1984 CanLII 25 (SCC)1984 CanLII 25 (SCC) 1984 CanLII 25 (SCC) Created Date: 20120810161120Z ...
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Transcript of Scc
Squamous Cell Carcinoma
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
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
• Skin pigmentation• Age• Primary dermatoses –
xeroderma pigmentosa, oculocutaneous albinism
• 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
Histological subtypes
• Pleomorphic• Adenoid/Acantholytic• Simplex• Small cell• Verrucous• Keratoacanthoma• Actinic keratosis• Bowenoid/Erythoplasia of Queyrat
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
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
• 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
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
• 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
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
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
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
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
• 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
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
• 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
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
• 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
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
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
• 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
• 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
Immunosuppression
– Biologically more aggressive, with higher rates of lymph node metastases and deaths secondary to skin cancer
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%
Tumour depth and metastatic rate
Depth Metastatic rate
< 2mm 0
2 – 6mm 4.5%
> 6mm 15%
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
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
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
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