DERMATOPATHOLOGY: LECTURE 1 – Cutaneous Tumors Mon.

09/13/10

Normal Histology:

3 main layers. Hair follicles, sebaceous glands, etc. within.

• Many tumors originate from epidermis –

probably because it is the most superficial.
• Stratum corneum is outermost layer. Site of
keratinocytes being continuously sloughed off
– keratinocytes have lost nuclei.
• S. granulosum – cells are identifiable by
bluish granules in the cytoplasm.
• S. spinosum – can see web-like connections.
• Lamina densa = basement membrane.
Attaches epidermis to dermis.
• Merkel cell – involved in mediating reception
of light touch.
• Melanocytes – have dendritic processes.
Melanin is involved in protecting keratinocyte
DNA from damage.

Definitions:
Hyperkeratosis Parakeratosis Acanthosis

Increase in stratum corneum (scale) Abnormal keratinization characterized by Thickened epidermis

retained nuclei in stratum corneum (scale)

Papillomatosis Dysplasia
 Acanthosis Cytologic atypia: 
w/upward 1) Variation in size
projections and shape of nucleus
(wart; (nuclear
seborrheic pleomorphism)
keratosis) 2) Variation in
staining
(hyperchromatism)
3) Increased and
abnormal mitotic
figures (cancer;
precancer)
Solar Elastosis

Bluish discoloration of collagen in the dermis.

Cutaneous Tumors Epidermal Tumors

• Epithelial • Benign Epithelial Tumors
• Epidermal tumors – Seborrheic keratosis
• Adnexal tumors • Premalignant/Malignant Epithelial Tumors
• Melanocytic – Actinic keratosis
• Nevi – Squamous cell carcinoma
• Melanoma – Basal cell carcinoma
• Mesenchymal – from fibroblasts in the dermis. – Keratoacanthoma (controversial) – malignancy
• Dermatofibroma – benign. or not?
• Dermatofibrosarcoma protuberans (DFSP) –
malignant.
• Hematopoietic
• Mycosis fungoides
• Langerhans cell histiocytosis
• Mastocytosis – tumor of mast cells

Seborrheic Keratosis
• Common
• Occur >30 years
• Trunk/face Irritation
• Rarely as paraneoplastic syndrome Inflammation
w/an internal malignancy.
– Sign of Leser-Trelat
• Papules – raised.
• Smooth, rough, or “greasy” surface
• Light to dark brown
• “Stuck on” appearance ^ Solitary ^ Multiple
• People often scratch them off.

• Hyperkeratosis – increased s. corneum 

• Acanthosis (bland keratinocytes)
• Epidermal invaginations; keratin-filled
“pseudo-cysts”
Test q: A 45y/o male develops multiple seborrheic keratosis
over a period of a few months. He is diagnosed w/Leser-Trelat
syndrome which is associated with: internal malignancy.
Test q: A 56y/o farmer presents w/numerous macules and
papules on his face. Biopsy shows hyperkeratosis,
parakeratosis, and dysplasia in the lower dermis. Diagnosis:
Seborrheic keratosis

Above: Dermatosis
Papulosis Nigra – Multiple
seborrheic keratoses.
Actinic Keratosis
• Fair-complexioned individuals (Irish/Anglo-Saxon
heritage)
• Chronically sun-exposed areas
• Induced by ultraviolet radiation
• Course
– stable
– regress
– progress to squamous cell carcinoma
• Macules - flat
• Papules - raised
• Scale
• Hyperkeratosis (increased stratum corneum); Test q: A 58y/o farmer has had a lesion on his face that has been enlarging for
the past 3yr. This lesion is excised, and microscopic exam shows basal cell
parakeratosis hyperplasia. Some of the basal cells show nuclear atypicality associated
• Dysplasia of lower epidermis w/marked hyperkeratosis and parakeratosis. Solar elastosis is present. Which of
• Solar elastosis the following lesions best accounts for these findings? Actinic keratosis.
Test q: A 50y/o male presents w/a maculopapular scaly lesion on the back of his
neck. A biopsy shows dysplasia of the keratinocytes in the lower epidermis and
marked solar elastosis in the dermis. Diagnosis: actinic keratosis.

Squamous Cell Carcinoma

• Common: >200,000 cases/year
• May metastasize
• M>F; >70 years
• Head and neck
• Predisposing factors:
– Ultraviolet light exposure
– Industrial carcinogens (tars
and oils)
– Chronic ulcers
– Immunosuppression; HIV
infection
– Mutations in p53 common
• Flesh-colored to erythematous (red)
• Smooth or warty surface
• Ulceration
• Firm

• Hyperkeratosis; parakeratosis
• Acanthosis
• Dysplasia of entire epidermis – large
nuclei within the entire epidermis
• Extension of tumor into dermis
• Squamous “pearls”
• Solar elastosis

Cells still make keratin – result is keratin pearls. Have s. corneum but it’s trapped beneath rather than being at the
surface of the skin.

Basal Cell Carcinoma

• Most Common malignant skin tumor: >700,000/year
• Locally invasive; rarely metastasize
• M>F; 60 years
• Head and neck
• Predisposing factors:
– Fair complexion
– Chronic sunlight exposure Test q: The most common cutaneous
malignancy is: basal cell carcinoma
– Immunosuppression
– Nevoid basal cell carcinoma syndrome
Nevoid Basal Cell Carcinoma Syndrome
• Autosomal dominant
• PTCH gene
• Receptor for SHH (sonic hedgehog) gene product
• PTCH mutation present in 30% of sporadic BCC

Test q: A 22y/o male develops more than a dozen basal cell carcinomas on his upper face. This syndrome is autosomal dominant and is associated
w/mutation of which gene? PTCH.
Test q: A 5y/o male presents w/a basal cell carcinoma on his forehead. The genetic basis for this disease is: PTCH.

Basal Cell Carcinoma

• Papules or nodules (nodules = big papules)
• Smooth surface
(translucent; pearly)
• Telangiectasia – dilated blood vessels within the
lesion
• Central ulcer

See peripheral palisading (below) – cells lined up

parallel to the periphery of the lobule.

Test q: A 66y/o female farmer has a pearly nodule on her forehead. The nodule is focally ulcerated and shows prominent dilated blood vessels.
Histologically you would expect to see: peripheral palisading.
Test q: All of the following regarding basal cell carcinoma are true except: Tumor exhibits full thickness atypia of the epidermis (Other choices –
Retraction spaces are seen around tumor lobules; Peripheral palisading is a feature; The nose is a frequent site; Sun exposure is a risk factor)

Keratoacanthoma
• Benign vs. malignant
• Rapidly growing tumor
• M>F
• Sun-exposed skin
• May spontaneously involute (regress)
• Rarely aggressive

• Cup-shape
• Keratin plug
• Glassy keratinocytes

Test q: A 70y/o man develops a keratoacanthoma on his nose. The lesion is cup-
shapes and filled w/glossy keratinocytes. The lesion can be expected to:
Spontaneously regress.
Test q: A 60y/o man has noted the appearance of a nodule on his ear during the past
month. On phys exam, there is a 1.2cm flesh-colored, dome-shaped nodule on his
right ear lobe. The nodule has a central keratin-filled crated surrounded by
proliferating epithelium. The lesion regresses and disappears within 1mo. Which of
the following is the most appropriate diagnosis of this lesion? Keratoacanthoma.
Adnexal Tumors
• Most benign
• Derived from adnexal structures including follicle, sebaceous gland, eccrine gland, apocrine gland

Cylindroma 
• Benign adnexal tumor, derived from eccrine glands
• Occurs on forehead and scalp
• Multiple lesions may coalesce into hat-like growth (“turban
tumor”)

Similar to basal cell carcinoma,

but cells are a little more
responsible – try to make
basement membrane (pink web)
and ducts (eccrine glands). 

Melanocytic Tumors:

Melanocytic Nevi (Moles)

• Common
– Congenital (1% of population)
– Acquired (1-35 years)
• Trunk, extremities, face

Acquired Melanocytic Nevi:

- Macules and papules
- Tan to black
- Regular in shape and border
- <5mm diameter

Nevus
• Nests of cells
– epidermis (junctional nevus)
– dermis (intradermal nevus)
– epidermis + dermis (compound
nevus)
• Nevus cells
– round with oval nucleus
– variable melanin
• Summary of histologic features
– Symmetric
– Predominant nest pattern
– Cytologically bland melanocytes
– No dermal mitotic figures
– “Maturation” (nuclei get smaller
with descent into dermis)
Test q: Characteristics of benign nevi include:
maturation; smaller cells in dermis.
Congenital Melanocytic Nevi: Dysplastic Nevi:
• Macules and papules
• Irregular: shape, border, color
• >5mm diameter
• Occur on sun-exposed and non-
sun-exposed skin
• Clinical significance unclear:
– Isolated lesions: not very
significant
– Multiple lesions: probably
increased risk of melanoma
(only very slightly)
– Dysplastic nevus syndrome
(atypical mole syndrome)
• Autosomal dominant

Malignant Melanoma:

 Very irregular in shape

and color.

 Middle picture shows

regression in the middle –
immune system attacks and
partially destroys the
melanoma.

Melanoma is not in the overall top 10 reasons for cancer death,

however, it is one of the most deadly skin cancers 

Test q: In the US, the malignant tumor most commonly causing death in females
is: Lung.

Test q: The malignancies responsible for the most cancer deaths in women and
men in the US (currently) is (are): Lung for both

Test q: The most common cause of cancer-related mortality in US women aged

20-25 is: melanoma. (From 2005 test. Did he say that this year?)
Melanoma Sites
Malignant Melanoma
In Blacks and Asians
• Soles
• Mucous membranes
• Palms
• Nail beds

Chest in men. Lower legs in females. Faces in both.

Melanoma Risk Factors

• Light complexion, hair, eyes – don’t make as much melanin.
• History of blistering sunburn(s)
• Proximity to the equator
• Indoor occupation; outdoor hobbies – more likely to get burnt.
• Family history of melanoma or dysplastic nevi
• Precursor lesions (congenital or dysplastic nevi)
• Xeroderma pigmentosa – inhibits ability to repair DNA.

Test q: In the US, the highest incidence of melanoma can be found in: Texas
(other choices: CA, ME, NC, IN. Proximity to equator)
Test q: Malignant neoplasms develop in patients w/xeroderma pigmentosum
because these patients: Lack an enzyme necessary for DNA repair.

Melanoma
• Not just a disease of older patients
– Most common cause of cancer-related mortality in young women
– Well documented pediatric cases
• Warning signs
– Change in pre-existing mole
– Itching/pain in pre-existing mole
– New pigmented lesion as adult
– ABCDs

Malignant Melanoma: ABCD’s 

A: Asymmetry
B: Border
C: Color
D: Diameter – anything over 10mm should be looked at more
closely.

Melanoma: Pathologic Concepts

• Radial and vertical growth phase
– RGP: intraepidermal growth +/- minimal involvement
of dermis
– VGP: significant invasion into dermis

Radial Growth Phase: Spread of melanoma cells within the

epidermis and papillary dermis, often for a prolonged time. No
capacity for metastasis.

Vertical Growth Phase: Pattern of growth assumes a vertical

component, the melanoma grows downward into the deeper
dermis as an expansile mass. This correlates with the
emergence of a clone of cells with true metastatic potential.
 • Depth of dermal involvement correlates with prognosis.
– Clark’s level (anatomic location of tumor)
– Breslow level (quantitative measurement)

Test q: In melanoma, the single most important prognostic factor is: depth of
invasion
Test q: The Breslow measurement is used to: assess melanoma tumor
stage and prognosis (as opposed to tumor grade and prognosis)

 Vertical – growing down into the dermis and subcutaneous

fat.

Clark’s Levels 
I – tumor cells are confined to the epidermis (melanoma in situ)
II – superficial papillary dermis
III – filling papillary dermis
IV – in reticular dermis, where collagen fibers are thicker (distinguishes from papillary
dermis)
V – has the greatest risk of metastasis.
Test q: A 37y/o red-haired female has a pigmented papule on her back that measures 0.8cm in diameter. On excisional biopsy, melanoma is
diagnosed. The melanoma is confined entirely to the epidermis. The Breslow measurement is .75mm. This melanoma is most accurately described as:
Melanoma in situ REPEATED x2 (once – it was 1.0cm in diameter)
Test q: A 39y/o woman has a nodule on her back that has become larger over the past 2mo. On phys exam, there is a 2.1cm pigmented lesion
w/irregular borders and an irregular brown-black color. An excisional biopsy w/wide margins is performed and microscopic exam of the biopsy specimen
shows a malignant melanoma composed of epithelioid cells that extends 3.5mm (one year, was “2mm”) down to the reticular dermis. There is a band of
lymphocytes beneath the melanoma. Which of the following statements is most appropriate to make to this patient regarding these findings?
Metastases are probable. REPEATED x2 (One year, answer was “The prognosis is poor.” Other choices were the same both times: Her immune
system will prevent metastases; Other family members are at risk for this condition; The primary site for this lesion is probably the eye; Nevi elsewhere
on her body will become malignant.)

Breslow Level:
• Perpendicular distance from granular layer
• Measured in mm
• More reproducible

Melanoma can metastasize to various locations in the body, including

axillary nodes, lung, and liver. 
Melanoma:
Histologic features
• Asymmetric
• Irregular nests
• Single cell pattern
• Pagetoid spread – upward
spreading of melanocytes
into the epidermis.
• Nuclear atypia
• Absence of maturation
Above: Pagetoid spread. Can see nests of melanocytes. Also single cells growing into the epidermis.
• Dermal mitotic figures

Pagetoid spread. 

Nuclei do not get smaller

as they grow down.

In the middle picture, see

atypical cells.

In the picture on the right,

see mitotic figures.

Melanoma – Molecular mechanisms: Test q: A 20y/o man has a raised, irregular, pigmented lesion
• Deletions of CDKN2A (INK4A) on his forearm that has increased in size and become more
– Deletion of p16 protein product leads to: irregular in color over the past 4 months. An excisional biopsy
specimen shows a malignant melanoma that extends into the
• Unrestricted phosphorylation of Rb (inactive Rb) reticular dermis. Family history indicates that the patient’s
• Unrestricted cell growth paternal uncle died of metastatic melanoma that spread to the
– Deletion of p14 (alternative protein product) leads to liver after excision of a primary lesion on the foot. His
• Decreased p53 function (via decreased function of MDM2) grandfather required enucleation of the left eye because of a
“dark brown” mass in the eyeball. Which of the following
• Enhanced growth of altered cells genes is most likely to have undergone mutation to produce
• BRAF mutations these findings? p16 (cell cycle inhibition) REPEATED x2
– Found in melanomas and nevi
– Part of RAS/RAF/MAP kinase pathway

Mesenchymal Tumors:

Benign Fibrous
Histiocytoma(BFH)/Dermatofibroma (DF)
Clinical Features:
• Solitary, slow-growing nodule, often red-brown in
color
• Usually on extremities in dermis or superficial
subcutis Dermatofibroma. Large dark pink
• Presents in early or mid-adult life area = lesion. Proliferation induces
• Spindled tumor cells acanthosis (thickening) of the
• Collagen trapping – at the periphery of the overlying epidermis.
tumor, the tumor cells interdigitate around
preexisting collagen fibers of the reticular dermis

Test q: A pigmented skin lesion measures 1cm in diameter.

Biopsy shows a proliferation of spindled cells in the dermis that
appear to “trap collagen”. The epidermis is not involved.
Mitoses are not identified. The subcutaneous fat is not
involved. Diagnosis: Dermatofibroma

Test q: A 50y/o male develops a slightly pigmented nodule on

his forearm. On biopsy, one sees a proliferation of spindle-
shaped cells in the dermis. Collagen trapping is present, but
fat-trapping is absent. There are no mitoses. Diagnosis?
Dermatofibroma
Dermatofibrosarcoma Protuberans (DFSP) Clinical Features:
• Slow-growing plaque, later nodular
• Usually occurs in mid-adult life
• Men > women
• Trunk, proximal extremities most common site
• Locally recurrent (very)
• Metastasis <5% cases

DFSP: White spaces = what is left of the subcutaneous fat. Below: cells are a bit amorphic. Can see mitoses.

Hematopoietic Tumors:

Mycosis Fungoides:
• Uncommon (<1% of lymphomas)
• Older adults
• Clinical progression in disease:
patch  plaque  nodule
• Patch Stage: Scaly, reddish plaques that arise Patch stage Plaque stage Plaque stage
mainly on clothed areas of the body – sun
exposure actually acts as a treatment.
• T cell lymphoma – uncommon relative to
systemic lymphomas, but one of the most
common skin lymphomas. Some people never
progress through the disease. Nodule (Tumor) Stage 
Not everyone evolves to this
stage – some people are in
Cutaneous T-cell Lymphoma patch stage their whole life.
(Mycosis Fungoides)

 Sezary Syndrome
(Erythrodermic Stage)

Can evolve from patch stage to Sezary syndrome,

but some people go straight to Sezary syndrome
(involves peripheral blood).

Mycosis Fungoides: Histologic Features

• Psoriasiform epidermal hyperplasia (acanthosis) – looks
like psoriasis
• Epidermotropism
– Lymphocytes in epidermis without spongiosis
– Pautrier’s microabscesses: collections of atypical
lymphocytes in epidermis
– Cerebriform nuclei – very convoluted lymphocyte
nuclei

Above: Hyperkeratosis = increased s. corneum. See lymphocytes

in the papillary dermis. Lymphocytes also in the epidermis (bigger,
hyperchromatic).
  Mycosis Fungoides: Atypical T-helper lymphocytes (CD4 -
positive) in dermis and epidermis
Test q: Mycosis fungoides is: a tumor of CD4+ T-cells.

Langerhans Cell Histiocytosis (Histiocytosis X): Langerhans cell = APC typically found in epidermis
• Children > adults
• Solitary or multiple
• Papules, nodules or plaques
• Proliferation of Langerhans cells

Langerhans Cell Histiocytosis: Histologic Features

• Proliferation of cells with reniform (bean-shaped) nuclei and
eosinophilic cytoplasm
• Often involve epidermis (their origin) and dermis
• Eosinophils present in variable amounts
• Immunostains: CD1a and S100 positive
• EM: Birbeck granules – look like tennis racket. Thought to be
involved in antigen presentation.
Test q: A 13y/o male presents w/a solitary nodule on his
forehead. Histologically, there is a proliferation of cells
w/bean-shaped or reniform nuclei and eosinophilic
cytoplasm. Malignant cells are present in both dermis
and epidermis. Many eosinophils are present in the
dermis. On immunohistochemistry you would expect:
CD1a and S100 (+) REPEATED x2

Above: Langerhans cell Above: Langerhans Cell

histiocytosis: Kidney bean-shaped Histiocytosis: CD1a Stain (CD1a
nuclei immunostain is very sensitive and
specific for Langerhans cells.)
Mastocytosis
• Spectrum of diseases
• Variety of clinical entities
• Urticaria pigmentosa
– 50% of cases
– Localized cutaneous disease
– Multiple red-brown papules
– Darier’s sign – traumatize/scratch 
mast cells degranulate, get a wheal.
• Systemic disease (multiple organs)
– 10 %
– Worse prognosis
– Pruritis, flushing, rhinorrhea, diarrhea,
GI bleeding, bone pain
Above: Mastocytosis. Non-descript cell type on H&E. Have granules in the
cytoplasm. Blue stain – granules are stained bright blue.
DERMATOPATHOLOGY: LECTURE 2 – Inflammatory Dermatopathology Tues. 09/14/10

General Principles:
• Thousands of inflammatory dermatoses
• Limited number of histologic reaction patterns
• Significant histologic overlap
• Correlation of histologic features with clinical presentation essential
• Dermatopathologist dependent on history and clinical description of lesions by dermatologist or family practitioner

Histologic Classification:
Based on “pattern” of inflammatory changes. Some patterns:
– Spongiotic (intraepidermal edema) ex: contact dermatitis/eczema
– Psoriasiform (epidermal acanthosis) ex: psoriasis
– Interface (damage to basal layer)
• Perivascular (inflammatory cells predominant ly around blood vessels) ex: erythema multiforme, lupus
• Lichenoid (inflammatory cells arranged as dense band beneath epidermis) ex: Lichen Planus
Other patterns:
– Perivascular infiltrate (no epidermal changes)
– Interstitial infiltrate (inflammatory cells between collagen bundles)
– Bullous disease (blister)
• Intraepidermal – blister within epidermis
• Subepidermal – blister beneath epidermis
– Panniculitis (inflammation in subcutaneous fat)
– Miscellaneous

Patterns:
• Represent starting point (defines category)
• Individual differentiating microscopic features
• Correlation with clinical features often necessary to make final diagnosis

Spongiotic Dermatitis
• Primary feature: intraepidermal edema (ECF as a result of inflammation)
– Accumulation of edema fluid within epidermis
– Keratinocytes pull apart (easy to see intercellular bridges)
– May see intraepidermal vesicles
– May see some acanthosis – thickening – in older lesions (overlap with
psoriasiform pattern)
• Red,papulovesicular, oozing and crusting
• Prototype: contact dermatitis

Eczematous Dermatitis
Histologic Features:
• Spongiotic dermatitis
– Intercellular edema in epidermis
– Small vesicles in epidermis due to edema fluid 
– Inflammatory infiltrate in dermis (typically lymphocytes and eosinophils
– clue that it’s an allergic process)

Pathogenesis of Contact Dermatitis

• Antigens processed by dendritic Langerhans cells Test q: Allergic contact dermatitis is
• Langerhans cells migrate to regional lymph nodes related to: Type IV hypersensitivity
• Antigen presentation stimulates naive T-cells reaction. (Cell-mediated rather than
• Rash develops on re-exposure secondary to cytokine production from T-cells antibody-mediated)

Psoriasiform Dermatitis
• Epidermal acanthosis most important feature
• Variable perivascular infiltrate
• Variable spongiosis
• Prototype: psoriasis
Psoriasis
• Chronic dermatitis
• Affects 1-3% of the population
• May develop at any age; genetic predisposition
• Psoriatic arthritis
– Overall incidence ~5%
– Usually seen in patients with severe skin
disease
• HIV: psoriasis can be presenting sign
• Red plaques with loose silvery scale 
• Pitted nails with yellow discoloration 
• Frequent sites: extensor surfaces, scalp,
lumbosacral region, gluteal cleft, glans penis

Psoriasis: Histologic Features

• Uniform acanthosis
• Confluent parakeratosis (retained
nuclei in stratum corneum – mainly see
neutrophils here.)
• Diminished to absent granular layer
• Thinned suprapapillary plate – will see
Above: Psoriatic Arthritis thickening of epidermis except this
(very disruptive). area.
• Parakeratotic scale with neutrophils
• Spongiform pustules in epidermis
• Dilated tortuous vessels in dermal
papillae

Interface Dermatitis
Key feature: damage to basal layer of epidermis, usually by lymphocytes
• Damage to basal layer of epidermis with perivascular inflammation
 Erythema Multiforme
 Toxic Epidermal Necrolysis (TEN)
 Lupus Erythematosus
• Damage to basal layer of epidermis with lichenoid inflammation (dead span of lymphocytes underneath the epidermis)
• Lichen Planus

Interface Dermatitis w/perivascular Inflammation:

Erythema Multiforme:
• Spectrum of disease (EM, TEN)
• EM = less severe end of the spectrum
• TEN = toxic epidermal necrolitis (most severe end of the spectrum)
• Dramatic hypersensitivity response with a wide range of possible causes
– Infections: HSV, mycoplasma, histoplasmosis, coccidiomycosis, typhoid, leprosy
– Drugs: Sulfa drugs, PCN, barbiturates, salicylates, hydantoins, antimalarials
– Malignancies: carcinomas and lymphomas
– Collagen vascular disease: Lupus erythematosus, dermatomyositis, periarteritis nodosa
– Idiopathic ~ 50% of cases
• Clinical lesions variable (multiple forms)
– Papules
– Targetoid lesion (most characteristic)
– Vesicles
– Bullae
 Rapid onset of red papules: Target lesions:
Above: Central area = necrosis
of the epidermis
Test q: A 25y/o female had a child in daycare that develops diarrhea
which the patient also developed. Both were treated w/trimethaprim –
sulfa methoxazole (Septra). The mother develops a targetoid rash
w/vesicles and bullae. You suspect: Erythema multiforme.
Test q: A 40y/o male AIDS patient is treated w/Septra (trimethaprim
sulfamethoxazole) for Pneumocystis pneumonia. His CD4 count is
<200. He develops a papular rash which eventually shows a targetoid
pattern. A biopsy shows full thickness necrosis of keratinocytes. The
most likely diagnosis is: Erythema multiforme.
Test q: A 28y/o AIDS patient suffers from Histoplasmosis and
Nocardiosis. He is treated w/Itraconazole and Trimethiprim
Sulfamethoxazole. He develops vesicles and target-shaped red skin
papules. This history is consistent with: Erythema multiforme.

Stevens-Johnson Syndrome   Toxic Epidermal Necrolysis

– Extensive disease with oral and (TEN)
ocular involvement • Widespread epidermal
– Fever necrosis
– Children more than adults • Extensive sloughing
– Drugs are most common cause • Resembles burns
– Get mucosal involvement. Very
severe.

Erythema Multiforme: Histologic Features

• Degeneration and necrosis of keratinocytes leading to full thickness necrosis
• Superficial perivascular lymphocytic infiltrate, usually mild in nature
• Prominent edema of papillary dermis

 Figure: Erythema Multiforme/TEN:

Mild (left); severe (right)
Whole epidermis is necrotic
Can see necrotic, apoptotic cells –
distinguish by small, darkened nucleus and
orange cytoplasm
See lymphocytes around blood vessels

Lupus Erythematosus (Interface Dermatitis w/perivascular inflammation)

Acute Lupus Erythematosus: Subacute Lupus Erythematosus:

• Annular,
polycyclic,
blanchable
erythema
• Mild systemic
involvement
(arthralgias, fever,
malaise)
• Illness is
intermediate in
severity between
ALE and CLE
Blanchable erythema Systemic symptoms: Circulating antibodies; •15% progress to acute LE
Photo-distribution immunoglobulin deposition in the skin
Malar rash and other organs
Chronic Lupus Erythematosus (aka discoid LE)
 Figure: Damage to
basal layer of epidermis
– can see vacuoles
within basal
keratinocytes as a result
of damage.
Can see dramatically
thickened basement
membrane here.
Discoid Lupus – much more skin limitied. Very rarely
progresses to systemic disease. See post-inflammatory
hypopigmentation.

Perivascular lymphocytes

Above: Mucin production – collagen

bundles here are separated by mucin.

Test q: Histologic features of Lupus Erythematosus include: interface vacuoles and focal epidermal atrophy

Interface Dermatitis w/lichenoid (band-like) inflammation

Lichen Planus
• Chronic but self-limiting disease
• Multiple, symmetric lesions on extremities (especially
wrists) 
• Pruritic, purple, polygonal papules
• Oral mucosal involvement common (see right)
– oral lesions have lacy, white pattern.
• Dense band-like lymphocytic infiltrate hugs epidermis
• Epidermal changes:
– Hyperkeratosis
– Wedge-shaped hypergranulosis

• “Saw-toothed” basal layer 

• Thickening of granular layer

• Individual necrotic
keratinocytes (circled) 

Above: Lichen Planus – Interface dermatitis,

Test q: A 40y/o woman goes to her dentist who notes that she has 0.2 to 1.5cm scattered,
white, reticulated areas on the buccal mucosa. The woman says that these lesions have so damage to the basal layer of keratinocytes
been present for one year. She also has some 0.3-cm purple, pruritic papules on each elbow. – due to attack by lymphocytes. Circle –
A biopsy specimen of a skin lesion shows a bandlike infiltrate of lymphocytes at the dermal- necrotic keratinocytes. See band-like infiltrate
epidermal junction as well as degeneration of basal keratinocytes. The most likely diagnosis of lymphocytes. Thickening of epidermis –
is: Lichen planus. increase in granular layer.
Bullous Dermatosis:
• Bullae and vesicles are primary clinical manifestations
• Bullae = large blisters; vesicles = tiny blisters
• Diagnostic categories based on level of split in epidermis
– Subcorneal (beneath SC), intraepidermal or subepidermal
• Diseases caused by Ig deposition i.e. autoimmune diseases

Pemphigus Vulgaris:
• Presents in the 4th-6th decades, M=F
• Autoimmune blistering disease
– IgG against desmoglein 3 in desmosomes
– Desmosomes hold epithelial cells together – loss of cell
adhesion within the epidermis
• Test q: In pemphigus vulgaris, IgG autoantibodies are directed against:
Desmosomes REPEATED x2
• Variants: pemphigus vegetans and foliaceus
• Flaccid, fragile bullae 
• Oral mucosa involvement (typically ruptures before you see it
clinically)

 Pemphigus vulgaris.
• Intraepidermal, suprabasilar blister
with “tombstone” basal layer
• Mixed dermal inflammatory
infiltrate, often with eosinophils
• Intraepidermal: looks like this
blister is under the whole epidermis,
but note the one layer of cells left
underneath. The rest makes up the
roof of the blister.

Above: In the base of the blister is one layer of the Above: Pemphigus Vulgaris Immunofluoresence
epidermis. The rest makes up the roof of the blister.

Bullous Pemphigoid:
• Generally affects elderly patients
• Bullae on extremities, intertriginous areas, abdomen and oral mucosa (1/3
pts)
• Autoimmune disease
• IgG against hemidesmosome proteins
• Hemidesmosomes bind epidermis to basement membrane
• Subepidermal blistering process – blisters have more strength because of
more material in the roof. Blisters are tense and stay intact longer (as
compared to fragile blisters of PV, described above).
• Tense bullae 
Above: Bullous Pemphigoid. Subepidermal Above: Blister contains edema Bullous Pemphigoid: Immunofluorescence.
blister without “tombstones” or acantholysis. fluid and eosinophils. IgG bound to hemidesmosome – located in
No epidermis in the base of the blister. basement membrane.

Dermatitis Herpetiformis
• Vesicular dermatosis not bullous
rd th
• 3 and 4 decades, M>F
• Pruritic, burning vesicles, especially on extensor surfaces of extremities
• Strongly associated with celiac disease – everyone w/DH either has Celiac disease or sub-clinical Celiac disease.
• Responds to gluten free diet (like celiac)
• IgA deposited in dermal papillae of skin

Incredibly itchy – patients will scratch blisters DH Histologic Features- Subepidermal vesicles Neutrophilic microabscess
before you ever see them in clinic.

Test q: A 35y/o female presents w/small vesicles on extremeties. The rash is

extremely pruritic. She also has been diagnosed w/celiac disease. Diagnosis:
Dermatitis herpetiformis REPEATED x2

Test q: A person w/dermatitis herpetiformis should avoid what food substance: gluten.

Test q: A 35y/o man has had an outbreak of pruritic lesions over the extensor surface
of the elbows and knees during the past month/ He has a history of malabsorption
that requires him to eat a special diet, but he has had no previous skin problems. On
phys exam, the lesions are 0.4-0.7cm vesicles. A 3mm punch biopsy of one of the
lesions over the elbow is performed. Microscopic exam of the biopsy specimen shows
accumulation of neutrophils at the tips of dermal papillae and formation of small
blisters due to separation at the dermo-epidermal junction. Immunofluorescence
studies performed on this specimen show granular deposits of IgA localized to tips of
dermal papillae. Lab studies show serum anti-gliadin antibodies. Which of the
following is the most likely diagnosis? Dermatitis herpetiformis.
DH Immunofluorescence.
Test q: Neutrophilic microabscesses and fluffy IgA deposits on basement membrane
IgA deposits recruit in neutrophils.
anchoring febrils are characteristic of: Dermatitis herpetiformis.

Infections and Infestations:

Dermatophytosis:
• AKA: Tinea (capitis – scalp, corporis – body, barbae – beard area, cruris – groin, pedis – foot), “ringworm”
• Dermatophytes infect outer keratin layer of skin
 Dermatophytosis

Above: Tinea corporis – expanding, annular,

erythematous plaque w/elevated, scaly border.
Annular because dermatophytes start in a
small area and grow outwards = ring.

Dermatophyte Infection: Histologic Features:

• Hyperkeratosis
• Parakeratosis
• Neutrophils in keratin
• Hyphae in keratin
• Difficult to see on H&E
• Organisms grow in the stratum corneum – do not
go down into epidermis at all.

Test q: Neutrophils in the stratum corneum are a common PAS stain

feature in: Psoriasis and dermatophytosis.
Test q: A 25y/o male joins a gym and works out regularly. He
demonstrating
develops a pruritic rash on his feet which shows white centers hyphae
w/a red, scaly border. A diagnostic stain would be: PAS stain.
Shows fungal hyphae/spores very
clearly – but only in s. corneum.

Warts (verrucae):
• Benign neoplasms caused by human papillomavirus (HPV)
– >60 subtypes
– Certain subsets associated w/squamous cell carcinoma
• Common
– Common wart (verruca vulgaris)
– Plantar/palmar wart - caused by diff HPV subtypes
– Genital wart (condyloma acuminatum)
– Flat wart
• Occur at any age
• Self-limited

Verruca Vulgaris: Histologic Features

• Histology similar across all
the different subtypes.
• Papillomatosis – projections
of epidermis
• Acanthosis – thickening of
epidermis
• Tortuous vessels within
papillae

KEY FEATURE = Koilocytes.

Have clear area within
cytoplasm – due to viral
particles present.
Molluscum Contagiosum:
• Common especially in children
• Dome-shaped papules with a central keratin-
filled crater
• Easily spread through contact
• DNA poxvirus
• Histologic Features: large, bright pink viral
inclusions.
• Molluscum body: eosinophilic cytoplasmic
inclusion in upper layers of epidermis.

Test q: A 35y/o man has noted a bump on his upper trunk for the past 6wk. On phys exam, there is a solitary 0.4cm flesh-colored nodule on the upper
trunk. The dome-shaped lesion is umbilicated, and a curd-like material can be expressed from the center. This material is smeared on a slide, and
Giemsa stain shows many pink, homogenous, cytoplasmic inclusions. The lesion regresses over the next 2mo. Which of the following infectious agents
most likely produced this lesion? Molluscum contagiosum

Impetigo:
• Common superficial infection
• Staphylococcus or streptococcus
• Exposed surfaces
• Characteristic honey-colored crust
• Histologic Feature: Subcorneal pustule
• A lot of neutrophils in the stratum corneum –
can see gram positive cocci here.

Infestations: Scabies (Sarcoptes scabiei)

Above: The scabies mite. Scabies feces. Linear burrows.

Scabies like to burrow underneath the stratum corneum. Find them on the penis and web spaces of the fingers.

Figure: Scabies organism

underneath the stratum corneum.
Scabies feces underneath? 
Herpesvirus infections:
• HSV-1
– Cold sores, fever blisters
– Oral infection most common
– Cutaneous blistering eruption, usually linear
• HSV-2
– Genital herpes
• VZV – varicella zoster
– Chicken pox
 Figure: Germline mutation: born w/one mutated allele and one wild-
type allele. During life, you’ll have hits – from viruses, chemicals, other
environmental factors – and you will lose the wildtype allele. Called LOH
(loss of heterozygosity)  uncontrolled proliferation.
 Figure:
Herpes infects keratinocytes – see
multinucleated cells (circled one
has 10-15 nuclei)