pathology, investigations, staging and treatment options

1. Malignant Melanoma
Clinical Features, Pathology and Management
By
Dr Madhu kumar
Under guidance
Dr PV Budha MS
Dr Venkat Reddy MS
Dr Sailajarani MS
Dr Satyanaryana MS
Dr Ayyapasrinivas MS

2. 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.

3. 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

4. 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

5. Causes of Melanoma
• 90% of all melanomas are linked to UV
radiation. (Sun exposure)
• 8% are due to chromosomal abnormalities
• About 2% are unknown

6. 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

7. 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

8. 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.

9. Biopsy
Small and accessible lesions
– Excision with 1 cm margins in suspicious lesions
Large lesions
– Incisional or punch biopsy ?
Shave biopsy discouraged

10. Histomorhological types
• Superficial Spreading Melanoma
• Nodular Melanoma
• Lentigo Maligna Melanoma
• Acral Lentiginous Melanoma
• Amelanotic Melanoma

11. • Superficial Spreading
Melanoma
– Most common histologic
type (70%)
– Appear as a flat,
pigmented lesion
growing in the radial
pattern

12. • Nodular Melanoma
– Second most common
type (15%)
– Vertical growth pattern
– Worst prognosis based
on a higher average
tumor thickness.

13. • Lentigo Maligna
Melanoma
– Sun-damaged skin
– Flat,darkly pigmented
lesion with irregular
borders and a history of
slow development

14. • Acral Lentiginous
Melanoma
• Subungual areas and
the glabrous skin of the
palms and soles
• Seen in blacks

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

16. • Antibodies for immunohistochemistry
– S - 100
– HMB - 45
• Mutations
– BRAF
– NRAS
– AKT

17. Stage (Clark’s level or Breslow Depth)

18. 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.

19. 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

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

25. Treatment of Melanoma

26. • 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

28. 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

31. SLN biopsy using TC99

32. 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

33. • 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

34. Complications
• Wound seroma
• Cellulitis
• lymphedema

35. 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

36. • 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%

37. Targeted therapies
• BRAF Inhibitor
– PLX4032(vemurafenib)
• KIT Inhibitor
– Imantinib mesylate

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

39. 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

40. Radiation
• Used in some cases
• High doses
• Not so useful

41. 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