Symptoms of Melanoma

ABCDE Criteria: Asymmetry (one half unlike the other), Border irregularity (notched, scalloped, poorly defined), Color variation (different shades of brown, black, red, white, blue), Diameter >6mm (pencil eraser size), Evolution (changing in size, shape, color, elevation, or new symptom: bleeding, itching, crusting).

Ugly Duckling Sign: A mole that looks different from all other moles on the individual. More sensitive than ABCDE alone. Patients often identify their own melanoma by this sign.

Nodular Melanoma: May not follow ABCDE. Presents as rapidly growing, firm, dome-shaped nodule. Often uniformly dark or amelanotic (pink/red). Ulceration and bleeding common. More aggressive.

Acral Lentiginous: Palms/soles: irregular pigmented macule/patch. Subungual: longitudinal brown/black band (melanonychia striata) with Hutchinson sign (pigment extension to proximal/lateral nail fold).

Metastatic Symptoms: Regional lymphadenopathy. In-transit metastases (tumor deposits between primary site and regional nodes). Distant: liver (pain, LFTs), lung (cough, dyspnea), brain (seizures, focal deficits), bone (pain, fractures).

Treatment of Melanoma

Surgery: Primary: wide local excision with margins based on Breslow depth (in situ: 5mm, ≤1mm: 1cm, 1-2mm: 1-2cm, >2mm: 2cm). Sentinel lymph node biopsy (SLNB) for Breslow >1mm or >0.75mm with adverse features. Completion lymphadenectomy no longer routinely recommended for positive SLNB (MSLT-II, DeCOG-SLT). Local recurrence: excision, isolated limb infusion/perfusion for in-transit disease.

Adjuvant Therapy: Stage III: nivolumab, pembrolizumab (anti-PD-1), or dabrafenib + trametinib (BRAF/MEK inhibitors for BRAF-mutant). All significantly improve RFS vs. observation. Stage IIB/IIC: pembrolizumab (KEYNOTE-716) improves RFS. Adjuvant RT for select high-risk nodal disease (extracapsular extension, multiple nodes).

Advanced/Metastatic: Immunotherapy first-line: anti-PD-1 monotherapy (nivolumab, pembrolizumab) or nivolumab + ipilimumab (anti-CTLA-4) for higher tumor burden/BRAF wild-type/LDH-elevated. ORR 40-60%, durable responses. Targeted therapy first-line for BRAF-mutant: dabrafenib + trametinib, vemurafenib + cobimetinib, encorafenib + binimetinib. ORR 65-70% but median PFS 12-14 months.

Other: Intralesional therapy: talimogene laherparepvec (T-VEC, oncolytic virus) for injectable dermal/subcutaneous/ nodal lesions. RT for symptomatic metastases (bone, brain). Temozolomide in selected cases.

Prognosis of Melanoma

By Stage (AJCC 8th): Stage 0: 5-year OS 100%. Stage I: IA 99%, IB 97%. Stage II: IIA 94%, IIB 87%, IIC 82%. Stage III: IIIA 93%, IIIB 83%, IIIC 69%, IIID 32%. Stage IV: M1a 32%, M1b 25%, M1c 16%, M1d (CNS) 10%.

Prognostic Factors (primary): Breslow thickness (most powerful predictor of survival), ulceration (upstages to next T category), mitotic rate (≥1/mm² for T1), lymphovascular invasion, microsatellitosis, regression.

Prognostic Factors (nodal): Number of positive nodes, size of nodal metastasis, extracapsular extension, matted nodes, micro vs. macrometastasis.

Prognostic Factors (metastatic): LDH (most important), site and number of metastases, BRAF mutation status, ECOG performance status.

Immunotherapy Era: 5-year OS for advanced melanoma improved from <10>

Precautions for Melanoma

Sun Protection: Broad-spectrum sunscreen (SPF 30+, UVA/UVB), reapply every 2 hours. Wear protective clothing, wide-brimmed hats, UV-blocking sunglasses. Avoid peak sun hours (10am-4pm). No tanning beds. Vitamin D supplementation if sun avoidance (600-800 IU/day).

Skin Self-Examination: Monthly full-body skin self-examination (mirror for back, scalp, buttocks, genitalia). Photographic documentation of moles. The ugly duckling sign. Any new or changing lesion should be evaluated by dermatologist.

Professional Screening: Annual total body skin examination by dermatologist. More frequent (every 3-6 months) for high-risk: personal history, family history, >50 nevi, atypical nevi, prior NMSC, immunosuppression. Dermoscopy significantly improves diagnostic accuracy.

Family Screening: First-degree relatives of melanoma patients have 2-3x increased risk. Genetic counseling for familial melanoma (≥2 first-degree relatives, multiple primaries, pancreatic cancer association). CDKN2A testing in appropriate context.

Immunotherapy Monitoring: Immune-related adverse events: skin (rash, vitiligo), colitis/diarrhea, hepatitis, pneumonitis, endocrinopathies (thyroiditis, hypophysitis, adrenalitis, T1DM). Patient education on reporting symptoms early. Can occur at any time, even months after stopping therapy.

Targeted Therapy Monitoring: Pyrexia (dabrafenib + trametinib - prophylaxis with antipyretics), cutaneous SCC/keratoacanthomas (paradoxical MAPK activation), LVEF decline, ocular toxicity (retinal vein occlusion), photosensitivity.