Surgical Treatment of Malignant Melanoma

Yağmur AYDIN, M.D.,Asc. Prof.

University of Istanbul, Cerrahpaşa Medical School

Department of Plastic, Reconstructive and Aesthetic Surgery

Malignant Melanoma Arise from melanocytes in basal layer in the epidermis The worst prognosis and morbidity in all skin cancers Incidence is increasing by every year (% 6 per year) accounts for only 4% of all skin cancers, but responsible

for more than 77% of skin cancer deaths Early detection and treatment important, because it

reduces the mortality and increases survival Prognosis ( 5 years) Local disease > % 90

Regional disease % 60Distant metastasis % 5

Mostly arise from skin ( 95 % ) But also found in the eyes, ears, GI tract,

leptomeninges, and mucous membranes Unknown primary or metastasis (3 %) May develop in precursor melanocytic

nevi(common, congenital, and atypical/dysplastic types (25 %)

Commonly arise from de-novo (not from a preexisting pigmented lesion)

Causes

Melanoma tends to occur at sites of intermittent, intense sun exposure

an increased worldwide incidence in fair-complexioned individuals living in sunny climates and nearer the equator, suggesting a causative role for ultraviolet radiation.

Precursor Lesions

Atypical or Displastic nevi Congenital nevi Lentigo maligna Acquired nevi

Risk Factors - I

Very fair skinned, particularly those with fair or red hair

Tendency to sun burn Excessive childhood sun exposure and

blistering childhood burns Age : the incidence steadily rises with

age.  The highest incidence is in those over 80

The more moles you have on your body, the higher your risk of melanoma (more than 100 Atypical or dysplastic nevi)

The development of melanoma is multifactorial and appears to be related to multiple risk factors

Risk Factors -II Born in a hot country, such as

Australia or Israel Malignant melanoma in the first

degree relative (3-10 %) Giant congenital nevi (5-40 ) Second malignant melanoma (3-6 %) Sunbeds (Solarium) People who work outdoors and so are

in the sun (sailors, farmers ..)

People who have risk factors should be follow and have preventive efforts

Early Diagnosis

A changing mole is the most common warning sign for melanoma

Early Signs of Melanoma The most common early sign of melanoma is

pruritis A,B,C,D,E warnin signs

Asymmetry: One half of the lesion does not match the other half.

Border irregularity: The edges are ragged, notched, or blurred.

Color variegation: Pigmentation is not uniform and may display shades of tan, brown, or black; white, reddish, or blue discoloration is of particular concern.

Diameter: A diameter greater than 6 mm is characteristic, although some melanomas may have smaller diameters; any growth in a nevus warrants an evaluation.

Evolving: Changes in the lesion over time Bleeding and ulceration are late signs showing

advanced disease

All suspected lesions are removed for histopathologic examination

Biopsy

Excision (Golden standard) *İncision biopsy *Punch biopsy Partial thickness or shaving

biopsies are contraindicated

*All dermis layers should be removed

Balch CM, Houghton AN, Sober AJ, Soong S. Cutaneous Melanoma. St Louis QMP 1998

Melanoma is divided into the four major subtypes

1. Superficial spreading melanoma

2. Nodular melanoma3. Lentigo Maligna Melanoma4. Acral Lentiginous Melanoma

Superficial spreading melanoma

most common subtype of melanoma, occurring in approximately 70% of patients

most common on the trunk in men and women and on the legs in women

most commonly seen in individuals aged 30-50 years

Manifest as a flat or slightly elevated brown lesion with variegate pigmentation (ie, black, blue, pink, or white discoloration)

generally greater than 6 mm in diameter Irregular asymmetric borders are characteristic

Superficial spreading melanoma

Superficial spreading melanoma ; Level III

Superficial spreading melanoma ; Level IV

Superficial spreading melanoma ; Level IV

Superficial spreading melanoma ; Level V

Superficial spreading melanoma

The most common melanoma mimickers are seborrheic keratoses Qenign keratinocytic proliferations) and traumatized nevi, which often present as a "bleeding mole." A mole showing severely atypical features may be clinically indistinguishable from a melanoma

Superficial spreading melanoma

Nodular Melanoma Nodular melanoma is the second most common

subtype of melanoma, occurs in 15-30% of patients

Seen most commonly on the legs and trunk Rapid growth occurs over weeks to months Lack of an identifiable in situ (or radial growth)

phase Responsible for most thick melanomas Manifests as a dark brown-to-black papule or

dome-shaped nodule, which may ulcerate and bleed with minor trauma

Tends to lack the typical ABCDE melanoma warning signs

Nodular Melanoma

Nodular Melanoma : Level IV

Nodular Melanoma NÜKS

Nodular Melanoma : Level IV

Nodular Melanoma : Level V

Nodular Melanoma : Level V

Lentigo Maligna Melanoma accounts for 4-15% of cutaneous melanoma cases typically located on the head, neck, and arms

(sun-damaged skin) of fair-skinned older individuals (average age 65 y)

grows slowly over 5-20 years Only 5% to 8% of lentigo maligna are estimated to

evolve to invasive melanoma.

Lentigo maligna appears as a tan to brown macule or patch with variation in pigment or areas of regression that appear hypopigmented clinically.

Lentigo maligna melanoma is characterized by nodular development within the precursor lesion.

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Level II

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Lentigo Maligna Melanoma

Acral Melanoma Acral lentiginous melanoma is the least

common subtype, representing only 2% to 8% of melanoma in Caucasians,

It typically occurs on the palms or soles or beneath the nail plate (subungual variant). Irregular pigmentation, large size (>3 cm diameter), and plantar location are characteristic features of acral lentiginous melanoma.

Acral Melanoma Subungual melanoma may be confused with

a benign junctional nevus, pyogenic granuloma, or subungual hematoma.

Rapid onset of diftuse nail discoloration or a longitudinal pigmented band within the nail plate warrants biopsy of the nail matrix, from which these melanomas arise.

The additional presence of pigmentation in the proximal or lateral nail folds (Hutchinson's sign) is diagnostic of subungual melanoma

Acral Lentiginous Melanoma

Acral Lentiginous Melanoma

Acral Lentiginous Melanoma

Histopathologic Examination

Spread of melanoma with the depth of invasion from its origin in the epidermis. There are five levels of invasion

The histopathologic classification of the Melanoma by Clark

Level I — the atypical melanocytes are confined

to the epidermis (in situ melanoma);

Level II — the atypical melanocytes have extended into

the papillary dermis but have not reached

the reticular dermis;

Level III — the atypical melanocytes have penetrated to

the interface between the papillary dermis and

the reticular dermis but do not extend into the

reticular dermis;

Level IV — the atypical melanocytes have extended

into the reticular dermis;

Level V — the atypical melanocytes have reached into the

subcutaneous fat.

Clark Clasification

The histopathologic classification of the M Melanoma by Clark

According to the thickness of the lesion as measured by an ocular micrometer

from the top of the granular zone of the epidermis to the base of the neoplasm

The histopathologic classification by Breslow

Breslow Classification

Level 1: less than 0.76 mm thick

Level 2: between 0.76– 1.50 mm

Level 3: between 1.50 - 4.00 mm

Level 3: exceed 4.00 mm in thickness

Prognostic Factors

Breslow thickness (most important) Clark invasion level Ulceration Age, sex, location Size and surgical margins Others (Mitotic index, growth phase,

regression...)

Staging

Stage I : No metastasis (Local Disease)

Stage II : Nodal metastasis (Regional Disease)

Stage III : Distant Metastasis (Systemic Diasese )

T Staging: Primary tumor thickness

T x : tm confined to the epidermis

T1 : </= 1 mm a) no ulceration, mitosis < 1mm2

b) ulceration exist, mitoz > 1mm2

T2 : 1-2 mm a) no ulceration

b) ulceration exist T3 : 2,01-4 mm a) no ulceration

b) ulceration exist T4 : >4 mm a) no ulceration

b) ulceration exist

TNM Classification AJCC 2009

TNM Classification AJCC 2009

N Staging : Lymph node status

N1 : 1 Lymph Node a) micrometastasis (SLN biopsy)

b) palpable LAP

N2 : 2-3 Lymph Node a) micrometastasis (SLN biopsy)

b) palpable LAPc) In-transit metastasis\satellit

w/o met. N3 : > 4 metastatic nodes, or matted nodes, or in transit

metastases/satellites with metastatic nodes

M Staging: Distant Metastases

M1 : Distant skin,subcutaneous or lymph node Normal LDH

M2 :Pulmonary metastases Normal

LDH

M3 : Visceral Organ or other distant metastases

Normal LDHYüksek LDH

TNM Classification AJCC 2009

Staging in Melanoma

Stage I : T1, T2, N0, M0

Stage II : T3, N0, M0

Stage III : T4, N0, M0 or Lymph node met.

Stage IV : Distant Met.

AJCC 2002

Surgical Treatment

Surgical Treatment

Biopsy Wide Local Exsicion Staging with Sentinel Lymph Node

biopsy Therapeutic Lymph Node Dissection Treatment of Distant Metastasis

Main treatment in melanoma is wide surgical excision of the tumor

Wide Surgical Excision Suggested surgical margins:

(according to breslow thickness)

In-situ MM 0,5-1 cm

Breslow thickness < 1mm : 1 cm

Breslow thickness 1-4 mm: 2 cm

Breslow thickness >4 mm: > 3 cm

• Lymphatic metastases

• Heamatogenic metastases

In-transit metastases

• Local satellite metastases

Metastases of Malignant Melanoma

Effect of Lymph Node metastases on Survival

10 years Survival%

Microscopic Lymph Node metastases

48

No Lymph Node metastases

65

Palpabl Lymph Node metastases

12

Treatment of Lymph Nodes

Wait and see (no treatment) Elective Lymph Node Dissection Sentinel Lymphadenectomy

Elective Lymph Node Dissection

Removing the regional lymph nodes for prevention in no clinical palpable lymph node

There is no consensus on survival advantage of Elective Lymph Node Dissection (ELND)

Survival advantage has been shown on retrospective studies but not in progressive studies

Complications for ELND

Early: Wound healing problems,

necrosis, and wound seperation Infection

Late: Lymphedema

Sentinel Lymphadenectomy

Sentinel Lymphadenectomy

Morton introduced for Stage I Melanoma patients in 1992

Vital blue dye intradermal injection was used for lymphatic mapping

Lymphatic drainage of primary tumor goes specific lymph node in regional lymph basin. This is the first node in the basin. This is called as sentinel lymph node

Sentinel Lymphadenectomy Sentinel lymph node shows the regional

node status If sentinel lymph node negative, others

lymph nodes in the basin are also negative

If sentinel lymph node contains tumor cells, It means disease spread to the regional nodal basin

Sentinel Lymphadenectomy

Sentinel node negative

no additional treatment, follow the patient

Sentinel lymph node positive

Therapeutic lymph node dissection

Multidiscipliner Team

Surgery Nuclear Medicine Pathology

Sentinel Lymphadenectomy

Intradermal injection of tc99 m labeled sulfur colloid and lymphoscintigraphy

intra-operative vital blu dye injection Removing blue stained and hot lymph node as

sentinel nodes Serial section of nodes, immunohistopathologic

examination by S 100, HMB 45 (melenoma spesific)

Advantages of Sentinel Lymphadenectomy Provides staging Prevents of Electice Lymph node dissection

morbidity Gives a specimen to pathologist to examine

in detail Provides psychological support Can be done by local anesthesia Less costly

Distant Metastases

Sites of Distant Metastasis

Skin Subcutaneous Tissue Distant Lymph Nodes Pulmonary Liver Brain Bone Intestine

Treatment of Distant Metastases

Soliter skin and distant lymph nodes are removed

İsoleted pulmonary metastases can be removed in selected cases

Brain and GI metastases are removed for palliation

Radiotherapy may be benefical for selected patients (mainly for pain treatment)

Treatment of Distant Metastases

Avarege life expentancy is 6-9 months There is no real treatment for Stage IV

patients Most realistic goal is palliation and

preservation of quality of life Experimental therapies may be

considered in the first line therpeutic approach

Cases

AK, E, 47 years old. Darkening of congenital nevi(1 year), biopsy : Clark Level IV, Breslow 2 mm.

Wide reexcison (1,5 cm) ve primary closure + SLN, SLN: negative

AÇ, W 48 years, DM

Nevi on the sole of the foot for 15 years, history of unhealed wound for 2 years

Biopsy at a private clinic nodular MM, Clark Level IV

•Wide excision ( 2 cm) and reconst. With SSG + SLN (2 nodes)•Breslow:17,2, Clark Level V•SLN +•Right Inguinal lymph node dissection• 1/19•Chemotherapy•Local recurrence at 6 months

18, W SE, Reexcion and ve primary closure+ SLN SLN -, Follopw –up 5 years, No diease