Melanoma is most deadly of all skin cancers

Melanoma:
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:white_check_mark: Melanoma is most deadly of all skin cancers.

:white_check_mark: It is strongly associated with acquired mutations caused by exposure to UV
radiation in sunlight.

:white_check_mark:More common in whites and common sites on the skin are trunk in male
and legs in female.

:white_check_mark:Cutaneous melanoma is mostly asymptomatic but it can present with pain or pruritus.
:white_check_mark:Most consistent clinical signs are recent changes in size, shape, or color.

:white_check_mark:Risk factors are:
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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
e) Useoftanningbooths
f) History of a family member with melanoma.

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:cherry_blossom:Types of malignant melanoma::cherry_blossom:
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  1. Superficial spreading melanoma (SSM):
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    :white_check_mark: Most common type (70% of cases).

:white_check_mark: Common sites are lower extremities, arms, upper back.

  1. Lentigo maligna melanoma (lMM):
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:white_check_mark:Common in the elderly population

:white_check_mark: Occurs on parts of the face most exposed to the sun.

:white_check_mark: good prognosis.

  1. Acral lentiginous melanoma:
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:white_check_mark:Most frequent type in the dark skinned.

:white_check_mark:They are not related to sun exposure.

:white_check_mark:Uneven pigmentation, nodulation, and ulceration.

:white_check_mark:Has an aggressive course with early metastases.

:white_check_mark:Palms, soles, and around the nails.

  1. Nodular malignant melanoma:
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    :white_check_mark:Most aggressive type of melanoma.

:white_check_mark:Well-demarcated, smooth or nodular and pigmented tumor which may be amelanotic sometime.

:white_check_mark:Worse prognosis.

:traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light::traffic_light:
:red_circle:Pathogenesis:
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:white_check_mark:sun exposure and inherited genes are most important.

:white_check_mark:Most melanomas arise in sun-exposed areas, severe sunburns early in life are
the most important risk factor.

:white_check_mark:10% to 15% of melanomas are familial and associated with dysplastic nevus syndrome.

:white_check_mark:Mutations that increase Ras and PI3K/AKT proliferation pathways are strongly associated with sporadic melanomas.

:white_check_mark:Activating BRAF mutations occur in 60% to 70% of melanomas.

:white_check_mark: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.

:white_check_mark:Melanomas progress from radial to vertical growth patterns:

A) Radial growth:
:heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
:white_check_mark:It describes horizontal spread within the epidermis and superficial dermis.
:white_check_mark:Tumor cells typically lack the capacity to metastasize.
:white_check_mark:Examples are Lentigo maligna, Superficial spreading, and Acral/mucosal lentiginous types of melanoma.

B ) Vertical growth
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:white_check_mark:It occurs unpredictably and is characterized by dermal invasion of an expanding clonal mass of cells, lacking cellular maturation.
:white_check_mark:These cells often have the capacity to metastasize.

:white_check_mark:Microscopically tumor cells are large cells with expanded, irregular nuclei containing peripherally clumped chromatin and prominent eosinophilic nucleoli.
:white_check_mark:Fontana-Masson stain is used to reveals melanin granules in the cytoplasm of tumor cells.

:white_check_mark:Immunohistochemical markers for melanoma cells are:

a) HMB-45 (Most specific)
b) S-100 (Most sensitive)
c) Melan-A

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:microscope:Histological staging:
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:white_check_mark:Histological depth of involvement can be helpful in predicting prognosis.

:white_check_mark:Following two systems of grading are used :
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  1. Breslow’s method:
    :heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign::heavy_minus_sign:
    :white_check_mark:It measures the vertical distance (in mm) from granular cell layer to the deepest part of tumor by using a microscopic micrometer.

:white_check_mark:Most commonly used as prognostic predictor.
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2) Clark’s method:
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:white_check_mark:It assesses depth of penetration of melanoma in relation to different layers of dermis.

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:gem:Diagnosis:
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:white_check_mark: 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

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:red_circle:Favorable Prognostic factors are:
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  1. Breslow thickness (less than 1.7 mm)
  2. Number of mitoses (few)
  3. Evidence of regression (absent)
  4. Presence of tumor-infiltrating lymphocytes (many)
  5. Gender (female)
  6. Location (extremity)
  7. Sentinel node micrometastasis (absent)

:white_check_mark:Prognosis in malignant melanoma is best correlated by depth of invasion