Squamous Cell and Basal Cell Carcinomas (Nonmelanoma Skin Cancers)
BACKGROUND
What is the incidence of nonmelanoma skin cancer (NMSC) in the U.S.?
>2 million cases/yr in the U.S. and rising (exceeds incidence of all other cancers combined)
Which is more common: basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)?
BCC (80%) is more common than SCC (20%).
What is the sex predilection for skin cancers?
Males are more commonly affected than females (4:1).
What is the most common genetic mutation in NMSC?
p53 mutations
What signaling pathway is involved in BCC pathogenesis?
Sonic hedgehog signaling pathway
What are the areas represented by the letters H, M, and L?
H: “mask areas” (central face, eyelids, eyebrows, periorbital nose, lips, chin, mandible, preauricular, postauricular, temple, ear), genitalia, hands, feet
M: cheek, forehead, scalp, neck, pretibial
L: trunk and extremities (except pretibial, hands, feet, nails, ankles)
(Connolly et al., Dermatol Surg 2012)
What does the “mask area” correspond to?
Midface, where the embryologic fusion lines lie (high risk for deep invasion and high risk for LR).
What are the high-risk factors for BCC?
Area L ≥20 mm, area M ≥10 mm, area H ≥6 mm, ill-defined borders, recurrent, poorly differentiated, immunosuppressed, prior RT, PNI, aggressive histology (morpheaform, sclerosing, mixed infiltrative, micronodular)
What are the high-risk factors for SCC?
Those listed above for BCC and rapidly growing, neurologic symptoms, moderately or poorly differentiated, unfavorable histology (adenoid, adenosquamous, desmoplastic), ≥2-mm thick or Clark level IV or V.
What genetic/inherited disorders are associated with skin cancer?
Phenylketonuria, Gorlin syndrome (PTCH), xeroderma pigmentosa, and albinism have a genetic/inherited association with skin cancer.
What is the incidence of PNI and mets with BCC?
PNI: 1%
Mets: <0.1% (nodes > distant sites)
What is the incidence of PNI and mets with SCC?
PNI: 2%–15%
Mets: nodes: 1%–30% (1% grade 1, 10% grade 3, 30% from burns); distant: 2% (lung > liver > bones)
What are the major determinants of LN spread for SCC?
Poor differentiation, size/depth (>3 cm/>4 mm), PNI/LVI, location (lips, scars/burns, ear), and recurrent lesions
What LN regions are most commonly involved in SCC?
The upper cervical and deep parotid regions (with the H&N as the most frequent site) are most commonly involved in SCC.
Sun exposure at what stage of life correlates with BCC vs. SCC?
BCC: early in life/childhood
SCC: decade preceding Dx
What is Bowen Dz?
Bowen Dz is SCC in situ.
What is erythroplasia de Queyrat?
Erythroplasia de Queyrat is Bowen Dz of the penis.
What is a Marjolin ulcer?
Marjolin ulcer is SCC arising in a burn scar.
Which is more common when the ear is the primary site: BCC or SCC?
External ear: BCC more common
Internal/canal: SCC more common
What is the most common site for sebaceous carcinomas?
Ocular adnexa
What is the most common primary in a pt with SCC of intraparotid LN?
SCC of the skin
WORKUP/STAGING
On what is the latest AJCC (7th edition, 2011) T staging based for SCC/BCC?
T1: ≤2 cm (<2 high-risk features)
T2: >2 cm (≥2 high-risk features)
T3: invasion of maxilla, mandible, orbit, or temporal bone
T4: skeletal invasion, PNI of skull base
Per the latest AJCC classification, to what other site is N staging for skin cancer similar?
Skin cancer N staging is similar to that of the H&N:
N1: single, ipsi ≤3 cm
N2a: single, ipsi 3–6 cm
N2b: multiple, ipsi ≤ 6 cm
N2c: bilat or contralat LNs ≤6 cm
N3: LNs >6 cm
What defines stage groupings I, II, III, and IV?
Stage I: T1N0
Stage II: T2N0
Stage III: T3N0 or T1–3N1
Stage IV: N2–3, or T4, or M1
What are considered high-risk features for staging per the 7th edition of AJCC?
High-risk features include >2-mm DOI/thickness, Clark level ≥IV, +PNI, poor differentiation, an ear or hair-bearing lip site.
For what is a “pearly papule” lesion pathognomonic?
BCC lesions
How does SCC appear on the skin?
SCC is flesh toned and variably keratotic.
On H&P, what aspects should be the focus of the exam?
Palpate extent of tumor, CN exam for H&N lesions, regional LN evaluation, audiometry/otoscopy for cancers of the ear, and CT/MRI to verify extent
TREATMENT/PROGNOSIS
Name 4 Tx options for NMSC
SCC/BCC of the skin Tx options:
1. Surgery (WLE, Mohs surgery, surgical excision with complete circumferential peripheral and deep margin assessment)
2. Curettage and electrodesiccation (C&E)
3. Superficial therapies
4. Primary RT
Describe Mohs surgery.
In Mohs surgery, a superficial slice of skin is taken and then sectioned into quadrants. Additional layers are taken in the quadrants that show persistent Dz.
When are C&E and superficial therapies appropriate for skin cancer?
Low-risk NMSC. (Cannot evaluate histologic margins with these techniques.)
List the superficial therapies.
Topical 5-FU, imiquimod, photodynamic therapy, cryotherapy
What % of BCC recurs if margin+ at the time of resection?
BCC recurs in 30% for a +lat margin and >50% for a +deep margin.
What % of SCC recurs if margin+ at the time of resection?
Nearly 100% of SCCs recur if margin+.
When is RT preferred as the primary Tx modality for skin cancer?
RT is preferred for pts >60 yo and who are not candidates for primary surgery. RT should be offered for lesions of the central face, lip, eyelid, and ears if surgery will lead to inferior cosmetic or functional outcomes.
What is the best predictor of LC after definitive RT?
T stage is the best predictor for LC
What is the LC after definitive RT for BCC vs. SCC?
LC is similar for BCC and SCC with T1 lesions (95%) and lower for SCC than BCC if T2 (75%–85%) or T3 (50%).
What should be done with +margin resection?
Re-excise if possible, otherwise adj RT.
What are 3 indications for adj RT to the primary site with skin cancer?
Indications for adj RT to the primary in skin cancer:
1. +Margin (per NCCN)
2. PNI of named nerve (per NCCN)
3. Invasion of bone, cartilage, or skeletal muscle
What are relative contraindications to RT in the Tx of skin cancers?
Relative contraindications to RT for skin cancer include areas prone to trauma (hand dorsum or beltline) or with poor blood supply (below knees/elbows), age <50 yrs, post-RT recurrence, Gorlin syndrome, CD4 count <200, high occupational sun exposure, and exposed area of bone/cartilage.
When should adj nodal RT be considered after surgical resection for skin cancers?
Consider adj nodal RT after surgical resection for multiple (>1) +LNs, large (>3 cm) LNs, ECE.
What fields and dose schemes are typically employed with photons/orthovoltage in the Tx of skin cancers?
Treat the tumor/tumor bed + 1–2 cm to 60–66 Gy (2 Gy/fx), especially for involvement of cartilage, or to 50–55 Gy (2.5–3 Gy/fx). For the elderly/poor performance status, 3.5–4 Gy × 10 fx or 10 Gy × 2 fx can be used.
What is the margin/dose modification if electrons are used? Why?
If electrons are used, add an additional 0.5-cm margin on the skin surface and use 10%–15% higher daily/total dose b/c of bowing out of isodose curves and a lower RBE (0.85–0.9) of electrons.
What is the Rx point if orthovoltage (100–200 kV) RT is employed?
Dmax (90% of the IDL has to encompass the tumor). Do not use this if the lesion is >1-cm deep.
When treating with electrons, how deep should the 90% IDL extend in relation to the lesion?
The IDL should extend at least 5–10 mm deeper than the deepest aspect of the lesion.
When treating skin lesions with electrons, what rule is typically employed to choose the correct beam energy?
Electron energy (in MeV) should be >3 times the lesion depth (i.e., a 9-MeV beam is needed for a 2-cm lesion depth).
What is the RT volume if a named nerve is involved by SCC?
The RT volume should include nerve retrograde to the skull base. Consider IMRT/elective nodal RT.
Where do basosquamous skin cancers occur? What is the Tx paradigm?
Basosquamous skin cancers occur on the face. These are treated like SCC, as they have similar rates of nodal mets.
What kind of shields are used, and where should they be placed? Why?
Wax-covered lead shields are used b/c of backscattered electrons with low E beams. They are typically placed behind/downstream of tumor, as hotspots occur upstream of the shield.
How is SCC of the pinna approached?
For SCC of the pinna, use RT with 2.5–4 Gy/fx to 45–65 Gy in 2–3 fx/wk to the lesion + a 1–2-cm margin (using bolus and shielding as necessary).
When should surgery be recommended for pinna lesions?
Recommend surgery when cartilage is involved or with tumor extension to the canal.
When is adj RT generally recommended for ear lesions?
Pinna: if +margin, ≥T3
Middle ear/mastoid: if ≥T2
Can definitive RT be done for canal/middle ear lesions?
Yes. Good outcomes have been reported with RT alone for T1 lesions. (Ogawa K et al., IJROBP 2007)
What RT fields/margins are used for middle ear/canal lesions?
For middle ear/canal lesions, include the entire canal/temporal bone + a 2–3-cm margin and ipsi regional nodes (preauricular, postauricular, level II).
How should fx size be tailored for skin cancer depending on the RT field size used?
The larger the field size, the smaller the fx size should be.
If simple excision is performed for BCC, what are the min margins required?
Low risk: 4 mm
High risk: 10 mm
What is the 1st step to take when the pt has a +margin after excision?
Send the pt back to the surgeon to be evaluated for re-excision if there is a +margin.
What is the preferred RT modality for bone-invasive skin cancer? For cartilage invasion?
Megavoltage photons are the preferred Tx modality for bone invasion b/c of a more homogenous distribution compared to orthovoltage due to the f-factor; however, this is not so with cartilage invasion, as orthovoltage beams have little difference in distribution in cartilage regardless of energy.
If treating recurrent BCC or morpheaform BCC, what type of margins should be used?
Because these tumors infiltrate more extensively, an extra 0.5–1-cm margin should be added on the surface.
How long should be the wait for a skin graft to heal before starting RT?
6–8 wks of healing time is required after skin grafting before RT can be initiated.
How should an SCC of the mastoid be treated?
Treat SCC of the mastoid with mastoidectomy or temporal bone resection → PORT.
How should the RT doses be modified based on tumor size/extent for ear primaries?
Conventional fx of 1.8–2 Gy:
Small thin lesions <1.5 cm: 50 Gy
Larger tumors: 55 Gy
Min cartilage/bone involvement: 60 Gy
Cartilage/bone involvement: 65 Gy
TOXICITY
What are some toxicities expected after RT for skin cancer?
Telangiectasia, skin atrophy, hyperpigmentation, skin necrosis, fibrosis, osteonecrosis, chondritis; xerostomia/hearing loss for the ear
If cartilage is in the RT field, what should the dose/fx be kept below?
The dose should be kept at <3 Gy/fx to reduce chondritis.
What is the incidence of skin necrosis after RT?
Skin necrosis occurs in 3% of pts (in 13% if fx size is >4–6 Gy).
To what dose should middle ear/canal lesions be limited? Why?
Limit middle ear/canal lesions to 65–70 Gy b/c of higher rates (>10%) of osteoradionecrosis with doses >70 Gy.
What must be done to reduce the toxicities to normal tissues from skin irradiation in the H&N region?
To reduce toxicities to normal tissues, use lead shielding to block the lens, cornea, nasal septum, teeth, and gums. Use dental wax on the side from which the beam enters to absorb backscatter.
Per the latest NCCN guidelines, what should be the follow-up intervals for pts with nonmelanoma skin cancers?
NCCN nonmelanoma skin cancer follow-up intervals:
1. Complete skin exam for life at least once/yr
2. For local Dz: H&P q3–6 mos for yrs 1–2, q6–12 mos for yrs 3–5, then annually
3. For regional Dz: H&P q1–3 mos for yr 1, q2–4 mos for yr 2, q4–6 mos for yrs 3–5, then q6–12 mos for life
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