Pathological aspects of Skin Malignancy -Dr. Arushi Agarwal (JR-1) (Pathology)
Pathological aspects of Skin Malignancy
-Dr. Arushi Agarwal (JR-1)(Pathology)
ClassificationKeratinocytic tumors
◦Basal cell carcinoma◦Squamous cell carcinoma
Melanocytic tumors◦Malignant melanoma
Appendageal tumors
Follicular Differentiation◦ Pilomatric Carcinoma◦ Trichilemmal
CarcinomaSebaceous
Differentiation◦ Sebaceous Carcinoma
Apocrine Differentiation◦ Malignant apocrine
cylindromaEccrine
Differentiation◦ Porocarcinoma◦ Malignant eccrine
spiroadenoma
Tumors of cellular migrants of the skin◦Mycosis Fungoides
Tumors of the dermis◦Dermatofibrosarcoma
Secondary tumors
Basal Cell Carcinoma Most common skin
cancer Slow growing Rarely metastasise Occur at sun-exposed
sites More common in
lightly pigmented elderly adults
Also called tear cancer,
rodent ulcer
Most common sites on
face
Incidence increases with
immunosuppression and
DNA repair
Basal Cell Carcinoma
• A group of malignant cutaneous tumors characterised by
- lobules, columns, bands or cords of basaloid cells
• Distinctive locally aggressive cutaneous tumor
• associated with mutations that activate the Hedgehog Pathway Signaling.
Hedgehog Signaling Pathway
MorphologyPearly papules containing
prominent dilated sub-epidermal blood vessels
Some tumors contains melanin;◦ May resemble melanoma
Neglected and unusually aggressive tumors◦ May ulcerate◦ Show extensive local invasion
of bone and facial sinusesSuperficial BCC : erythematous
pigmented plaques
Histologically Tumor cells resemble cells of normal basal
cell layer of epidermisArise from epidermis or follicular epitheliumDo not occur on mucosal surfacesTwo types
◦ Multifocal growths◦ Nodular lesions
Multifocal growths
◦Originating from epidermis
◦Sometimes extending over several square cms of skin surface
Nodular lesion◦Growing downward
deeply into the dermis◦Cords and islands of
variably basophilic cells
◦Hyperchromatic nuclei◦Embedded in
mucinous matrix
◦Often surrounded by
lymphocytes and
fibroblasts
◦Palisading pattern
◦Presence of clefts and
separation artifacts
Squamous Cell Carcinoma
Squamous Cell Carcinoma2nd most common tumorArise on sun exposed
sites in elderlyMen>womenOther factors : radiation,
carcinogens, immunosuppression, HPV infection
Squamous Cell CarcinomaOlder fair
skinned personsHyperkeratotic
and often ulcerates
Pathophysiology
Mutation of TP53
DNA Damage by UVR
Sensed by check-point kinases
Up-regulation ofTP53
Apoptosis
Repair damage
In situ carcinoma◦ Sharply defined, red scaling
plaques◦ Cells with atypical nuclei in all
levels of epidermis Advanced, invasive
◦ Nodular◦ Ulceration◦ Variable keratin production◦ Variable degrees of
differentiation
Squamous Cell CarcinomaMalignant
neoplasm of epidermal keratinocytes
component cells show variable squamous differentiation
Tongues of atypical
squamous epithelium
have trangressed the
basement membrane
and invaded deeply
into the dermis
Melanoma
Melanoma
It is the most deadly of all skin cancers
Strongly linked to acquired mutations and
exposure to UV-radiation
Can be cured if detected at early age
Inherited as an autosomal dominant traits
Common in:
Light skinned populationUV rays exposureUpper back in malesBack and legs in femalesSevere sun burns, early in life are also
predisposing factors.
Characterised by:
ssymetry order irregularity olour variation iameter>6mm volution
ABCDE
In Situ Malignant Melanoma
Melanoma cells confined
to the epidermis
Lack in invasion may
persist for months to years
Simple excision is often
curative
1) Superficial Spreading Melanoma
Most common in middle age
Develops anywhere on the
body, back in both sexes
and legs in females
Haphazard combination of
colors but may be uniformly
brown or black
2) Nodular Melanoma Occurs in the 5th or 6th decade More frequent in males with a
ratio of 2:1 Found anywhere on the body Most frequently misdiagnosed
because it can resemble a blood blister, hemangioma, dermal nevus or polyp
3) Lentigo Maligna Melanoma
Lentigo of the face in the elderly
Flat, brown/black, irregular
Grows slowly over yearsSun-exposed areas of the
skinUsually very long radial
growth phase
4)Acral Lentigenous Melanoma
Most common in blacks and orientals
Appears on the palms, soles terminal phalanges and mucous membranes
The tumor is very aggressive and metastasizes early
5) Subungual MelanomaPigmentation in the nail
area2-3% of melanomas in
white skinnedMore common in dark-
skinnedFirst sign is ‘black
linear discolouration’
Amelanotic Melanoma
Breslow’s thickness
D using a
Melanoma cells
◦ Large nuclei,
irregular contours
◦ Clumped chromatin
at the periphery
◦ Prominent red
nucleoli
Initial radial growth phase
Spread in epidermis and superficial dermis
Inability to metastasise
Most common type Involves sun exposed skin
Irregular nested and single-cell growth of melanoma cells within the epidermis
And an underlying inflammatory response in the dermis
Vertical growth phase◦Invade deeper dermal layers
◦Metastatic potential◦Appearance of nodule
◦Emergence of tumor sub-clone
Demonstrating nodular aggregates of infiltrating cells
Pilomatric CarcinomaRare malignant counterpart of
pilomatricomaMale predominanceTendency to recurPulmonary and bony metastasis
may occur
HistologicallyAssymetryPoor circumscriptionBasaloid aggregation
of tumor cellsExtensive areas of
necrosis Infiltrating growth
pattern
Sebaceous Carcinoma
Occurs in adult females commonly
Painless massesOcular sites- meibomian glandExtraocular sites- head, neck,
genitaliaNodules that may or may not
ulcerate
HistologicallyIrregular lobular
formationSebaceous cells with
foamy cytoplasmUndifferentiated and
atypical sebaceous cells
Infiltrative growth pattern
Mycosis fungoidesCutaneous T-cell lymphoma are
lymphoproliferative disorder affecting the skin
Lymphoma of skin-homing CD+ T helper cellsCan occur at any age, but commonly is
>40yrsRemains localised for many years May evolve into lymphoma
Raised, indurated irregularly
outlined erythematous plaques
Multiple large red-brown nodules:
systemic spread
Plaques and nodules may ulcerate
Seeding of blood by T cells,
diffuse erythema, scaling of entire
body: Sezary syndrome
MorphologyHallmark: Sezary-
lutzner cells Infolded nuclear
membrane Hyperconvoluted /
cerebriform contour
In advance stages, T-cells:
◦lose
epidermotropic
tendency
◦Grow deeply in
to dermis
◦Spread
systemically
Dermatofibrosarcoma Protuberance
Uncommon but the commonest of all dermal sarcomas
Commonly develops during 3rd and 5th decades
More common in femalesMore common in blacks
than whites
Well differentiated primary fibrosarcoma
Locally invasive tumorArise in the dermisShow fibroblastic
differentiation
Site of previous trauma,
burn scar, site of
vaccination
PathologyTumor is usually a solitary multinodular massDermis and subcutaneous tissue are
replaced by: bundles of uniform spindle shaped cells with
little cytoplasm elongated hyperchromatic nuclei little mitotic activity
Deeper involvement in some cases
Laterally :Storiform pattern
Interstitial tissue contains collagen fibres
Subcutaneous tissue: Lace-like pattern
Myxoid changes : Focal or prominent
CD34 positive but not specific
Thank you
Occurs largley on faceSlow growing epidermal papule,
induratedUnusual finding in Cowden’s
diseaseRecurrece and metastases are
uncommon
Trichilemmal Carcinoma
Occurs histologically invasiveCytologically clear cells present,
atypia prominent lesional cells form solid lobular
or trabecular patternPeripheral palisading of cells
Morphology
Pathogenesis