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Skin -Normal Skin -Normal Stratified Squamous epithelial

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Title: Skin -Normal Skin -Normal Stratified Squamous epithelial


1
Skin -Normal
2
Skin -Normal
  • Stratified Squamous epithelial cells
    (keratinocytes) production of keratin protein,
  • Melanocytes production of a brown pigment
    (melanin)
  • Langerhans cells take up and process antigens
  • Neural end-organs and axonal processes
  • Merkel cells
  • within the basal cell layer
  • mechanoreceptors or neuroendocrine function

3
Skin -Normal
  • Sweat glands - temperature control
  • Specialized dermal cells (dendrocytes) - for
    antigen presentation as well as for production of
    molecules (e.g., factor XIIIa)
  • Hair follicle- harbor protected repositories of
    epithelial stem cells

4
Skin - Pathology
  • DEFINITIONS OF MACROSCOPIC TERMS
  • Macule
  • Circumscribed lesion of up to 5 mm in diameter
    characterized by flatness and usually
    distinguished from surrounding skin by its
    coloration.
  • Patch
  • Circumscribed lesion of gt 5 mm in diameter
    characterized by flatness and usually
    distinguished from surrounding skin by its
    coloration.
  • Papule
  • Elevated dome-shaped or flat-topped lesion 5 mm
    or less across.
  • Nodule
  • Elevated lesion with spherical contour gt 5 mm
    across.

5
Skin - Pathology
  • Plaque
  • Elevated flat-topped lesion, usually gt 5 mm
    across (may be caused by coalescent papules).
  • Vesicle
  • Fluid-filled raised lesion 5 mm or less across.
  • Bulla
  • Fluid-filled raised lesion gt 5 mm across.
  • Blister
  • Common term used for vesicle or bulla.
  • Pustule
  • Discrete, pus-filled, raised lesion.
  • Wheal
  • Itchy, transient, elevated lesion with variable
    blanching and erythema formed as the result of
    dermal edema.

6
Skin - Pathology
  • Scale
  • Dry, horny, plaque like excrescence usually the
    result of imperfect cornification.
  • Lichenification
  • Thickened and rough skin characterized by
    prominent skin markings usually the result of
    repeated rubbing in susceptible persons.
  • Excoriation
  • Traumatic lesion characterized by breakage of the
    epidermis, causing a raw linear area (i.e., a
    deep scratch) often self-induced.
  • Onycholysis
  • Separation of nail plate from nail bed.

7
Skin - Pathology
  • Hyperkeratosis
  • Thickening of the stratum corneum, often
    qualitative abnormality of the keratin.
  • Parakeratosis
  • Modes of keratinization characterized by the
    retention of the nuclei in the stratum corneum.
  • Hypergranulosis
  • Hyperplasia of the stratum granulosum, often due
    to intense rubbing.
  • Acanthosis
  • Diffuse epidermal hyperplasia.
  • Papillomatosis
  • Surface elevation caused by hyperplasia and
    enlargement of contiguous dermal papillae.

8
Skin - Pathology
  • Dyskeratosis
  • Abnormal keratinization
  • Acantholysis
  • Loss of intercellular connections resulting in
    loss of cohesion between keratinocytes.
  • Spongiosis
  • Intercellular edema of the epidermis.
  • Hydropic swelling (ballooning)
  • Intracellular edema of keratinocytes, often seen
    in viral infections.
  • Exocytosis
  • Infiltration of the epidermis by inflammatory or
    circulating blood cells.
  • Erosion
  • Discontinuity of the skin exhibiting incomplete
    loss of the epidermis

9
Skin - Pathology
  • Ulceration
  • Discontinuity of the skin exhibiting complete
    loss of the epidermis and often of portions of
    the dermis and even subcutaneous fat.
  • Vacuolization
  • Formation of vacuoles within or adjacent to
    cells often refers to basal cell-basement
    membrane zone area.
  • Lentiginous
  • Referring to a linear pattern of melanocyte
    proliferation within the epidermal basal cell
    layer. occur as a reactive change or as part of a
    neoplasm of melanocytes.

10
Disorders of Pigmentation and Melanocytes
  • 1.VITILIGO
  • loss of pigment-producing melanocytes within the
    epidermis
  • All ages and races, noticeable in darkly
    pigmented individuals
  • Clinical lesions
  • macules and patches of pigment loss
  • Hands and wrists, axillae and perioral,
    periorbital, and ano-genital skin (Muco-cutaneous
    Jxns)
  • Koebnerization (as in Lichen planus)- lesions at
    sites of repeated trauma
  • Morphology.
  • Loss of melanocytes revealed by electron
    microscopy
  • IHC for melanocyte-associated proteins (e.g.,
    tyrosinase or Melan-A, or S-100

11
Disorders of Pigmentation and Melanocytes -
VITILIGO
  • Pathogenesis.
  • Theories
  • 1) autoimmunity,
  • 2) neurohumoral factors
  • 3) self-destruction of melanocytes by toxic
    intermediates of melanin synthesis
  • interesting facet of vitiligo -therapy with UVA
    with use of the photosensitizing drug, psoralen
    (known as PUVA)
  • Regain pigment initially at the ostia of hair
    follicles,
  • Other causes of Hypopigmentation
  • 1.Postinflammatory hypopigmentation
  • 2.Albinism
  • melanocytes are present but melanin pigment is
    not produced
  • lack or defect in Tyrosinase

12
Disorders of Pigmentation and Melanocytes
  • 2. FRECKLE (EPHELIS)
  • MC pigmented lesions of childhood in lightly
    pigmented individuals
  • after sun exposure
  • Small (1 to several mm in diameter), tan-red or
    light brown macules cyclic fashion with winter
    and summer
  • DD from a Lentigo, which maintains stable
    coloration independent of sun exposure.
  • Clinically
  • hyperpigmentation -result of increased amounts
    of melanin pigment within basal keratinocytes
  • melanocytes are normal in slightly enlarged
  • café au lait spots are histologically
    indistinguishable from freckles (evolve
    independent from sun exposure)

13
Disorders of Pigmentation and Melanocytes
  • 3.MELASMA
  • mask-like zone of facial hyperpigmentation
  • association with
  • pregnancy "mask of pregnancy."
  • oral contraceptives
  • administration of Hydantoins,
  • Idiopathic, resolves spontaneously
  • poorly defined, blotchy, tan-brown macules and
    patches involving the cheeks, temples, and
    forehead bilaterally
  • Sunlight -accentuate

14
Disorders of Pigmentation and Melanocytes
  • 4. LENTIGO (plural-lentigines)
  • Hyperplasia of melanocytes often in infancy and
    childhood
  • no sex or racial predilection
  • Cause and pathogenesis - unknown.
  • mucous membranes as well as the skin
  • No change on exposure to sunlight.
  • Essential histologic feature- hyperpigmented
    basal cell layer
  • Elongation and thinning of the rete ridges
  • variant - solar or actinic lentigo
  • alteration in keratinocyte maturation in
    sun-damaged skin of older pts.
  • Lentiginous -proliferation within the basal cell
    layer in melanocytic tumor
  • Lentiginous nevi and melanomas (Acral lentiginous
    melanomas).

15
Disorders of Pigmentation and Melanocytes
  • 5.MELANOCYTIC NEVUS (PIGMENTED NEVUS, MOLE)
  • (NEVI/ NEVUS benign lesion of the skin may be
    pigmented or nonpigmented, flat or raised, smooth
    or warty. May become malignant).
  • tan to brown, uniformly pigmented, small (usually
    lt6 mm across), solid regions of relatively flat
    (macules) to elevated skin (papules) with
    well-defined, rounded borders
  • Morphology.
  • formed by melanocytes grow in aggregates, or
    "nests," along the dermoepidermal junction called
    junctional nevi ? grow into the underlying dermis
    as nests or cords of cells (compound nevi) ?older
    lesions - intradermal
  • Maturation- correlates with enzymatic changes
    (progressive loss of tyrosinase activity and
    acquisition of cholinesterase activity
  • sequence of maturation - diagnostic importance in
    distinguishing benign nevi from melanomas, which
    usually show little or no maturation
  • Clinically, compound and dermal nevi are often
    more elevated than junctional nevi

16
Disorders of Pigmentation and Melanocytes
  • 6. DYSPLASTIC NEVI
  • BK moles (initial two families studied)
  • Clinically
  • larger than most acquired nevi (often gt5 mm
    across)
  • hundreds of lesions on the body surface
  • flat macules, slightly raised plaques
  • variability in pigmentation (variegation)
  • borders that are irregular in contour
  • occur on non-sun-exposed as well as on
    sun-exposed body surfaces
  • in multiple members of families prone to the
    development of malignant melanoma (the heritable
    melanoma syndrome).
  • autosomal dominant
  • peculiar linear fibrosis surrounding the
    epidermal rete ridges

17
Disorders of Pigmentation and Melanocytes
  • DYSPLASTIC NEVI
  • Cytologic atypia ,irregular, often angulated,
    nuclear contours and hyperchromasia
  • sparse lymphocytic infiltrate, loss of melanin
    or melanin pigment incontinence
  • single nevus cells replace the normal basal cell
    layer dermoepidermal junction, - lentiginous
    hyperplasia
  • Precursors of malignant melanoma
  • gt 5 of family members - melanoma
  • probability of developing melanoma is 56 at age
    59 years
  • Clark and associates
  • steps? benign nevi ? aberrant differentiation ?
    dysplastic ? metastasizing malignant tumors

18
7. MALIGNANT MELANOMA
  • Skin, other sites (oral and anogenital mucosal
    surfaces, esophagus, meninges eye)
  • Skin Mc site
  • Non cutaneous UVEA of the eye
  • Sunlight - important role
  • Men - on upper back
  • Women -both the back and legs
  • Higher risk
  • Carcinogens
  • dysplastic nevus
  • ( pre malignant ) gt 5 lt10mm
  • hereditary factors
  • Lightly pigmented individuals
  • Clinical Features
  • early feature itching ( itching moles bad)
  • greater than 10 mm in diameter
  • most important clinical sign -change in color,
    size, or shape in a pigmented lesion
  • variations in pigmentation
  • Borders not smooth, round, and uniform,
  • If the size is more than 5mm follow

19
MALIGNANT MELANOMA
  • Clinical warning signs
  • 1) enlargement of a pre-existing mole,
  • 2) itching or pain in a pre-existing mole,
  • 3) development of a new pigmented lesion during
    adult life,
  • 4) irregularity of the borders of a pigmented
    lesion, and
  • 5) variegation of color within a pigmented lesion
  • Growth Patterns and Morphology
  • radial and vertical growth (longitudinal growth
    into the epidermis, into blood vessels if more
    than 1.7mm thick. Radial or horizontal not
    important still limited to the dermis)
  • vertical component of growth
  • clinically
  • nodule in the relatively flat radial growth phase
  • emergence of a clone of cells with true
    metastatic potential ( moves from monoclonal to
    multiclonal )
  • probability of metastasis predicted by simply
    measuring in millimeters the depth of invasion
    below the granular cell layer

20
MALIGNANT MELANOMA
  • Melanoma cells -
  • larger than nevus cells
  • large nuclei with irregular contours
  • chromatin clumped at the periphery of the nuclear
    membrane
  • large prominent red (eosinophilic) nucleoli
  • nature and extent of the vertical growth phase
    determine the biologic behavior of malignant
    melanoma
  • Diagnostic Criteria and Prognostic Attributes
  • assessment of prognosis based on
  • 1) measurement of tumor depth in millimeters
  • 2) number of tumor cell mitoses per square
    millimeter in the microscope
  • 3) evidence of an immune response to the
    superficial (radial) growth component (termed
    regression)
  • 4) presence and degree of tumor infiltrating
    lymphocytes (TILs)
  • 5) gender FEMALES GOOD
  • (6) location

21
MALIGNANT MELANOMA
  • More favorable prognosis
  • tumor depth of less than 1.7 mm, (more than 1.7mm
    bad prog.)
  • absence or low numbers of mitoses,
  • presence of a brisk TIL tumor infultrating
    lymphocytes response,
  • absence of regression,
  • female gender, and
  • location on extremity skin
  • Gray zone - melanocytic tumors of uncertain
    malignant potential (MELTUMP)

22
Benign Epithelial Tumors
  • Derived from
  • keratinizing stratified squamous epithelium of
    the epidermis
  • hair follicles (keratinocytes)
  • ductular epithelium of cutaneous glands
  • confused with malignancy,
  • Biopsy required
  • 1. SEBORRHEIC KERATOSES
  • arise spontaneously, on the trunk
  • Face- Dermatosis papulosa nigra
  • Clinically - round, flat, coin like waxy plaques
  • uniformly tan to dark brown
  • "stuck on" appearance easily peeled off.
  • small, round, pore like ostia impacted with
    keratin seen with a hand lens. (Differentiating
    between malignant melanomas)
  • Part of paraneoplastic syndrome (Leser-Trélat
    sign)
  • whorling" squamous cells resembling eddy currents
    in a stream

23
2. ACANTHOSIS NIGRICANS
  • Acanthosis proliferation hyperplasia of the
    stratum spinosum of the epidermis
  • Hyperpigmented zones and "velvet-like" texture
  • flexural areas
  • cutaneous marker for associated benign and
    malignant conditions
  • Benign type
  • childhood or during puberty
  • autosomal dominant
  • with obesity or endocrine abnormalities (excess
    cortico steroids)
  • pituitary and pineal tumors and with diabetes
  • congenital syndromes
  • Malignant type
  • underlying GI adenocarcinoma.

24
3. FIBROEPITHELIAL POLYP
  • squamous papilloma, skin tag
  • Most common cutaneous lesions, during pregnancy
  • part of a syndrome called Birt-Hogg-Dubé syndrome.

4. EPITHELIAL CYST (WEN)
  • Invagination and cystic expansion of epidermis or
    of the epithelium forming the hair follicle
  • filled with keratin and lipid-containing debris
  • Histologic types
  • Epidermal inclusion cyst
  • Pilar or trichilemmal cysts
  • Dermoid cyst (air follicles) budding outward from
    its wall.
  • steatocystoma multiplex -resembling the sebaceous
    gland duct

25
ADNEXAL (APPENDAGE) TUMORS
  • Mendelian patterns of inheritance multiple
    disfiguring
  • Eccrine poroma on the palms and soles derived
    from eccrine sweat glands
  • Cylindroma on the forehead and scalp
  • hat like growth turban tumor
  • Syringomas, lesions of eccrine differentiation
  • multiple, small lower eyelids
  • Trichoepitheliomas, - follicular differentiation
  • Markers for internal malignancy (trichilemmomas
    and breast carcinoma of Cowden syndrome, also
    seen in familial polyposis coli) cells try to
    differentiate into hair follicles

26
KERATOACANTHOMA
  • sun-exposed skin of whites older than age 50
    years, facial skin
  • mimic squamous cell carcinoma (mutations in the
    p53 gene)
  • heal spontaneously, without treatment
  • flesh-colored, dome-shaped nodules
  • central, keratin-filled plug, imparting a
    crater-like topography
  • NB squamous cell carcinomas usually develop at a
    site of chronic irritation

27
Premalignant and Malignant Epidermal Tumors
  • ACTINIC KERATOSIS chronic exposure to sunlight
    UVB ( sun light causes MCC in skin basal cell
    carcinoma, best prognosis ,squamous cell
    carcinoma, second best prognosis and malignant
    melanomas, worse prognosis chronic exposure to
    sunlight
  • excess keratin in lightly pigmented individuals.
  • ionizing radiation, hydrocarbons, and arsenicals
  • less than 1 cm in diameter are tan-brown, red,
    or skin-colored
  • sandpaper-like consistency
  • dyskeratosis with pink or reddish cytoplasm
  • Dermis shows thickened, blue-gray elastic fibers
    (elastosis),
  • nuclei in stratum corneum (parakeratosis)
  • intercellular bridges are present

28
SQUAMOUS CELL CARCINOMA
  • 2nd MC tumor arising on sun-exposed sites in
    older people,
  • men gt women (Except for lesions on the lower
    legs)
  • predisposing factors
  • sunlight
  • industrial carcinogens (tars and oils),
  • chronic ulcers and
  • draining osteomyelitis,
  • old burn scars,
  • ingestion of arsenicals,
  • ionizing radiation,
  • tobacco and betel nut chewing (in the oral
    cavity).

Basal cell Carcinoma pallisding peripheral
cell Perpendicular to rest
29
SQUAMOUS CELL CARCINOMA
  • exposure to UV light with subsequent DNA damage
  • Immunosuppressed Drugs
  • chemotherapy
  • organ transplantation
  • Xeroderma pigmentosum
  • Sunlight has transient immunosuppressive effect
    on
  • antigen-presenting Langerhans cells in the
    epidermis
  • chemical agents- direct mutagenic effects by
    producing DNA adducts
  • Morphology.
  • less than 5 have metastases to regional nodes

30
BASAL CELL CARCINOMA
  • Common, slow-growing ,rarely metastasize
  • sites subject to chronic sun exposure
  • in lightly pigmented people
  • Immunosuppression
  • defects in DNA repair (e.g., Xeroderma
    pigmentosum
  • pearly papules often containing prominent,
    dilated sub epidermal blood vessels
    (telangiectasias)
  • unusually aggressive tumors- rodent ulcers
  • resemble normal basal cell layer of the epidermis
  • Two patterns
  • multifocal growths originating from the epidermis
  • nodular lesions growing downward deeply into the
    dermis
  • islands of variably basophilic cells with
    hyperchromatic nuclei surrounded by many
    fibroblasts and lymphocytes
  • cells forming the periphery arranged radially
    (pallisading)

31
Basal Cell Nevus Syndrome
  • dominantly inherited
  • numerous basal cell carcinomas in early life
  • abnormalities of bone, nervous system, eyes, and
    reproductive organs

32
MERKEL CELL CARCINOMA
  • Merkel cell of the epidermis (neural
    crest-derived cell)
  • for tactile sensation in lower animals
  • clinically
  • ulcerated nodules
  • cytokeratin 20 positive
  • capable of metastasis and are potentially lethal
  • Fast metastasizing bad prognosis but rare

33
MOLECULAR GENETICS OF SKIN CANCERS
  • organ constantly exposed to environmental hazards
    most commonly affected by neoplasms
  • Basal cell carcinoma is the most common invasive
    cancer in humans,
  • 1 million estimated cases per year in the United
    States
  • incidence of malignant melanoma risen almost
    exponentially
  • hereditary cancer syndromes provided important
    insights of molecular pathogenesis of sporadic
    nonmelanoma skin tumors and melanomas
  • basal cell nevus syndrome or Gorlin syndrome
  • autosomal dominant
  • multiple basal cell carcinomas - lt age 20
  • other conditions
  • tumors (especially Medulloblastoma a rapidly
    growing tumor usually of the vermis of the
    cerebellum, composed of preneurogliar cells and
    ovarian Fibroma),

34
MOLECULAR GENETICS OF SKIN CANCERS
  • pits of the palms and soles
  • odontogenic keratocysts
  • generalized overgrowth
  • systemic manifestations
  • intracranial calcification, cleft lip and palate,
    abnormal segmentation of the vertebra, and rib
    anomalies (bifid, fused, missing, splayed ribs)
  • Gene for NBCCS chromosome 9 (PTCH) (nevoid basal
    cell carcinoma syndrome)
  • "two-hit" hypothesis
  • born with a germ-line mutation
  • second mutation either by environmental mutagens
    or random genetic rearrangement
  • PTCH mutations in 30 of sporadic basal cell
    carcinomas
  • Link- sun exposure and defects in PTCH and p53
  • one-third have mutations (C to T transitions)
  • Mutations in p53 occur in 40 to 60-60 of these
    have UV signature
  • mutations in PTCH and p53 in Xeroderma
    pigmentosum (90 and 40, bear the UV signature).

35
MOLECULAR GENETICS OF SKIN CANCERS
  • Squamous Cell Carcinoma
  • no inherited single gene defect associated with
    squamous cell carcinomas
  • mutations in p53 in Caucasian patients with
    actinic keratoses is high
  • Sunlight-alterations at the early stages of
    carcinogenesis
  • pyrimidine dimers
  • Unlike basal cell carcinomas, aneuploidy (
    abnormal of chromosomes) is very common in
    squamous cell carcinomas, loss of heterozygosity
    of chromosomes 3, 9, and 17 occurs in
    approximately 30 of cases
  • in severely immunosuppressed
  • HPV types 5 and 8,
  • pathogenesis of epidermodysplasia verruciformis
  • formation of numerous cutaneous squamous cell
    carcinomas

36
MOLECULAR GENETICS OF SKIN CANCERS
  • Melanomas
  • 10 to 15 arise in a familial setting
  • familial melanoma syndrome (FMS)
  • the familial BK mole syndrome
  • have large numbers of dysplastic nevi
  • is frequently deleted in melanomas
  • main locus chromosome on 9p21and it encodes
    p16INK4A
  • p16INK4A is the most commonly mutated gene in
    familial melanoma
  • other genes CDK4 and BRAF

37
Tumors of the Dermis
  • BENIGN FIBROUS HISTIOCYTOMA (DERMATOFIBROMA)
  • family of benign dermal neoplasms of fibroblasts
    and histiocytes.
  • adults and
  • legs of young to middle-aged women
  • Morphology
  • Most common form -dermatofibroma
  • benign, spindle-shaped fibroblasts arranged in a
    well-defined, nonencapsulated mass within the
    mid-dermis
  • overlying epidermal hyperplasia forms downward
    elongation of hyperpigmented rete ridges ("dirty
    fingers" pattern)
  • express coagulation factor XIIIa

38
Tumors of the Dermis
  • DERMATOFIBROSARCOMA PROTUBERANS
  • primary Fibrosarcoma of the skin.
  • slow growing, locally aggressive, rarely
    metastasize.
  • Clinically firm, solid nodules ,most frequently
    on the trunk
  • Morphology
  • In contrast to dermatofibroma, the overlying
    epidermis is generally thinned
  • extension from the dermis into subcutaneous fat
    (honeycomb" pattern)
  • composed of fibroblasts arranged radially,
    reminiscent of blades of a pinwheel, a pattern
    referred to as storiform
  • Mitoses not as numerous good prognosis

39
Tumors of the Dermis
  • XANTHOMAS
  • collections of foamy histiocytes within the
    dermis lipid filled
  • Familial or acquired resulting in hyperlipidemia
  • five types.
  • Eruptive wax and wane according to variations in
    plasma triglyceride and lipid contents
  • Tuberous and tendinous Achilles tendon extensor
    tendons of the fingers
  • Plane with primary biliary cirrhosis
  • Xanthelasma (without lipid abnormality) -eyelids.

40
Tumors of the Dermis
  • DERMAL VASCULAR TUMORS
  • Benign (capillary and cavernous hemangiomas),
  • malformations (nevus flammeus or port-wine
    stain), gone with age 14 to15
  • malignant vascular tumors (Angiosarcomas) bad
    prognosis seen in liver patients exposed to
    plastics
  • angioproliferative lesions (Kaposi sarcoma HIV
    (tumor like- bacillary angiomatosis)

41
Tumors of Cellular Immigrants to the Skin
  • Primary cutaneous disorders
  • Epidermal Langerhans cells- Langerhans cell
    histiocytosis
  • T lymphocytes -cutaneous T-cell lymphoma (CTCL),
    sezary syndrome
  • Dermal mast cells Mastocytosis
  • See table in WBC review

42
Tumors of Cellular Immigrants to the Skin
  • LANGERHANS CELL HISTIOCYTOSIS
  • Histiocytosis X, multiple forms
  • histologic patterns
  • First-dermal infiltrate of large, round to ovoid
    cells
  • second pattern -that resemble granulomas
  • Third-xanthoma-like cytoplasm
  • IHC methods -CD1a antigen
  • ultrastructural identification of specific
    organelles (Birbeck granules),

43
Tumors of Cellular Immigrants to the Skin
  • MYCOSIS FUNGOIDES
  • (CUTANEOUS T-CELL LYMPHOMA) ( seen in celiac
    sprue and HTLV)
  • lymphoproliferative disorders affecting the skin
  • Two different clinical types
  • Mycosis fungoides, a chronic proliferative
    process
  • Nodular eruptive variant, mycosis fungoides
    d'emblée
  • Mycosis fungoides
  • primarily in the skin and that may evolve into
    generalized lymphoma
  • most commonly persons older than age 40.

44
Tumors of Cellular Immigrants to the Skin
  • MYCOSIS FUNGOIDES
  • (CUTANEOUS T-CELL LYMPHOMA)
  • Clinically
  • scaly, red-brown patches raised, scaling plaques
    that may even be confused with psoriasis
  • Fungating nodules- Development of multiple
    red-brown nodules correlates with systemic
    spreading
  • seeding of the blood by malignant T cells is
    accompanied by diffuse erythema and scaling of
    the entire body surface (erythroderma), a
    condition known as Sézary syndrome

45
Tumors of Cellular Immigrants to the Skin
  • MYCOSIS FUNGOIDES
  • (CUTANEOUS T-CELL LYMPHOMA)
  • Morphology
  • histological hallmark -Sézary-Lutzner cells they
    have cerebriform nuclei ie looks like brain
    (T-helper cells (CD4 positive) that
    characteristically form band like aggregates
    within the superficial dermis
  • infolded nuclear membranes -hyperconvoluted or
    cerebriform contour
  • (epidermotropism) and form clusters Pautrier
    microabscesses.

46
Tumors of Cellular Immigrants to the Skin
  • MASTOCYTOSIS -? mast cells in the skin other
    organs
  • Localized cutaneous form
  • children and accounts for more than 50 of all
    cases is termed urticaria pigmentosa
  • shortly after birth
  • Systemic mastocytosis- 10
  • adults
  • prognosis may be poor
  • Darier sign -localized area of dermal edema and
    erythema (wheal) that occurs when lesion skin is
    rubbed.
  • Dermatographism -area of dermal edema resembling
    a hive that occurs in normal skin as a result of
    localized stroking with a pointed instrument
  • Pathogenesis.-point mutation of the c-KIT
    proto-oncogene

47
Disorders of Epidermal Maturation
  • ICHTHYOSIS
  • Hyperkeratosis-fishlike scales
  • around the time of birth
  • ichthyosis vulgaris (autosomal dominant or
    acquired)
  • congenital ichthyosiform erythroderma (autosomal
    recessive),
  • lamellar ichthyosis (autosomal recessive),
  • X-linked ichthyosis.
  • Acquired (noninherited) -in adults
  • Associated with lymphoid and visceral malignant
    neoplasms

48
ICHTHYOSIS
  • Morphology
  • compacted stratum corneum
  • loss of the normal basket-weave pattern
  • Pathogenesis
  • primary abnormality -defective mechanisms of
    desquamation
  • retention of abnormally formed scale
  • adhesive organelles called Odland bodies, or
    membrane-coating granules

49
Acute Inflammatory Dermatoses
  • 1. URTICARIA
  • characterized by
  • localized mast cell degranulation
  • dermal microvascular hyperpermeability
  • pruritic edematous plaques called wheals
  • Angioedema-deeper edema of both the dermis and
    the subcutaneous fat
  • develop and fade within hours (usually lt24 hours)
    or last for days or persist for months
  • superficial perivenular infiltrate of
    mononuclear cells Eosinophils

50
URTICARIA
  • Pathogenesis
  • IgE-dependent degranulation can follow exposure
    to a number of antigens
  • IgE-independent urticaria from substances
    directly incite the degranulation of mast cells
    (opiates, curare, and radiographic contrast
    media)
  • Hereditary Angioneurotic edema- production of
    vasoactive mediators (complement-mediated
    urticaria). Deficiency complement 1 inhibitor

51
  • 2. ACUTE ECZEMATOUS DERMATITIS
  • Eczema
  • Early lesion - red, papulovesicular less than
    5mm, oozing, and crusted
  • Later - raised, scaling plaques
  • acute spongiotic dermatitis
  • chronic form - epidermal hyperplasia and
    excessive scale
  • Clinical classification -allergic contact,
    atopic, drug-related, primary irritant
    photo-eczematous

52
. ACUTE ECZEMATOUS DERMATITIS
  • Poison ivy- most obvious example is an acute
    contact reaction
  • Edema
  • in urticaria - localized to the perivascular
    spaces of the superficial dermis
  • in spongiotic dermatitis - seeps into the
    intercellular spaces of the epidermis,
  • Spongy like epidermis is due to prominent
    Intercellular bridges
  • Intraepidermal vesicles are due to shearing of
    intercellular attachment sites (desmosomes) and
    cell membranes

53
ACUTE ECZEMATOUS DERMATITIS
  • The pattern and composition of infiltrate give
    clues to the underlying cause
  • systemic antigens (drugs) -lymphocytic
    infiltrate, eosinophils, and extending deep as
    well as superficial dermal vessels
  • surface contact with antigens -affects the more
    superficial dermal layer

54
  • 3. ERYTHEMA MULTIFORME
  • hypersensitivity reaction to certain infections
    and drugs
  • Infections-typhoid, and leprosy, herpes simplex,
    mycoplasmal infections, histoplasmosis
  • drugs (sulfonamides, penicillin, barbiturates
  • collagen vascular diseases (SLE, PAN,
    dermatomyositis,).
  • malignant disease (carcinomas and lymphomas

55
3. ERYTHEMA MULTIFORME
  • "multiform" lesions, including macules, papules,
    vesicles, and bullae
  • symmetric involvement of the extremities
  • extensive and
  • toxic epidermal necrolysis -clinical situation
    analogous to an extensive burn like a 3rd degree
    burn
  • Stevens-Johnson syndrome seen in children
  • symptomatic febrile form of the disease, result
    in life-threatening sepsis ( sulfonamide use kids
    causes) derm. Emergency
  • The target lesion exhibits central necrosis
    surrounded by a rim of perivenular inflammation.
  • immunologic similarities
  • fixed drug eruptions
  • GVHD
  • skin allograft rejection

56
Chronic Inflammatory Dermatoses
  • 1. PSORIASIS
  • 1 to 2 of people in the United States
  • associated with arthritis, myopathy, enteropathy,
    spondylitic joint disease, or the acquired
    immunodeficiency syndrome
  • Clinically
  • skin of the elbows, knees, scalp, lumbosacral
    areas, intergluteal cleft, and glans penis.
  • Most typical lesion - salmon-colored plaque
    covered by adherent scales (silver-white in color
    )
  • Erythroderma-total body erythema
  • Nail changes- separation of the nail plate from
    the underlying bed (onycholysis), thickening, and
    crumbling
  • pustular psoriasis-rare variant most dangerous
  • generalized and life-threatening

57
2. SEBORRHEIC DERMATITIS
  • More common than psoriasis
  • Regions with a high density of sebaceous glands,
    (scalp, forehead (especially the glabella),
    external auditory canal, retroauricular area,
    nasolabial folds)
  • Not a disease of the sebaceous glands
  • Macules and papules with extensive scaling and
    crusting
  • Fissures- behind the ears
  • Dandruff is the common
  • Infants-presents as cradle cap
  • also be part of Leiner disease (with diarrhea and
    failure to thrive)
  • severe and refeactory in HIV patients

58
2. SEBORRHEIC DERMATITIS
  • Features
  • both spongiotic dermatitis and psoriasis
  • parakeratosis containing neutrophils and serum
    are present at the ostia of hair follicles
    (so-called follicular lipping)
  • HIV-apoptotic keratinocytes and plasma cells
  • Etiology is unknown
  • yeast Malassezia furfur with tinea versicolor
    play a pivotal role (Rx.ketoconazole)
  • sebum is also involved
  • patients with Parkinsonism show increased sebum
    production increased incidence of seborrheic
    dermatitis

59
3.LICHEN PLANUS
  • "Pruritic, purple, polygonal papules"
  • of the skin and mucous membranes
  • self-limiting resolves spontaneously 1 to 2
    years after onset
  • in chronic mucosal and para -mucosal
    lesions-Malignant degeneration
  • zones of postinflammatory hyperpigmentation
  • Wickham striae -papules are highlighted by white
    dots or lines
  • zones of hypergranulosis
  • loss of melanin pigmentation into the dermis as
    the basal cell layer is destroyed

60
3.LICHEN PLANUS
  • Multiple, symmetrically distributed on wrists and
    elbows glans
  • 70 of cases, oral lesions are white, or netlike
    areas
  • Koebner phenomenon
  • infiltrate of lymphocytes along the
    dermoepidermal junction - angulated zigzag
    contour (saw- toothing) ,
  • basal keratinocytes resemble of the stratum
    spinosum (squamatization) also seen in vetaligo
  • Anucleate, necrotic basal cells inflamed
    papillary dermis
  • colloid or Civatte bodies (also in any chronic
    dermatitis)
  • epithelium of hair follicles is referred to as
    lichen planopilaris.
  • pathogenesis -not known
  • cell-mediated immune reactions

61
4. LUPUS ERYTHEMATOSUS
  • SLE
  • systemic manifestations,
  • localized, cutaneous form -discoid lupus
    erythematosus (DLE).
  • discoid lupus erythematosus (DLE).
  • poorly defined malar erythema or erythematous
    scaling plaques
  • develop or worsen with sun exposure
  • keratotic plugs in follicular ostia
  • lateral compression often produces wrinkling, a
    sign of epidermal atrophy
  • lymphocytes along the dermoepidermal or the
    dermal-follicular epithelial junction
  • Deep perivascular and periappendageal (e.g.,
    around sweat glands) infiltrates

Band test
62
4. LUPUS ERYTHEMATOSUS
  • infiltration of subcutaneous fat is called lupus
    profundus.
  • basal cell layer -diffuse vacuolization
  • epidermal layer -atrophied, with loss of the
    normal rete ridge pattern
  • Involved hair follicles -epithelial atrophy,
    dilated and plugged with keratin
  • Periodic acid-Schiff (PAS) -marked thickening of
    the epidermal basement membrane zone
  • direct immunofluorescence - characteristic
    granular band of immunoglobulin and complement
    along the dermoepidermal and dermal-follicular
    junctions ( lupus band test)
  • both lesional and normal skin in many cases of
    SLE
  • seen in lesional skin but not normal skin in DLE
  • Both formation and deposition of immune complexes
    and complement components C5b to C9 -humoral
    mechanisms of injury
  • In DLE band test positive only in affected skin
    SLE both affected and normal skin

63
Blistering (Bullous) Diseases
  • 1.PEMPHIGUS
  • autoimmune blistering disorder resulting from
    loss of the integrity of normal intercellular
    attachments within the epidermis and mucosal
    epithelium
  • life-threatening
  • fourth to sixth decades of life
  • 1) Pemphigus vulgaris -MC type (more than 80)
  • mucosa and skin, especially on the scalp, face,
    axilla, groin, trunk,
  • (2) Pemphigus vegetans -rare (groin, axillae, and
    flexural surfaces)
  • presents not with blisters but with large, moist,
    verrucous (wartlike), vegetating plaques,
  • (3) Pemphigus foliaceus -more benign form,
    epidemic form in South America
  • (4) Pemphigus erythematosus rare, groin,
    axillae, and flexural surfaces
  • face in a lupus erythematosus-like fashion.
  • localized, less severe form of pemphigus foliaceus

64
1.PEMPHIGUS
  • In all forms
  • Acantholysis-dissolution, or lysis, of the
    intercellular adhesion sites within a squamous
    epithelial surface
  • Blister
  • P. vulgaris - suprabasal acantholytic bliste
  • P. foliaceus -selectively involves the
    superficial epidermis at the level of the stratum
    granulosum
  • Sera-antibodies (IgG) to intercellular cement
    substance of skin and mucous membranes
  • Basis for direct and indirect diagnostic
    immunofluorescence testing of skin and serum,
    respectively
  • P. vulgaris antibody reacts with desmoglein 3
  • P.foliaceus antibody reacts with desmoglein 1

65
2. BULLOUS PEMPHIGOID
  • common autoimmune, vesiculobullous disease
  • elderly
  • less often
  • involvement of mucosal surfaces
  • bullae do not rupture as easily
  • inner aspects of the thighs, flexor surfaces of
    the forearms, axillae, groin, and lower abdomen
  • heal without scarring
  • subepidermal, nonacantholytic blister
  • Eosinophils showing degranulation
  • beneath the epidermal basal cell layer.
  • vacuolated basal cell layer

66
2. BULLOUS PEMPHIGOID
  • subepidermal, nonacantholytic blister
  • Eosinophils showing degranulation
  • beneath the epidermal basal cell layer.
  • vacuolated basal cell layer
  • antibodies directed against proteins at the
    dermal-epidermal junction.
  • linear zone deposition of immunoglobulin and
    complement
  • lupus erythematosus is similar, but granular
  • circulating antibody reacts with antigen
  • (hemidesmosomes)
  • Degranulating eosinophils are often associated
    with necrosis of basal keratinocytes

67
3.DERMATITIS HERPETIFORMIS
  • papules, vesicles, and occasional bullae on an
    erythematous, often urticarial base
  • Malesgt Females
  • third and fourth decades
  • with celiac disease (both enteropathy respond to
    a diet free of gluten)
  • plaques and vesicles are extremely pruritic
  • bilaterally and symmetrically
  • extensor surfaces, elbows, knees, upper back, and
    buttocks grouped, name herpetiformis
  • early lesions
  • Fibrin and neutrophils
  • tips of dermal papillae, forming small
    microabscesses subepidermal blister
  • Eosinophils of older lesions (creating confusion
    with bullous pemphigoid)

68
3.DERMATITIS HERPETIFORMIS
  • immunofluorescence
  • granular deposits of IgA selectively localized in
    the tips of dermal papillae
  • antibodies against gliadin, reticulin (IgA and
    IgG )
  • HLA-B8 and HLA-DRw3- prone

69
Immunofluorescence
pemphigus vulgaris
Bullous pemphigoid
Dermatitis herpetiformis
lupus band test
70
4. NONINFLAMMATORY BLISTERING DISEASES
EPIDERMOLYSIS BULLOSA, PORPHYRIA
  • vesicles and bullae are not mediated by
    inflammatory mechanisms.
  • Epidermolysis bullosa
  • group of disorders with blisters at sites of
    pressure, rubbing, or trauma, at or soon after
    birth
  • Simplex type
  • degeneration of the basal cell layer of the
    epidermis
  • mutations in the genes encoding keratins 14 and 5
  • Junctional type
  • blisters in normal skin at lamina lucida
  • scarring dystrophic types, blisters
  • beneath the lamina densa,
  • inherited disease
  • mutations in the COL 7A1 gene that encodes type
    VII collagen

71
NONINFLAMMATORY BLISTERING DISEASES
EPIDERMOLYSIS BULLOSA, PORPHYRIA
  • Porphyria
  • inborn or acquired disturbances of porphyrin
    metabolism
  • Classification based on clinical and biochemical
    features
  • five major types
  • Cutaneous
  • urticaria and vesicles that heal with scarring
  • exacerbated by exposure to sunlight
  • subepidermal vesicle
  • marked thickening of the walls of superficial
    dermal vessels

72
Disorders of Epidermal Appendages
  • ACNE VULGARIS
  • middle to years late teenage males have more
    severe disease
  • milder in Asian descent
  • in adolescents result of physiologic hormonal
    variations and alterations in hair follicle
    maturation
  • induced or exacerbated by drugs
  • occupational contactants
  • Some families
  • heavy clothing and tropical climates
  • noninflammatory and inflammatory types
  • without a visible central plug
  • Open comedones
  • central black keratin plug
  • oxidation of melanin pigment (not dirt)
  • Closed comedones
  • open and closed comedones

73
ACNE VULGARIS
  • Four key components
  • changes in keratinization of follicular
    infundibulum
  • increase in size of sebaceous glands with puberty
    or increased activity
  • lipase-synthesizing bacteria (Propionibacterium
    acnes)
  • induction of inflammation in the follicle
  • Dermal abscesses with scarring
  • Pathogenesis is incompletely understood
  • Endocrine (especially androgens)
  • bacterial lipases of Propionibacterium acnes
  • resulting in the earliest inflammatory phases
  • clinical improvement with synthetic vitamin A
    derivative 13-cis-retinoic acid (isotretinoin)

74
Panniculitis
  • ERYTHEMA NODOSUM MCC ERYTHEMA
  • INDURATUM
  • Panniculitis
  • inflammatory reaction in the subcutaneous fat
  • Erythema nodosum
  • the most common form of panniculitis
  • acute presentation in infections (beta-hemolytic
    streptococcal infection, tuberculosis and, less
    commonly, coccidioidomycosis, histoplasmosis, and
    leprosy
  • drug (sulfonamides, oral contraceptives),
    sarcoidosis, inflammatory bowel disease)
  • malignant neoplasms
  • lower legs
  • erythematous plaques and nodules
  • better felt than seen
  • Biopsy usually required

75
Panniculitis
  • Erythema induratum
  • uncommon type of panniculitis
  • adolescents and menopausal women
  • cause is not known
  • primary vasculitis affecting deep vessels
  • most commonly occurs without an associated
    underlying disease.
  • Erythema nodosum
  • Vasculitis is not present
  • erythema induratum,
  • necrotizing vasculitis
  • granulomatous inflammation and zones of caseous
    necrosis
  • Weber-Christian disease (relapsing febrile
    nodular panniculitis) is a rare form of lobular,
    nonvasculitic panniculitis seen in children and
    adults
  • Factitial panniculitis caused by self-inflicted
    trauma or injection of foreign or toxic substances

76
Infection and Infestation
  • 1. VERRUCAE (WARTS)
  • common lesions of children and adolescents
  • caused by HPV, self-limited, regressing
    spontaneously
  • Classification
  • Verruca vulgaris is the most common type of wart
  • hands, dorsal surfaces and periungual areas
  • Verruca plana, or flat wart- face or the dorsal
  • hands
  • Verruca plantaris and verruca palmaris -soles and
    palms
  • Condyloma acuminatum (venereal wart) occurs on
    the penis, female genitalia, urethra, perianal
    areas, and rectum
  • cytoplasmic vacuolization (koilocytosis)
  • verrucous or papillomatous epidermal hyperplasia

77
2. MOLLUSCUM CONTAGIOSUM
  • common, self-limited viral disease of the skin
    caused by a poxvirus
  • brick shaped,
  • largest pathogenic poxvirus in humans
  • largest viruses in nature
  • children and young adults
  • trunk and anogenital areas
  • Firm, pruritic, pink to skin-colored umbilicated
    papules
  • curd-like material on staining with Giemsa show
    diagnostic molluscum bodies
  • cytoplasmic inclusion in cells of the stratum
    granulosum and the stratum corneum
  • virions are present within molluscum bodies.

78
3. IMPETIGO
  • Common superficial bacterial infection of the
    skin
  • Highly contagious - healthy children, adults in
    poor health
  • impetigo contagiosa and impetigo bullosa (differ
    in size of the pustules)
  • Staphylococcus aureus
  • Face and hands
  • Honey-colored crust.
  • characteristic microscopic features
  • accumulation of neutrophils beneath the stratum
    corneum
  • Sub-corneal pustule
  • Blister formation - due to bacterial production
    of a toxin specifically cleaves the desmoglein 1
    cell-to-cell adhesion within the uppermost
    epidermis

79
4. SUPERFICIAL FUNGAL INFECTIONS
  • confined to the stratum corneum
  • caused primarily by dermatophytes
  • organisms grow in the soil and on animals
  • Tinea capitis usually occurs in children
  • Scalp-asymptomatic, often hairless patches of
    skin
  • erythema, crust formation, and scale
  • Tinea barbae - uncommon disorder beard area of
    adult men
  • Tinea corporis - common superficial fungal
    infection of children affecting body surface

80
4. SUPERFICIAL FUNGAL INFECTIONS
  • Tinea cruris - inguinal areas of obese men during
    warm weather
  • Tinea pedis (athlete's foot) affects 30 to 40
    of the population
  • diffuse erythema and scaling of web spaces
  • Spread to nails- onychomycosis.
  • Tinea versicolor - upper trunk
  • Caused by Malassezia furfur, a yeast
  • present in cornified layer of lesional skin,
    hair, or nails
  • scraping - produce colonies
  • Fungal cell walls, rich in MPS, stain bright pink
    to red with PAS stain

81
5 . ARTHROPOD BITES, STINGS, AND INFESTATIONS
  • Arachnida (spiders, scorpions, ticks, and mites),
    Insecta (lice, bedbugs, bees, wasps, fleas,
    flies, and mosquitoes), and Chilopoda
    (centipedes)
  • Vectors for secondary invaders, such as viruses,
    bacteria, rickettsiae, and parasites
  • Black widow spider venom -severe cramps and
    excruciating pain
  • Brown recluse spider venom - enzymes that produce
    tissue necrosis
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