STEPTRACKERSKIN + ONCOLOGY | PATHOLOGY + GENETICS + PHARMACOLOGY | HIGH-YIELD REVIEW

Melanoma

The skin cancer that kills — recognized by ABCDE, staged by depth, and treated increasingly with targeted drugs and immunotherapy.

FOCUS ON
Risk: intermittent intense UV (childhood sunburns), fair skin, many/dysplastic nevi, CDKN2A, xeroderma pigmentosum. ABCDE. Radial growth (no metastasis) → vertical growth (metastasis). Breslow depth is the strongest prognostic factor. Subtypes: superficial spreading (most common), nodular, lentigo maligna, acral lentiginous (dark skin). S100, HMB-45; BRAF V600E.
TOPIC · SUBTYPE
MECHANISM · DETAILS
FEATURES
CLUE
Risk factors
UV (intense intermittent), fair skin, many or dysplastic nevi, family history (CDKN2A/p16), xeroderma pigmentosum, immunosuppression
Can arise de novo or from a nevus
Childhood sunburns matter most
Warning signs (ABCDE)
Features of disordered growth
Asymmetry, Border irregular, Color variation, Diameter > 6 mm, Evolution
"Ugly duckling" lesion
Growth phases
Radial: spreads within epidermis/superficial dermis · vertical: invades deep dermis as a nodule
Radial phase can't metastasize; vertical phase can
Vertical phase = metastatic potential
Prognosis
Depth and spread
Breslow thickness (mm from granular layer to deepest cell), ulceration, mitotic rate, sentinel node
Thin (< 1 mm) → excellent
Superficial spreading
most common
Long radial phase; BRAF V600E common
Trunk (men), legs (women); intermittently sun-exposed skin
Flat irregular multicolored lesion
Nodular melanoma
Early vertical growth
Rapidly growing dark (or amelanotic) nodule; may ulcerate
Worst prognosis of the subtypes
Lentigo maligna melanoma
Long radial phase on chronically sun-damaged skin
Elderly; large flat irregular brown patch on face
Best prognosis
Acral lentiginous
Not UV-related; KIT mutations
Palms, soles, nail beds (Hutchinson sign: pigment spreading to nail fold)
Most common type in darker skin
Mucosal & uveal melanoma
Uveal: GNAQ/GNA11
Uveal melanoma spreads to the liver
Most common primary intraocular tumor in adults
Markers & spread
S100, HMB-45, Melan-A, SOX10
Lymph nodes, then anywhere: lung, liver, brain (hemorrhagic), heart, GI, skin
Late recurrences possible
Treatment
Excision + targeted/immune therapy
Wide local excision, sentinel node biopsy; BRAF inhibitors (vemurafenib, dabrafenib) + MEK inhibitors (trametinib); PD-1 (nivolumab, pembrolizumab), CTLA-4 (ipilimumab)
Checkpoint inhibitors → immune-related colitis, hepatitis, endocrinopathies

Mechanism — sun to vertical growth

UV damagePyrimidine dimers
→
BRAF V600E / NRASMAPK on
→
CDKN2A lossCell cycle free
→
Radial growth
→
Vertical growthInvasion, metastasis

BRAF inhibitors work only in BRAF-mutant tumors and are paired with MEK inhibitors to delay resistance.

Subtypes at a glance

SUBTYPE
SITE
GROWTH
PROGNOSIS
Superficial spreading
Trunk, legs
Long radial
Intermediate
Nodular
Anywhere
Early vertical
Worst
Lentigo maligna
Sun-damaged face
Very long radial
Best
Acral lentiginous
Palms, soles, nails
Radial then vertical
Often late diagnosis

How it's tested

COMMON CONFUSIONBreslow thickness (measured depth in mm) is the key prognostic factor; Clark level (anatomic layer) is older and less used.
THE TRAPA dark streak under the nail with pigment on the surrounding nail fold is acral melanoma (Hutchinson sign), not a bruise — especially in people with darker skin.
YOUR APPROACHABCDE → biopsy → subtype (site, growth phase) → Breslow depth and ulceration → sentinel node → BRAF status → targeted or checkpoint therapy.

If you see… think…

Changing mole with irregular border and several colors → melanoma — excisional biopsy
Single most important prognostic factor → Breslow thickness
Flat irregular lesion on a man's back → superficial spreading melanoma
Rapidly enlarging black nodule → nodular melanoma
Large brown facial patch in an 80-year-old → lentigo maligna melanoma
Dark lesion on the sole of a Black patient → acral lentiginous melanoma
Pigmented tumor cells positive for S100 and HMB-45 → melanoma
Melanoma with BRAF V600E → vemurafenib/dabrafenib + MEK inhibitor
Uveal melanoma metastasis site → liver
Colitis after ipilimumab → immune-related adverse event (CTLA-4)