Malignant Melanoma

1. MALIGNANT MELANOMA
- JENEFFAR ROSELIN C

2.  Malignant melanoma or melanocarcinoma arising from melanocytes is one of the
most rapidly spreading malignant tumour of the skin that can occur at all ages but
is rare before puberty.
 The tumour spreads locally as well as to distant sites by lymphatics and by blood.
The etiology is unknown but there is role of excessive exposure of white skin to
sunlight
e.g. higher incidence in New Zealand and Australia where sun exposure in high.

3. SITES:
• Besides the skin, melanomas may occur at various other sites such as oral
and anogenital mucosa, oesophagus, conjunctiva, orbit and leptomeninges.
• The common sites on the skin are the
1. trunk (in men),
2. legs (in women).
• other locations are face, soles, palms and nail-beds.

4. RISK FACTORS
Some high risk factors associated with increased incidence of malignant
melanoma are as under:
i) Persistent change in appearance of a mole.
ii) Presence of pre-existing naevus (especially dysplastic naevus).
iii) Family history of melanoma in a patient of atypical mole. iii) Higher age of the
patient.
iv) More than 50 moles, 2 mm or more in diameter.
Molecular studies in familial and hereditary cases have revealed germline
mutation in CDKN2A gene which encodes for cyclin-dependent kinase inhibitor,
mutational loss of PTEN gene and mutation in several other tumour suppressor
genes but not p53.

5. CLINICAL FEATURES:
• Melanoma often appears as a flat or slightly
elevated naevus which has variegated
pigmentation, irregular borders and, of late, has
undergone secondary changes of ulceration,
bleeding and increase in size.
• Many of the malignant melanomas, however, arise
de novo rather than from a pre-existing naevus.
• Malignant melanoma can be differentiated from
benign pigmented lesions by subtle features, the
dermatologists term this as ABCD of melanoma.

8. MORPHOLOGIC FEATURES:
Grossly, depending upon the clinical course and prognosis, cutaneous
malignant melanomas are of the following 4 types:
1. Lentigo maligna melanoma
2. Superficial spreading melanoma
3. Acral lentigenous melanoma
4. Nodular melanoma

9. i) Lentigo maligna melanoma:
• This often develops from a pre-existing lentigo (a flat naevus
characterised by replacement of basal layer of epidermis by
naevus cells).
• It is essentially a malignant melanoma in situ. It is slow
growing and has good prognosis.
ii) Superficial spreading melanoma:
• This is a slightly elevated lesion with variegated colour and
ulcerated surface. It often develops from a superficial
spreading melanoma in situ (pagetoid melanoma) in 5 to 7
years.
• The prognosis is worse than for lentigo maligna melanoma.

10. iii) Acral lentigenous melanoma:
• This occurs more commonly on the soles, palms and
mucosal surfaces. The tumour often undergoes ulceration
and early metastases.
• The prognosis is worse than that of superficial spreading
melanoma.
iv) Nodular melanoma:
• This often appears as an elevated and deeply pigmented
nodule that grows rapidly and undergoes ulceration.
• This variant carries the worst prognosis.

11. Histologically, irrespective of the type of malignant melanoma, the following
characteristics are observed:
i) Origin:
The malignant melanoma, whether arising from a pre-existing naevus or
starting de novo, has marked junctional activity at the epidermo-dermal junction
and grows downward into the dermis.
ii) Inflammatory infiltrate:
Some amount of inflammatory infiltrate is present in the invasive
melanomas. Infrequently, partial spontaneous regression of the tumour occurs due
to destructive effect of dense inflammatory infiltrate.

12. iii) Tumour cells:
• The malignant melanoma cells are usually larger than the naevus cells.
• They may be epithelioid or spindle-shaped, the former being more common.
• The tumour cells have amphophilic cytoplasm and large, pleomorphic nuclei
with conspicuous nucleoli.
• Mitotic figures are often present and multinucleate giant cells may occur.
• These tumour cells may be arranged in various patterns such as solid masses,
sheets, island, alveoli etc.

13. iv) Melanin:
• Melanin pigment may be present (melanotic) or absent (amelanotic melanoma)
without any prognostic influence.
• The pigment, if present, tends to be in the form of uniform fine granules (unlike the
benign naevi in which coarse irregular clumps of melanin are present).
• At times, there may be no evidence of melanin in H&E stained sections but
Fontana-Masson stain or dopa reaction reveals melanin granules in the cytoplasm
of tumour cells.
• Immunohistochemically, melanoma cells are positive for HMB-45 (most specific),
S-100 and Melan-A.

15. METASTASIS:
 Metastatic spread of malignant melanoma is very common.
 It takes place via lymphatics to the regional lymph nodes and through
blood to distant sites like lungs, liver, brain, spinal cord, and adrenals.
 Rarely, the primary lesion regresses spontaneously but metastases are
present widely distributed.

20. MANAGEMENT
• Surgical excision of tumour.
• MOHS technique, microscopically controlled surgery developed in
1938 by a general surgeon, Frederic E. Mohs.
• Lymphnode dissection
• Chemotheraphy
• Immunotheraphy

25.  The prognosis for patients with
malignant melanoma is related to the
depth of invasion of the tumour in the
dermis.
 Depending upon the depth of invasion
below the granular cell layer in
millimeters, Clark has described 5
levels.
PROGNOSIS

26. Level I: Malignant melanoma cells confined to the epidermis and its appendages.
Level II: Extension into the papillary dermis.
Level III: Extension of tumour cells upto the interface between papillary and
reticular dermis.
Level IV: Invasion of reticular dermis.
Level V: Invasion of the subcutaneous fat.