PA33.1-4 | Skin — Glossary

Clinical screening tool for differentiating naevi from melanoma: Asymmetry, Border irregularity, Colour variation, Diameter >6 mm, Evolution (change over time); Evolution is the most critical criterion.

Diffuse epidermal hyperplasia (thickening of the spinous layer).

Melanoma arising on palms, soles, and subungual areas; NOT UV-driven; most common subtype in Asian, African, and South American populations; c-KIT mutations common; Hutchinson's sign indicates subungual involvement.

A soft, pedunculated benign skin tag; histologically a fibrovascular core covered by normal epithelium.

A premalignant lesion of the skin characterised by atypical keratinocytes in the lower epidermis, solar elastosis, and an intact basement membrane; the direct precursor to invasive SCC; caused by chronic UV exposure.

The most common human malignant tumour; arises from basal keratinocytes; driven by PTCH1 mutation and constitutive Hedgehog pathway activation; locally destructive but almost never metastasises.

Small cells resembling the basal layer keratinocytes, with scant cytoplasm and dark, oval nuclei; seen in BCC and SK.

SCC in situ — full-thickness epidermal atypia with an intact basement membrane.

SCC in situ of the skin; full-thickness epidermal atypia ('windblown' appearance, parakertosis) without breach of the basement membrane; may progress to invasive SCC.

A point mutation (valine to glutamate at codon 600) in the BRAF kinase, present in ~50% of cutaneous melanomas; creates constitutive MAPK pathway activation independent of upstream signals; targeted by vemurafenib and dabrafenib.

The primary prognostic measurement in melanoma; the distance in millimetres from the granular layer of the epidermis to the deepest tumour cell in the dermis; measured by the pathologist on H&E sections; determines T stage and eligibility for sentinel lymph node biopsy.

Depth of melanoma invasion in millimeters from the top of the granular layer to the deepest invasive cell; the primary prognostic measure.

An anatomical classification of melanoma invasion depth (I–V), from confined to epidermis (I) to subcutaneous fat (V); superseded by Breslow depth in current AJCC staging but still encountered in older literature and exams.

A melanocytic nevus with nests at the dermo-epidermal junction AND within the dermis.

Benign adnexal tumor of apocrine derivation; histology shows jigsaw-puzzle basaloid nests surrounded by a pink hyaline sheath.

Benign dermal spindle cell tumor with a storiform pattern and overlying epidermal hyperplasia; characterized clinically by the dimple sign.

Premature keratinization of individual cells, visible as eosinophilic cells with dense cytoplasm within the spinous layer.

An atypical melanocytic naevus with architectural disorder and cytological atypia; a precursor lesion and risk marker for melanoma; individuals with >50 atypical naevi and family history have near-100% lifetime melanoma risk.

An atypical melanocytic nevus with architectural disorder and cytological atypia; may serve as a melanoma precursor.

Anucleate keratinocytes retaining their cell outline, characteristic of pilomatricoma.

Naevoid basal cell carcinoma syndrome; autosomal dominant germline mutation in PTCH1 causing hundreds of BCCs from early adulthood, jaw keratocysts, calcification of the falx cerebri, and medulloblastoma risk.

A developmental signalling cascade in which PTCH1 normally inhibits SMO; when PTCH1 is inactivated (UV mutation), SMO constitutively activates GLI transcription factors, driving uncontrolled cell proliferation in BCC.

An antibody against gp100 (a melanocyte-specific premelanosomal protein); more specific than S100 for melanoma (~80% sensitivity); positive in naevi (especially junctional) but strongly expressed in melanoma.

A spherical, fully enclosed collection of laminated keratin within a seborrheic keratosis.

Pigment extending from a subungual melanoma onto the proximal or lateral nail fold; a reliable clinical indicator of subungual acral lentiginous melanoma requiring urgent biopsy.

A mature melanocytic nevus with nests entirely in the dermis; shows maturation (cells become smaller deeper).

A melanocytic nevus with nests confined to the dermo-epidermal junction; appears as a flat pigmented macule.

A concentric whorl of squamous cells undergoing premature keratinisation, forming an eosinophilic lamellar structure in tumour nests; pathognomonic of squamous differentiation; seen in well-differentiated SCC.

Melanoma in situ on sun-damaged facial skin of the elderly; the radial (horizontal) growth phase before invasion.

Melanoma arising from lentigo maligna (Hutchinson's freckle) on chronically sun-damaged skin of elderly patients; long radial growth phase; relatively better prognosis than nodular subtype.

Squamous cell carcinoma arising in a chronically inflamed or scarred site (burn scar, chronic venous ulcer, osteomyelitis sinus), with a long latent period and higher metastatic risk (~30%) than sun-induced SCC.

Progressive decrease in cell size with depth in a benign melanocytic nevus; loss of maturation is a feature of melanoma.

A melanocyte differentiation antigen; specific IHC marker for melanoma and naevi (~85% sensitivity); not expressed in spindle cell or desmoplastic melanoma; used in the standard melanoma IHC panel.

A benign proliferation of naevus cells (melanocytes clustered as nests) classified as junctional, compound, or intradermal based on the position of nests; exhibits maturation from superficial to deep layers.

Malignant tumour of melanocytes; driven by BRAF V600E or NRAS mutations; characterised by radial and vertical growth phases; staged by Breslow depth; highly metastatic via lymphatic and haematogenous routes.

An aggressive melanoma subtype (~15%) with vertical growth phase from the outset; presents as a rapidly enlarging dark nodule; associated with high Breslow depths at diagnosis and poor prognosis per unit time.

The upward migration of single atypical melanocytes through the epidermis, including above the basal layer; a histological hallmark of superficial spreading melanoma; distinguishes melanoma from benign naevi.

Retention of nuclei in the stratum corneum, indicating accelerated epidermal turnover; seen in AK and psoriasis.

The arrangement of basaloid cells perpendicular to the basement membrane at the edge of tumour nests in BCC, resembling a picket fence; a pathognomonic histological feature of BCC.

Benign calcifying hair follicle tumor (calcifying epithelioma of Malherbe); shows basaloid cells, ghost cells, and calcification.

An invagination of surface keratin into a seborrheic keratosis that is open to the surface (contrast with a true horn cyst).

The early horizontal spreading phase of melanoma within the epidermis and superficial dermis; tumour cells lack metastatic capacity; associated with excellent prognosis.

A clear space between BCC tumour nests and the surrounding stroma, created during tissue processing when mucin-rich stroma shrinks away from the tumour; a diagnostically important fixation artifact.

Clinical term for nodular BCC with central ulceration and rolled, pearlescent edges; named for the progressive tissue erosion resembling rodent gnawing.

A calcium-binding protein expressed in melanocytes, Schwann cells, Langerhans cells, and adipocytes; the most sensitive (~97%) but least specific IHC marker for melanoma; used in combination with HMB-45 and Melan-A.

Surgical sampling of the first draining lymph node from a melanoma site, indicated for tumours >0.8 mm Breslow depth; a negative sentinel node predicts low risk of regional nodal spread; guides decision for completion lymph node dissection.

Sudden eruption of multiple pruritic seborrheic keratoses as a paraneoplastic sign of internal (often GI) malignancy.

A cutaneous metastasis presenting as an umbilical nodule from GI or pelvic malignancy, indicating peritoneal spread.

Degenerated elastic fibres in the dermis appearing basophilic (blue-grey) on H&E staining; a direct histological marker of chronic UV exposure and a key feature of sun-damaged skin.

A cartwheel or woven basket arrangement of spindle cells in a tumor; characteristic of dermatofibroma and other fibrous tumors.

The most common melanoma subtype (~70%); arises on any skin site; characterised by pagetoid spread, irregular junctional nests, and a radial growth phase before vertical invasion.

Benign eccrine sweat duct tumor with comma-shaped (tadpole) ductal structures in a fibrous dermis; predilection for lower eyelids.

The deep invasive phase of melanoma into the dermis; tumour cells acquire metastatic potential; corresponds to increasing Breslow depth and worsening prognosis.

A small-molecule SMO inhibitor; the first targeted therapy for BCC; FDA-approved for locally advanced or metastatic BCC; acts by blocking constitutive Hedgehog signalling at the SMO level.