Pathophys-Day 2 Skin Cancer

Question 1

BCC, SCC, melanoma arise from which layers?

Answer 1

BCC:germ keratinocytes/basal layer
SCC: epidermal keratinocytes/spiny
Melanoma: melanocytes

Question 2

PTCH mutations are found in __% of ___ cancers

Answer 2

30% of BCC

Question 3

What does PTCH do?

Answer 3

Regulate keratinocyte proliferation as a tumor suppressor

Question 4

Immunosuppressed patients are at greatest risk for which skin cancer

Answer 4

SCC, but also more for BCC

Question 5

What are some risk factors for BCC?

Answer 5

UV
Fair complexion
BLISTERING sunburns
Family hx
Immunosuppression

Question 6

What are some characteristic features of BCC gross appearance?

Answer 6

Teliangectasia

Question 7

BCC histo appearance?

Answer 7

Blue nodules in dermis with PALISADES and RETRACTION from stroma which is required for survival (thus low metastasis)

Question 8

Topical treatment for superficial and nodular?

Answer 8

Not for nodular

5-FU

Question 9

nodular/’classic’ bcc appearance gross

Answer 9

pearly rolled border
central erosion
telangiectasia

Question 10

sclerotic/morpheaform bcc appearance gross

Answer 10

crusty, ill-defined

Question 11

Gorlin syndrome mutation, S/S?

Answer 11

PTCH tumor suppressor
AD
M/S defects, jaw cysts
BCCs in 20's
Inc risk of other neoplasms inc medulloblastoma, fibrosarcoma

Question 12

PTCH signaling overview

Answer 12

PTCH tumor suppressor inhibits SHH from binding to SMO (TKI inhib vesmodegib inhibits SMO)

Question 13

Does BCC usually metastasize?

Answer 13

Almost never, <1%

Question 14

Tx for BCC

Answer 14

Excision is first choice

Electrodessication, cryosurgery, radiation…topical for superficial (imiquimod/5FU)

Question 15

Compare the prognosis for head/neck/cervical vs mucosal/lung SCC

Answer 15

H/N/C less aggressive than mucosal/lung

Question 16

SCC gross path

Answer 16

Well demarcated and crusty

Question 17

Contrast SCC mutagenesis to BCC

Answer 17

While BCC often involves an identified gene defect, PTCH, SCC arises from any number of mutants with the ‘2 hit’ hyp.

Classically SCC begins in basal area/lower epi and progress upwards

Question 18

Compare SCC to SCCis

Answer 18

SCCis is defined as atypical keratinocytes found throughout entire thickness of epidermis

Question 19

What is the progression of SCC?

Answer 19

Actinic keratosis -> SCCis (i.e. Bowen’s or Erythroplasia of Queyrat - penis) -> SCC

Question 20

Actinic keratosis micro path

Answer 20

Parakeratosis: nuclei in stratum corneum

Pleomorphic

Question 21

AK gross path

Answer 21

Thin lesions that lack induration (superficial)

Question 22

SCC micro path

Answer 22

Pink and keratinizing like stratum spinosum, with islands of squamous cells extending into dermis

keratin pearls

Question 23

Major risk factors for SCC?

Answer 23

UV, HPV 16, 18
Chronic inflammation
Immunosuppression
Chronic skin irritation/ulceration
Arsenic
Radiation

Question 24

What factors influence SCC metastasis risk?

Answer 24

Size
Depth
Site
Status

Question 25

**Highest risk sites for metastasis of SCC?

Answer 25

Lips and ears for both mets and local spread Also vulvar, penile, HPV-induced

Question 26

What are Marjolin ulcers?

Answer 26

Areas of previously severely/chronic traumatized skin that are at high risk for SCC

Question 27

Where does SCC met to?

Answer 27

Lymph nodes and lung

Question 28

SCC gross path

Answer 28

Central ulceration Rolled borders Crusty

Question 29

Describe keratoacanthoma

Answer 29

``` Neoplasm of keratinocytes Rapid growth over 2-6 weeks Painful Spontaneous involution Well-differentiated ```

Question 30

SCC treatment?

Answer 30

AK: topical/cryo SCCis: topical/intralesion/excision Invasive: excision

Question 31

Who is at highest risk for melanoma?

Answer 31

White men over 50

Question 32

What is the gold standard for melanoma Dx?

Answer 32

biopsy

Question 33

Who is melanoma on the rise in?

Answer 33

Old men and women with hx of tanning

Question 34

Contrast SCC and melanoma pathogenesis

Answer 34

Melanoma is not step-wise like SCC; malignant melanocytes from the beginning

Question 35

Melanoma vs mole?

Answer 35

80% of melanoma de novo not from moles

Question 36

Where is melanoma in situ?

Answer 36

Just epidermis only

Question 37

Where is mel in situ common?

Answer 37

face, good for topical

Question 38

Melanoma must reach the __ to metastasize

Answer 38

dermis

Question 39

What are the three types of nevi and their characteristics?

Answer 39

Junctional: ? Compound: dermis+epidermis Intradermal: nests in bottom?

Question 40

Describe a common acquired melanocytic nevus

Answer 40

Small, well circumscribed, uniform pigment, symmetrical Nests in epidermis and dermis

Question 41

Nev vs melanomas in terms of maturation?

Answer 41

Nevi: melanocytes mature with descent (get smaller); confined to basal layer Melanoma: melanocytes do not mature with desc

Question 42

Micro path of melanoma?

Answer 42

Large melanocytes with halo artefacts around; melanocytes will be up above basal layer and look funny/disorganized

Question 43

Describe radial growth

Answer 43

Growth outward, as opposed to downward which is bad for metastasis

Question 44

Describe vertical growth

Answer 44

Journey toward metastasis, blue tumor pushes down into dermis

Question 45

Melanoma riskf actors

Answer 45

``` Large # moles Giant congenital nevi Blistering sunburns Fam hx Fair skin / tanning bed Immune dysfunction ```

Question 46

Melanoma ABCDE

Answer 46

``` Assymetry Borders: irregular Color: mottled, not uniform Diameter: >6 Elevation ```

Question 47

What form of melanoma is commonly found on the hands and feet?

Answer 47

Acral lentiginous

Question 48

What form of melanoma on face usually?

Answer 48

Lentigo maligna

Question 49

Nodular mel less or more aggressive?

Answer 49

Aggressive

Question 50

What is the most common type of malignant melanoma in patients with dark skin?

Answer 50

Acral lentiginous (hands and feet)

Question 51

Who commonly gets lentigo maligna?

Answer 51

Old people on face with sun exposure

Question 52

What does it indicate when a nodule arises on top of a lentigo maligna?

Answer 52

metastasis

Question 53

Nodular melanoma facts

Answer 53

Sun exposed skin No preceding radial growth Men > Women

Question 54

Superficial spreading melanoma gross appearance

Answer 54

Multicolored, partially regressed from immune attack

Question 55

Red, white, and blue sign?

Answer 55

superficial spreading melanoma

Question 56

Keratin cysts on the surface of a suspicious dark lesion suggest what?

Answer 56

Not mel

Question 57

Explain why melanomas can be found outside of the skin

Answer 57

Melanocytes are derived from the neural crest, as are the eyes/retina, inner ear, and medulla

Question 58

How does melanoma usually spread?

Answer 58

Lymphatics

Question 59

What is the single most important prognostic factor in Mel met?

Answer 59

lymph node involvement

Question 60

What is the most important histo prog factor in mel met?

Answer 60

Breslow thickness and ulceration

Question 61

What is the Breslow thickness for Mel IS?

Answer 61

0

Question 62

What is Breslow's thickness?

Answer 62

Distance of involvement from stratum granulosum top to deepest tumor cell

Question 63

What is the most common single gene mutation in melanoma?

Answer 63

BRAF, 50%

Question 64

What targeted therapy for melanoma?

Answer 64

Vemurafenib, BRAF inhibitor | Survival benefit is modest

Question 65

Vemurafenib facts

Answer 65

Metastatic/unresectable mel Benefit with Ipilimumab combo 50% mel have it, 50% respond

Question 66

Specific relationships between the cancers and sunlight?

Answer 66

SCC: cumulative clearly BC: UV imp but maybe not cumulative Mel: has a role, w other factors