PATHOLOGY OF THE SKIN

GORDON WRIGHT
What you should learn from this LRGS
• 1. Outline the incidence and mortality of
common skin diseases
• 2. Describe the aetiology and pathogenesis of
common skin diseases
• 3. Describe the macroscopic and microscopic
features of common skin diseases
 The problem for you
• What are common skin diseases?
 ANATOMY OF THE SKIN
MORPHOLOGY MULTIPLE FUNCTIONS
• PROTECTION FROM THE
ENVIRONMENT
• PROTECTION OF
UNDERLYING ORGANS
• TEMPERATURE REGULATION
• OTHERS
 PREVALENCE OF SKIN DISEASE
• Skin diseases are common, with 16% of
Australian general practice consultations
containing a dermatological element.
 Recent Trends
• Fewer infections
• More neoplasms
• Overall about the same number of patients
presenting to general practitioners

• Ageing of the population leads to more

degenerative diseases and more neoplasms
 Mortality Data
• Skin diseases caused 1 male death per
100,000 population in Australia 2002 (AIHW
Mortality Database, Australia’s Health 2004)
• Skin diseases caused 2 female deaths per
100,000 population in Australia 2002 (AIHW
Mortality Database, Australia’s Health 2004)

• I am not sure how accurate these data are

because validation is limited.
Age and skin cancer mortality
 APPROACH TO CLASSIFICATION
there are several options
• AETIOLOGY
• Congenital, genetic, infectious, immunological,
neoplastic, deposition, unknown
• CLINICAL PROBLEM
• Macule, papule, nodule, plaque, ulcer, alopecia,
scale, pustule, itch, nail abnormality, blisters,
purpura, altered pigmentation
• BIOPSY PATTERN
• Hyperkeratosis, spongiosis, dermatitis, lichenoid
infiltration etc.
 What are the common skin diseases?
Based on GP studies of prevalence.
• Acne
• Psoriasis
• Eczema
• Ulcers
• Naevi
• Warts
• Actinic keratosis
• BCC SCC
 Pathology of disease is influenced by
natural history of the disease
• Example of dermatitis (eczema)
• This is the most common problem in general
practice (up to 20%)
 What is the cause?
• Atopy is the hereditary predisposition toward
developing some hypersensitivity reactions,
such as hay fever, asthma, chronic urticaria,
and some types of eczema. Atopic eczema,
therefore, means a form of eczema
characterized by atopy.
Dynamic nature of skin disease
 Spongiotic dematitis
-this is what would be seen in a biopsy
biopsy description

• Thickened epidermis
• Intercellular oedema
• Oedema of papillary dermis
• Superficial inflammatory
infiltration
 PROGNOSIS MAY BE DIFFICULT TO
DETERMINE
• Of the 571 children with reported or
examined eczema by the age of 7 years, the
proportion of children who were clear in
terms of examined eczema or reported
eczema in the last year at ages 11 and 16
years was 65% and 74%, respectively.
We shall present the remaining cases
linked to aetiology/pathogenesis
 INFECTIONS OF THE SKIN
• VIRAL
• BACTERIAL
• FUNGAL
• PROTOZOAN
• METAZOAN
 VIRAL INFECTIONS
• HUMAN PAPILLOMA VIRUS
• MOLLUSCUM CONTAGIOSUM
• HERPES SIMPLEX
• HIV

• EXANTHEMS - MACULOPAPULAR RASH

ASSOCIATED WITH VIRAL INFECTIONS
 PLANTAR WART
usually related to HPV 1
 HPV types and various non genital
diseases
• Common warts - HPV types 2 and 4 (most common),
followed by types 1, 3, 27, 29, and 57
• Deep palmoplantar warts (myrmecia) - HPV type 1
(most common), followed by types 2, 3, 4, 27, 29, and
57
• Flat warts - HPV types 3, 10, and 28
• Butcher's warts - HPV type 7 (although some data
suggest the association may be weak)
• Focal epithelial hyperplasia (Heck disease) - HPV types
13 and 32
• Cystic warts - HPV type 60
Common wart
 HPV
• Warts are tumours or growths of the skin caused
by infection with Human Papillomavirus (HPV).
More than 70 HPV subtypes are known.
• Warts are particularly common in childhood and
are spread by direct contact or autoinocculation.
This means if a wart is scratched, the viral
particles may be spread to another area of skin. It
may take as long as twelve months for the wart to
first appear.
 GENITAL WARTS
• At least 75% of sexually active adults have
been infected with at least one type of genital
HPV at some time in their life.
• Most do not develop visible warts; the
infection may show up on a cervical cytology
smear. This is known as subclinical infection.
• Visible genital warts are often easy to
diagnose by their typical appearance. They are
usually due to HPV Types 6 and 11.
 TRANSMISSION OF GENITAL HPV
• Visible genital warts and subclinical HPV
infection nearly always arise from direct skin
to skin contact.
• Sexual contact. This is the most common way.
• Oral sex. HPV appears to prefer the genital
area to the mouth however.
• Vertical (mother to baby) transmission.
• Auto (self) inoculation from one site to
another.
GENITAL WARTS
 VACCINE PREVENTION
• Researchers have reported a significant
decline in the proportion of young women
diagnosed with genital warts in Australia
following the implementation of the national
HPV vaccine program. The finding was
published by the British Medical Journal
online on April 18, 2013.
Decline in incidence of genital warts
(Australia)
 MOLLUSCUM CONTAGIOSUM
• Molluscum contagiosum (MC) is a viral infection
of the skin or occasionally of the mucous
membranes, sometimes called water warts. It is
caused by a DNA poxvirus called the molluscum
contagiosum virus (MCV). MCV has no
nonhuman-animal reservoir (infecting only
humans). There are four types of MCV, MCV-1 to
-4; MCV-1 is the most prevalent and MCV-2 is
seen usually in adults and often sexually
transmitted. This common viral disease has a
higher incidence in children, sexually active
adults, and those who are immunodeficient.
MOLLUSCUM CONTAGIOSUM
Molluscum bodies
HERPES SIMPLEX
COLD SORE
NOTE VESICLE AND INFLAMMATION
HSV
 HIV
• Dermatological disorders are a frequent presenting feature of HIV
infection and/or AIDS. More than 90% of HIV-infected patients will
suffer from one or more skin diseases during the course of their
illness. This trend is reflected in the increasing number of skin
biopsies from HIV-positive patients in those parts of the world
where HIV infection/AIDS is highly prevalent. Histopathologists are
therefore required to possess a working knowledge of the broad
spectrum of cutaneous manifestations of HIV infection. These
include the range of dermatoses that are specific to HIV infection,
the more common dermatoses occurring with greater frequency (or
modified by) HIV infection/AIDS, the spectrum of infectious
diseases (often opportunistic) caused by viruses, bacteria, fungi,
protozoa and even arthropods, and neoplastic conditions such as
Kaposi sarcoma and B-cell non-Hodgkin lymphoma.
THIS IS ACUTE EXANTHEM IN HIV
 ACUTE EXANTHEM
• This is non specific and seen in many
other viral disorders
• An exanthem is any eruptive skin rash that
may be associated with fever or other
systemic symptoms.
 HIV RELATED DISORDERS
• KAPOSI SARCOMA HHV8
• BLCL
 Kaposi sarcoma
• From the earliest days of the AIDS pandemic, it has
been clear that patients with HIV disease are at
increased risk for neoplastic events. KS was recognized
at the outset of the pandemic as a marker for AIDS.
• The search for a new virus in KS tumours was
motivated principally by powerful epidemiologic
studies that pointed to the involvement of a sexually
transmitted factor other than HIV in KS
tumourigenesis. Among AIDS patients, KS
disproportionately affected men who have sex with
men (MSM).
KAPOSI SARCOMA
 DISCOVERY OF HHV8 IN KS
• A major breakthrough occurred in 1994 when
Chang, Moore, and their collaborators, using a
technique based on the polymerase chain
reaction (PCR), identified 2 small fragments of
DNA that were reproducibly present in AIDS-KS
specimens but absent in most non-KS tissues. The
nucleotide sequences of these 2 fragments
revealed homology to 2 known gamma-
(lymphotropic) herpesviruses, indicating that
these fragments were derived from a novel
herpes viral genome.
KAPOSI SARCOMA
HHV 8 STAIN IN KAPOSI SARCOMA
ISSUES OF RISK OF MALIGNANCY IN
HIV PATIENTS
B CELL LYMPHOMA IN HIV
 BACTERIAL SKIN INFECTIONS
• IMPETIGO
• Infectious
• Streptococci
• Pustules
• Crusts

• Associated glomerulonephritis
IMPETIGO
CELLULITIS
 DEFINITION
• Cellulitis is an acute, spreading pyogenic
inflammation of the dermis and subcutaneous
tissue, usually complicating a wound, ulcer, or
dermatosis. The area, usually on the leg, is
tender, warm, erythematous, and swollen. It lacks
sharp demarcation from uninvolved skin.

• It is one of the commonest of the dermatological

conditions seen in accident and emergency in our
region.
 OTHER SKIN BACTERIAL INFECTIONS
ARE IMPORTANT BUT RARE
• TUBERCULOSIS
• LEPROSY
• ANTHRAX

• We will not present them at this time.

 FUNGAL INFECTIONS
• COMMON
• MAY BE ASSOCIATED WITH
IMMUNOSUPPRESSION
• VARIETY OF DIFFERENT FUNGI
TINEA PEDIS
NOTE FUNGAL HYPHAE
 Protozoa
• Includes Leishmania and Amoeba
• There are various species.
TYPICAL CUTANEOUS LEISHMANIASIS
LEISHMANIA
Sir William Boog LEISHMAN
Leishman stain
Visceral Leishmaniasis
 MICROSCOPY

Amastigotes are seen with

monocytes or, less commonly in
neutrophils, of peripheral blood
and in macrophages in aspirates.
They are small, round bodies 2–
4 μm in diameter with indistinct
cytoplasm, a nucleus, and a
small, rod-shaped kinetoplast.
 Leishmaniasis
presentation
• The symptoms of leishmaniasis are skin sores which
erupt weeks to months after the person affected is
bitten by sand flies. Other consequences, which can
manifest anywhere from a few months to years after
infection, include fever, damage to the spleen and liver,
and anaemia.
• In clinical medicine, leishmaniasis is considered one of
the classic causes of a markedly enlarged (and
therefore palpable) spleen; the organ, which is not
normally felt during examination of the abdomen, may
become larger even than the liver in severe cases.
 NON INFECTIOUS DERMATOSES
• Pathological changes may arise in epidermis, dermis and/or
subcutaneous tissue. The pattern of changes may allow a diagnosis
to be made or it may be non-specific. The appearance of many skin
diseases vary at different stages of their development and may be
altered by attempted treatment and secondary changes such as
scratching or infection.
• Understanding the terminology used in describing pathological
changes in the skin will help interpret pathology reports. The
reporting pathologist will generally make or suggest a diagnosis or
possible diagnoses, but it is especially important in inflammatory
conditions that the report be correlated with the clinical features.
If the clinical and pathological diagnoses do not tally, the case
should be discussed with the pathologist to arrive at a consensus
diagnosis.
 COMMON DISEASES
• Eczema / dermatitis - see earlier information
• A number of skin diseases are referred to as eczematous, in which
there is diffuse ill-defined scaling and itching. Swelling and blistering
may arise in acute eczema. Eczema or dermatitis are often
synonymous.
• The histological features of eczema are:
• Spongiosis (which may be patchy) in acute eczema with associated
lymphocyte exocytosis
• Acanthosis (thick skin) in chronic eczema
• Parakeratosis and a (usually superficial) perivascular
lymphohistiocytic infiltrate
• Excoriation and signs of rubbing (irregular acanthosis and
perpendicular orientation of collagen in dermal papillae) in chronic
cases (lichen simplex)
 NOTE HYPERKERATOSIS,
HYPERGRANULOSIS, SPONGIOSIS AND
PERIVASCULAR INFLAMMATION
 COMMON DISEASES
• Psoriasis
• There are various subtypes of psoriasis, a common dermatosis with well
demarcated erythematous scaly plaques.
• Due to the dynamic nature of psoriasis, this disease frequently does not show all
classical histological features, but the typical changes of chronic plaque psoriasis
are:
• Hyperkeratosis: mainly composed of parakeratosis, some orthokeratosis
• Neutrophils in stratum corneum (Munro's microabscesses) and squamous cell
layer (spongiform pustules of Kogoj)
• Hypogranulosis
• Epidermis is thin over dermal papillae (thinned suprapapillary plates)
• Regular acanthosis, often with clubbed rete ridges
• Relatively little spongiosis
• Dilated capillaries in dermal papillae
• Perivascular lymphohistiocytic infiltrate
PSORIASIS
 Common diseases
LICHEN PLANUS
• Lichen planus is the idiopathic version of a group of
lichenoid disorders characterised by scaling papules or
plaques.
• The histological features of lichen planus are:
• Orthokeratosis
• Hypergranulosis
• Irregular acanthosis with saw-toothed rete ridges
(older lesions)
• Colloid bodies in lower epidermis and upper dermis
• Liquefaction degeneration of the basal layer
• Lichenoid lymphohistiocytic infiltrate in upper dermis
LICHEN PLANUS
 NON MELANOMA SKIN CANCER
• Australia:
• skin cancers account for around 80% of all newly
diagnosed cancers
• THEY ARE SO PREVALENT CANCER REGISTRATION IS
NOT CARRIED OUT IN AUSTRALIA
• between 95 and 99% of skin cancers are caused by
exposure to the sun
• GPs have over 1 million patient consultations per year
for skin cancer
• the incidence of skin cancer in Australia is one of the
highest in the world, two to three times the rates in
Canada, the US and the UK.
UK data
 TUMOURS OF THE SKIN
• Australia has the highest rates of skin cancer
in the world and most Australians are at risk.
Overexposure to ultraviolet radiation can lead
to burning and tanning in the short-term, as
well as premature skin aging and skin cancer
in the long-term.
 MORTALITY
• In 2011 in Australia, there were 543 deaths
non-melanoma skin cancer. Most patients had
Squamous cell carcinoma.
 Incidence Data

• Of these 430,000 NMSC cases, an estimated

296,000 were Basal cell carcinoma (BCC)
cases, and an estimated 138,000 were
Squamous cell carcinoma (SCC) cases. It
should be noted however, that NMSC is not
reportable by law to cancer registries, like
other cancers including melanoma, therefore
the true incidence of BCC and SCC is not
known
 NON MELANOMA SKIN CANCER
• Australia has the highest incidence of NMSC in
the world; 2% of the Australian population
(364 000 people) were treated for NMSC in 2001,
with a total expenditure of $264 million making it
the most expensive cancer.
• The increase in NMSC treatments could be
explained in part by population growth; from
1997 to 2015 the number of people aged 65–
74 years will increase by around 57% and the
number of people ≥ 75 years by 68%.
NON MELANOMA SKIN CANCER
BASAL CELL CARCINOMA
SQUAMOUS CELL CARCINOMA
PRIMARY PREVENTION
 MALIGNANT MELANOMA
• Everyone is at some risk for melanoma, but
increased risk depends on several factors: sun
exposure, number of moles on the skin, skin
type and family history.
 EPIDEMIOLOGY
• In 2009 there were over 11,500 new cases of
melanoma diagnosed in Australia, accounting for
nearly one in ten cancer diagnoses. (NMSC not
included)
• Melanoma is more commonly diagnosed in men than
women. The risk of being diagnosed with melanoma by
age 85 is 1 in 14 for men compared to 1 in 23 for
women.
• In Australia in 2011, there were 1544 deaths due to
melanoma.
• Melanoma is the seventh most common cause of
cancer death in Australia.
INCIDENCE DATA
 Data for Queensland
• Annual melanoma incidence in Qld
• •Far north 153 (61 cases per 100,000 people)
• •North 120 (57 per 100,000)
• •Central 120 (57 per 100,000)
• •Mackay 79 (60 per 100,000)
• •Bundaberg 165 (69 per 100,000)
• •Sunshine Coast 386 (71 per 100,000)
• •Brisbane 1176 (68 per 100,000)
• •Gold Coast 460 (70 per 100,000)
• •South west 275 (76 per 100,000
 MORTALITY
• In 2010, there were 1,452 deaths from melanoma of
the skin (993 men and 459 women), accounting for 3.4
per cent of all cancer deaths in Australia.
• The age-standardised mortality rate for melanoma of
the skin is higher for men: In 2010, there were 8.9
deaths per 100,000 men from melanoma of the skin,
compared with 3.5 deaths per 100,000 women.
• In 2010, the risk of dying from melanoma of the skin
before the age of 85 was 1 in 128.
• Between 1982 and 2010, the age-standardised
mortality rate for melanoma of the skin increased from
4.7 to 5.9 deaths per 100,000 people.
 PREVENTION GUIDELINES
• Seek the shade, especially between 10 AM and 4 PM.
• Do not burn.
• Avoid tanning and UV tanning booths.
• Cover up with clothing, including a broad-brimmed hat and UV-blocking
sunglasses.
• Use a broad spectrum (UVA/UVB) sunscreen with an SPF of 15 or higher
every day. For extended outdoor activity, use a water-resistant, broad
spectrum (UVA/UVB)
sunscreen with an SPF of 30 or higher.
• Apply 1 ounce (2 tablespoons) of sunscreen to your entire body 30
minutes before going outside. Reapply every two hours or immediately
after swimming or excessive sweating.
• Keep newborns out of the sun. Sunscreens should be used on babies over
the age of six months.
• Examine your skin head-to-toe every month.
• See your physician every year for a professional skin exam.
 PATHOGENESIS
• Most malignant melanomas arise as superficial
indolent tumours that are confined to the
epidermis, where they remain for several years.
During this stage, known as the horizontal or
"radial" growth phase, the melanoma is almost
always curable by surgical excision alone. At some
point, probably in response to the stepwise
accumulation of genetic abnormalities, the
melanoma is transformed into an expansile
nodule which extends beyond the biologic
boundary of the basement membrane and
invades the dermis.
 Types of cutaneous melanoma
• Superficial spreading type
• Nodular type
• Lentigo maligna type
• Acral lentiginous type
Superficial spreading type melanoma
Nodular malignant melanoma
Lentigo maligna (HMF)
Acral lentiginous malignant melanoma
 Occult Melanoma
• An occult melanoma is where the primary
tumour is unknown or could not be found,
possibly due to regression of the lesion. In
some cases, although the melanoma may
have disappeared from the skin surface,
melanoma cells have still been able to spread
further through the body.
 Prognosis
• Importance of stage

• Type
• Depth of invasion
• Lymphovascular invasion
• Perineural invasion
 PROGNOSIS
• Around 97 out of every 100 men (97%) will
live for at a least year after they are diagnosed
with melanoma. Around 88 out of every 100
men (88%) will live for at least 5 years. And
around 86 out of every 100 men (86%)
diagnosed will live for at least 10 years.
Stage
 Metastases
• Metastases in internal organs are sometimes removed,
depending on how many there are, where they are,
and how likely they are to cause symptoms. Metastases
that cause symptoms but cannot be removed may be
treated with radiation, immunotherapy, targeted
therapy, or chemotherapy.

• The treatment of widespread melanomas has changed

in recent years as newer forms of immunotherapy and
targeted drugs have been shown to be more effective
than chemotherapy.
 New approaches
• Checkpoint inhibitors such as pembrolizumab
(Keytruda), nivolumab (Opdivo), and
ipilimumab (Yervoy) have been shown to help
some people with advanced melanoma live
longer. These drugs can sometimes have
serious side effects
• In about half of all melanomas, the cancer
cells have changes in the BRAF gene. If this
gene change is found, treatment with newer
targeted therapy drugs such as vemurafenib
(Zelboraf), dabrafenib (Tafinlar), trametinib
(Mekinist), and cobimetinib (Cotellic)