Melanoma

Question 1

Melanoma originates from these embyonic cells?

Answer 1

neural crest cells which migrate to skin, aerodigestive tract and uvea

Question 2

Recognized risk factors?

Answer 2

• personal or family history
• multiple benign or atypical nevi (>50)
• intermittent severe sunburns
• sensitivity to sun exposure

Question 3

Subtypes of melanoma (order of frequency) ?

Answer 3

• Superficial spreading (70%): sun-exposured, classic irregular nodule
• Nodular (20%): rapid growing, homogenous darkly pigmented
• Lentigo maligna: chornically solar-damaged skin, older pts on head and neck
• Acral lentiginous: Asian and african descent: subungually on the palms and soles
• Desmoplastic: rare and aggressive; usually amelanotic
• Uveal melanoma: can dx w/o biopsy, usually met to liver

Question 4

Most common molecular features and historical correlate?

Answer 4

• Activating BRAF (50%) mutations; usually seen in intermittently solar damaged skin rather than chronic
• KIT: usually acral lentignous
• NRAS (15%): can be seen in both
• GNAQ or GNA11: 50% of uveal

Question 5

What is molecular feature of inherited melanoma

Answer 5

-alteration of tumor suppressor CDKN2A encoding p16INK4A and p19ARF

Question 6

What is summary of TNM staging in melanoma?

Answer 6

0: confined to epidermins
I: Ib: 4cm with ulceration
III: positive nodes: IIIa: Ib disease with 1-3micronodes, IIIb: any size with 1-3 macro nodes no ulceration, IIIc: IIIb with ulceration or in-transit mets/satellites
IV: metastasis

Question 7

Prognostic variables in primary cutaneous melanoma?

Answer 7

Lymph node positivity
Breslow depth (tumor thickness)
microscopic ulceration
mitotic rate (thin primary

Question 8

Melanoma with no nodes is treated how?

Answer 8

Surgery with adequate margins

Question 9

Margin recommendations for melanoma?

Answer 9

Tumor size: Margin
melanoma in situ: 0.5 cm
0.5-1mm: 1.0 cm
1-2mm: 1.0-2.0 cm
>2mm: 2.0cm

Question 10

When do you perform sentinal lymph node mapping/ biopsy? Data? Survival Benefit?

Answer 10

lesions >=1cm in breslow depth; if high risk features than

Question 11

What is standard of care for positive nodes on SLN mapping in melanoma?

Answer 11

complete lymphadenectomy (this is being formally answered in MSLT-II)

Question 12

What is satellitosis?

Answer 12

at least 1 seperate focus adjacent to primary

Question 13

What is in-transit?

Answer 13

not immediately adjacent but within draining nodal basin

Question 14

Standard of care for in-transit?

Answer 14

surgical resection if possible

Question 15

What is survival for Stage IIIA, IIIB & IIIC in melanoma respectively?

Answer 15

80, 60, & 40%

Question 16

What defines Stage III disease in melanoma and how is it managed?

Answer 16

Lymph node involvment,

surgical resection followed by adjuvant therapy or observation

Question 17

What are adjuvant options?

Answer 17

clinical trial, radiotherapy (for regional control) or high dose interferon alpha-2b

Question 18

How is interferon usually given?

Answer 18

20 million units/m2 IV M-Fx4 weeks followed by 10 million units/m2 subq 3xweek for 48 weeks

Question 19

What’s the data show for interferon in stage IIB-III melanoma?

Answer 19

OS and DFS at 5 years that disappears in meta-anaysis with median follow-up of 12.6 years

Question 20

In addition to standard toxicities, what else are you concerned for with interfereon therapy?

Answer 20

liver dysfunction myeosupression and depression

Question 21

What is standard surviellance for early stage melanoma followed by resection?

Answer 21

Exam 3-4 months, for first 2 years, then q6 months for next 3 years
NO imaging, only at clinican’s discretion
LDH is only lab value to follow

Question 22

What is management of recurrent disease?

Answer 22

Depends:

- if local can resect; if unresectable considered hyperthermic or isolated limb infusion

Question 23

What is Stage IV melanoma further classified by? (2 factors beginning with L)

Answer 23

location and LDH

Question 24

What is M1a, M1b or M1c disease imply? And respective survival?

Answer 24

M1a: distant skin, subcutaneous or nodal metastatic disease with normal LDH (30%)
M1b: lung metastasis with normal LDH (20%)
M1c: visceral mets or any mets with LDH elevation (10%)

Question 25

What if available, is the most important therapeutic option, melanoma?

Answer 25

surgical resction

Question 26

What are your options for unresectable melanoma?

Answer 26

• Dacarbazine
• IL-2
• ipilumumab
• vemurafenib
• nivolumab +/- ipi
• dabrafenib + trametinib (mek inhibitor)
• clinical trial

Question 27

Name an unusual side effect of vemurafenib therapy?

Answer 27

incidence of squamous cell carcinoma and keratoacanthoma

Question 28

what is a common complicating factor limiting treatment options in melanoma?

Answer 28

brain involvement