Dermatopathology Foundations.pdf

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HISTOLOGY OF THE SKIN
Henry Haskell
Skin consists of epidermis and dermis (Fig. I-I). Beneath
the dermis lies the subcutis (or hypodermis).
esses provide contact points for desmosomes, which are
the ultrastructural basis for the tight binding of kerati-
nocytes to one another. These processes may be difficult
to visualize in normal skin, but they become more evi-
dent by intercellular edema (also known as spongiosis).
The stratum granulosum, or granular cell layer, is
named for the irregular, darkly basophilic keratohy-
alin granules that accumulate in the cytoplasm of
the cells in this layer as they flatten and mature. At
the superficial edge of the stratum granulosum, pro-
grammed cell death occurs.
On most parts of the body, the skin possesses a single
layer of dead (but functional) cells, the stratum corneum,
consisting mostly of keratin. The cells in this layer are
sometimes called corneocytes, to distinguish them from
the living cells in the layers below. The stratum corneum
varies widely in thickness according to site: in glabrous
skin, it is only a few cell layers thick, and forms a char-
acteristic "basket weave" pattern; whereas at acral sites,
it is both thicker and more compact (Fig. 1-2). Where
the stratum corneum is particularly thick, another layer,
the so-called stratum lucidum, may be present between
it and the stratum granulosum. The stratum lucidum
differs from the stratum corneum only by a pale eosino-
philic appearance and higher lipid content. Although
pyknotic nuclei may appear in the stratum corneum or
stratum lucidum in pathologic processes, in normal skin
the keratinocytes of both these layers are anucleate.
Keratinocytes stain positively for high molecular
weight cytokeratins such as 34betaEl2, but negatively
for Cam 5.2.
MELANOCYTES
EPIDERMIS
The epidermis is a stratified squamous epithelium that
consists mainly of keratinocytes, with an admixture of
melanocytes, Langerhans, and Merkel cells. Of these,
keratinocytes are by far the most numerous, making up
the bulk of the epidermis and giving it its characteris-
tic microscopic appearance. The epidermis is typically
divided into four layers (see Fig. I-I):
1.
Stratum basale (SB)
2. Stratum spinosum (SS)
3. Stratum granulosum (SG)
4. Stratum corneum (SC)
The stratum basale (or stratum germinativum), also
known as the basal cell layer, consists of a single layer
of cuboidal keratinocytes that lie atop the basement
membrane (see the following) and are connected to it
by numerous hemidesmosomes. At this depth, keratino-
cytes have abundant eosinophilic cytoplasm and ovoid
nuclei. As its name implies, division of keratinocytes
occurs primarily in the stratum germinativum, although
mitotic activity is occasionally seen in the lower part of
the stratum spinosum, in particular the cell layer imme-
diately above the stratum basale, the parabasallayer. In
the process of self-renewal, these cells gradually ascend
into the upper layers and are replaced.
The stratum spinosum, also known as the spinous cell
layer, is named after the spinous processes (or "prick-
les"), which connect the keratinocytes in this layer and
the stratum basale to one another. These spinous proc-
Melanocytes are found along the dermoepidermal
junction as well as within hair follicles (Fig. 1-3).
1
2
DERMATOPATHOLOGY
Epidermis
SC
SG
SS
S8
Reticular
Dermis
FIGURE 1-1
Normal skin with epidermis, papillary and reticular dermis. The epidermis
consists of stratum basale (58), stratum spinosum (55), stratum granulo-
sum (5G), and stratum corneum (5C).
They are responsible for the production and secretion
of melanin pigment. Histologically the cells are char-
acterized by small, dark, ovoid nuclei and scant, clear
cytoplasm. Depending on anatomic site they number
from one per ten to one per five basal keratinocytes,
with higher concentrations on the face and genitalia.
Although melanocytes produce melanin, pigment is
not normally visible in their cytoplasm, as it is rapidly
secreted through their network of dendritic processes
and taken up by basal keratinocytes, where it is stored
and gradually broken down. Although the amount of
melanin produced and stored varies between darker-
and lighter-skinned individuals, the number of mel-
anocytes does not.
Normal intraepidermal melanocytes stain immuno-
histochemically best for tyrosinase, Melan-A/Mart-1,
and microphthalmia transcription factor. HMB-45 may
decorate some normal melanocytes, but it is not a sensi-
tive reagent for visualizing normal resting melanocytes.
8-100 protein stains normal intraepidermal melano-
cytes, but it is neither very sensitive nor specific. It also
stains Langerhans cells.
I.ANGERHANS CELLS
FIGURE 1-2
Normal acral skin with thick compact stratum corneum and acrosyringeal
duct
(arrow).
The Langerhans cell is a dendritic cell that functions
in antigen presentation, and travels between the skin
and draining lymph nodes. In routine tissue sections
of uninflamed skin, these cells are difficult to iden-
tify on hematoxylin and eosin (H&E)-stained sec-
tions. They are best seen on immunostains for 8-100
protein andlor CD1a, which highlight their charac-
teristic location above the stratum basale (Fig. 1-4).
FIGURE 1-3
FIGURE 1-4
Melanocytes
(arrow)
are present at the dermoepidermal junction.
Langerhans cells are immunoreactive for COla and recognized as dendritic
cells within the spinous cell layer.
SECTION I
Histology of the Skin
3
Historically the characteristic Birbeck granule, a rod-
or tennis-racket-shaped body seen by electron micros-
copy, identified these cells. Langerhans cells are easily
recognized when they aggregate as Langerhans cell
abscesses; for example, in allergic contact dermatitis
or Langerhans cell proliferative lesions. They are rec-
ognized by a reniform nucleus.
DERMIS
The dermis has a deeper and a superficial layer. The pap-
illary dermis lies immediately below the basement mem-
brane. It is highly irregular, possessing an undulating
system of dermal papillae, which complement the rete
ridge
sy~tem
of the epidermis. It consists mainly of fine,
fluffy, pale eosinophilic fibers of collagen (see Fig. I-I). It
contains a number of free nerve endings (not visible on
routine preparations) as well as Meissnerian corpuscles
(Fig. 1-6), a specialized mechanoreceptor involved in tac-
tile sensation that is found in greatest concentration on
the hands, feet, and lips, and is characteristically located
in the dermal papillae. The inferior edge of the papillary
dermis is bounded by the subpapillary (or superficial vas-
cular) arterial, venous, and lymphatic plexuses.
The much thicker reticular dermis lies beneath these
plexuses, and is easily distinguished at low power by its
thick, interlacing bundles of more deeply eosinophilic
collagen (see Fig. I-I) . It possesses a rich vascular sup-
ply, with a system of anastomosing small arteries, veins,
and lymphatics called the cutaneous (or deep vascular)
plexuses at its inferior border. It has adnexal structures
embedded and the pilar erector muscle (Fig. 1-7) . Nerve
trunks (Fig. 1-8) are also present. They may connect
with Pacinian corpuscles (Fig. 1-9), a specialized type of
nerve ending that participates in the sensation of deep
pressure and vibration. These are also found in the sub-
cutis, as well as certain internal organs, and are found in
greatest concentrations in the palms, soles, dorsal digits,
and genitalia.
In addition to the common vascular structures of arter-
ies, veins, and lymphatics, the reticular dermis may also
contain a special type of arteriovenous shunt called a glo-
mus body (Fig.
1-10).
The glomus body consists of arterial
MERKEL CELLS
Nerve endings from the dermis are frequently associ-
ated with Merkel cells in the basal epidermis, which are
believed to playa role in tactile sensation. Merkel cells
are rarely visible on routine sections. They are best iden-
tified by electron microscopy (where they show charac-
teristic features of neuroendocrine differentiation) or by
immunohistochemical stains for cytokeratin 20 or chro-
mogranin (Fig. 1-5).
BASEMENT MEMBRANE
The basal layer of the epidermis is attached to the super-
ficial epidermis by the basement membrane, a complex
structure with a deceptively simple appearance under
routine light microscopy. By electron microscopy, it con-
sists of a superficial lamina lucida, which binds to the
hemidesmosomes of the epidermis, and a deeper lamina
densa, consisting mostly of type IV collagen, which binds
the collagen fibrils of the superficial dermis. In routine
practice, the basement membrane is visible under H&E,
but may be emphasized using the periodic acid-Schiff
reaction. Immunohistochemistry for type IV collagen is
also available.
FIGURE 1-5
FIGURE 1-6
A Merkel cell is recognized by the immunoreactivity for cytokeratin 20.
Meissnerian corpuscle.
4
DERMATOPATHOLOGY
FIGURE 1-7
FIGURE 1-10
Smooth muscle bundle with blunt-ended nuclei (pilar erector muscle).
Glomus body.
FIGURE 1-8
Nerve trunks adjacent to a blood vessel.
and venous limbs surrounded by several layers of glomus
cells, modified smooth muscle cells that have round to
ovoid nuclei and characteristically express smooth mu -
cle actin (SMA) in their cytoplasm. Glomus bodies func-
tion in thermoregulation and are most frequently found
in distal sites such as the ears and fingertips.
Whereas the epidermis is densely cellular, the dermis
is paucicellular. It consists mainly of the extracellular
matrix. The three main extracellular proteins that make
up the dermis are collagen, providing strength; elastin,
providing elasticity; and ground substance. In normal
skin elastin is a minor component, consisting of slen-
der, amphophilic fibers that may be difficult to distin-
guish without the use of various special stains (e.g., van
Gieson). Ground substance is also difficult to see in rou-
tine preparations, as it comprises only a very minor pro-
portion of the overall dermis, and is finely intermixed
with the more obvious collagen. The basic cellular com-
ponent of the dermis is the fibroblast, which produces
and maintains all three extracellular components-col-
lagen, elastin, and ground substance.
APPENDAGES
There are five appendages commonly found in normal
skin: eccrine, apocrine, and sebaceous glands; hair; and
nail.
ECCRINE GLANDS
FIGURE 1-9
Pacinian corpuscle.
The most numerous glands in the skin, eccrine glands are
present on
all
skin surfaces, but are most concentrated on
SECTION I
Histology of the Skin
5
the palms, soles, forehead, and axillae. They are respon-
sible for thermoregulation, and secrete a watery, hypo-
tonic fluid. The glands consist of an unbranched, coiled,
secretory component, usually found surrounded by fat
in the deep dermis, which feeds into the duct, which is
at first coiled, then straight, and finally exits through
the epidermis in a coiled structure of dermal origin
known as the acrosyringium. The secretory gland con-
sists of a single layer of cuboidal epithelium surrounded
by myoepithelial cells, whereas the duct has two layers
of epithelium and no myoepithelial cells (Fig. 1-11). The
cytoplasm of both portions is typically eosinophilic, but
in the secretory gland the cytoplasm may retain sig-
nificant amounts of glycogen, resulting in clearing or
vacuolation.
Eccrine glands express cytokeratins (e.g., Cam
5.2, CK7) , CEA, and EMA immunohistochemically.
Myoepithelial cells can be identified with antibodies to
S-100 protein, p63 (4A4), calponin, and smooth muscle
actin.
FIGURE 1-12
Apocrine glands with snouts (decapitation secretion").
ApOCRINE GLANDS
Apocrine glands are much less numerous than eccrine
glands. They differ from eccrine glands in their dis-
tribution (they are found mainly in the axillae, ano-
genital region, areola, and eyelid) and their mode of
secretion. In apocrine glands, the apices of the secre-
tory cells break down during the secretion process and
appear to pinch off ("snouts"), leading to a histologic
picture of "decapitation secretion" into the glandular
lumen (Fig. 1-12). The secretory portion of an apocrine
gland is a coiled, nonbranching tube lined by a layer of
cuboidal to columnar epithelial cells with round nuclei
and brightly eosinophilic cytoplasm, surrounded by a
layer of myoepithelial cells. The apocrine ducts per se
are morphologically indistinguishable from eccrine
ducts.
Apocrine glands develop in association with hair fol-
licles. The apocrine duct opens near the skin surface
into the infundibulum of the associated hair follicle. The
secretions from apocrine glands are at first odorless, but
are converted to odorous products by surface bacteria.
The scent and musk glands of mammalians are regarded
as modified apocrine glands. Specialized apocrine glands
in humans are found in the external ear canal (cerumi-
nous glands) and the eyelid (Moll's glands).
SEBACEOUS GLANDS
FIGURE 1-11
Eccri ne glands.
Unlike eccrine and apocrine glands, sebaceous glands
are holocrine glands; that is, they secrete by slough-
ing of entire cells into the ductal lumen. The result is a
thick, oily secretion known as sebum. Sebaceous glands
generally have a branched, acinar pattern, with multi-
ple lobules, each consisting of an outer rim of cuboidal
basophilic germinative cells surrounding multiple inner
layers of cells with vacuolated, lipid-filled cytoplasm
(Fig. 1-13). The cells' lipid content increases as they
approach the sebaceous duct, which is lined by stratified
squamous epithelium. Although sebaceous glands in
some areas, such as the labia minora, prepuce, or areola
(where they are known as Montgomery's glands) may
empty directly onto the surface of the skin, in general, a
sebaceous gland exists in continuity with a hair follicle,
either terminal or vellus; the combination is known as a
pilosebaceous unit. When part of a pilosebaceous unit,
the sebaceous duct empties onto the hair shaft; the duct
is continuous with the outer root sheath, and the gland
as a whole is surrounded by the fibrous root sheath.

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