Classification
• Tumours ofskin are broadly classified as Benign,
Premalignant and Malignant
• They may also be classified according to their origin as:
• Epidermal
• Appendageal – Pilar (hair), sebaceous and sweat gland
• Melanocytic
• Mesodermal origin (vascular and connective tissue)
Benign and Premalignant
EpithelialLesions
• Benign epithelial neoplasms are common and
probably arise from stem cells residing in the
epidermis and hair follicles.
• These tumors grow to a limited size and generally do
not undergo malignant transformation.
6.
Seborrheic keratosis
• Themost common benign skin neoplasm.
• No malignant potential.
• Origin is unknown.
• more frequent in middle age and older persons
• Tend to occur on trunk most often, but can appear
on head and extremities.
• Lesions contained entirely in epidermis
7.
Appearance
• Size canrange from 0.2 to 3.0 cm in diameter.
• Can have smooth surface or be rough and cracked.
• Characteristic "stuck-on" appearance.
• Color can be tan, brown, or black.
• Can resemble melanoma (SK has uniform surface
• appearance).
• Key to visual diagnosis is identification of horn cysts
• Black or pearly-white cysts either embedded in or on the surface of
the lesion.
• These are dilated follicular Ostia filled with keratin.
Seborrheic keratosis
• SeborrheicKeratosis: have characteristic horn cysts. They can be white
and deeper seated (left) or black and superficial (right).
10.
Seborrheic Keratosis: Melanoma
Look-Alikes
•Seborrheic Keratosis: Has dark pigmentation, irregular borders, and some
variation of color, but horn cysts help to make diagnosis clinically.
11.
Actinic Keratosis
Definition
• Actinic(or solar) keratosis is a premalignant epithelial
lesion directly related to long-term sun exposure
• classically found on sun-exposed areas of the
skin( face,arm,dorsum of hand)
• A small percentage of these lesions will transform
into squamous cell carcinoma.
12.
• Also calledsolar keratosis.
• Lesions increase with age.
• Can spontaneously regress if sun-exposure is removed.
• Lesions have increased vascularity (erythematous).
• Develops adherent white or yellowish scale.
• Can bleed if picked.
• Many lesions are more readily identified by rough texture
than appearance.
Actinic Keratosis
Actinic Keratosis
• Keratosis:classic appearance with scale and crust on an
erythematous base (left). Many AKs on the face, the
surrounding skin has irregular pigmentation and some dilated
vessels (right).
15.
Actinic Keratosis
• ActinicKeratosis: thicker lesions can develop into squamous cell
carcinoma (left). AK's can often clinically appear like SCC (right).
Squamous Cell Carcinoma
•Squamous cell carcinoma is a common tumor arising on
sun exposed sites in older people.
• higher incidence in men than in women.
• these lesions have significant chance of metastasis.
• UV radiation is involved in the pathogenesis of SCC.
• Found in sun-exposed areas (scalp, back of hands, pinna).
• Actinic keratosis is most common precursor lesion.
18.
Risk Factors
• Inaddition to sunlight, predisposing factors include :
• industrial carcinogens (tars and oils)
• chronic ulcers
• old burn scars
• ingestion of arsenicals
• ionizing radiation.
20.
Features Of SquamousCell
Carcinoma
• Clinically, Squamous cell carcinoma presents as a
shallow ulcer with raised, everted, firm border
• Wide surgical excision in sun exposed cases is usually
curative
• Radical lymph node dissection and other forms of
adjuvant therapy may be necessary in management of
other squamous carcinomas with a higher metastatic
potential
21.
Squamous Cell Carcinoma
•Less than 5% have metastasized to regional nodes at
diagnosis.
• The likelihood of metastasis is related to the
thickness of the lesion and degree of invasion into
the subcutis.
22.
Histology
• Histlologically, thetumour is composed of large
polygonal cells with abundant pink cytoplasm (ie,
they resemble cells of prickle layer)
• Atypia, pleomorphism and mitotic activity vary from
minimal to marked
• Keratin - containing epithelial pearls are porominant
in well differentiated tumours
• Invasion is usually present.
Squamous Cell Carcinoma
•Squamous Cell Carcinoma: Asymmetrical lesion; Occurs on
sun - damages skin; Grows slowly; Metastasizes late
25.
Squamous Cell Carcinoma
•A nodular and hyperkeratotic lesion occurring on the ear,
unfortunately with early metastasis to a prominent post
auricular lymph node (arrow)
26.
Squamous Cell Carcinoma
•In situ carcinoma :
• Sharply defined, red scaling plaques
• Cells with atypical nuclei in all
levels of epidermis
• Advanced, invasive :
• Nodular
• Ulceration
• Vvariable keratin production
• Variable degrees of differentiation
27.
Squamous Cell Carcinoma
•Well differentiated squamous cell carcinoma skin. The tumour cells are strikingly
similar to squamous epithelial cells.
• with intercellular bridges and nests of keratin pearls
Basal Cell Carcinoma
•Cell Carcinoma Basal cell carcinoma is a common skin neoplasm
• Occurs in sun exposed areas of light skinned individuals
• Usually over the age of 40 years Face is the most common site
involved
• Clinically, early basal cell carcinoma arises from the basal layer of
the epidermis and invades the dermis as nests and cords of cells.
• Basal cell carcinoma is locally aggressive
• It may invade deeply to involve bone and muscle but almost never
metastasizes
30.
Basal Cell Carcinoma
•Advanced lesions may ulcerate and extensive local
invasion of bone or facial sinuses may occur after
many years of neglect or unusually of aggressive
tumours, justifying the past designation "Rodent Ulcer"
• Wide surgical excision is curative.
• associated with mutations that activate the Hedgehog
Pathway Signalling.
Morphology
• Pearly papulescontaining prominent
dilated sub epidermal blood vessels
• Some tumours contains
• melanin; May resemble melanoma
• Neglected and unusually aggressive
tumours:
• May ulcerate
• Show extensive local invasion of
bone and facial sinuses
33.
Histologically
• Tumor cellsresemble cells of normal basal cell layer of
epidermis
• Arise from epidermis or follicular epithelium
• Do not occur on mucosal surfaces
• Two types:
• Multifocal growths
• Nodular lesions
Nodular lesion
• Growingdownward deeply
into the dermis
• Cords and islands of variably
basophilic cells
• Hyper chromatic nuclei
Embedded in mucinouss
matrix
36.
• Multiple nodulesof basaloid
cells infiltrating a fibrotic
stroma.
• The cells have a scant
cytoplasm, small hyper
chromatic nuclei, and a
peripheral palisading pattern
with clefting the stroma.
37.
• Nests areoften separated from the adjacent
stroma by thin clefts
• Composed of nests of basaloid cells
within the dermis
• The TermNEVUS: Latin naevus
means Mole
• The Term NEVUS is used in general
sense for many cutaneous lesions
present at birth
41.
Nevocellular Nevus
(Melanocytic nevus)
•Melanocytic Nevi are usually not present at birth but
appear in childhood and stop growing soon after puberty.
• Extremely common.
• They are benign and present clinically as flat, papular,
papillomatous or pedunculated pigmented (black or
brown)lesions
• If a nevus changes its form in any way, malignancyshould
be suspected.
42.
Nevocellular Nevus
1. Histologically,moles are composed of nests of nevus
(Melanocytic) cells, which may be found in the:
2.Dermis: Inradermal Nevus
3.At the junction between epidermis
and dermis: Junctional Nevus
OR
4. in both locations: Compound Nevus
43.
Nevocellular Nevus -Junctional
Type
• A: In clinical appearance, lesions are small, relatively flat,Symetric and uniform
• B: On histological examination, Junction nevi are charterized by rounded nests of
nevus cells originating at the tips of rete ridges along the dermoepidermoid junction
44.
Nevocellular Nevus Junctional
Type
•A: In clinical appearance, lesions are small, relatively flat, symmetric and uniform
• B: On histological examination, Junctional nevi are charterized by rounded nests of nevus cells
originating at the tips of rete ridges along the dermoepidermoid junction
45.
Dysplastic Nevi
• Specialtype of nevus that tend to be:
• (a) familial
• (b) frequently multiple
• (C) commonly more than 5 mm in diameter
• In affected families, the disease has an autosomal dominant inheritance pattern
• show disordered architecture features on histological examination and may
show cytologic atypia
• Dyspalstic nevi are premalignant
• Families with dysplastic nevi have an increased risk (5 -10%) of developing
malignant melanoma
46.
Dysplastic Nevi
• usuallylarger than most acquired nevi (more than 5mm
across)
• May occur as hundreds of lesions on the body surface
• Flat macules to slightly raised plaques with a "pebbly
surface Usually show variable pigmentation (variegation)
and irregular borders
• Unlike ordinary nevi,dyspalstic nevi have a tendency to
occur on body surfaces not exposed to the sun, as well as
on sun exposed body surfaces
47.
Dysplastic Nevi
• Numerousirregular nevi on the
back of this individual suggest the
dysplastic nevus syndrome; the
clinical features are intermediate
to those of benign nevi and
melanoma. The lesions are usually
greater than 5 mm in diameter
with irregular borders and variable
pigmentation
48.
Dysplastic Nevi
• -Acentral dermal component, which correlates the more pigmented and raised central zone - An
asymmetric "shoulder" of exclusively junctional melanocytes, which correlates the less pigmented
flat peripheral rim
• - An important feature is presence of cytologic atypia (irregular,Dark-stained nuclei)
Malignant Melanoma
• MalignantMelanom a relatively common neoplasm.
• Although the great preponderance of melanomas arise in
skin, other sites of origin are oral and anogenital mucosal
surfaces, esophagus, meninges and notably eye.
• Once was considered almost uniformly deadly Today as a
result of increased public awarness of the earliest signs
of melanomas, most are cured surgically. The incidence
of these lesions is on the rise, necessitating vigorous
surveillance of their development
52.
Malignant Melanoma
• Incidenceis highest in sun exposed skin and in
geographic locales such as New Zealand and
Australia where sun exposure is high and protective
mantle of melanin is sparse
• Predisposing factors other than sunlight are:
• - Presence of preexisitng nevi
• - Hereditary predisposition
Predisposing Factors
• Aswith epithelial malignant neoplasms of the skin,sunlight
appears to play an important role in the development of skin
malignant melanomas
• Lightly pigmented individuals are at higher risk for the
development of melanomas than are darkly pigmented
individuals. Sunlight, however does not seem to be the
predisposing
• factor Presence of a prexisitng nevus (Dysplastic nevus),
hereditary factors or even exposure to certain carcinogens may
play a role.
55.
Molecular Genetics ofmalignant melanoma show
association
• Melanomas which run in families shows association with
• - Dyspasitic nevi
• - Genetic events
• Genes involved in Malignant Melanoma
• Genes which promote malignant proliferation
• - CMM1 Gene
• -DCK4 Gene
• Tumour suppression Gene: Its mutation leads to malignant
• growth
56.
Molecular Genetics ofmalignant melanoma
As with other tumours, malignant transformation is a multistep
process with:
• a) Activating mutations in proto-oncogenes
• b) Loss of tumour suppressor genes
57.
Clinical features ofMalignant
Melanoma
• Malignant melanoma of skin is usually asymptomatic
• Itching may be the early manifestation
• The most important clinical sign of the disease is the
change in colour in a pigmented lesion. Unlike benign
(nondyspasltic) nevi, melanomas exhibit striking variations
in pigmentation, appearing in shades of black, brown, red,
dark blue and gray.
• On occasion zones of white or flesh coloured
Hypopigmentation are also present
58.
Clinical warning signsof Malignant Melanoma
• (1) Enlargement of pre-existing mole
• (2) Itching or pain in a pre-existing mole .
• (3) Development of a new pigmented lesion during adult life
• (4) Irregularity of the borders of a pigmented lesion
• (5) Variegation of colour within a pigmented lesion
Borders of Benign Nevi Borders of Malignant
Melanoma
Smooth, round and
uniform
Irregular, coarse and often
notched
59.
Malignant Melanoma:
Recognizing SuspiciousNevi
• ABCD's of moles:
• Asymmetry
• Borders : irregular edges
• Color :Uneven pigmentation ,Various
shades brown,black, red
• Diameter :Greater than 6mm
60.
Growth pattern ofMalignant
Melanoma
• A: Radial Growth: Indicates the tendency of
melanoma to grow horizontally within the epidermal
and superficial layers, often for a prolonged time
• B: Vertical Growth: After passage of time the
pattern of growth assumes a vertical component and
the melanoma now grows downward into the deeper
dermal layers as an expensile mass.
Morphological findings in
MalignantMelanoma
• Individual cells are usually considerably larger that nevus cells. They
contain large nuclei with irregular contours, having chromatin
characteristically clumped at the periphery of the nuclear membrane
and prominent red (eosinophilic) nucleoli;often described as "Cherry
Red" nucleoli.
• These cells proliferate as poorly formed nests or as individual cells at
all levels of the epidermis in the radial phase of growth and in the
dermis as expansile, balloon like nodules in the vertical phase of the
growth.
• Thus it is important to observe and record vertical growth phase
parameters in a pathology report.
65.
Malignant Melanoma:
Microscopic Features
•Melanoma cells have
hyper chromatic
nuclei of iregular size
and shape with
prominent nucleoli.
Mitosis, including
atypical forms such as
seen in the center of
this field are often
encountered