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 rate 5 yr disease free survival T1
< 2
1.4%
95-99% T2
2 – 4
9.2%
85-60% T3
> 4
> 13%
75-60% T4
Invading deep structures
< 40%

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

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

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 Cryosurgery
Lesions less than 2cm diameter have cure rates of %
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