SKIN PATHOLOGY NOTES (BS)

General Remarks

1. The epidermis is composed of stratified squamous epithelium with the following layers:
* stratum corneum composed of anucleate, cornified cells
* the stratum granulosum, or granular layer, containing squamous cells with basophilic
straining keratohyaline granules; the stratum spinosum composed of squamous cells
with intercellular attachments appearing like bridges between cells.
* basal cell layer (stratum basale) where new cells are manufactured (stem cells) and
eventually displaced upward to displace old cells.
2. Mitotic activity in normal skin should be limited to the basal portion of the epithelium.
3. Melanin is synthesized in melanocytes, which are derived from neural crest cells and are
located in the epidermis.
* melanosomes are organelles that synthesize melanin.
* melanin is formed when the enzyme, tyrosinase, converts tyrosine to 3,4
dihydroxyphenylalamine, which, in turn, is polymerized in the Golgi apparatus into
membrane bound organelles called melanosomes.
* skin color is based on the number and size plus packaging of melanosomes in cells
other than the one in which they are formed.
* melanin granules are transferred by dendritic processes from melanocytes to
keratinocytes which serves to protect the skin from UV light.
* Blacks have the same number of melanocytes as whites, but the melanocytes are larger
and have more dendritic processes.
* both sunlight and ACTH (ectopic production of decreased cortisol feedback) stimulate
melanin synthesis.
4. Langerhans cells are antigen-processing cells located in the epidermis that contain Birbeck
granules, the same granules that are seen in eosinophilic granulomas.
5. Merkel cells are neuroendocrine cells in the basal layer of the epidermis that have
neurosecretory granules like those seen in small cell (oat cell) carcinomas of the lung and
other neuroendocrine tumors.
* may have tactile function
6. The term hyperkeratosis refers to increased thickness of the stratum corneum, which
clinically presents as a white patch (leukoplakia).
7. Rete ridge hyperplasia refers to the accentuation of the basal cell layer of the epidermis into
the underlying superficial dermis giving a saw-tooth appearance.
8. Spongiosis refers to the accumulation of fluid between keratinocytes that may lead to
vesicle formation manifested as blisters on the skin.
9. Parakeratosis refers to the persistence of nuclei in the stratum corneum layer.
10. Acanthosis refers to generalized thickening of the epidermis, which most commonly (MC)
is secondary to hyperkeratosis.
11. Acantholysis refers to the separation of epidermal cells usually as the result of an
immunologic destruction of the intercellular bridges as in pemphigus.
12. A pustule refers to a pus-filled abscess within the epidermis.
13. Dyskeratosis refers to premature keratinization and early cell death.

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14. Grentz zone is a zone of sparing beneath the epidermis (characteristic of lepromatous
leprosy)
15. Liquefactive degeneration refers to vacuolization of the keratinocytes in the basal cell
layer) characteristic of lupus involvement of skin).
16. Nummular means coin shaped (e.g., nummular eczema, tinea corporis).
17. A macule is a colored lesion on the epidermis that is not elevated.
18. A papule is a peaked area of elevation on the epidermis that is less than 5 mm in diameter.
19. A plaque is a flattened, elevated area on the epidermis that is greater than 5 mm (e.g.,
psoriasis).
20. A vesicle is a fluid filled blister that is less than 5 mm.
21. Type IV collagen is in the basement membrane.
22. The dermis is composed of papillary dermis and reticular dermis.
* papillary dermis is directly below the epithelium; loose connective tissue; commonly
altered with epidermal diseases, particularly the vasculature (e.g., psoriasis).
* reticular dermis contains most of the dermal collagen; more often involved in systemic
diseases (e.g., PSS).
23. Functions of the skin include:
* protective function against microorganisms (T. pallidum, filariform larvae of
Strongyloides, Larvae of hookworm can penetrate intact skin).
* regulation of temperature
* immune function (keratinocytes and Langerhans cells)

Infections Involving Skin

Viral Diseases
1. Human papillomavirus types 6 and 11 Æcondyloma acuminta (venereal warts).
2. Molluscum contagiosum is characterized by a bowl shaped lesion filled with keratin, the
latter containing the viral inclusions (molluscum bodies) in the squamous cells.
* poxvirus
* disseminated in AIDS
3. Measles (rubeola)
* incubation period 7 to 14 days (only common childhood virus with incubation under 2
weeks); extremely contagious.
* begins with fever (up to 40 degrees C), cough, conjunctivitis (photophobia is first sign),
and coryza (excessive mucous production)Æfollowed by Koplik's spots (red with white
center) in the mouth, posterior cervical Lymphadenopathy, and a generalized,
blanching, maculopapular, brownish-pink rash (viral induced vasculitis) beginning at
the hairline and extending down over the body which gradually resolves in 5 days with
some desquamation.
* unlike German measles, rubeola is not associated with fetal congenital anomalies.
* otitis media MC complication Æsecondary bacterial.
* pneumonia MCC death; characteristic Warthin Finkeldey giant cells (lymph nodes,
lung, appendix).
* other complications:
- subacute sclerosing panencephalitis (SSPE) months to years later with extensive
demyelination; latent virus infection Ædeath; encephalitis.

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 * an attenuated live vaccine; part of MMR vaccine (mumps, measles, rebels)Ægiven at
15 months.
4. German measles (rubella)
* sometimes called "three day measles".
* incubation 14-21 days; infectious 7 days before the rash and 14 days after the onset of
the rash.
* in adults, rubella present with fever, headache, and painful postauricular
Lymphadenopathy 1 to 2 days prior to the onset of rash, while in children, the rash is
usually the first sign.
- rash (vasculitis) consists of tiny red to pink macules (not raised) that begins on the
head and spreads downwards and disappears over the ensuing 1-3 days; rash tends
to become confluent.
- 1/3rd of young women develop arthritis due to immune-complexes.
- splenomegaly (50%)
* rubella contracted during pregnancy produces teratogenic effects in the developing
fetus--see Genetics Notes.
* an attenuated live vaccine is available and should not be given to a pregnant woman;
part of MMR vaccine (mumps, measles, rubella)Ægiven at 15 months.
5. Parvoviruses
* smallest DNA virus
* erythema infectiosum (fifth disease) is characterized by a confluent rash usually
beginning on the cheeks ("slapped face") which extends centripetally to involve the
trunk; fever, malaise and respiratory problems; and arthralgias and joint swelling
(50%).
* other associations:
- aplastic anemia in patients with chronic hemolytic anemias (e.g., sickle cell disease,
spherocytosis).
- repeated abortions associated with hydrops fetalis.
- pure RBC aplasia by involving the RBC precursors (no reticulocytes peripherally).
-chronic arthritis
6. Smallpox (variola)
* vesicles are well synchronized (same stage of development) and cover the skin and
mucous membranes.
* vesicles rupture and leave pock marks with permanent scarring.
* vaccine available
7. Herpes simplex is subdivided into type 1 and 2, the former usually developing lesions
around the lips and mouth and the latter producing vesicular lesions in the genital region
(see Gynecology notes).
* contracted by physical contact; incubation 2-10 days.
* primary HSV I usually is accompanied by systemic signs of fever and
Lymphadenopathy, while recurrent herpes is not associate with systemic signs.
* dentists often become infected by contact with patient saliva and often develop
extremely painful infections on the fingers (herpetic whitlow).
* Herpes viruses remain dormant in sensory ganglia and are reactivated by stress,
sunlight, menses, etc.

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 * Herpes gingivostomatitis is MC primary HSV 1 infectionÆpainful, vesicular eruptions
that may extend for the tongue to the retropharynx.
* Herpes keratoconjunctivitis (HSV 1)--see CNS notes
* Kaposi's varicelliform eruption refers to an HSV 1 infection superimposed on a
previous dermatitis, usually in an immunodeficient person.
* laboratory: culture; ELISA test on vesicle fluid; intranuclear inclusions within
multinucleated squamous cells in scrapings (Tzanck preps) of vesicular lesions.
8. Chickenpox (varicella)
* primarily a childhood disease (70%)
* incubation period 14-16 days; highly contagious; infectious 2 days before the vesicles
until the last one dries.
* present with generalized, intensely pruritic skin lesions starting as
maculesÆvesiclesÆpustules (MVP-most valuable player) usually traveling
centrifugally to the face and out to the extremities; unlike smallpox vesicles,
chickenpox vesicles appear in varying stages of development as successive crops of
lesions appear; intranuclear inclusions similar to HSV.
* pneumonia develops in 1/3 of adults; MCC death in chickenpox.
* association with Reye's syndrome if child takes aspirin.
9. Herpes zoster, or shingles
* represents reactivation of a latent varicella-zoster infection.
* virus lies dormant in sensory dorsal root ganglia and when activated involves the
distribution (dermatome) of the sensory nerve with a painful vesicular eruption.
* trigeminal verve distributionÆRamsay Hunt syndrome
* may indicate the presence of advanced neoplastic disease or be a complication of
chemotherapy.
10 Roseola
* alias exanthem subitum; caused by Herpes virus type 6.
* children 6 months to 2 years old; spring and fall; incubation 10-15 days.
* sudden onset of a high fever with absence of physical findings; febrile convulsions are
particularly common.
* fever falls by crisis on the 3rd or 4th dayÆ48 hours after temperature returns to normal
Æmacular or maculopapular rash starting on the trunk and spreading centrifugally.
11. The verruca, or the common wart, is caused by papovaviruses, which produce a
hyperplastic epidermal lesion located on the hands or soles of the feet.
* hyperkeratosis and papillary epidermal hyperplasia are present.

Bacterial

1. Staphylococcal aureus
* cutaneous infections
- furuncles (boils)
- carbuncles (more complicated furuncle with multiple sinuses)
- impetigo (often mixed with Streptococcus and has a more bullous appearance than
crusted)
- hidradenitis suppurative (abscess of apocrine glandsÆe.g., axilla)
- nail bed (paronychial infection)

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 - postoperative wound or stitch abscess
- postpartum breast abscesses
* toxin related skin rashes
- infants and young children develop toxic epidermal necrolysis or Ritter's syndrome
(scalded baby syndrome)Ælarge, red areas of denuded skin and generalized bulla
formation.
- toxic shock syndrome (TSS) is due to a toxin producing strain of Staphylococcus
aureus (bacteriophage induced) usually, but not exclusively in tampon wearing
(hyperabsorbent type), menstruating women; 1-4 day prodrome of high fever,
myalgias, arthralgias, mental confusion, diarrhea and on erythematous rash that
occurs during or soon after menses; rash predominantly on hands and feet with
eventual desquamation in 5-12 days.
2. Group A Streptococcus
* scarlet fever usually begins as a Streptococcal pharyngitis/tonsillitis and then develops
an erythematous rash beginning on the trunk and limbs with eventual desquamation.
- rash is due to elaboration of erythrogenic toxin by the organism
- face is usually spared, but, if involved there is a characteristic circumoral pallor and
the tongue becomes bright red, thus the term "strawberry tongue".
- post-streptococcal immune complex glomerulonephritis is a possible sequela of
scarlet fever.
- Dick test is a skin test that evaluates immunity against scarlet fever; no response
indicates immunity (anti-toxin antibodies present); erythema indicates no immunity.
* impetigo due to Streptococcus pyogenes is characterized by honey colored, crusted
lesions, while those with a predominantly bullous pattern are primarily due to
Staphylococcus aureus.
* cellulitis with lymphangitis ("red streaks") is characteristic of Streptococcus pyogenes.
- hyaluronidase is a spreading factor that favors the spread of infection throughout
the subcutaneous tissue unlike Staphylococcus aureus which generates coagulase to
keep the pus confined.
* erysipelas refers to a raised, erythematous ("brawny edema"), hot cellulitis, usually on
the face that commonly produces septicemia, if left untreated.
3. Bacillus anthrax
* large Gram (+) rods that produce heat resistant spores; Clostridia and Bacillus species
are the two bacterial spore formers; they do not form spores in tissue; produces a
powerful exotoxin.
* contracted by direct contact with animal skins or products (MC sheep and cattle--
veterinarians) and entry of the organisms through abrasions or cuts; through inhalation;
or through ingestion of contaminated meat.
* four forms of anthrax are recognizedÆcutaneous (MC), pulmonary, oral-
oropharyngeal, and gastrointestinal.
* cutaneous anthrax (90 to 95% of cases) occurs through direct contact with infected or
contaminated animal products.
- lesions resemble insect bites but eventually swell to form a black scab, or eschar,
with a central area of necrosis ("malignant pustule").
* pulmonary form is almost always fatal.

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 - inhalation of spores in contaminated hides (e.g., woolÆWoolsorters disease) with a
necrotizing pneumonia.
- used in germ warfare.
4. Mycobacterium leprae
* cannot be cultivated in culture media; can survive in the footpad of mice; resident and
can be grown in armadillos.
* leprosy, or Hansen's disease, has localized endemic areas in the United States including
Texas, Louisiana, Florida, California, and Hawaii.
* organisms have low infectivity and the disease is contracted from direct contact with
active cases or by droplet infection.
* based on host resistance, the disease is subdivided into tuberculoid, lepromatous, and
indeterminate types.
* tuberculoid type has intact cellular immunity
- forms granulomas and kill the organisms (very few present).
- evokes a positive lepromin skin test
- localized skin lesions that lack symmetry
- nerve involvement (organisms invade Schwann cells) that dominates the clinical
picture and leads to skin anesthesia, muscle atrophy and autoamputation.
* lepromatous leprosy patients lack cellular immunity
- no granulomas
- organisms readily identified
- negative lepromin skin test
- Bacteremia disseminates to cooler areas like the digits.
- symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals
grentz zone in superficial dermis and then organisms in macrophages.
- neural involvement is a late feature of the disease.
* lepromin skin test is to determine host immunity; not a diagnostic test.
* treatment: dapsone + rifampin
* prognosis: with treatment, excellent prognosis; death usually the result of some other
disease such as infection or secondary amyloidosis.
Fungal
Superficial mycoses overview

1. Superficial mycosesÆoutermost layers of the skin or its appendages; skin, nails and/or
hair.
2. Dermatophytoses transmitted by contact with man (anthropophilic; weak inflammatory
response), animals (zoophilic; brisk inflammatory response), or contact with soil
(geophilic; strongest inflammatory response).
3. TrichophytonÆhair, skin, or nails; MicrosporumÆhair and skin; and
EpidermophytonÆskin alone.
4. The diagnosis is best made by culture of skin scrapings secured from the leading edge of
the lesion.
* use Wood's light to check for fluorescing metabolites.
* direct KOH preparations of the scraped material.
5. Therapy: topical clotrimazole for skin infections; griseofulvin for hair and nail infections
(other agents cannot penetrate hair and nails).

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Superficial mycoses: Tinea
1. Tinea capitis refers to infection of the hair and scalp and is MC in children.
* Microsporum or Trichophyton species but not Epidermophyton; M. canis MC.
* circular, or ringed shaped patches of alopecia ("black dot" remaining of hair) with
erythema and scaling.
* severe inflammatory reaction is called a kerion.
* Trichophyton tonsurans negative on Wood's light exam (endothrix--in hair shaft).
* M. canis Wood's lamp positive (ectothrix--outside hair shaft).
* favus MCC by T. schoenleinii
- eczematous rash and matting of the hair together and replacement of broken off hair
by scaly, yellow crusts with an unpleasant odor.
2. Tinea barbae is infection of the beard hairs.
3. Tinea corporis refers to ringworm of the face, trunk or limbs.
4. Tinea cruris is "jock itch".
5. Tinea unguium is infection of the nails.
6. Tinea pedis is "athlete's foot".

Other Superficial Mycoses

1. Tinea versicolor only grows in the stratum corneum and is caused by Malassezia furfur.
* skin lesions can be hypo or hyperpigmented and produces an uneven tan.
* fluoresce yellow and the organisms are identified in skin scrapings.
2. Piedra, both white and black, primarily infects the hair shafts and not the skin.
3. Candida albicans can also cause cutaneous disease involving
* skin (diaper rash).
* nails (onychomycosis).

Subcutaneous Mycoses
1. Subcutaneous mycoses are usually related to traumatic implantation into the skin.
2. Chromoblastomycosis, or verrucous (wart-like) dermatitis, is a chronic skin lesion
associated with several pigmented fungi (Fonsecaea, Phialophora, and Cladosporium).
* granulomatous reaction in subcutaneous tissue are pigmented, thick walled bodies are
visible in tissue section.
3. Mycetomas (maduromycosis) are characterized by a localized, tumorous nodule (usually
foot) that occurs in response to chronic progressive destruction of skin, subcutaneous
tissue, fascia, muscle and bone.
* in the United States, they are MCC by Pseudallescheria boydii, but in other countries
they can be associated with Actinomyces, Nocardia, Phialophora, Aspergillus, and even
bacteria.
* draining sinuses frequently contain granules containing the infecting agent(s).
4. Sporotrichosis is caused by the dimorphous fungus, Sporothrix schenckii.
* traumatic implantation of the fungus growing in soil, thus the association with "rose
gardeners disease".
* MC lymphocutaneous disease Æ painless nodule at inoculation site Æchain of
suppurating subcutaneous nodules that drain to the skin surface along the course of the
lymphatics.

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 * cigar shaped yeast forms are seen in the suppurative nodules and asteroid bodies
(Splendore-Hoeppi phenomenon) are noted within granulomatous microabscesses.
* treatment: oral potassium iodide

Parasitic
1. Leishmania produce 3 kinds of disease in manÆvisceral leishmaniasis (kala azar) due to
Leishmania donovani complex, cutaneous leishmaniasis due to Leishmania tropica
complex, and mucocutaneous leishmaniasis due to Leishmania braziliensis.
* the organism is introduced into man via the bite of an infected sandfly (Phlebotomus)
or by self-inoculation (cutaneous type).
* visceral leishmaniasis is characterized by intracellular invasion of reticuloendothelial
cells by leishmanial forms with massive hepatosplenomegaly and anemia.
* cutaneous (Oriental sore) and mucocutansous leishmaniasis limit themselves to the skin
alone (ulcers) in the former disease and skin plus mucous membranes in the latter
variant.
* the laboratory diagnosis of visceral leishmaniasis is made by performing a bone
marrow aspirate and finding the leishmanial forms in macrophages, by culture, by
hamster inoculation, or by serology.
* the diagnosis of cutaneous or mucocutaneous leishmaniasis is made by biopsy, culture,
skin test, or serologic tests.
* recovery from the cutaneous form incurs immunity.
* treatment: stibogluconate
2. cutaneous larva migrans is caused by dog and cat hookworms, Ancylostoma species.
* it is usually contracted by children playing on sandy beaches or sandy playgrounds.
- the larvae penetrate the skin and produce serpiginous tunnels in the skin which
causes intense pruritus and scratching
- adults do not form in man, only in infected dogs and cats.
* the diagnosis is made by direct observation of the tunnels in the skin
* treatment: ethyl chloride spray and thiabendazole.
3. Wuchereria bancrofti, Brugia malayi (Filariasis)
* the microfilaria of Wuchereria bancrofti or Brugia malayi (nematodes) are transmitted
to man by the bite of infected mosquitoes (Anophele, Aedes, Culex).
* microfilaria characteristically circulate in the bloodstream at night and enter into the
lymphatics, where they mature and produce an inflammatory reaction resulting in
lymphedema (elephantiasis) of the legs, scrotum, etc.
* the laboratory diagnosis is made by finding microfilaria in the blood at night that are
sheathed and lack nuclei in the tail; skin tests; and by serology; peripheral blood
eosinophilia is present.
* treatment: diethylcarbamazine or invermectin.
4. Onchocerca volvulus (Onchocerciasis or River Blindness)
* The microfilaria of Onchocerca volvulus are transmitted to man via the bite of an
infected blackfly (Simulium).
* the larva migrate into the skin and lymphatic tissue.
* larvae can migrate across the eye and produce blindness, thus the name "river
blindness".

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 * adult worms lodge in the lymphatics where they produce subcutaneous nodules and
host an inflammatory response.
* microfilaria do not enter the bloodstream and there is no periodicity.
* other clinical signs include dermatitis, pruritus, and peripheral blood eosinophilia.
* the laboratory diagnosis is made by finding microfilaria in a skin biopsy that are
unsheathed and do not have nuclei extending to the tail.
* treatment: ivermectin and removal of the nodules
5. Loa loa (Loiasis)
* the microfilaria of Loa loa are transmitted to man via the bite of an infected deer fly
(Chrysops).
* microfilaria invade subcutaneous tissue and become adults that discharge microfilaria
into the bloodstream in diurnal (daytime) fashion
* clinically, patients develop swelling of subcutaneous tissue (calabar swelling), pruritus,
conjunctival irritation (microfilaria migration).
* the laboratory diagnosis is made by finding sheathed microfilaria in the blood during
the daytime that have nuclei extending to the tip; eosinophilia is present.
* treatment: diethylcarbamazine
6. Dracunculus medinensis (Dracunculiasis)
* the microfilaria of Dracunculus medinensis (guinea worm) are contracted by man after
eating the fresh water crustacean of the genus Cyclops.
* the microfilaria migrate through the intestinal tract into deep subcutaneous tissue where
they develop into migrating adults that attain great length
* clinically, patients have pruritus, blisters, ulcers, calcification of the organisms in the
tissue, and peripheral blood eosinophilia.
* the laboratory diagnosis is made by finding skin lesions with the adult worm in the
lesion and the larvae in the ulcer
* treatment: mebendazole and removal of the worm.
7. The Black Widow spider (Latrodectus mactans) has a red hour glass on the undersurface of
the thorax (not on dorsal surface) and is very common in the Southern states, Arizona, and
California.
* neurotoxic venom, which produces swelling and intense pain in the area of the bite
(usually the genitalia from sitting in outdoor privies, or the fingers) followed by intense
abdominal contractions that simulate an acute appendicitis.
* other possible sequelae include hemoglobinuria, glomerulonephritis and hypertension
* treatment: intravenous calcium gluconate.
8. The Brown Recluse spider (Loxosceles reclusum, or violin spider) is common in the
Midwest and Southwest.
* the spiders are a glossy brown and have a prominent violin (no stripes) on their dorsum.
* they possess a very powerful necrotoxic venom and their bites are initially painless and
the skin progressively ulcerates.
* treatment: colchicines and dapsone have had some success.
9. Only 2 species of scorpions can cause fatalities in the United States and these are located in
Arizona deserts.
* scorpion venom is neurotoxic and in the non-lethal varieties of scorpions, produces a
local, painful reaction with swelling similar to a bee sting.

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 * in the poisonous varieties, the bite site shows no initial reaction followed by increased
sensation and then no sensation in the area of the bite.
a. eventually, the whole extremity becomes numb, the patient develops increased
blood pressure, and an ascending motor paralysis, which can lead to death.
* treatment: non-lethal Æ cryotherapy and ligature; no specific treatment for the
poisonous species.
10. Mites include chiggers and the human itch mite (scabies, or Sarcoptes scabiei).
* chiggers produce a pruritic dermatitis best treated with topical anti-pruritic agents
(crotamiton and calamine lotion).
* the human itch mite (scabies) causes tissue injury by adult females boring into the
stratum corneum (burrows are visible as dark lines between the fingers at the wrists, on
the nipples or on the scrotum) and laying their eggs at the end of the tunnel, thus
creating an intensely pruritic lesion.
- in adults, the disease is limited to the intertriginous areas and spares the soles,
palms, face and head.
- in infants, there are no burrows and the palms, soles, face and head are involved.
* treatment: topical benzene hexachloride (lindane).
11. Live include the head, body, and the public lice ("crabs")
* Pediculus humanis capitis is the head louse, which lays its "nits", of eggs on hair shafts.
- treatment: benzene hexachloride (lindane)
* Pediculus humanis corporis is the body louse, which lives on the surface of the skin and
breeds in the clothing.
- treatment: benzathine hexachloride (lindane).
* Phthirus pubis is the pubic louse, which lives in the pubic hairs.
- treatment: benzene hexachloride (lindane).

Keratoses (Horny Growth)

1. Seborrheic keratosis is a common benign epidermal tumor composed of basaloid (basal
cell-like) cells with increased pigmentation that produce a raised, pigmented, "stuck-on"
appearance on the skin of middle-aged individuals.
* they can easily be scraped from the skin's surface.
* frequently enlarge of multiply following hormonal therapy.
* sudden appearance of large numbers of Seborrheic keratosis is a possible indication of a
malignancy of the gastrointestinal tract (Leser-Trelat sign).
2. An actinic keratosis is a pre-malignant skin lesion induced by ultraviolet light damage.
* sun exposed areas.
* parakeratosis and atypia (dysplasia) of the keratinocytes.
* solar damage to underlying elastic and collagen tissue (solar elastosis).
* may progress to squamous carcinoma in situ (Bowen's disease) or invasive cancer.
3. A keratoacanthoma is characterized by the rapid growth of a crateriform lesion in 3 to 6
weeks usually on the face or upper extremity.
* it eventually regresses and involutes with scarring.
* commonly confused with a well-differentiated squamous cell carcinoma.

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Disorders with Cysts
1. An epidermal inclusion cyst is derived from the epidermis of a hair follicle and contains
lipid-rich debris intermixed with keratin material, and may be located anywhere on the
body.
* a pilar cyst is similar to an epidermal inclusion cyst except for the absence of a granular
cell layer in the cyst wall, absence of keratin in the cyst, and a location MC on the
scalp.
* epidermal inclusion cysts and pilar cysts commonly rupture and produce a foreign body
giant cell reaction in the underlying superficial dermis.

Adnexal Tumors
1. Adenexal tumors are neoplasms arising from cutaneous appendages that are capable of
pilosebaceous, eccrine or apocrine differentiation.

Bullous and Vesicular Disease

1. There are many diseases characterized by the presence of vesicles and bullae filled with
fluid.
2. In pemphigus vulgaris, large, flaccid bullae filled with fluid occur on the skin and within
the oral mucosa.
* immunologic disease with IgG antibodies against the intercellular attachment sites
between keratinocytes (type II hypersensitivity).
* the vesicle in pemphigus vulgaris has a suprabasal location (just above the basal cell
layer and resembling "tombstones")
* scattered keratinocytes in the fluid as a result of acantholysis.
* Nikolsky's sign is where the epidermis slips when touched with the finger.
* fatal disease if left untreated (systemic corticosteroids)
3. Bullous pemphigoid is an immunologic vesicular disease whose vesicle are in a
subepidermal location.
* circulating IgG antibody against antigens in the basement membrane (type II
hypersensitivity).
4. Dermatitis herpetiformis is an immunologic vesicular lesion characterized by the presence
of IgA immune complexes (type III hypersensitivity) at the tips of the dermal papilla at the
dermal/epidermal junction producing a subepidermal vesicle filled with neutrophils.
* strong association with gluten-sensitive enteropathy, or celiac disease.

Eczematous Dermatitis
1. Eczematous dermatitis includes a large category of skin lesions characterized by severe
pruritus and distinctive gross and microscopic features.
* type I hypersensitivity is involved with atopic dermatitis in patients who have an
allergic history.
* type IV hypersensitivity is involved in contact dermatitis (poison ivy).
* acute eczematous dermatitis is characterized by a weeping, pruritic rash, while a
chronic eczematous dermatitis presents with dry, scaly, plaque-like thickening of the
skin, a process called lichenification.

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Miscellaneous Non-Neoplastic Diseases

1. Urticaria (hives) refers to the presence of edema within the dermis and itchy elevations of
the skin which may relate to either a Type I (MC) or Type III hypersensitivity reaction.
Type III hypersensitivity reaction.
* exaggerated venular permeability MC related to IgE mediated disease and release of
histamine from mast cells.
2. Erythema multiforme is a hypersensitivity reaction to an infection (Mycoplasma), drugs or
various autoimmune diseases.
* probable immunologic disease
* lesions vary from erythematous macules, papules, or vesicles.
* papular lesions frequently look like a target with a pale central area.
* extensive erythema multiforme in children is called Stevens-Johnson syndrome, where
there is extensive skin and mucous membrane involvement with fever and respiratory
symptoms.
3. Erythema nodosum is the MCC of inflammation of subcutaneous fat (panniculitis).
* it may be associated with tuberculosis, leprosy, certain drugs (sulfonamides), and is
commonly a harbinger of coccidioidomycosis and sarcoidosis.
* commonly presents on the lower extremities with exquisitely tender, raised
erythematous plaques and nodules.
* self-limited disease.
4. Acne vulgaris is a chronic inflammatory disorder usually present in the late teenage years
characterized by comedones, papules, nodules, and cysts.
* subdivided into obstructive type with closed comedones (whiteheads) and open
comedones (blackheads) and the inflammatory type consisting of papules, pustules,
nodules, cysts and scars.
* pathogenesis of inflammatory acne relates to blockage of the hair follicle with keratin
and sebaceous secretions, which are acted upon by Propionibacterium acnes (anaerobe)
that causes the release of irritating fatty acids resulting in an inflammatory response.
* pathogenesis of the obstructive type (comedones) is related to plugging of the outlet of
a hair follicle by keratin debris.
* chocolate, shellfish, nuts iodized salt do not aggravate acne.
* obstructive type is best treated with benzoyl peroxide and triretnoin (vitamin A acid)
* treatment of inflammatory type is the above plus antibiotics (topical and/or systemic;
erythromycin, tetracycline, clindamycin).
5. Lichen planus is an itchy, violaceous, flat-topped papule highlighted by white dots or lines
called Wickham's striae.
* lichen planus may occur in the oral mucosa, where it has a fine white net-like
appearance.
* increased epidermal proliferation; ? immunologic; initiated by epidermal injury from
drugs, viruses, or topical agents.
* characteristic histologic features include:
- hyperkeratosis
- absence of parakeratosis
- prominent stratum granulosum
- an irregular "saw toothed" accentuation of the rete pegs.

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 - dermal-epidermal junction obscured by a band-like infiltrate of lymphocytes.
6. Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which
histologically are secondary to epidermal proliferation.
* genetic factors (HLA relationships), environmental (physical injury, infection, drugs,
photosensitivity), abnormal cellular proliferation (deregulation of epidermal
proliferation) and microcirculatory changes in the papillary dermis (diapedesis of
neutrophils into the epidermis) are all interrelated.
* the plaques of psoriasis are characteristically well-demarcated pink or salmon colored
lesions covered by a loosely-adherent silver-white scale which, when picked off,
reveals pinpoint bleeding sites (Auspitz sign).
* the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a
yellowish-brown discoloration of the nail plate.
* the characteristic histologic features of psoriasis include:
- hyperkeratosis
- absence of the granulosa cells (present in lichen planus).
- parakeratosis
- regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen
planus) with vessel proliferation in the papillary dermis (reason for the bleeding
associated with Auspitz sign).
- characteristic subcorneal collection of neutrophils called a Munro's microabscess
(diapedesis from vessels in papillary dermi).
* 7% develop HLA B27 positive psoriatic arthritis (see Connective Tissue Disease
Notes).
7. Ichthyosis vulgaris is a genetic disease characterized by increased cohesiveness of the cells
in the stratum corneum, resulting up in a piling up stratum corneum (scales like a fish).
8. Vitiligo is an autoimmune destruction of melanocytes resulting in areas of depigmentation.
* commonly associated with other autoimmune diseases such as pernicious anemia,
Addison's disease, and thyroid disease.
* common in the Black population
9. Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a
phenotypic marker for an insulin-receptor abnormality as well as a marker for
adenocarcinoma, most commonly of gastric origin.
10. A dermatofibroma is a benign tumor of the dermis, MC located on the lower extremity,
where it has a nodular, pigmented appearance.
* composed of benign histiocytes.
11. A nevus refers to any congenital lesion of the skin, while a nevocellular nevus specifically
refers to a benign tumor of neural crest-derived cells that include modified melanocytes of
various shapes (nevus cells).
* nevocellular nevi are generally tan to deep brown, uniformly pigmented, small papules
with well-defined, rounded borders.
- most nevocellular nevi are subdivided into junctional, intradermal, or compound
types.
- most nevocellular nevi begin as junctional nevi with nevus cells located along the
basal cell layer producing small, flat lesions, which are only slightly raised.

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 - junctional nevi usually develop into compound nevi as nevus cells extend into the
underlying superficial dermis forming cords and columns of cells (compound: nevi
at junction and in the dermis).
- eventually, the junctional component of a nevocellular nevus is lost, leaving only
nevus cells within the dermis, thus the term intradermal nevus.
- junctional Æ compound Æ intradermal nevus.
* although uncommon, certain nevi may evolve into a malignant melanoma, particularly
those which are congenital and those which are referred to as dysplastic nevi.
- a dysplastic nevus is commonly associated with patients who have multiple
scattered nevi over the entire body (dysplastic nevus syndrome) with individual
lesions that have a diameter greater than 1 cm.
12. Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
* due to Pitysporium species
* can be seen in AIDS as an opportunistic infection
13. Lupus erythematosus
* chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin
and other systems.
* pathogenesis: light and other external agents plus deposition of DNA (planted antigen)
and immune complexes in the basement membrane.
* histology:
- basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia)
are vacuolated (liquefactive degeneration)
- thickening of lamina densa as a reaction to injury.
- immunofluorescent studies reveal a band of immunofluorescence (band test) in
involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
- lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.

Malignant Diseases of Skin

1. Bowen's disease refers to a carcinoma in situ on sun-exposed skin or on the vulva, glans a
penis, or oral mucosa which has an association, in some cases, with a visceral malignancy.
2. Skin cancers associated with ultraviolet light damage include basal cell carcinoma,
squamous cell carcinoma, and malignant melanoma.
3. A basal cell carcinoma (BCE) is the MC malignant tumor of the skin and occurs on sun-
exposed, hair-bearing surfaces.
* BCE's are locally aggressive, infiltrating cancers arising from the basal cell layer of the
epidermis and infiltrate the underlying superficial dermis.
* they do not metastasize
* BCE's are commonly located on the face on the inner aspect of the nose, around the
orbit and the upper lip where they appear as raised nodules containing a central crater
with a pearly-colored skin surface and vascular channels.
* microscopically, they have cords of basophilic staining cells originating from the basal
cell layer infiltrating the dermis.
* they commonly recur if they are not totally excised, because they are frequently
multifocal.

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 * the basal cell nevus syndrome is an autosomal-dominant disorder characterized by the
development of basal cell carcinomas early in life with associated abnormalities of
bone, skin, nervous system, eyes, and reproductive system.
4. Squamous cell carcinomas (SCC) of the skin have a low but significant potential for
metastasis, the latter more likely to occur if the cancer is on a mucosal surface.
* SCCs are commonly located on the face and favor areas such as the ears, nose, and
lower life (BCE upper lip).
* occur secondary to:
- ultraviolet light damage
- arsenic ingestion
- chronic ulcers or sinus tracts
- chewing tobacco (inside mouth)
- radiation
- burn scars
- patients who are immunocompromised
* gross:: shallow ulcer with a raised edge.
* microscopic: usually well differentiated tumor with invasion of the dermis; often
confused with keraroacanthoma.
* unlike BCEs, SCCs may develop on both sun-exposed and non exposed areas of the
body, the latter areas more likely to metastasize.
5. Malignant melanomas derive from melanocytes.
* the incidence of malignant melanoma is increasing in the United States, which may in
part be explained by an increase in outdoor recreational activities.
* affects both sexes equally, is more common in whites than blacks, and has a
predilection for fair skinned, blue eyed persons with red or blonde hair.
* they can arise de novo, from a preexisting lesion (e.g. congenital nevus, dysplastic
nevus), or from a lentigo maligna.
* most variants have an initial radial growth phase that lasts for a few years to a decade of
longer.
- during this phase, the melanocytes proliferate laterally within the epidermis,
dermoepidermal junction, or the papillary dermis.
- metastasis does not occur while malignant melanoma is in this phase.
- after a variable amount of time, they may enter a vertical growth phase, where the
malignant melanocytes penetrate into the underlying reticular dermis.
- the appearance of a nodule along the lateral margin of the radial growth phase is a
marker for the vertical phase.
* exposure to excessive sunlight is the single most important predisposing cause of
malignant melanoma.
* superficial spreading melanoma is the MC type of melanoma.
- it primarily affects women over 50 years of age
- the lower extremities and back are the MC locations
* lentigo maligna melanoma is an extension of a lentigo maligna.
- it primarily occurs on the sun exposed face in elderly people.
- it has an irregular, mottled pigmentation.
- the radial growth phase occurs over 10 to 15 years before entering a vertical growth
phase.

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 * nodular melanoma is a particularly aggressive type of melanoma that is more common
in elderly men than in women.
- it lacks a radial growth phase and invades into the dermis.
* acral lentiginous melanoma is the least common type of melanoma in the white
population.
- however, it has an increased incidence in the black population, who as a rule, are
not predisposed to melanomas by virtue of the protective effect of melanin against
ultraviolet light.
- it occurs on the palms, soles or in subungual regions.
* excisional biopsy is the recommendation for all suspicious lesions.
* the stage of the disease is the single most important prognostic factor.
- the Breslow system measures the depth of invasion from the outermost granular
layer to the deepest margin of the tumor.
- in general, lesions with less than 0.76 mm of invasion do not metastasize, while
those over 1.7 mm of invasion have lymph node metastasis.
- the Clark system uses levels of invasion from level I to V.
* the overall 5 year survival is 81%
- nodular melanomas and acral lentiginous melanomas have the worst prognosis.

Porphyria
1. The classification for porphyria may be based on the tissue of origin of excess metabolites
or on the clinical manifestations of the disease.
2. The two MC porphyries in the United States are acute intermittent porphyria (AIP) and
porphyria cutanea tarda (PCT).
3. Porphyrins are involved in oxidative or oxygen-transferring functions and are precursors
for heme synthesis.
* enzyme defects in the heme synthesis pathway account for the clinical porphyries (refer
to the chart)

LA synthase (↑ AIP)
lycine + succinyl CoA---Æ
Delta aminolevulinic acid
↓
↓ ALA dehydrase
Porphobilinogen
↓
↓ Uroporphyrinogen synthetase
↓ (↓ AIP)
↓ Uroporphyrinogen isomerase
Uroporphyrinogen III
↓ Uroporphyrinogen
↓ decarboxylase (↓ PCT)
Coproporphyrinogen III
↓
Protoporphyrinogen IX
↓
Protoporphyrin IX
↓ + iron
Heme

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 * ALA synthetase is the rate-limiting enzyme in heme synthesis and has a negative
feedback with its end product, heme.
* when drugs are being metabolized in the liver by the cytochrome-P 450 system, heme is
utilized in the process and is decreased, thus allowing ALA synthetase activity to go
unchecked, which may precipitate an acute porphyria attack.
* porphyrinogen compounds, or reduced porphyrin compounds, are colorless and non
fluorescent in the reduced state; but, when "oxidized" in voided urine upon exposure to
light, they become "porphyrins" and have a wine-red color.
* oxidized porphyrins under UV light have an intense reddish-orange fluorescence.
* in certain porphyrias (PCT), porphyrins in the peripheral circulation absorb UV light
near the skin surface, and become photosensitizing agents, which can damage the skin
and produce vesicles and bullae.
4. Acute intermittent porphyria (AIP) has two basic defects: increased activity of ALA
synthetase and decreased activity of uroporphyrinogen synthetase.
* the net effect of the two defects in AIP is an excessive quantity of delta aminolevulinic
acid (ALA) and porphobilinogen (PBG)
* autosomal dominant disease characterized by intermittent exacerbations of neurologic
dysfunction including psychosis, neuropathy, severe colicky abdominal pain, the latter
often mistaken for a surgical emergency necessitating an operation.
- a patient with AIP presenting with abdominal pain often has the classic "bellyful of
scars" from previous surgeries.
* AIP is often precipitated by drugs, which induce hepatic ALA synthetase activity by the
mechanisms previously discussed.
- drugs which may precipitate AIP include alcohol, oral contraceptives, barbiturates,
phenytoin, and numerous others.
* the classic laboratory findings in AIP include a colorless fresh-voided urine which,
when left standing in light, will turn a wine-red color (window sill test).
- measurement of RBC uroporphyrinogen synthetase activity reveals decreased levels
even when the patient is asymptomatic and is also a good method for detecting
carriers of the trait as well.
- there are increased amounts of porphobilinogen in urine, as well as increased
amount of ALA in AIP.
* patients commonly have inappropriate ADH syndrome with hyponatremia MC related
to CNS damage and the organic brain syndrome.
5. Porphyria cutanea tarda (PCT) is due to decreased activity of uroporphobilinogen
decarboxylase.
* the net result of the enzyme defect in PCT is an increased excretion of uroporphyrin, a
slight increase in formation of coproporphyrins and normal porphobilinogen levels.
* like AIP, PCT is often precipitated with drugs, the two MC being alcohol and oral
contraceptives.
* clinical:
- photosensitive skin lesions in sun-exposed areas
- hyperpigmentation
- fragile skin and increased hair, the latter findings often exaggerated in the numerous
Werewolf horror stories on TV.
* laboratory:

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 - inspecting voided urine, which is a wine-red color secondary to uroporphyrins.
- normal porphobilinogen levels in the urine.
- decreased RBC uroporphyrinogen decarboxylase in red blood cells.

Skin Pathology Test Questions

1. Benign crateriform lesion often confused grossly and histologically as a well differentiated
squamous carcinoma.
Answer: keratocanthoma
2. Marker for gastric carcinoma and insulin receptor deficiency.
Answer: acanthosis nigricans
3. Crateriform lesion commonly located on the inner aspect of the nose, the eyelid, and the
upper lip; most common skin cancer; invades but rarely metastasizes.
Answer: basal cell carcinoma
4. Bullseye appearing lesion associated with the Stevens Johnson syndrome and Mycoplasma
pneumonia.
Answer: erythema multiforme
5. Lacy appearing white lesion on the oral mucosa; Wickham's stria.
Answer: lichen planus
6. Malignant melanoma commonly located on the face.
Answer: lentigo maligna melanoma
7. Malignant melanoma with no radial growth phase; very poor prognosis.
Answer: nodular melanoma--depth of invasion is the key to prognosis in any melanoma.
Clark and Breslow's system
8. Erythematous, weeping lesion associated with pruritus.
Answer: acute eczematous dermatitis
9. Raised, pigmented, verrucoid appearing lesion with a stuck on appearance; if suddenly
increased in number suggests gastric malignancy (Leser-Trelat sign).
Answer: Seborrheic keratosis
10. Scaly dermatitis on the scalp and face; due to Pitysporium species; can be seen in AIDS as
an opportunistic infection.
Answer: Seborrheic dermatitis
11. Cancer associated with chronic sinus tracts on the skin; associated with sun exposure;
metastasizes if on mucosal surfaces; lower lip.
Answer: squamous carcinoma
12. Malignant melanoma with Pagetoid appearing cells in the epidermis; most common
malignant melanoma.
Answer: superficial spreading melanoma
13. Porphyria associated with a "belly full of scars"; precipitated by alcohol and drugs; no skin
lesions; dementia; increased activity of ALA synthetase and decreased activity of
uroporphyrinogen synthetase; window sill test; increased porphobilinogen and delta ALA
in urine.
Answer: acute intermittent porphyria
14. Porphyria associated with a deficiency of uroporphyrinogen carboxylase; hypertrichosis;
photophobia; precipitated by drugs; photosensitive skin lesions; increase in urine
uroporphyrin and coproporphyrins.
Answer: porphyria curanea tarda

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15. Autoimmune bullous disease with flaccid vesicles in a suprabasal location; tombstone
effect of basal cells at base of vesicle; Nikolsky sign (rub off skin with gentle pressure);
acantholytic squamous cells in vesicle fluid.
Answer: pemphigus vulgaris
16. Vesicular disease associated with celiac disease; subepidermal bullae; vesicle fluid with
neutrophils.
Answer: dermatitis herpetiformis
17. The common wart; papovavirus.
Answer: verruca vulgaris
18. Autoimmune vesicular disease with vesicles in a subepidermal location.
Answer: bullous pemphigoid
19. Painful nodule on the lower leg associated with coccidioidomycosis and sarcoidosis;
inflammation of fat.
Answer: erythema nodosum
20. Silver white patches which have pinpoint areas of hemorrhage when picked off (Auspitz
sign); Munro's microabscesses in epidermis; pits in nails; HLA B27 positive destructive
arthritis; hyperkeratosis, parakeratosis and accentuation of rete ridges; methotrexate
excellent therapy.
Answer: psoriasis
21. Premalignant skin lesion secondary to ultraviolet light damage.
Answer: actinic keratosis--if carcinoma in situ, Bowen's disease.
22. The common mole; dysplastic type can predispose to cancer; junctional, compound and
intradermal types.
Answer: nevocellular nevus
23. Plugging of the hair follicle with inflammatory response due to release of irritating fatty
acids; Propionibacterium involved.
Answer: acne vulgaris
24. Type of malignant melanoma that occurs under the nails or on the palms or soles of the
feet; poor prognosis; can be seen in Blacks; unlike the other types.
Answer: acral lentiginous malignant melanoma

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