Melanoma is most deadly of all skin cancers.
It is strongly associated with acquired mutations caused by exposure to UV
radiation in sunlight.
More common in whites and common sites on the skin are trunk in male
and legs in female.
Cutaneous melanoma is mostly asymptomatic but it can present with pain or pruritus.
Most consistent clinical signs are recent changes in size, shape, or color.
Risk factors are:
a) single most important risk factor is exposure to excessive sunlight (UVA
and UVB) at an early age.
b) Dysplastic nevus syndrome
c) History of melanoma in first – or second-degree relative
d) Xeroderma pigmentosum
f) History of a family member with melanoma.
Types of malignant melanoma:
- Superficial spreading melanoma (SSM):
Most common type (70% of cases).
Common sites are lower extremities, arms, upper back.
- Lentigo maligna melanoma (lMM):
Common in the elderly population
Occurs on parts of the face most exposed to the sun.
- Acral lentiginous melanoma:
Most frequent type in the dark skinned.
They are not related to sun exposure.
Uneven pigmentation, nodulation, and ulceration.
Has an aggressive course with early metastases.
Palms, soles, and around the nails.
- Nodular malignant melanoma:
Most aggressive type of melanoma.
Well-demarcated, smooth or nodular and pigmented tumor which may be amelanotic sometime.
sun exposure and inherited genes are most important.
Most melanomas arise in sun-exposed areas, severe sunburns early in life are
the most important risk factor.
10% to 15% of melanomas are familial and associated with dysplastic nevus syndrome.
Mutations that increase Ras and PI3K/AKT proliferation pathways are strongly associated with sporadic melanomas.
Activating BRAF mutations occur in 60% to 70% of melanomas.
Mutations that reduce RB protein activity or affect genes encoding CDK inhibitors (e.g., p16/iNK4a) are strongly associated with both familial and sporadic melanomas.
Melanomas progress from radial to vertical growth patterns:
A) Radial growth:
It describes horizontal spread within the epidermis and superficial dermis.
Tumor cells typically lack the capacity to metastasize.
Examples are Lentigo maligna, Superficial spreading, and Acral/mucosal lentiginous types of melanoma.
B ) Vertical growth
It occurs unpredictably and is characterized by dermal invasion of an expanding clonal mass of cells, lacking cellular maturation.
These cells often have the capacity to metastasize.
Microscopically tumor cells are large cells with expanded, irregular nuclei containing peripherally clumped chromatin and prominent eosinophilic nucleoli.
Fontana-Masson stain is used to reveals melanin granules in the cytoplasm of tumor cells.
Immunohistochemical markers for melanoma cells are:
a) HMB-45 (Most specific)
b) S-100 (Most sensitive)
Histological depth of involvement can be helpful in predicting prognosis.
Following two systems of grading are used :
- Breslow’s method:
It measures the vertical distance (in mm) from granular cell layer to the deepest part of tumor by using a microscopic micrometer.
Most commonly used as prognostic predictor.
2) Clark’s method:
It assesses depth of penetration of melanoma in relation to different layers of dermis.
It can be remembered as ABCDE of melanoma:
a) Asymmetrical pigmented nodule.
b) Border irregularity: Nodule shows scallops and notches. c) Color variability: This is very striking.
d) Diameter: Size >5 mm.
e) Elevation irregularity
Favorable Prognostic factors are:
- Breslow thickness (less than 1.7 mm)
- Number of mitoses (few)
- Evidence of regression (absent)
- Presence of tumor-infiltrating lymphocytes (many)
- Gender (female)
- Location (extremity)
- Sentinel node micrometastasis (absent)
Prognosis in malignant melanoma is best correlated by depth of invasion