Skin Pathology - 2024

(Dermatopathology)
Tan Yongcheng Benjamin
MBBS, FRCPath
< single image > Senior Consultant
4.3cm x 5.5cm
Department of Anatomical Pathology
Division of Pathology
Singapore General Hospital
Contents
Terminology

Inflammatory conditions

Infections

Blistering conditions

Neoplasia
 SKIN
The skin is the largest organ in the body
Skin conditions are very common
There are thousands of specific skin diseases
 Skin - Components
• Epidermis
• Squamous cells (keratinocytes)
• Melanocytes
• Dermis
• Reticular and papillary dermis
• Pilosebaceous units
• Sweat glands
 Terminology - Macroscopic
• Macule: Flat, circumscribed area of any size distinguished from surrounding
skin by coloration
• Papule: Elevated solid area 5 mm or less in diameter
• Nodule: Elevated solid area more than 5 mm in diameter
• Plaque: Elevated flat-topped area, usually more than 5 mm in diameter
• Vesicle: Fluid-filled raised area 5 mm or less in diameter (small blister)
• Bulla: Fluid-filled raised area more than 5 mm in diameter (big blister)
• Wheal: Itchy, transient, elevated lesion with variable blanching and erythema
(result of dermal oedema)
 Terminology - Macroscopic
• Blister: Common term used for vesicle or bulla
• Pustule: Discrete, pus-filled raised area
• Scale: Dry, horny, platelike excrescence; usually the result of imperfect cornification
• Lichenification: Thickened and rough skin characterized by prominent skin
markings; usually the result of repeated rubbing or scratching
• Excoriation: A traumatic lesion characterized by breakage of the epidermis, causing
a raw linear area usually due to scratching.
 Terminology - Macroscopic
• Verrucous: Like a wart, also described as warty
• Erythematous: Red, due to inflammation and congestion etc
• Ulcerated: Break on the surface, resulting in a “crater” area
• Hyperpigmentation: Darkening of the skin due to increased pigmentation eg after
inflammation
• Hypopigmentation: Pale color in the skin due to decreased pigmentation eg after
inflammation
• Induration – firmness, usually due to fibrosis after inflammation
 Terminology - Macroscopic
• Rash
• Non-specific term
• Multiple causes – Infections (viral, bacterial, fungal), inflammation etc.
• History is essential:
• exposure, allergies, contact, drugs, constitutional symptoms e.g. fever
Wheal - Transient, circumscribed, elevated papules or plaques, often
with erythematous borders and pale centers.
Vesicle - A small, superficial, circumscribed elevation of the skin, less than 0.5 cm,
that contains serous fluid.
Pustules (acne)
Plaque - A circumscribed, elevated, superficial, solid lesion, greater than 1
cm in diameter.
 Terminology - Microscopic
dont need to know
• Hyperkeratosis: Hyperplasia of the stratum corneum, often associated with a
qualitative abnormality of the keratin
• Parakeratosis: Mode(s) of keratinization characterized by retention of the nuclei in
the stratum corneum; on mucosal membranes, parakeratosis is normal.
• Acanthosis: Epidermal hyperplasia preferentially involving the stratum spinosum
• Dyskeratosis: Abnormal keratinization occurring prematurely within individual cells
or groups of cells below the stratum granulosum
 Terminology - Macroscopic
• Acantholysis: Loss of intercellular connections resulting in lack of cohesion between
keratinocytes
• Papillomatosis: Hyperplasia of the papillary dermis with elongation and/or
widening of the dermal papillae
• Lentiginous: Refers to a linear pattern of melanocyte proliferation within the
epidermal basal cell layer; lentiginous melanocytic hyperplasia can occur as a
reactive change or as part of a neoplasm of melanocytes
• Spongiosis: Intercellular edema of the epidermis
 Inflammatory Conditions
(inflammatory dermatoses)
 Inflammatory Conditions

• Acute or chronic
• Acute – days to weeks
• Chronic – months to years
• Various causes e.g. autoimmune, allergic reactions, infective etc.
• Cardinal signs of inflammation
– swelling {e.g. due to oedema} (tumor)
– redness (rubor)
– heat production (calor)
– pain (dolor)
– loss of function/ altered function (functio laesa)
 Inflammatory Conditions

Urticaria (hives)
• Mast cell degranulation – dermal vascular hyperpermeability
• IgE-dependent: exposure to antigens (pollen, food, drugs, insect
venom, etc)
• IgE-independent: drugs (antibiotics, opiates, radiographic contrast
media, aspirin)
• Hereditary (hereditary angioneurotic oedema)
• Clinically – wheals, papules, plaques, itchy, red (erythema)
• Redness and swelling due to local vascular dilatation and increased
vascular permeability
• Angioedema – deeper oedema of dermis and subcutaneous fat
• Usually fade or resolve in 24 hours
 Inflammatory Conditions

Eczema (eczematous dermatitis)

• Various causes: allergic, atopic, drug-related, photo-eczematous,
primary irritant
• Example: Contact with poison ivy
• Acute stages - Red itchy papules, vesicles, oozing (wet), crusted
lesions
• Later – raised plaques, scaly, lichenification – which can be due to
scratching and rubbing (lichen simplex chronicus)
• Treatment: Search for offending substances that can be removed,
steroids
Eczematous dermatitis. A. The patterned erythema and scale stems from a nickel-induced contact dermatitis produced by
this woman's necklace. B. Microscopically, there is fluid accumulation (spongiosis) between epidermal cells that can
progress to small vesicles if intercellular connections are stretched until broken. Downloaded from: StudentConsult (on 9 April 2013 08:37 AM)

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Lichen simplex chronicus. Acanthosis with hyperkeratosis and hypergranulosis are distinctive. Superficial
dermal fibrosis and vascular ectasia, both common features, also are present.
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 Inflammatory Conditions

Erythema multiforme
• Associated with infections and drugs
• Multiforme = varied appearances – macules, papules, vesicles, as
well as characteristic targetoid lesion
• Can progress and worsen to mucosal involvement and sloughing of
the epidermis – life threatening (Stevens-Johnson Syndrome (SJS),
Toxic Epidermal Necrolysis (TEN))
 Targetoid lesions

Erythema multiforme. A. The target-like lesions consist of a pale central blister or zone of epidermal necrosis
surrounded by macular erythema. B. Early lesions show a collection of lymphocytes along the dermoepidermal
junction (interface dermatitis) associated with scattered keratinocytes with dark shrunken nuclei and
eosinophilic cytoplasm that are undergoing apoptosis.
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 Inflammatory Conditions

Lichen planus
•May be due to altered antigens at basal cell/ dermo-epidermal
junction impt
•6 Ps – pruritic (itchy), purple, polygonal, planar papules and plaques
•Symmetrical distribution on extremities (often wrists and elbows)
and glans penis
•Skin: itchy, violaceous, flat-topped papules that may coalesce to form
plaques
•Papules often highlighted by white dots/ lines called Wickham striae
•Oral lesions: white, netlike areas involving the oral mucosa
 Lichen planus

• Pruritic (itchy), purple,

polygonal planar papules
and plaques
• Aetiology not known
?infection, local irritation
• Self limiting – resolves
spontaneously

http://emedicine.medscape.com/article/455021-overview
 classic pattern of
inflammation

Lichen planus. A.This flat-topped pink-purple polygonal papule has white lacelike markings referred to as Wickham striae.
B. Microscopic features include a bandlike infiltrate of lymphocytes along the dermoepidermal junction, hyperkeratosis,
hypergranulosis, and pointed rete ridges ("sawtoothing"), which results from chronic injury of the basal cell layer.
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 Inflammatory Conditions
Psoriasis 银屑病
•Common chronic inflammatory skin condition; multifactorial
pathogenesis
•Affects all ages
•Multisystemic disease –joints, muscle, gastrointestinal tract
• Pink to salmon-coloured plaques covered by loose, silvery-white
scales
•Plaques affecting scalp
•Other areas affected by plaques: elbows, knees, lower back, gluteal
cleft, glans penis
•Nail changes – pitting, discoloration, thickening, separation from nail
bed
•Lesions can be worsened by local trauma
•Total body erythema and scaling: Erythroderma
Regions involved in
psoriasis
Psoriasis. A. Chronic plaques of psoriasis show silvery-white scale on the surface of
erythematous plaques. B. Microscopic examination reveals marked epidermal hyperplasia,
uniform downward extension of rete ridges (psoriasiform hyperplasia), and prominent
parakeratotic scale that is focally infiltrated by neutrophils.
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 Blistering
Conditions
 Blistering Conditions
• Usually a secondary phenomenon - Infections, inflammatory
conditions
• Primary bullous disorders – mainly immune-mediated
(autoantibodies), some non-inflammatory (inherited)
• Blisters can occur at different levels within the epidermis –
subcorneal, suprabasal and subepidermal
• Antibodies appear to cause disruptions and loss of cell-to-cell or
cell-to-matrix adhesion
• Role of immunoflorescence to detect the deposits of antibodies at
the various levels

must rmb
• Examples: Pemphigus, bullous pemphigoid,
dermatitis herpatiformis, epidermolysis bullosa
Figure 23-8
Levels of blister formation
A. Subcorneal (as in pemphigus foliaceus)
B. Suprabasal (as in pemphigus vulgaris)
C. Subepidermal (as in bullous pemphigoid or dermatitis herpetiformis
The level of epidermal separation forms the basis of the differential diagnosis for blistering
disorders.

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Figure 23-10 Pemphigus vulgaris A. This erosion on the leg represents a group of confluent, "unroofed" blisters. B.
Suprabasal acantholysis results in an intraepidermal blister in which rounded, dissociated (acantholytic) keratinocytes are
plentiful (inset). Downloaded from: StudentConsult (on 9 April 2013 08:37 AM)

© 2005 Elsevier
Figure 23-11 Pemphigus foliaceus A. Gross appearance of a typical blister, which is less severely eroded than those
seen in pemphigus vulgaris. B. Microscopic appearance of a characteristic subcorneal blister.
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Figure 23-12 Bullous pemphigoid A. Deposition of IgG antibody detected by direct immunofluorescence as a linear band
outlining the subepidermal basement membrane zone (epidermis is on the left side of the fluorescent band). B. Gross appearance of
characteristic tense, fluid-filled blisters. C. A subepidermal vesicle with an inflammatory infiltrate rich in eosinophils.(C, Courtesy of Dr.
Victor G. Prieto, Houston, Texas.)
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Figure 23-13 Dermatitis herpetiformis A. Selective deposition of IgA autoantibody at the tips of dermal papillae is
characteristic. B. Lesions consist of intact and eroded (usually scratched) erythematous blisters, often grouped (seen here
on elbows and arms). C. The blisters are associated with basal cell layer injury, initially caused by accumulation of
neutrophils (microabscesses) at the tips of dermal papillae.(A, Courtesy of Dr. Victor G. Prieto, Houston, Texas.)
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Figure 23-9 Direct immunofluorescence findings in pemphigus. A. Pemphigus vulgaris. There is uniform deposition of
immunoglobulin and complement (green) along the cell membranes of keratinocytes in a characteristic "fishnet" pattern. B.
Pemphigus foliaceus. Immunoglobulin deposits are confined to superficial layers of the epidermis.
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Infections
 Skin Infections

group them
in terms of causes

Impetigo
• Bacterial – skin organisms
• Staphylococcus, Streptococcus
• Others e.g. mycobacteria Impetigo
• Fungal – Tinea
• Viral – Human papillomavirus (HPV), molluscum
contagiosum, etc.
Fungal infection (tinea)
Viral warts – verruca Viral wart

very contagious
Viral infection - Chicken
pox
Herpes
Zoster
Pseudomonas folliculitis

http://emedicine.medscape.com/article/1053170-overview
Figure 23-6 Impetigo. This child's arm is involved by a superficial bacterial infection producing the characteristic
erythematous scablike lesions crusted with dried serum.(Courtesy of Dr. Angela Wyatt, Bellaire, Texas.)

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Neoplasia
 Neoplastic Lesions
• Benign, malignant
• Can arise from any component of the skin
• Seborrhoeic keratosis - benign
• Moles (naevi) – can turn malignant
• Actinic keratosis - premalignant
 Neoplastic Lesions
Mole (melanocytic nevus)
• Congenital or acquired neoplasm of melanocytes
• Benign
• Maturation (of cells) with depth of lesion
 Neoplastic Lesions
Mole (melanocytic nevus)
• Superficial – less mature – larger, produce (and contain) melanin,
grow in nests
• Deeper cells – more mature – produce little or no melanin, grow in
cords
• Varied appearance and can mimic melanoma – requiring excision
Figure 23-19 Melanocytic nevus. A. Melanocytic nevi are relatively small, symmetric, and uniformly pigmented.
B. This nevus shows rounded melanocytes that lose their pigmentation and become smaller and more
separated as they extend into the dermis-all signs of cellular senescence that speak to the benign nature of the
proliferation.

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Figure 23-20 Dysplastic nevus. A. Numerous irregular nevi on the back of a patient with the dysplastic nevus syndrome. The
lesions usually are greater than 5mm in diameter and have irregular borders and variable pigmentation (inset). B.
Compound dysplastic nevi feature a central dermal component with an asymmetric "shoulder" of exclusively junctional
melanocytes (lentiginous hyperplasia). The former corresponds to the more pigmented and raised central zone (see A,
inset), and the latter, to the less pigmented flat peripheral rim. C. Other important features are cytologic atypia (irregular,
dark-staining nuclei) and characteristic parallel bands of fibrosis-part of the host response to these lesions.
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 Neoplastic Lesions
Seborrhoeic Keratosis
•Benign, increased incidence with age
•Head, neck and trunk
•Raised papules or plaques, granular surface, pigmented (“stuck on”
appearance)
Figure 23-14 Seborrheic keratosis This roughened, brown, waxy lesion almost appears to be "stuck on" the skin
(inset). Microscopic examination shows the lesion to consist of an orderly proliferation of uniform, basaloid keratinocytes
that tend to form keratin microcysts (horn cysts).
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Seborrhoeic keratosis
 Neoplastic Lesions
Actinic Keratosis 光化性角化病
•Chronic sun exposure
•Red, raised, rough surface
•Premalignant lesion i.e. can transform and progress into cancer
•Cytological atypia present in lower parts of epidermis
Figure 23-15 Actinic keratosis.A. Most lesions are red and rough (sandpaper-like), owing to excessive scale, as seen in
the lesions on the cheek, nose, and chin of this female patient. B. Basal cell layer atypia (dysplasia) with epithelial buds, and
associated with marked hyperkeratosis, parakeratosis, and dermal solar elastosis (asterisk). C. More advanced lesions show
full-thickness atypia, qualifying as squamous carcinoma in situ.
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 Neoplastic Lesions
Malignant neoplasms
•Melanocytic and non-melanocytic
• Basal cell carcinoma (BCC)

• Squamous cell carcinoma (SCC) 鳞状细胞癌

• Melanoma 黑色素瘤
• Skin adenexal neoplasia (other tumours)
 Skin Cancer
• Age – older
• Individuals with light-colored skin
Risk factors for Skin Cancer
• Sun exposure/ damage/ UV radiation
• Fair skin
• History of sunburns
• Personal/ family history of skin cancer
• Presence of precancerous skin lesions
• Immunodeficiency/ weakened immune system (e.g. HIV/ AIDS,
immunosuppression)
• Chronic irritation (or examples of such, e.g. chronic discharging sinus)
• Drugs (or examples e.g. arsenic)
 Skin Cancer
Squamous cell carcinoma
• Sun-exposed areas
• Older individuals
• UV exposure leads to DNA damage
• UVB also impairs immunological response in skin
• Red scaly plaques
• Ulcer that does not heal – Marjolin’s ulcer (chronic irritation)
Squamous cell carcinoma
Figure 23-16. Squamous cell carcinoma A. A nodular, hyperkeratotic lesion occurring on the ear, associated with
metastasis to a prominent postauricular lymph node (arrow). B. The tumor invades the dermis infiltrating collagen as
irregular projections of atypical squamous cells, which in this case exhibit acantholysis.
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 Skin Cancer
Basal cell carcinoma
•Slow-growing neoplasm
•Rarely metastasize
•Pearly papules with prominent blood vessels, can be pigmented
•“Rodent” ulcer
Basal cell carcinoma
Figure 23-17 Basal cell carcinoma A. A prototypical pearly, smooth-surfaced papule with associated telangiectatic
vessels. B. The tumor is composed of nests of basaloid cells infiltrating a fibrotic stroma. C. The tumor cells have scant
cytoplasm and small hyperchromatic nuclei that palisade on the outside of the nest. The cleft between the tumor cells and
the stroma is a highly characteristic artifact of sectioning.
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 Skin Cancer
Malignant Melanoma produces melanine
•Develop from dysplastic naevus or de novo
•Change in colour or size of pigmented lesion
•Highly aggressive
Malignant melanoma
 Worrisome symptoms/ signs
impt
for melanoma
• Asymmetry
• Uneven/ irregular borders
• Colour – variety of colours
• Large/ increasing size/ diameter
• Evolving/ new changes in shape
• Bleeding
• Itching
• Crusting
Figure 23-22 Melanoma A. On clinical evaluation, lesions tend to be larger than nevi, with irregular contours and pigmentation. Macular areas indicate
early superficial (radial) growth, while elevated areas often indicate dermal invasion (vertical growth). B. Radial growth phase, with spread of nested and single-
cell melanoma cells within the epidermis. C. Vertical growth phase, with nodular aggregates of infiltrating tumor cells within the dermis (epidermis is on the
right). D. Melanoma cells have hyperchromatic nuclei of irregular size and shape with prominent nucleoli. Mitoses, including atypical forms such as seen in the
center of this field, often are encountered. The inset shows a sentinel lymph node containing a tiny cluster of metastatic melanoma cells (arrow), detected by
staining for the melanocytic marker HMB-45.
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very serious melanine pigment production
Figure 23-21 Possible steps in development of melanoma. A. Normal skin shows only scattered melanocytes. B. Lentiginous melanocytic
hyperplasia. C. Lentiginous compound nevus with abnormal architecture and cytologic features (dysplastic nevus). D. Early or radial growth
phase melanoma (large dark cells in epidermis) arising in a nevus. E. Melanoma in vertical growth phase with metastatic potential. Note
that no melanocytic nevus precursor is identified in most cases of melanoma. They are believed to arise de novo, perhaps all using the
same pathway.
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 Other conditions
• Many other non-neoplastic and neoplastic skin conditions
exist

• When in doubt, consult/ refer – dermatologist

 Thank you

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