Inflammatory Skin & Tumours Flashcards
What are the 4 major types of tissue reaction patterns seen in inflammatory skin disease?
- Spongiotic reaction pattern
- Psoriasiform reaction pattern
- Lichenoid reaction pattern (’interface dermatitis’)
- Vesiculobullous reaction pattern
What type of tissue reaction pattern is ‘eczema’?
Spongiotic reaction pattern
What type of tissue reaction pattern is ‘psoriasis’?
Psoriasiform reaction pattern
What type of reaction pattern is Licen planus?
Lichenoid reaction pattern
What type of reaction pattern is lupus erythematosus?
Lichenoid
What type of reaction pattern is lupus erythematosus?
Lichenoid
What are the 3 clinical stages of eczema? Describe the appearance of the skin for each
- Acute dermatitis; skin red, weeping serous exudate +/- small vesicles
- Subacute; skin is red, less exudate, itching ++, crusting
- Chronic; skin thick and leathery secondary to scratching
What characterises a ‘spongiosis’ reaction?
Characterised by intercellular oedema within the epidermis (spongiosis)
How is the epidermis affected in chronic eczema?
Epidermal hyperplasia and hyperkeratosis – mild in acute dermatitis, marked in chronic dermatitis
What other 2 conditions is atopic eczema typically associated with?
Asthma and hayfever
What type of hypersensitivity reaction is atopic eczema?
Type 1 reaction to allergen
Define atopic
denoting a form of allergy in which a hypersensitivity reaction such as eczema or asthma may occur in a part of the body not in contact with the allergen.
What are the 2 types of contact dermatitis?
- Contact irritant
- Contact allergic
mechanism behind contact irritant dermatitis?
direct injury to skin by irritant
What irritants can cause contact irritant dermatitis?
acid, alkali, strong detergent, etc
Mechanism behind contact allergic dermatitis? What hypersensitivity reaction is this?
- Act as haptens which combine with epidermal protein to become immunogenic
- This is a delayed ‘type 4’ hypersensitivity reaction
What allergens are responsible for contact allergic dermatitis?
Nickel, dyes, rubber
What are the 2 morphological subtypes of ‘dermatitis of unknown aetiology’?
- Seborrhoeic dermatitis
- Nummular dermatitis
What areas does seborrhoeic dermatitis affect?
affect areas rich in sebaceous glands: scalp, forehead, upper chest
How does nummular dermatitis appear?
Coin shaped lesions
Presentation of psoriasis?
- Well defined, red oval plaques on extensor surfaces; knees, elbows, sacrum
- Fine silvery scale
- ‘Auspitz sign’
- +/- sero-negative arthritis
- Oral manifestations
- Can cause alopecia
What is an ‘Auspitz sign’?
refers to a bleeding point that can occur when the surface of a scaling rash has been removed
What is parakeratosis?
Parakeratosis is defined as the presence of nucleated keratinocytes in the stratum corneum
What is the histological appearance of psoriasis?
“Psoriasiform hyperplasia”
- i) Regular elongated club shaped rete ridges
- ii) Thinning of epidermis over dermal papillae.
- iii) Parakeratotic (contain nuclei) scale.
- iv) Collections of neutrophils in scale (Munro micro abscesses)
What are Munro micro abscesses?
This is a collection of neutrophils (abscess) in the stratum corneum of the epidermis due to infiltration of neutrophils from papillary dermis.
Describe the cell turnover time in psoriasis
Massive cell turnover –> causes clinical and microscopic features
Environmental trigger factors for psoriasis?
Infection, stress, trauma, drugs
What are the psoriasis susceptibility genes?
PSORS genes (many in region of major histocompatibility complex on Chromosome 6p2 implicated)
Associated co-morbidities of psoriasis?
- Arthropathy, 5-10% associated
- Psychosocial effects
- Cardiovascular disease; 2-3x risk.
- May be due to inflammation/drugs/stress/smoking
- Increased risk of non-melanoma skin cancer e.g. BCC, lymphoma
How do the treatment and asociated comorbidity risk of skin cancer conflict in psoriasis?
One main treatment of psoriasis is UV light –> increases risk of non-melanoma skin cancer
What characterises a ‘Lichenoid’ reaction pattern?
Characterised by epidermal basal cell damage
What is Lichen planus?
Lichen planus is an inflammatory skin condition, characterised by an itchy, non-infectious rash that affects the flexor surfaces, mucous membranes and genitals
What type of hypersensitivity reaction is Lichen planus?
Type 4
How long does Lichen planus typically last?
1-2 years but longer in oral cavity
What other conditions can Lichen planus be associated with?
Viral hepatitis, HIV (and some drugs)
What is lupus erythematosus?
- Auto-immune disorder primarily affecting connective tissues of the body; connective tissue disorder
- May affect any part of the body, but importantly kidneys (major predictor of outcome)
What is the type of lupus that affects the skin only?
Discoid lupus erythematosus (SDE)
how does DLE present?
Red scaly patches on sun-exposed skin +/- scarring, scalp involvement causes alopecia.
What is the characteristic facial feature of SLE?
Butterfly rash on cheeks and nose
What type of hypersensitivity reaction is lupus?
Type III
What is epidermal atrophy?
Epidermal atrophy is characterised by the reduction in the number of epidermal cells leading to the reduced thickness of the epidermis.
How does lupus erythematosus present microscopically?
- Thin atrophic epidermis
- Inflammation and destruction of adnexal structures.
- IgG deposited in basement membrane
Which antibody is deposited in basement membrane in lupus?
IgG
Which technique gives the best diagnostic yield in lupus?
Direct immunofluorescence (DIF) of skin in conjunction with histopathology gives the best diagnostic yield
What type of reaction pattern is dermatomyositis?
Lichenoid
What is dermatomyositis? What do symptoms include?
Dermatomyositis is an autoimmune condition that causes skin changes and muscle weakness.
Symptoms;
- Peri-ocular oedema and erythema (Heliotropic rash)
- Erythema in photosensitive distribution
- Myositis; proximal muscle weakness (check for creatinine kinase)
In adults, what are 25% of dermatomyositis cases associated with?
Underlying visceral cancer
Microscopy of dermatomyositis?
- Similar to lupus
- Often a lot of dermal mucin
What characterises a vesiculobullous reaction pattern?
The vesiculobullous reaction pattern is characterised by the presence of vesicles or bullae (fluid filled blisters) at any level within the epidermis or at the dermoepidermal junction.
What type of reaction pattern in pemphigus?
Vesiculobullous reaction pattern
What type of reaction pattern in pemphigoid?
Vesiculobullous reaction pattern
What is pemphigus/pemphigoid?
- Pemphigus is a group of skin disorders that cause blisters or pus-filled bumps.
- Autoimmune.
- Can be detected by immunofluorescence (IMF)
- Can be localised or extensive
Pemphigus vs pemphigoid;
a) location of blisters?
b) deposition of autoantibodies?
Pemphigus;
a) intra-epidermal blisters
b) intercellular deposition of autoantibodies
Pemphigoid;
a) sub-epidermal bullae
b) Deposition of autoantibodies at basement membrane
Describe the difference in blisters present in pemphigus vs pemphigoid?
Pemphigus - affects the outer of the skin (epidermis) and causes lesions and blisters that are easily ruptured (very fragile).
Pemphigoid - affects a lower layer of the skin, between the epidermis and the dermis, creating tense blisters that do not break easily.
How are blisters formed in pemphigus?
Group of disorders characterised by loss of cohesion between keratinocytes resulting in an intraepidermal blister.
Pathogenesis behind pemphigus vs pemphigoid?
- Pemphigus - Autoantibodies directed against intercellular material.
- Pemphigoid - Autoantibodies to glycoprotein in basement membrane
Which age group is pemphigus/pemphigoid more commonly seen in?
Elderly
What type of tissue reaction pattern is dermatitis herpetiformis?
Vesiculobullous reaction pattern
What is dermatitis herpetiformis? Symptoms?
- A rare, chronic, autoimmune skin condition
- Symptoms;
- severely itchy blisters
- raised red skin lesions
What age group does dermatitis herpetiformis usually affected?
Young patients
What disease is dermatitis herpetiformis associated with?
Coeliac disease
In which inflammatory skin condition is there IgA deposition in the dermal papillae on IMF?
Dermatitis herpetiformis
Histopathology of dermatitis herpetiformis?
Neutrophil microabscesses in dermal papillae
Skin lesions can be signs of systemic disease. What underlying pathology can the following skin conditions indicate;
a) dermatomyositis
b) dermatitis herpetiformis
c) Acanthosis Nigricans (dark warty lesions in armpits)
d) Necrobiosis Lipoidica (red + yellow plaque on legs)
e) Erythema Nodosum (red tender nodules on shins)
a) visceral cancer
b) Coeliac disease
c) internal malignancy
d) diabetes mellitus
e) associated with infections elsewhere especially lung, drugs, and other diseases
Which inflammatory skin condition is characterised by epidermal hyperplasia and hyperkeratosis?
Chronic dermatitis
Which type of dermatitis affects areas rich in sebaceous glands: scalp, forehead, upper chest?
Seborrhoeic dermatitis
Which type of dermatitis presents with coin shaped lesions?
Nummular
Which type of inflammatory skin condition can present with ‘Auspitz signs’?
Psoriasis
Which type of inflammatory skin condition can present with a fine silvery scale?
Psoriasis
Which type of inflammatory skin condition can present with parakeratosis?
Psoriasis
Which type of inflammatory skin condition can Munro micro abscesses?
Psoriasis
Which type of inflammatory skin condition involves massive cell turnover?
Psorasis
Which type of reaction pattern is characterised by epidermal basal cell damage?
Lichenoid
Which type of inflammatory skin condition is associated with viral hepatitis or HIV?
Lichen planus
Which type of inflammatory skin condition can present with IgG deposited in basement membrane?
Lupus
Which type of inflammatory skin condition can present with a thin atrophic epidermis?
Lupus
Which type of inflammatory skin condition can present with peri-ocular oedema?
Dermatomyositis
Which type of inflammatory skin condition can present with proximal muscle wasting?
Dermatomyositis
Which type of inflammatory skin condition is caused by a loss of cohesion between keratinocytes?
Pemphigus
Which type of inflammatory skin condition is caused by autoantibodies to glycoprotein in basement membrane?
Pemphigoid
Which type of inflammatory skin condition can present with IgA deposition in dermal papillae?
Dermatitis herpetiformis
Which type of inflammatory skin condition can present with neutrophil micro abscesses in dermal papillae?
Dermatitis herpetiformis
What is the commonest malignant skin tumour?
Basal cell carcinoma
Does BCC tend to metastasise?
no
Aetiology of BCC?
- Sun exposed site, especially face
- Occasional secondary to radiotherapy
- Pale skin that burns easily
- Immunosuppression
- Rare; Gorlin’s syndrome (increases risk of developing various cancerous and non-cancerous tumours)
What is Gorlin’s syndrome?
a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.
Presentation of BCC lesion?
rodent ulcer with rolled edge
Microscopically, what would a tumour composed of islands of basaloid cells with peripheral palisade indicate?
BCC
What cell type does squamous cell carcinoma arise from?
Keratinocytes
Causes of SCC?
- U.V. irradiation
- Usually occurs in sun exposed sites
- Increased risk in tropical countries.
- Radiotherapy
- Hydrocarbon exposure - tars, mineral oils, soot
- Percival Pott noted SCC scrotum in chimney sweeps
- Chronic scars/ulcers - SCC arises within these (Marjolins ulcer).
- Immunosuppression - renal transplant patients at increased risk.
- Drugs, some newer drugs for melanoma (BRAF inhibitors)
Presentation of SCC lesion?
Nodule with ulcerated, crusted surface
Microscopically, what would invasive islands and trabeculae of squamous cells showing cytological atypia indicate?
SCC
What is known as the ‘pre-malignant’ form of SCC?
Actinic (solar) keratosis –> dry scaly patches of skin that have been damaged by the sun;
- Dysplasia to squamous epithelium
- Very common on chronic sun exposed sites.
- Scaly lesion with erythematous base
- Only rarely progresses to invasive disease.
- May spontaneously resolve
Where are melanocytes derived from?
Neural crest
Function of melanocytes?
To form melanin which is transferred to epidermal cells to protect the nucleus from UV radiation
Melanocytes can give rise to benign or malignant tumours. What are the names of each?
Benign - naevi (moles)
Malignant - melanoma
What are naevi?
- Local benign collections of melanocytes
- Diameter <6mm
- Several types;
- Superficial; congenital or acquired
- Deep; blue naevi (mongolion spot)
What is atypical mole syndrome? What can it increase your risk of?
- Multiple clinically atypical moles
- Histologically atypical/dysplastic naevi
- Increased risk of developing melanoma
Does melanoma metastasise?
Very dangerous malignancy which can metastasise widely
Size of melanoma lesion?
>6mm
Aetiology of melanoma?
- a) Sun exposure - especially short intermittent severe exposure
- b) Race - Celtic with red hair, blue eyes, fair complexions who tan poorly most at risk. Melanoma rare in dark skinned people.
- c) Family history – Atypical mole syndrome (multiple large atypical moles)
- d) Giant congenital naevi - small risk of turning malignant (<5%)
What is the most common form of melanoma?
Superficial spreading melanoma –> a type of skin cancer that slowly grows horizontally across the top layer of skin before moving to the deeper layers (Proliferation of atypical melanocytes which invade epidermis and dermis).
What specific gene mutation havs been detected in many superficial spreading melanomas?
BRAF mutations (target for anticancer agents)
Microscopy of nodular melanoma?
Invasive atypical melanocytes invade dermis to produce nodules of tumour cells.
What is lentigo maligna?
- Lentigo maligna is an early form of melanoma in which the malignant cells are confined to the tissue of origin
- Typically arises on face in elderly people
- Slow growing, flat, pigmented patch
Microscopy of lentigo maligna?
- Micro: Proliferation of atypical melanocytes along basal layer of epidermis. Skin also shows signs of chronic sun damage.
- Late in disease, melanocytes may invade dermis (lentigo maligna melanoma) with potential to metastasise.
Are BRAF mutations seen in lentigo maligna?
Typically no
What is acral lentiginous melanoma?
is a type of melanoma arising on the palms or soles (occasionally sublingual)
What is the commonest form of melanoma in afro-carribeans?
Acral lentiginous melanoma
Microscopy of acral lentiginous melanoma?
Micro: Similar to lentigo maligna except no marked sun damage.
Naevus vs melanoma
What is pagetoid spread?
An individual cell proliferation in the upper levels of the epidermis.
Which type of melanoma exhibits pagetoid spread?
Superficial spreading melanoma
60% melanoma’s have mutation in which gene?
BRAF
What syndrome can be associated with an increased risk of BCC?
Gorlin’s syndrome
What is a heliotrope rash? What condition is it associated with?
- A heliotrope rash is a reddish purple rash on or around the eyelids
- Heliotrope rash is caused by dermatomyositis
