Challenges in Surgery of

Cutaneous Melanoma:

Indications for Margin Control

Prior to Reconstruction

Christopher J. Miller, MDDirector of Dermatologic Surgery

Assistant Professor of Dermatology

I have no conflicts of interest

or relevant ties with industry.

Challenges for conventional surgery of

specialty-site melanoma

Tis/ Stage 0

Wide local excision with 0.6 mm margin

and reconstruction before microscopic margin assessment

Upstaged from MIS to IIA

Positive margins

1.62 mm, 1 mit/mm2, no ulceration

T2b/Stage IIA

*Upstaged to SLNB candidacy

Outline

• Define the problem:

–Rule of 10s

• Define the solution:

–Microscopic margin-controlled

surgery before reconstruction

Problems with conventional surgery

of specialty-site melanomas

Head and neck, hands and feet, genitals, pretibial leg

• Upstaging

• Positive excision margins

• Local recurrence

• Complex reconstruction

>10%

10x ↑

Rule of 10s

Conventional Surgery

Rule of 10s

>10% risk of

upstaging after

reconstruction

1332 melanomas treated with

conventional WLE at Penn

Primary outcome: upstaging

(defined as increase in the AJCC T stage

after excision)

J Am Acad Dermatol 2017;77:341-8

Specialty site is

most powerful predictor of upstaging

Risk factorOdds Ratio

(multivariate analysis

with step-wise

regression)

P-value

Anatomic location on head, neck, hands,

feet, genitals, or pretibial leg7.06 <0.001

Extension of melanoma to base of

biopsy specimen3.24 <0.001

Multiple preoperative biopsies 1.89 0.004

Older age 1.03 (per year) 0.002

Non-LM histologic subtype 3.6 0.003

Etzkorn JR, Miller CJ et al. Frequency of and risk factors for tumor upstaging after WLE of primary

cutaneous melanoma. JAAD 2017

Rates of upstaging of melanoma

Specialty site rule of 10s

Head, neck,

hands, feet,

genitals, pretibial

leg

Trunk and

proximal

extremities

12%

(33/277)

1.8%

(19/1055)

Etzkorn JR, Miller CJ et al. Frequency of and risk factors for tumor upstaging after WLE of primary

cutaneous melanoma. JAAD 2017.

Upstaging may affect surgical

management

Chance that upstaged

tumor will change

margin

recommendations

Chance that upstaged

tumor will qualify for

SLNB

62%

(32/52)

27%

(14/52)

Etzkorn JR, Miller CJ et al. Frequency of and risk factors for tumor upstaging after WLE of primary

cutaneous melanoma. JAAD 2017

Upstaging may complicate surgical management

Preoperative staging:

T1a Melanoma, 0.22 mm

Postoperative staging:

T2a Melanoma, 1.65 mm

Recon delayed for SLNB

Upstaging complicates:

Patient counseling

Margin determination

Sentinel lymph node biopsy

Conventional Surgery

Rule of 10s>10% risk of positive

margins after

reconstructionExcision with positive margins

Specialty site melanomas are

commonly poorly defined and may be

difficult to excise with wide margins

Diagnosis: MIS

Inaccurate clinical margins =

Inaccurate surgical margins

1345 melanomas treated with

conventional WLE at Penn

Primary outcome:

Frequency of positive or equivocal margins

Miller CJ, Etzkorn JR et al. JAAD 2017;77:333-40

Predictors of positive margins on

conventional WLE

Risk factorOdds Ratio

(multivariate analysis

with step-wise

regression)

P-value

Non-compliance with recommended

margins5.57 0.002

Anatomic location on head, neck, hands,

feet, genitals, or pretibial leg5.07 <0.001

Histologic regression 2.78 0.007

Melanoma in situ 2.27 0.011

Multiple preoperative biopsies 1.92 (per biopsy) 0.004

Older age 1.049 (per year) <0.001

Miller CJ, Etzkorn JR et al. Risk factors for positive or equivocal margins after WLE of 1345 cutaneous

melanomas. JAAD 2017. Provisional acceptance 2/2017

Rates of positive margins after WLE

Non-compliant

surgical margins

Compliant

surgical margins

22.6%

(7/31)

3.2%

(41/1282)

Rates of positive margins after WLE

Specialty site rule of 10s

Head, neck,

hands, feet,

genitals,

pretibial leg*

Trunk and

proximal

extremities

11.5%

(32/278)

2.2%

(24/1067)

Miller CJ, Etzkorn JR et al. Risk factors for positive or equivocal margins after WLE of 1345 cutaneous

melanomas. JAAD 2017.

*Compliance with recommended surgical margins: 94.7% (250/264)

Conventional Surgery

Rule of 10s>10% risk of

local recurrence

Local recurrence rates

after WLE of melanoma

Head and

neck

Trunk and

extremities

13%

(388/2984)

1.7%

(144/8400)

Historical data from Table IV in Etzkorn JR, Miller CJ et al J Am Acad Dermatol 2015;72:840-50

1.7% (144/8400)

Range: 0.8-12.4%

8% (240/2984)

Range (2.8-21.4%)

Etzkorn JR, Miller CJ et al J Am Acad Dermatol 2015;72:840-50

Local recurrence rates are higher for specialty-site MM

Rule of 10s10x increased likelihood of

complex reconstruction

10x greater likelihood of complex reconstruction

for specialty site melanomas

Anatomic

location

Frequency of

flap or graft

reconstruction

Odds Ratio

(95% CI)P-value

Specialty site 53.7% (275/512) 10.3 (4.86-21.8) 0.0001

Trunk and

proximal

extremity

10.1% (8/79) 1 (reference)

Etzkorn JR, Miller CJ et al. Dermatol Surg 2016;42:471-476

Previously treated melanomas are significantly

more likely to require more complex reconstruction

10/11/2011

Linear scar previous surgery

Final Mohs defect

4 stages

Etzkorn JR, Miller CJ et al. Dermatol Surg 2016;42:471-476

3 conditions for optimal surgery

of melanomas

• Accurate pathologic staging

prior to reconstruction

• Clear microscopic margins

• Reconstruction in tumor-free

skin

Solution for optimal melanoma surgery:

Combine breadloaf sectioning of central

tumor with microscopic margin

assessment prior to reconstruction

Numerous methods of margin control improve

surgical management of melanoma

• Mohs surgery

• Slow Mohs

• Square procedure

• Spaghetti technique

• Mapped serial excision

• Staged excision with radial sections

Table from Mayo K et al. Chapter 6. Staged Excision Techniques. In LMM. Springer 2016. Eds Nehal and Busam

Thank you to Drs. Zitelli and Brodland for

their pioneering work in Mohs for melanoma

J Am Acad Dermatol 2005;52:92-100

Dermatol Surg 2004;30:403-408

H&E and MART-1 frozens on all sections

of debulk and Mohs layer

H&E frozen

section

MART-1

frozen

section

597 melanomas treated with Mohs surgery at Penn

• Two outcome measures

– Accuracy of staging prior to recon: 99.8% (596/597)

– Local recurrence rate: 0.34% (2/597)

• average f/u: 2.8 years

JAAD 2015

Both in situ and invasive melanoma

Melanoma in situ

73%

(436/597)

Invasive melanoma

27%

(161/597)

80%

(475/597)

Vast majority of lesions were

“specialty site melanomas”

Trunk and proximal

extremities

9.7%

(58/597)

Example of primary melanoma on dorsal

forearm treated with Mohs surgery

Preoperative Dxs:

Lentigo malignaMargins outlined Mohs defect

Final diagnosis: LMM, 0.28 mm

16% (98/597) of melanomas

had been previously treated

Recurrent lentigo maligna

Video of Mohs for Melanoma

Data show that we met 3 conditions for

optimal surgery of melanoma

• Accurate pathologic staging

prior to reconstruction

• Clear microscopic margins

• Reconstruction in tumor-free

skin

Treatment goal #1:

Accurate pathologic

staging prior to

reconstruction

99.8% accurate

(596/597)

Breadloaf sectioning of the

central tumor prior to

reconstruction

34/614 (5.5%) patients

upstaged AJCC T category

8

97% (33/34) detected by Mohs surgeon prior to reconstruction

23.5% (8/34) upstaged to criteria qualifying for SLNB

3 patient elected to undergo SLNB (1 was positive)

Melanoma, 0.22 mm Melanoma, 1.65 mm

Recon delayed for SLNB

Treatment goal #2:

-Clear microscopic

margins

100% microscopic margin

assessment of the Mohs layer with

MART-1 frozen section

immunostains

Local recurrence rate

0.34% (2/597)

(Mean follow time: 2.8 years)

0.8-12.4%

2.8-28%

10%

Comparison historical rates of local recurrence after conventional surgery

Penn local recurrence rate

(published Penn data)

Estimated local

recurrence rate after

conventional surgery

(historical published data)

2/597 (0.34%) 60/597 (10%)

Treatment goal #3:

-Reconstruction in

tumor-free field

100% microscopic margin

assessment of the Mohs layer with

MART-1 frozen section

immunostains

Complex reconstruction in tumor-free skin>55% of head and neck melanomas were

repaired with either a flap or graft

45.4

3.97.4

38.6

0.6 0.4 1.6 2.1

11

0

7.1

76.4

0 0

5.5

00

10

20

30

40

50

60

70

80

Flap Flap andgraft

Graft Linear Linear + graft Linear +second intent

Secondintent

Referred out

Chart Title

Head and neck Trunk and extremity

People place highest priority on

restoring a normal face, compared

to all other body parts

Borah GL, Rankin MK. Plast Reconstr Surg 2010;125:873

Outline

• Define the problem:

–Rule of 10s

• Define the solution:

–Microscopic margin-controlled

surgery before reconstruction