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ABDUL-GHANI KIBBI, MD
I. INTRODUCTION:
Dermatologists have a relatively unique opportunity to study, with ease, the clinical
and pathologic correlations of disease. With the naked eye, a disease process can be
clinically observed through its course without need of special techniques such as
intubation or use of X-rays. The skin biopsy technique is fast, simple, and done at
little inconvenience to the patient. The entire spectrum of the disease process can be
correlated clinically and pathologically.
II. Anatomic Features important in the Study of the Pathology of the Skin:
The outer portion of the skin, the epidermis, is a stratified squamous epithelium, with
each layer recognizable. The outer layer is the horny layer, or stratum corneum, made
up of biologically dead, but functionally mature, fully keratinized cells. It usually has
an appearance of faintly woven, thick fibers lying parallel to the surface. Beneath the
horny layer, in sequential order, are the granular layer, one-to-three cells thick; the
squamous cell layer, several cells thick, made up of polygonal cells; and, finally, the
basal layer made up of a single row of basal cells that are cuboidal. the epidermal
cells, or keratinocytes, all connect to each other by intercellular bridges, called also
prickles. These prickles are most obvious in the squamous cell layer, which is
therefore also known as the prickle cell layer. Scattered among the basal cells are the
melanocytes, or pigment-forming cells, which, by light microscopy, have an
apparently clear cytoplasm with a dark staining nucleus.
The epidermis sits upon a basal lamina. Basal cells attach to this structure by half-
desmosomes. The basal lamina separates the epithelium from the connective tissue,
or dermis, below. Over much of the body surface, the epidermis, in its lower portions,
forms rete ridges that insert into the upper layer of the dermis. In histologic section of
the skin that are two-dimensional, the rete ridges appear as downward-pointing ridges
that interdigitate with the upper layer of the dermis. The dermal insertions are called
papillae.
The dermis is composed of two layers, the papillary, or the upper, and the reticular, or
the lower. The dermis rests upon subcutaneous fat, which is made up of lobules of
fatty tissue separated by fine fibrous septae that appear continuous with the collagen
of the reticular layer. The fatty tissues irregularly interdigitate with the reticular layer,
especially around the coils of the eccrine glands and the hair follicles.
The upper, or papillary, layer is made up primarily of fine bundles of collagen that lie
in haphazard arrangement and an admixture of reticulum fibers and elastic fibers.
Other disorders are the result of more than one abnormality of the keratinocyte. For
example, acute eczema is characterized by epidermal hyperplasia and intraepidermal
vesicle formation due to intercellular fluid accumulation (spongiosis); However, the
chronic forms of eczema typically demonstrate only hyperkeratosis and hyperplasia.
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1. Hyperkeratosis-Ichthyosis Vulgaris:
a. Clinical Manifestations:
b. Histopathology:
2. Blistering Disorders:
l) Clinical Manifestations:
2) Histopathology:
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Characteristically these acantholytic cells appear as rounded up cells with a
rim of cytoplasm about half the width of the nucleus. The nuclear detail may
be obliterated by granular basophilic material, or may be obvious with
nucleolus and chromatin disposed around the periphery of the nucleus.
The acantholytic changes may extend down the external root sheath.
1) Clinical Manifestations:
Contact with persons with herpes zoster has frequently been cited as resulting
in the occurrence of chicken pox in susceptible children or adults. Contact
with patients with chicken pox, however, has rarely been cited as resulting in
the occurrence of herpes zoster in a susceptible person.
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2) Histopathology:
The roof of the vesicle is formed by layers of keratinocytes cells that are often
necrotic. The base is made up of basal cells and virus-infected balloon cells.
The underlying dermis contains an inflammatory infiltrate consisting of acute
and chronic inflammatory cells. Vesicles of herpes simplex, herpes zoster,
and varicella all reveal this same basic histopathologic picture.
a. Clinical Manifestations:
b. Histopathology:
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In chronic eczema the epithelium is irregularly thickened, the papillary dermis
is often hyperplastic, and a chronic inflammatory infiltrate is present in the
dermis. Perineural fibrosis is often present in cutaneous nerves in the
superficial portion of these lesions. The reticular dermis is usually unaffected.
The region of the basement membrane, or basal lamina, may be affected in various
ways. There may be striking inflammation of the region and vacuolation, as in lichen
planus, or there may be thickening and vacuolation, as in the epidermolysis-bullosa
group, includes heritable diseases that result in blister formation in the skin in
response to slight trauma. According to ultra structure studies, different types of
epidermolysis bullosa affect different portions of the basement membrane region. The
disorder chosen to illustrate the group, epidermolysis bullosa, dystrophic type
(recessive inheritance), results in a tearing of the epidermis and basal lamina from the
dermis in response to mild trauma. The tear occurs just below the basal lamina in the
upper layer of the papillary dermis. The end result of this tear is the formation of a
subepidermal bulla, the top of which is formed by the epidermis and basal lamina, the
bottom by the dermis.
l. Clinical Manifestations:
2. Histopathology:
A subepidermal bulla is formed. The roof of the bulla is the epidermis, and
the base of the bulla is the dermis. If the section is stained with PAS stain (the
periodic-acid-Schiff reaction), the basement membrane is clearly delineated in
scarlet red as lying above the bulla attached to the epidermis.
Alterations in the SVP occurring in the course of acute inflammatory disorders may
vary from slight increases in permeability that result in the accumulation of fluid in
the papillary dermis that can be reabsorbed within hours, to marked increase in
permeability of vessels with exudation of fibrin, red blood cells, various inflammatory
cells with embarrassment of oxygen of the epidermis and resulting focal infarction
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and/or bulla formation. Any inflammatory reaction that is present for several hours
and involves the SVP will have some effect on the epidermis. Epidermal alterations
range from mild spongiosis to frank necrosis and bullae formation.
l. Clinical Manifestation:
As already pointed out, when systemic diseases affect the skin, they involve
principally the reticular layer of the dermis and spare the "reactive unit" involved in
diseases that are primarily cutaneous, that is, the unit consisting of the epidermis and
the papillary layer of the dermis and its capillary and venule.
l. Clinical Manifestations:
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Scleroderma occurs in two forms: a localized form and a systemic form. The
localized type, called morphea, affects the skin and the subcutaneous tissue
below the involved skin. The lesions are usually well circumscribed. They are
smooth -surfaced and shiny, and they frequently have a grey-white color
surrounded by a violaceous halo. They are typically firm, and the skin feels
taut. A linear form of morphea occurs.
2. Histopathology:
Biopsies taken from ivory-colored areas of morphea and from areas of the skin
involved in progressive systemic sclerosis show similar finding. The dermis
appears thickened. There is hypertrophy of the collagen bundles. Hair
follicles and sebaceous glands are absent; however, sweat glands, which
are normally surrounded by fat, persist and are completely entrapped by
broad collagen fibers. Broad collagen bands streak into the
subcutaneous fat, which may appear atrophic. In systemic scleroderma, many
of the visceral changes are related to extensive fibrosis of the organs.
C. Granulomatous Dermatitis:
A. Disorders in which blood vessels are primarily affected but where the major
change is in the panniculus - erythema nodosum.
l. Clinical Manifestations:
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especially the lower extremities and is usually associated with fever, some
malaise, and sometimes with arthralgias. The course of erythema nodosum
is usually circumscribed and the syndrome is generally considered to be
an allergic or reactive process occurring either idiopathically or in response
to a variety of systemic illnesses, infections or drugs. More exactly, the
lesions vary in size from l to 5 centimeters. They are present on the
anterior aspects of the legs, occasionally on the extensor aspects of the
arms, and have been noted as well on the trunk. They are bright to deep
red, and at times hemorrhagic. They may be slightly elevated or
nodular and are often surrounded by a zone of erythema. The lesions
may last anywhere from a week to several months. The systemic symptoms
associated may include arthralgias, malaise, gastro-intestinal disturbances,
and fever, sometimes as high as l03 -l05 F. The different illnesses that
may be associated with this disorder are: sarcoidosis, coccidior mycosis,
tuberculosis, streptococcal infection, "collagen" diseases and others. The
lesions may occur in response to drugs, especially sulfonamides or halides.
2. Histopathology:
Erythema nodosum is typically a septal panniculitis. The septa are the site of
marked edema, infiltration with acute and chronic inflammatory cells and a
deposition of fibrin in the collagen. The venules are involved with a
perivascular inflammatory infiltrate, and there may be fibrin deposited about
these vessels. At times, medium sized veins may also be involved with
inflammation and exhibit fibrin deposited in their walls. Hemorrhage
accompanies these changes. The lobules of fat are principally spared in
erythema nodosum, save for a few foci of infiltration by lymphocytes along
the septa. Fat necrosis is not a prominent feature of this disorder. In
addition, erythema nodosum is frequently associated with a perivenular
lymphosytic infiltrate in the dermis.
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General References:
Wolff K, Kibbi A-G, and Mihm Mc, Jr.: Basic pathologic reactions of the skin. In
TB
Fitzpatrick, et. al. (Eds) Dermatology in General Medicine. New York: McGraw-Hill
Co., l986.
Lever, W.F., & Schaumburg-Lever, G. Histopathology of the skin. 5th edition. J.B.
Lippincott Co., l975.
Icthyosis:
Pemphigus:
Elias, P.M., et al. Childhood pemphigus vulgaris. NEJM 287: 758 -760, l972.
Eczema:
Mihm, M.C. Soter, N.A., Dvorak, H.F. and Austen, K.F. The structure of normal skin
and the morphology of atopic eczema. J. of Invest. Derm. 67: 305-312. 1976.
Prose, P.H., Pathologic changes in eczema. J. Pediat. 66: 178 - 199, l965.
Epidermolysis Bullosa:
Lowe, L.B. Hereditary Epidermolysis Bullosa. Arch. Derm. 95: 587-595, l967.
Erythema Multiforme:
Scleroderma
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Fleischmajer, R., Damiano, V. and Nedwick, A. Alteration of subcutaneous tissue in
systemic scleroderma. Arch. Derm. l05: 59, l972.
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