Non-melanoma skin cancer

Summary of margins:

• • SCC: low-risk 5mm, high-risk 1cm
  • BCC: 5mm
  • SCC in situ: 5mm

Risk factors in common

• • Most important: cumulative UV exposure (more important for SCC)
  • Fair skin (Fitzpatrick I and II)

Fitzpatrick skin phototypes

Skin type	Reaction to sun exposure*
I	Always burns, never tans
II	Always burns, minimal tan
III	Burns minimally, gradually tans
IV	Burns minimally, tans well
V	Very rarely burns, tans profusely
VI	Never burns, tans deeply

• • Genetics - nothing firmly proven
  • Immune suppression
  • Smoking

Epidemiology

• • The most common type of malignant neoplasm in the world
  • 80% BCCs, 19% SCCs, 1% other

Clinical evaluation

• • History
  • Tumour location and size, describe appearance
    • BCC: pink, firm, opalescent, generally well-circumscribed. Often telangiectasia and redness of surrounding skin.
    • SCC: flat, red, scaly appearance with occasional cutaneous horn formation. Bleeding.
  • Examine entire local area and regional nodes
  • Full skin exam
  • Nerve symptoms - concerning

SCC

Risk factors

• • • Exposure to sunlight - cumulative chronic UV radiation
      • Direct carcinogenic effect of UV light on the keratinocytes within the basal layer of the epidermis
    • Susceptible skin types
    • Compromised immunity
      • Especially after transplant - 65x that of normal population
    • Environmental exposures
      • Arsenic
      • Organic hydrocarbons
      • Ionising radiation
      • Cigarette smoke
    • Underlying genetic disorders
      • Xeroderma pigmentosum
      • Albinism

Pathophysiology

• • • Arise as a proliferation of keratin cells in the basal layer of epidermis - appear as red or pink areas (actinic/solar keratoses).
    • >90% have p53 silencing
    • Classification: (divide into two main groups)
      • Well-differentiated
      • Moderately, poorly, and undifferentiated
        • Worse prognosis
        • Tend to treat with wider and deeper margins, consider SLNB if >2cm wide or 2mm deep, and histologic confirmation of margins prior to closure/reconstruction
    • Subtypes
      • Keratoacanthoma - subtype of invasive SCC
      • Marjolin's ulcer - arises in chronic scarred tissue - burn scars, draining sinuses, infections
        • Refers to all skin cancers within damaged tissue, but is most commonly SCC
        • Malignant transformation due to chronic inflammation, repeated injury, and impaired immune surveillance within non-healing wounds or scars
        • Aggressive, poor prognosis, high recurrence rate, much higher metastatic potential than non-Marjolin SCC
        • Commonly excised with 2-3cm margins down to fascia. Amputate if there is bony involvement or WLE is impossible. Lymphadenectomy or radiotherapy to nodes.

Clinically

• • • Most frequent on face, hands, forearms
    • More indolent when it arises in chronically sun-exposed areas
    • Hyperkeratotic, flesh-coloured, raised, with possible ulceration or erythema
      • Pre-malignant: scaly lesions with an uneven surface and an erythematous base
      • Invasive: palpable, scaling lesions with central ulcerations and elevated, firm edges

Risk profile

• • • From Sabiston:

• • • Based on 2021 NCCN guidelines
      • High-risk cutaneous SCC:
        • Lesions of any size on head/neck, feet, pretibia, anogenital regions
        • Lesions >=2cm on trunk or extremities
        • Recurrent tumour
        • Histopathologically acantholytic, adenosquamous (mucin production), or metaplastic (carcinosarcomatous) subtypes
        • Perineural invasion
      • Very high-risk:
        • Lesions >=4cm in any location
        • Histopathologically poorly differentiated tumour
        • Desmoplastic cSCC
        • >6mm thickness
        • Invasion beyond subcutaneous fat
        • PNI - tumour cells within the nerve of a nerve lying deeper than the dermis or >=0.1mm
        • Lymphatic or vascular involvement

Work-up

• • • • Indications for imaging: (CT or MRI is best tool for finding nodes)

• • • • • Tumour >2cm
        • Tumours near major head/neck nerves
        • In transit mets
        • Tumours invading deep structures
        • Systemic signs or symptoms of extracutaneous involvement
        • Findings suggestive of perineural invasion
        • Multiple high-risk features

Staging

• • • • There isn't an AJCC staging TNM system for non-head and neck SCC

Brigham and Women's Hospital tumor (T) staging system for cutaneous squamous cell carcinoma

Tumor staging system	Definition
BWH
T1	0 high-risk factors*
T2a	1 high-risk factor
T2b	2 to 3 high-risk factors
T3	≥4 high-risk factors or bone invasion

• • Use very high-risk features above, only difference size cut-off for this can be >-2cm instead of >=4cm

Treatment

• • • Local options:
      • Excision with 5-10mm margins (depending on ease of reaching these margins, and risk profile of lesion)
        • Often surrounding inflammation and hard to determine the exact extent of tumour. Can perform punch biopsies prior to excision. May just need to treat the edge of inflammation as the edge of the lesion.
        • MMS can be a good option for sensitive areas
      • Field therapies
        • Cryotherapy (small superficial lesions - effective >90%)
        • Curettage - superficial lesions <2cm
        • Topical therapies
          • See separate section under 'oncology'
          • Biopsy is indicated when the actinic keratosis is raised or recurrent after topical therapy
        • Electrodessication and curettage
        • Carbon dioxide laser
        • Dermabrasion
        • Chemical peel
    • Management of nodal disease:

• • • • Aggressive surgical resection of involved nodal disease
      • One positive lymph node <3cm with no extracapsular extension can also have adjuvant RTX
      • SLNB indications are not well-defined, but can be considered for high-risk lesions

• • Adjuvant radiotherapy indications:

• • • High-risk tumours with clear margins
    • Salvage therapy for incomplete resection
    • Perineural invasion
    • Recurrence following clear margins

• • Adjuvant systemic therapy

• • • Usually platinum-based with variable response rates
    • There is a new PD-1 inhibitor (cemiplimab), however advanced SCC remains a difficult disease to treat

• • Follow-up: full skin examination and regional node examination

• • • Local disease: every 3-6 months for 2 years, then 6-12 months for 3 years, then annually for life
    • Regional: 1-3 months for 1 year, then 2-4 months for 1 year, the 4-6 months for 3 years, then 6-12 months for life

BCC

• • Risk factors

• • • Exposure to sunlight - intense intermittent exposure to UV radiation
    • Susceptible skin types
    • Compromised immunity
      • Transplant - 10x that of normal population
    • Environmental exposures
    • Underlying genetic disorders

• • Pathophysiology
    • Arises from basal layer of epidermis and its appendages - from immature, pluripotent cells associated with the hair follicle
    • No precursor lesion
    • Classification (divide into two main groups)
      • Nonaggressive: keratotic, infundibulocystic, nodular (most common - almost 80% of all BCCs), superficial (15% of all BCCs)
        • Generally managed with 5mm resection margins
      • Aggressive: micronodular, infiltrative, sclerosing, morpheaform, desmoplastic, basosquamous (this is a 'collision' type lesion containing parts SCC/keratinizing squamous component, treated according to differentiation of the SCC component)
  • Clinically

• • • 86% occur on head
    • Rare on hand, penis and lower lip - more likely SCC here
    • Lesions on upper lip are almost always BCC
    • Most common malignant eyelid tumour
    • Nodular subtype appearance is pearly, dome-shaped, well-circumscribed, telangiectasias, possible ulceration
    • Superficial BCC
      • Macular growth pattern
      • Appears similar to psoriasis/tinea/eczema
    • Morphoeic/sclerosing BCC
      • Usually mid-facial
      • Waxy, scar-like plaque with indistinct borders
      • Wide and deep subclinical extension

• • Treatment

Treatment:

• • First, determine whether there is a HIGH or LOW risk of recurrence

	Low	High
Size	<10mm in high-risk areas (see fig)	Any size in high-risk areas of face (fusion planes and nasolabial folds)
Size	<20mm in low-risk areas	>=10mm in other areas of face/neck/pretibia
		>=20mm in all other body areas
Histo	Nodular or superficial histopathology pattern	micronodular, infiltrative, sclerosing, morpheaform, desmoplastic, basosquamous
Perineural	Lack of perineural invasion	Perineural invasion
	Primary lesion (not recurrent)	Recurrent
	Well-defined clinical borders	Scarred area (Marjolin's ulcer)
	No history of radiotherapy at site	Site of prior radiotherapy
	Immunocompetent patient	Immunocompromised

• • Workup:

• • • Lesions with large nerve perineural involvement should have a Gadolinium MRI to exclude perineural spread
    • Lack of guidelines on when to image looking for mets

• • Surgery:

• • • For low-risk BCC in non-critical areas of head/neck, surgery with 4-5mm margins is first-line

• • • • Generally easy to tell where the tumour ends, except for infiltrative and morphoeic BCCs
      • Consider Moh's microsurgery for tissue conservation

• • • For high-risk BCC, MMS is recommended if available
    • Margins:
      • Non-critical head/neck areas and low-risk: 4-5mm
      • For high-risk, >5mm is recommended
    • SLNB is unnecessary, as lymph node metastases are very rare

• • Medical:

• • • If surgery is not preferred, try topical imiquimod or fluorouracil (see above under SCC section for details)
    • For locally advanced or metastatic BCC, hedgehog inhibitors can be used

Merkel cell carcinoma

• • Risk factors
    • Older age - median 75yo
    • Light skin
    • Immunosuppression
    • Merkel cell polyomavirus infection
    • UV exposure
    • Genetic syndromes
  • Pathophysiology
    • Controversial cell of origination
      • Originally thought to be Merkel cells - found in basal layer of epidermis
      • Possibly from immature multipotent stem cell which acquires neuroendocrine features
      • Might not have a single cell of origin
    • May be associated with Merkel cell polyomavirus
      • Found in 80% of MCC
      • May be part of normal flora
    • Aggressive
  • Clinically
    • Red-pink to violaceous, firm, solitary, rapidly growing nodule
    • Typically head and neck, but can occur on extremities and buttocks
    • A symptomatic
    • E xpanding rapidly
    • I mmunosuppression
    • O lder that 50yo
    • U V exposed area
  • Workup
    • Should have imaging of regional nodes
    • CT-PET (FDG) +/- MRIB
  • Staging

Merkel cell carcinoma TNM pathologic staging AJCC UICC 8th edition

Primary tumor (T)
T category	T criteria
TX	Primary tumor cannot be assessed (eg, curetted)
T0	No evidence of primary tumor
Tis	In situ primary tumor
T1	Maximum clinical tumor diameter ≤2 cm
T2	Maximum clinical tumor diameter >2 but ≤5 cm
T3	Maximum clinical tumor diameter >5 cm
T4	Primary tumor invades fascia, muscle, cartilage, or bone
Regional lymph nodes (N)
Pathological (pN)
pN category	pN criteria
pNX	Regional lymph nodes cannot be assessed (eg, previously removed for another reason or not removed for pathological evaluation)
pN0	No regional lymph node metastasis detected on pathological evaluation
pN1	Metastasis in regional lymph node(s)
pN1a(sn)	Clinically occult regional lymph node metastasis identified only by sentinel lymph node biopsy
pN1a	Clinically occult regional lymph node metastasis following lymph node dissection
pN1b	Clinically and/or radiologically detected regional lymph node metastasis, microscopically confirmed
pN2	In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis
pN3	In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis
Distant metastasis (M)
Pathological (M)
M category	M criteria
M0	No distant metastasis detected on clinical and/or radiologic examination
pM1	Distant metastasis microscopically confirmed
pM1a	Metastasis to distant skin, distant subcutaneous tissue, or distant lymph node(s), microscopically confirmed
pM1b	Metastasis to lung, microscopically confirmed
pM1c	Metastasis to all other distant sites, microscopically confirmed
Prognostic stage groups
Pathological stage group (pTNM)
When T is...	And N is...	And M is...	Then the stage group is...
Tis	N0	M0	0
T1	N0	M0	I
T2-3	N0	M0	IIA
T4	N0	M0	IIB
T1-4	N1a(sn) or N1a	M0	IIIA
T0	N1b	M0	IIIA
T1-4	N1b-3	M0	IIIB
T0-4	Any N	M1	IV

• • Treatment
    • cN0: excision with 1-2cm margins and SLNB
      • Negative SLNB: still consider RTX to nodes if high-risk features are present
      • Positive SLNB: either clearance or RTX
    • cN1: Excision with 1cm margins and radical lymphadenectomy
    • M1: Immunotherapy (avelumab or pembrolizumab). Radiotherapy is often useful to primary tumour.
    • Radiotherapy:
      • Consider in those with <1cm margins, LVI, head and neck primaries, immunocompromise, large primary tumour (>1cm)
      • Consider to nodal bed with high-risk features but negative SLNB
  • Prognosis
    • Poor - 70% overall survival at 5 years
    • High local recurrence rates

Cutaneous angiosarcoma

• • See separate topic under soft tissue sarcoma

Extramammary Paget disease

• • Rare form of adenocarcinoma
  • Arises from apocrine glands of the skin
  • Most commonly perianal, vulva and scrotum
  • Similar clinical characteristics to eczema, bacterial and fungal infections, and non-specific dermatitis - therefore often diagnosed by biopsying lesions not responding to normal treatment
  • Mostly confined to epidermis and well-controlled with excision
  • Very difficult to control when deeper structures are involved
  • Associated with malignancies in GUT and GIT - should work up for these
  • Local recurrences are common, but may be reduced by radiotherapy

Dermatofibrosarcoma protuberans

• • Under soft tissue sarcoma

Kaposi sarcoma

• • Under soft tissue sarcoma