Melanoma

Melanoma is a malignant proliferation of melanocytes. This article details the features, diagnosis, role of sentinel node biopsy and staging.

Definition of Melanoma

Melanoma is a malignant tumour of melanocytes. Melanocytes are derived from the neural crest and synthesise melanin.  

Risk Factors for Melanoma

Ultraviolet Radiation

The risk of melanoma increases with age from natural cumulative sun exposure. There is a strong correlation with the following:

• UVA (315-400nm): sunbeds, DNA damaged by oxygen radicals
• UVB (280-315nm): sunburn, absorbed by DNA, chromosomal damage.
• UVC (200-280nm): filters by ozone

Fitzpatrick Type I + II

• Individuals with fair skin, hair, and eye colour
• Susceptibility to oncogenic UV damage in genes linked with pigmentation

Co-Morbidities

• Skin Lesions: previous melanoma, dysplastic lesions, giant CMNs
• Organ transplantation/immunosuppression
• Genetic syndromes: FAMM Syndrome

Diagnosis of Melanoma

Clinical Suspicion

Cutaneous melanoma can be clinically suspected based on a history of lesion evolution and specific features on examination.  

The classic feature is an asymmetrically pigmented lesion of variegated colour with an irregular border that is evolving. The ABCDE provides a diameter >6mm.

Histological Diagnosis

Melanoma is a histological diagnosis. This is a key differentiator to basal cell and squamous cell carcinomas, which can be resected based on a confident clinical examination.  

Initial histology can be obtained by:

1. Excisional Biopsy with a 2mm margin and cuff of fat
2. Incisional biopsy if primary closure is not possible and reconstruction required
3. Punch Biopsy can be considered but can affect Breslow thickness.
4. Shave or curettage is not recommended.

A melanoma histology report will provide the following information:

1. Relevant clinical information
2. Type of surgery: excisional, incisional, punch
3. Location: most commonly on the trunk
4. Macroscopic: vertical and depth dimensions
5. Subtype: superficial, nodular, acral, lentigo, amelanocytic, desmoplastic
6. Margins: margins excised if excisional biopsy performed
7. Ulceration: full thickness loss of epidermis, a poor prognostic sign
8. Mitosis: a marker for tumour activity, a poor prognostic sign
9. Breslow Thickness: status granulosum to the deepest part of the lesion.
10. BRAF status: if requested, can decide suitability for immunotherapy.
11. Clarkes Level: level of dermal invasion
12. Growth: radial or vertical, regression, LVI, PNI, microsatellites

Types of Melanoma

There are several different histological melanoma subtypes. These subtypes have specific clinical features and prognoses. The most common melanomas are superficial spreading.

• Superficial spreading: radial then vertical growth phases.
• Nodular: is more aggressive because it lacks a radial growth phase
• Lentigo Maligna Melanoma: arising from a lentigo maligna.
• Acral Lentiginous: usually occurs on palms, soles and nails.
• Amelanocytic: a melanoma without pigment.
• Desmoplastic: high local recurrence rates.

Wide Local Excision of Melanoma

Wide Local Excision

The current guidelines for the excision of a histological-confirmed melanoma are based on the Breslow thickness of the lesion.  

• Lentigo Maligna (in-situ): 0.5mm with a cuff of fat
• Breslow ≤ 1mm: 1cm peripheral margin, down to fascia deep margin
• Breslow 1-2mm: 1-2cm peripheral margin, down to fascia deep margin
• Breslow >2mm: 2 cm peripheral margin, down to fascia deep margin

Sentinel Lymph Node Biopsy

A sentinel node is the first lymph node receiving lymphatic drainage from a specific area and is representative of that nodal basin¹. The sentinel node has a role in prognosis, treatment pathways and staging.  It should be performed at the time of wide local excision, if indicated.

Indications for SLNB

The primary role of sentinel node biopsy is changing from that of a prognostic indicator to one that now influences access to adjuvant therapy^​6​.  

• Primary Cutaneous Melanoma ≥ pT2a
• Primary Cutaneous Melanoma ≥ pT1b considered if LVI or Mitotis ≥ 2mm

It is not currently indicated for pT1a melanomas because the frequency of sentinel lymph node metastasis is <5% ^8,9 compared to 4-12% for pT1b⁶ and 30% for BT>4mm^8.10.

Effect of SLNB on Treatment

For those with a positive sentinel node, upstaging the disease allows earlier identification for adjuvant therapies. It also allows them to be categorized in a “high-risk follow-up group”^​7​.

A patient with pT1b melanoma has 2 options:

• No SLNB = clinical Stage 1B with a 5-year survival of 97%^​3.
• Negative SLNB = pathological Stage 1A with a 5-year survival of 99%^​3.
• Positive SLNB = pathological Stage 1B.

Techniques

The 3 commonly used techniques for sentinel node biopsies are radioactive isotope, blue dye or indocyanine green.

Radioactive Isotope

• Intradermal injection of a radiotracer at the tumour site & lymphoscintigraphy
• A handheld gamma probe guides dissection
• Usually, Technetium-99m–labelled radiocolloids

Blue Dyes (initially used by Morton et al)

• Blue dye alone sensitivity of 81% (Silvestri, 2019).
• Patent Blue V, isosulfan blue and methylene blue are commonly used.
• Anaphylaxis, obscured dissection, tattooing, interferes with pulse oximetry.

Indocyanine Green

• Indocyanine green is a fluorescent tricarbocyanine dye
• Sensitivity: 91- 98%, with a specificity of 100% (Clloyd, 2014).
• It cannot be used in patients with iodine or shellfish allergies.

Positive Sentinel Node in Melanoma

Completion Lymph Node Dissection in Melanoma

Complete lymph node dissection should not be routinely recommended for patients who have a positive sentinel node biopsy^​6​. Consider this treatment option in patients who are high risk of regional relapse based on their sentinel node results:

• Extra-capsular spread
• 3 or more sentinel nodes
• Dewar Criteria^​12​ (multifocal and extensive).
• Node-only recurrence having failed first-line systemic treatment.

The MSLT-2^​13​ and DeCOG^​14​ Trials reported on the outcome of patients with a positive sentinel node randomised into observation and surgery. Key results include:

• No survival advantage over radiological observation
• Increase risk of nodal recurrence in those patients with observation

Patients undergoing immediate lymph node dissection have

• Increased rate of regional disease control^​13​
• Prognostic information^​13​
• No increase in melanoma-specific survival^​13​
• An increased risk of morbidity in nodal dissection patients^​15​

With head and neck melanomas, adjuvant therapy is preferred to neck dissection^​3​.

Adjuvant Therapy in Melanoma

Discussed in more detail: Oncological Adjuvant Therapies in Melanoma

Current guidelines state adjuvant therapy should be available to Stage 3 patients.

Generally speaking, patients deemed at high risk with a positive sentinel node should be considered for melanoma adjuvant therapy. A lymph node dissection could be considered if they have a node-only recurrence post-adjuvant treatment.

Radiological Observation in Melanoma

There is currently no consensus for ideal imaging in melanoma^​7​

Current options include:

• Ultrasound: MLST and DeCOG Trials but does have operator dependability^​5​
• CT/PET: more sensitive to picking up recurrences^​5​
• MRI is used in some UK centres^​6​

Imaging surveillance will differ for those on adjuvant systemic therapy.

Staging Melanoma

AJCC Version 8 Updates

This article is written with the most recent version of AJCC and other publications, as referenced below. The following is a list of V8 updates^​3​

Histology Reports

• Tumour thickness: record to the nearest 0.1 mm, not 0.01 mm
• Mitotic rate no longer a T category criterion (increased mitotic rate decreases melanoma-specific survival^​3)

Pathological Staging

• pT1a <0.8 mm without ulceration
• pT1b 0.8‐1.0 mm with or without ulceration or <0.8 mm with ulceration
• Pathological stage IA is revised to include T1b N0 M0 (formerly stage IB);

Metastatic disease

• N: “microscopic” and “macroscopic” is now clinically "occult" and "apparent".
• M1 subcategory designation for LDH (no longer upstages to M1c).
• M1d designation is added for central nervous system metastases.

Flashcards

References

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