Classification and Pathology of Basal Cell Carcinoma, Squamous Cell Carcinoma and Tumours

Classification and Pathology of Basal Cell Carcinoma, Squamous Cell Carcinoma and Tumours of the Dermis and Adnexae

Classification of Skin Tumours

1. Tumours of Epidermal Origin
2. BENIGN
3. Surface Epidermis
4. Viral tumours

(1)Human papilloma virus

(2)Molluscum contagiosum

1. Seborrheic keratosis
2. Cutaneous cysts

(1)Epidermal inclusion cysts (eg sebaceous cyst)

(2)Dermoid cysts

(3)Milia

1. Achrochordon (skin tag)
2. Keratoacanthoma
3. Epidermal naevi (naevus verrucosus)

1. Epidermal Appendages
2. Pilar (hair) structures

(1)Pilar (trichilemmal) cysts

(2)Pilomatrixoma

(3)Trichoepithelioma

1. Sebaceous glands

(1)Rhinophyma

(2)Sebaceous hyperplasia

(3)Naevus sebaceous

1. Sweat glands

(1)Syringoma

(2)Eccrine poroma

(3)Hidradenoma papilliferum

(4)Cylindroma

1. PREMALIGNANT
2. Surface Epidermis
3. Bowen’s disease
4. Actinic keratosis
5. Leukoplakia
6. Erythroplakia
7. Paget’s disease

1. Epidermal Appendages
2. Naevus sebaceous of Jadassohn

1. MALIGNANT –
2. Basal Cell Carcinoma
3. Squamous Cell Carcinoma

1. Tumours arising from the Melanocyte system
2. TUMOURS ARISING FROM NEVUS CELLS
3. TUMOURS ARISING FROM MELANOCYTES (epidermal / dermal)
4. MALIGNANT MELANOMA

1. Tumours of Mesodermal origin
2. CONNECTIVE TISSUE
3. VASCULAR
4. FAT / MUSCLE / BONE
5. LYMPHORETICULAR SYSTEM

1. Cutaneous Endometriosis

1. Visceral Metastases to Skin

Basal Cell Carcinoma

Malignant tumour arising from basal layer of the epithelium or from the external root sheath of the hair follicle

Greatest concentration in areas that have the highest concentration of pilosebaceous units

Does not possess cellular aplasia (required for a true carcinoma and (almost) never metastasizes

Basal cell carcinoma differs from squamous cell carcinoma in that it does not arise from malignant changes occurring in pre-existing mature epithelial structures

Jacob first described in 1827 – three cases of an ulcer in Celts from Dublin

Krompecher 1900 – pathological description

Aetiology

oGenetic

Gorlin-Golt Syndrome

• childhood onset.
• Palmar pits, Calcification of the falx, bifid ribs,jaw keratocysts esp after puberty, other craniofacial
• autosomal dominant
• tumors have a benign clinical course until after puberty, when malignant degeneration

Xeroderma Pigmentosum

• incomplete sex-linked recessive gene.
• onset during early childhood
• extreme sensitivity to sunlight.
• Initially, diffuse lentigos are noted, with progressive drying and thinning of the skin.
• The primary deficiency is that of the enzyme endonuclease, which is needed to repair sunlight-damaged DNA.

Malignant degeneration into basal cell carcinoma, squamous cell carcinoma, or melanoma is noted during early adult life, with death due to metastatic disease. Prolongation of life is possible by absolute protection from sun exposure and continual aggressive treatment of all developing tumors. The prognosis is dismal.

oAcquired

Sun

• Fitzgerald Skin types I and II

Immune-suppression (x20)

Arsenic ingestion (Bell’s Asthma Mixture)

Scar

• Smallpox vaccination scars
• Burns scars

XRT

Viral infection (small pox vac, HZV, HPV)

Sebaceous naevus (10%)

Classification

oALocalised or diffuse

oBClinicopathological type

Papulonodular (45%)

solid, cystic

Infiltrating (8%)

primary (8%), secondary characteristic (16.6% total), 35% recurrent BCC’s

Multifocal (35%)

superficial, centre-healing/field fire/cicatrising, multifocal in depth

Morphoeic / sclerosing (8.9%)

Metatypical / basisquamous(1.4%)

rare metastatic BCC (1:50000)

oCSecondary characteristics

Pigmented, naevoid, ulcerated, recurrent, arising in scar/XRT

Clinical manifestations

oPapulonodular

raised pearly edge, surface venules, depressed or ulcerated centre.

May be very well circumscribed.

Infiltrative component in ~15%.

oInfiltrating

Diverse appearance, scaly red or grey with induration.

May lack the characteristic edge.

Invade deeply along tissue planes and nerves.

oMultifocal

Red scaly patch 5-10mm diameter with multiple foci, micropearly edge, field fire surface with multiple small ulcerations.

~10% infiltrative component.

oMorphoeic

Whitish grey plaque, may be hollowed.

May be a red ring with the pearly plaque only visible on tensing the skin.

Dangerous because poorly recognised and infiltrative in >50%.

oMetatypical

Characteristics of SCC & BCC.

More aggressive.

oOther

Pigmented- can be any type.

Histology:

oNests or sheets of uniform basophilic cells

oPeripheral palisading (basaloid cells in a single line at the periphery of the tumour)

oHigh mitotic and apoptotic rates (Councilman bodies)

oAcid mucopolysaccharide stroma- cysts

oPigment- Haemosiderin and melanin within stromal macrophages

oInfiltrating components are thin strands, +/- spindle cells, palisading gone

Rx:

oExcision with margin: PN localised (? 1mm), infiltrating 5mm, recurrent infiltrating up to 10mm

oDifficult recurrent tumour: horizontal histologically sectioned

oDermatological:

Cryotherapy (liquid nitrogen -195 degrees)

Topical 5-FU

Moh’s microscopically controlled surgery

oXRT

Outcome:

o5% recurrence at 5yrs

o10% recurrence if BCC < 1 hpf from margin

o33% if positive margin

oRe-excision for positive margin only 50% with residual BCC

oDANGER ZONES: areas of embryonic cleavage (along the frontonasal prominence, eg alar base, nasolabial fold, inner canthus, nose-cheek angle; also the postauricular region, pinna, ear canal, ?forehead, and ?scalp)

Squamous Cell Carcinoma

Malignant tumour of epidermal keratinocytes characterised by invasive nests of prickle cells showing variable central keratinisation and pearl formation.

Arises from the stratum spinosum

Incidence 201/100000 (Aust 1 SCC: 4 BCC)

Aetiology

oSunlight (stronger correlation with damage to skin by actinic radiation then BCC – occurs in areas of direct sunlight)

oskin type

oviral infection (VZV, HPV)

oimmunosuppression

oscars (burn, trauma, vaccination, XRT)

ochemical (tars, nitrogen mustard, polycyclic hydrocarbons, nitrosureas, arsenic, soot)

ogenetic (xeroderma pigmentosa)

Classification: Based on clinical features and is tempered by the knowledge that diagnostic accuracy for SCC <50% for Dermatologists/Surgeons and ~15% for GP’s

oSite

oDescriptive: superficial, proliferative, scar, recurrent, metastatic

oHistology:

Spindle cell: bundles of spindle cells

Adenoid: islands or columns with tubular differentiation

Verrucous: WD, slow growth, warty appearance

oDifferentiation: Well, moderate, poor

DDx

oHyperkeratosis

oBCC

oKA

oAmelanotic melanoma

oMerkel Cell Ca

oLeukaemic skin deposit

oChronic ulcer

oFungal infection

Histology:

• consists of irregular masses of squamous epithelium that proliferate downward to the dermis
• The degree of cellular differentiation determines the grade of the tumour and is measured in the ratio of atypical pleomorphic and anaplastic cells to normal epithelium
• Changes in size and shape of the cells, hyperchromasia, keratinization, and the proportion of mitotic figures influence the determination of grade

oPrickle cell

oKeratin pearl

oSpindle cells

oMajority arise in solar keratosis

oInvolve full thickness epidermis before dermis

oInvade dermis in large tongues vs strands (BCC)

oEosinophilic cells

• Epidermal Cytokeratin Antibody is specific for squamous epithelium

Natural History

Recurrence: adequate margins ~4%, total ~10%

• Predictors of recurrence:
• Degree of cellular differentiation
• Depth of tumour invasion
• Perineural invasion by the tumour
• Clinical signs include parasthesia, pain, numbness, and paralysis, but frequently no symptoms

Metastasis:

oActinic SCC 0.5%

oAcantholytic variety 2%

oNon-sun exposed skin 2-3%

oLip 2-16%

oMarjolin’s ulcer 10-30%

Rx:

oExcision margin:

5-7(20) mm

wider for proliferative, inflammatory, scar, recurrent, perineural spread or symptoms, poor differentiation, extensive.

oLymph Node Involvement

TLND (no place ELND or sentinel biopsy in actinic SCC)

oAdjuvant Therapy

XRT

Tumour spill, PD, perineural spread, close/incomplete margin, extracapsular spread, extensive disease.

Merkel Cell Carcinoma

Aggressive cutaneous malignancy, cell of origin unproven, propensity for LN & distant spread.

Cell of origin

o?cutaneous stem cell capable of differentiation into both neuroendocrine and keratinocyte lineages (favoured)

o?neuroendocrine cell of non-neural crest origin

o?APUD less favoured now

Normal Merkel Cell described 1875 = associated with a slow adapting mechanoreceptor

oTumour described by Toker 1972 = trabecular ca skin

Clinical manifestations.

oPink to violaceous, hard nodule with shiny epithelium, +/- telangiectasia,

o6th - 7th decades

oSun exposed areas

o50% head and neck

o40% limbs

o10% trunk

oDiagnosis is histological

Histology:

oeM: paranuclear aggregates of intermediate filaments, dense cytoplasmic core granules

oCellular patterns

a. trabecular “classical pattern”

b. intermediate: most, solid nests, peripheral trabecular

c. small cell- diffuse sheets

oFeatures: involved dermis, spared epidermis, round-oval cells, large nuclei, high mitotic rate, high apoptosis, perineural & lymphatic invasion

Immunohistochemistry:

ojuxtanuclear labelling for cytokeratins (8, 18, 19)

oWidespread cytoplasmic positivity for neurone specific enolase (NSE)

• Negative staining for S100 & leukocyte common antigen (LCA)

Staging;

I Local disease only

II LN mets (mean <4/12 post Dx)

III Distant disease (mean <12/12 post Dx)

Natural History:

o1/3 develop recurrence

o1/2-2/3 develop LN spread

o1/3-1/2 develop distant spread (all die)

Prognostic factors:

oLN mets strongest predictor of death

oOthers:

tumour >2 cm

Head and neck primary

Histology: LN or perineural spread, small cell type, mitotic rate

Rx:

oStage I: ?WLE 3cm margin, ?XRT

oStage II: WLE & TLND, ?XRT

oStage III: Palliative surg, XRT and CT

Adjuvant therapy:

oMCC is radiosensitive and postop XRT imparts improved locoregional control but not a survival advantage

Areas of contention

oManagement of LN basins in stage I disease

Victor, Morton & Smith 1996: ELND in stage I disease improved locoregional control, 15 P

Messina, Reintgen et al 1997: 12 P sentinel LN biopsy, all alive at 10.5 months, only 2 with mets

Smith et al. Locoregional XRT in stage I disease had improved survival and locoregional controls local treatment only

oCurrent management is WLE, TLND +/- XRT according to pathology

Benign Adnexal Tumours

Hair follicle tumours

Sebaceous tumours

oGlands confined to hairy skin except eyelids (Glands of Zeus and Meibomian glands), lips (white roll), papillae of the breast, labia minora

Apocrine tumours

oSweat; open onto hair follicles on the areola, axilla, vulvogenital & eyelids.

Eccrine tumours

oSweat, distributed throughout the body, most numerous on soles, palms and face

Hair Follicle Tumours

Infundibular Lesions: Epidermal Cyst/ Sebaceous cyst/ Infundibular Cyst

oCommon after puberty, cyst attached to epidermis, expands into subcutaneous fat, Central punctum

oHistology: Laminated keratin (NOT sebaceous)

oRx: EDC with a small skin ellipse including the punctum

Outer Root Sheath Tumours: Tricholemmal Cyst

oPilar Cyst, equivalent to an infundibular cyst but involves the scalp

Hair Germ lesions: Trichoepithelioma:

oCommon, young patient, central face

oHistology: nests of basaloid cells, peripheral palisade, keratinous cyst, abortive dermal papilla

oRx: EDC

Matrical Tumours: Pilomatrixoma

oCalcifying Epithelioma of Malherbe

oCommon, 60% <20yrs (child)

ohead/neck/arms

oSolitary, firm nodule, chalky discharge

oHistology: basophilic cells, eosinophilic keratinising cells, foreign body response with calcification in 2/3

oRx: EDC

Sebaceous Tumours

Sebaceous Naevus (of Ja Dusscha)

oEmbryonic streak along fusion planes (developmental malformation)

oComplex hamartoma of epidermal and adnexal structures

oMalignant degeneration in adults - 10% (BCC mostly)

oYellowish hairless warty plaque, forehead/face/scalp

oHistology: Epidermal naevus, apocrine glands in 50%, sebaceous glands (age dependent activity in infants & puberty)

oRx: EDC

Sebaceous hyperplasia

oYellowish papule, often multiple especially the forehead/cheek

oHistology: enlarged mature sebaceous gland with a central follicle

oRx: Cosmetic, Shave, dermabrade, laser

Sebaceous adenoma

oSolitary, head and neck, elderly

oHistology: Gland less mature with lobules

oRx: Cosmetic, EDC

Apocrine Tumours

Markers are CEA – 180,BGP, NCA, multiple monoclonal antibodies (SKH1, ferritin AB, anti-IgA Ab, Dako-CK1 and Cam 5.2)

Apocrine Cystadenoma /hidrocystoma

oAdenomatous cystic proliferation of apocrine glands

• Small, naevoid, dome-shaped, often translucent nodule on the face
• Frequently pigmented
• When cut contains brownish fluid

oHistology: originate in Glands of Moll

oRx: EDC

Hidradenoma papilliferum

oFemale, vulva/perineum

Syringocystadenoma papilliferum

oCommonly Scalp/forehead

• Verrucous
• Frequently develops in within associated organoid naevus
• 50% present at birth or childhood
• 10% coexisting BCC

Apocrine adenoma

Tubular apocrine adenoma

Apocrine mixed tumor

Eccrine Tumours

markers are lysozyme, Leu MI and GCDFP -15

Eccrine cystadenoma

oPeriorbital most common

oDDx: Apocrine cystadenoma, Chalazion, Lacrimal cystitis, sebaceous carcinoma

oRx: EDC

Papillary eccrine adenoma

Aggressive digital papillary adenoma

Eccrine poroma

Eccrine spiradenoma

Eccrine acrospiroma

Syringoma

omainly multiple flesh coloured nodules 2-3mm

oAdolescent female, multiple papules lower lids/face/genitals/trunk

• clear cell variant associated with DM
• more common in Downs syndrome

oHistology: multiple small eccrine ducts with "comma-like" tail, actively secrete

• removal for cosmetic purposes

Cylindroma

oUsually single, head/neck, mid age-elderly female

• occurs predominantly on scalp
• solitary or multiple, firm smooth pink nodules
• large variants form multiple, coalescent (turban) tumours
• multiple variant inherited as AD trait
• assoc with multiple, inherited form of trichoepitheliomas
• simple excision usually adequate
• Histology -poorly circumscribed, islands of basaloid cells surrounded by hyaline bands

oRx: EDC

Malignant Adnexal Tumours

Sebaceous carcinoma:

Head & neck, especially eyelids

Arise: glands of Zeiss or Meibomian glands

Mimic chalazion (“recurrent chalazion”)

Aggressive 1/3 mets

Local spread down NL duct

Rx: WLE & TLND

Extramammary Paget’s disease:

?insitu apocrine ca with 25% associated with adnexal ca

Axilla & anogenital slow growing erythematous plaque in elderly

50% pruritic

Rx: Biopsy, Excision

Sclerosing Sweat Duct Carcinoma:

Adult, upper lip/face or elsewhere

Slow growing, high recurrence, rare mets

Infiltrative growth, perineural invasion

Evidence of eccrine and pilar differentiation

Biology similar to BCC

Rx; Excision

Tumours of Dermal Fibrous Origin

Dermatofibroma

Dermatofibroma Sarcoma Protuberans (DFSP)

Atypical Fibroxanthoma (AFX)

Malignant Fibrous Histiocytoma (MFH)

Dermatofibroma

Benign (?post traumatic)

Cell of origin: Factor XIIIa positive dermal dendrocyte

Cx: young adult, legs, red/brown/purple/yellow

Histology:

oproliferation fibroblast like cells in dermis

ovariable other elements: vessels, histiocytes, haemosiderin, collagen

oEpidermal changes: acanthosis, basal hyperpigmentation, sebaceous glands, BCC (rare)

Dermatofibroma Sarcoma Protuberans

Low-grade locally infiltrative malignancy involving the dermis and subcutis, composed of spindle cells. Marked tendency to recur and rarely metastasises.

Cell of origin: ?CD34 positive dermal dendrocyte

oCx: Firm intradermal plaque, red/pink, 0.5-10cm, single or multiple coalescing nodules.

oWith extended duration often with multiple recurrences may become a fibrosarcoma

Histology:

oUniform plump cells: spindle shaped

oStoriform pattern centred on dermis

oSuperficial grenz zone

oInvolve subcutis

Macro:

osolid whitish whorled tissue with softer myxoid areas

Rx:

oWLE with 5 cm margin and down to next fascial plane

Atypical Fibroxanthoma

Presumably benign neoplasm of unknown origin with sarcomatous histology.

Cx:

o1-2 cm papule/nodule, face/hands, elderly in sun damaged skin, recur 5%

Histology:

oSarcomatous (like MFH)

oSpindle, polyhedral and giant cells

oAberrant mitoses

oFactor XIIIa positive

Rx: Excision, diagnosis made retrospectively

Malignant Fibrous Histiocytoma

Sarcoma usually of deep tissues from pleuripotential mesenchymal cells with uncommon cutaneous involvement

Cx:

oProx limbs/retroperitoneum, later adult life

Histology:

oUndifferentiated with various variants

Pleomorphic, angiomatoid, myxoid, giant cell

Rx:

oWLE +/- amputation

oCT & XRT may be useful