Derm Path: Lecture 3: Cutaneous Neoplasia Ii

Front 1

Melanocytic neoplasia

Melanocytes:
Origins:

Back 1

- Melanocytes originate in the neural crest and migrate to the skin and mucous membranes near the end of the first trimester of fetal life.

- Number of melanocytes to keratinocytes varies with body site from 1:10 (trunk) to 1:3 (face/genitalia)

- Melanocytes produce and export melanin pigment to keratinocytes (1:36)

Eumelanin is brown-black (stable)

Phaeomelanin is yellow-red (less stable --> predisoposes to skin cancer)

Function: produce pigment

Melanin comes in two forms:
- eumelanin which is responsible for black/brown pigment

- phaeomelanin which is responsible for yellow/red pigment

- melanin granules are packaged in melanosomes and exported to keratinocytes via the dendritic processes of the melanocytes

- each melanocyte provides melanosomes to approximately 36 keratinocytes

The variety of benign and malignant melanocytic lesions is extensive.

Front 2

NEVUS

- define:

(most = melanoctyic)

congential vs. acquired?

Back 2

- a benign, congenital lesion

- a hamartoma which is an overgrowth of normal tissue(s) at its usual site

Acquired
- Majority are acquired lesions
- Generally <6 mm,
- Regularly pigmented and have symmetry and regular borders

Congenital
- Small (<2 cm),
- Intermediate (2-20 cm)
- Large (> 20 cm)
The large congenital nevi carry some increased risk of malignant transformation (5-15%)

A variant of congenital nevus on the scalp or posterior neck is associated with involvement of the leptomeninges; this is called neurocutaneous melanosis.

Front 3

Melanocytic Nevi

Acquired nevi go through a progression that includes:

Back 3

- Lentigo simplex – increased numbers of individual melanocytes

- Junctional melanocytic nevus – nests only in the epidermis

- Compound melanocytic nevus – nests in the epidermis and dermis

- Intradermal melanocytic nevus – nests only in the dermis

Front 4

Some common variants of acquired nevi include:

Back 4

Blue nevus
clinically blue instead of brown

Dysplastic nevus:
can be either a distinctive histologic type OR a marker of the dysplastic nevus syndrome which carries nearly a 100% risk of melanoma development.

Spitz nevus
-commonly mistaken for non-melanocytic lesions on clinical exam. For instance the clinical appearance may be more suggestive of a vascular lesion. They have been mistaken on histologic grounds for melanoma

Front 5

BENIGN

Melanocytic Nevus - Usual type

Clinical Features:

Histologic Presentation:

Back 5

Clinical features:
Small, most <6 mm
Symmetric
Borders are smooth/regular
Pigment is evenly distributed
Once established does not change and is not symptomatic

Histologic features:
Melanocytes are small, round and in clusters (nests)
Nests are fairly uniform in size, shape and distribution
Nests are seen at all edges of the nevus
Pigment and inflammation are evenly distributed
Melanocytes in the dermis are smaller than in the epidermis

Front 6

The events that are responsible for the formation of a nevus are not well understood. We currently know:

Back 6

+ That we acquire nevi until late in middle age, predominantly at sites of sun exposure. The older we get the less common it is to acquire benign pigmented lesions.

+ It is not common to have acquired nevi on sun-protected sites such as the soles of the feet, buttocks, scalp or external genitalia.

+ Most acquired nevi have a BRAF mutation which is not present in congenital nevi.

+ The “dysplastic phenotype” is hereditary and associated with a family history of melanoma; specific genes have not been clearly identified.

+ Different “types” of melanoma have different genetic abnormalities/ genetic signatures.

Based on comparative genomic hybridization, melanomas from chronically sun-exposed skin, intermittently sun-exposed skin and non sun-exposed skin can be separately classified because they have distinctive patterns of chromosomal gains and losses.