Non-Melanoma Skin Cancer

Question 1

Actinic Keratosis Subtypes

Answer 1

Acantholytic AK, Bowenoid AK, Lichenoid AK, Atrophic AK, Hypertrophic AK, Pigmented AK, Actinic Cheilitis, Cutaneous Horn

Question 2

AK Treatment Options

Answer 2

Cryotherapy, 5-FU, imiquimod, chemical peels, PDT

Question 3

Bowen’s Disease variants

Answer 3

Atrophic, Verrucous, Pigmented, Pagetoid, Erythroplasia of Queyrat (on glans penis)

Question 4

Erythroplasia of Queyrat

Answer 4

Bowen’s Disease of glans penis

Question 5

Bowen’s Disease treatment options

Answer 5

Excision, C&E, PDT, Cryosurgery, imiquimod

Question 6

SCC sites with high risk of metastasis

Answer 6

Lip or ear (10-20%), recurrent SCCs (up to 30%), arising within scars/chronic ulcers, perineural invasion, poor differentiation on histology, immunosuppression

Question 7

Fold Increase Risk of SCC in organ transplant patients

Answer 7

65-fold

Question 8

KA centrifugum marginatum

Answer 8

KA that may reach several centimeters in diameter, concomitant expansion of border and central healing

Question 9

Giant KA

Answer 9

rapid enlargement of nodule to several centimeters

Question 10

Ferguson-Smith type

Answer 10

sudden-onset of multiple KAs in childhood which will slowly resolve on their own; autosomal dominant

Question 11

KA of Grzybowski type

Answer 11

sudden onset of multiple KAs in adulthood (eruptive pattern); very pruritis; mask like facial appearance due to thickened face skin; +Ectropion (drooping lower eyelids w/ retraction); hoarseness due to nodules on larynx

Question 12

Fold Increase Risk of BCC in organ transplant patients

Answer 12

10-fold

Question 13

Variants of BCC

Answer 13

Nodular, Superficial, Morpheaform, Basosquamous, Micronodular, Adenoid, Cystic, Fibroepithelioma of Pinkus

Question 14

Fibroepithelioma of Pinkus

Answer 14

BCC variant appearing as pink plaque or smooth nodule on lower back

Question 15

Most common BCC metastatic sites

Answer 15

Lymph nodes and lung

Question 16

Treatment options for BCC

Answer 16

Excision, Mohs, C&E, RT, topical imiquimod (superficial BCCs)

Question 17

Merkel Cell Carcinoma 5-year mortality

Answer 17

30%

Question 18

Merkel Cell Metastasis rate at time of diagnosis

Answer 18

40%

Question 19

Immunohistochemistry markers for Merkel Cell Carcinoma

Answer 19

CK20+, CK8/18/19 (CAM 5.2)+, chromogranin+, somatostatin+, calcitonin+, synaptophysin+, VIP+, neuron-specific enolase+

Question 20

Merkel Cell Carcinoma treatment

Answer 20

Wide local excision (3cm margins) often with adjuvant chemo and/or radiation; sentinel node biopsy

Question 21

Mutation in BCC (and role in pathway)

Answer 21

Patched- 12 transmembrane protein that binds to Smoothened (7 transmembrane G-protein) to prevent constitutive activation of Gli (also Bcl2 and TGF beta)

Question 22

6 Hallmarks of Cancer

Answer 22

(1) self sufficiency in regards to growth signals
(2) insensitivity to anti-growth signals
(3) evasion of apoptosis
(4) limitless replicative potential
(5) sustained angiogenesis
(6) tissue invasion and metastasis

Question 23

5-FU Mechanism

Answer 23

Blocks methylation reaction of deoxyuridylic acid to thymidylic acid, thus interfering with DNA/RNA synthesis

Question 24

Ingenol mebutate mechanism

Answer 24

Hydrophobic diterpene ester (from plant Euphorbia peplus); induces mitochondrial swelling leading to cell death of keratinocytes by necrosis

Question 25

Mechanism of Diclofenac in hyaluronic acid

Answer 25

NSAID that inhibits COX2 and reduces prostaglandin synthesis (thought to be increased in exposed skin)

Question 26

Mechanism of PDT with ALA

Answer 26

Application of ALA leads to formation of protoporphyrin IX (PpIX), which can be irradiated with certain wavelengths, leading to reactive singlet oxygen formation

Question 27

FAMMM Syndrome mutation

Answer 27

some cases...CDKN2A (p14ARF, p16); screen patients if 3 or more MM OR if 1 MM with family history (2 affected with MM or 1 pancreatic cancer)

Question 28

3 wavelengths of UVR

Answer 28

UVC: 200-290nm; extremely mutagenic; mostly filtered out by atmosphere UVB: 290-320nm; most important to carcinogenesis UVA: 320-400; less potent mutagen but greater intensity than B so important

Question 29

UVB mutagenesis

Answer 29

formation of cis-syn diastereomers of cyclobutane pyrimidine dimers and pyrimidine [6-4] pyridimidine adducts; both C-->T and CC-->TT at sequences with adjacent pyrmidine residuces (signature of UV-induced mutagenesis)

Question 30

UVA mutagenesis

Answer 30

mediated through action of reactive oxygen species; T--> G transversions

Question 31

Imiquimod mechanism

Answer 31

activates TLR7 and TLR8 leading to increased expression of NFKb

Question 32

Bowenoid papulosis and associated infectious etiology

Answer 32

Verrucous papules/plaques (2-3mm) on penis or external femal genitalia; associated w HPV 16 or HPV 18

Question 33

5 risk factors for leukoplakia transformation to SCC

Answer 33

Verrucous appearance, ulceration, presence of inlying nodule, induration, and presence on anterior floor of mouth or underside of tongue

Question 34

Differential for Spindle Cell Skin Neoplasm

Answer 34

"SLAM"; SCC, leiomyoma, AFX, melanoma

Question 35

Oral florid papillomatosis

Answer 35

HPV 11; verrucous carcinoma seen in mouth of elderly males and associated with tobacco use

Question 36

Buschke-Lowenstein tumor

Answer 36

HPV 6, 11; giant condyloma acuminata

Question 37

Epithelium cuniculatum

Answer 37

HPV 6, 11, 16, 18; verrucous carcinoma on plantar feet of elderly men

Question 38

Muir-Torre Syndrome

Answer 38

KA, sebaceous neoplasms, and GI tumors; mutation of DNA mismatch repair genes MSH2, MSH6, MLH1, PMS2; autosomal dominant

Question 39

Nevoid Basal Cell Carcinoma Syndrome

Answer 39

AD; Patched mutation; Multiple BCCs, palmar/plantar pits, skeletal abnormalities (increased head circ, frontal bossing, mild hypertelorism, rib abn, shortening of 4th metacarpal, jaw cysts- odontogenic keratocysts, calcification of flax cerebri); other neoplasms: medulloblastoma, ovarian fibromas, mesenteric cysts, meningiomas, fibrosarcomas, cardiac fibromas, ovarian desmoids

Question 40

DDx for small round blue cell tumors

Answer 40

LEMMMONS: lymphoma, Ewings, Merkel cell, melanoma, metastasis, oat cell lung ca, neuroblastoma, small cell neuroendocrine tumor

Question 41

Bazex Syndrome

Answer 41

B (BCCs), A (Atrophoderma), Z (zero hair), E (eccrine abn; anhidrosis), X (X-linked dominant)

Question 42

Rombo Syndrome

Answer 42

similar to Bazex; KP-like lesions on face (atrophoderma vermiculatum), hypotrichosis, blepharitis, milia, peripheral vasodilation with cyanosis, multiple BCCs

Question 43

Huriez syndrome

Answer 43

high risk cutaneous SCC and GI tumors; sclerodactyly, nail anomalies, and PPK

Question 44

Xeroderma Pigmentosa

Answer 44

SCC=BCC>melanoma; AR; defect in DNA repair enzymes (XPA, XPC, and XPV); assoc with neuro abn and internal malignancies

Question 45

Epidermadysplasia Verruciformis

Answer 45

AR; EVER1/EVER2; predisposes to widespread HPV infection; most common HPV 3, 5, 8; nail dystrophy +/- hyperkeratosis of plams/soles; can get early-onset SCCs