Nodular Melanoma: Symptoms, Types, Causes and Treatment

Nodular melanoma is one of the most aggressive and rapidly progressing forms of skin cancer. Although it accounts for a smaller percentage of all melanoma cases, it is responsible for a disproportionate number of melanoma-related deaths. This article aims to provide a comprehensive, evidence-based overview of nodular melanoma, covering its symptoms, types, causes, and the latest treatment approaches. Understanding the unique characteristics of this melanoma subtype is crucial for both patients and healthcare providers, as early detection and intervention can make a significant difference in outcomes.

Symptoms of Nodular Melanoma

Nodular melanoma often presents differently from other types of melanoma, making it especially challenging to detect early. Its rapid growth and atypical appearance can be mistaken for benign skin lesions, leading to delayed diagnosis and poorer prognoses. Recognizing the early warning signs is therefore vital for timely treatment.

Symptom	Description	Time Course	Source
Coloration	White, blue, black, or pink/red; can be amelanotic	Rapid or sudden change	1, 2
Elevation	Raised, puffy, or "bump-like"	Develops over months	1
Texture	Firm, smooth, sometimes "does not feel right"	Within 6–12 months	1
Growth	Fast increase in size or diameter	Over weeks to months	1, 2
Borders	Round or oblong, sometimes jagged or irregular	Early to late	1
Sensation	Itching or unusual feeling	Variable	1

Table 1: Key Symptoms

Early Clinical Features

Nodular melanoma typically emerges as a new, rapidly growing nodule rather than developing from an existing mole. Unlike superficial spreading melanoma, which evolves over months or years, nodular melanoma can change noticeably within weeks. Key early features include:

• Color changes: Patients often report moles that appear white, blue, black, or even pink/red. A significant percentage of nodular melanomas are "amelanotic" (lacking pigment), making them especially difficult to identify visually 1, 2.
• Elevation and texture: The lesion becomes raised and may feel puffy or firm. Some individuals describe a sensation that the spot "does not feel right" even before it becomes visibly abnormal 1.
• Rapid changes: Growth in diameter or height can be observed over a matter of weeks or a few months, with some lesions doubling in size in less than a month 1, 2.

Differences from Other Melanomas

Unlike superficial spreading melanoma, which often shows a radial (outward) growth phase first, nodular melanoma typically skips this phase and grows vertically from the outset. This means:

• Fewer early warning signs: There may be little to no change in pre-existing moles.
• Symmetrical appearance: Despite its aggressiveness, nodular melanoma can sometimes look more regular or symmetrical than expected, especially in pigmented forms 2.
• Less pigment: Up to 37% of nodular melanomas are amelanotic or hypomelanotic (lacking or having little pigment), compared to only 7.5% of other invasive melanomas 2.

Patient-Identified Warning Signs

Recent studies have highlighted symptoms that patients themselves have noticed early on:

• "Dot-like" size at the start
• Fast changes in shape or color within 2 weeks
• Elevated, pimple-like bumps
• Persistent itchiness or discomfort
• Borders that become jagged or irregular as the nodule grows 1

Understanding and acting on these signs can be lifesaving.

Types of Nodular Melanoma

While nodular melanoma itself is a distinct subtype, there are variations within it based on location, pigmentation, and other clinical or histological features. Recognizing these types helps tailor both diagnosis and management.

Type	Location/Features	Distinguishing Trait	Source
Classic Nodular	Anywhere on the skin	Rapid vertical growth	3, 4
Amelanotic	Any site	Little/no pigment (pale)	2, 5
Pigmented	Any site	Dark coloration	2
Acral Nodular	Palms, soles, under nails	Occurs on hands/feet	6

Table 2: Types of Nodular Melanoma

Classic Nodular Melanoma

This is the most common form, characterized by:

• Sudden appearance: Arises rapidly as a new lesion.
• Vertical growth: Penetrates deeper layers of skin quickly, increasing risk of metastasis 3, 4.
• Any location: Can occur anywhere but often affects the trunk, head, neck, and lower limbs.

Amelanotic Nodular Melanoma

A challenging variant due to its lack of color:

• Pigmentless or pale: May be mistaken for benign skin growths or inflammatory lesions 2.
• Difficult diagnosis: Requires a high index of suspicion, especially for new, rapidly growing nodules 2, 5.

Pigmented Nodular Melanoma

• Dark lesions: Display black, blue, or brown coloration.
• Dermoscopic features: May show symmetrical pigmentation, blue-white veil, and peripheral black dots or globules 2.

Acral Nodular Melanoma

• Unusual sites: Appears on the palms, soles, or under the nails (subungual).
• Association with trauma: Sometimes develops at sites of previous injury 6.
• Higher risk: Acral melanomas are often diagnosed late due to their hidden locations.

Causes of Nodular Melanoma

Nodular melanoma arises from complex interactions between genetic, environmental, and behavioral factors. Understanding these causes can help guide prevention and early detection strategies.

Factor	Description	Contribution	Source
Genetic	Family history, gene mutations	Increases susceptibility	5
UV Exposure	Sunlight, tanning beds	Strong risk factor	5
Phenotype	Fair skin, freckles, light eyes/hair	Higher vulnerability	5
Trauma	Injury to skin (esp. acral sites)	Possible trigger	6

Table 3: Causes of Nodular Melanoma

Genetic Factors

• Family history: Individuals with a family history of melanoma are at increased risk.
• Gene mutations: Changes in specific genes (e.g., CDKN2A, BRAF) can predispose to melanoma, though nodular melanoma sometimes develops without known mutations 5.

Environmental and Lifestyle Factors

• Ultraviolet (UV) exposure: Prolonged or intense exposure to sunlight or tanning beds is a well-established risk factor. However, nodular melanoma can occur in areas not typically exposed to the sun, suggesting that other factors also play a role 5.
• Physical trauma: Particularly in the case of acral nodular melanoma, previous injury to the skin may sometimes precede the development of the tumor 6.

Individual Phenotype

• Skin type: People with fair skin, freckles, light-colored eyes, and hair are more susceptible.
• Age and gender: While melanoma can affect any age group, nodular melanoma tends to occur in older adults and may be more common in men 5.

Other Contributing Factors

• Immunosuppression: Individuals with weakened immune systems may be at higher risk.
• Moles and atypical nevi: Unlike other melanomas, nodular melanoma often arises de novo (as a new growth) rather than from an existing mole 3.

Treatment of Nodular Melanoma

Due to its aggressive nature and tendency for early spread, nodular melanoma requires prompt and comprehensive treatment. Advances in surgery, immunotherapy, and targeted treatments have significantly improved outcomes in recent years.

Treatment	Description	Indication	Source
Surgical excision	Removal of tumor with margin	First-line for localized	4, 5
Lymph node management	Sentinel node biopsy, dissection	For suspected spread	7
Immunotherapy	Checkpoint inhibitors, interferon	Advanced/metastatic	7, 8
Targeted therapy	BRAF/MEK inhibitors	BRAF-mutant melanoma	7, 8
Radiotherapy	Local or brain metastases	Adjuvant/palliative	8

Table 4: Treatment Approaches

Surgical Management

• Wide local excision: The primary treatment is surgical removal of the tumor with an adequate margin of normal tissue to ensure complete excision 4, 5.
• Sentinel lymph node biopsy (SLNB): Used to assess whether the melanoma has spread to regional lymph nodes. If positive, further management may be needed 7.

Lymph Node Management

• Observation vs. dissection: Recent clinical trials indicate that, for patients with positive SLNB, completion lymph node dissection does not always improve survival compared to careful observation. Decisions are individualized 7.
• Therapeutic lymphadenectomy: Reserved for patients with clinically evident nodal disease 7.

Systemic Therapies

• Immunotherapy: Immune checkpoint inhibitors (such as PD-1 or CTLA-4 inhibitors) have revolutionized treatment for advanced melanoma, improving recurrence-free and overall survival. Interferon alpha may be used in some cases 7, 8.
• Targeted therapy: For melanomas with specific mutations (e.g., BRAF V600E), targeted drugs (BRAF and MEK inhibitors) are effective 7, 8.

Radiotherapy

• Adjuvant or palliative: Radiation may be used for local control, especially in cases with brain metastases or when surgery is not feasible 8.
• Combination with immunotherapy: Emerging evidence shows that combining radiotherapy with immunotherapy can have synergistic effects, particularly in advanced disease 8.

Follow-up and Surveillance

• Regular check-ups: Due to the risk of recurrence and metastasis, ongoing follow-up is crucial.
• Patient education: Individuals who have had nodular melanoma should be vigilant for new or changing skin lesions.

Conclusion

Nodular melanoma stands out as one of the most aggressive forms of skin cancer, demanding prompt recognition and intervention. Here are the main takeaways from this comprehensive review:

• Symptoms: Nodular melanoma often presents as a rapidly growing, raised skin nodule, sometimes lacking pigment, making early detection challenging 1, 2.
• Types: Variants include classic, amelanotic, pigmented, and acral nodular melanoma, each with unique features 2, 3, 4, 6.
• Causes: Multiple factors contribute, including genetics, UV exposure, phenotype, and possibly trauma, especially for certain subtypes 5, 6.
• Treatment: A multidisciplinary approach is essential, with surgery as first-line, supported by lymph node management, immunotherapy, targeted therapy, and radiotherapy as appropriate 4, 7, 8.

Remember: Early recognition of warning signs and immediate medical evaluation are vital. Nodular melanoma progresses quickly, but with advances in treatments and a better understanding of its unique features, outcomes are improving.

Stay vigilant, protect your skin, and consult a healthcare professional for any suspicious or rapidly changing skin lesions.