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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