Melanoma clinical features, pathology and management
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Transcript of Melanoma clinical features, pathology and management
Malignant Melanoma Clinical Features
Pathology and
Management
Dr SD Sanyal Lt Col VP Singh
Cl Spl Surg & Surg Oncologist
Melanocytes & Melanoma• Melanoma is a neoplastic disorder produced by malignant transformation of the
normal melanocyte
• Melanocytes are cells responsible for the production of the pigment melanin
• During the first trimester of fetal life, precursor melanocytes arise in the neural crest
• As the fetus develops, these cells migrate to areas including the skin, meninges, mucous membranes, upper esophagus, and eyes
• In each of these locations, melanocytes have demonstrated a potential for malignant transformation
• The site most commonly associated with melanocytic transformation is the skin, where melanocytes reside at the dermal/epidermal junction.
• Melanocytes are located in the Stratum Basale and produce melanin
Pathogenesis Melanocyte
melanocytic atypia
atypical melanocytic hyperplasia
radial growth phase melanoma
vertical growth phase melanoma
metastatic melanoma
Epidemiology & Incidence
• 4% new cancer diagnosis and 1.5% deaths• Life time risk:
- 1:1500 1:56(W)/1:39(M)• Higher incidence amongst whites• Highest per capita incidence amongst
Australians• Median age for diagnosis is 58 yrs
Causes of Melanoma
• 90% linked to UV radiation (Sun exposure)- UVB radiation
• 8% are due to chromosomal abnormalities- p16/CDK4- CDK6- p14/p53- CDKN2a
• 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• Estrogen
Signs and symptoms of melanoma• Melanoma can appear suddenly as a:
- new mole - develops slowly in or near an existing mole
• Men:- found between the shoulders and hips - the head and neck area
• Women:- lower legs - between the shoulders- hips.
• May also appear:- underneath fingernails & toenails - 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 – may include shades of brown or black, or sometimes with
patches of pink, red, white, or blue.• D is for Diameter:
– The spot is > 6 mm across• E is for Evolving:
– The mole is changing in size, shape, or color.
Histomorphological types
• Superficial Spreading Melanoma• Nodular Melanoma• Lentigo Maligna Melanoma• Acral Lentiginous Melanoma• Amelanotic Melanoma/ Desmoplastic
Superficial Spreading Melanoma
– Most common histologic type (70%)
– Appear as a flat, pigmented lesion growing in the radial pattern
– Most commonly associated with sun exposure
– Sparing of acral sites
Nodular Melanoma
– Second most common type (20%)
– Vertical growth pattern– Worst prognosis based
on a higher average tumor thickness
– Lack RGP
Lentigo Maligna Melanoma
– Sun-damaged skin– Flat, darkly pigmented
lesion with irregular borders and a history of slow development
– Older individuals– Extensive RGP– In situ: Hutchison’s
freckle
Acral Lentiginous Melanoma
• Subungual areas and the glabrous skin of the palms and soles
• Seen in blacks and hispanics
• Prolonged RGP• Confused with
haematomas & chronic fungal infections
• Amelanotic Melanoma/Desmoplastic– Uncommon– Difficult to diagnose– Lacks pigmentation– Negative for MART/Melan-A gp-100 & tyrosinase– Positive for S-100
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• Breslows level of :
- < 1mm- 1 to 4mm - > 4 mm
used for TNM staging
Staging
Management
Prognostic markers
• Depth of invasion• Ulceration• Females < Males• Head & Neck+ Mucosal>Trunk>Extremities• Greater risk of LN metastasis in <35 yrs• Mitotic rate> 6/sq mm• Angio-lymphatic invasion• Microscopic satellites
Imaging & Laboratory Tests
• Metastatic workup done for stage III onwards• Chest X Ray• CT Chest and Abdomen• PET CT• MRI brain• LDH• Biopsy
Management
• Early stages: – Wide local excision
• More advanced:– Wide local excision plus sentinel node biopsy, – Based on the pathology
• Lymphadnectomy• observation• interferon
• Metastatic: – Clinical trial– Radiation and systemic therapy
Preliminary Work Up
Stage 0 & IA
Stage IB & II
Stage III
Stage III (In Transit)
Stage IV
Persistant disease/ True local scar recurrence
Nodal recurrence
Follow Up
Principles of biopsy
• Excisional bx with 1-3mm margins preferred• Incisional/ punch full thickness bx of the lesion
over palm, sole, digit, face, ear or for large lesions
• Shave biopsy may interfere with assessment of Breslow’s thickness
Principles of Pathology• Elements to be reported:
- Breslow’s depth- Ulceration- Mitosis- Clark’s level- Peripheral and deep margin status
• ADA recommendations:- Location - Regression- Tumour infiltrating lymphocytes- VGP- Angiolymphatic invasion- Neurotropism- Histologic subtype- Pure desmoplasia
Wide Excision• Trunk and proximal extremities: • - WLE should involve measuring the appropriate
margin (usually 1-2cm) around the entire scar from the bx/visible edge of residual melanoma and extending the incision to make an ellipse that is approximately three times as long as it is wide
• Direction of the scar:- longitudinal on the extremities, occasionally with some modification at joints- along skin lines on the trunk and neck- upper back transversely
Wide Excision• Excision should include:
- All skin and subcutaneous tissue to the deep fascia, but not including the fascia
- When a major cutaneous nerve runs along the deep fascia to innervate distal cutaneous structures, it is appropriate to preserve that nerve
SLND & Lymphatic mapping
• Concept and method for sentinel node originally developed by Cabanas for management of penile carcinomas
• Initial experience with lymphatic mapping and sentinel node biopsy for melanoma was the work of Morton et al. at the John Wayne Cancer Institute
• They injected a vital blue dye (isosulfan blue) intra-dermally and found that this stained the draining lymphatics & the first node(s) into which these lymphatics empty.
SLND & Lymphatic mapping• Lymphoscintigraphy has been coupled with the blue dye
injection to support identification of the sentinel node(s), using hand held probes for detection of 'Y radiation emitted by technetium-99( 99Tc )
• Most surgical oncologists performing sentinel node biopsy use a combination of radionuclide injection several hours preoperatively ( in the nuclear medicine suite, up to 1 mCi of 99Tc) and intraoperative intradermal injection of isosulfan blue dye ( up to 1 mL) a few minutes prior to the incision
• The sentinel node ( s ) should be both blue and radioactive ( " hot " )
SLN biopsy using TC99
SLND & Lymphatic mapping
• Typical results o f SNBx reveal that the rate of positive nodes increases with increasing tumour thickness
• The overall rate of positive SNB in most series (typically for melanomas > 1 mm) is in the range of 15 % to 25 %
• False-negative SNB in experienced hands + radiocolloid + handheld gamma probe +/- blue dye = 1.9 % to 4 %
SLND & Lymphatic mapping• Lymphatic mapping and SNBx:
- all cutaneous sites - may also be useful for melanomas of mucous
membranes • A challenging area for SNBx is the head and neck• Melanomas of the scalp and of the face may drain to parotid
nodes or periparotid nodes for which sentinel node biopsy is more complex, technically challenging and associated with greater morbidity
• False-negative sentinel node biopsies are more common than in trunk and extremity melanomas
Patient selection for SLND/Bx
• Depth > 1mm or < 1mm with positive deep margins
• Mitotic rate > 1• Pure desmoplastic melanomas
Principles of LN dissection
- Levels I, II & III of Axillary Lymph Nodes to be removed
- No added survival benefit in ELND
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 heated to 41.5°C/106.7°F and perfused for 60 to
90 minutes• High response rate > 50%• Complications
– neutropenia– amputation– death
• TNF- alpha /Interferon-alfa + melphalan regression rate = 90%
Principles of Adjuvant therapy
-May be considered from Stage IB onwards- Agents:
Targeted therapies
• BRAF Inhibitor– PLX4032 (vemurafenib)
• KIT Inhibitor– Imantinib mesylate
Immunotherapy • Interlukin IL-2 and Interferon in 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
Principles of RT
Prevention & Screening
• Protection from sun exposure:- Building > Clothing > Sun screens
• Self examination • Consultation of Dermatologist
Thank You
Biopsy
Small and accessible lesions– Excision with 1 cm margins in suspicious lesions
Large lesions– Incisional or punch biopsy ?
Shave biopsy discouraged