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

Keratinocyte & Other Skin Tumors

Benign stuck-on growths, sun-damaged precursors, and the two most common skin cancers — plus the aggressive neuroendocrine one.

FOCUS ON
Basal cell carcinoma: most common skin cancer, upper face, pearly papule with rolled edges and telangiectasias, palisading nuclei, rarely metastasizes; hedgehog/PTCH1. SCC: sun-exposed lower lip, hands, ears; keratin pearls; from actinic keratosis; transplant patients, arsenic, chronic wounds. Seborrheic keratosis: stuck-on, benign; sudden many = Leser-Trélat.
TUMOR
MECHANISM · RISK
FEATURES · HISTOLOGY
CLUE
Seborrheic keratosis
Benign proliferation of basal-like keratinocytes
Older adults; waxy "stuck-on" tan-brown plaques; horn cysts (keratin pseudocysts)
Sudden eruption of many → Leser-Trélat (GI adenocarcinoma)
Actinic keratosis
UV-induced keratinocyte dysplasia
Rough "sandpaper" scaly papules on sun-exposed skin; parakeratosis, basal atypia
SCC precursor · cryotherapy, 5-FU, imiquimod
Squamous cell carcinoma
2nd most common
UV, immunosuppression (organ transplant), arsenic, chronic wounds/burns/sinus tracts (Marjolin), xeroderma pigmentosum, HPV
Ulcerated or scaly nodule on lower lip, ears, hands; keratin pearls, intercellular bridges
Local invasion; lip and scar SCC metastasize more
SCC in situ (Bowen disease)
Full-thickness dysplasia without invasion
Red, scaly, well-defined plaque
Arsenic → multiple lesions
Keratoacanthoma
Well-differentiated SCC variant
Rapid growth over weeks into a crateriform nodule with central keratin plug; may regress
Treated as SCC
Basal cell carcinoma
most common skin cancer
UV; PTCH1 loss → hedgehog activation; Gorlin syndrome
Pearly papule with rolled borders, telangiectasias, central ulcer ("rodent ulcer"); upper face, nose, eyelid · nests with peripheral palisading, retraction artifact
Almost never metastasizes · Mohs surgery, vismodegib
Merkel cell carcinoma
Neuroendocrine; Merkel cell polyomavirus, UV, immunosuppression
Older adults; fast-growing painless red-violet nodule on head/neck; CK20 perinuclear dot
Aggressive · checkpoint inhibitors
Xeroderma pigmentosum
AR defect in nucleotide excision repair → UV thymine dimers persist
Severe sunburn, freckling in infancy; BCC, SCC, melanoma in childhood
Strict sun avoidance
Mycosis fungoides
Cutaneous CD4 T-cell lymphoma
Patches → plaques → tumors; Pautrier microabscesses (lymphocytes in epidermis); Sézary syndrome: erythroderma + circulating cerebriform cells
Long "eczema" that won't resolve
Dermatofibroma
Benign fibrohistiocytic nodule, often after minor trauma (insect bite)
Firm brown papule on legs; dimple sign when pinched
Benign
Dermatofibrosarcoma protuberans
COL1A1-PDGFB fusion
Slow-growing indurated trunk plaque that becomes nodular; CD34 ⁺
Recurs locally · imatinib

Mechanism — UV damage and repair

UVB
→
Pyrimidine (thymine) dimers
→
Nucleotide excision repairEndonuclease → polymerase → ligase
Repair failsTP53 (SCC), PTCH1 (BCC), BRAF (melanoma)

UVA penetrates deeper (aging); UVB burns and causes most mutations. Sunscreens need both.

BCC vs SCC

FEATURE
BASAL CELL
SQUAMOUS CELL
Frequency
Most common
Second
Typical site
Upper lip, nose, eyelid
Lower lip, ears, hands
Look
Pearly, rolled edges, telangiectasias
Scaly, ulcerated, keratotic
Histology
Palisading basaloid nests
Keratin pearls
Precursor
None
Actinic keratosis
Metastasis
Very rare
Uncommon (lip, scar higher)
Transplant risk
↑
↑↑ (most common in transplant)

How it's tested

COMMON CONFUSIONUpper-lip skin cancer is usually basal cell; lower-lip cancer is usually squamous cell (more sun on the lower lip, smoking).
THE TRAPIn organ transplant recipients, SCC outnumbers BCC — the usual ratio reverses with immunosuppression.
YOUR APPROACHLook (pearly, scaly, stuck-on, crater) → site → exposure (sun, arsenic, transplant, scar) → histology clue → behavior and treatment.

If you see… think…

Pearly papule with rolled edges and telangiectasias on the nose → basal cell carcinoma
Tumor nests with peripheral palisading and clefting → BCC
Ulcerated nodule on the lower lip of a farmer → squamous cell carcinoma
Kidney transplant recipient with many scaly skin cancers → SCC
Rough sandpaper papules on a bald scalp → actinic keratoses
Waxy stuck-on lesions with horn cysts → seborrheic keratosis
Sudden appearance of dozens of seborrheic keratoses → Leser-Trélat — look for GI cancer
Crater-shaped nodule with keratin plug grown in 6 weeks → keratoacanthoma
Child with severe freckling and multiple skin cancers → xeroderma pigmentosum
Rapid red nodule on an older man's face, CK20 dot-like → Merkel cell carcinoma