Disorders of Pigmentation and Melanocytes (Dr. C.

Ayochok)
Rocky June 14, 2013

DISORDERS OF PIGMENTATION AND

MELANOCYTES
Freckles (Ephelis)

Most common pigmentation skin lesion

during childhood among light-skinned
individuals
Start to appear during childhood, then a
cycle happens involving waxing or
waning (light colored during winter &
darker during summer)
Macular lesions that range in color from
tan-red or light brown
Microscopic
o Increase in amount of melanin
located within the basal
keratinocytes
o *there is increased melanin
pigment (NOT the number of
melanocytes)

Melanocytic Nevus (Pigmented Nevus, Mole,

Nevus Cellular Nevus)

Lentigo (Lentigines)

Macular lesions (distinguished from

freckles in a way that they do not darken
during the summer)
Uniform in color throughout the year
Microscopic
a) Linear proliferation of
melanocytes as to cause a
hyperpigmented basal cell layer
among the epidermis
b) Elongation & thinning of the rete
ridges

Refers specifically to any neoplasm of

melanocytes
Could be flat or elevated
*Have a uniform pigmentation & has
smooth borders
*most would run a benign course
P16: tumor-suppressor gene involved
Clinical & histologic feature predicts the
progression
Initially, the nevus is called a junctional
nevus, commonly macular lesions that
are variably pigmented, with the nevus
cells (transformed melanocytes) which
become spherical cells occurring in nests
characterized with round/spherical nuclei
surrounded by a clear cytoplasm
o Nevus cells are confined at the
dermo-epidermal junction
As the nevus cells mature, they descend
into the dermis
In the process of descent, the nevus cells
will not only be located at the dermoepidermal junction but also at the
dermis, hence, called a compound
nevus (elevated lesions)
o Smooth contoured & uniformly
pigmented
The most mature is called the
intradermal (dermal) nevus
o Occurs as an elevated, smoothcontoured, uniformly pigmented
lesion
o Nevus cells are seen at the
dermis
As the nevus evolves from a junctional
type, to an intradermal type, it also goes
through a process of maturation wherein,
the more superficial nevus cells tend to
be larger & have more capacity to
produce pigment, more often seen in
nests; compared to more mature nevus
cells which are smaller in size & do not
produce pigment, & when located in the
dermis, they are no longer arranged in
nests but in cords of cells
There would be an acquisition of
cholinesterase activity & lose
tyrosinase (as they reach the dermis,
they no longer produce melanin)
*compared to melanoma, there is lack of
maturation of melanoma cells

Disorders of Pigmentation and Melanocytes (Dr. C. Ayochok)

Rocky June 14, 2013

Figure 25-3.Melanoyctic nevus, junctional

type.A. In clinical appearance, lesions are small,
relatively flat, symmetric, and uniform. B. On
histologic examination, junctional nevi are
characterized by rounded nests of nevus clls
originating at the rete ridges along the
dermoepidermal junction.

Figure 25-4. Melanocytic nevus, compound type.

In contrast to the junctional nevus, the compunt
nevus (A) is more raised & dome-shaped. The
symmetry and uniform pigment distrubution
suggest a benigh process. Histologically (B)
compound nevi combine the features of
junctinoal nevi (intraepidermal nevus cells
nests) with nests & cords of nevus cells in the
underlying dermis.
Dysplastic Nevus (BK Mole)

Clinical significance: increased

correlation with the development of
melanoma in individuals having the
heritable melanoma syndrome
Also occurs on non-sun-exposed areas

Has an irregular border & pigmentation

is variegated (some parts of the mole is
lightly colored & other parts of the mole
are dark colored)
Microscopic
o Generally speaking, a dysplastic
nevus is a compound nevus
o On high power, dysplastic nevus
cells are coalescent, & some of
them tend to drop off & align
themselves along the basal cell
layer forming some sort of
lentiginous hyperplasia
o (+) atypia
Nuclear irregularities
Nuclear hyperchromasia
o Some will release melanin, which
would be engulfed by dermal
macrophages: Melanin pigment
incontinence
May develop to a melanoma only in
susceptible individuals (most of the time,
a dysplastic nevus is clinically stable)

Figure 25-6. Dysplastic nevus. A. Numerous

clinically atypical nevi on the back. B. One such
lesion (inset A) has compund nevus component
(left side of scanning field) and an asymmetric
junctional nevus component (right side of
scanning field). The former correlated grossly
with the more pigmented and raised central
zone & the latter with the less pigmented, flat
peripheral rim. C. An important feature is the
presence of cytologic atypia (irregularly shaped,
dark-staining nuclei). The dermis underlying the
atypical cells characteristically shows linear, or
lamellar, fibrosis.
Melanoma

All melanomas are malignant

Unlike benign nevi, melanomas show
striking variations in color, appearing in
shades of black, brown, red, dark blue
and gray. On occasion, zones of white or
flesh-colored hypopigmentation also
appear, sometimes due to focal
regression of the tumor.

Disorders of Pigmentation and Melanocytes (Dr. C. Ayochok)

Rocky June 14, 2013

The great preponderance of melanomas

arises in the skin; other sites of origin
include:
o Oral & anogenital mucosal
surfaces
o Esophagus
o Meninges
o Eye
Risk Factors
a. Sun exposure
b. Genetic susceptibility
*ABCs of melanoma (important warning
signs)
1. Asymmetry
2. Irregular borders
3. Variegated color (more
variegated than a dysplastic
nevus)
Clinically, there would be:
o Enlargement
o Pain
o Itching
Microscopic:
o Melanoma cells are monotonous
& infiltrating the epidermis

numbers of malignant cells in a draining lymph

node may confer a worse prognosis.

Radial Growth Phase: describes the

horizontal spread of melanoma within
the epidermis & superficial dermis
o Tumor cells seem to lack the
capacity to metastasize
o Examples
a. Lentigo
malignalentiginous
proliferation of
melanocytes with
proliferation of tumor
cells; usually presents as
an indolent lesion on the
face of older men that
may remain in the radial
growth phase for several
decades
b. Superficial spreading
the most common type of
melanoma, usually
involving sun-exposed
skin
c. Acral/mucosal lentiginous
melanoma unrelated to
sun exposure
o Range of time: months to several
decades (unpredictable)
o Appear monotonous & lack
maturity (large nuclei &
prominent eosinophilic nucleoli)
usually arranged in nests

Figure 25-8. Melanoma. A. Typically, lesions are

irregular in contour & pigmentation. Macular
areas corrlated with the radial growth phase,
while raised areas usually correspond to nodular
aggregates of malignant cells in the vertical
phase of growth. B. Radial growth phase,
showing irregular nested & single-cell growth of
melanoma cells within the epidermis & an
underlying inflammatory process within the
dermis. C. Vertical growth phase, demonstrating
nodular aggregates of infiltrating cells. D. Highpower view of melanoma cells. The inset shows
a sentinel lymph node with a tiny cluster of
melanoma cells (arrow) staining for the
melanocytic marker HMB-45. Even small

Levels

Clark
Level
I
II
III

Location

Epidermis
Papillary dermis
Papillary-reticular dermal
interface
IV
Reticular dermis
V
Subcutaneous tissue
o A nodule of melanoma cells
indicates that it is ready to go to
the vertical growth phase
Vertical Growth Phase
o Acquisition of the potential to
metastasize
o Tumor cells invade downward into
the deeper dermal layers as an
expansile mass

Disorders of Pigmentation and Melanocytes (Dr. C. Ayochok)

Rocky June 14, 2013

Often heralded by the

appearance of a nodule &
correlates with the emergence of
a clone of cells with metastatic
potential
o Unlike melanocytic nevi,
maturation is absent from the
deep invasive portion of
melanoma
o The probability of metastasis in
such lesions correlates with the
depth of invasion, which by
convention is the distance from
the superficial epidermal granular
cell layer to the deepest
intradermal tumor cells
Breslow thickness
o Other histologic features that
correlate with outcome:
Number of mitoses
Presence of ulceration
Lymphocytic infiltration as a prognostic
factor: GOOD immunosurveillance
o Other variables that predict a
good outcome:
Tumor depth (the Breslow
thickness) <1.7 mm
Number of mitoses
none or very few
Evidence of tumor
regression (presumably
o

due to the host immune

response) absent
Presence & number of
tumor infiltrating
lymphocytes (TILs)
brisk
Gender female
Location (central body or
extremity) extremity
Individual melanoma cells are usually
considerably larger than normal
melanocytes or cells found in
malanocytic nevi. They contain large
nuclei with irregular contours, chromatin
that is characteristically clumped at the
periphery of the nuclear membrane,
prominent red (eosinophilic) nuclei. The
appearance of the tumor cells is similar
in the radial & vertical phases of growth.
While most nevi & melanomas are easily
distinguished based on their appearance,
a minority of atypical lesions occupy a
histologic gray zone & have been termed
melanocytic tumors of uncertain
malignant potential; such lesions
require complete excision & close clinical
follow-up