Post on 13-Dec-2015
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November 13, 2013
Surgical pathology – diseases of the skin
Layers of the skin:
Epidermis Dermis
o Papillary dermiso Reticular dermis
*subcutis: altered to appear tissue-like tendon/fascia
Other structures seen:o Sweat glandso Hair follicle o Sebaceous gland
EPIDERMIS
Layers (bottom to top)o Basal layer/stratum basale
Low columnar to cuboidal cells Mitotic activity Aka. Stratum germinativum
o Spinous cell layer/stratum spinosum Spindle shaped cells Abundant: keratin filaments
o Stratum granulosum 2-3 layers More flattened Fusiform nuclei that lie parallel to
the skin surface Abundant: keratohyaline keratids
o Stratum corneum Cant see nuclei inside
keratinocytes because they are already flattened
o Stratum lucidum Found between corneum and
granulosum Cells
o Most of the cells are referred to as KERATINOCYTES
Keratin is elaborated by cells from stratum basale to s. spinosum, hence the abundance of keratohyaline keratids
o MELANOCYTES Normally seen at stratum basale
Produces the pigment melanin Transfers the pigment inside
melanosomes to its neighboring keratinocytes
o EPIDERMAL MELANIN UNIT 1 melanocyte + satellite
keratinocytes One melanocyte to a group of
keratinocytes to which it will donate melanosomes
o LANGERHANS CELL Attaches to the MC receptor of IgA
and IgE as well as CD3 Antigen receptor cells Filters antigens
o MERCKEL CELLS Hard to identify using H&E Forms complex cells and functions
as tactile receptorso RUFINI CELLSo PACINIAN CELLS
Basal Laminao Lamina densa
In contact with stratum basaleo Lamina lucida
Inferior layero Lamina intermedia
Middle layer
MACROSCOPIC TERMS
Excoriationo Traumatic lesion that results in a liner skin
lesiono Most of the time inducedo Looks like a deep scratch
Lichenification o Thickened and rough skin characterized by
prominent skin markings (as lichen on a tree trunk)
o Usually the result of repeated rubbingo Prominent skin markings
Maculeo Flat well circumscribed, maximum of 5mm
November 13, 2013
Surgical pathology – diseases of the skin
o Characterized by flatness and distinguished by coloration
o Called a patch if more than 5mm Onycholysis
o Separation of nail plate from nail bed Papule
o Elevated dome-shaped or flat-topped lesion 5mm or less across
o Nodule is greater than 5mmo Solid and raised
Plaqueso Psoriasiso Elevated flat-topped lesion, usually greater
than 5 mm acrosso May be caused by coalescent papules
Pustuleso Discrete, pus-filled, raised lesiono Ex: chicken pox
Scaleso Dry, horny, platelike excrescenceo Result of imperfect/abnormal cornification
Blistero Vesicle if <5mmo Bullae if >5mmo Fluid-filled raised lesiono Commonly seen in burn patients
Whealo Itchy, transient, elevated lesion with
variable blanching and erythema formed as the result of dermal edema
o Urticaria
MICROSCOPIC TERMS
Acantholysis o Loss of intercellular cohesion between
keratinocytes Acanthosis
o Epidermal hyperplasia Interdigitating papillary dermis Thickening of the epidermis Widening and elongation of the
rete ridges Dyskeratosis
o Prematurely keratinized cells beneath stratum granulosum
o Not dysplastic because there is still polarity of the cells
o Abnormal, premature keratinization within cells below the stratum granulosum
Erosiono Discontinuity of the skin resulting to
incomplete loss/separation of the epidermis
Exocytosiso Infiltration of the epidermis by
inflammatory cells such as lymphocytes Hydropic swelling (ballooning)
o Intracellular edema of keratinocyteso Often seen in viral infectionso Swollen because of accumulation of
cellular fluids Hypergranulosis
o Hyperplasia of the stratum granulosumo Due to intense/repeated rubbing
Hyperkeratosiso Secondary to qualitative abnormality of the
keratin or keratinization resulting to hyperplastic/thickened stratum corneum
Lentiginouso A linear pattern of melanocyte
proliferation within the epidermal basal cell layer
o Results into a hyperpigmented stratum basale
Papillomatosiso Surface elevation caused by hyperplasia
and enlargement of contiguous dermal papillae
o Resut: Whitening of dermal papillae Thickening of rete ridges
Parakeratosiso Keratinization with retained nuclei in the
stratum corneumo On mucous membranes, parakeratosis is
normal Spongiosis
o Intercellular edema of the epidermis
November 13, 2013
Surgical pathology – diseases of the skin
o Accumulation of fluid in between cellso Do not appear separated unlike
acantholysis Ulceration
o Discontinuity of the skin showing complete loss of the epidermis revealing dermis or subcutis
o Ex: cutaneous leishmaniasiso Complete separation of the epidermis
Vacuolizationo Formation of vacuoules within or adjacent
to cellso Often occurs to the area between basal cell
– basement membrane zone area
DISORDERS OF MELANOCYTES AND PIGMENTATION
Freckles
Medical term: Ephelis Most common pigmented skin lesion during
childhood among Caucasians. Appear during childhood cycle happens (waxing
and waning) winter: light colored; summer: dark colored
Macular lesions Tan to pink to brown Under the microscope:
o Increase in the amount of melanin located within the basal keratinocytes
o Increased melanin pigment and not in the number of melanocytes
o In some there is slight enlargement of melanocytes
Lentigo/Lentigins
Will not have darkening in color Uniform in color throughout the year Under the microscope:
o Linear proliferation of melanocytes causing hyperpigmented basal cell layer along the epidermis
o Elongation and thinning of the rete ridges
Nevus/nevi/melanocytic nevi
Old term: nevucellular nevus Tumors of the melanocytes Could either be macules, flat or elevated Have a uniformed coloration or pigmentation With smooth borders (distinguished from
melanoma) Most but not all would run a benign course Has something to do with the cell signaling
pathwayso A set of genes tend to control the
proliferationo P16 – tumor suppressor gene
Permanent growth arrest Nevus cells – transformed melanocytes that
become spherical cells occurring in nests and further characterized as having round or spherical nuclei surrounded by a clear cytoplasm
o Seen at the dermo-epidermal junctiono Junctional nevuso As the nevus cells mature, they descend
down into the dermis Compound nevus – elevated nevus
on the dermis .. Intradermal/dermal nevus
o nevus cells at the dermiso Most matureo All nevus evolve from junctional to dermal
Evolution is accompanied by a process of maturation
o No longer arranged in nests in dermal Rather, arranged in cords
o Cells tend to produce more cholineresterase enzymes and lose tyrosinase activity
In melanoma: lack of maturation of melanocytes
Dysplastic nevus
November 13, 2013
Surgical pathology – diseases of the skin
Increased correlation with the development of melanoma in individuals harboring the heritable melanoma syndrome
Other term: BK moleo Initials of the families wherein these nevus
were first documented Also occurs on non-sun exposed areas Irregular border Pigmentation is variegated Under the microscope:
o Histologically a compound nevus lightero However, there a junctional type nevus on
some areas darker o On HPO:
Coalescent groups along the dermo-epidermal junction
Some tends to drop off and align themselves along the basal keratinocytes
Atypia is visible Nuclear irregularities –
angulations, nuclear hyperchromatia
Releases the pigment melanin engulfed by dermal macrophage termed as “melanin pigment incontinence”
May develop to a melanoma in susceptible individuals so for most of the time it is clinically stable
Melanoma
All are malignant 2 risk factors:
o Sun exposureo Genetic susceptibility
ABC’s of melanoma:o A: asymmetry
A part is flat and others are elevated
o B: border Irregular
o C: color Variation in color
Mole melanoma
o Enlargemento Paino Itching
Under the microscope:o Melanoma cells are monotonouso Infiltrating (on LPO) the epidermis
Equivalent to Clark’s method 5 levels 1- epidermis 2 – papillary dermis 3 – papillary-reticular
dermal interface 4 – reticular dermis 5 – subcutaneous tissue
Central to the understanding of melanoma:o Radial growth
Confined in the epidermis Superficial spreading type of
melanoma Period is non-predictable Lentigo melanoma
Manifestation of melanoma in its radial growth phase
Lentiginous proliferation of melanocytes on the melanoma
Medium to large cells, large nuclei, prominent nucleoli, found arranged in nests
o Vertical growth Herald down into a tumor Once melanoma is in its vertical
growth phase, it already has the potential to metastasize
Lymphocytic infiltration alongside any tumor is a good sign good immunosurveillance
BENIGN EPITHELIAL TUMORS
Seborrheic keratosis
Commonly occurs in middle aged or older individuals
November 13, 2013
Surgical pathology – diseases of the skin
Called senile keratosis Plaque-like lesion with velvety to granular texture There are small holes Occurring on the face, extremities and neck Variable pigmentation Well-delineated Under the microscope:
o Corned cysto Pseudo-corned cyst
Downward vagination of keratin into the tumor
o Acanthosiso Hyperkeratosiso Irritation squamous edi?
Whorls of squamous cells o Lesion is sharply demarcated
Very clue that its benigno Does not manifest peaks and valleys
Used as a marker of underlying malignancy: Leser-trelat
o Gastrointestinal carcinoma
Acanthosis Nigricans
Present as a thickened darkened velvety area commonly noted along the flexural regions of the body
Its presence might signal either a benign or malignant process
o 80% is benign Endocrine disorder DM or
pineal gland tumor Obesity Syndrome
o 20% malignancy: gastrointestinal carcinoma
Microscope:o Epidermis and the underlying enlarged
dermal papillae forming peaks and valleyso Hyperpigmented stratum basaleo Hyperplasia of stratum corneum
hyperkeratosis
Fibroepithelial polyp
Skin tag or Acrochordon
Squamous papilloma – but epidermal feature is not the same
Sac-like attacked to the surface of the skin via a slender skin stalk
Frequently remains small: <1cm in diameter May increase in size presumably secondary to
hormonal differences Microscopic:
o Fibrovascular core covered by unremarkable squamous epithelium
If no vascular it is called: fibronal
Epithelial cyst (Wen)
Anglosaxon of Wenn meaning a lump or tumor Invagination with cystic expansion of the epidermis
or the hair follicle Variant:
o Epidermal inclusion cyst Dermal or subcutaneous nodule A cyst with a lining made of mature
squamous epithelium (reminiscent of normal epidermis)
Content is made of laminated strands of keratin
Wall made of normal epidermiso Pilar or trichellemal cyst
Sculp – common location Made up of a wall consisting of
follicular epithelium (epidermis without a granular cell layer)
Content: lipid (from sebaceous glands) + keratin mixture
o Dermoid cyst Wall: normal epidermis + skin
appendages protruding out of its wall
Sebaceous glands Hair follicle
Content: keratin debriso Steatocystoma simplex
Wall: sebaceous gland duct made up of stratified squamous epithelium
Ccompressed sebaceous gland nodules along its wall
November 13, 2013
Surgical pathology – diseases of the skin
Steatocystoma complex – a __ secretion of keratin 17
Adnexal tumors
Differentiates from or have the tendency towards skin adnexae: apocrine, eccrine, hair follicles
o Cylindroma, equinchoroma Papular nodular lesions Cylindroma would coalesce when
not treated and occur on the entire head Turban tumor
Microscope: Basaloid cells arranged in
islands that fit each other like pieces of jigsaw puzzle
o Trichoepithelioma Microscope
Basaloid cells seen in aggregates
Seen to be forming hair follicle-like structures
o Looks like keratinizing squamous cell ca
o Sebaceous adenoma Popular lesions seen on areas of
the body with abundant sebaceous glands
Microscope: Proliferation of the lobules
of sebaceous glands characterized by:
o Hyperplastic or less mature at the periphery
o Mature sebocytes centrally (bubbly or frothy cytoplasm)
Multiple: ___o Pilomatrixsoma
Nodular lesion said to be semitransparent and firm
Microscope Two types of cells:
o Basaloid cells (darker)
o Ghost cell Histologically resembles
the hair root of a hair follicle
o Apocrine carcinoma Large, necrotic and ulcerated Microscope
Well-differentiated glandso Malignant sweat
glands HPO: decapitation
secretion – characterizes a normal apocrine gland
o Secretion will pinch up from..
Abortive tumor gland formation – tumor gland in cluster that may seem more of a malignant tumor rather than benign
PREMALIGNANT, MALIGNANT EPIDERMAL TUMORS
Actinic keratosis
Most significant: Sun-exposed areas of the body Arsenicals Associated with hyperkeratosis Scaly plaque-like lesions
o Secondary to overproduction of keratino Exaggerated keratin can look like a horn
Hard when touched Microscopic
o Cytologic atypia emphasized only in the stratum basale
o Hyperkeratosiso Parakeratosis
Cells still retain their nucleio Dermal elastosis
Secondary or reactive to the tumor H&E: bluish hue of the dermal
elastosis
November 13, 2013
Surgical pathology – diseases of the skin
o When it becomes malignant squamous cell carcinoma
Squamous cell carcinomao Most significant causative factor: UV light
or sun exposure Damages DNA
o 2nd most important factor: immunosuppression
May also be caused by UV light by dampening the immunosurveillance factor of the langerhan’s cells: p53 (tumor suppressor gene
P53’s function becomes directed more towards cell proliferation and abnormal gene rearrangement
Increased risk for infection Like HPV type 5 & 8
o Other risk factors: Tobacco and betel nut chewing
o Lightly pigmented individualso Second most common tumoro Two types:
In situ Plaque-like scaly lesion Much like actinic
Invasive Nodular appearance and
may ulcerate Good differential: basal cell
….
o In situ squamous cell carcinoma – malignant
Limited by a clean basement membrane
Atypical cell with pyknotic nucleus surrounded by cytoplasm dyskeratotic cell
o Invasive squamous cell ca
Atypical squamous cells arranged in sheaths and are infiltrating the dermis
Differentiation varies Keratinized well
differentiated No keratinization poorly
differentiatedo Pinkish moderate
to abundant cytoplasm
o Distinct feature: Prominent intracellular ridges
o Immunohistochemical screening – next step
o Keratoacanthomas – benign proliferative lesions that has to be differentiated from squamous cell carcinoma
Cup-shaped Common location: vermillion
border of the lips Filled with keratin debris Regresses spontaneously even
without treatment Base is clean
BASAL CELL CARCINOMA
Most common invasive cancero MC skin cancer
Occurs on lightly pigmented individuals Exposure to UV light Two hit hypothesis –
o Ex: nevoid basal cell ca syndrome – germ line mutation for PTCH
o Abnormality occurs in the first allele at birth then later in life second allele activated from acquired mutation from sunlight
o Has to be complexed with sonic hedgehog protein in order to have a normal signaling which involves normal polarity for the normal effect of the hair follicle. Also involved in the normal cycle.
November 13, 2013
Surgical pathology – diseases of the skin
o PTCH when inactivated, SNO favor cell proliferation enhacing basal cell ca
DNA damage Pearly papule with telangiectasia – markedly
subepidermal blood cells Clinical course:
o Slow growing tumor Can be pigmented basal cell ca
o Clinically mistaken as melanoma Chronic neglected type basal cell ca
o With ulcerationo Can erode through the sinuses Rodent
ulcers Divided into three types
o Superficial type Groups of tumor cells Basal cell is not expected to occur
along the … Basaloid Islands infiltrating downward
Periphery arranged in a pallisading manner. Distinguished from benign or trichoepithelioma:
o Cleft/ matrix – retracts to form cleftso Mucinous matrix
Variable amounts of lymphocytic infiltrates surrounding the islands
TUMORS OF THE EPIDERMIS
Dermatofibroma
Common type of benign fibrous histiocytoma Arise as a consequence of rupture Interpreted as an abnormal form of repair after
trauma Popular or nodular, well demarcated, elevated Distinguished from acrochordon which is surround
by a slender stalk Spindle shaped cells (fibroblasts) producing a mass-
like effect No capsule Often accompanied by hyperplasia of the
epidermis acanthosis
Unencapsulated only proliferation of fibroblasts. Benign group of cells that proliferated together to
form a mass Leiomyoma – spindle shaped cells ihn fascicles
abnd whirl like pattern
Dermatofibrosarcoma protuberans
Arising from the fibroblasts of the skin Because of blanaced translocation between the
collagen and platelet derived growth factor Overexpression of PTGF which is a promoter of
survival and product Lesions: variable, plaque-like Irregular: erythematous border May develop nodular lesions Fish flesh appearance Microscopi c
o Tumor cellso Thinning of the epidermiso Storey form patterno Well-differentiatedo No severe atypia and mitosiso Mitotic figures are rare or absento Cytologic atypia
Nuclear enlargement Nuclear irregularity Nuclear hyperchromasia
Can extend as far as the subcutaneous tissue which contains the fat cells produces a honeycomb pattern
TUMORS OF CELL MIGRANTS TO THE SKIN
Lymphocytes and mast cells
Mycosis fungoides
Forms: Cutaneous T cell Lymphoma (CTCL) o Cell of origin: CD4 + T lymphocytes (helper
T cells) Evolves into Occurring into the skin Initial stage: Patch stage
o Usually seen on the trunk Plaque stage
November 13, 2013
Surgical pathology – diseases of the skin
o Multiple plaques Nodular stage
o Tumor stageo Occur if there’s many plaque
Generalized erythema erythrodermao Sezary syndromeo Final stage
Distinctive histologic feature: sezary-lutzner cellso Arranged in bands on superficial dermiso Seen as individual cells or clusters when it
invades the epidermis Called Pautrier microabscesses
Mastocytosis
Disorder that involves proliferation of mast cells Variants:
o Urticaria pigmentosa variant Papules develop into small plaques
or nodules and end up into blisterso Solitary mastocytosis
Nodular blistero Systemic
Multiple plaques Abnormality
o C-KIT activation mutation Mast cell degranulation releasing heparin and
histamine Dermatographism
o Dermal edema after stroking the surface of the skin
Darier signo Wheal formation
GI bleedingo Due to heparin
Mast cells – characterized by a round to oval hyperchromatic nucleus with moderate amount of granular cytoplasm
o Toluidine blue or giemsa highlights the mast cells
o Metachromatic
ICHTHYOSIS
Skin lesions characterized by fish-like scales
Secondary to defective desquamation Not a secondary inflammation Appears weeks after birth Thickened plaque-like scales Represents compacted stratum corneum Microscopic
o Lamellated layers of stratum corneumo Basket weave pattern lamellated
ACUTE INFLAMMATORY DERMATOSES
Urticaria
Pruritic Papular or in the form of wheals that are due to
dermal edema Histologic features
o Secondary to localized mass cell inflammation
o Epidermis is unremarkableo Normal appearance: Bundles of collagen
fibers became far aparto Mild lymphocytic infiltrateso Lymphangectasia – lymphatic vessels
dilated
Acute eczematous dermatitis
Contact dermatitis Plaque like appearance
Erythema multiforme
Target lesion central macule surrounded by a pale area
Clinical variant associated with a systemic febrile disease that is typically seen in children: steven-johnson syndrome
Toxic epidermal necrolysis: similar appearance to burns
Microscopico Interface dermatitiso Vacuolization or vacuolar change
Should be noted at the dermo-epidermal junction
November 13, 2013
Surgical pathology – diseases of the skin
o Necrotic keratinocyteo Dominating cell: CD8 T lymphocytes
CHRONIIC INFLAMMATORY DERMATOSES
Psoriasis
Areas frequently affectedo Scalpo Elbowso Gluteal
Caused by HLA-C Other factors:
o Interleukinso Cytotoxic t cellso Interferon
Pink or salmon colored plaques covered by silvery white scales
Erythroderma Nail changes: yellow brown discoloration
o Pittingo Dimplingo Onicholysis/separation from nail bed
Pustula psoriasis – a variant of psoriasis that causes pustules
Microscopic:o Hyperparakeratosiso Regular downward elongation of the rete
ridgeso Deposition of neutrophilic infiltrates within
the stratum corneum called munro microabscesses
o Suprapapillary plane- thinning of the epidermis at the dermal papillary thick
capillary bleeding auspitz sign
Seborrheic dermatitis
Dandruff Not a disease of the sebaceous glands Papulopustular lesions External ear is also susceptible
o Sometimes fissures develop in the retroauricular region
Histologic features:o Like eczematous dermatitis and…o Acanthotic lesions seen during the later
part of the diseaseo Hyperkeratosis falling into the hair follicles
together with neutrophils follicular limping
o Perivascular inflammatory infiltrates – mixture of lymphocytes, histiocytes and neutrophils
Lichen planus
6 Po Pruritico Purpleo Polygonalo Papuleso Planar plaques
Distinguished from psoriasis through:o Wickham striae hypergranulosis
Oral lesions – fish net or reticulated patterned T cell mediated skin disorder Microscopic
o Hypergranulosis Hyperplasia of the granular layer of
the epidermiso Interphase dermatitis
Along the dermo-epithelial junction
o Retention of nuclei in the stratum corneum – parakeratosis
o Necrotic keratinocytes at the epidermiso Stratum basale cuboidal spindle o Change in contour of the dermo-epidermal
contour unangulated appearance saw-toothing
o Dead keratinocytes at the stratum basale they are called Civatte bodies
BULLOUS DISEASES
Pemphigus vulgariso With oral ulcers
Pemphigus vegetanso Verrucous wart-like lesions
Pemphigus folliaceous
November 13, 2013
Surgical pathology – diseases of the skin
o Erythematous o Not as raw as vulgariso Occur in mallar area
Paraneoplastic pemphiguso Autoantibodies against desmolgelins
Prominent feature in pemphigus Microscopic
o Acantholytic keratinocytes are prominently seen between stratum corneum and basale
Suprabasal acantholytic blister Under immunofluorescence
o Immunoglobulinso Entire epidermiso Distinguished from pemphigous
Pemphigus vegetans – microabsecces, verrucous hyperplasia of the epidermis, severe acanthosis
Inflammatory blistering disorders
Bullous pemphigoid
Blisters are tense Do not easily rupture Heal without scarring Microscopic:
o Subepidermal blister Immunofluorescence:
o Linear deposits of immunoglobulins
Dermatitis herpetiforms
May appear as grouped vessicles Microabscess beneath the dermal papilla Subepidermal blisters Immunofluorescence
o Granular IgA deposits along the DEJ but more prominently seen at the dermal papillae
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