Surgical Incisions in Thoracic Trauma · A. 0.7 mm melanoma over right tibia with clinically negative right groin ... 2 -existing mole on RLE that became raised, multi-color, crusted.

Melanoma

Jason P. Sulkowski MD

www.downstatesurgery.org

Question 1 • In which of the following cases should a sentinel

lymph node biopsy be performed?

– A. 0.7 mm melanoma over right tibia with clinically negative right groin

– B. 1.0 mm melanoma overlying the left groin

– C. 1.5 mm melanoma of RUE and clinically negative right axilla

– D. 1.7 mm melanoma of left thigh with palpable adenopathy of left groin


Question 2 • Melanoma

– A. Incidence is decreasing in the U.S.

– B. Most commonly presents as the nodular subtype.

– C. Is best biopsied using a shave technique.

– D. Should be excised with a 2 cm margin if >2 mm

thick.

– E. Rarely spreads to lymph nodes.


Case - AM • HPI: 27y F presented with pre-existing mole on

RLE that became raised, multi-color, crusted. 1 month prior had excisional biopsy in dermatology office.

• PMH: significant sun exposure, multiple sun burns in past

• Medications/Allergies: none

• Family Hx: no history of skin cancer


Case - AM

• Physical Exam: – Vitals: wnl – HEENT: wnl – CV: wnl – Pulm: wnl – Abd: wnl – LNs: no cervical axillary or inguinal

lymphadenopathy


Case - AM

• Physical Exam: – RLE: 4 cm well-healing

incision on posteromedial calf

– LLE: no abnormal lesions


Case - AM

• Pathology (1): – Malignant melanoma – 1.9 mm thick – Tumor within 1 mm of margin


Case - AM

• Lymphoscintigraphy: – Three sentinel lymph nodes identified in

right inguinal region


Case - AM • Procedure:

– Wide local excision (WLE) of melanoma site • Elliptical incision, 2 cm margins, dissection down

to fascia

– Sentinel lymph node biopsy (SLNB) of right groin

• Radiocolloid only • One node excised • All other nodes had <10% signal • Frozen section negative for malignancy


Case - AM

• Pathology (2): – No residual melanoma cells

– One of one lymph nodes negative for

malignancy • Negative for S100 and HMB45 immunostains

– T2a N0 M0 Stage Ib


Management of Melanoma • Epidemiology • Diagnosis • Staging & Work-Up • Surgical Management

– WLE – SLNB

• Adjuvant Therapy • Follow-Up • Outcomes


Epidemiology

• Incidence increasing – Men

• 28.2 per 100,000

– Women • 16.8 per 100,000

– #6 most common (incidence)

Source: seer.cancer.gov


Presenter

Presentation Notes

Data from 2008-2012

Epidemiology

• Reasons for increase? – Increased number of skin biopsies

– Increased screening

– Increased sun exposure

• Duration • Ultraviolet radiation levels


Epidemiology • Risk factors

– Sun exposure • Fair skin • Geography • Tanning beds • Peeling sunburns

– Genetics (10-15%)

• CDKN2A – most common mutation • Familial atypical multiple mole melanoma

syndrome (FAMMM) • Xeroderma pigmentosa

previsecare.wordpress.com


Presenter

Presentation Notes

FAMMM – 100% will develop melanoma by age 76 Xeroderma pigmentosa – autosomal recessive disorder associated with reduced ability to repair DNA damaged by UV light.

Melanocytes

• Neural crest derived

• Located at basal layer of epidermis

• Produce melanin


Melanin Transport

qsystem.gblifesciences.com


Melanin Transport

• Produces skin pigment

apple.com


Malignant Transformation • MAP Kinase

– Constitutive activation leads to activation of NFκB

– Result: aggressive growth

• ras oncogene – Mutation leads to malignant

transformation in human melanocytes Baskaran Govindarajan et al. J. Biol. Chem. 2003


Diagnosis

• Asymmetry

• Border

• Color

• Diameter

• Evolving skincancer.org


Presenter

Presentation Notes

A – asymmetry, the halves of the mole do not match B – border is irregular, notched C – color is not uniform for the whole thing with various colors including brown, black, red, white, blue D – width is greater than 6mm (size of eraser) E for evolving – probably the most importan

Diagnosis • Biopsy techniques

– Excisional • Small lesions • Incision oriented longitudinally

– Incisional, punch or

saucerization • Large lesions, cosmetically

sensitive area • Must include base of lesion

– Do not perform shave biopsy

• e.g. Mohs us.vwr.com


Superficial Spreading

• 70% • Arises from pre-

existing nevus • Exhibits classic

melanoma features – ABCD

cancernetwork.com, ispub.com


Lentigo Maligna Melanoma

• 10-15% • Sun exposed areas • Growth beyond

clinical lesion • Often preceded by

lentigo maligna – In situ melanoma

skincareguide.ca


Nodular

• 15-30% • Most aggressive

– Vertical growth • Often without classic

melanoma features – Evolution

malignant-melanoma.org


Acral Lentiginous

• 35-60% in non-white • Feet, hands, subungual • Later diagnosis

– Lower suspicion – Location not easily or

frequently examined

cancer-network.org, healthh.org


(Other) • Mucosal • Anal • Vulvovaginal • Desmoplastic • Amelanotic

• All have worse

outcomes – Atypical presentation delayed identification dermis.net, ilmelanoma.net, melanoma.org


Staging • TNM system

• 7th Ed American Joint Committee on

Cancer Staging Manual

• J Clin Oncol 2009; 27:6199-6206


Tumor

aboutcancer.org


Presenter

Presentation Notes

Clark level is not an independent predictor of survival when mitotic index is included in regression analysis.

Tumor www.downstatesurgery.org

Presenter

Presentation Notes

A and B distinction has to do with either presence of ulceration or mitoses seen on histology!!

Node www.downstatesurgery.org

Metastasis www.downstatesurgery.org

Staging www.downstatesurgery.org

Laboratory Studies • Pre-Op Labs

• LDH

– Elevated LDH 1 year survival 32% (vs. 65% for normal level) in Stage IV disease

• S-100B

– Elevated pre-op S-100B 2.6x more likely to have

recurrent disease

Ann Surg Oncol 2009, 16:3455-3462


• Stage II and III patients

• Serial LDH & S-100B levels

• S-100B first sign of distant mets – >50% of patients

• S-100B > LDH

Melanoma Research 2009, 19:31-35


Radiographic Studies • Chest X-ray

– Stage Ib & II, optional

• CT chest & abdomen/pelvis – Stage IIC and higher – Symptoms – Anemia – LDH – Clinically positive inguinal nodes

• CT/MRI brain

– Stage IV – Stage III, optional

• PET

– Increases accuracy of CT/MRI

Source: Annals of Oncology 2009, 20 (Supp 6): vi14-vi21


Surgical Management • Wide local excision

• Melanoma in situ

– To mid subcutaneous tissue

• Melanoma (T1-3) – To fascia

• Melanoma (T4)

– Beyond fascia or into muscle


Margins

Breslow Depth of Primary Pathologic Margin

in situ 5 mm

≤ 1 mm 1 cm

1.01 – 2 mm 1 – 2 cm

2.01 – 4 mm 2 cm

> 4 mm ≥ 2 cm Source: Current Surgical Therapy, 11th Ed.


Wound Closure • Elliptical incision

– 3:1 length to width




• Local advancement flaps

Current Surgical Therapy, 11th Ed.





• Other skin flaps – Rotational rhomboid – VY – Z-plasty

intechopen.com, thefreedictionary.com





• Other skin flaps – Rotational rhomboid – VY – Z-plasty

• Skin grafts

– Split-thickness – Full-thickness

dermnetnz.org, openi.nlm.nih.gov


Sentinel Lymph Node Biopsy

• Node status: most important survival predictor

• Indicated for all tumors > 1 mm thick – Clinically negative nodes

• Premise: If the sentinel node is

negative, the entire basin is negative


SLNB: Contraindications

• T1 (< 1 mm)

• High risk histology – Ulceration, high mitotic rate (“b”) – Positive deep margin (e.g. shave biopsy) – Clark level IV depth

• Clinically positive nodes


SLNB: Technique

Sulfur Colloid and/or Vital Blue Dye

Current Surgical Therapy, 11th Ed.


Vital Blue Dyes: Truly Vital? • Methylene blue • Isosulphan blue (aka lymphazurin)

• Addition of blue dye provided only 1.8%

localization advantage – Study of Stage I/II breast CA – Surgery, 2008; 144:606-610

• Blue dye downsides:

– Allergic reaction/anaphylaxis (0.5-3%) – Skin staining – Increased cost to provider (Medicare does not

reimburse!)


Ann Surg 2015, Epub ahead of print

• 215 patients

• 100% localization with radiocolloid only – No comparison group

• 6/175 (3.4%) with negative SLNB had

recurrence in regional nodes – Negative predictive value: 96.6%


MSLT-1 • Multicenter Selective Lymphadenectomy

Trial – NEJM 2006; 355:1307-17

• ~1300 patients with intermediate

thickness melanoma (T2-T3) – Survival out to 5 years

• WLE & nodal observation • WLE & SLNB

– Lymphadenectomy for + SLNB


MSLT-1 • In SLNB group, + node:

– 2.48 HR for death – 3.04 HR for recurrence

• Mortality in those with lymphadenectomy:

– SLNB: 26.2% – Observation: 48.7%

• Nodal stage 1 after lymphadenectomy:



MSLT-1 • Final report – 10 year outcomes

– NEJM 2014; 370: 599-609

• In SLNB group, + node: – 2.40 HR for death – 2.64 HR for recurrence

• Mortality in those with lymphadenectomy:



MSLT-2

• Ongoing trial, enrollment closed – NCT00297895

• All patients receive SLNB

• Randomized to:

– Completion lymphadenectomy – Observation with nodal ultrasound


Metastatic Disease • Most common sites:

– Lung – Brain – Liver – Bone

• More commonly presents as disease

recurrence – Time to recurrence inversely related to

disease stage at initial diagnosis

Source: J Oncology 2012; vol 2012: 1-9.


Metastatic Disease • Metastasectomy indicated in selected patients

– Slow progression (doubling time > 40 days) – Extent (single vs multiple sites) – Resectability

• Improved survival in patients who were able to

undergo metastasectomy

• Most cases will be palliative, not curative – Bleeding GI metastases – Ulcerated cutaneous metastases – Symptomatic brain metastases


In Transit Disease • Spread via dermal or sub-

dermal route – Difficult to manage – Poor prognosis

• Local

– Intralesional • BCG, IFN α-2b, IL-2

– Electrochemotherapy • Regional

– Isolated limb perfusion – Isolated limb infusion

• Both use melphalan

www.intochopen.com, Current Surgical Therapy, 11th Ed.


Adjuvant Therapy

• Radiation – Some benefit in poor prognosis Stage III – Large (>3 cm) or numerous (>5) nodal

mets

• Chemotherapy – Dacarbazine

• Poor results, significant toxicity


Adjuvant Therapy • Immune Therapies

– Interferon α-2b – IL-2 – Vaccines – Activated cytotoxic T-lymphocytes

• Molecular targeted therapies

• Modulators of MAP kinase pathway – BRAF inhibitors (vemurafenib, dabrafenib) – MEK inhibitors (binimetinib) – CKIT inhibitors (imatinib)


Follow-Up • Clinical exam, labs (LDH, S-100B)

• Thin primary, negative nodes

– q6 months, x3 years – q1 year, x2 years

• Moderate/thick primary, positive nodes

– q3 months, x3 years – q6 months, x2 years – q1 year, indefinitely


Outcomes

• 5-year survival (all) 91.5% – Source: SEER, 2005-2011

Stage 5 year survival (%)

I 89 - 95

II 45 - 78

III 24 - 69

IV 6 - 18 Source: ACS Surgery 7


Management of Melanoma • Epidemiology: Incidence is increasing • Diagnosis: ABCD(E) • Staging: Breslow thickness, Nodal status • Surgical Management

– WLE – SLNB

• Adjuvant Therapy: Select patients • Follow-Up: Evaluate for recurrence • Outcomes: 91% overall, <20% Stage IV





















thick.








thick.



Textbook References • Leung AM, Faries MB, Morton DL. “The Management

of Cutaneous Melanoma.” From: Current Surgical Therapy – 11th Ed. Editors: Cameron JL, Cameron AM. 2014.

• Wargo JA, Tanabe K. “Surgical Management of Melanoma and Other Skin Cancers.” From: ACS Surgery 7. Editors: Ashley SW, Cance WG, et al. 2014.


Questions? www.downstatesurgery.org

Surgical Incisions in Thoracic Trauma · A. 0.7 mm melanoma over right tibia with clinically negative right groin ... 2 -existing mole on RLE that became raised, multi-color, crusted.

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