Ebook Histopathology of the skin: Part 1

Histopathology
of the Skin

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Histopathology
of the Skin

Ashok Aggarwal

MBBS, MD

Dean and Senior Consultant
Skin Institute and School of Dermatology
New Delhi-110048

JAYPEE BROTHERS
MEDICAL PUBLISHERS (P) LTD
New Delhi


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printed version of the book.

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Histopathology of the Skin
© 2007, Ashok Aggarwal
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First Edition: 2007
ISBN 81-8061-951-6

Typeset at JPBMP typesetting unit
Printed at Ajanta Offset


Dedicated to

Late Prof. Pran Nath Behl



Foreword
Indeed it is intriguing to have a title on Histopathology of the Skin in the Indian context. It is unique for it embraces the
various relevant facets which need to be appraised to the native students. The endeavor to write a book on the title has
been made by Dr Ashok Aggarwal who had done his postgraduate degree in Dermatology and Venereology in the year
1978 from Maulana Azad Medical College, New Delhi. He had the privilege of working under Dr Pran Nath Behl in Skin
Institute and School of Dermatology. Over the years his interest in histopathology of skin was recognized and he went
for short training to Edinbur gh under Prof. Hunter and his group. After his return he had a privileged opportunity of

streamlining the services in dermatopathology in the Institute. He has now utilized his acumen in preparing a dissertation
in the form of a booklet hugging various dermatoses attempting to bring about a correlation for the purposes of ultimate
diagnosis of the disease. It’s a worthwhile endeavor and should help all those who are interested in clinical histopathological
and treatment aspect of various dermatoses. The illustrations contain therein are of good quality , and may serve as a
ready reckoner or accomplishing for the diagnosis of dermatoses in question. The sincere attempt therefore is worth
applauding and augurs well for the future of the specialty .
Virendra N Sehgal

MD, FNASc, FAMS, FRAS (Lond.)
Former Professor/Head Department of Dermatology and
Venereology, Goa Medical College, Panji

• Professor/Head Department of Dermatology and Venereology,
UCMS, Safdarjung Hospital
• Professor/Head (Acting Dean), Director-Professor,
Department of Dermatology and Venereology,
Maulana Azad Medical College/LNJP Hospital, New Delhi
• Principal/Medical Superintendent/Director-Professor Dermatology and
Venereology, Lady Hardings Medical College, New Delhi
• Director -Professor Dermatology/Venereology/Medical Superintendent,
UCMS-GTB Hospital, Delhi
Sehgal Nursing Home
Dermato-Venereology (Skin/VD) Centre
A-6 Panchwati, Delhi-110033 (India)



Preface
The book “Histopathology of the Skin” is a much awaited book in the Indian context on dermatopathology designed for
postgraduate students of dermatology. It is also meant for general pathologist dealing with the cutaneous morbid conditions.

The chapters on Normal Histology of Skin and Recognition of Inflammatory Cells will enable beginners to identify
common skin structures and inflammatory cells in tissue sections. The chapter on Special Stains has been included to
give insight into the role of these stain in diagnoses of different skin conditions. The histopathological findings of
different skin diseases are described in detail but in a simple and straightforward fashion.
A lar ge number of
microphotographs included in this book will further help the readers to assess their histopathological tissue sections.

Ashok Aggarwal



Contents
1.

Histology of Normal Skin ..................................................................................................................................... 1

2.

Techniques of Skin Biopsy ................................................................................................................................. 14

3.

Dermoepidermal Junction ................................................................................................................................... 18

4.

The Cells of the Skin and their Identification ..................................................................................................... 20

5.

Common Terminologies Used in Dermatopathology .......................................................................................... 26

6.

Staining Techniques in Dermatopathology ......................................................................................................... 33

7.

Dermatitis and Eczema (Spongiotic Dermatitis)................................................................................................. 46

8.

Lichen Planus ..................................................................................................................................................... 53

9.

Vesiculobullous Disorders ................................................................................................................................... 63

10.

Dermatophytosis (Superficial Fungal Infections) ............................................................................................... 74

11.

Yeast Infections .................................................................................................................................................. 80

12.

Viral Infections of Skin ....................................................................................................................................... 83

13.

Tuberculosis of the Skin .................................................................................................................................... 92

14.

Hansen’s Disease (Leprosy) ............................................................................................................................... 98

15.

Leishmaniasis .................................................................................................................................................... 106

16.

Disorders of Hypopigmentation ......................................................................................................................... 110

17.

Erythema Multiforme ......................................................................................................................................... 114

18.

Lichen Sclerosus et Atrophicus (LSA) .............................................................................................................. 116

19.

Scleroderma .......................................................................................................................................................118

20.

Lichen Simplex Chronicus (Circumscribed Neurodermatitis) .......................................................................... 123

21.

Pigmented Purpuric Dermatosis (Schamber g’s Disease) ................................................................................. 126

22.

Dermatitis Herpetiformis .................................................................................................................................. 129

23.

Sarcoidosis ....................................................................................................................................................... 135

24.

Lupus Erythematosus (LE) .............................................................................................................................. 138

25.

Pyoderma Gangrenosum .................................................................................................................................. 146

26.

Urticaria Pigmentosa (UP) ................................................................................................................................ 148

27.

Gyrate and Annular Erythemas ......................................................................................................................... 150

28.

Seborrheic Keratosis (Senile Warts) ................................................................................................................. 152

29.

Basal Cell Carcinoma (BCC) ............................................................................................................................. 156

30.

Verrucous Epidermal Nevus ............................................................................................................................. 160

31.

Epidermal or Infundibular Cyst ........................................................................................................................ 163

32.
33.
34.
35.

Keratoacanthoma .............................................................................................................................................. 167
Squamous Cell Carcinoma (SCC) .................................................................................................................... 169
Actinic Keratosis (Solar Keratosis)................................................................................................................... 172
Bowen’s Disease ............................................................................................................................................... 174


xii
36.
37.

38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.

Histopathology of the Skin
Oral Leukoplakia ............................................................................................................................................... 176
Paget’s Disease ................................................................................................................................................. 178
Alopecias ........................................................................................................................................................... 180
Psoriasis ............................................................................................................................................................ 188
Lymphocytoma Cutis (Cutaneous Lymphoid Hyperplasia) .............................................................................. 198
Disorders of Hyperpigmentation ....................................................................................................................... 200
Syringoma/Trichoepithelioma/Cylindroma ....................................................................................................... 208
Acne Vulgaris ..................................................................................................................................................... 211
Polymorphous Light Eruption ........................................................................................................................... 216
Dermatofibroma (Benign Fibrous Histiocytoma, Sclerosing Hemangioma) ..................................................... 220
Mycosis Fungoides (MF) ................................................................................................................................. 226
Ichthyosis Vulgaris ........................................................................................................................................... 229
Porokeratosis .................................................................................................................................................... 231
Xeroderma Pigmentosum ................................................................................................................................. 233
Erythema Nodosum (EN) ................................................................................................................................. 235
Urticaria ............................................................................................................................................................ 238
Erythema Elevatum Diutinum ........................................................................................................................... 241
Pityriasis Lichenoides ....................................................................................................................................... 243
Acanthosis Nigricans ........................................................................................................................................ 245
Fixed Drug Eruption ......................................................................................................................................... 247
Granuloma Annulare ......................................................................................................................................... 249
Hemangiomas Lymphangiomas ........................................................................................................................ 251
Syringocystadenoma Papilliferum .................................................................................................................... 258
Leiomyoma ....................................................................................................................................................... 261
Sweet’s Syndrome ............................................................................................................................................ 263
Secondary Syphilis ........................................................................................................................................... 264
Arthropod Bite Reactions (Papular Urticaria) ................................................................................................... 266
Keratosis Pilaris ................................................................................................................................................ 268
Lichen Amyloidosis and Macular Amyloidosis ................................................................................................. 269

Malignant Melanoma......................................................................................................................................... 271
Cutaneous Neurofibroma .................................................................................................................................. 274
Index ................................................................................................................................................................. 277


1

CHAPTER

Histology of Normal Skin
Skin is the largest organ of the body measuring 1.7 square meters in an adult male with an average weight of 60 kg.
Sections of skin stained with hematoxylin and eosin when examined under light microscope show three distinct
zones:
• Epidermis
• Dermis and
• Hypodermis or subcutaneous fat which actually is a soft tissue and not truly a part of the skin, but because of its
exceedingly close anatomic relationship to the skin and its tendency to respond together with the skin in many
pathological processes, it is considered to be a third compartment of the skin.
Epidermis
The epidermis is the thinnest portion of skin, varying in thickness from 0.04 mm on the eyelids to 1.6 mm on the palms,
the average thickness being 0.1 mm. It is a metabolically active, stratified squamous, cornifying epithelium. The lower
portion of the epidermis has an undulating surface with downward invagination termed rete and interdigitating mesenchymal
cones called dermal papillae (Fig. 1.1).
•
•

Two main types of cells constitute the epidermis:
Keratinocytes and
Dendritic cells.


Fig. 1.1: Histology of normal human epidermis and
upper dermis showing rete ridges and dermal papillae


2

Histopathology of the Skin

The keratinocytes constitute more than 90 percent of cell population of epidermis and differ from the dendritic cells
or clear cells by possessing intercellular bridges and ample amount of stainable cytoplasm. The main dendritic cells of the
epidermis are melanocytes, Langerhans’ cells and indeterminate cells. Other cells that are present in epidermis are Merkel
cells (neuroendocrine) as well as unmyelinated axons.
The epidermis shows four distinct but related cellular layers (Fig. 1.2) which from below upwards are:
• Basal cell layer (Stratum basale)
• Squamous cell layer (Stratum spinosum)
• Granular layer (Stratum granulosum)
• Horny layer (Stratum corneum)
The term stratum malpighii is often applied to the three lower layers which includes the basal, squamous and granular
cells and comprises the viable nucleated portion of the epidermis.
Stratum lucidum is the lowest portion of stratum corneum seen in those areas of skin where the horny layer normally
is very thick, i.e. on palms and soles. It is seen as a thin homogenous eosinophilic zone and is rich in protein-bound lipids.
It is also called stratum conjunctum in contrast to the overlying basket weave stratum corneum which is also called
stratum dysjunctum.
Basal Cell Layer
The basal cells form a single layer , are columnar in shape and lie with their long axis perpendicular to the dividing line
between the epidermis and the dermis. They have a deeply basophilic cytoplasm and a dark-staining oval or elongated
nucleus. They are connected with each other and with the overlying squamous cells by intercellular bridges or desmosomes.
These desmosomes are less distinct than those in the squamous cell layer. At their base the basal cells are attached to the
subepidermal basement membrane zone. The amount of melanin present in the basal cells parallels the skin color.

Squamous Cell Layer
The cells of the squamous cell layer are polygonal and are named “spinous cells” because of the presence of distinct but
delicate spine like intercellular bridges or desmosomes that with conventional microscopy are seen to cross intercellular
spaces and form contact between adjacent cells (Fig. 1.3). Squamous cell layer is five to ten layers thick. The cells
become flattened towards the surface with their long axis arranged parallel to the skin surface.

Fig. 1.2: Epidermis showing horny layer , granular
layer and squamous cell layer

Fig. 1.3: Squamous cell layer showing polygonal cells
and delicate spine like intercellular bridges or
desmosomes


Histology of Normal Skin

3

Granular Cell Layer
The cells of the granular layer are diamond-shaped or flattened. Their cytoplasm is filled with keratohyaline granules that
are deeply basophilic and irregular in size and shape (Fig. 1.4). The thickness of the granular layer in normal skin is
proportional to the thickness of the horny layer; it is only one to three-cell layers thick in areas in which the horny layer
is thin but measures up to ten layers in thickness in areas with a thick horny layer , such as palms and soles.
Horny Layer
Horny layer or stratum corneum is the outermost anucleated layer of the skin, which stains eosinophilic in contrast to the
underlying stratum malpighii. It consists of layers of flattened anucleated cells with dense cell wall and apparently empty
interiors (Fig. 1.5). In formalin fixed histologic sections it is difficult to ascertain the exact thickness of stratum corneum
because some of the outer cell layers get detached during fixation and processing.
Melanocytes
Under light microscopy in hematoxylin and eosin stained skin sections melanocytes appear as clear cells in and immediately

beneath the row of epidermal basal cells. The clear space characteristic of melanocytes is actually an artifact of fixation
during which cytoplasm shrinks and becomes concen-trated around the nucleus, thereby creating a space. Melanocytes
in fact are not clear cells but possess abundant translucent cytoplasm. The nucleus of a melanocyte is smaller and more
deeply basophilic than that of a basal keratinocyte and the cytoplasm of it is dendritic, unlike that of a keratinocyte.
Dendrites of melanocytes are revealed more effectively with silver salts that stain melanin black; they then are seen to
arborize in all directions among neighboring keratinocytes and even into the upper most part of the dermis. It has been
estimated that, a single melanocyte is connected to about 36 keratinocytes, constituting “the epidermal melanin unit.” In
sections stained by hematoxylin and eosin, the average ratio of melanocytes to basal keratinocytes is about 1 to 10.
Langerhans’ Cells
Langerhans’ cells are dendritic cells that are present just above the middle of the spinous zone of the epidermis. Langerhans’
cells represent about 4 percent of the entire population of cells in the epidermis. Fine unmyelinated nerve fibers ascend
into the epidermis where they touch Langerhans’ cells, thereby creating a link between the nervous and immune systems.

Fig. 1.4: Granular layer showing diamond- shaped
or flattened cells filled with kerato-hyaline granules
that are deeply basophilic and irregular in size and
shape

Fig. 1.5: Basket weave horny layer comprising of
flattened anucleated cells with dense cell wall and
apparently empty interiors


4

Histopathology of the Skin

In sections stained by hematoxylin and eosin Langerhans’cells like melanocytes appear as clear cells.As identification
of Langerhans’ cell is difficult in conventional sections, special stains are generally required for their detection. Enzyme
histochemical stains employed for such purpose are adenosine triphosphatase and aminopeptidase. These stains demonstrate

Langerhans’ cells in the mid epidermis from each of which up to 12 dendritic cytoplasmic processes extend between
keratinocytes to reach the granular zone above and the dermoepidermal junction below. Electron microscopy is the only
reliable method of identifying Langerhans’ cells.
Merkel Cells
Merkel cells are present within the basal cell layer of the epidermis, oral mucosa and in the bulge region of hair follicles.
They cannot be recognized in light microscopic sections.
Dermoepidermal Junction (Basement Membrane Zone)
With conventional light microscopy the basement membrane zone is best visualized with Periodic acid-Schif
f (PAS) stain
which makes the basement membrane zone appear as magenta colored linear band situated immediately beneath the basal
keratinocytes (Fig. 1.6).
Hair Follicle
Three types of hairs are seen on a human body:
“Lanugo” hairs (L. Lana “wool”) which are soft, fine, lightly pigmented hairs that cover the body of a fetus. “V
ellus” hair
(L.Vellus “fleece”) are fine hairs that cover most of the body of children and adults. “T erminal hairs” are long coarse
pigmented hairs with larger diameter present on the scalp, beard, eye-brows, eyelashes, axillae and pubes.Terminal hairs
are the only type of hair that consistently possesses a medulla.
The hair follicle as seen in longitudinal sections of skin is divided into two segments: upper segment and lower
segment. Upper segment includes infundibulum and isthmus. Infundibulum is the uppermost part of hair follicle that
extends from the ostium or surface opening of the follicle to the entrance of the sebaceous duct below . Isthmus is the
shorter portion of the hair follicle that extends from entry of sebaceous duct above to attachment site of arrectores
pilorum muscle below. Lower segment also consists of two parts, i.e. stem and a bulb. S tem is that portion of the hair
follicle, which stretches from the base of the isthmus to the end of the keratogenous zone atAdamson’s fringe. Bulb is the
lowest portion of the follicle below the Adamson’s fringe.


Fig. 1.6: Periodic acid-Schiff stain showing basement membrane
zone which appears as magenta coloured linear band immediately
beneath the basal keratinocytes

Histology of Normal Skin

5

Adamson’s fringe represents the zone where the process of keratinization starts and forms the boundary between the
nucleated cells in the bulb of a follicle and anucleated cells of stem of a follicle. The bulk of a follicular bulb consists of
matrical epithelial cells among which melanocytes are interspersed. The bulb in its lower most part is expanded to enclose
a follicular papilla formed of connective tissue which is continuous with the connective tissue sheath (perifollicular) that
envelops the rest of the follicle up to the infundibulum. The infundibulum is surrounded by a connective tissue which is
similar to connective tissue in the papillary dermis.
The perifollicular sheath has two components, an outer one with bundles of collagen arranged longitudinally and an
inner one with bundles of collagen that encircle the follicle. Sheath has fibrocytes that produce it and capillaries that lie
parallel to collagen bundles of the outer compartment.
A “glassy” periodic acid-Schiff positive basement membrane separates the follicular papillae and perifollicular sheath
from the follicle itself.Abutting the basement membrane are pale or clear epithelial cells of the outer sheath that represents
the periphery of the follicular bulb. These cells are columnar in shape and arrange in a palisade. Melanocytes in considerable
number are interspersed among matrical cells in the bulb, but only few melanocytes are found along the course of the
stem and the isthmus; in the infundibulum melanocytes are present in a manner similar to that in the normal epidermis.
The matrical cells of follicular bulb differentiate along six different pathways, giving rise to six different layers of hair
follicles which from outside inwards are (Fig. 1.7):
• Henle’s layer of the inner sheath—one cell thick with prominent, brightly eosinophilic trichohyaline granules and the
first to cornify .
• Huxley’s layer of the inner sheath—two cells thick and characterized by numerous trichohyaline granules.
• Cuticle of the inner sheath—one cell thick.
• Cuticle of the hair—single layer of imbricated squames that wrap around the hair shaft and interdigitate with cornified
cells of the cuticle of the inner sheath.
• Cortex of the hair.
• Medulla of the hair—present only in terminal hair.

Matrical epithelium of the follicular bulb consists of a pool of undifferentiated cells that have large round pale staining
finely stippled monomorphous nuclei with a prominent nucleolus. They differ from germinative cells who have smaller
darker nuclei devoid of discernible nucleoli.
Hair grows in a cyclical fashion comprising of three phases:
• Anagen (growing phase).
• Catagen (involuting phase) and
• Telogen (resting phase).


Fig. 1.7: Cross sections through different levels of the bulb
and stem of hair follicles in the subcutaneous tissue


6

Histopathology of the Skin

In histological sections identification of hair in different phases is important.
Fully developed anagen hair is identified by the presence of hair bulb consisting of matrical cells and enveloping a
follicular papilla (Fig. 1.8).
Early catagen (Fig. 1.9) is characterized by follicular bulb that looses its bulbous shape, becomes flattened forming
the base of the inferior segment of the involuting follicle. Follicular papilla lies adjacent to the flattened base.A markedly
thickened basement membrane surrounds the atrophic lower segment of the follicle and separates it from the perifollicular
sheath.
In well advanced catagen the lower segment of the involuting follicle consists of an effete column of epithelial cells
surrounded by thickened, corrugated basement membrane. At the base of the column is present an ill formed follicular
papilla.
Far-advanced catagen shows a shrunken column of epithelial cells, the residuum of the lowest segment of a follicle,
forming a pincer around a well defined follicular papilla. and the lower segment is surrounded by a markedly thickened,
corrugated basement membrane. Tracking behind the involuting follicle is a fibrous tract within which the events of the

follicular cycle takes place (Fig. 1.10).
Late catagen is characterized by remnants of follicular epithelium resembling that of normal isthmus. The follicular
papilla is seen only as scattered fibrocytes at the base of a follicle now entering into resting stage.
Telogen or resting phase consists only of infundibulum and an isthmus (Fig. 1.1 1). Few scattered fibrocytes which
are remanants of a follicular papilla are seen at the base of the isthmus. Periphery of the isthmus shows columnar cells
aligned in a palisade. The bowed cords of undifferentiated epithelial cells that emanate from the junction of infundibulum
and isthmus are called mantles.
Sebaceous Glands
The sebaceous gland is a lipid producing gland that is present all over the body with the exception of the palms, soles and
dorsa of feet. Most of the sebaceous glands are connected to a hair follicle. In areas like buccal mucosa and vermilion of
the lip (Fordyce’ s spots), areolae of women (Montgomery’ s tubercles) internal fold of the prepuce (T yson’s glands),
labia minora and eyelids (Meibomian glands), sebaceous glands are joined to hair follicles that consist of infundibula only;
no bulb or stem is present.

Fig. 1.8: Fully developed anagen hair follicle is
identified by the presence of hair bulb and a follicular
papilla

Fig. 1.9: Early catagen showing flattened base of
the inferior segment of the involuting hair follicle


Histology of Normal Skin

Fig. 1.10: Advanced stage of cat agen showing
involuting hair follicle and a tracking fibrous tract

7

Fig. 1.11: Telogen hair follicle consist s of

infundibulum and isthmus

In histologic sections sebaceous gland is seen to be formed of several lobules. Each lobule has an outer row of
undifferentiated somewhat flattened germinative cells with large nuclei and a homogenous basophilic cytoplasm. The
cells in the central portion of the lobule are larger in size with a characteristic foamy pale staining cytoplasm and nuclei
that become scalloped owing to their compression by lipid vacuoles (Fig. 1.12).
The sebaceous duct is lined by cornifying squamous epithelium and contains a thin granular zone. The sebaceous
gland is surrounded by a PAS- positive basement membrane zone and a thin highly vascular zone of periadnexal connective
tissue.
Apocrine Glands
Apocrine glands are found only in certain areas of the body like axillae, areola, periumbilical region, perineal and circumanal
areas, prepuce, scrotum, mon spubis, labia minora, external auditory canals (ceruminous glands) and on the eyelids
(Moll’s glands).


Fig. 1.12: Sebaceous gland showing several lobules. Nuclei of cells
nearest to the peripheral germinative layer of a sebaceous lobule are
round but become scalloped as they differentiate, owing to
compression by droplets of lipid


8

Histopathology of the Skin

In histologic sections apocrine gland consists of secretary part and excretory duct. Secretory part of the gland is a
coiled structure that is situated in the lower part of the dermis or in the subcutaneous fat. In cross section, the apocrine
secretary coil has a diameter almost ten times greater than that of the eccrine coil (Fig. 1.13). The lumen of the secretory
coil is lined by a single layer of cells that are either cuboidal or columnar in shape, and have abundant pale staining
cytoplasm and round nuclei situated near the base of the cells. The convex apical borders of the secretory cells project

within the lumen to a variable extent. The secretory cells are surrounded by a layer of contractile myoepithelial cells, a
PAS-positive basement membrane zone and fibers of the periadnexal dermis.
Excretory duct of the gland is a straight structure that empties into the infundibulum of a hair follicle, slightly above
the entrance of sebaceous duct. Apocrine duct may also open directly on to the skin surface. It is composed of two layers
of cuboidal cells with an inner periluminal cuticle and an outer myoepithelial lining.
By conventional microscopy it is difficult to distinguish between apocrine and eccrine ducts.
Eccrine Glands (Sweat Glands)
Eccrine gland is the sweat producing gland. They are present all over the body including the glans penis and prepuce but
excluding the oral lips, clitoris, labia minora and external auditary canal. Palms, soles, axillae and forehead are areas that
show maximum number of sweat glands. The sweat glands are located around the junction of the dermis and the
subcutis.
The eccrine unit consists of secretory part, an irregularly coiled structure which leads to coiled dermal excretory duct
which leads to straight duct that traverse the dermis. The spiraled intraepidermal portion of the duct is called acrosyringiu
m
(Fig. 1.14).
In histologic sections coiled glandular portion of the eccrine unit is found to be formed of two rows of cells (Fig.
1.15):
• An outer row of spindle shaped, contractile myoepithelial cells which are located in a discontinuous manner .
• A single inner row of secretory epithelial cells which are pyramidal in shape and line the lumen of the gland. The row
of secretory epithelial cells also consists of two types of cells. Large pale or clear cells (containing glycogen) and
smaller dark cells (containing mucopolysaccharide). The dark cells mostly line the luminal surface, whereas the pale
cells are situated peripheral to the dark cells and for the most part do not abut the lumen itself. Peripheral to the outer
row of myoepithelial cells is a basement membrane that separates glandular epithelium from the richely vascular
connective tissue of the periadnexal dermis.

Fig. 1.13: Cross section of an apocrine gland which is identified
by its diameter which is ten times greater than that of the
eccrine gland

Fig. 1.14: Acrosyringium which is the intraepidermal

portion of the eccrine duct. It spirals through the
epidermis in a cork screw pattern


Histology of Normal Skin

9


Fig. 1.15: Showing eccrine gland and eccrine duct. The secretory
portion of an eccrine gland consists of two layers of cells: (1) a thin
outer row of myoepithelial cells and (2) an inner row of cuboidal
secretory cells. Eccrine ducts, like apocrine ducts, are lined by two
layers of small cuboidal epithelial cells whose luminal edge is rimmed by
homogenous eosinophilic material

The dermal portion of the eccrine duct is lined by a double row of small, darkely basophilic, cuboidal epithelial
cells. A homogenous eosinophilic cutical lines the luminal margin of the entire eccrine duct.
The cells that contribute the intraepidermal portion of the eccrine duct are called as acrosyringeal cells.The
acrosyringeal cells that line the lumen are designated “cuticular” and peripheral cells are named “poroid”. The
acrosyringium spirals through the epidermis in a corkscrew pattern.
DERMIS
The dermis consists mostly of relatively noncellular connective tissue composed of collagen bundles, elastic fibers and
ground substance. A variety of cells are scattered in variable numbers throughout the mature dermis: fibrocytes, dermal
dendrocytes, histiocytes, Langerhan’ s cells, mast cells and rarely lymphocytes. Within the dermis are lodged nerves,
blood vessels, lymph vessels, smooth muscles and epithelial structures of adnexa, namely the folliculo-sebaceous apocrine
units and the eccrine units. The dermis is 15 to 40 times thicker than the epidermis, depending on the anatomic site.
A fully formed dermis is divisible into two distinct compartments.
A thin zone immediately beneath the epidermis (papillary dermis) and around adnexa (periadnexal dermis). Papillary
and periadnexal dermis together constitute the adventitial dermis.Adventitial dermis is formed of thin haphazardly arranged

collagen bundles, delicate branching elastic fibers, plentiful fibrocytes, abundant ground substance and many capillaries.
A thick zone that extends from the base of the papillary dermis to the surface of the subcutaneous fat (reticular
dermis). The reticular dermis is formed predominantly of thick bundles of collagen arranged in an orthogonal pattern.
Elastic fibers course among these bundles. Proportionately fewer fibrocytes and blood vessels and less ground substance
are present in the thick reticular dermis than in the thin adventitial dermis.Adipocytes of the subcutaneous fat commonly
extend in broad columns into the reticular dermis, where they envelop eccrine units and terminate at bases of hair
follicles.
Extracellular Matrix
The extracellular matrix of the dermis is composed of collagen and elastic fibers which are embedded in a ground
substance. All three components are formed by fibroblasts.
Collagen
Most of the dermis is formed of collagen. On light microscopy collagen is seen as finely woven network of fibers or as
thick bundles. Collagen as a finely woven meshwork of fibers is found in the subepidermal papilla and also in the narrow


10

Histopathology of the Skin

zone between rete ridges and subpapillary blood vessels. The pilosebaceous units and the eccrine and apocrine glands are
also encircled by a thin meshwork of collagen fibers similar to that present in the papillary dermis. Thus the papillary and
the periadnexal dermis forms an anatomical unit, the adventitial dermis. The blood vessels of the dermis are also surrounded
by a thin layer of fine collagen fibers.
In the reticular dermis which is the major portion of the dermis the collagen fibers occur as thick bundles (Fig. 1.16).
These collagen bundles are oriented horizontally and extend into various directions.
Reticulum fibers are special type of very thin collagen fibers, unrecognized with routine stains. In normal skin they are
only present in certain areas like basement membrane zone, the region of the adventitial dermis that lies closest to the
epidermis and its appendages, around blood vessels and as a basket- like capsule around each fat cell. Special stains are
required for identifying reticulum fibers.
Elastic Fibers

Elastic fibers are inconspicuous in routine hematoxylin-eosin stained sections seen under light microscopy.Special stains
such as orcein or resorcin-fuschin are required for their visualization. The elastic fibers are thinner than collagen fibers,
wavy and are found entwined among the collagen bundles. As elastic fibers are wavy , in histopathologic sections they
appear fragmented as only a small part of the fiber is included in any one section. In the lower portion of the dermis,
elastic fibers are thicker and towards the epidermis they become thinner .
Ground Substance
The ground substance is an amorphous structure that fills the spaces between collagen fibers and bundles.
Subcutaneous Fat
Subcutaneous fat consists of lobules composed of adipocytes with cytoplasm markedly expanded by nonvacuolated or
membrane-bound lipid which displaces the cell nucleus eccentrically to produce a thin, fusiform contour compressed
along the inner plasma membrane (Fig. 1.17). The lipid is removed in routinely processed specimens, giving adipocytes
an empty look. The lobules are separated by thin fibrous septae through which small vessels course.

Fig. 1.16: Collagen occurs as finely woven
network of fibers in the subepidermal papilla.
The reticular dermis collagen fibers occur as
thick bundles

Fig. 1.17: Subcutaneous fat showing adipocytes


Histology of Normal Skin

11

Nerves
Skin possesses both somatic sensory and autonomic motor nerves. Two main types of cutaneous sensory receptors are
seen.
• “Specialized” receptors (end organs) and
• “Unspecialized” receptors.

Pacini corpuscles, Meissner's corpuscles and mucocutaneous end organs are the “specialized” receptors. Pacini
corpuscles and Meissner’s corpuscles can be visualized in sections prepared conventionally and stained by hematoxylin
and eosin. They possess terminal nerve endings surrounded by morphologically distinctive lamellar condensations of
connective tissue and Schwann cells. Mucocutaneous end organs on exposure to silver stains are seen to consist of loops
of loosely wound branching axons that form irregular masses.
“Unspecialized” receptors are devoid of distinctive structural features and include most of the sensory nerves that
supply the skin, including those linked to Merkel cells (Figs 1.18 and 1.19).
Blood Vessels
The dermal vasculature consists of a superficial and deep plexuses of arterioles and venules (Fig. 1.20). Communicating
vessels connect superficial and deep plexuses. The deep plexus is situated in the lower part of the reticular dermis at the
dermal-subcutis interface and the superficial plexus is positioned at the junction of the papillary dermis with the reticular
dermis. The arterioles have a homogenous basement membrane, discontinuous subendothelial elastic lamina and 4-5
layers of smooth muscle cells. In contrast, the venules have a multilayer basement membrane along with 5-6 layers of
pericytes. In larger venules the pericytes take on the characteristic of smooth muscle cells and are separated by layers of
elastic fibers.
Capillary networks also surround the sweat glands and hair bulbs. The capillary walls lack elastic fibers and contain
a basement membrane which changes from homogenous to multilayered as the capillary changes from an arteriolar
capillary to a venous capillary.
Lymphatic Vessels
Lymph vessels are difficult to recognize in histologic sections because of their resemblance to blood vessels. In areas of
lymph stasis they are seen as spaces lined only by a few endothelial cells. In contrast to blood capillaries they lack

Fig. 1.18: Peripheral nerve. A thin fibrous
capsule, the perineurium surrounds the bundle
of myelinated nerve axons

Fig. 1.19: Nerve bundle showing wavy nerve
fibers and spindle shaped nuclei

12

Histopathology of the Skin

Fig. 1.20: Blood vessels in the dermis

Fig. 1.21: Oral mucosal epithelium devoid
of granular and horny layer

pericytes and do not possess a basement membrane. The lumina are surrounded by loosely arranged collagen fibers and
elastic fibers.
Mucosal Epithelium
Granular and horny layer is absent in epithelium of the normal oral mucosa with the exception of the dorsum of the
tongue and hard palate (Fig. 1.21). In the absence of granular and horny layer, the epithelial cells migrate from the basal
layer to the surface first appearing vacuolated because of the presence of glycogen, then these cells shrink and finally
desquamate.


Fig. 1.22: Arrector pilorum muscle showing cigar shaped nuclei with
rounded ends. The nucleus is present in the center of muscle cells