Glossary

A specific mutation in the BRAF gene (most often V600E or V600K) found in about 40–50% of cutaneous melanomas. It drives the cancer's growth and can be blocked with targeted drugs.

BRAF V600 mutations activate the MAPK growth pathway. Drugs that inhibit BRAF (dabrafenib, vemurafenib, encorafenib) are paired with MEK inhibitors (trametinib, cobimetinib, binimetinib) to delay resistance. BRAF testing is standard at advanced-stage diagnosis and increasingly in earlier-stage disease for adjuvant decisions.

What this means for you: A BRAF test result decides whether targeted tablets are an option for you — it is worth asking whether your melanoma has been tested and what the result was.

Source: COMBI-d / COMBI-v trials; NCCN Melanoma Guidelines.

How deep a melanoma goes into the skin, measured in millimetres from the top of the epidermis to the deepest cancer cell.

Breslow thickness is the single strongest prognostic factor for primary melanoma. It is measured in millimetres on the biopsy slide and drives AJCC T-staging: T1 ≤1 mm, T2 1–2 mm, T3 2–4 mm, T4 >4 mm.

What this means for you: This is usually the first number your clinician looks at on a pathology report; ask what your thickness means for follow-up and whether a sentinel node biopsy applies to you.

Source: AJCC Cancer Staging Manual, 8th edition.

Circulating tumour DNA — fragments of cancer DNA shed into the bloodstream. Detected in blood (a "liquid biopsy"), it can signal residual or relapsing disease earlier than imaging.

ctDNA is being studied as a way to detect minimal residual disease after surgery and to escalate or de-escalate adjuvant treatment. The MRD-positive signal often precedes radiologic recurrence by months. Not yet routine standard of care but trial-ready in melanoma.

What this means for you: You may be offered a ctDNA blood test inside a trial; it is a research tool for spotting changes early, not yet a routine test — ask whether any relevant trial is open to you.

Source: Lee RJ et al., Ann Oncol 2018; multiple ongoing trials.

Another immune-system brake, blocked by ipilimumab. Combining anti-CTLA-4 with anti-PD-1 increases response rates but also irAEs.

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) acts earlier in T-cell activation than PD-1. Ipilimumab was the first checkpoint inhibitor (FDA approved 2011). Ipilimumab + nivolumab combination is a standard option for advanced melanoma despite higher irAE rates.

What this means for you: This drug is often combined with a PD-1 drug for stronger effect but more side effects — a trade-off worth discussing openly with your oncologist.

Source: Hodi FS et al., NEJM 2010; Larkin J et al., NEJM 2015 (CheckMate-067).

Immune-related adverse event — side effects from checkpoint-inhibitor immunotherapy where the activated immune system attacks healthy tissue.

irAEs can affect any organ: skin (rash, vitiligo), gut (colitis), endocrine (thyroid, pituitary, adrenal), liver (hepatitis), lungs (pneumonitis), joints, kidneys, and rarely heart or brain. Most are manageable with prompt steroid treatment; some require holding or stopping the drug. Patients on PD-1 (e.g. nivolumab, pembrolizumab) and CTLA-4 (ipilimumab) drugs must report new symptoms early.

What this means for you: If you are on immunotherapy, the practical takeaway is: report new or unusual symptoms early (rash, diarrhoea, fatigue, breathlessness) — most irAEs are very manageable when caught quickly.

Source: ESMO Clinical Practice Guidelines for irAE management 2022; ASCO irAE guideline.

A third immune checkpoint, blocked by relatlimab. Combined with nivolumab (as Opdualag) for first-line advanced melanoma.

LAG-3 (lymphocyte activation gene 3) is another co-inhibitory receptor on T-cells. Relatlimab + nivolumab (the combination is called Opdualag) was FDA-approved in 2022 for unresectable or metastatic melanoma based on the RELATIVITY-047 trial, where PFS was longer than nivolumab alone with manageable toxicity.

What this means for you: If you hear "Opdualag", this is the combination it refers to — a newer first-line option to ask about for advanced melanoma.

Source: Tawbi HA et al., NEJM 2022 (RELATIVITY-047).

How many cancer cells are actively dividing per square millimetre — a clue to how fast the melanoma is growing.

Pathologists count mitotic figures in the dermal component of the melanoma. A higher rate (>1 / mm²) is associated with worse outcomes. Removed from the formal T-category in AJCC 8th edition but still reported and informs treatment decisions.

What this means for you: You may see a mitotic count on your report; on its own it is one input among several — ask your clinician how it fits the overall picture rather than reading it in isolation.

Source: AJCC 8th edition staging notes.

A landmark randomised trial showing that completion lymph node dissection after a positive sentinel node did NOT improve melanoma-specific survival.

MSLT-II (Multicenter Selective Lymphadenectomy Trial II, Faries et al. NEJM 2017) compared immediate completion dissection vs. observation with ultrasound after a positive sentinel node biopsy. The two arms had similar melanoma-specific survival, but the dissection arm had much more lymphoedema. The trial moved practice toward observation + close follow-up for many sentinel-node-positive patients.

What this means for you: This is why many people with a positive sentinel node are now offered close monitoring instead of a bigger operation — ask your team which path fits your situation.

Source: Faries MB et al., NEJM 2017 — PMID 28591523.

A molecular brake the immune system uses to avoid attacking healthy cells. Tumours often exploit it to hide from the immune system; anti-PD-1 drugs release the brake.

PD-1 (programmed cell death protein 1) sits on T-cells; PD-L1 is the ligand on tumour cells (and others). When they engage, the T-cell is dampened. Antibodies like nivolumab, pembrolizumab, and cemiplimab block this interaction and restore the immune attack. PD-1 inhibition transformed advanced melanoma outcomes after 2014.

What this means for you: These are the most common immunotherapy drugs for melanoma; if one is proposed, ask how it works for your stage and what side effects to watch for.

Source: Robert C et al., NEJM 2015 (KEYNOTE-006).

Sentinel lymph node biopsy — a procedure that samples the first lymph node(s) draining from a melanoma to check whether the cancer has spread.

A surgeon injects a dye and/or weak radioactive tracer near the melanoma site. The tracer travels to the first ("sentinel") lymph node, which is removed and examined. If the sentinel node is clear, distant nodes are very likely clear too. SLNB is typically offered for melanomas thicker than 0.8 mm, or thinner melanomas with adverse features.

What this means for you: If a biopsy is offered, it is staging information, not treatment — a clear sentinel node is reassuring news about how far the melanoma has travelled.

Source: NCCN Melanoma Guidelines; NCI Dictionary of Cancer Terms.

AJCC sub-stages for melanomas ≤1 mm thick: T1a is ≤0.8 mm without ulceration; T1b is 0.8–1.0 mm OR any ≤1.0 mm melanoma with ulceration.

The T1a/T1b split (AJCC 8th edition, 2017) replaced the older mitotic-rate-based split. T1b carries a meaningfully higher recurrence risk than T1a and is the threshold above which sentinel node biopsy is more commonly offered.

What this means for you: If your report says T1b rather than T1a, it simply means a slightly higher-risk thin melanoma — a common point at which a sentinel node biopsy is discussed. It is a category, not a prognosis.

Source: AJCC 8th edition; Gershenwald JE et al., CA Cancer J Clin 2017.

Tumour-infiltrating lymphocyte therapy — harvesting the patient's own immune cells from inside the tumour, growing them in a lab, and infusing them back to attack the cancer.

Lifileucel (Amtagvi) is the first FDA-approved TIL therapy for melanoma (Feb 2024), for patients with advanced melanoma who progressed on checkpoint inhibitor and (if BRAF V600+) targeted therapy. The process takes weeks and requires lymphodepleting chemotherapy + IL-2; it is delivered at specialised centres only.

What this means for you: This is a specialised, intensive option delivered only at certain centres and usually after other treatments — ask for a referral if you want to know whether you might be eligible.

Source: Sarnaik AA et al., J Clin Oncol 2021; FDA approval 2024.