2. Squamous Cell Carcinoma

5. Incidence
• 2nd most common skin cancer
– Behind BCC, accounting for 20% skin cancers
• Due to propensity to metastasise, makes them
responsible for majority of NMSC deaths

6. Pathogenesis
• UV
– Incidence doubles with 8-10 degrees decrease in
latitude
– Induces formation of pyrimidine dimers resulting
in DNA point mutations
– Causes mutations in p53 tumour suppressor gene

7. • Skin pigmentation
• Age
• Primary dermatoses –
xeroderma
pigmentosa,
oculocutaneous
albinism

8. • Immunosuppression – due to
immunosuppressive drugs, UVR, viral infection
esp HPV
– Reversed ratio of BCC:SCC, SCC being 3x more
common in transplant patients
– Higher rates – cumulative risk of SCC/ BCC in heart
transplant recipient is 3% at one year, 21% at 5
years, 35% at 10 years

9. Histological subtypes
• Pleomorphic
• Adenoid/Acantholytic
• Simplex
• Small cell
• Verrucous
• Keratoacanthoma
• Actinic keratosis
• Bowenoid/Erythoplasia of Queyrat

10. Simplex
• Majority of SCCs
• Atypical keratinocytes
develop within epidermis and
invade the dermis
• Tumour cells are enlarged,
hyperchromatic, variably
pleomorphic nuclei,
prominent mitotic activity
• Keratin pearls

11. Actinic Keratosis
• Also SCC in situ, micro
invasive SCC, as there is
considerable overlap in the
histology
• Atypical keratinocytes that
have not breached the
dermal barrier
– SCCIS is typically full thickness
keratinocyte atypia

12. • Rate of malignant
transformation is 0.1%
per lesion per year
– About 16% will
eventually transform
– Can progress to other
skin cancers such as
sebaceous carcinoma

13. Pleomorphic
• AKA spindle / sarcomatoid, RARE
• Associated with previous trauma
or RTX
• Most commonly found on face
or sun exposed areas of elderly
• Commonly ulcerate, but may
present as an exophytic mass

14. • Microscopically whorls of
atypical squamous cells co-
mingle with collagen fibres
• Pleomorphic giant/spindle
cells may be present
• Neoplastic keratinocytes
have hyperchromatic
eosinophilic cytoplasm,
elongated, pleomorphic and
veiscular nuclei with multiple
nucleoli

15. Small cell
• May resemble metastatic small
cell neuroendocrine carcinoma
or Merkel cell carcinoma
• Invades in cohesive nests with
adjacent intense inflammatory
and desmoplastic host response
• Stains for cytokeratin, but may
stain for neuron specific enolase
(NSE), a neuroendocrine marker

16. Verrucous
• Exophytic or endophytic masses
growing at sites of chronic
irritation
• Slowly locally invasive, little or no
propensity to metastasise
• Morphologically appear well
differentiated with little atypia
• Thickened papillae composed
with well differentiated
squamous cells invading into
dermis

17. Verrucous
• 3 distinct clinicopathologic subtypes
– Oral
• Associated with tobacco chewing, betel
nut chewing, HPV, poor oral hygiene
• Typically wart like white/gray lesion
• Well differentiated
– Plantar
• Many crypt like openings
• Slowly enlarging, fleshy pink exophytic
mass
• Verrucous hyper/para keratotic
component, epithelial crypts with
keratinaceous debris
– Buschke-Loewenstein
• Anogenital type, described by B-L in 1925
• Occur most commonly in uncircumcised
men under 50, associated with HPV 6 & 11
• Present as caulflower like lesions most
commonly on glans penis
• Extensive verrucous acanthosis with
dermal extension, keratinocyte atypia
minimal, hypergranulosis and crypt/sinus
formation

18. Keratoacanthoma
• Period of rapid growth lasts 4-8
weeks
• Potential for spontaneous
involution usually within 4-6
months, sometimes with
considerable scarring
• Clinically tend to be rapid
growing smooth, firm nodule
with central keratin plug

19. • Histologically difficult to
distinguish between benign KA
and SCC KA type, so being
amalgamated by
histopathologists
• Atypical squamous proliferation
with intradermal invasion
• Typically crateriform
architecture with keratin plug
and well developed collarette

20. Adenoid / Acantholytic
• Form a pseudoglandular
appearance
• Cells arranged in cords and
nests with clefts produced by
acantholysis of cells leaving
spaces that superficially
resemble glands

21. • Enlarged free floating dysplastic
keratinocytes found in lumina
• Clinically appear as ulcer on head
& neck of men in 5th to 6th
decade
• High incidence of recurrence
after radiation therapy
• Tend to be more locally
aggressive but metastasise less

22. Bowenoid
• Considered to be SCC in situ
• Most common site is head and
neck, followed by limbs and
then trunk
• Well demarcated, slow
growing, erythematous scaly
patch, usually small in size

23. • Histologically shows
hyperkeratosis, acanthosis,
psoriasiform hyperplasia, full
thickness atypia, loss of polarity
reflecting cessation of
maturation
• When neoplastic keratinocytes
invade the dermis, this lesion is
termed Bowenoid SCC
• Especially associated with HPV
– HPV2 with extragenital
lesions, HPV16 with genital
lesions

24. Metastasis
• Overall risk is 2 – 6%, not 0.5%
• Recurrent SCC has metastatic rate of 30%, and
metastatic cases had a survival rate of 1/3
• Metastases tend to be to regional lymph nodes
• Most mets (and local recurrences) are found within
first 2 years, and 95% within first 5 years

25. Risk factors for metastasis and recurrence
• Recurrence rate doubled and tripled metastatic rate
– Size > 2cm
– Grade 3 & 4 vs. Grade 1 & 2 tumours
• Well differentiated has recurrence 7%, mod well diff 23%, poor
diff 28%
• Tumour thickness
– 3 year recurrence free survival is 98% for <3.5mm, 84%
for > 3.5mm (Breslow thickness)
• Rapid growth rate

26. • Sun exposed areas tend to metastasise and recur less than mucosal SCC
• Scar SCC are very aggressive
• Lip and ear SCC have higher metastatic rate than other head and neck
sites (16 & 10%)
– Probably due to decreased subcutaneous fat
– Nose and scalp, anogenital are intermediate risk
– Periungal SCC has high recurrence rate but almost never metastasises
• Previous treatment – recurrent cancers have a metastatic rate of 25%
– Location – ear 45%, lip 32% metastatic rate

27. • Histopathology
– Isolated strands, infiltrative pattern, haphazard growth vs.
broad pushing borders
– Perineural invasion (occurs in 2-14% SCC, most commonly
H&N in elderly men)
• Has been quoted as local recurrence 47%, regional mets 35%,
distant nodes 15%; so post op RTX commonly offered
– NO good evidence that any subtype has greater risk
recurrence or metastasis

28. Immunosuppression
– Biologically more aggressive, with higher rates of
lymph node metastases and deaths secondary to
skin cancer

29. Tumour size
Size (cm) Metastatic 5 yr disease free
rate survival
T <2 1.4% 95-99%
1
T 2–4 9.2% 85-60%
2
T >4 > 13% 75-60%
3
T Invading deep < 40%
4 structures

30. Tumour depth and metastatic rate
Depth Metastatic rate
< 2mm 0
2 – 6mm 4.5%
> 6mm 15%

31. Grades
Broder’s Grade Undifferentiated Ratio of
cells differentiated cells
I – Well < 25% 3:1
differentiated
II – Moderately 25 – 50% 1:1
well differentiated
III – Poorly 50 – 75% 1:3
differentiated
IV – Anaplastic or > 75% Nil
pleomorphic

32. Surgical Management
• Tumours < 2cm diameter are
successfully excised 95% of the
time with a margin of 4mm,
6mm for high risk cases
(Brodland & Zitelli)
• Tumours > 2cm diameter
require margin of 10mm for
equivalent local control rates
• Moh’s surgery

33. Other modalities
• Dessication and curettage
– Lesions less than 2cm diameter have cure rates of
97-98.8%
• Cryosurgery
– Well localised, superficial lesions on trunk or limbs
• 5FU & Imiquimod & Photodynamic therapy
– Useful for actinic keratoses

34. Radiation Therapy
– < 2cm tumours have a cure rate of 95%
– Adjunctive RTX must be given within 8 weeks for greatest efficiency
– (Late) changes include :
– atrophy, fibrosis, hypopigmentation, telangiectasia, ulceration
– “As late results of RTX can be poor, it is not recommended for patients
under 60 yo with uncomplicated primary SCC”
– May hasten natural history of KA