Squamous Cell Carcinoma (and other skin lesions)


INTRODUCTION

Included here are:

Marjolin's Ulcer
Bowen's Disease
Verrucous Carcinoma
Keratoacanthoma
Actinic Keratoses
- (aka solar / senile keratosis)

D I A B M I M


EPIDEMIOLOGY

2nd most common skin malignancy.
Age
Peak incidence 40-80 years.
Increasing in young due to childhood sun over-exposure.
Sex
M>F; occupational.
Geography
Predominantly Caucasians.

Risk Factors

Environmental:
Exposure to UVB is central.
- more exposure = more SCC
Carcinogens (cigarette smoke, pesticides, radiation).
Chronic irritants.

Personal
Fair hair, fair skin, blue eyes.

Precursors:
SCCs arise in an area that have had premalignant change.
- precursors are solar (actinic) keratosis, Bowen's disease (in situ SCC); see below.
- may occur in scars (Marjolin's Ulcer; see below).

Comorbidities:

Past hx of skin cancers.
HPV for mucocutaneous surfaces.
Xeroderma pigmentosum, albinism.
Immunosuppression after kidney transplants may lead to multiple / confluent SCCs (perhaps virally-related):

- associated drugs: prednisone, cyclosporine, eosothyoprin
Other acquire cell-mediated immune deficiencies:
- lymphomas, leukemias, autoimmune diseases.

D I A B M I M


AETIOLOGY

Tumour
.
Arises from the Malpighian layer.
- ie those that normally migrate out to from the keratinised squamous layer.
D I A B M I M


BIOLOGICAL BEHAVIOUR


ACTINIC KERATOSIS
Aka senile / solar keratoses.
Arise from sun damaged skin.
- mostly elderly men who ignore them.
- often on hands / face and helix of ears.
Are Premalignant
- 6-10% lifetime SCC risk
- watch for any change in size or appearance.
Areas of epidermal dysplasia usually on sun-exposed fair skin.
Give rise to painless cutaneous scaling.
- raised plaque of skin with keritonous layer.
- should be confined to skin; if tethered suspect invasive SCC
- local lymph should not be enlarged.
Must rule out SCC
Remove then with liquid nitrogen / diathermy preceded by curettage (more scarring with diathermy).
- multiple lesions treated with 5FU cream; not radiotherapy.
- further sun protection essential.


KERATOACANTHOMA
Similar in appearance to SCC
But rapid growth for 1-2m then involution for 1-2 months
Treated by excision biopsy
- must rule out SCC
iamge

BOWEN DISEASE
Intraepidermal SCC (SCC in situ)
Premalignant (3-5% transform)
Frequent in elderly.
Persistent, progressive, usually flat, scale / crusted plaque.
- often flat pink papular pactures covered in crusts.
- often mistaken for eczema

- when crusts removed, oozy bloody papilliferous surface.
Rule out invasion.
If diagnosis uncertain, biopsy & lack of response to steroid may help.
Excision is best
- recurrence if not taken deep enough or skin appendage structures involved.
- radiotherapy has to be full tumour doses.
- chemo with 5FU may be effective if very large or field change.
- cryotherapy / curettage & cautery often undertaken instead.

MARJOLIN'S ULCER
SCC arising in a longstanding ulcer or scar.
- commonest in a venous ulcer or a burns scar.
Similar to other SCC, but not usually so florid.
Edge not always raised; may be subtle & masked.
View unusual nodules / changes in a chronic lesion with suspicion
- particularly if enlarging / discharging foul matter.
Lymph is usually involved late as local drainage damaged in scar.


VERRUCOUS CARCINOMA
Well-differentiated SCC
Appear warty.

Invade locally but rarely metastasise
More commonly on palm and soles - 'carcinoma ciniculatum'.


SCC

Pathogenesis

Role of UV radiation

UVB thought to cause most SCCs
i) Direct carcinogenesis
- keratinocytes in the basilar layer affected.
- tumor promotion & growth result from unrepaired mutations.
ii) Depression of cutaneous immune surveillance
- inhibition of tumor rejection.
- p53 tumor suppressor genes mutated in >90% of SCCs.

Natural History
Routinely begin as solar keratoses (see below)
- best differentiated by feeling the lesion; base has concerning thickness to palpation
- appear on chronically sun-damaged skin.
- 80% arise on arms, head and neck.
When develops a plaque-like thickening, termed Bowen's disease (see below)
Later invades epidermis, dermis and adjacent tissues.
- overall conversion rate low, ie ~1/1000 lesions/year.

Pathology
Histology shows invasive nests of cells.
- spread in all directions.
- clusters of cells show concentric rings of flattened squamous cells.
- often called 'epithelial pearls'.
Variable central keratinisation.
Horn cell formation.
No peripheral palisading as for BCC.
Cells vary from large, well differentiated cells to anaplastic cells.

Complications
Metastasis
3-10% metastasise (when not treated).
- ie rare unless lesions are large and neglected
- very rare for tumours less than 0.5cm.
- lip / ear lesions metastasise earlier, even when well differentiated.
First spreads to regional lymph nodes.
- nb these may be enlarged simply due to associated infection
And then may spread systemically.
Once SCC has metastasised to nodes the 5 year survival is 35%.
- but rare to die of SCC (~1/500).

Recurrence

Similar risk factors to BCC
Associated with:
- tumor size (>2cm face; >1cm head/neck; >0.6cm other)
- depth of invasion
- perineural invasion
- immune status of pt
- borders poorly defined
- earlier recurrence
- pst radioRx / inflammation
- rapid growth
- mod-poor differentiation.

D I A B M I M


MANIFESTATIONS

Symptoms
Local
Initially an area of crusting
- usually hyperkeratotic
- may be clinically indistinguishable from solar keratoses.

Progress to form a palpable scaly nodule or plaque - irregular in shape.

May ulcerate centrally with a pink rolled edge.


Metastatic
Spreads as above.

Signs
They appear more inflammatory, feel more indurated and ulcerate sooner than BCC.
One key to diagnosis is surface keratin.
Initially indistinguishable from solar keratosis.

Other Differential Diagnoses

Keratoacanthoma

Overgrowth of hair follicle cells
- produce a central plug of keratin.

Rapidly growing, often for 6-8 wks
- are benign lesions that regress spontaneously over months when the plug separates
- may leave a small scar.
Can look very similar to SCCs.
- conical 'volcanic' appearance.
- have an irregular crater centre and keratotic plug
- undamaged surrounding skin helps make distinction possible.
- usually solitary, on face or hands
- rubbery feel, with hard central core.

- necrotic centre may be brown or black.
Excision to confirm.

D I A B M I M


INVESTIGATIONS
Clinical diagnosis.

Pathology
Histopathology for excised lesion or biopsy.
Shows above features and degree of invasion.

Stage
Same for BCC and SCC:
Stage 0
Tis
N0
M0
Stage I
T1
N0
M0
Stage II
T2 or T3
N0
M0
Stage III
T4
Any T
N0
N1
M0
M0
Stage IV
Any T
Any N
M1
T-stage
Tx = unassessable
Tis = in-site
T1 = ≤2cm (any dimension)
T2 = >2cm but not >5cm
T3 = >5cm
T4 = invasive deep to dermis (cartilage, bone, muscle, etc)
N-stage
Nx = unassessable
N0 = nil
N1 = nodes.
M-stage
Mx = unassessable
M0 = nil
M1 = nodes.
D I A B M I M


MANAGEMENT

Either surgery or radiotherapy.

Prevention

Limit UV exposure.
Precancerous lesions in high risk pts (e.g. AKs) should be aggressively managed
- shave excision or topical therapies (cryotherapy, photodynamic therapy, topical 5FU)
- lesions resistant to nonsurgical therapy should undergo excision or biopsy.
If the frequency and severity of skin tumours becomes life theratening, reduction of immunosuppresion meds must be considered in some transplant pts.

Treatment options

Surgical vs 'Field Treatment'
Field treatments work on a generalized area, but don't define margins
Consider carefully in terms of lesion, patient and risk factors for recurrence
Surgical excision preferable for most.

Surgical

Surgical excision

Cure rate ~90% at 5y.
Re-excision for +ve margins.

Margins
As per BCC
Low risk = 4-6mm
High risk = 10mm
- primary risk factors are site and size
- Ie trunk / extremities >2cm, head/neck >1cm, eyes ears, nose mouth, hands feed >6mm
- recurrent
- immunocompromised, radiotherapy,
- poorly differentiated, adenoid, adenosquamous or desmoplastic types

Moh's micrographic surgery
99.5% cure rate
Serial transverse slices under frozen section until clearly free of tumour.
- recommended for lesions of  high-risk of recurrence in anatomic areas where preservation of tissue important (eye, nasal ala, mouth, ear).

Nodes palpable
Need FNA
Note negative FNA with suspicion does not rule out metastatic spread
--> repeat FNA or proceed to open biopsy.

Technical Notes
Mark edges to include appropriate oncologic margin.
Excision line injected with local + adrenaline
Excise before planning closure
Orient specimen for histologic margins
Incise down to deep fascia, beveling blade to prevent undermining.
Atraumatic handling with toothed forceps.

Reconstruction and closure
Small defects closed with ellipse.
- Avoid long ellipses as enlarge the scar, which will need total reexcision if margins +ve
Fashion along skin tension lines
Deep dermis closure with buried 3-0 vicryl
Then epidermis with prolene 5-0 to 6-0, removed at 5-7d
Chronic steroids or wound beds irradiated --> epidermal suture closure with 10-14d tensile strength.

Small low risk lesions closed at excision
High-risk lesions with dubious margins:
- secondary intention, primary closure or skin graftin.
Local flap closures when margins are in question is contraindicated.
Avoid wide undermining unless known that tumour margins negative

Definitive reconstruction when histopath is back.
- most can be closed with V-Y closure, rotation flap, transposition flaps, or advancement flaps.
- larger defects with pedicled flaps, or free-flaps.
- pectoralis myocutaneous flap commonly used in head and neck but not well suitable to defects superior to the mandible.
Free tissue transfer recommended in radiotherapy fields, when separating skin from saliva or CSF covering vital structures.

Complications
Bad scar
- allow to mature for 3m before considering reexcision
- if crosses tension lines, can contract and be unacceptable.
- Z-plasty can align the scar
- patients with keloid should be aggressively managed with silicone dressings and steroid injections; performed at initial resection and repeated

Alternatives to Excision

1. Electrodissection and curretage
- low risk lesions / multiple lesions
- tension on the underlying dermal sling; sequentially smaller curettes followed by cautery

2. Cryotherapy
- excellent cosmesis; recurrence ~1-%

3. Chemotherapy
- low risk BCCs / superficial BCCs and AKs
- respond to topical 5FU cream, b.d. for 4-8 weeks
- also used in Bowen's disease though not well established evidence
- inflammatory reaction with burning, redness oozing
- 5% imiquimod; apoptosis promoter for low-risk lesions' 1cm margin for 8h (overnight) 5x per week for 6-12w
--> cure in 80% superficial BCC and 66% nodular BCCs
--> brisker skin reactions.
Oral retinoids effective as well.

4. Radiation therapy
Primarily or post-operatively for very high risk lesions
Suitable for pts >50y who want to avoid surgery (deformity, or comorbidity)
Outcomes below surgery (local control 80-90%)
- and recurrences are aggressive.
Primay radiotherpya produces local tissue effects; dermatitis and alopecia
- can be more severe skin breakdown
Adjuct for inovlved margins where further excision has unacceptable morbidity.


Field Treatments

Cryotherapy, electrodesiccation, 5FU
Usually for small lesions (2-5mm)
Local control >90% for cryotherapy.
- heal slowly and leave a pale scar.

Radiotherapy
Highly effective for BCC and SCC
- also useful for difficult areas / skin at high risk of recurrence.
Adjunct to lymph node dissection for metastatic disease
- recommended for multiple lymph node involvement OR extra-capsular nodal spread.
Generally reserved for elderly pts unsuitable for surgery / certain anatomical sites.

FAQs
Do I need to conduct routine follow-up
No, unless they have Gorlin's syndrome.


D I A B M I M


References
Browse 4th
Sabistons 17th

SCC

Malignancy of epidermal keratinocytes

Aetiology

Risk factors

UV exposure – UVB is thought to be responsible via a direct mutagenic effect on dividing keratinocytes in the basilar layer of the epidermis depression of cutaneous immune surveillence

XRT

Smoking

— Oral

Viral infection

— HPV infection

— EBV infection

Organic hydrocarbons

Ingestion of arsenicals

Immunosuppression – the intensity and duration of immunosuppression is associated with disease.       Immunosuppressive drugs, leukemia, lymphoma and auto-immune disease. HPV is causative             factor in genital acral and peri-ungual regions

Chronic ulceration

Actinic keratosis

Bowen’s

Xeroderma pigmentosa

— RR 1000x

— Autosomal recessive

— susceptibility to sunlight induced damage

— inability to repair DNA damage

Albanism – partial or complete deficiency of melanin production

Pathology

Macro

Area of keratosis with small oozing ulcer

Widely ulcerated with raised indurated everted edges

Occasionally inflammatory appearance

— Tend to be poorly diff.

Micro

Tongues of squamous cells invading BM of dermis

Pale nucleus, eosinophilic cytoplasm

Intercellular bridges

Keratin pearls of central keratin surrounded by prickle cells

Variants

Spindle cell

            — Poorly diff

Pseudoglandular

            — Acantholysis pseudoacinar pattern

            — Can be mistaken for adenoCa

Verrocous

            — Slow growing

            — Mouth, larynx, genitalia and occasionally skin

            — Fungating

            — Invade deeply and extensively

            — Rarely metastasis

            — Can progress to high grade SCC after XRT

Staging

TNM

T

T1      2cm

T2        2-5cm

T3        >5 or deep dermal invasion

T4        Invasion of other extra-dermal structures (skeletal muscle, bone, tendon)

 

            N

N1 movable ipsilateral

N2 movable contralateral or bilateral

N3 fixed regional

Spread

Rate of lymph node metastasis depends on site of origin

Sundamaged skin 3%

Mucocutaneous 11%

Clinical

Middle age – elderly

— 40-80yrs

Exposed skin

— Nose

— Ear lips forehead

Relatively more common on non-exposed skin than BCC

Rx

Treatment of primary site

A skin biopsy is important before treatment of any skin cancer.

Most non-melanoma skin cancers are small low risk lesions that respond with a 90-95% success rate to standard treatment.

Excision

— with margins clear of carcinoma typically 5-10mm of normal appearing skin for low risk SCC (the evidence regarding the adequacy of margins is less clear than melanoma).

Radiotherapy

Can be used for 1° treatment

Avoid pinna (radionecrosis) and scalp (hair loss)

Cosmetic results good to excellent especially for preserving large areas of skin in head and          neck region.

            — small amount of hypopigmentation or telangiectasia in the treatment

Indications

— Recurrence after surgery where re-excision is not possible

— H&N

Contraindications:

— xeroderma pigmentosum,

— epidermodysplasia verruciformis

— basal cell nevus syndrome: may induce more tumors in Rx area

Adjuvant XRT to primary site and draining lymph nodes may also be used when many high risk factors (see Mohs) are present, or there is extensive neurotrophism

Mohs micrographic excision

—    Mohs may reduce recurrence rate when there are risk factors for subclinical invasion and recurrence.

o   Recurrent tumour

o   Tumour is on the hand/foot, genitals, in front or behind ear, temple, mandible or chin, lip, nose, peri-orbital region or central face and >6mm

o   Cheek, forehead, scalp or neck and >10mm

o   Trunk or extremity and >20mm

o   Poorly differentiated

o   Clark level V or >4mm deep

o   Perineural invasion

o   Rapid growth

o   Associated with scars or prior radiotherapy

o   immunosuppression

Field therapy techniques

Cryotherapy

Can be used for well defined in situ lesions

Absolute C/I

— abnormal cold tolerance

— cryoglobulinemia

— cryofibrinogenemia

— Raynaud's disease

only for treatment of lesions on hands and feet

— platelet deficiency disorders

— Morphea (localized cutaneous scleroderma)

— sclerosing basal cell carcinoma

Relative C/I

            tumors of scalp

            ala nasi, nasolabial fold, upper lip vermillion border

            tragus, postauricular sulcus

            free eyelid margin

            lower legs

Morbidity

— Oedema

especially around the periorbital region, temple, and forehead

— Treated tumors usually exude necrotic material, after which an eschar forms and persists

for about 4 weeks

— Permanent pigment loss at the treatment site is unavoidable

— Atrophy and hypertrophic scarring have been reported, as well as instances of motor and

sensory neuropathy.

Topical 5FU

Can be used for Rx of in-situ lesions and small superficial lesions

N+

Excision and block dissection

Prognosis

Variable behavior

SCC in burns and irradiated skin aggressive and frequently metastasise

Recurrence

Usually appear within 6/12

Depends on grade and depth

— Low grade 7%

— Moderate 23%

— High 28%