STEPTRACKERSKIN | PATHOLOGY + BIOCHEMISTRY + GENETICS | HIGH-YIELD REVIEW

Pigment Disorders & Nevi

Too little or too much pigment — sorted by whether melanocytes are missing or just making the wrong amount — and the moles that are benign or warning signs.

FOCUS ON
Vitiligo: melanocytes destroyed (autoimmune). Albinism: melanocytes present, melanin not made (tyrosinase). Melasma: hormone-driven facial pigment (pregnancy, OCPs). Nevi mature from junctional (flat) → compound → intradermal (raised, pale). Dysplastic nevi (CDKN2A) are melanoma precursors and risk markers.
DISORDER
MECHANISM
FEATURES
CLUE
Vitiligo
Autoimmune destruction of melanocytes (↓ number)
Sharply demarcated depigmented patches, often symmetric (face, hands, genitals); white hair
Autoimmune thyroid, Addison, T1DM, pernicious anemia · Wood lamp
Albinism
Normal melanocyte number, ↓ melanin: tyrosinase deficiency (OCA1) or defective transport; AR
White hair and skin, nystagmus, ↓ visual acuity, photophobia
↑ skin cancer risk
Ocular albinism
X-linked; melanosome defect in the eye
Vision problems with normal skin
Boys
Melasma
↑ melanin from hormonal (estrogen) and UV stimulation
Symmetric brown patches on cheeks, forehead, upper lip; pregnancy ("mask of pregnancy"), OCPs
Sun protection, fades postpartum
Ephelides & solar lentigines
Freckles: ↑ melanin, normal melanocyte number · lentigo: ↑ melanocyte number
Freckles darken with sun; solar lentigines ("age spots") don't fade
Both benign
Café-au-lait macules
↑ melanin in basal keratinocytes
Uniform light-brown flat patches
Many → NF1; jagged borders → McCune-Albright
Junctional nevus
Nests of melanocytes at the dermal–epidermal junction
Flat, uniformly brown macule; children
Earliest stage
Compound nevus
Junctional nests + dermal nests
Slightly raised, pigmented papule
Teens, young adults
Intradermal nevus
Nests only in the dermis; cells mature (smaller) with depth
Raised, flesh-colored to light papule; adults
Maturation with depth = benign
Dysplastic (atypical) nevus
Architectural and cytologic atypia; familial CDKN2A
Larger (> 6 mm), irregular border, variegated color; many → dysplastic nevus syndrome
Melanoma precursor and risk marker
Spitz & blue nevi
Spitz: epithelioid/spindle melanocytes · blue: dermal dendritic melanocytes (Tyndall effect)
Spitz: pink dome on a child's face · blue: blue-black papule
Spitz mimics melanoma histologically
Large congenital nevus
Present at birth; > 20 cm adult size
"Bathing trunk" nevus; can involve leptomeninges
↑ melanoma risk

Mechanism — making melanin

MelanocyteNeural crest, basal layer
→
Tyrosine → DOPA → melaninTyrosinase (needs copper)
→
Melanosomes
→
Transferred to keratinocytesCap over nuclei

MSH (from POMC, as is ACTH) stimulates melanocytes — why high ACTH (Addison, ectopic ACTH) darkens skin.

Pigment change: number or output?

CONDITION
MELANOCYTE NUMBER
MELANIN
Vitiligo
↓ (destroyed)
↓
Albinism
Normal
↓
Freckle (ephelis)
Normal
↑
Melasma
Normal
↑
Lentigo
↑
↑
Nevus
↑ (nests)
Variable

How it's tested

COMMON CONFUSIONVitiligo has no melanocytes; albinism has normal numbers of melanocytes that can't make pigment. A biopsy (or Wood lamp) separates them.
THE TRAPA benign nevus shows maturation — cells get smaller deeper in the dermis. A deep nodule of large atypical cells without maturation is melanoma.
YOUR APPROACHHypo- or hyperpigmented → melanocyte number vs melanin output → distribution and trigger → associated systemic disease or syndrome.

If you see… think…

Depigmented patches with Hashimoto disease → vitiligo
White hair, pale skin, nystagmus, normal melanocyte count → albinism (tyrosinase)
Pregnant woman with brown patches on cheeks → melasma
Brown spots on sun-exposed hands of an older adult → solar lentigines
Six café-au-lait spots + axillary freckling → NF1
Flat uniform mole in a child, nests at the junction → junctional nevus
Soft flesh-colored dome on an adult's face, dermal nests → intradermal nevus
Many large irregular moles and family melanoma → dysplastic nevus syndrome (CDKN2A)
Pink dome-shaped papule on a child's face → Spitz nevus
Hyperpigmentation of creases and gums with hypotension → Addison disease (↑ ACTH/MSH)