19. Skin Cancer

https://www.youtube.com/watch?v=vqq7X3XB7Do

basal cell carcinoma

pearly papule with telangiectasias

rolled borders central ulceration ("rodent ulcer")

basal cell carcinoma

• Most common skin cancer!

• usually slow-growing and locally invasive, with metastasis being extremely rare.

• orgin: Basal cells of the epidermis

• #1 RF: sun exposure

Older fair-skinned patient + sun-exposed face/nose + slowly enlarging pearly papule with rolled borders and telangiectasias

• Surgical excision;

• Mohs surgery — (face, recurrent, high-risk lesion)

first line treatment for BCC

BCC = 3 P's:

• Pearly papule
  Palisading cells
  Poor metastatic potential

histo: Nests of basaloid cells with peripheral palisading

Topical	MOA	High-yield use
Imiquimod ⭐	TLR-7 agonist → stimulates local immune response	Superficial BCC
5-Fluorouracil (5-FU)	Inhibits thymidylate synthase → ↓ DNA synthesis	Superficial BCC

topicals for basal cell carcinomas superficial lesions (2)

_{Actinic = related to sunlight / UV radiation ☀}

• _{Actin- = ray/radiation}

• _{-ic = pertaining to}

_{Keratosis = abnormal keratin/thickening of the outer skin}

• _{Kerat- = keratin / horny tissue}

• _{-osis = abnormal condition}

_{➡ Actinic keratosis = UV-induced abnormal keratinization/thickening of the skin.}

Older patient + sun-exposed skin + rough, gritty/sandpaper lesion

& is a precursor of skin SCC

One AK → cryotherapy (liq. nitrogen)
Many AKs → topical 5-FU

treatment for actinic keratosis

#1 cumulative Sun exposure (UVB)

Actinic keratosis (precursor)

Immunosuppression (transplant patients)

Chronic wounds/scars (Marjolin ulcer)

HPV (especially genital SCC)

Smoking (lip/oral SCC)

risk factors of skin SCC

Marjolin ulcer

SCC arising from chronic wound such as previous burn scar, tends to be very aggressive

HPV 5 & 8 → skin SCC (epidermodysplasia verruciformis)

HPV 16 & 18 → cervical/anogenital SCC

HPV is a risk factor for this type of skin cancer

clinical appearance of SCC

Scaly, erythematous plaque or nodule

May ulcerate or bleed

2 classic histologic findings are:

1. Keratin pearls

   • Concentric layers of keratinizing malignant squamous cells

   • Look like round, pink/eosinophilic “onion rings”

2. Intercellular bridges

   • Connections between adjacent squamous cells caused by desmosomes

_{Other findings include atypical keratinocytes, pleomorphism, hyperchromatic nuclei, mitotic figures, and invasion through the basement membrane into the dermis.}

#1 UV exposure, especially intermittent intense sunburns

Fair skin, light eyes

Multiple or atypical nevi

major risk factors for melanoma

CDKN2A (p16)

• _{Loss → impaired cell-cycle regulation → ↑ melanoma risk}

• _{Also associated with increased pancreatic cancer risk}

genetic marker associated with familial melanoma

BRAF V600E

mutation associated with sporadic melanoma

pancreatic cancer

cancer associated with familial melanoma syndrome (CDKN2A (p16))

dysplastic nevi

atypical moles that can develop into skin cancer

define the ABCDE appearance of melanoma

>6 mm

(1/4 inch)

diameter associated with melanoma

Breslow thickness

measures depth of tumor invasion in mm

breslow thickness (depth)

most important prognostic factor for melanoma

<1mm

low risk breslow depth

1-2 mm

intermediate risk breslow depth

>4mm

high risk breslow depth

Surgical margins &

Need for sentinel lymph node biopsy

clinical implications of breslow depth

Clark Levels of Melanoma Staging

I: intraepidermal

II: in papillary dermis

III: fills papillary dermis

IV: reticular dermis

V: enters subcutaneous tissue

0.5-1 cm

recommended surgical margins for in situ melanoma

2cm

recommended surgical margins for >2mm depth

Mohs is NOT standard (except select in situ cases on face)

is Mohs standard therapy for all skin cancers?

Breslow thickness	Sentinel lymph node biopsy?
<0.8 mm AND no ulceration	❌ Usually NO
<0.8 mm + ulceration	⚠ Consider SLNB
0.8–1.0 mm	⚠ Discuss/consider SLNB
>1.0 mm	✅ Recommend/offer SLNB ⭐

& >0.8 —> consideration

indications for sentinel node biopsy in skin cancer

Immune checkpoint inhibitor–based therapy is a major first-line approach. ⭐

Drug/class	MOA
Pembrolizumab / Nivolumab ⭐	Anti–PD-1
Nivolumab + ipilimumab	PD-1 + CTLA-4 blockade
Nivolumab + relatlimab	PD-1 + LAG-3 blockade

If the melanoma has a BRAF V600 mutation, targeted BRAF + MEK inhibition (e.g., dabrafenib + trametinib) is another important first-line option.

Board answer:

Metastatic melanoma → immune checkpoint inhibitor (anti–PD-1) ⭐

BRAF V600+ metastatic melanoma → BRAF inhibitor + MEK inhibitor is a key targeted option.

first line medical treatment of metastatic melanoma

Immunosuppressed patients = dramatically increased risk

-esp with SCC

why do transplant patients have a higher risk of skin cancer

merkel cell carcinoma

rare, aggressive neuroendocrine skin cancer

Often on sun-exposed areas (head/neck)

Rapidly growing, painless, firm red/pink/purple nodule

“Painless, rapidly growing violaceous nodule”

Merkel cell polyomavirus (MCPyV)

what virus maybe associated with Merkel Cell Carcinoma?

Merkel Cell Carcinoma

Small round blue cells

markers: CK20+ classically in a perinuclear dot-like pattern; neuroendocrine markers such as synaptophysin+

Wide local excision + SLNB ⭐

Radiation therapy (often used)

Immunotherapy for advanced disease

treatment for merkel cell carcinoma

systemic therapy, NOT automatic dissection

mgmt of a positive sentinel lymph node biopsy