (light complexion, freckles, red or blond hair) increases susceptibility due to reduced melanin protection 3 10 12.
• Multiple moles: A large number of nevi, especially atypical ones, are associated with higher risk 3 12.
• Immunosuppression, certain rare genetic syndromes, and possibly hormonal or dietary factors are under investigation as contributors 12 14.

Other Environmental and Lifestyle Factors

• Sun-seeking behavior: Outdoor activities and recreational sun exposure (especially in childhood) are strongly associated with increased risk 10 11 14.
• Urban vs. rural residence: Higher incidence in urban and indoor-working populations may reflect intermittent sun exposure patterns 14.

Treatment of Melanoma

Melanoma treatment has evolved rapidly in the past decade. Early-stage melanoma is often curable with surgery, but advanced disease requires a combination of innovative therapies.

Treatment Type	Best For	Key Features	Source(s)
Surgery	Early/localized melanoma	Wide excision, sentinel node biopsy	3 15 17
Immunotherapy	Advanced/metastatic	Checkpoint inhibitors (PD-1, CTLA-4)	17 18 19
Targeted Therapy	BRAF-mutant melanoma	BRAF/MEK inhibitors	5 17 18 19
Chemotherapy	Metastatic, less common	DTIC, temozolomide	15 16
Radiation Therapy	Palliation (brain/bone mets)	Stereotactic, whole-brain	16
Palliative Care	Advanced, symptomatic	Symptom relief, quality of life	4 16

Table 4: Current Treatment Approaches in Melanoma

Surgery

• Wide Local Excision: The primary treatment for early-stage melanoma. Removing the tumor with a margin of healthy tissue offers an excellent prognosis in thin lesions 3 15 17.
• Sentinel Lymph Node Biopsy: Recommended for tumors ≥1 mm thick or with other high-risk features. This helps stage the disease and guide further management 17.

Immunotherapy

• Checkpoint Inhibitors: Drugs such as anti-PD-1 (nivolumab, pembrolizumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment, significantly improving survival in advanced cases 17 18 19.
  • Combination Therapy: Using both PD-1 and CTLA-4 inhibitors can increase response rates, though side effects are also higher 17 18.
  • Indications: First-line for metastatic melanoma, especially in patients without BRAF mutations 17 18 19.

Targeted Therapy

• BRAF/MEK Inhibitors: For melanomas with BRAF V600 mutations, combinations like dabrafenib plus trametinib are highly effective 5 17 18 19.
• Considerations: Resistance can develop, and these therapies may be used alone or in combination with immunotherapy 18 19.

Chemotherapy and Other Approaches

• Chemotherapy: Once the standard for metastatic melanoma, drugs like dacarbazine (DTIC) now have limited use due to lower efficacy compared to newer therapies 15 16.
• Radiation Therapy: Mainly for palliation, especially in brain or bone metastases 16.
• Adjuvant and Neoadjuvant Therapies: Used in stage III/IV disease to reduce recurrence risk or shrink tumors before surgery 17.

Palliative and Supportive Care

In advanced, incurable melanoma, symptom management and maintaining quality of life become the priorities. Psychological support is vital, given the significant mental health burden associated with the disease 2 4 16.

Conclusion

Melanoma is a complex cancer, but advances in understanding its symptoms, types, causes, and treatments are saving lives. Early recognition and prompt intervention remain critical, while ongoing research continues to improve outcomes for advanced disease.

Key Takeaways:

• Early symptoms include changes in mole size, shape, or color; late symptoms can be severe and non-specific.
• Melanoma types vary by location, appearance, and genetic profile; superficial spreading is most common, but rarer forms occur on non-sun-exposed sites.
• Causes involve a mix of UV exposure (especially intermittent, intense sunburns), genetic predisposition, and individual risk factors like skin type and nevi count.
• Treatment is tailored to stage and genetic profile, with surgery for early disease and immunotherapy or targeted therapy for advanced cases.
• Holistic care includes addressing psychological symptoms and providing palliative support in advanced stages.

Melanoma remains a public health challenge, but awareness and medical advances offer hope for better outcomes and lives saved.