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