malignant melanoma

Malignant MelanomaClinical Features, Pathology and Management

ByDr Madhu kumar

Under guidanceDr PV Budha MS

Dr Venkat Reddy MS Dr Sailajarani MS

Dr Satyanaryana MS Dr Ayyapasrinivas MS

What is Melanoma

• Melanoma is a very serious form of skin cancer.

• Melanoma is cancer of the melanocytes.

• Melanocytes are located in the Stratum Basale and produce melanin.

Melanocytes• When skin is exposed to sunlight, melanocytes

produce more pigment, causing the skin to tan.• Sometimes, clusters of melanocytes form

noncancerous (benign) growths called moles. • Moles can be either flat or raised, round or oval, and

are smaller than a pencil eraser. – Generally harmless, but can become cancerous

Incidence

• Although melanoma accounts for only about 5% of all skin cancer cases, it causes most skin cancer-related deaths

• The incidence is rising by 3% a year

Causes of Melanoma

• 90% of all melanomas are linked to UV radiation. (Sun exposure)

• 8% are due to chromosomal abnormalities• About 2% are unknown

Risk Factors• Family history of melanoma • Dysplastic nevi (noncancerous, but unusual- looking moles) • Previous melanoma • Many nevi (ordinary moles): more than 50 • Severe, blistering sunburns • Freckling tendency• Fair skin• Excessive use of tanning beds• Genetic predisposition

Signs and symptoms of melanoma

• Melanoma can appear suddenly as a new mole, or it can develop slowly in or near an existing mole.

• In men, melanomas are often found between the shoulders and hips, or the head and neck area.

• In women, melanoma often develops on the lower legs as well as between the shoulders and hips.

• It may also appear under the fingernails or toenails or on the palms or soles

ABCDE of melanoma• A is for Asymmetry:

– One half of a mole or birthmark does not match the other.• B is for Border:

– The edges are irregular, ragged, notched, or blurred.• C is for Color:

– The color is not the same all over and may include shades of brown or black, or sometimes with patches of pink, red, white, or blue.

• D is for Diameter: – The spot is larger than 6 millimeters across (about ¼ inch – the size

of a pencil eraser), although melanomas can sometimes be smaller than this.

• E is for Evolving: – The mole is changing in size, shape, or color.

Biopsy

Small and accessible lesions– Excision with 1 cm margins in suspicious lesions

Large lesions– Incisional or punch biopsy ?

Shave biopsy discouraged

Histomorhological types

• Superficial Spreading Melanoma• Nodular Melanoma• Lentigo Maligna Melanoma• Acral Lentiginous Melanoma• Amelanotic Melanoma

• Superficial Spreading Melanoma– Most common histologic

type (70%)– Appear as a flat,

pigmented lesion growing in the radial pattern

• Nodular Melanoma– Second most common

type (15%)– Vertical growth pattern– Worst prognosis based

on a higher average tumor thickness.

• Lentigo Maligna Melanoma– Sun-damaged skin– Flat,darkly pigmented

lesion with irregular borders and a history of slow development

• Acral Lentiginous Melanoma

• Subungual areas and the glabrous skin of the palms and soles

• Seen in blacks

• Amelanotic Melanoma– Uncommon– Difficult to diagnosis– Lacks pigmentation

• Antibodies for immunohistochemistry– S - 100– HMB - 45

• Mutations– BRAF– NRAS– AKT

Stage (Clark’s level or Breslow Depth)

Clark Classification (Level of Invasion)• Level I: Lesions involving only the epidermis (in

situ melanoma); not an invasive lesion.• Level II: Invasion of the papillary dermis but does

not reach the papillary-reticular dermal interface.• Level III: Invasion fills and expands the papillary

dermis but does not penetrate the reticular dermis.

• Level IV: Invasion into the reticular dermis but not into the subcutaneous tissue.

• Level V: Invasion through the reticular dermis into the subcutaneous tissue.

Breslow level of invasion

• Current stage system is based on depth of invasion

• Measured using ocular micrometer• Currently Breslows level 0f < 1mm, 1 to 4mm

and > 4 mm is used for TNM staging

• Metastatic workup done for stage III onwards• Chest x ray• CT Chest and abdomen• PET CT• MRI brain

Treatment of Melanoma

• Early stages: – Wide local excision

• More advanced:– Wide local excision plus sentinel node biopsy, – Based on the pathology• Lympadnectomy• observation• interferon

• Metastatic: – Clinical trial– Radiation and systemic therapy

Wide Excision

• Regardless of tumor depth or extension, surgical excision is the management of choice

• If the deep fascia is not involved fascia is left intact

SLN biopsy using TC99

Elective lymph node dissection (ELND)

• Use of prophylactic dissection (clinically negative nodes) is controversial

• No prospective, randomized studies have demonstrated that elective LN dissection improves survival in patients with intermediate-thickness melanomas

• By SLN biopsy micrometastasis is identified removed node sent for frozen-section examination, a complete LN dissection is performed

• Dissection should be complete• Groin dissection – Deep (iliac) nodes must be removed along with

the superficial (inguinal) nodes• Axillary dissection– All levels I, II, III should be removed

• Head and Neck– Superficial parotidectomy to remove parotid

nodes and a modified neck dissection

Complications

• Wound seroma• Cellulitis• lymphedema

In-transit disease (local disease in lymphatics)

• 5 to 8% of melanoma patients with a high-risk primary melanoma (>1.5 mm)

• Hyperthermic regional perfusion • Melphalan is the chemotherapeutic agent

used

• Melphalan generally is heated to an elevated temperature [up to 41.5°C, (106.7°F)] and perfused for 60 to 90 minutes

• Produce a high response rate (greater than 50%)

• Complications – neutropenia, amputation, death

• Tumor necrosis factor alpha or interferon-alfa along with melphalan regression rate 90%

Targeted therapies

• BRAF Inhibitor– PLX4032(vemurafenib)

• KIT Inhibitor– Imantinib mesylate

Chemotherapy

• Dacarbazine is drug of choice• Other drugs– Cisplatine– Paclitaxel– Docetaxel– Temozolomide

Immunotherapy • Interlukin IL-2 and Interferon on high doses• BCG• Monoclonal antibodies

– Ipilmumab• Tumour vaccine

– Polyvalent melanoma vaccine (Canvaxin)– Allogenic melanoma cell lysate (Melacin)– Detoxified endotoxin/myco bacterial cell wall skeleton (DETOX)– Gp 100 DNA vaccine– GM-CSF 2nd generation oncolytic herpes virus vaccine

Radiation

• Used in some cases • High doses• Not so useful

Follow up

• Early melanomas– Every 6 months for 2 yrs them annually

• Advanced melanomas– Every 3-4 months for 3-4 yrs, every 6 months for 1

year, latter annually

Thank You