Malignant Melanoma
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Transcript of Malignant Melanoma
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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
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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.
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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
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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
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Causes of Melanoma
• 90% of all melanomas are linked to UV radiation. (Sun exposure)
• 8% are due to chromosomal abnormalities• About 2% are unknown
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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
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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
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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.
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Biopsy
Small and accessible lesions– Excision with 1 cm margins in suspicious lesions
Large lesions– Incisional or punch biopsy ?
Shave biopsy discouraged
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Histomorhological types
• Superficial Spreading Melanoma• Nodular Melanoma• Lentigo Maligna Melanoma• Acral Lentiginous Melanoma• Amelanotic Melanoma
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• Superficial Spreading Melanoma– Most common histologic
type (70%)– Appear as a flat,
pigmented lesion growing in the radial pattern
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• Nodular Melanoma– Second most common
type (15%)– Vertical growth pattern– Worst prognosis based
on a higher average tumor thickness.
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• Lentigo Maligna Melanoma– Sun-damaged skin– Flat,darkly pigmented
lesion with irregular borders and a history of slow development
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• Acral Lentiginous Melanoma
• Subungual areas and the glabrous skin of the palms and soles
• Seen in blacks
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• Amelanotic Melanoma– Uncommon– Difficult to diagnosis– Lacks pigmentation
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• Antibodies for immunohistochemistry– S - 100– HMB - 45
• Mutations– BRAF– NRAS– AKT
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Stage (Clark’s level or Breslow Depth)
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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.
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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
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• Metastatic workup done for stage III onwards• Chest x ray• CT Chest and abdomen• PET CT• MRI brain
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Treatment of Melanoma
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• 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
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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
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SLN biopsy using TC99
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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
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• 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
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Complications
• Wound seroma• Cellulitis• lymphedema
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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
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• 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%
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Targeted therapies
• BRAF Inhibitor– PLX4032(vemurafenib)
• KIT Inhibitor– Imantinib mesylate
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Chemotherapy
• Dacarbazine is drug of choice• Other drugs– Cisplatine– Paclitaxel– Docetaxel– Temozolomide
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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
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Radiation
• Used in some cases • High doses• Not so useful
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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
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Thank You