• Malignant tumor arising from melanocyte.
• Increasing incidence over last 20 years.
• Currently there are 13 melanoma/100,000 population
• 10% are familial melanomas (with or without dysplastic nevi)
• 3% of patients have multiple melanoma
  (most commonly in patients with dysplastic nevi)

• Family history of melanoma and familial dysplastic nevi
• Precursor lesions (65% melanomas have histologic evidence of precursor nevus cells)
• UV exposure
• Skin Type I
• Xeroderma pigmentosa
• Immunosuppressive condition

• Congenital nevus
• Acquired nevus
• Dysplastic nevus
• Lentigo melanoma

• Acquired nevi: The risk is very low (1:15,000).
• Congenital nevi:
• Small congenital nevi (surface area less than 10 sq. cm) Risk 1:250
• Large congenital nevi especially giant nevi. Risk 1:20
• Dysplastic nevi. Risk 1:500
• Lentigo melanoma (Hutchinson’s Freckle) Risk 1:20.

• Very common.
• Average person have 14 nevi.
• New acquired nevus after age 30 is unusual.
• Most are less than 5mm diameter and have well defined margin and uniform color.

Congenital nevus is present at birth. Both giant congenital nevus (over 10 sq cm) and small congenital nevus has higher incidence of subsequent development of melanoma.
 

• Conceptuality it occupies a position between common nevus and melanoma
• Has atypical melanocytes
• Immunologic and Immunohistologic characteristics of melanoma
• It is a benign lesion.
• Usually seen after age 60
• Presents as a light brown patch almost always in head and neck region.
• Subsequent development of melanoma after long latent period.

• Appears at prepubertal age
• Increase in number of nevi up to age 20/21 and then number of nevi remains stable
• Uncommon in hand, sole & covered area of body
• Usually 0 to 30 in number
• Usually smaller than 0.5 cm and has smooth margin
• Matured nevus cell; no fibrosis; no lymphocytic infiltration, no increased vascularity

• Appears early age (8 to 9 yr.)
• Number of nevi increase throughout the life
• Involves all surface skin
• May be numerous
• Usually larger than 0.5cm, irregular margin, variegated color and has pinkish hue
• Melanocytes are atypical with large nucleus, lymphocystic infiltration, Desmoplasia and increased vascularity.

• Familial: with or without family history of melanoma
• Sporadic: with or without personal history of melanoma

• If patient has melanoma and familial dysplastic nevi, their all 1st degree relative who exhibit dysplastic nevus will have nearly 100% chance of subsequent development of melanoma
• Over all incidence of melanoma among patient with sporadic dysplastic nevi is increased (RR 2 to 3)
• Patient who has sporadic dysplastic nevi and also has melanoma has 6 to 10 fold increase in the incidence of 2nd primary melanoma compared to melanoma patients without dysplastic nevi
• Risk of 2nd primary melanoma correlated to number of dysplastic nevi.

• Sun protection
• Careful selection of the lesions for biopsy to prevent unnecessary excision
• Examination by nevoscope (a camera with different wavelength to examine the lesion at a different depth from surface).

What is bad in sunlight?
It is the ultraviolet light specifically UVB.
UVA: Damage to elastic tissue
UVB: Moderately carcinogenic (Melanoma and non-melanoma skin cancer)
UVC: Highly carcinogenic

• Epidemiological studies strongly suggest influence of sunlight on formation of melanoma.
• Prior to 1920’s – suntan branded one as inferior person
• Coco Chanel : The French fashion queen came to Palm Beach and spent over 6 weeks there. By the time she returned to Paris and appeared in a prescheduled fashion show she was completely tanned, since appearance of tanned Coco Chanel suntans became fashionable.
• Incidence of both melanoma and non-melanoma skin cancer increased remarkably from 1940

• Most of the UV light does not reach the earth
• Thirty miles above the surface, atmosphere filters the sunlight
• The ozone layer 12 miles above the surface strips most of UV light
• No UVC reaches the earth surface
• Small portion of UVB and most of UVA (less energy packed reached earth surface)

• For each 10 million air molecules, 2 million are normal oxygen molecules and only 3 molecules are ozone
• Natural destruction and construction of ozone are balanced

• Made from atmospheric oxygen at a high temperature
• Lightening in atmosphere makes most ozone (approximately 5,682 lightening per second hits the surface of earth)

• Volcanic eruption
  -Large amounts of tiny particles called aerosols which increases effectiveness of chlorine
• Natural occurrences
  -Chemical reaction in stratosphere with NO2, HCl and HNO3
• Manmade industrial chemical such as CFC, methyl chloroform, carbon tetrachloride, Halon, etc. Markedly destroy ozone layer known as ozone depleting substances (ODS)

• CFC doesn’t get removed from lower atmosphere (not soluble in water)
• Vortex force of earth’s rotation carries it mostly to South Pole but also to North Pole
• UV light breaks ODS releasing CLO, Halon and BrO, which in turns goes through following chemical reaction and destroys ozone.
  ODS + hv = ClO and BrO
  ClO + ClO + M = Cl2O2 + M
  Cl2O2+hv = Cl + ClO2
  Br202 + hv = Br + BrO2
  Cl + O3 = ClO + O2
  Br + O3 = BrO + O2
  ClO + BrO = Cl + Br + O2
• Each atom of Chlorine and Bromine destroys 100,000 molecules of ozone before removed from the cycle.
• Because the diameter of the sun is approximately 1,400 times larger than the earth, even a small ozone hole permits UVB light to a much larger surface area of earth due to divergence of light.

• Polar winter results in polar vortex
• Cold temperatures within vortex form polar stratospheric clouds
• Heterogenous reaction takes place in extremely cold temperatures forming inactive chlorine and bromine reservoir
• When sunlight returns to pole after winter, photo degradation of inactive chlorine and bromine compound releases active chlorine and bromine that results in destruction of ozone

• Almost immediate tanning
• Pigmentation is short lived
• Depends on skin type
• UVA induced tan does not protect the skin and melanocytes from UVB induced damage on UVB exposure

• Takes 48 hours for tanning
• Pigmentation lasts longer
• Depends on skin type

• DNA damage of melanocyte
• UV light yields super oxidase from pheomelanin (red melanin) which damages guanine-cytosine link and also damages cell membrane

• Sex predilection: Equal distribution among male and female
• Age: Increasing incidence with age. Older patient has higher incidence of melanoma.

• Lower limb-most common in women
• Trunk-most common in men
• Upper limb
• Head and neck region

• Changing color and size of pre-existing lesion
• Appearance of new skin lesion
• Itching, bleeding
• Axillary, groin, or cervical lymphadenopathy: 3 to 4% melanoma patients present with evidence of metastatic melanoma in the lymph node without any demonstrative primary site (unknown primary metastatic melanoma).

• The diagnosis of a suspected lesion is established by excisional biopsy
• This excisional biopsy should include 1 to 2 mm of surrounding normal skin and underlying fat below the lesion
• Shave biopsy or incisional biopsy should not be done unless the lesion is very large

Extent of metastatic work-up depends on risk of recurrence and metastasis

• Chest X-ray
• CT Scan
• LFT
• PET Scan

No metastatic work up is done for melanoma less than 1.0mm thickness with clinically negative lymph nodes.
Melanoma more than 2mm in thickness or with positive regional lymph node and evaluated with CT scan and PET scan.

• Lentigo Maligna Melanoma 10%
• Superficial Spreading 65%
• Nodular 20%
• Acrolentigenous 5%

• Is it a melanoma.
• Is it Invasive.
• Thickness (in mm).
• Clark’s level.
• Ulceration.
• Angiolymphatic invasion.
• Regression.
• Does the tumor extend to the deep margin.

• How wide an excision should be done.
• Is there a need for lymphadenectomy.

Surgical therapy for primary lesion:

• For melanoma in situ or level I Melanoma-excision with 0.5 cm margin is adequate
• Melanoma 1mm or less in thickness-excision with 1 cm margin is adequate
• Melanoma 1 to 2mm in thickness needs excision with 2cm margin
• Melanoma more than 2mm in thickness needs excision with 3cm margin

• Randomized studies have shown no improved survival with elective regional node dissection.

Elective Vs. Therapeutic
Node Dissection
WHO Study
5yr survival

Type of RND	N	5 Year Survival
Elective RND	267	74%
Therapeutic RND	286	76%
______________
Veromasi U. 1977

Type of Treatment	N	10 Year Survival
Elective RND	54	87%
Therapeutic RND	55	91%
No Node Dissection	62	85%
______________
Veromasi U. 1977

Routine elective node dissection is not indicated at present, a selective node dissection is done if the first draining
lymph node (sentinel lymph node) has spread or melanoma.

Therapeutic node dissection for metastatic node is done when node is palpable.

Patient with melanoma over 1mm thickness are considered to be at high risk for microscopic metastasis and should undergo
sentinel lymph node dissection and biopsy.
If sentinel lymph node shows metastasis then a standard lymphadenectomy is done.

Method of sentinel lymph node detection:

• Technetium lymphoscintigraphy
• Isosulfan blue dye
• Combination of blue dye and radio scintigraphy

Randomized study 1269 patients sentinel lymph node biopsy done for melanoma 1.2mm to 3.5mm thickness. Randomly assigned distribution for study was selected at 60:40 ratio.

533 patients underwent wide excision and observation and delayed node dissection for clinically positive lymph node.

814 patients underwent wide excision sentinel lymph node biopsy and regional lymph node if sentinel lymph node was positive.

Median follow up 60 months
_________________________________________________
Morton 2006

Melanoma Specific Survival
	3yrs.	5yrs.
SLN Bx	93%	87%
Observation	87%	86.5%
Morton 2006

• If sentinel lymph node is positive then a regional node dissection must be done.
• For microscopic positive lymph node in superficial groin, following superficial groin dissection, if Cloquet’s node is negative then a deep groin dissection is not done.

Indicated in patient with:

• Melanoma more than 4mm in thickness
• Melanoma of any thickness with histologically positive lymph node
• Most effective adjuvant therapy is high dose Interferon 2a (Intron A) given for 1 year.
• Approximately 3% to 5% improved 5-year survival
• Vaccine therapy is ineffective.

Indicated in patient with:

• It is rare a disease.
• Most commonly located in nasal mucosa.
• No correlation between thickness and incidence of nodal metastasis.

• Treated with wide excision.
• Anal melanoma is treated with trans anal excision rather than APR.
• Lymphadenectomy is done only for clinically or radiologically positive lymph node.

Indicated in patient with:

• Beside conjunctional melanoma 5yr. survival is 10% or less.