Skin Flashcards

Question

Describe the clinical presentation of cutaneous basal cell carcinoma 7

Answer 1

- Slow growing but can be locally destructive - Nodular and pearly - Prominent telangiectasia - Raised borders - Centrally ulcerative - Pruritic - RARELY metastasizes (< 0.5%) - relies on dermal stroma underneath for its growth

Answer 2

GORLIN SYNDROME: - = Nevoid Basal Cell Carcinoma Syndrome INHERITANCE/GENETICS: - Autosomal Dominant - PTHC gene on Chromosome 9q CLINICAL PRESENTATION: - Multiple (hundreds) of small cutaneous nodules appear in childhood - As child ages, multiple basal cell carcinomas develop and lesions become aggressive - invasion, destruction, mutilation - Rib and Vertebral abnormalities - Frontal bossing - Falx cerebri calcification - Mental retardation - Cataracts - Odontogenic keratocysts (OKC) - 75% - Scoliosis - Bifid ribs - Pitting of the palms and soles DIAGNOSTIC CRITERIA: 2 Major OR 1 major + 2 minor MAJOR CRITERIA: 1. ≥2 BCCs or 1 BCC in a person younger than 20 years 2. Odontogenic keratocysts of the jaw 3. 3 or more palmar or plantar pits 4. Ectopic calcification or early (< 20 years) calcification of the falx cerebri 5. Bifid, fused, or splayed ribs 6. First-degree relative with NBCCS MINOR CRITERIA: 1. Macrocephaly 2. Congenital malformations - cleft lip or palate, frontal bossing, eye anomaly (cataract, coloboma, micro-ophthalmia, nystagmus) 3. Other skeletal abnormalities - Sprengel deformity (shoulder blade too high on one side), pectus deformity, polydactyly, syndactyly, or hypertelorism 4. Radiologic abnormalities - bridging of the sella turcica, vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet 5. Ovarian and cardio fibroma or medulloblastoma (the latter is generally found in children ≤2 years old)

Answer 3

XERODERMA PIGMENTOSA (XP): - Genetic defect that impairs ability to repair skin damage by UV light (causes extreme UV light sensitivity of the skin and eyes) GENETICS/INHERITANCE: - Autosomal Recessive cr 9 - Multiple genes, including: - XPA/B/C/D - ERCC2 & 3 - POLH RISK FACTORS: 1. 6x more common in Japanese CLINICAL FEATURES: - Dry skin - Irregular freckles - Severe burns from being in sun for a few minutes - Eye/eyelid problems - Progressive neurologic abnormalities - Multiple BCCs (most common), but also high risk for SCC and melanoma - First skin cancer usually < 10 yo (especially without skin protection) PROGNOSIS: - Early death most often secondary to metastatic SCC/melanoma

Answer 4

SIRS PRay for LeBanese Size Immunosuppression Radiation exposed-site Subtype (aggressive vs. non-aggressive forms) Perineural invasion Recurrent vs primary BCC Location Borders LOW RISK: 1. Trunk, extremities < 2cm 2. Well-defined borders 3. Primary BCC 4. No immunosuppression 5. No radiation exposure to site 6. Nodular and superficial subtypes 7. No perineural involvement HIGH RISK: 1. Trunk and extremities ≥ 2cm 2. Cheeks, forehead, scalp, neck, and pretibial any size 3. Head, neck, heads, feet, pretibia, and anogenital (any size) 4. Poorly defined borders 5. Recurrent BCC 6. Immunosuppression history 7. Site of previous radiation 8. Aggressive growth patterns/subtypes 9. Perineural involvement

Answer 5

2. OVERALL HIGH RISK CLINICAL FEATURES: A. Local clinical features - Primary site ear or non-hair-bearing lip (vermillion of the lip) - Size with site including the erythema part - M Area: Cheek, Forehead, Scalp, Neck > 10mm - H Area (face) > 6mm - Ill-defined borders - Recurrent - Extensive disease - Arising from pre-existing scar, burn (Marjolin's ulcer) B. Symptoms - Rapidly growing (>4mm/month) - Neurological symptoms (suggest PNI) C. Systemic: - Immunosuppression (transplant, HIV, CLL, Drugs) - Chronic inflammatory disease - Xeroderma Pigmentosa - Previous Radiation D. Palpable Regional disease

Answer 6

A. Tumor > 2cm B. Poor differentiation or undifferentiated C. High risk subtypes: - Adenoid or Acantholytic, Adenosquamous, Metaplastic (carcinosarcomatous), Basosquamous - Spindle cell associated with high risk PNI but itself is not listed as high risk - Presence of Desmoplasia (growth of fibrous connective tissue) D. Depth: - > Clark IV - > 2mm depth (vertical distance from top to the bottom of the tumor);; Meta-analyses show 4mm and 6mm cutoffs as prognosis for recurrence and metastasis;; NCCN chose thickness >6mm or invasion beyond subcutaneous fat to be considered high risk (Scottish Guidelines - 6mm very high risk, 4mm high risk) E. Perineural invasion, lymphovascular invasion

Answer 7

1. Acantholytic/adenoid (worse) 2. Spindle cell (worse) 3. Conventional 4. Clear cell 5. Desmoplastic 6. Lymphoepitheliomatous 7. Verrucous 8. Keratoacanthoma (KA) - low grade squamous neoplasm

Answer 8

1. Spindle cell – pleomorphic, anaplastic, little/no keratinization, lymphoepithelioma-like carcinoma 2. Adenoid – Adenosquamous, pseudo-glandular arrangement, similar to mucoepidermoid, mucinous 3. Generic – well-differentiated, actinic changes 4. Bowenoid – from Bowen’s disease 5. Verrucous – white cauliflower like lesion, HPV associated Very SAGgy Boobs are anNOIying

Answer 9

Note: General characteristics (clinical and histologic) are similar to the ones in the BCC risk of recurrence flash card Thinks: SIRS PRay for LeBanese Size Immunosuppression Radiation exposure Subtype / scar Perineural/lymphovascular invasion Recurrent vs. primary Location Borders LOW RISK: - Trunk, extremities ≤ 2cm - Well defined borders - Primary SCC - No immunosuppression - Not at site of previous radiation - No neurologic symptoms - No rapid growth - Well or moderately differentiated - None of the following histologic features: Acantholytic (adenoid), adenosquamous (showing mucin production), or metaplastic (carcinosarcomatous) subtypes - Dpeth (thickness/level of invasion): ≤6mm and no invasion beyond subcutaneous fat - No perineural involvement - No lymphatic or vascular involvement

Answer 10

Thinks SIRS PRay for LeBanese Size/depth Immunosuppression Radiation site history / scar history/background of inflammation Subtype Perineural/lymphovascular invasion Recurrent vs primary SCC Location Borders HIGH RISK: - Trunk, extremities > 2cm, ≤ 4cm - Head, neck, hands, feet, pretibia, and anogenital (any size) - Poorly defined borders - Recurrent tumor - History of immunosuppression - Site of prior RT or chronic inflammatory process - Rapidly growing tumor - Neurologic symptoms - Presence of one of the histologic features: Acantholytic (adenoid), adenosquamous (showing mucin production), or metaplastic (carcinosarcomatous) subtypes - Positive perineural involvement - No lymphatic or vascular involvement

Answer 11

Think T3/4 criteria, plus poor differentiation and desmoplastic SCC VERY HIGH RISK: - > 4cm in any location - Poor differentiation - Desmoplastic SCC - >6mm or invasion beyond subcutaneous fat - Tumor within the nerve sheath of a nerve lying deeper than the dermis or measuring ≥0.1mm - Positive lymphatic or vascular involvement

Answer 12

BCC 1. Sclerosing/morpheaform BCC (clinical) 2. Keratotic BCC (histologic) 3. Recurrent SCC: 1. Spindle cell 2. De novo SCC (not pathological - non-skin damaged skin) 3. Adenoid / Acantholytic also bad

Answer 13

1. Extensive disease (deeper than what you think) 2. Palpable positive regional disease (CT of nodal basin, plus CT A/P or FDG-PET/CT) 3. Imaging to determine the extent of a primary tumour (Scottish guideline) - e.g. Symptoms suggestive of perineural invasion (e.g. numbness), or Clinical evidence of bony erosion 4. High risk sites (e.g. on or around the ear) Modalities 1. U/S ± FNA 2. CT 3. MRI 4. PET scan

Answer 14

1. Observation 2. Medical (e.g. topical 5-FU, imiquimod, retinoic acid, interferon-a) 3. Surgical: electrodessication & curettage, excision, cryosurgery, photodynamic therapy, mohs surgery 4. Radiotherapy: Generally not indicated due to duration, complications, carcinogenesis, lack of margin control, and increased aggressiveness of recurrences 5. Systemic therapy/chemotherapy 6. Elective neck dissection in cSCC (not BCC): controversial but may be considered in T3/4 and high risk lesions - Posterior scalp and upper neck: posterolateral SND (II-V + postauricular + suboccipital LN) - Preauricular, anterior scalp, and temporal region: parotidectomy and facial, II, III, Va - Anterior and lateral face: SND partoidectomy and facial, level I-III

Answer 15

INDICATIONS: - Local Low-risk cSCCs, Superficial lesions (Biopsies must be taken to ensure no high-risk pathologic features require additional therapy) - Pre-malignant (Carcinoma in situ) - Alternative primary treatment for local high/very-high risk tutors in the M area (cheek, forehead, scalp, neck, pre-tibial) that are < 6mm in depth and confined to the dermis) for patients with ++comorbidities or factors making surgical excision difficult CONTRAINDICATIONS: - Areas with terminal hair growth (scalp, pubic or axillary regions, beard area in males) - risk of tumor extending down follicular structures and not adequately removed - Subcutaneous layer reached - surgical excision should be performed instead (hard to distinguish tumor in sub-cut area) DISADVANTAGES: - No histologic margin assessment

Answer 16

Margins: must include any peripheral rim of erythema counted as tumor 1. Local low-risk cSCC, well-circumscribed - < 2cm diameter: 4mm margins (clear margin 95%) - >2cm diameter: 6mm margins (clear margin 95%) 2. Local high/very-high risk cSCC - High-risk locations (scalp, ears, eyelids, nose, lips) or other high-risk features (Grade ≥ 2, invasion of subcutaneous tissue) a. Diameter < 1cm - 4mm margin b. 1-1.9cm - 6mm margin c. ≥2cm - 9mm margin - European Guidelines: 6-10mm peripheral clinical margins for high/very high risk cSCC - greater if indicated, if clinically feasible - Margins generally based on location (hard to go all the way) - In general, BCC/SCC low risk 3-4mm sufficient; high risk 5-10mm dependent on location - Re-excision with post-operative margin assessment recommended after all excisions (Tissue rearrangement/flaps should not be undertaken until clear margins identified;; Close multiple disease - avoid local flap)

Answer 17

INDICATIONS: - Treatment option for all types of lesions because of intra-operative analysis of 100% of excision margin - Preferred for local, very high risk cSCC CONTRAINDICATIONS: - Non-melanoma skin cancer that extends into the subcutaneous tissue RISK FACTORS FOR METS POST MOHS: - Size >2cm - Clark level III-V - Poor differentiation - Areas of prior radiation - Small tumor nests and infiltrative tumor strands - Single cell infiltration - PNI - Acantholysis

Answer 18

1. Curettage & electrodessication (C+E) 2. Shave removal (shoudl not be considered if tumor extends beyond dermis) 3. Standard excision with 4mm margin assessment 4. Radiation therapy (non-surgical candidates) 5. Non-surgical modalities for superficial tumors without dermal extension - Topical imiquimod (preferred) - Topical 5-fluorouracil - Photodynamic therapy (e.g. topical aminolevulinic acid, porfimer sodium) - Cryotherapy Positive margins after excision options: 1. Mohs 2. Re-excision 3. Radiotherapy

Answer 19

1. Mohs 2. Standard excision with margins 3. Radiotherapy Positive margins options: 1. Re-resect if possible 2. Radiotherapy 3. Systemic therapy Negative margins options: 1. Consider adjuvant RT if extensive perineural or large-nerve involvement

Answer 20

LOCALLY ADVANCED BCC: 1. Surgery ± neoadjuvant systemic therapy 2. Mohs 3. Radiotherapy 4. Systemic therapy NODAL DISEASE: 1. Surgery 2. Systemic therapy 3. Clinical trial DISTANT METASTASES: 1. Systemic therapy 2. Radiotherapy 3. Surgery for limited metastatic disease 4. Palliative and best supportive care Can say clinical trial for anything advanced - wouldn't be wrong

Answer 21

1. Low risk BCC after positive margins with standard excision. 2. High-risk BCC as additional treatment after standard excision, Mohs, or other forms of PDEMA with positive margins 3. Adjuvant treatment after negative margins in case of extensive perineural or large-nerve involvement.

Answer 22

INDICATIONS: 1. Massive tumors (SCC >2 cm) 2. Very aggressive (Merkel cell) 3. Invasive (bone, muscle, cartilage, and nerve) 4. Resection margins uncertain or positive 5. Multiple recurrences 6. Marjolin’s ulcer (ie. Cancer arising from scar) 7. To the neck – Multiple positive nodes, extracapsular spread and lymphovascular invasion CONTRAINDICATIONS: 1. BCC arising from underlying syndrome (e.g. Xeroderma pigmentosum, Gorlin, SLE) 2. Scleroderma 3. Relatively in verrucous carcinoma (radioresistant)

Answer 23

1. Superficial BCC (not invading into dermis) 2. Surgery or Radiotherapy is contraindicated or impractical 3. Pre-malignant lesions

Answer 24

1. IMIQUIMOD 5% - Immune response modular - Toll-like receptor 7 agonist (TLR7) - Indications: Nodular and superficial BCC, premalignant lesions - Dosage for AK: 5% 2 times per week prior to bedside for 8 hours, remove with soap and water, x 16 weeks - Dosage for BCC: Apply once daily prior to bedside, 5 days/week for 6 weeks 2. 5-FLUOROURACIL (5-FU) - 1% cream for pre-cancerrous - BID application x 3-6 weeks

Answer 25

INDICATIONS: 1. Locally advanced BCC (Vismodegib, Cemiplimab, Sonidegib) 2. Metastatic BCC (Vismodegib, Cemiplimab) 3. Nodal BCC (Vismodegib, Cemiplimab, Sonidegib) 4. Recurrence following surgery 5. Unresectable or not candidates for Surgery/RT HEDGEHOG SIGNALING PATHWAY INHIBITORS (HHI): 1. Vismodegib (locally advanced or metastatic, recurrence) - Also reduced incidence in BCC lesions in Nevoid BCC syndrome - Side effects: Muscle spasm, alopecia, taste loss, weight loss, decreased appetite, fatigue, nausea, diarrhea 2. Sonidegib (locally advanced, recurrence) – similar side effects as Vismodegib Limitation to HHI: Advanced BCC can develop resistance

Answer 26

PD-1 inhibitors (checkpoint inhibitors)/anti-PD-1 immunotherapy: - Cemiplimab (only one approved) - Nivolumab - Pembrolizumab Indications: 1. Locally advanced BCC (including neoadjuvant) 2. Metastatic BCC 3. Previously treated with HHI 4. HHI not appropriate

Answer 27

Limited due to rarity of advanced BCC in general (limited to case reports)

Answer 28

1. Aggressive histology or growth pattern - morpheaform or keratotic for BCC; infiltrative type; sclerosing and keratinizing (basosquamous or metatypical); poorly differentiated SCC; de novo lesion 2. Incompletely excised tumor 3. Tumors with poorly defined margins 4. Immunosuppressed patients 5. High risk location (H-zone) 6. Skin cancer in irradiated skin 7. Recurrent tumor or positive margins 8. Tumors with neurotropism 9. Size > 0.6cm in high risk area, or > 1cm on scalp, face, neck 10. Young patients, cosmetically important area 11. Tumors involving vital structures Again, think about SIRS PRay for LeBanese risk factors! Matches all of them!

Answer 29

1. BCC 2. Cutaneous SCC 3. Selected mucosal SCC 4. Bowen's disease 5. Keratoacanthoma 6. Verrucous carcinoma 7. Microcystic or other adnexal neoplasms 8. Dermatofibrosarcoma protuberans 9. Malignant fibrous histiocytoma 10. Atypical fibroxanthoma 11. Extramammary Paget's disease 12. Merkel cell carcinoma 13. Cutaneous rhabdomyosarcoma 14. Lentigo Maligna ## Footnote Vancouver Pg 90

Answer 30

OPTIONS: 1. Porphyrin 2. 5-ALA (5-Aminolevulinic acid) MECHANISM OF ACTION: - Give a photosensitizing medication topically - Activated by light (laser) --> causes necrosis EFFICACY: - Low ~ 45% - Can treat many lesions simultaneously or used in palliative cases SIDE EFFECTS: - Edema - Erythema - Ulceration/blistering

Answer 31

DERMATOFIBROSARCOMA PROTUBERANS: - Rare aggressive soft tissue sarcoma Genetics: - t(17;22) translocation (chromosome translocation from 17 to 22) - Results in fusion of PDGFB to COLIA1 gene Histology: - CD34 staining CLINICAL PRESENTATION: - Most commonly found on torso, but can also be seen on the arms, legs, and H/N - Tendency to recur - Behaves like a "benign" tumor in many areas, but in 2-5% can metastasize - 1-5% risk of metastasis. high rate of local recurrence RISK FACTORS: - Associated with re-arrangement of genetic material between chromosome 17 + 22 - Scar that develops after a burn or surgery/keloids may increase risk for DFSP - Women - Adults 3-5yo - African americans TREATMENT: 1. Surgical excision with 2-4cm margins and reconstruction (OR preferable) 2. Moh's surgery 3. Adjuvant radiotherapy in high risk patients (e.g. positive or close margins) 4. Imatinib: BCR-ABL/cKIT TKI has been approved for treatment in patients with recurrent, unresectable or metastatic tumors

Answer 32

1. C&E 2. Shave removal (unless tumor obviously extends beyond dermis) 3. Standard excision with margins 4. Mohs 5. Radiotherapy Positive margins: 1. Mohs 2. Re-excision 3. Radiotherapy

Answer 33

1. Consider SLNB in recurrent or multiple high-risk features cases 2. Mohs 3. Standard excision 4. Radiotherapy 5. Systemic therapy Positive margins: 1. Re-resect 2. Radiotherapy 3. Systemic therapy Negative margins: 1. Consider adjuvant radiotherapy

Answer 34

1. Consider SLNB 2. Consider neoadjuvant cemiplimab if: - Very rapid growth - In-transit metastasis - Lymphovascular invasion - Borderline resectable - Surgery that may not be curative or significant functional limitation PRIMARY TREATMENT: 1. Mohs 2. Standard excision 3. Definitive Radiotherapy Positive Margins: 1. Re-resect 2. Radiotherapy 3. Systemic therapy Negative Margins: 1. Consider adjuvant radiation

Answer 35

1. Neoadjuvant therapy with Cemiplimab, plus: 1. Mohs 2. Standard excision with wider margins (if positive or negative margins, same treatment as previous card) 3. Radiotherapy ± 4. Systemic therapy

Answer 36

PATIENT FACTORS: 1. Male 2. Immunosuppression 3. Delayed presentation TUMOR FACTORS: 1. Tumor size 2cm (13 vs. 68%) 2. Depth 4mm, thickness 6mm 3. Clark level IV 4. Invasion of adjacent tissue 5. Location 6. Presence of perineural and lymphovascular invasion 7. Tumor grade (17% vs 4%) 8. Growth Rate INITIAL TREATMENT FACTORS: 1. Inadequate primary treatment including incomplete resection 2. Failure to consider re-excision or adjuvant EBRT with subsequent persistent disease RECURRENCE FACTORS: 1. Site: Local recurrent specifically lip and ear (35 and 45% risk) Study of D'Souza and Clark: High Risk Factors for LN Metastases 1. Size > 2cm: 20-30% 2. Invasion into subcutaneous fat (Depth >5mm): 16-45% 3. Poorly differentiated/ metatypical/ morpheophorm phenotype: 12-32% 4. High grade or desmoplasia: 12% 5. Perineural invasion: 40-47% 6. Lymphovascular invasion: 40% 7. Location near parotid (ear, temple, forehead, anterior scalp) or lip: 10-30% 8. Local recurrence: 25-62% 9. SCC in pre-existing scar (burn or trauma): 38% 10. Immunosuppression: 13-20%

Answer 37

1. Cheek 2. Pinna 3. Temple Forehead

Answer 38

PAROTID 1. P0: No clinical disease in the parotid 2. P1: Metastatic node up to 3cm in diameter 3. P2: Metastatic node >3cm and up to 6cm in diameter, or multiple nodes 4. P3: Metastatic node >6cm in diameter or disease involving 7th nerve or skull base NECK 1. N0: No clinical disease 2. N1: Single ipsilateral neck node up to 3cm in diameter 3. N2: Single node >3cm in diameter or multiple nodes or contralateral nodes

Answer 39

Superficial parotidectomy is sufficient if no facial nerve involvement (deep parotid often not involved; however often will get irradiated after superficial parotidectomy)

Answer 40

Vertical line drawn through EAC - Anterior - parotid is the first Echelon ± EJ - Posterior - level V first Echelon ± EJ P0 N+ - Elective Parotidectomy is not generally advocated for patients with isolated neck disease - General guideline: Comprehensive neck dissection + adjuvant radiotherapy (radiation includes the parotid gland in patients where the parotid intervenes between the primary and known nodal disease - Anterior lesion P0N+ = consider parotidectomy - Posterior lesion P0N+ = may not necessarily include the parotid P+ N0 & Anterior or external ear - Parotidectomy + SND I-III - Adjuvant rads if neck negative = parotid - Adjuvant rads if neck positive = parotid & neck P+ N0 & Posterior, scalp, or neck - Parotidectomy + SND (II-V) - Adjuvant rads if nodes negative = parotid - Adjuvant rads if neck positive = parotid + neck P+ N0 & NOS - Parotidectomy & comprehensive neck dissection - Adjuvant rads neck negative = parotid - Adjuvant rads neck positive = parotid + neck P+ N+ & Any primary site - Parotidectomy & comprehensive neck dissection - Adjuvant rads: Parotid and neck ## Footnote SCC Notability lecture/Nadia ppt

Answer 41

Controversial Treatment Options: 1. Observation 2. Elective Neck Dissection 3. SLNB (some European sites do this) High Risk Primary with N0 Disease: Elective Neck Dissection options: 1. Face, scalp, anterior to half of EAC: Superficial Parotidectomy, Level II-IV neck dissection 2. Posterior to half of EAC: Level II-V neck dissection, sub-occipital and post-auricular LN 3. Lips, mid-face: Level I-III neck dissection, Consider bilateral in midline lesions

Answer 42

1. Primary for poor surgical candidates ADJUVANT: 1. Primary lesion - Lesions with positive margins - Extensive PNI or large-nerve involvement 2. Regional Disease - Optional if < 3cm with no ECE/ENE - >3cm nodes - Multiple LN - ENE + Adjuvant radiotherapy has been the only factor that improved local control in metastatic cutaneous SCC in retrospective studies

Answer 43

1. Very High-Risk Disease: Consider Neoadjuvant Cemiplimab-rwlc indications: - Very rapid growth (>4mm/month) - In-transit metastasis - Lymphovascular invasion - Borderline resectable - Surgery alone may not be curative 2. Primary & Recurrent Locally advanced SCC or Unresentable - Radiotherapy ± Systemic therapy; or Systemic therapy alone 3. New regional disease - Fully resected regional disease: Adjuvant systemic therapy NOT recommended - Resected High-risk regional disease, consider RT ± Systemic therapy - For unresectable, inoperable, or incompletely resected disease: RT ± Systemic vs, Systemic Alone 4. Regional recurrence or distant metastasis - Systemic therapy alone ± RT

Answer 44

1. Cisplatin 2. Epidermal growth factor receptor (EGFR) inhibitors (Cetuximab, Erlotinib, Gefitinib, Panitumumab) 3. Cisplatin + 5-FU 4. Carboplatin ± Paclitaxel 5. Anti-PD-1 Inhibitors - Cemiplimab-rwlc and pembrolizumab are the two preferred by NCCN - Nivolumab - No age cut off for systemic therapy

Answer 45

BENIGN: 1. Spitz nevus 2. Mongolian spot 3. Nevus of Ota 4. Compound Nevus 5. Seborrheic keratoses 6. Other types of Nevi: Junctional (flat), Compound, Intradermal (dome shaped) MALIGNANT: 1. Malignant melanoma 2. Pigmented BCC 3. Merkel cell carcinoma 4. Kaposi sarcoma

Answer 46

BENIGN: 1. Keratoses 2. Keratoacanthoma 3. Scar tissue 4. Neurofibroma 5. Squamous papilloma 6. Non-pigmented seborrheic keratoses MALIGNANT: 1. Desmoplastic melanoma 2. BCC (morphea) 3. SCC 4. Bowen's disease 5. Dermatofibrosarcoma (keloid looking lesions) 6. Cutaneous T-cell lymphoma

Answer 47

MERKEL CELL CARCINOMA - Arises from straum basale in epidermis - Merkel mechanoreceptor is thought to be the originating cell (controversial regarding origin: neuroendocrine vs. ectodermal) RISKS: 1. Association with Polyoma virus 2. Fair skin 3. Sun exposure 4. UVA therapy 5. Immunosuppression HISTOLOGY: 1. No epidermal involvement 2. Poorly differentiated 3. Neuroendocrine origin STAINS: "Stupid NCCN" 1. CK20 2. Synaptophysin 3. Chromogranin 4. NSE 5. Neurofilament protein BEHAVIOUR: 1. High recurrence rate (45-75%) 2. High lymphatic metastasis rate (50%) 3. 2x recurrence rate of melanoma TREATMENT: 1. Primary: Wide excision 1-2cm margin 2. Neck: - N0 = SLNB - SLNB+ = Metastatic work up followed by either radiation or surgery to the basin - SLNB- = Consider radiation to the neck 3. Post-op XRT required after wide resection

Answer 48

- Pigmented cells at the dermal-epidermal junction - Produce melanin and package into melanosomes - Melanin = pigments skin + hair, provides photoprotection of the skin/eye - Derived from neural crest cells (neuroectodermal origin)

Answer 49

1. NEVOCELLULAR NEVUS (ie. Common Mole) 2. JUNCTIONAL NEVUS 3. INTRADERMAL & COMPOUND NEVI 4. SPITZ NEVUS 5. CONGENITAL NEVUS 6. DYSPLASTIC NEVUS 7. OTHER: BLUE, HALO NEVI

Answer 50

1. NEVOCELLULAR NEVUS (ie. Common Mole) - Simple, small uniform brown macule

Answer 51

2. JUNCTIONAL NEVUS - Flat, well-circumscribed brown macule, may have darker flecks, even pigmentation - Can look like melanoma (biopsy if unsure) - 25% transformation risk to melanoma (therefore need to monitor!!)

Answer 52

3. INTRADERMAL & COMPOUND NEVI - Usually asymptomatic, may be irritated with shaving/rubbed by clothing - Variable appearance: flat or raised (well circumscribed), pigmented or not (compound usually hyperpigmented, intradermal is skin colored/slightly erythematous) - Never transform

Answer 53

4. SPITZ NEVUS - Melanocytic lesion - Often presents as erythematous papule on the head (usually in child/teenage years) - If cytologic atypia is seen on histology, requires resection)

Answer 54

5. CONGENITAL NEVUS - Big, brown hairy patch, present since birth - 5% of the population - Classification (Large and Giant 15% transformation risk) a. Small < 1.5cm b. Medium 1.5-20cm c. Large 20-50cm d. Giant > 50cm

Answer 55

6. DYSPLASTIC NEVUS - Iffy features (approaching ABCDE of melanoma) - Biopsy if unsure, surgical removal often recommended - Associated with BK Mole Syndrome (CDKN2A gene - encodes for p16)

Answer 56

1. All the risk factors of BCC/SCC (esp. Fitzpatrick 1 - red or blonde, light or blue eyes, fair skin and can't tan) 2. Multiple benign nevi (> 20 increases relative risk to 12:1, > 50-100 of any size is high risk ) 2. p16 mutation (CDKN2a tumor suppressor gene mutation) 3. CDK4 gene mutation 4. MC1R gene mutation 4. Family history of melanoma (1st degree) or BK mole syndrome 4. Congenital nevi (especially large or giant types, > 5% TBSA) 5. Junctional nevi (at dermal-epidermal junction; 25% transformation risk) 6. Dysplastic nevi > 3-5 (dysplastic nevus syndrome, Familial atypical multiple mole-melanoma FAMMM syndrome) 7. Arsenic exposure 8. Artificial UV or solar UV radiation 9. Personal history of melanoma Think: Regular skin cancer risks, syndrome/genetic related risks, and nevus related risks Note: - 50-70% of all melanoma arise from pre-existing benign nevi - Multiple congenital dysplastic nevi - P16 mutation increases risk - Unknown primary of melanoma in 1-5%

Answer 57

BK MOLE SYNDROME: - Aka. Familial Atypical Mole-Melanoma syndrome (FAMM) - Dysplastic nevus syndrome - Atypical mole syndrome - Familial Melanoma GENETICS/INHERITANCE: - Autosomal Dominant - CDKN2A gene mutation (which encodes tumor suppressor p16) CLINICAL PRESENTATION: - Multiple, large, congenital and dysplastic nevi - Often seen in non-sun exposed areas DIAGNOSTIC CRITERIA: Requires ALL 3 criteria: 1) Malignant Melanoma in one or more first- or second-degree relatives 2) High total body nevi count (often >50) including some of which are clinically atypical (based on ABCD) 3) Nevi with certain histologic features on microscopy (ie. lentiginous pattern, nuclear atypic) PROGNOSIS: 1. 10 year risk of melanoma - 10% 2. Lifetime cumulative incidence/risk = 100%!!

Answer 58

1. SUPERFICIAL SPREADING (Most common 75%) 2. NODULAR (2nd most common 15-20%) 3. LENTIGO MALIGNA MELANOMA (4-10%) 4. MUCOSAL (2% of all H/N melanoma, 50% in nasal cavity) 5. ACRAL LENTIGINOUS 6. DESMOPLASTIC/NEUROTROPIC (< 1%, 75% in H/N) 7. AMELANOTIC 8. UVEAL MELANOMA 9. METASTATIC WITH UNKNOWN PRIMARY Head and Neck Melanoma ~20% of total incidence

Answer 59

1. SUPERFICIAL SPREADING (Most common 75%) - Intermediate prognosis - Horizontal superficial spread, Late invasion as it doesn't travel deep - Often from transformation of existing nevus in the 40-50th decade - ABCDE criteria

Answer 60

2. NODULAR (2nd most common 15-20%) - Bad prognosis due to vertical growth - BAD AND DEEP - Early invasion - Blue-red nodule typically - DDx: Hemangioma, blue nevus, pyogenic granuloma, pigmented BCC

Answer 61

3. LENTIGO MALIGNA MELANOMA (4-10%) - Best prognosis - Transformation of lentigo maligna (5%) - Large ill defined mottled brown patch, asymmetric - Lateral spread common - Only 30% ever metastasize (usually < 30%) - Often extensive peripheral involvement of atypical junctional melanocytic hyperplasia (AJMH)

Answer 62

4. MUCOSAL (2% of all H/N melanoma, 50% in nasal cavity) - Common sites in order: 1. Nasal 2. Paranasal sinuses, 3. Oral cavity 4. Nasopharynx - Nasal cavity and oral cavity best prognosis - Paranasal sinuses worst prognosis

Answer 63

5. ACRAL LENTIGINOUS - Not much in Head/neck, occurs on soles/palms - More common in Black/dark skinned people, not from sun

Answer 64

6. DESMOPLASTIC/NEUROTROPIC (< 1%, 75% in H/N) - WORST prognosis - highly aggressive (PNI, skull base involvement common, recurrence/spread common - 50% recur) - Amelanotic lesions - Pure desmoplastic vs. mixed desmoplastic (mixed have high met rates - 22%, pure acts like a regular melanoma)

Answer 65

aka. Lentigo maligna, or melanoma in situ PATHOLOGY: - Atypical melanocytes - Radial spread along dermal/epidermal junction - Focal nests of melanocytic cells CLINICAL PRESENTATION: - Irregular, patchy brown skin discoloration - Usually on face - Probability of melanoma transformation ~5% - Presence of a nodule carries likelihood of invasion of 100% ASSOCIATIONS: 1. Solar damage 2. Atypical melanocytes ## Footnote Vancouver 92

Answer 66

Breslow Depth - From the Stratum GRANULOSUM layer down

Answer 67

1. Level I: Within epidermis only 2. Level II: Invasion into papillary dermis (through basement membrane) 3. Level III: Invasion to papillary-reticular dermis interface 4. Level IV: Invasion into reticular dermis 5. Level V: Invasion into subcutaneous tissues - 20% nodal spread if sun-induced - 50% nodal spread if de-novo

Answer 68

1. < 0.75mm = 0% risk 2. 0.75-1.5mm = 25% risk 3. 1.5-4mm = 50% risk 4. > 4mm = 75% risk

Answer 69

1. Presence or absence of lymph node metastasis (micro better than macro)

Answer 70

1. Asymmetry (lesion itself is asymmetrical) 2. Border irregularities 3. Color variation 4. Diameter ≥ 6mm 5. Evolution: a lesion that is changing in size, shape, or color, or a new lesion Other signs: 1. Ulceration 2. Visible skip lesions 3. Palpable lymphadenopathy

Answer 71

1. H&P with attention to locoregional area, draining lymph nodes, complete skin exam (Dermatology) 2. Biopsy (ideally excision with 1-2mm rim of normal appearing skin and cuff of subdermal fat); if technically not feasible then punch or incision okay. DO NOT SHAVE (affects accuracy); DO NOT use wider initial margins as may affect accuracy of SLNB if you're going into an area where SLN may be 3. Ensure ulceration is documented 4. Neck: SLNB for ≥T1b (highest sensitivity/specificity of any staging modality) 5. Imaging: Consider CT C/A/P, LDH, PET-CT, CT/MRI Brain/neck - see next card for indications - To evaluate specific symptoms; OR - Baseline staging if clinically indicated, or SLNB+ lymph nodes (≥ Stage III) 6. Lab Work (Stage ≥ III) - LDH only if distant metastatic disease - BRAF mutation testing (modifies chemotherapy regime) - BRAF, MEK, C-KIT mutations in >50% of acquired

Answer 72

STAGE IA-IIB (T1a-T4a, clinically N0, before SNB) - None Stage IIC (T4b, clinically N0, before SNB) - Consider PET-CT + MRI Brain - Consider BRAF testing Stage IIIA: SN+ - Prior to completion dissection - no imaging is necessary (Caveat: if planning groin dissection = morbidity or need to evaluate pelvic nodes) - May consider PET-CT prior to surgery if doing surgery - If thick, ulcerated primary, or significant nodal burden: PET-CT + MRI brain prior to potential completion dissection + BRAF testing (ideally reflex testing) Stage IIIB-D: Palpable, in-transit, recurrent - PET-CT + MRI Brain - LDH - BRAF Testing (ideally reflex testing) Stage IV: - PET-CT (esp. oligo-metastatic considering resection) - MRI Brain - LDH a MUST and BRAF testing (ideally reflex testing)

Answer 73

MECHANISM OF ACTION: 1. FDG (FluoroDeoxyGlucose) radiotracer is injected (similar to glucose) 2. Gamma radiation taken up by area of high FDG uptake = areas of high metabolic activity 3. Image often combined with CT overlay to improve anatomical localization INDICATIONS (not exhaustive): 1. Melanoma 2. Unknown primary 3. Staging of poorly differentiated thyroid cancer or hurthle cell carcinoma NORMAL AREAS OF HIGH ACTIVITY: 1. Brain 2. Liver 3. Kidney 4. Heart FALSE POSITIVE: 1. Recent biopsy 2. Recent surgery 3. Recent XRT 4. Infection (e.g. tonsillitis) 5. Region of hyperactivity (e.g. thyroiditis) 6. Sarcoidosis 7. ORN FALSE NEGATIVE: 1. Tumors in region of baseline high activity (variable success) 2. Tumors of low glycolitic activity: - Adenomas - Carcinoid - Low grade lymphoma

Answer 74

PATHOLOGY: 1. "Lentiginous" spread: linear proliferation of melanocytes along basement membrane 2. "Pagetoid" spread: melanocytes floating up through epidermis to surface 3. Invasion: Dark melanin deposits in derms STAINS: 1. Melan-A 2. HMB-45 3. S-100 4. Tyrosinase 5. SOX10 6. Ki-67 (MIB-1)

Answer 75

SATELLITE: - Grossibly visible cutaneous or subcutaneous metastases occuring within < 2 cm of the primary melanoma MICROSATELLITE: - Microscopic cutaneous and/or subcutaneous metastases found adjacent or deep to the primary melanoma on pathology IN-TRANSIT METASTASES: - Cliniically evident dermal and/or subcutaneous metastases identified at a distance >2cm from the primary site, in the region between the primary and first echelon of regional lymph nodes - Still within the regional nodal bason (otherwise it becomes a distant skin met = M1a)

Answer 76

1. Ultrasound 2. CT/MRI 3. SPECT or PET 4. Elective LN dissection (no benefit found except in 1-2mm thick lesions in patients < 60year of age - MSLT1) 5. Sentinel LNB (should be offered to Stage IB and above

Answer 77

1. Anyone with ≥ T1b (>5% risk of occult nodal metastasis) 2. If < 1mm but > 0.5mm, can be considered depending on pathologic features: - Age ≤ 42 year old - Lymphovascular invasion - Head and neck - consider - Mitotic index ≥ 1-2/mm^2 - Deep positive margin - Extensive regression to 1mm

Answer 78

OBJECTIVE: - Patients with cutaneous melanoma following wide local excision, comparing survival between: (1) Observation for development of lymphadenopathy (if develop = ND); and (2) SLNB (if positive = ND) RESULTS: - No difference in overall survival - Subgroup analysis (comparing patients in observation group who went on to develop + neck nodes, vs SLNB+ patients) found a melanoma specific survival benefit for SLNB+ patients with intermediate thickness disease (less nodal recurrence and distant metastasis) CONCLUSION: 1. Nodal status is the strongest predictor of disease recurrence and melanoma specific death 2. SLNB provides a disease-specific survival benefit in intermediate thickness disease 2. Unclear if SLNB+ patients get the survival benefit of SLNB itself, or from the neck dissection that follows

Answer 79

OBJECTIVE: - In patients with intermediate thickness melanoma and positive SLNB, comparison between (1) Immediate LN dissection, (2) Observation with U/S, if develop clinically N+ then LN dissection RESULTS: - No difference in melanoma specific survival at 3 years, but immediate neck dissection reduced the rate of regional nodal recurrence by 70% CONCLUSION: - In patients with SLNB+, completion lymphadenectomy appears to offer no survival advantage but improves local regional disease - Data slightly conflicts with MSLT1; author's theory is that the actual volume of nodal disease is often low, and therefore "most patients have all nodal metastasis removed" during SLNB - Some surgeons do not offer completion neck dissection with SLNB+ (careful discussion required) NOTE: Patients that have clinical positive disease is different. They need a neck dissection followed by immunotherapy. Think of it like RAI for thyroid cancer, need to get the big stuff out then immunotherapy to kill the rest

Answer 80

1. N+ (MSLT-1) 2. Elevated LDH (indicator of hypoxic local environment as melanoma outgrows its blood supply) 3. Depth ? - controversial and debated

Answer 81

NUCLEAR MEDICINE 1. Injection lymphoscintigraphy isotope evening before or day of surgery at least 1-2 hours before (more common) 2. 0.2-0.3mL of filtered 99mTc sulfur colloid + isosulfane blue dye is injected intradermally in four quadrants at edge of the lesion, or at either side of the middle of a scar if previous biopsy (6 quadrants if > 2cm lesion) 3. 99mTc phagocytosed by macrophages in lymph nodes, therefore the activity will not "wash out" of lymph nodes 4. Lymphoscintigraphy imaging is done immediately, and can be co-localized with SPECT-CT PRE-OPERATIVELY: 1. OPTIONAL: Injection of 0.5-1mL of 1% isosulfan blue (lymphazurin; methylene blue) intradermally into the tumor 10-15 minutes prior to skin incision INTRA-OPERATIVELY: 1. Skin incision in anticipation of future surgery (e.g. Mod Blair for parotid) 2. Remove the primary first (reduces shine through effect from gamma counter) 3. Elevate skin flap, then re-scan area of the gamma counter for precise location 4. Find the LN in the bed, then 10-second count over encountered lymph node - "IN VIVO COUNT" recorded 5. Dissect the lymph node out (don't crush node - may leak Technetium Tc 99m into surrounding tissues and make counts inaccurate) 6. Remove lymph node and perform two more counts: - "EX VIVO" 10s count = lymph node itself (usually higher than IN VIVO count) - 10s wound bed count (should be < 10% than the EX VIVO reading) - If post-excision count of the tumor bed is > 10% of the EX VIVO SLNB, further dissection indicated 7. For every LN excised, the take IN VIVO, EX VIVO and post-excision wound bed readings - Once the wound bed reading drops under 10% of EX VIVO reading, SLN successfully removed 8. Nodes sent for permanent pathology

Answer 82

1. Merkel cell carcinoma 2. Melanoma 3. SCC oral cavity 4. SCC cutaneous also debated

Answer 83

Tis = 0.5cm ≤ 1mm = 1cm 1-2mm = 1-2cm > 2mm = 2cm

Answer 84

- Melanoma is not a very radio-sensitive tumor - May improve local-regional control (88% vs. 75%), but there is no survival benefit - Systemic therapies therefore preferred, with better survival benefit INDICATIONS: 1. Elderly poor candidate for operative resection 2. Extensive facial LMM which would required significant resection 3. Primary for desmoplastic histology with extensive neurotropism 4. Metastatic/recurrent 5. Close margin, ENE+, PNI or large nerve involvement, or in-transit disease 6. Inoperable disease/non-surgical candidate 7. Thick/deep invasion ± satellitosis 8. Unresectable nodal, satellite, or in-transit disease 9. Stereotactic radiotherapy (either radiosurgery or fractionated therapy) is the primary treatment modality for brain mets 10. Palliative intent 11. Multiple regional metastasis - Parotid > 1LN, any size - Cervical > 2LN and/or > 3cm

Answer 85

1. Stage III or higher (T3b) 2. Metastatic 3. Unresectable disease

Answer 86

IMMUNOTHERAPY: 1. PD-1 Inhibitor (Antibody) monotherapy - E.g. Pembrolizumab, Nivolumab, Cemiplimab - Indicated for Stage 3 and greater - Act as immune checkpoint inhibitors. Checkpoinit proteins (PDL-1 on tumor cells and PD-1 on T cells) keep the immune system in check. When PDL-1 binds to PD-1 it prevents T-cells from killing the cell. If PD-1 is blocked by the checkpoint inhibitor, then the T-cell is able to kill the tumor cell TARGETED THERAPY (If BRAF V600 activation mutation is present - 65%) 1. Dabrafenib/Trametinib (preferred) - TKI/MEK inhibtors - MAP kinase pathway (mitogen activated protein kinase) 2. Vemurafenib/Cobimetinib - Vemurafenib - TKI, inhibits MAP kinase pathway - 12% of patients will get cutaneous SCCs as a result of Vemurafenib (severe and undesirable side effects)

Answer 87

1. Interferon-alpha 2b 2. IL-2 3. Checkpoint inhibitors 4. Targeted therapies (Tyrosine Kinase inhibitors)

Answer 88

MECHANISM OF ACTION: 1. Biologic response modifier 2. Direct anti-tumor effects 3. Increase host anti-tumor immune response (T-cells, NK cells, etc.) INDICATIONS: 1. Stage III + (T4 or N+) - can be used as adjuvant treatment - Still indicated, but seemingly less popular now with the newer checkpoint inhibitors and targeted tyrosine kinase inhibitors 2. Thickness ≥ 4mm 3. In transit metastasis 4. Positive SLNB 5. Clinical nodes 6. Nodal recurrence 7. Unknown primary REGIMEN: 1. High dose IV - 20 million units (MU) / m^2 - 5d/wk x 4 weeks, then 2. Low dose IV 10 MU SC 3d/wk x 48 weeks (maintenance) RISKS (50% need dose reduction due to intolerable side effects): 1. Severe fatigue 2. Psych (depression, suicide) 3. MI, arrhythmias 4. Liver 5. Myelosuppression BENEFIT: 1. 10% relapse-free survival increase 2. LImited overall survival benefits

Answer 89

MECHANISM OF ACTION: Boosts host immune system by: 1. Activating T-cells, NK, monocytes, cytokines, etc. 2. No direct anti-tumor effects INDICATIONS: 1. Stage 4 (M+) RISKS (Potentially severe and lethal - only for the healthiest patients): 1. MI, arrhythmia 2. Resp issues 3. Hypotension 4. Capillary leak syndrome 5. Nephrotoxicity 6. Hepatic toxicity 7. Sepsis 8. Anemia 9. Thrombocytopenia BENEFIT: 1. 10% Response Rate

Answer 90

CHECKPOINT INHIBITORS: - Checkpoint inhibitors block key immune checkpoinits, including PD-1 and CTLA-4, and therefore kick the immune system into hyperdrive (by blocking the proteins that typically keeep the immune system in check) - "-mabs" 1. Anti-PD-1 Monoclonal antibody agents = Nivolumab (Anti-PDL-1 = Pembro) = "Programmed cell death 1" 2. Anti-CTLA-4 monoclonal antibody agents = Ipilimumab = Cytotoxic T-lymphocyte associated protein 4 - Both have been shown to prolong progression-free and overall survival INDICATIONS: 1. Stage 3+ disease 2. Nivolumab recommended over Ipilimumab, as it has better efficacy and less toxicity than ipilimumab - Combination therapy is being trialled but definitely has more toxicity

Answer 91

TYROSINE KINASE INHIBITORS - MAP Kinase (MAPK) pathway inhibitors - ≥50% of melanoma is positive for BRAF V600 (which upregulated MAPK) - "-nibs" EXAMPLES: 1. Multiple agents target BRAF V600, including Vemurafenib, Dabrafenib 2. Agents often combined with MEK inhibitors (mitogen-activated protein kinase kinase) - Cobimetinib, Trametinib - Improves survival - Reduces development of treatment resistance (often seen after 6-7 months in single agent therapy - Vemurafenib is combined with Cobimetinib "VC" - Dabrafenib is combined with Trametinib "DT" INDICATIONS: 1. Stage 3+ with BRAF V600 activating mutation - Increase progression-free survival - Increase overall survival SIDE EFFECTS: 1. Vemurafenib - arthralgia, cutaneous SCC, rare complication of cardiac tamponade IMATINIB (GLEEVEC): - Patients with activating mutations in KIT (c-KIT, also encodes tyrosine kinase) show meaningful response to Imatinib in small trials - KIT mutation in ~15% melanoma - Short duration of benefit - Indications: Metastatic or unresectable disease

Answer 92

1. Ipilimumab - Binds to Cytotoxic T-lymphocyte associated antigen 4 (CTLA4), blocks this inhibitory signal to allow the cytotoxic T-cell to destroy cancer cells 2. High dose IL-2 3. Imatinib - BCR-ABL (gene)/cKIT tyrosine kinase inhibitor

Answer 93

- Melanoma not very chemosensitive (< 20% response rate) - No survival benefit OPTIONS: 1. Dacarbazine (only chemo agent approved for Stage IV; response 10-20%, often used in combo with others) 2. Temozolomide 3. Paclitaxel 4. Carboplatin INDICATIONS (essentially palliative): 1. Advanced (metastatic or unresectable) disease that has failed trial of other systemic options (immunotherapy, targeted therapy) 2. Advanced stage IV disseminated melanoma

Answer 94

- "Talimogene Laherparepvec" (T-VEC) - Attenuated HSV virus, that expresses GM-CSF (Granulocyte-macrophage colony-stimulating factor) - Injection into unresectable tumor causes tumor lysis and enhances immune response (local tumor cell death, increase systemic clearance of tumor cells at uninjected sites)

Answer 95

- < 0.7mm = 98% - > 3mm = 53% - Recurrence will occur 70% within 2 years, 80% within 3 years

Answer 96

- Stage IA: Annual Exam - Stage IB and above: standard HN follow up regimen and annual LDH level; CBC ± imaging if suspicious clinical features arise

Answer 97

All comers = 20% Desmoplastic = 5-10% False negative = 5%

Answer 98

Perineural invasion (like adenoid cystic carcinoma)