Squamous cell carcinoma - Mohs Ron Rapini MD No conflict of interest Josey Chair, Dept Dermatology • I am paid zero to speak at this Univ Texas Medical School at Houston MD Anderson Cancer Center course, other than travel • The tuition helps to run the ASMS programs

Duplicate Actinic keratosis Actinic keratosis Rx • Whether you call it a “precancer” or • Treating orAKs is beyond this lecture “squamous cell carcinoma grade 1/2” or • Ill-defined dysplasias – usually a “field-effect” “SCC – AK type”, or “keratinocytic • Trying to eradicate totally is like playing intraepithelial neoplasia = KIN”, it still “whack a mole” so goal is to eradicate most doesn’t need Mohs surgery significant areas • Don’t over-read as invasive squamous cell ca • Cryo, curettage, laser, imiquimod, • AK and squamous cell carcinoma are often fluorouracil, diclofenac, etc multifocal with field effects in margins

Keratinocytic intraepithelialDistribute Grading dysplasia in neoplasia = KIN 1, 2, 3 dysplastic nevi is analogous • Analogous to CIN, PIN, VIN 1,2,3 • Really in SKIN with most popular • NIH consensus conference 1992 system, we don’t have a “2”: recommended grading cytology despite Not lack of concordance AK = KIN-1 • I grade only cytology as mild, moderate, SCC in situ (Bowen’s) = KIN-3 Do severe

1 Lack of concordance on grading “dysplasia” in dysplastic nevi Other terms Piepkorn (J Cutan Pathol 6:542, 1992) • Bowenoid AK – “just call it found only 38% agreement SCCis?” Similar situation with KIN-2 (in between • Advanced AK – “beware” AK and SCC in situ) – you have to grade • SCC of AK type – “hysterical” it up or grade it down because we don’t really use KIN-2 • Solar keratosis (I don’t use because abbreviates SK) Duplicate Actinic keratosis mythology • Dogma: AKs spare the follicles or • And Bowen’s (SCC in situ) regularly goes down the follicles The truth: AKs CAN extend down follicles: “follicular AKs” = “proliferative AKs”: reason for liquid nitrogen failure

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Do Actinic keratosis Actinic keratosis

2 Hyperkeratotic “hypertrophic” AK = HAK, not invasive SCC Acantholytic actinic keratosis Duplicate Bowen’s disease (squamous cell carcinoma in situ) or • Indication for Mohs if good reason (not routine in my opinion) • If you feel Mohs is indicated for certain lesions, then document reasons in the chart Bowen’s

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DoBowen’s disease = SCC in situ Bowen’s disease = SCC in situ

3 Clear cell Bowen’s disease – Pagetoid cells Irritated “clonal” seborrheic keratosis resemble Paget’s disease or Melanoma might resemble Bowen’s Duplicate Inverted follicular keratosis = IFK • Hyperkeratoticor facial papule • Downward growing lobule , sometimes with squamous eddies • Variant of inward-growing irritated SK? • Less clear cells than trichilemmoma, Irritated seborrheic keratosis can closely which has a similar silhouette resemble squamous cell carcinoma

IFK = Distribute Inverted The art of treating skin cancers follicular keratosis, a • Know which lesions are high risk “downward growing • Use multiple modalities: SK” curettage, simple excision, Mohs, Not radiation, topical-5FU, imiquimod, intralesional chemo, Do etc

4 High risk squamous cell carcinoma • Large size (> 2 cm) or depth (> 3mm,1 cm) • Poorly differentiated, spindle cell • Perineural invasion • Recurrent • Scar, burn, osteomyelitis, post-radiation • Immunosuppression (CLL, drugs ) • Pseudoglandular (acantholytic) – prob not • Location on lip, ear, temple ? Duplicate Metastasis from squamous cell carcinoma or • Sun-exposed 0.5% • Lower lip 10% • Chronic leg ulcers 20% • Burn scars 20% • Irradiated sites 20% • Osteomyelitis 30%

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5 Where to start? Where are the invasive SCCs and which are just AKs? Duplicate Periungual SCC SCC histology types resembles wart, eczema or • Well-differentiatedor paronychia – get X-ray before • Moderately-differentiated Mohs to assess boney • Poorly-differentiated involvement • Adenoid (acantholytic) • Spindle cell

Well- Poorly differentiated Distribute differentiated SCC SCC Not Do

6 Acantholyic or pseudoglandular SCC Duplicate Spindle cell SCC or

Spindle cell SCC Distribute Not Do

7 Single cell seeding Scanning for SCC on low power • Single dyscohesive squamous • Beware – the SCC is pink and can cells in dermis indicate poor be subtle in the dermis or in muscle prognosis and high chance of • Look for atypical cells as a clue – but well-differentiated SCC might metastasis not have them • Keratin stain may help, subject of another lecture Duplicate or

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8 Perineural invasion • ?10-20% of SCCs – over or underdiagnosed? • Real examples have tumor tracking down nerve – not just innocent bystander nerve • Most common if tumor recurrent or > 2 cm • 40% of pts have pain, dysesthesia, nerve palsy • S-100 can find nerve • 5 year local control only 55% (Head Neck Surg 25:1027, 2003) Duplicate Keratoacanthomas usually are squamous cell carcinomas or • Exception: Multiple KA syndromes • Most important criterion: tendency toward spontaneous resolution – not often seen! • Rapid growth: not always present, and can occur with SCC too! • Keratin-filled crater – not specific • If lots of atypia, never call it KA! • Eosinophils, more with KA, per Dr Ackerman Keratoacanthoma

Keratoacanthoma DistributeKeratoacanthoma (a well-differentiated SCC in most cases) • Dr Goltz: If margin involved, never Not called it KA • Lawsuits over KA that did bad things • “Squamous cell carcinoma (KA-type)” Do • Dr C: “KA is benign, not SCC”

9 Basosquamous cell carcinoma Infundibulocystic SCC (metatypical BCC) • Term coined to encompass KA-like • Features of both SCC and BCC SCCs with keratin cystic areas • Probably has intermediate prognosis • Supposed to be follicular differentiation • Use the term sparingly • Some cases are a “collision” Kossard et al: Am J Dermatopath • BCCs will keratinize under ulcers and 2008;30:127. those are just BCCs – not true basosquamous Duplicate or

Basosquamous carcinoma

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10 Duplicate or

Verrucous carcinomaDistribute • Pale and glassy with minimal atypia • Pushing border rather than infiltrative • Mainly is a huge wart (HPV) • Does not metastasize • EpitheliomaNot cuniculatum - sole • Buschke-Lowenstein tumor of genitals • Oral florid papillomatosis of mouth Do Verrucous carcinoma

11 Verrucous Verrucous carcinoma carcinoma resembles giant wart, even with koilocytes

Duplicate Verrucous carcinoma –Rx intralesional bleomycin, one unit/one ml weekly SCCor Look-Alikes • Hypertrophic lichen planus • Hypertrophic lupus erythematosus • Healing wounds • Prurigo nodularis and LSC • Granular cell tumor • Deep fungus and AFB preRx, one month, three months

DistributeRe-excision of SCC vs Pseudocarcinomatous hyperplasia Spitz nevus with pseudo- • Mainly distinguished by the carcinomatous clinical situation (healing wound, hyperplasia fungus or AFB found, etc) • PEHNot (pseudoepitheliomatous hyperplasia) tends to have jagged irregular edges with fibrosis in Do dermis and no atypia

12 Pseudocarcinomatous hyperplasia (pseudoepitheliomatous Muscle degeneration hyperplasia) • Can be nearly impossible to • Weird looking nuclei in distinguish from well- damaged or degenerating differentiated squamous cell muscle can closely resemble carcinoma unless you have history SCC

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Adnexal metaplasiaDistributeSweat duct metaplasia • Sweat duct metaplasia or hair resembling follicle metaplasia is most SCC SCC common in previous biopsy sites • DamagedNot or regenerating adnexal structures look atypical and keratinize, resembling carcinoma Do

13 Huge meningioma Warty dyskeratoma attacked by Mohs Duplicate Proliferating pilar cyst (pilar tumor) or • A pilar cyst (trichilemmal cyst, follicular isthmus-catagen cyst) in which the wall proliferates • Usually scalp • Ackerman feels they are all SCC, but most feel they just mimic SCC • Metastases have been reported

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14 Abrupt (“trichilemmal”) keratinization in proliferating pilar cyst Duplicate Trichoadenoma or

Trichoadenoma

Distribute Tangential sectioning of epidermis Beware • Can resemble SCC • In Mohs, when you section • But there usually is no atypia and tangentially, an AK can look noNot inflammatory reaction like superficial invasive SCC • You can see dermal islands Do

15 Tangential sectioning – NOT SCC

Duplicate Malignant Follicular Tumors: Pilomatrix carcinoma Trichilemmocarcinoma or • Lumpers would say these are all just squamous cell carcinomas with follicular differentiation (just SCCs that have shadow cells or abrupt trichilemmal keratinization) Trichilemmocarcinoma

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